Missions were established in California in the eighteenth and nineteenth centuries to convert Native Americans to Christianity and enculturate them into a class of laborers for Californios (Spanish/Mexican settler). The concentration of large numbers of Native Americans at the Missions, along with the introduction of European diseases, led to serious disease problems. Medicinal supplies brought to California by the missionaries were limited in quantity. This situation resulted in an opportunity for the sharing of knowledge of medicinal plants between the Native Americans and the Mission priests. The purpose of this study is to examine the degree to which such sharing of knowledge took place and to understand factors that may have influenced the sharing of medicinal knowledge. The study also examines the sharing of medicinal knowledge between the Native Americans and the Californios following the demise of the California Missions.Two methods were employed in the study: (1) a comparison of lists of medicinal plants used by various groups  prior to, during, and after the Mission period and (2) a close reading of diaries, reports, and books written by first-hand observers and modern authorities to find accounts of and identify factors influencing the exchange of medicinal information.A comparison of the lists of medicinal plants use by various groups indicated that only a small percentage of medicinal plants were shared by two or more groups. For example, none of the 265 taxa of species used by the Native Americans in pre-Mission times were imported into Spain for medicinal use and only 16 taxa were reported to have been used at the Missions. A larger sharing of information of medicinal plants took place in the post-Mission period when Native Americans were dispersed from the Missions and worked as laborers on the ranches of the Californios.Sharing of information concerning medicinal plants did occur during the Mission period, but the number of documented species was limited. A number of possible factors discouraged this exchange. These include (1) imbalance of power between the priests and the Native Americans, (2) suppression of indigenous knowledge and medical practices by the Mission priests, (3) language barriers, (4) reduction of availability of medicinal herbs around the Mission due to introduced agricultural practices, (5) desire to protect knowledge of medicinal herbs by Native American shaman, (6) administrative structure at the Missions which left little time for direct interaction between the priests and individual Native Americans, (7) loss of knowledge of herbal medicine by the Native Americans over time at the Missions, and (8) limited transportation opportunities for reciprocal the shipment of medicinal plants between California and Spain. Three possible factors were identified that contributed to a greater sharing of information between the Native Americans and the Californios in the post-Mission period. These were (1) more one-to-one interactions between the Californios and the Native Americans, (2) many of the Californios were mestizos whose mothers or grandmothers were Native Americans, and (3) lack of pressure on the part of the Californios to suppress Native American beliefs and medicinal practices. Rubus (blackberries) were used to control diarrhea by people in Asia as well as by Native Americans living in different parts of North America [Rubus to combat diarrhea [Aesculus californica), a California endemic, to treat snakebites [The migration of people to North America began about 21,000-40,000 years BP over a great land bridge between Siberia and Alaska . The immdiarrhea . Once inakebites . Variousakebites –19. ThesThe culture and economy of Native Americans was changed significantly beginning in 1769 with the European colonization of California. An integral part of the Spanish colonization process was the establishment of a system of Missions  were assigned to care for the sick in these hospitals. The enfermeros used medicinal herbs and Spanish medicine to treat the neophytes. Medicinal herbs used by the Native Americans were collected from around the Missions [neophytes succumbing to both native and exotic diseases. At times of shortages of medical supplies, the priests and enfermeros exchanged knowledge of medicinal plants to broaden the supply of medicines to treat the sick [Neophytes were sometimes dispatched by the priests to collect medicinal plants from the wild (Engelhardt 1922).The California Missions were under the control of Spain from 1769 to 1821. During this time the Native Americans who were converted to christianity at the Missions were known to as smallpox . Contagithe sick . Neophythuertas, were an essential part of the Mission landscapes. They provided growing space for food plants, as well as trees, flowers, and medicinal herbs. Plants grown in the huertas were used by both the priests and the Native Americans. The importation of seeds and other goods was curtailed after 1810 when shipping from Spain and the Spanish colonies in the New World was interrupted by the rebellion in Mexico [neophytes, but most neophytes were transferred to nearby ranches during the Mexican period (1821-1848) were they worked as laborers. Some Native Americans were paid modest salaries for their labor, while most worked for food and a place to live. Individual Native American families and extended families lived on the ranches. A striking contrast to the hundreds who had resided at the missions. The relocation of Native Americans to local ranches provided an opportunity for the sharing of information concerning medicinal plants between the Native Americans and the Californios.During the Mission period, seeds of plants for the mission gardens periodically arrived via ships from Europe, South America, and Mexico. Walled gardens, known as n Mexico . Mexico The secularization period ended in 1848 with the annexation of California by the USA following the war with Mexico. Following the annexation, most of the Missions were abandoned and began to fall into disrepair. Without active parishes to maintain the Missions, the old buildings fell prey to the weather. Their roofs gave way first, exposing the soluble adobe walls to the rain. Many of the old buildings were abandoned as unsafe or unsalvageable, many were torn down. For many decades the decay of buildings at the Missions, the missions continued until citizens began to take an interest in them and to propose their restoration. Old records, drawing, and photographs were studied to perform reconstruction of historic buildings, patios, and gardens. At several Missions, medicinal plants were incorporated into the restored gardens.The purpose of this study is to examine the exchange of medicinal plant information at the California Missions during the Mission and post-Mission periods. Specifically, the exchange between the Native Americans and the priests during the Mission period and the exchange between the Native Americans and the Californios during and following the secularization of the Missions. We hypothesize that an exchange of information on medicinal plants can be identified by comparing the numbers of taxa from Spain that were introduced into California and adopted for use by the Native Americans and the number of taxa from California that were introduced into Spain and adopted by Spanish citizens for medicinal purposes. Furthermore, the exchange of information concerning medicinal plants between the Native Americans and the Californios can be identified by the number of medicinal taxa from Spain and Mexico that were introduced into California and used by the Native Americans and the number of California taxa adopted for medicinal use by the Californios.Two methods were employed in this study: (1) comparison of lists of medicinal plants used by Native American in California before the Mission period, medicinal plants used in Spain, medicinal plants used in Mexico before it gained its independence from Spain, and medicinal plants used by Californios and Native Americans in the post-Mission period and (2) a close reading of diaries, journals, reports, and books written by (i) first-hand observers during the Mission and post-Mission periods and, (ii) modern anthropologists, ethnobotanists, and historians to find accounts of the sharing of information about medicinal plants and to identify reasons why an exchange of information may or may not have taken place.The lists of medicinal plants and their uses were assembled from a number of sources Table  for the www.ipni.org).The data provided were grouped into 14 categories depending on the pathology they treated , 38, 44:www.floraiberica.es; www.fitoterapia.net [To determine if any California species were introduced in Spanish and/or European botanical gardens a literature review was carried conducted –54. Seveapia.net –57;.A comparison of the assembled lists identified medicinal plant taxa that were used in two different areas . If taxa native to California were reported to be used in present-day Spanish medicinal gardens, then we assumed information of the medicinal use of these plants had been shared between the Native Americans and the Spanish priest. Likewise, if taxa native to Spain were present in herb gardens at the Missions or reported to have been used by Native Americans during the post-Mission period, we assumed that sharing of knowledge had taken place.Rhamnus californica Eschsch.—treat rheumatism); drinking water in which the plant material had been boiled ; application of a poultice prepared from the plant material , eating the plant or plant part  Hayek—treat liver ailments), bathing the skin with water in which to plant had been boiled  Nutt.—treat sores); rubbing dry ashes of a plant on the skin  Steudel—treat poison oak); chewing plant parts  J. Coulter & Rose—treat pain).A total of 822 taxa belonging to 136 botanical families were identified  C.A. Paris, Anemopsis californica (Nutt.) Hook. & Arn, Artemisia ludoviciana Nutt, Baccharis glutinosa Pers., Cucurbita foetidissima Kunth, Equisetum arvense L., Larrea tridentata (DC.) Cov., Opuntia sp., Quercus sp., Rorippa nasturtium-aquaticum (L.) Hayek, Salvia sp. and Sambucus mexicana C. Presl.  A significant power imbalance existed between the priests and the Native Americans.(2) Priests thought the Native Americans were savage heathens or children who knew nothing.(3) Language barriers to communication.(4) Reduction in the availability of medicinal herbs due to the elimination of Native American burning and the introduction of Spanish livestock.(5) Knowledge of medicinal plants was a source of power and income for the Native American shamans who did not want to share it.(6) Structural organization of the administration of Missions left little time for direct communication between priests and neophytes.(7) Knowledge of herbal medicine was lost at the Missions by the neophyte’s children and grandchildren.(8) Transportation limitations during the Mission period may have limited reciprocal shipments of medicinal plants between Spain and California.The list of medicinal plants used both by Natives Americans and Californios indicates a much greater sharing of medicinal knowledge following the secularization of the Missions , 43. Theneophytes to collect food plants and herbs during times of shortages [The results of this study suggest limited sharing of information about medicinal plants occurred during the Mission Period. There are direct reports of the sharing of information such as the dispatching of hortages . Additiohortages ; Flora [hortages , 53, 81)hortages , 38. TheMuch more evidence was discovered in this study to suggest many possible factors contributed to constraining the sharing of information about medicinal plants. These factors and the sources of information about these factors are presented in Table neophytes hiding some information concerning medicinal plants and shaman treating neophytes out of sight of the priests [The priests maintained significant power over the Native Americans at the missions. Their power was enforced by corporal punishment and confinement of the neophytes who did not work or who behaved badly in the eyes of the priests , 82. Thi priests , 79. AnyMany of the priests regarded the Native Americans as pagan savages whose customs needed to be suppressed. Interest in or communication about native medicinal plants would have been considered a way of endorsing native beliefs that the priests were dedicated to eliminating.Language was also a barrier to communication between the priests and the Native Americans. Several quite distinct languages and dialects were spoken by Native Americans living along the California coast. Although the Mission priests were expected to learn the native languages and instruct the Native Americans in their native languages this was seldom the case . The lanThe use of land for farming and livestock grazing along with the elimination of Native American burning of the landscape resulted in fewer medicinal plants in the vicinity of the Missions , 62, 74.The power and income Native American shamans received from their use of medicinal herbs were values that they would not have wanted to give up. The shamans continued their treatment of sick Native Americans at the Missions, but not in situations where they would be observed by the priests  shipments to California were for the most part halted  shipment. The SpaA greater exchange of information occurred during the post-Mission Period. The high number of plants used for medicinal purposes might be explained by the closer working relationships that occurred on the local ranches between the Native Americans and the Californios. Furthermore, the Californios had less incentives to “deculturalize” the Native Americans. Preparation of 46 of the herbal remedies reported by Garriga included ingredients  that were not available to the Native Americans in pre-Spanish times . This suWe conclude from this study that there was a limited transfer of information on the medicinal use of plants between the Native American and Spanish priests during the Mission period. Many factors related to the obligations of the priests, their attitudes toward the Native Americans, language barriers, and cultural differences interfered with a more complete sharing of information. A primary factor in the lack of transfer of medicinal information between the Native American and the priest was the imbalance of power. This imbalance of power kept the Native Americans from sharing information. The fact that none of the 15 most commonly used California species were not transported to Spain for medicinal uses presents an interesting question: were these plants not considered of superior value to the plants in Spain for the treatment of illnesses or did the Native American not share their knowledge of these plants with the priests? The magnitude sharing of information about medicinal plants between the Native Americans and the Californios increased in the post-Mission Period. This increase was due to a greater contact between the Native Americans and the Californios and a different relationship that existed between the two groups. Important aspects of this relationship were increased one-on-one communication, mestizo background of the Californios, and the lack of responsibility on the part of the Californios to convert the Native Americans to christianity.


In the current paper the implied interactions of the dendritic structure of the copper strand in terms of homogeneity at the cross-section of its electrical, mechanical and plastic properties determined based on the samples taken parallelly and perpendicularly to the surface of the dendritic boundaries were analysed. The obtained results were confronted with scanning electron microscopy (SEM) images of the fractures formed during uniaxial tensile test. It has been observed that when the crystallites were arranged perpendicularly to the tensile direction the yield strength (YS) was lower and the fractures were brittle. On the other hand, when the crystallites were arranged parallelly to the tensile direction the fractures were plastic and elongated necking was observed along with the higher YS and total elongation values. The differences in values vary in terms of the applied direction of the tensile force. A characteristic positioning of the Cu2O oxide particles inside the fracture depending on the crystallite alignment and the direction of the applied tensile force has been observed. The properties of copper in its solid state are strongly affected by the crystallization conditions of the liquid material. ETP grade copper (Electrolytic Tough Pitch Copper) contains oxygen, which causes Cu The authors in [2O eutectic forming along the grain boundaries in the casted strand may be a stress concentrator, which might lead to cracks at later stages of processing. Numerous gassings and porosities occurring in the strand when combined with Cu2O oxide constitute areas of increased risk of prospective material continuity loss and may also adversely affect the properties of copper such as electrical conductivity [2O oxide may be beneficial in terms of e.g., materials hardness [2O eutectic may also influence the type of fracture during tensile testing. However, oxygen presence in the copper structure has a numerous beneficial functions. A carefully controlled amount of oxygen throughout the manufacturing process of copper reduces the negative impact of impurities as it is involved in the formation of oxides or conglomerates of oxides of other less noble than copper elements, and therefore reducing their negative impact on material properties such as ductility and annealing by removing them from the solid solution into the form of precipitates [2O oxide at the fracture surface. The novelty of the conducted research in the current paper was also the determination of Cu2O oxide location in the casted strand and its coherence with the copper matrix. The mean shape and size of the oxide was specified as well. The identification of the initial size of the oxide will allow to analyse its evolution in further plastic working processes including but not limited to hot rolling (wire rod manufacturing) and wire drawing process of ETP grade copper. The latter being a cold working process is characterized with significant level of strengthening of copper matrix and high unit pressure value on the wall of the die approach angle.The mechanical properties such as ultimate tensile strength (UTS) and YS of the material depend on its structure, which may be controlled throughout the technological processes. However, appropriate control of the material structure is much more difficult when the processes is conducted continuously such as strand casting process of copper intended for direct processing into wire rod designated for electrical purposes (Cu-ETP). It is, in fact, a continuous casting process of copper strand directly subjected to the hot-rolling process. The strand is obtained via a mobile casting mould ,2 and dumaterial ,13. Regaobserved . Regardiobserved . Howeverc spaces ,17. The r matrix ,19. Accor matrix ,21 the Cthors in ,23 stateuctivity ,25, howehardness . One of hardness  is that ipitates ,29. The 2 (60 × 120 mm) obtained via continuous casting process with average amount of oxygen equal to 200 ppm has been tested. The casted strand was obtained with the defined casting parameters which were collectively presented in An ETP grade copper strand with a cross section of 7200 mm2O oxide morphology and the type of Cu-Cu2O boundaries. The macrostructure of the copper strand is presented at 2O oxides) were performed and the spectra of characteristic X-rays were obtained.The strand was cut crosswise to the casting direction in several slices with thickness of 10 mm and was subjected to material properties analysis, in particular, macrostructural studies and micro-analysis of its chemical composition. Microstructural analysis of the copper strand using light microscope  was also conducted with specific emphasis on the observations of CuElectrical conductivity test was carried out in order to determine the homogeneity of the structure and the correctness of the copper strand casting process. Conductivity measurements were conducted at a grid of 72 equal fields with dimensions of 10 × 10 mm marked at the cross section of the strand using SigmaTest model 2.069 , which is an eddy current device allowing accurate, non-destructive measurements of non-ferrous metals electrical conductivity based on the impedance of a measuring probe i.e., the relation between the voltage drop on the measured impedance and the current flowing in alternating current circuits. When measuring an unknown material the device converts the complex impedance value into an electrical conductivity value given in MS/m with a measuring range of the instrument determined by the calibration. The test was carried out at a constant ambient temperature of 20 °C. Absolute accuracy of the device is equal to ±0.5% of the measured value and the resolution is ±0.1% of measured value at 60 kHz frequency. Each of the 72 areas was measured three times and two different slices with 10 mm thickness were tested.2O oxides. 0) equal to approximately 60 mm2. The marked arrows indicate the direction of the tensile force during uniaxial tensile test.The strands’ mechanical properties were assessed in the uniaxial tensile test using ProLine Z020 testing machine  and the obtained values of UTS, YS, and elongation were in detail analysed in terms of their relation with the fracture observations concerning the morphology and concentration of Cu2O oxide undergoes segregation and according to the observations in 2O monocrystals located in the spaces between grains and dendrites, which was confirmed with light microscopy images. Characteristic is the distribution of oxide, which form lines (paths) of discrete division of structure elements  or large clusters at the junction of several elements, which are flat images of spatially formed discrete clusters of oxide monocrystals and filling intracrystalline spaces/voids. The longitudinal section of the cast material, similarly to the cross section images, shows that the oxide crystallizes into large, regular clusters of monocrystals revealing various components of the copper matrix.During solidification Cu2O oxides inclusions an analysis of the microstructure was performed and the characteristic X-rays spectra were presented. In order to accurately recognize and confirm Cu2O oxides inclusions. Each of the analysed particles of Cu2O confirmed the atomic ratio of oxygen to copper to be approximately 1:3, which is in agreement with stoichiometry of the Cu2O compound. The shape has been identified to be axi-symmetrical and oval with the size of approximately 2–5 μm.EDX analysis of the material did not show any other than presented CuHomogeneity of the structure and therefore the correctness of the strand casting process of copper was determined by electrical conductivity test using eddy current device. The mean electrical conductivity of the material at the cross section was 56.77 MS/m with calculated standard deviation equal to 0.73. The tested material had similar electrical properties, which might indicate high homogeneity of the strand after the casting process. The crystallization front resulting from water cooling of the casted copper strand during the casting process is clearly visible at the cross section of the strand. Lower values of electrical conductivity being a consequence of oxygen macrosegregation at the axis of the crystallization fronts were recorded. It confirms the theoretical assumptions that at the place of contact of crystallization fronts the highest content of oxygen and interdendritic boundaries are present resulting in the reduction in electrical conductivity. Numerous accumulation of impurities in the material might lower its mechanical properties and may be the cause of materials discontinuity during its further processing.2O oxide is not wettable by copper causing the interfacial surfaces to be characterised with low mechanical strength, then in order to determine the places of Cu2O oxides crystallization and the bond strength of Cu-Cu2O at the interfacial surfaces and to define the mechanical properties of the copper strand a uniaxial tensile test was carried out using a testing machine with a maximum load of up to 2 tonnes. In order to perform the test from the prepared slices of strand samples were prepared as described in Since CuThe study focused on determining the mechanical properties of the copper strand in uniaxial tensile strength did not show significant differences in terms of UTS regardless of the direction of the applied force. When considering YS it may be stated that the measured values are higher when the dendrite orientation and tensile force are parallel and the direction of the tensile force is parallel to the shorter side of the strand and the fractures of these samples were characterized as ductile. However, when the direction of the tensile force is perpendicular to the shorter side of the strand the YS values did not show significant differences. When considering total elongation, the values are visibly higher when the direction of the tensile force is parallel to the shorter side of the strand. The average UTS was approximately 163.9 MPa and the mean YS was equal to 46.1 MPa. The divergence in elongation values of the tested samples was between 7 and 27%. Sample marked as 13 had an internal defect that made it impossible to correctly read the given values. In order to determine the cause of the differences in total elongation values SEM analyses of the fractures were conducted and the places of fracture were marked at Only one of the tested samples ruptured at the crystallization front (sample marked as 5). Prior to the conducted tests it was assumed that the crystallization front would be a place where numerous impurities in the material would accumulate and therefore the material would lose its cohesion and fracture at this area. Additionally, in both of the analysed cases it is easily noticeable that the rupture points are fairly symmetrical. The analysis of the stress-strain curves shows that the material, depending on the grain orientation had two types of characteristic courses of the curve. 2O oxides. Because of the observed and discussed previously symmetricity of the places where fractures occurred the analysis was carried out only for the first six samples in both parallel and perpendicular orientation of tensile force direction in relation to the shorter side of the strand. SEM analysis was conducted on the obtained fractures of the copper strand samples in order to determine the morphology and concentration of Cu2O oxide particles deeply embedded in the craters. In the case of samples marked as 3–6, 15 and 16 a higher ductile properties were observed as the crystallites were arranged parallelly to the direction of the tensile force. These results are in agreement with the studies conducted in [2O oxides were shallowly located in the fracture craters, however, not as numerous as in the former analysed case. Clearly visible are the surfaces of division of copper matrix confirming the location of deformation and necking formation.It may be stated that the crystallization zones strongly affect the macroscopic plastic properties of the material. Based on the obtained images presented in ucted in ,30,31. L2O oxides on the surfaces of dendrites (in interdendritic spaces) is present in the copper strand.As a result of the conducted research concerning microstructure analysis, chemical composition analysis, mechanical and electrical properties tests it was found that a discrete distribution of Cu2O oxides are not wettable by copper and therefore the interfacial surfaces are characterised with low strength properties. The analysis of own research conducted in this paper shows that the crystallographic orientation of the structure (dendrite orientation) has a huge impact on the behaviour of copper during deformation in the uniaxial tensile test.CuRegardless of the direction of the tensile force and orientation of the dendrites there were no visible changes in UTS values. However, when YS is considered it was confirmed that the measured values were higher when dendrite orientation and tensile force were aligned parallelly and the direction of the tensile force was parallel to the shorter side of the strand. The observed fractures of these samples were visibly ductile. On the other hand, when the direction of the tensile force was perpendicular to the shorter side of the strand the YS values did not show significant changes. Total elongation values were also higher when the direction of the tensile force was parallel to the shorter side of the strand.2O oxide particles is characteristic for specific fractures. Concerning brittle fractures, numerous oxides were located at the bottom of the craters while in the case of ductile fractures, the oxides were located shallowly (the oxides were pulled out of the copper matrix).The location of the Cu


Eosinophil granulocytes (eosinophils) belong to the family of white blood cells that play important roles in the development of asthma and various types of allergy. Eosinophils are cells with a diameter of 12–17 µm and they originate from myeloid precursors. They were discovered by Paul Ehrlich in 1879 in the process of staining fixed blood smears with aniline dyes. Apoptosis (programmed cell death) is the process by which cells lose their functionality. Therefore, it is very important to study the apoptosis of eosinophils and their survival factors to understand how to develop new drugs based on the modulation of eosinophil apoptosis for the treatment of asthma and allergic diseases.In the past 10 years, the number of people in the Czech Republic with allergies has doubled to over three million. Allergic pollen catarrh, constitutional dermatitis and asthma are the allergic disorders most often diagnosed. Genuine food allergies today affect 6–8% of nursing infants, 3–5% of small children, and 2–4% of adults. These disorders are connected with eosinophil granulocytes and their apoptosis. Eosinophil granulocytes are postmitotic leukocytes containing a number of histotoxic substances that contribute to the initiation and continuation of allergic inflammatory reactions. Eosinophilia results from the disruption of the standard half-life of eosinophils by the expression of mechanisms that block the apoptosis of eosinophils, leading to the development of chronic inflammation. Glucocorticoids are used as a strong acting anti-inflammatory medicine in the treatment of hypereosinophilia. The removal of eosinophils by the mechanism of apoptosis is the effect of this process. This work sums up the contemporary knowledge concerning the apoptosis of eosinophils, its role in the aforementioned disorders, and the indications for the use of glucocorticoids in their related therapies. Eosinophils play a key role in fighting large multicellular pathogens, such as nematode parasites. Although eosinophils are capable of bactericidal phagocytosis in vitro, it is not possible to effectively prevent bacterial infection in vivo if the function of neutrophils is reduced, such as in the case of pharmaceutically-induced neutropenia or leukocyte adhesion deficiency syndrome . EosinopParagonimus westermani causing pulmonary or extrapulmonary paragonimiasis induce eosinophil apoptosis ..125].There is ever-increasing evidence that eosinophil apoptosis can by delayed in cases of allergic disorders. There are at least two mechanisms responsible for this: the increased expression of eosinophil survival factors and the disruption of death signals. The identification of molecules participating in anti-apoptotic pathways in eosinophils offer hope for the development of new drugs to reduce the number of eosinophils and, accordingly, eosinophilic inflammation in cases of allergic diseases.


The World Health Organization (WHO) has recommended this type of care in both developed and developing countries as soon as the premature neonate is clinically stabilized2. The virus spread rapidly and by March 2020 over 100 countries were affected3. Owing to the high contagion and fatality rate of the virus and the WHO declaration of COVID-19 as a pandemic, routine medical care was impacted and consequently the rate of KMC may have also suffered.The COVID-19 pandemic originated in the Hubei province of China in December 20194. Human milk is a unique dynamic nutrition source for the newborn during the first 6 months of life. Human milk directly contributes to innate immunity of the newborn by shaping gut microbiota and milk oligosaccharides5.Clinical evidence shows KMC could be effective in improving the newborn's neurodevelopment outcomes, stabilize preterm newborn's physiological function and decrease maternal distress following the birth. KMC is effective in the initiation of exclusive breastfeeding6.Recently, the WHO recommended that mothers and newborns should not be separated. The dyads should enable the practice of KMC even in cases of suspected or confirmed COVID-19 by using personal protective equipment and the disinfection of used surfaces7, and as such consider KMC in the neonatal wards, with the use of all related precautions.We urge clinicians, midwives and policy makers to keep neonatal care at the frontline


In the Animals and housing subsection of the Materials and methods, there is an error in the sixteenth sentence of the first paragraph. The correct sentence is: After parturition, on post-partum day 1 (PPD 1), the size of litters with more than six puppies was adjusted by removing extra puppies by random selection to yield six puppies; the removed puppies were euthanized by intracardiac injection of sodium pentobarbital solution at 240 mg/mL and dose volume based on the standard operating procedures of the testing facility.


European Journal of Trauma and Emergency Surgery therefore focuses on recent aspects of chest trauma based on data from clinical and experimental studies, which underlines the relevance of bidirectional translational research.Chest trauma still represents one of the most frequent and devastating injuries after polytrauma. Besides the direct effects of the traumatic impact itself, lung integrity and function are also indirectly endangered by the systemic release of inflammatory mediators due to additional injuries of other body regions. Significant efforts have to be made to better understand the underlying pathomechanisms to improve diagnostic and therapeutic strategies. This issue of the The relevance of complications after chest trauma was a focus of the clinical studies of this issue. In a retrospective analysis, Huang et al. observed over an 8-year period  that almDue to a significant heterogeneity of the trauma population, experimental studies are of upmost importance to investigate the underlying pathomechanisms of posttraumatic complications and to establish new strategies. A model was introduced by Stormann et al., who investigated contributing factors for the development of acute lung injury (ALI) in a murine double hit model . To induThese innovations in diagnosis and therapy are essential to reliably prevent the patient from further harm and to improve posttraumatic outcomes. In this context, reliable assessment of the patient status is also necessary. Caspers et al. conducted a clinical study focusing on the role of microparticles (MP) after severe trauma . The autIn conclusion, the articles presented here reflect the current problems in patients with chest trauma and offer promising experimental models to study the pathomechanisms associated with this trauma entity. Furthermore, interesting aspects regarding future directions in diagnostic and therapeutic options are illustrated.We hope you enjoy reading our selections of topics around the importance of chest trauma in the clinical and experimental settings.


There is an error in the author designations. Linda Gailite and Anna Miskova do not share first authorship of the work. Instead, Linda Gailite and Anna Miskova share senior authorship of the work. The publisher apologizes for the error.


This paper considers a mathematical model of infectious disease of SIS type. We willanalyze the problem of minimizing the cost of diseases trough medical treatment.Mathematical modeling of this process leads to an optimal control problem with a finitehorizon. The necessary conditions for optimality are given. Using the optimalityconditions we prove the existence, uniqueness and stability of the steady state for adifferential equations system.


Concerns around assisted living (AL) quality have prompted the 2019 passage of the MN legislature, which provided funding for the development of an Assisted Living Report Card. We present results from the first two phases of this project. The first phase involved a national literature review of quality measures and technical advisory panels to understand the types of domains and indicators for AL quality that are measured. Nine quality domains were identified. The second phase focused on state-wide stakeholder engagement to determine priority rankings for nine AL quality domains and indicators identified. Quality of life, staff quality and resident safety were the top three domains across all stakeholder groups. The state will implement surveys of AL resident quality of life and family satisfaction as mandated by the legislature, but findings indicate that other aspects of quality such as staff-related measures and resident safety, are also important to address.


The pre-EMU pressure for structural adjustments and productivity gains would be restored.The coronavirus crisis has caused new distress in the European Economic and Monetary Union (EMU), as the southern part of the EMU has been hit stronger than the northern part. The common currency prevents nominal exchange rate adjustment in response to the asymmetric shock. Policymakers have therefore taken recourse to large-scale financial transfers. Based on the lessons from the German monetary union, this article proposes instead the introduction of parallel currencies to facilitate relative price changes. Parallel currencies in the south would allow an increase in competitiveness of the south via real depreciation. The introduction of a parallel currency in Germany would lead to capital inflows and a real appreciation of the


Welding technology may be considered as a promising processing method for the formation of packaging products from biopolymers. However, the welding processes used can change the properties of the polymer materials, especially in the region of the weld. In this contribution, the impact of the welding process on the structure and properties of biopolymer welds and their ability to undergo hydrolytic degradation will be discussed. Samples for the study were made from polylactide (PLA) and poly (PHA) biopolymers which were welded using two methods: ultrasonic and heated tool welding. Differential scanning calorimetry (DSC) analysis showed slight changes in the thermal properties of the samples resulting from the processing and welding method used. The results of hydrolytic degradation indicated that welds of selected biopolymers started to degrade faster than unwelded parts of the samples. The structure of degradation products at the molecular level was confirmed using mass spectrometry. It was found that hydrolysis of the PLA and PHA welds occurs via the random ester bond cleavage and leads to the formation of PLA and PHA oligomers terminated by hydroxyl and carboxyl end groups, similarly to as previously observed for unwelded PLA and PHA-based materials. Biodegradable polymers are the most developed class of new sustainable materials, leading to numerous technological innovations. In recent years, it has become extremely important to design polymer packaging materials that will be safe for human health and the environment, and to find new areas in which their unique properties can be adopted . The larThese applications usually require different joining methods of the polymeric materials. Welding could be considered the most effective method for thermoplastic polymeric materials such as PLA and PHB. The process of welding includes activation of the two surfaces, usually by heating them to a temperature higher than the melting point of a polymer, and joining the melted surfaces through the use of force. The most popular welding methods used in practice are heated tool welding, resistance welding, and ultrasonic and high-frequency welding. Butt and overlapping welding are also multipurpose methods that can be used for PLA and PHB biopolymers ,16. KlinAlthough the influence of processing methods  on the properties of the final products of PLA and PHA have previously been studied, the properties of welded products made of PLA and PHA polyesters have not been investigated in detail. Due to the fact that PLA and PHA are the most widely known biodegradable polyesters, and are currently produced on a large industrial scale, information on weld properties would be very important from an industrial application point of view.1H Nuclear Magnetic Resonance spectroscopy (NMR), Gel Permeation Chromatography (GPC), Differential Scanning Calorimetry (DSC), and Electrospray Ionization Mass Spectrometry (ESI-MS) have been used. Our approach is consistent with the concept of forensic engineering of advanced polymeric materials (FEAPM), which can help to understand the relationships between the structure of the biodegradable polymer material used, its properties, and behavior for practical applications . Th. ThTg waThe DSC trace of the starting PLA filament shows only a glass transition temperature that confirms the amorphous microstructure of this sample . The PLAmT value increase of the samples studied , the oligomers become water-soluble and diffuse into the surrounding medium. For all samples studied, a decrease of the pH values in the degradation media was observed, on account of the release of lactic or 3-hydroxybutyric acids and their low molar masses PLA and PHA oligomers terminated by hydroxyl and carboxyl end groups released from the tested samples into the water medium. This is accompanied by the disintegration of the tested solid samples (see further paragraphs). The smallest changes in pH were observed for sample PHA 3, due to the lower degradation rate of PHA than the PLA biopolymer. [gT from 1.7 to −2.8 °C , compared to other parts of PLA. After 84 days of incubation, PLA 1 completely lost its integrity and the degradation medium became turbid. In contrast, the surface of PLA 2 and PHA 3 and their welds remain unchanged for 14 days of hydrolytic degradation. After 42 days of incubation, the loss of weld cohesion of the weld was noticed in PLA 2; in the case of sample PHA 3, the weld bulges above the surface. However, it is worth noting that the parts of PLA 2 and PHA 3 in the vicinity of their welds did not disintegrate at that time. During further incubation, PLA 2 became swollen and prone to cracking, which resulted in the progression of disintegration of the sample and its disappearance after 182 days of degradation, similar to what was observed for PLA 1. In the case of PHA 3, the start of swelling of the weld was observed after 42 days of incubation while damages in the vicinity of the weld were only noticed after 182 days of incubation. The microscopic changes in PHA 3 were investigated using SEM analysis. As can be seen from the images of PHA 3 before degradation, weld cracks can be observed. This may be due to the internal tension or thermal treatment during welding. The visibly lighter color of the weld after 182 days of incubation indicates that the weld protrudes over the surface, which is in agreement with the macroscopic observation. The cracking process of the weld progresses during the incubation time, which may suggest faster degradation of the weld than the rest of PHA 3.The progress of the hydrolytic degradation process was also monitored by the analysis of the degradation media. It is well known that the hydrolysis of PLA and PHA occurs via random ester bond cleavage along the polyester chains which leads to the formation of shorter polyester chains. When the molar mass of the degraded PLA and PHA welded samples drops below a 700 g/mol, the oligomers become water-soluble and diffuse into the surrounding medium. To determine the chemical structure of water-soluble products formed during the hydrolytic degradation of PLA and PHA welded samples, mass spectrometry (ESI-MS) was used. The application of this technique in the structural studies of degradation products allowed us to detect even small amounts of the degradation products. Recently, ESI-MS techniques have been successfully used for the structural characterization at the molecular level of the degradation products of aliphatic polyesters ,35.The purpose of this research was to check whether the structure of degradation products released from welded PLA and PHA samples is the same as that previously observed in the case of unwelded PLA and PHA biopolyesters. Singly charged signals with a peak-to-peak mass increment of 72 Da, which is equal to the molar mass of the lactic acid repeating unit, were observed in this spectrum. The signals observed correspond to the sodium adducts of water-soluble lactic acid oligomers terminated by carboxyl and hydroxyl end groups  was higher than for the sample PHA (3). In the case of the PLA and PHA samples, the degradation process started in the region of the weld. The structural studies of the products released to the water were carried out with the aid of ESI-MS spectrometry. The lactic acid or 3-hydroxybutyrate oligomers terminated by hydroxyl and carboxyl end groups were identified as water-soluble degradation products for samples PLA (1 and 2) and PHA (3), respectively. No changes were observed in the structure of products released to media during hydrolytic degradation of welded materials when compared with the degradation products of unwelded PLA and PHA. The current study demonstrated the need for precise evaluation of the structure, properties, and behavior of advanced biodegradable polymer packing materials in order to avoid potential failures of the commercial products to be manufactured from them.


The doubling of genomic DNA during the S-phase of the cell cycle involves the global remodeling of chromatin at replication forks. The present review focuses on the eviction of nucleosomes in front of the replication forks to facilitate the passage of replication machinery and the mechanism of replication-coupled chromatin assembly behind the replication forks. The recycling of parental histones as well as the nuclear import and the assembly of newly synthesized histones are also discussed with regard to the epigenetic inheritance. The doubling of genomic DNA occurring in the S-phase involves a timely regulated remodeling of the entire chromatin. Indeed, each replication site requires the displacement of nucleosomes in front of the fork to enable the progression of the replication machinery and the reformation of chromatin behind the replication fork ,2. The mThe formation of nucleoprotein structures between histones and DNA facilitates the organization of the eukaryotic genome within the nucleus. Moreover, the histones and, specifically, the amino-terminal tails of core histones are subjected to post-translational modifications, which are involved in genetic regulation ,12. HencImportantly, during the S-phase of the cell cycle, the replication implies the doubling of the amount of DNA within the nucleus . Hence, The complex mechanism of chromatin duplication has been extensively studied over the past few decades. Chromatin replication involves the remodeling of the entire genome once per cell cycle to facilitate the passage of replication machinery and the reassembly of nucleosomes behind the replication fork. The focus of this review is to summarize and discuss the current knowledge on the processes occurring in front of and behind the replication fork. Here, we emphasize the histone processing rather than the bevy of chaperones and factors involved .Over the past few decades, replication-coupled assembly of chromatin has been extensively studied to understand how the cell packages the genetic material after its doubling . AlthougIt is generally believed that chromatin assembly is a stepwise process wherein the H3/H4 tetramer is first loaded onto DNA, followed by the deposition of the two heterodimers of H2A/H2B . This moXenopus laevis egg extracts revealed that the fate of the parental nucleosome did not follow a unique mechanism [Even though the mechanism of the deposition of the histone octamer behind the replication fork remains unclear, in recent years, it became important to explore the mechanism of inheritance of the epigenetic marks. This has been investigated by several groups, who revealed a number of difficulties in its achievement. The synchronization of the cells is clearly a critical point, as with any experiments focused on replication studies. The analyses of the inheritance of epigenetic marks require also the discrimination of newly synthesized histones and parental ones, and neo-synthesized DNA and parental DNA. Different strategies have been exploited for studying the transmission of the histone modifications following replication, which do not ease the interpretation and comparison of the details ,82. Impoechanism . In thesechanism ,86. Thusechanism . Physarum polycephalum [While it is generally believed that histone modifications contribute to the epigenetic information, histone variants have been associated with chromatin activities and, like histone modifications, are part of the epigenetic information . Therefocephalum . More recephalum ,91.In the present overview of chromatin remodeling associated with replication, we pinpointed some concerns that have been the focus of extensive research over the past few decades. Understanding the fine details of how the chromatin states are transmitted from one generation to the next one has a broad range of applications in life sciences. This leads researchers to revisit basic questions of chromatin replication for improving our knowledge, even though the basic chromatin subunit assembled behind the replication fork is a mixture of new and parental histones, which remains elusive. With the increasing evidence of relationships between epigenetics and cell destiny, recent works have hinted at the inheritance of histone modifications of parental histones through replication. It would be also interesting to collect experimental data on the inheritance of the parental histone variants and determine whether the positioning of new histone variants synthesized in the S-phase results in chromatin rearrangement behind replication fork. We must keep in mind that besides the obvious dynamics of replication, the chromatin subunit is not static as histone complexes are susceptible to exchange at different rates in living cells. The perspective of experiments providing information on the kinematics of chromatin replication in the nucleus rather than snapshots offers an exciting glimpse into the mechanisms of eukaryotic genetic transmission. It is certain that the field of chromatin biosynthesis will remain a challenging topic for future investigations.


This research analyses straw degradation inside straw bale walls in the region and develops the prediction of degradation inside straw bale walls. The results show that the straw inside straw bale walls have no serious concerns of degradation in the high hygrothermal environment in the region with only moderate concerns of degradation in the area 2–3 cm deep behind the lime render. The onsite investigations indicate that the degradation isopleth model can only predict straw conditions behind the rendering layer, whereas the isothermal model fits the complete situation inside straw bale walls. This research develops the models for predicting straw degradation levels inside a straw bale building in a warm (humid) continental climate. The impact of this research will help the growth of low carbon energy efficient straw bale construction with confidence pertaining to its long-term durability characteristics both in the region and regions sharing similar climatic features globally. Straw bale construction uses agricultural co-products in the building industry . This buThe climatic regions of China are classified by the Ministry of Housing and Urban-Rural Development (MOHURD) in the GB50178-93 . The cliThe construction technique was initially introduced to northern China by the Adventist Development and Relief Agency (ADRA) in 1998  and the To assess the durability issues of straw bale construction in the warm (humid) continental climate, this research aims to analyse the straw degradation through both experiments using specimens of straw bale walls and the inspection of an experimental building constructed in northeast China. Therefore, the objectives are to develop proper predicting models for straw degradation regarding the warm (humid) continental climate and to expand the construction of straw bale buildings in wider regions globally. The research begins with both laboratorial research and onsite research of straw degradation following the analysis of predicting models for the degradation process in comparison with the laboratorial and onsite research results.There are two kinds of degradation processes within straw bale walls, namely aerobic degradation and anaerobic degradation . The avaEven though different types of rendering materials have various permeabilities for water and air transmittances, all the rendering approaches typically provide a relatively sealed environment for the straw bales . The relThe environment inside straw bale walls can protect straw from the hostile activities of microorganisms. Bacteria and yeasts can only duplicate in high moisture conditions, and other than this, yeasts also need light to process the biochemical reactions which are essential for the growth of microorganisms . ConsideThe hygrothermal environment within the straw bale walls and absolute moisture content of straw are two critical factors that lead to straw degradation. As such, this section reviews the existing methods for predicting the critical hygrothermal within straw bale walls and the critical moisture content of straw for straw degradation.The isopleth system was designed to describe specific reactions from growth of different mould species in different hygrothermal environments . By consKey to understanding the potential degradation is an understanding of the relationship between the relative humidity, temperature, and the moisture content of the material. The sorption isotherm describes the direct relationship between the moisture content of hygroscopic materials and the surrounding RH environment . Hedlin The equation cannot convert the surrounding RH environments to moisture contents without knowing air temperatures. The air temperature can change rapidly in straw bale walls in real conditions which results in a restricted use of the equation in predicting the moisture content of straw bales in walls. Strømdahl used controlled climatic chambers to investigate the water absorption properties of four plant fibres in different temperatures . The sorn’ from 44 to 54 to indicate a closer prediction of the sorption isotherm of straw in diurnal situations [Yin et al.  further tuations .To assess the possibility of degradation induced by the high RH and high temperature conditions, an experimental investigation was designed to represent a typical wall build-up. The experimental results will be compared with onsite visits of one experimental building constructed in Changchun to access the degradation potential of straw within straw bale walls in northeast China.Changchun is the capital city of Jilin province  and the The monthly humidity levels are from 63% to 72% in summer during which the highest temperature appears. The climatic features of Changchun represent three typical climatic characteristics in the severe cold region in China: Firstly, both the air temperature and humidity are at high levels in summer months. The daily high temperatures are around 30 °C in the summer months. Due to the features of the warm (humid) continental climate, rainfalls are expected mostly in summer months which lead to high air humidity. Secondly, as the lowest rain potentials and air humidity are expected in spring months, the spring can be identified as a “dry” season in northern China. However, as air temperatures begin to rise above freezing in March, melting snow increases humidity levels in the severe cold region. Comparing the air humidity levels in April and May, the monthly average humidity of March is significantly higher than the one in April and May. Thirdly, the air temperatures are expected to be below freezing during the whole winter months in the severe cold region and the highest monthly air humidity levels present during the same period. In contrast, the high air humidity levels do not result in the humid environment inside and outside buildings . As the An experimental straw bale single-story bungalow with a double pitched roof was constructed in the southeast of Changchun . The layout of the building is similar to the existing residential building in rural regions of Northeast China. The structural frame and foundation of the experimental building are made of steel reinforced concrete, which is conventional in the area familiar to local builders. For the same reason, the building is designed to have a cold roof, thus the insulation layer in the roof is laid beneath the roof frames and above the ceiling. The experimental building is constructed in an open field on the campus of Jilin Jianzhu University. The building is oriented on cardinal directions and there are no structures or other obstructions around the building. As the building is for experimental purposes only, there is no heating system included in the building.There are two bale stacking methods used to examine the impact of straw orientation has on various properties, including durability and hygrothermal variation within the experimental building. The west flank of the building has laid-flat straw bales and the on-edge bales are used in the east flank . Due to The investigation of the degradation potential of straw uses a climate-controlled chamber to replicate the summer hygrothermal environments in Changchun. The model of the climatic chamber is DY110(C)  and can control the temperature to ±0.1 °C. Makhlouf et al., demonstrated the importance of measuring materials under representative environmental conditions within the lab , so the Straw bales and lime render are constructed in three transparent boxes to replicate walling constructions of straw bale buildings . The ricThe specimens were initially placed in a controlled climatic room (80% RH @ 20 °C) for one week to cure the lime render. The cured specimens are then placed in low temperature (40 °C) oven for one week to reach lower than 85% initial RH @ 30 °C before placing specimens in the climatic chamber. During the 12-week experimental period, the conditions of straw are visually checked once a week at the beginning of the four weeks and once a day for the following eight weeks.Due to different moisture adsorbing speeds of the straw, as demonstrated by Yin et al. , the limThe visual checks of the specimens do not identify any recognisable straw degradation both during the experimental process and at the end of the experiments . The surThe experimental results show that straw does not exhibit signs of notable degradation in the potential high hygrothermal environment in the severe cold regions of China. The property of low degradation potential of straw at high temperature has specific importance in building straw bale constructions in the severe cold region. Due to the low degradation potential of straw in the high hygrothermal environments behind lime render layers in the region, the straw bales in the buildings can be constructed in the summer months with a similar degree of degradation in other months in the climatic region.To examine the straw conditions behind the render in the experimental building, eight positions  were exaFrom the onsite investigation, the thickness of the render did not visibly impact the conditions of the straw, with even the thinnest render (40 mm) seeming to be sufficient. The thickness of lime rendering varies significantly from the design thickness , with thThe monitored results compare favorably to the isothermal models as presented by Lawrence et al.  and Yin While the overestimations of straw degradation by the isopleth model have been discussed in existing research, there has been little explanation for the inaccurate predictions of the isopleth model . In thisThe active PH range of the acidogenic and acetogenic bacteria is 6–10 and the methanogens have a smaller range of allowable pH range (7.5–8) . With thFirstly, the lime render would provide an unfavourable environment for the anaerobic decomposition of straw. The major content of lime is the calcium hydroxide which is a high alkaline pH material . The pH Secondly, the calcium hydroxide reacts with the intermediates of the anaerobic digestion of straw. Calcium hydroxide requires carbon dioxide in the chemical reaction of achieving calcium carbonate during the curing stage of lime based rendering and acetic acid is also neutralised by the high pH environment provided by the calcium hydroxide. As a result, the lime render reduces the intermediates of the anaerobic decomposition of straw and increasing the durability of straw bale walls. The effectiveness of lime rendering in increasing the durability of straw bale walls against anaerobic degradation remains uncertain .The degradation between the lime render and the straw bales indicates the effect of aerobic degradation of straw. Due to the relatively high breathability of the lime render, the oxygen condensation behind the lime render would not be as low as the one in the straw bales. As a result, the aerobic degradation happens in the area behind the lime render in straw bales. However, due to the alkaline environment provided by the lime render, the degradation of straw is not serious with a mix of lime render. The degradation of straw was identified 2–3 cm behind the lime render. Because of the oxygen inside straw bales are much lower than the adjacent area of lime render and the straw bales, the degradation does not penetrate straw bales . HoweverThe results of this research show moderate concerns of straw degradation between straw bales and the lime render regarding the climatic features in northern China. The experimental investigation shows that the hot and humid summer has insignificant impacts on the durability of straw bales within straw bale walls. The research has monitored a full-scale building in northeast China and compared it to laboratory scale results. This has resulted in lower degradation expectation of rice straw inside straw bale walls than the existing knowledge on the issue. In the small-scale, controlled conditions, rice straw has no notable degradation with two alignments in the 95% RH @ 35 °C for 12 weeks. Full scale building investigation identified limited degradation behind the render, whereas rice straw is in good condition with the protection of lime render and deep inside the walls. Due to the relatively high oxygen levels behind the lime render, the aerobic degradation is far more rapid than the anaerobic degradation, and the straw conditions against the lime render would be a concern pertaining to the durability of straw bale walls. Therefore, the isopleth models are suitable for predicting the straw degradation behind the rendering layer whereas the unsaturated isothermal model is more suitable for predicting degradation inside straw bale walls.The work of this research builds on the understanding of the application of existing predicting models of straw degradation inside straw bale walls in the warm (humid) continental climate. The research identifies a limited degradation risk of rice straw bales inside a lime-based render layer with both the flat laying and the on-edge laying methods in the climatic condition of the warm (humid) continental climate. Further, straw bale buildings in this area will benefit from the render construction with high properties of moisture transmittance and low breathability. The results of the research justify the feasibility of straw bale building in resisting degradation with the climatic features of the warm (humid) continental climate. The impact of this research will be the growth in low-carbon energy efficient straw bale construction with confidence pertaining to its long-term durability characteristics.


Extracellular vesicles are evolutionarily conserved nano-sized phospholipid membraned structures and released from virtually all types of cells into the extracellular space. Their ability to carry various molecular cargos  from one cell to the other to exert functional impact on the target cells enables them to play a significant role in cell to cell communication during follicular development. As the molecular signals carried by extracellular vesicles reflect the physiological status of the cells of origin, they are expected to mediate any effect of environmental or metabolic stress on the follicualr cells and the growing oocyte. Recent studies have evidenced that reproductive cells exposed to various environmental stressors (heat and oxidative stress) released extracellular vesicles enriched with mRNA and miRNA associated with stress response mechanisms. Moreover, the metabolic status of post-calving cows could be well-reflected in the follicular extracellular vesicle's miRNA profile, which signified the potential role of extracellular cellular vesicle molecular signals in mediating the effect of metabolic stress on follicular and oocyte development. In the present review, the potential role of extracellular vesicles in mediating the effect of environmental and metabolic stress in various reproductive cells and oocytes are thoroughly discussed Moreover, considering the importance of extracellular vesicles in shuttling protective or rescuing molecular signals during stress, their potential usage as means of targeted delivery of molecules to mitigate the effect of stress on oocytes are addressed as the focus of future research. Recurrent environmental and metabolic stress pose significant risk and disruption of the reproductive physiology. Over the past five decades, the intensive selection practices of dairy cows for higher milk yield have resulted in tremendous success in increasing the net milk yield. However, the increase in milk production has resulted in a concomitant reduction in fertility traits , which ipathways . ExperimDuring the course of folliculogenesis, continuous bi-directional communication between the oocyte and its encircling cumulus cells, granulosa cells, and theca cells, to exchange an oocyte and somatic cell factors, is indispensable for the ovulation of a developmentally competent oocyte, that can undergo through fertilization and the processes of embryogenesis . The gapThe formation of an antrum cavity filled with a serum-like fluid exudate called the follicular fluid is the defining phenomenon of the later stages of mammalian follicular development . The folExtracellular vesicles (EVs) are evolutionarily conserved nano-sized, phospholipid bilayer membraned structures of varying sizes released from virtually all types of cells through the exocytosis process into the extracellular space . EVs arein vitro oocyte maturation  . The CEEturation . In thatTo date, the role of EVs in shuttling the CEEF between the oocyte and the surrounding somatic cells is not reported. However, reports on the differential effect of EVs supplementation from the small and large follicles on cumulus expansion could indicate the potential role of EVs in shuttling the CEEFs between the ovarian somatic cells and gamete and vise versa . NeverthDue to its enclosed microenvironment, the follicle is convenient to study the EV-signaling mechanism, as the source of the EVs and recipient cells can easily be pinpointed. Another advantage of the follicular microenvironment is the remarkable stability of the RNA molecules in the follicular fluid and other reproductive biological fluid, irrespective of the higher nuclease activity, which could be attributed to the encapsulation in EVs . This maAmong the determinant factors that contribute to the decline of female fertility is exposure to both environmental and metabolic stresses. Among the environmental stressors, oxidative  and heat2O2 has a longer cellular half-life and can enter into the nucleus   . One of oduction . The ext process . Interes process .2O2 are enriched with NRF2 and antioxidant enzymes (CAT and TXN1), signifying the fact that EVs could partly reflect the cellular stress conditions considering the presence of stress-associated transcripts both in the cells and the released EVs  to bovine granulosa cells at a dose as low as 150 mM induced apoptosis and reduced proliferation of cells, which signifies the toxic effects of NEFA accumulation during the post-partum period on the follicular cells in bovine (The intensive selection for high milk yield in the past decades has resulted in a significant increment in the amount of milk per lactation per cow. However, a concomitant reduction in the fertility traits of high yielding dairy cows was also observed . The decn bovine .We recently examined the miRNAs content of EVs derived from follicular fluid of cows under divergent metabolic status post-calving and results showed a massive down-regulation of miRNAs in follicular fluid EVs of cows under NEB . Based oOne of the fundamental aspects of EVs-mediated transfer of bioactive molecules is the balance between the molecules remained in the cells and those released into the extracellular space. EVs released into the body fluid could indicate the level of intracellular hemostasis . Similarin vitro production of embryos, which arises from the various stress-inducing factors under in vitro environment including the oxygen tension and culture media constituents compared to their in vivo counterparts.The importance of EVs as molecular cargo in mediating mammalian follicular development has been characterized in several reproductive biofluids. Nevertheless, the functional role of these EVs and their cargo molecules are not fully understood. Considering the important roles of EVs in shuttling the protective and rescuing signals in follicular cells, it would highlight the potential usage of EVs as a means of molecule delivery, which could be utilized for future applications to mitigate the effect of stress on oocytes and embryo development. The molecular characterization of the cargo of EVs with a potential impact on oocyte and embryo development could lead to the discovery of molecular markers for the development of stress-associated infertility treatment strategies. Therefore, characterizing the content of EVs released from granulosa cells and oviductal epithelial cells after exposure to environmental and metabolic stress could provide useful insight about the survival mechanisms of reproductive cells and possible usage of these EVs as supplementation into the oocyte maturation and embryo culture medium to enhance stress-coping mechanism during oocytes maturation and embryos development. This will be relevant to address the issue of the qualitative and quantitative decline in the outcome of the SG and DT: literature searches. SG: writing. AA: illustration. DT, AA, AG, and RP: editing. DT, AG, and RP: approving and submission. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


A new approach for droplet coalescence in microfluidic channels based on selective surface energy alteration is demonstrated. The proposed method involves patterning the surface of cyclic olefin copolymer (COC), a hydrophobic substrate attached to a polydimethylsiloxane hydrophobic microchannel, with graphene oxide (GO) using standard microfabrication techniques. Surface wettability and adhesion analyses confirmed the enhancement of the COC surface energy upon GO patterning and the stability of the GO film on COC. Three representative cases are illustrated to demonstrate the effectiveness of the method on the coalescence of droplets for different droplet flow regimes, as well as the effect of changing the size of the patterned surface area on the fusion process. The method achieves droplet coalescence without the need for precise synchronization. Coalescence of droplets in microfluidic systems offers many advantages such as high mixing rates, continuous separation of multiphase systems, and creating reaction-controlled nanoliter-sized individual reactors ,2,3. TheDroplets coalescence techniques in microfluidic channels can be classified into active and passive techniques. Active techniques utilize an external field to generate energy that destabilizes the interfaces of adjacent droplets leading to droplet fusion ,3. Such Recent studies of geometrically induced coalescence included inducing droplet coalescence in the merging zone of Y- and T-junction channels ,16, and In the present paper we report a new approach for droplet coalescence based on selective alteration of the surface wettability of the microfluidic channel using graphene oxide (GO). This approach involves the fabrication of a polydimethylsiloxane (PDMS) microchannel on a hydrophobic planar cyclic olefin copolymer (COC) substrate patterned with hydrophilic graphene oxide (GO) using standard microfabrication techniques.The patterning of COC substrates  with GO  was achieved using plasma-enhanced lift-off method ,21. BrieThe surface energy enhancement of the COC substrate was assessed by measuring the static contact angle of a water droplet on the COC substrate with and without GO deposition. The surface energy enhancement was further investigated by measuring the contact angle for different concentrations of GO dispersion deposited on COC wafers. Five GO dispersions were prepared with concentrations of 2, 4, 6, 8, and 10 mg/mL, respectively, and were deposited on plasma treated COC wafers using a spin coater at 4000 rpm. The stability of the GO film on the COC wafer was also studied using the JIS K-6744 boiling water test. A COC wafer was coated with GO with a concentration of 4 mg/mL, as discussed above, and was immersed in boiling water for an hour. Optical microscopic images were taken at several locations of the COC wafer before and after the test. The ability to selectively enhance the surface energy of COC by GO patterning is used to control the wettability inside microfluidic systems to achieve droplet coalescence. The droplet coalescence mechanism observed in the proposed device is composed of three steps: trapping, fusion, and detachment of the merged composite droplet. The coalescence of water droplets using GO bands that are patterned perpendicular to the flow or with an angle along the channel is investigated. The succeeding droplets continue to coalesce with the merged droplet as long as the adhesion forces, due to the patterned enhanced surface energy of the surface, dominates the viscous drag force of the fluid. As the magnitude of the viscous drag force exceeds the surface forces, the merged droplet detaches from the GO pattern. Several case studies have been conducted to examine the effect of the length and the orientation of the GO pattern on 1) The coalescence of droplets exhibiting different flow regimes, and on 2) The detachment mechanism of the merged droplet. Three representative cases will be illustrated. The first case demonstrates the detachment process of the merged droplet created from disc or pancake-shaped droplets and its relation to the number of coalescing droplets, the second case demonstrates the coalescing of two slug droplets over a narrow band of GO (~10 µm), and the third case illustrates the effect of patterning GO for coalescing droplets and directing the motion of the merged droplet to a specific path.Disc-shaped droplets are the ones confined between the top and bottom sides of the channel with a size smaller than the width of the channel. Controlling the flow and the coalescence of such droplets permits the creation of microdroplet reactors, where merging droplets of different components is necessary at a selected site in the microchannel.Theoretically, the detachment of the merged droplet in this regime is initiated as the viscous drag force exerted by the continuous phase overcomes the force due to the enhanced surface energy . In the ed phase ) increasFrom the discussion above, the number of merging droplets depends on the competing forces of the increasing viscous drag force and the surface tension on the merged droplet. For example, an increase in the continuous flow velocity results in merging smaller number of droplets compared to a lower velocity of the continuous phase. Similarly, merging of droplets with large diameters will result in the merging of a fewer number of droplets compared to merging of droplets with smaller diameters. The second case demonstrates the coalescing of two slug droplets over a narrow band of GO ~10 µm). Slug droplets are droplets that are confined by the four walls of the channel and that have a length that is mainly affected by the phase flow rate ratio of the inlet streams at the droplet generation stage 0 µm. Slu. These fThe third case illustrates the effect of patterning GO for coalescing droplets and directing the motion of the merged droplet to a specific path. The coupled functions of coalescence and steering allow the construction of microfluidic systems that provide controlled reaction networks with no dispersion between the steered droplets . A narroIn this paper we present a new approach for droplet coalescence in microchannels by patterning the surface energy of a hydrophobic substrate with GO using standard microfabrication techniques. This approach is based on selective patterning of the surface energy of a hydrophobic surface for trapping dispersed droplets prior to their fusion. The GO patterned films on the COC were found to be stable at high thermal stresses without evidence of peeling off or deformation. Three representative cases were illustrated to demonstrate the effectiveness of the method on the fusion of droplets exhibiting different flow regimes and having different initial diameters, as well as the effect of changing the size of the patterned surface area on the fusion process. The results showed that the coalescence process depends on initial wetting of the GO with a thin film of water molecules prior to the trapping step. In addition, simultaneous coalescence and transport of the droplets inside the channel was achievable by manipulating the viscous drag forces in relation to the surface adhesion induced by the GO pattern. We believe this method will be useful for various micro-scale processes such as liquid–liquid phase separation, micro-extraction, and reaction networks.