bluuebunny/crossref_metadata_2025 huggingface dataset:
In vivo and in vitro Characterization of a Partial Mu Opioid Receptor Agonist, NKTR-181, Supports Future Therapeutic Development
Authors: Lee Alex S. , Tiwari Suchi , Bishop Isabel , Matossian Vartan , Romaneschi Nicole , Miyazaki Takahiro , VanderVeen Laurie , Zalevsky Jonathan , DeFea Kathryn , Cahill Catherine M. , Walwyn Wendy M.
Published: August 2021

Mu opioid receptor (MOPr) agonists are well-known and frequently used clinical analgesics but are also rewarding due to their highly addictive and often abusive properties. This may lead to opioid use disorder (OUD) a disorder that effects millions of people worldwide. Therefore, novel compounds are urgently needed to treat OUD. As opioids are effective analgesics and OUD often occurs in conjunction with chronic pain, these novel compounds may be opioids, but they must have a low abuse liability. This could be mediated by diminishing or slowing blood-brain barrier transport, slowing target receptor binding kinetics, and showing a long half-life. NKTR-181 is a PEGylated oxycodol and a MOPr agonist that has slowed blood-brain barrier transport, a long half-life, and diminished likeability in clinical trials. In this study, we examined the signaling and behavioral profile of NKTR-181 in comparison with oxycodone to determine whether further therapeutic development of this compound may be warranted. For this preclinical study, we used a number of in vitro and in vivo assays. The signaling profile of NKTR-181 was determined by the electrophysiological assessment of MOPr-Ca2+ channel inhibition in the nociceptive neurons of rodent dorsal root ganglia. Heterologous cell-based assays were used to assess biased agonism and receptor trafficking. Different rodent behavioral models were used to define the NKTR-181-induced relief of effective and reflexive nociception and drug-seeking behavior as assessed by an intravenous self-administration (IVSA) of NKTR-181. We found that NKTR-181 and oxycodone are partial agonists in G-protein signaling and Ca2+ channel inhibition assays and promote limited MOPr desensitization. However, NKTR-181 inhibits Ca2+ channels by a different mechanism than oxycodone and induces a different pattern of arrestin recruitment. In addition, NKTR-181 has a slower receptor on-rate and a slower rate of Ca2+ channel coupling than oxycodone. This signaling profile is coupled with a slower onset of antinociception and limited drug-seeking behavior in comparison with oxycodone. Together with its known long half-life and slow blood-brain barrier transport, these data suggest that NKTR-181 could be further studied as a pharmacotherapeutic treatment modality for OUD.
Molecular Characterization of α- and β-Thalassaemia Among Children From 1 to 10 Years of Age in Guangxi, A Multi-Ethnic Region in Southern China
Authors: He Sheng , Li Dongming , Yi Shang , Huang Xiuning , Zhou Chaofan , Chen Biyan , Zuo Yangjin , Lin Li , Chen Faqin , Wei Hongwei
Published: August 2021

Background: Thalassemia is one of the most common genetic diseases in southern China. Howerver, population in different regions or different population has their own spectrums of thalassemia. To investigate the prevalence and spectrum features of thalassemia among children in Guangxi. Hematology and genetic analysis were performed on 71,459 children aged 1–10 years in various regions of Guangxi.

Results: A total of 11,821 children were diagnoses with thalassemia including 7,615 (10.66%) subjects of α-thalassemia, 3,507 (4.90%) subjects of β-thalassemia, and 699 (0.98%) cases with both α- and β-thalassemia. Nine α-thalassemia mutations and 30 genotypes were identified among the α-thalassemia children. The - -SEA and - -SEA/αα were the most frequent mutation and genotype, respectively. One α-thalassemia fusion gene and a rare 2.4 kb deletion both causing α+-thalassemia were identified, respectively. Thirteen β-thalassemia mutations and 31 genotypes were characterized among the β-thalassemia children, with the most common mutation CD41-42 (-CTTT) accounting for 46.05% of the β-mutations. Two rare mutations IVS-II-5 (G>C), and IVS-I-2 (T>C) were firstly identified. Furthermore, 92 genotypes were identified among 699 children with both α- and β-thalassemia.

Conclusions: Our findings highlight the great heterogeneity and the extensive spectrum of thalassemia among children in Guangxi, which provide an available reference for prevention of thalassemia in this area.
A Metabolic Profiling Study of Realgar-Induced Acute Kidney Injury in Mice
Authors: Zhang Sheng , Li Chao , Feng Tingting , Cao Shuai , Zhou Heng , Li Limin , Hu Qing , Mao Xiuhong , Ji Shen
Published: August 2021

Realgar has been used as a type of mineral drug that contains arsenic for thousands of years. Previous studies have shown that Realgar-induced acute kidney injury is associated with abnormal metabolism, but the underlying mechanism is poorly understood. The aim of this study is to investigate the metabolic changes in serum and kidney tissues of mice exposed to Realgar by using a metabolomic approach and explore the molecular mechanisms of acute kidney injury induced by Realgar. Forty mice were randomly divided into four groups: Control group, 0.5-, 1.0, and 2.0 g/kg Realgar group. After 1 week, the body weight and kidney weight of the mice were measured. The serum and kidney samples were used for LC-MS spectroscopic metabolic profiling. Principal component analysis (PCA), correlation analysis, and pathway analysis were used to detect the nephrotoxic effects of Realgar. Body weight decreased significantly in the 2.0 g/kg group, and the kidney weight index also showed a dose-dependent increase in Realgar. The PCA score plot showed the serum and kidney tissue metabolic profile of mice exposed to 2.0 g/kg Realgar separated from the control group, while the lower-doses of 0.5 g/kg and 1.0 g/kg Realgar shown a similar view to the Control group. Thirty-three metabolites and seventeen metabolites were screened and identified in the serum and kidney of mice in a dose-dependent manner. respectively. Correlation analysis showed a strong correlation among these metabolites. Amino acid metabolism, lipid metabolism, glutathione metabolism, and purine metabolism pathways were found to be mainly associated with Realgar nephrotoxicity. This work illustrated the metabolic alterations in Realgar-induced nephrotoxic mice through a metabolomic approach.
Neuroprotective Potential of Non-Digestible Oligosaccharides: An Overview of Experimental Evidence
Authors: Divyashri Gangaraju , Sadanandan Bindu , Chidambara Murthy Kotamballi N , Shetty Kalidas , Mamta Kumari
Published: August 2021

Non-digestible oligosaccharides (NDOs) from dietary sources have the potential as prebiotics for neuroprotection. Globally, diverse populations suffering from one or the other forms of neurodegenerative disorders are on the rise, and NDOs have the potential as supportive complementary therapeutic options against these oxidative-linked disorders. Elevated levels of free radicals cause oxidative damage to biological molecules like proteins, lipids, and nucleic acids associated with various neurological disorders. Therefore, investigating the therapeutic or prophylactic potential of prebiotic bioactive molecules such as NDOs as supplements for brain and cognitive health has merits. Few prebiotic NDOs have shown promise as persuasive therapeutic solutions to counter oxidative stress by neutralizing free radicals directly or indirectly. Furthermore, they are also known to modulate through brain-derived neurotrophic factors through direct and indirect mechanisms conferring neuroprotective and neuromodulating benefits. Specifically, NDOs such as fructo-oligosaccharides, xylo-oligosaccharides, isomalto-oligosaccharides, manno-oligosaccharides, pectic-oligosaccharides, and similar oligosaccharides positively influence the overall health via various mechanisms. Increasing evidence has suggested that the beneficial role of such prebiotic NDOs is not only directed towards the colon but also distal organs including the brain. Despite the wide applications of these classes of NDOs as health supplements, there is limited understanding of the possible role of these NDOs as neuroprotective therapeutics. This review provides important insights into prebiotic NDOs, their source, and production with special emphasis on existing direct and indirect evidence of their therapeutic potential in neuroprotection.
New Peptides as Potential Players in the Crosstalk Between the Brain and Obesity, Metabolic and Cardiovascular Diseases
Authors: Czerwińska Magdalena , Czarzasta Katarzyna , Cudnoch-Jędrzejewska Agnieszka
Published: August 2021

According to the World Health Organization report published in 2016, 650 million people worldwide suffer from obesity, almost three times more than in 1975. Obesity is defined as excessive fat accumulation which may impair health with non-communicable diseases such as diabetes, cardiovascular diseases (hypertension, coronary artery disease, stroke), and some cancers. Despite medical advances, cardiovascular complications are still the leading causes of death arising from obesity. Excessive fat accumulation is caused by the imbalance between energy intake and expenditure. The pathogenesis of this process is complex and not fully understood, but current research is focused on the role of the complex crosstalk between the central nervous system (CNS), neuroendocrine and immune system including the autonomic nervous system, adipose tissue, digestive and cardiovascular systems. Additionally, special attention has been paid to newly discovered substances: neuropeptide 26RFa, preptin, and adropin. It was shown that the above peptides are synthesized both in numerous structures of the CNS and in many peripheral organs and tissues, such as the heart, adipose tissue, and the gastrointestinal tract. Recently, particular attention has been paid to the role of the presented peptides in the pathogenesis of obesity, metabolic and cardiovascular system diseases. This review summarizes the role of newly investigated peptides in the crosstalk between brain and peripheral organs in the pathogenesis of obesity, metabolic, and cardiovascular diseases.
Biochar-Enhanced Resistance to Botrytis cinerea in Strawberry Fruits (But Not Leaves) Is Associated With Changes in the Rhizosphere Microbiome
Authors: De Tender Caroline , Vandecasteele Bart , Verstraeten Bruno , Ommeslag Sarah , Kyndt Tina , Debode Jane
Published: August 2021

Biochar has been reported to play a positive role in disease suppression against airborne pathogens in plants. The mechanisms behind this positive trait are not well-understood. In this study, we hypothesized that the attraction of plant growth-promoting rhizobacteria (PGPR) or fungi (PGPF) underlies the mechanism of biochar in plant protection. The attraction of PGPR and PGPF may either activate the innate immune system of plants or help the plants with nutrient uptake. We studied the effect of biochar in peat substrate (PS) on the susceptibility of strawberry, both on leaves and fruits, against the airborne fungal pathogen Botrytis cinerea. Biochar had a positive impact on the resistance of strawberry fruits but not the plant leaves. On leaves, the infection was more severe compared with plants without biochar in the PS. The different effects on fruits and plant leaves may indicate a trade-off between plant parts. Future studies should focus on monitoring gene expression and metabolites of strawberry fruits to investigate this potential trade-off effect. A change in the microbial community in the rhizosphere was also observed, with increased fungal diversity and higher abundances of amplicon sequence variants classified into Granulicella, Mucilaginibacter, and Byssochlamys surrounding the plant root, where the latter two were reported as biocontrol agents. The change in the microbial community was not correlated with a change in nutrient uptake by the plant in either the leaves or the fruits. A decrease in the defense gene expression in the leaves was observed. In conclusion, the decreased infection of B. cinerea in strawberry fruits mediated by the addition of biochar in the PS is most likely regulated by the changes in the microbial community.
Innovation Strategy of Cultivating Innovative Enterprise Talents for Young Entrepreneurs Under Higher Education
Authors: Yu Xiao , Zhang Baoge
Published: August 2021

A time series model is designed based on the backpropagation neural network to further optimize the innovation and development of new ventures. The specific situation of two factors is primarily analyzed as follows: the supply and demand ratio of enterprise talents and the state of entrepreneurship in the development of new ventures. The results show that the potential demand of future enterprises for big data talents can be obtained by fitting prediction sequences. Based on the Backpropagation–Autoregressive Integrated Moving Average model, the post modeling and prediction are carried out, and the coefficient 0.6235 is obtained by substituting the equation of Pearson's correlation coefficient. The analysis results suggest that the matching needs to be strengthened between the cultivation of innovative talents in universities and the demand trend of big data-related positions in enterprises. Moreover, there is a mismatch between the cultivation of innovative talents and the demand for innovative talents. Meanwhile, the mental health level of young entrepreneurs is concerned. The mental health status of young entrepreneurs is compared with the national norm data through the questionnaire survey and statistical data analysis. The results reveal that the mental health level of young entrepreneurs is significantly lower than that of the national norm, and the proportion of anxiety and depression is 29.4% and 27.5%, respectively. Considering the professional characteristics and competitive environment of young entrepreneurs, busy work and the multiple missions given by society to entrepreneurs are the major reasons for their pressure, and mental health problems are serious.
Stressful Experiences, Connection, and Depressive Symptoms Among Taiwanese Han and Indigenous Youth
Authors: Yang Pei-Jung
Published: August 2021

This study examined Taiwanese Han and indigenous (Tayal) youth’s experiences of stressful life events, the association between stressful experiences and depressive symptomology, and also the indirect and interactive effects of connection on the relationship between stressful experiences and depressive symptomology. Taiwanese Han (97%) is the majority group, whereas indigenous people make up 2.3% of Taiwan’s population. Taiwanese indigenous people have experienced disparities across socio-historical, educational, and economic aspects of their lives. This study included 291 eighth-grade participants (40% from the Tayal tribe, 48.8% female, and Mage = 13.44). The Han sample in this study all lived in cities, and the Tayal sample all lived in the tribal areas of the Northern Taiwan mountain regions. Person-centered (latent class analyses) and cumulative (sum of items) approaches were used to investigate family and school stressful events, respectively. Hierarchical regression analyses were conducted separately for the Han and Tayal participants to examine the role of family and school connection in relation to family and school stressors and depressive symptomology. Our results showed that stressful experiences are clearly linked to depressive symptomology and family connection was important to both Tayal and Han youth in supporting their coping with depressive symptoms. However, Tayal youth might be particularly vulnerable to family stressful events because family stressors disrupted their connection with their parents and thereby minimized the protective function of family relationships. To decrease the likely onset of depression during early adolescence, our results suggest that it is important for parents and other family members to monitor adolescents’ daily experiences of stress and provide support when needed. Furthermore, mental health interventions need to be tailored specifically for youth in specific racial, social, and economic contexts. Tayal youth mental health might benefit particularly from increasing school connection and decreasing stresses experienced in family contexts. Implications, limitations, and recommendations for future research are discussed.
Scientific Creativity: Discovery and Invention as Combinatorial
Authors: Simonton Dean Keith
Published: August 2021

Although scientific creativity has often been described as combinatorial, the description is usually insufficiently formulated to count as a precise scientific explanation. Therefore, the current article is devoted to elaborating a formalization defined by three combinatorial parameters: the initial probabilityp, the final utilityu, and the scientist’s prior knowledge of that utilityv. These parameters then lead logically to an 8-fold typology involving two forms of expertise, two irrational combinations, and four “blind” combinations. One of the latter provides the basis for the definition of personal creativity asc=(1−p)u(1−v), that is, the multiplicative product of originality, utility, and surprise. This three-criterion definition then has six critical implications. Those implications lead to a discussion of various combinatorial processes and procedures that include a treatment of the No Free Lunch Theorems regarding optimization algorithms as well as the creativity-maximizing phenomena of mind wandering and serendipity. The article closes with a discussion of how scientific creativity differs from artistic creativity. Besides the obvious contrasts in the ideas entering the combinatorial processes and procedures, scientific combinations, products, and communities strikingly differ from those typical of the arts. These differences also imply contrasts in developmental experiences and personality characteristics. In sum, the formal combinatorial analysis enhances our understanding of scientific creativity.
Mapping Trends and Hotspots Regarding Clinical Research on COVID-19: A Bibliometric Analysis of Global Research
Authors: Xia Demeng , Yao Renqi , Wang Sheng , Chen Gaoqi , Wang Yin
Published: August 2021

Purpose: The coronavirus disease 2019 (COVID-19) outbreak, which began in December 2019, has not been completely controlled; therefore, COVID-19 has received much attention from countries around the world. Many related clinical studies, such as clinical trials, have been published, but to the knowledge of the authors, there has been no bibliometric analysis of these publications focusing on clinical research studies on COVID-19.

Methods: Global publications on COVID-19 from January 2020 to December 2020 were extracted from the Web of Science (WOS) collection database. The VOSviewer software and CiteSpace were employed to perform a bibliometric study. In addition, we obtained information on relevant clinical trials from the website http://clinicaltrials.gov.

Results: China published most of the articles in this field and had the highest number of citations and H-index. The Journal of Medical Virology published most of the articles related to COVID-19. In terms of institutions, Huazhong University of Science and Technology had the most publications, and Wang, JW received the highest number of citations.

Conclusion: The diagnosis, prevention, and prognosis of COVID-19 are still the focus of attention at present. The overall analysis of the disease were identified as the emerging topics from the perspectives of epidemiology and statistics. However, finding an effective treatment remains the focus of clinical trials.
Developmental Disability: Families and Functioning in Child and Adolescence
Authors: Rosenbaum Peter
Published: August 2021

The WHO's International Classification of Functioning, Disability and Health (ICF) provides an integrated framework for health for everyone. Several aspects of this approach to health allow us to see people's lives in a richer and more holistic manner than has traditionally been the case based on diagnosis alone. These features include the positive language (emphasizing in particular “activity,” “participation,” and “personal factors”); the interconnections of the parts of this “dynamic system,” in which every component can influence every other one; and the formal inclusion of “contextual factors”—personal and environmental—that are otherwise too easy to take for granted and then ignore. This paper addresses the “environmental” dimension of the ICF framework—specifically referring to “family” as the central environmental force in the lives of children and adolescents. The perspectives of the author are those of a developmental pediatrician, whose career has focused on children with conditions that challenge their development, and their families. Lessons learned from a lifetime of work—including teaching and research as well as clinical services—are offered. Particular emphases will be on (i) the importance of focusing on the family in a non-judgmental “family-centered” way; (ii) how conceptual ideas about child (and family) development and parenting are as important as technical approaches to intervention; and (iii) how the ICF framework “allows”—indeed encourages—such a focus to have value and importance equal to the best of biomedical interventions. Examples from current research will illustrate how these ideas can be implemented.
Osteoarthritis Progression: Mitigation and Rehabilitation Strategies
Authors: Drummer Devin , McAdam Jeremy , Seay Regina , Ferrando Arny , Bridges S. Louis , Singh Jasvinder A. , Bamman Marcas
Published: August 2021

Osteoarthritis is the most common form of arthritis and is a substantial burden for patients with the disease. Currently, there is no cure for osteoarthritis, but many emerging therapies have been developed to aid in the mitigation of disease progression. When osteoarthritis reaches the end-stage of disease many patients undergo total joint arthroplasty to improve quality of life, yet some experience persistent pain and mobility limitations for extended periods following surgery. This review highlights recent therapeutic advancements in osteoarthritis treatment consisting of pharmacologics, nutraceuticals, biologics, and exercise while emphasizing the current state of post-arthroplasty rehabilitation.
Quantifying Muscle Forces and Joint Loading During Hip Exercises Performed With and Without an Elastic Resistance Band
Authors: Buehler Callum , Koller Willi , De Comtes Florentina , Kainz Hans
Published: August 2021

An increase in hip joint contact forces (HJCFs) is one of the main contributing mechanical causes of hip joint pathologies, such as hip osteoarthritis, and its progression. The strengthening of the surrounding muscles of the joint is a way to increase joint stability, which results in the reduction of HJCF. Most of the exercise recommendations are based on expert opinions instead of evidence-based facts. This study aimed to quantify muscle forces and joint loading during rehabilitative exercises using an elastic resistance band (ERB). Hip exercise movements of 16 healthy volunteers were recorded using a three-dimensional motion capture system and two force plates. All exercises were performed without and with an ERB and two execution velocities. Hip joint kinematics, kinetics, muscle forces, and HJCF were calculated based on the musculoskeletal simulations in OpenSim. Time-normalized waveforms of the different exercise modalities were compared with each other and with reference values found during walking. The results showed that training with an ERB increases both target muscle forces and HJCF. Furthermore, the ERB reduced the hip joint range of motion during the exercises. The type of ERB used (soft vs. stiff ERB) and the execution velocity of the exercise had a minor impact on the peak muscle forces and HJCF. The velocity of exercise execution, however, had an influence on the total required muscle force. Performing hip exercises without an ERB resulted in similar or lower peak HJCF and lower muscle forces than those found during walking. Adding an ERB during hip exercises increased the peak muscle and HJCF but the values remained below those found during walking. Our workflow and findings can be used in conjunction with future studies to support exercise design.
Characterization and Analysis of a Flexural Shape Memory Alloy Actuator
Authors: Dauksher Richard , Patterson Zachary , Majidi Carmel
Published: August 2021

Shape memory alloys (SMAs) are popular as actuators for use in soft robots due to their high work density and compatibility with miniaturized on-board batteries and power electronics. However, because SMA actuators are activated through electrical Joule heating, they exhibit poor energy efficiency and low actuator frequencies that arise from long cool-down times. Moreover, in the case of SMA wires that are subject to flexural loading, their load capacity and mechanical work output decrease exponentially with decreasing cross-sectional area. In this study, we perform analytic and numerical analyses to examine the thermal and structural design space around a particular class of flexural SMA wire actuators with the intention of increasing actuator operating frequency and actuation forces. Measurements obtained through experimental testing are consistent with theoretical studies of actuator force output and provide additional insight into the efficiency of electrical-to-mechanical energy conversion. Together, the theoretical and experimental studies provide insights that have the potential to inform SMA wire design and usage in soft robotic applications.
Effects of Nitrification Inhibitors on Soil Nitrification and Ammonia Volatilization in Three Soils with Different pH
Authors: Cui Lei , Li Dongpo , Wu Zhijie , Xue Yan , Xiao Furong , Zhang Lili , Song Yuchao , Li Yonghua , Zheng Ye , Zhang Jinming , Cui Yongkun
Published: August 2021

The application of nitrification inhibitors (NIs) is considered to be an efficient way to delay nitrification, but the effect of NIs combinations on soil nitrification and ammonia (NH3) volatilization are not clear in soils with different pH values. In this study, we explored the effect of nitrapyrin (CP) and its combinations with 3, 4-dimethylepyrazole phosphate (DMPP), dicyandiamide (DCD) on the transformation of nitrogen, potential nitrification rate (PNR), and ammonia (NH3) volatilization in a 120-day incubation experiment with three different pH values of black soil. Treatments included no fertilizer (Control), ammonium sulfate (AS), AS+CP (CP), AS+CP+DMPP (CP+DMPP), and AS+CP+DCD (CP+DCD). The application of NIs significantly decreased NO3−-N contents and potential nitrification rate (p < 0.05), while significantly increased NH4+-N contents (p < 0.05), especially CP+DCD and CP+DMPP were the most effective in the neutral and alkaline soils, respectively. In the acid soil, CP significantly increased total NH3 volatilization by 31%, while CP+DCD significantly reduced by 28% compared with AS. However, no significant difference was found in NH3 volatilization with and without NIs treatments (p > 0.05) in the neutral and alkaline soils. In conclusion, the combined nitrification inhibitors had the better efficiency in all three tested soils. CP+DCD and CP+DMPP are the most effective in inhibiting soil nitrification in the clay soils with higher pH value and lower organic matter, while CP+DCD had the potential in mitigating environment pollution by reducing N loss of NH3 volatilization in the loam soil with lower pH value and higher organic matter. It provided a theoretical basis for the application of high efficiency fertilizer in different soils. Further studies under field conditions are required to assess the effects of these nitrification inhibitors.
A Comparative Study of Standard Center Pivot and Growers-Based Modified Center Pivot for Evaluating Uniformity Coefficient and Water Distribution
Authors: Al-Ghobari Hussein , Dewidar Ahmed Z.
Published: August 2021

The center pivot irrigation system is a type of irrigation technology used to apply water effectively and uniformly over a wide variety of areas and topographies. These irrigation systems’ uniformity of water application greatly affects water use, energy consumption, and crop production. Performance tests of the standard lateral galvanized and modified polyethylene plastic pipes in the center pivot irrigation systems were conducted in different regions of Saudi Arabia. Water distribution depths along the laterals, coefficient of uniformity (CU), and distribution uniformity of the low quarter (DU) were determined. The results revealed that profiles of water distribution ranged from 4 to 14 mm for the standard-center pivot irrigation systems, while those for the modified-center pivot irrigation systems ranged from 6.5 to 50 mm. Standard-center pivot irrigation systems’ CU values ranged from 74 to 90%, with an average of 86%. In comparison, the modified-center pivot irrigation systems’ CU values ranged from 62 to 83%, with an average of 78%. The DU values ranged from 60 to 82% for the standard-center pivot irrigation systems, with an overall average of 77%. For the modified-center pivot irrigation systems, the DU values, in contrast, ranged from 31 to 75%, with an average of 65%. Thus, the accuracy and uniformity of the standard-center pivot irrigation systems are superior to those that have been modified. Additionally, a statistical model was developed to investigate the relationship between the water losses and the main climatic factors under field operating conditions. Therefore, the study results are expected to draw attention to standard lateral pipes’ value on the one hand and demonstrate the detrimental consequences of growers’ incorrect practices in pivot irrigation systems, motivating them to take strong action against these activities, on the other hand.
Alfalfa Established Successfully in Intercropping with Corn in the Midwest US
Authors: Berti Marisol T. , Cecchin Andrea , Samarappuli Dulan P. , Patel Swetabh , Lenssen Andrew W. , Moore Ken J. , Wells Samantha S. , Kazula Maciej J.
Published: August 2021

Integrating alfalfa (Medicago sativa L.) with corn (Zea mays L.) for grain will increase biodiversity, reduce the negative environmental impact of corn monoculture and increase farm profitability. The objectives of this research were to evaluate forage productivity and nutritive value, along with stand establishment of alfalfa in a corn grain system in Iowa, Minnesota, and North Dakota. The experimental design was a randomized complete block with four replicates at each site. Treatments included were: sole corn (i.e., check; T1), sole alfalfa (T2), alfalfa intercropped into corn (T3), a prohexadione-treated alfalfa intercropped with corn (T4), and a spring-seeded alfalfa in the year after intercropping (T5), which was planted in plots with T1 the previous year. All sites had below normal rainfall in 2016 and 2017. Corn grain yield was significantly lower when intercropped with alfalfa (T3 and T4) compared with the check corn crop (no alfalfa, T1). Corn grain yield reduction ranged from 14.0% to 18.8% compared with the check (T1). Corn biomass yield was reduced by intercropped alfalfa (T3 and T4) by 15.9% to 25.8%. In the seeding year, alfalfa seasonal forage yield was significantly greater when corn competition was absent in all environments. The intercropped alfalfa from the previous season (T3 and T4) had almost double the forage yield than the alfalfa in the seeding year (spring-seeded alfalfa; T5). In the second production year, there were no meaningful forage yield differences (p > 0.05) across all treatments, indicating alfalfa in intercropping systems does not affect forage yield past the first production year. Prohexadione-calcium, a growth regulator, did not affect alfalfa stand density, forage yield and nutritive value. The forage nutritive value was dependent on harvest date not the alfalfa intercropping treatments. Results of our study suggest that establishing alfalfa with corn is feasible and can be a potential alternative for the upper Midwest region. However, when under drought conditions, this system might be less resilient since competition between alfalfa and corn for soil moisture will be intensified under drought or moisture-limited conditions, and this will likely depress corn grain yield. Research targeted to reintroduce perennial crops into the current dominant corn–soybean systems in the US Corn Belt is urgently needed to improve stability and resiliency of production systems.
Variable Distribution of DOCK-D Proteins between Cytosol and Nucleoplasm in Cell Lines, Effect of Interleukin-4 on DOCK10 in B-Cell Lymphoid Neoplasms, and Validation of a New DOCK10 Antiserum for Immunofluorescence Studies
Authors: Ruiz-Lafuente Natalia , Minguela Alfredo , Moraleda Jose M. , Muro Manuel , Parrado Antonio
Published: August 2021

Dedicator-of-cytokinesis (DOCK), a family of guanine-nucleotide exchange factors (GEFs), comprises four subfamilies, named from A to D. DOCK-D comprises DOCK9, DOCK10, and DOCK11. The GEF activity involves translocation from the cytoplasm to the plasma membrane (PM), as assessed by the transfection of tagged proteins. However, the cellular localization of endogenous DOCK proteins is poorly understood. In this paper, to gain a better understanding of the role of the DOCK-D proteins, we studied their distribution between cytosol and nucleoplasm in 11 cell lines. DOCK-D proteins were distributed with variable cytosolic or nuclear predominance, although the latter was common for DOCK9 and DOCK11. These results suggest that the DOCK-D proteins may perform new nuclear functions, which remain to be discovered. Furthermore, we found that DOCK10 levels are increased by interleukin-4 (IL-4) in B-cell lymphoid neoplasms other than chronic lymphocytic leukemia (CLL) such as mantle cell lymphoma and diffuse large B-cell lymphoma. We also found evidence for an induction of the cytosolic levels of DOCK10 by IL-4 in CLL. Finally, we obtained a valid DOCK10 antiserum for immunofluorescence (IF) microscopy that, as an antibody against the hemagglutinin (HA) tag, marked PM ruffles and filopodia in HeLa cells with inducible expression of HA-DOCK10.
Diversity of International High-Risk Clones of Acinetobacter baumannii Revealed in a Russian Multidisciplinary Medical Center during 2017–2019
Authors: Shelenkov Andrey , Petrova Lyudmila , Zamyatin Mikhail , Mikhaylova Yulia , Akimkin Vasiliy
Published: August 2021

Acinetobacter baumannii is a dangerous bacterial pathogen possessing the ability to persist on various surfaces, especially in clinical settings, and to rapidly acquire the resistance to a broad spectrum of antibiotics. Thus, the epidemiological surveillance of A. baumannii within a particular hospital, region, and across the world is an important healthcare task that currently usually includes performing whole-genome sequencing (WGS) of representative isolates. During the past years, the dissemination of A. baumannii across the world was mainly driven by the strains belonging to two major groups called the global clones or international clones (ICs) of high risk (IC1 and IC2). However, currently nine ICs are already considered. Although some clones were previously thought to spread in particular regions of the world, in recent years this is usually not the case. In this study, we determined five ICs, as well as three isolates not belonging to the major ICs, in one multidisciplinary medical center within the period 2017–2019. We performed WGS using both short- and long-read sequencing technologies of nine representative clinical A. baumannii isolates, which allowed us to determine the antibiotic resistance and virulence genomic determinants, reveal the CRISPR/Cas systems, and obtain the plasmid structures. The phenotypic and genotypic antibiotic resistance profiles are compared, and the possible ways of isolate and resistance spreading are discussed. We believe that the data obtained will provide a better understanding of the spreading and resistance acquisition of the ICs of A. baumannii and further stress the necessity for continuous genomic epidemiology surveillance of this problem-causing bacterial species.
Effectiveness of Natural Antioxidants against SARS-CoV-2? Insights from the In-Silico World
Authors: Rehman Muhammad Fayyaz ur , Akhter Shahzaib , Batool Aima Iram , Selamoglu Zeliha , Sevindik Mustafa , Eman Rida , Mustaqeem Muhammad , Akram Muhammad Safwan , Kanwal Fariha , Lu Changrui , Aslam Mehwish
Published: August 2021

The SARS CoV-2 pandemic has affected millions of people around the globe. Despite many efforts to find some effective medicines against SARS CoV-2, no established therapeutics are available yet. The use of phytochemicals as antiviral agents provides hope against the proliferation of SARS-CoV-2. Several natural compounds were analyzed by virtual screening against six SARS CoV-2 protein targets using molecular docking simulations in the present study. More than a hundred plant-derived secondary metabolites have been docked, including alkaloids, flavonoids, coumarins, and steroids. SARS CoV-2 protein targets include Main protease (MPro), Papain-like protease (PLpro), RNA-dependent RNA polymerase (RdRp), Spike glycoprotein (S), Helicase (Nsp13), and E-Channel protein. Phytochemicals were evaluated by molecular docking, and MD simulations were performed using the YASARA structure using a modified genetic algorithm and AMBER03 force field. Binding energies and dissociation constants allowed the identification of potentially active compounds. Ligand-protein interactions provide an insight into the mechanism and potential of identified compounds. Glycyrrhizin and its metabolite 18-β-glycyrrhetinic acid have shown a strong binding affinity for MPro, helicase, RdRp, spike, and E-channel proteins, while a flavonoid Baicalin also strongly binds against PLpro and RdRp. The use of identified phytochemicals may help to speed up the drug development and provide natural protection against SARS-CoV-2.
The Revival of Aztreonam in Combination with Avibactam against Metallo-β-Lactamase-Producing Gram-Negatives: A Systematic Review of In Vitro Studies and Clinical Cases
Authors: Mauri Carola , Maraolo Alberto Enrico , Di Bella Stefano , Luzzaro Francesco , Principe Luigi
Published: August 2021

Infections caused by metallo-β-lactamase (MBL)-producing Enterobacterales and Pseudomonas are increasingly reported worldwide and are usually associated with high mortality rates (>30%). Neither standard therapy nor consensus for the management of these infections exist. Aztreonam, an old β-lactam antibiotic, is not hydrolyzed by MBLs. However, since many MBL-producing strains co-produce enzymes that could hydrolyze aztreonam (e.g., AmpC, ESBL), a robust β-lactamase inhibitor such as avibactam could be given as a partner drug. We performed a systematic review including 35 in vitro and 18 in vivo studies on the combination aztreonam + avibactam for infections sustained by MBL-producing Gram-negatives. In vitro data on 2209 Gram-negatives were available, showing the high antimicrobial activity of aztreonam (MIC ≤ 4 mg/L when combined with avibactam) in 80% of MBL-producing Enterobacterales, 85% of Stenotrophomonas and 6% of MBL-producing Pseudomonas. Clinical data were available for 94 patients: 83% of them had bloodstream infections. Clinical resolution within 30 days was reported in 80% of infected patients. Analyzing only patients with bloodstream infections (64 patients), death occurred in 19% of patients treated with aztreonam + ceftazidime/avibactam. The combination aztreonam + avibactam appears to be a promising option against MBL-producing bacteria (especially Enterobacterales, much less for Pseudomonas) while waiting for new antimicrobials.
Effects of Incubation Time and Inoculation Level on the Stabilities of Bacteriostatic and Bactericidal Antibiotics against Salmonella Typhimurium
Authors: Laure Nana Nguefang , Dawan Jirapat , Ahn Juhee
Published: August 2021

This study was designed to evaluate the stability of chloramphenicol, erythromycin, tetracycline, cephalothin, ciprofloxacin, and tobramycin against antibiotic-sensitive Salmonella Typhimurium (ASST) and antibiotic-resistant S. Typhimurium (ARST) during the broth microdilution assay. The antimicrobial activity in association with antibiotic stability was measured by using antibiotic susceptibility, time-delayed inoculation, time-extended incubation, and inoculum effect assays. The loss of the antimicrobial activity of cephalothin against ASST exposed to 1 MIC was observed for the 10 h delayed inoculation. The antimicrobial activities of tetracycline and ciprofloxacin against ASST and ARST exposed to ½ MIC were significantly decreased after the 10 h delayed inoculation. All antibiotics used in this study, except for ciprofloxacin, showed the considerable losses of antimicrobial activities against ASST and ARST after 40 h of incubation at 37 °C when compared to the 20 h of incubation during AST. Compared to the standard inoculum level (6 log CFU/mL), the MIC0.1 values of bactericidal antibiotics, ciprofloxacin and tobramycin against ASST were increased by more than 4-fold at the high inoculum level of 9 log CFU/mL. This would provide practical information for better understanding the clinical efficacy of the currently used antibiotics by considering the antibiotic stability during incubation time at different inoculum levels.
Anti-MRSA Cephalosporin versus Vancomycin-Based Treatment for Acute Bacterial Skin and Skin Structure Infection: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Chen Ching-Yi , Chen Wang-Chun , Lai Chih-Cheng , Shih Tzu-Ping , Tang Hung-Jen
Published: August 2021

This systematic review and meta-analysis of randomized controlled trials (RCTs) compared the clinical efficacy and safety of anti-MRSA cephalosporin and vancomycin-based treatment in treating acute bacterial skin and skin structure infections (ABSSSIs). PubMed, Embase, Cochrane Central Register of Controlled Trials, Turning Research into Practice, and ClinicalTrials.gov databases were searched for relevant articles from inception to 15 June 2020. RCTs comparing the clinical efficacy and safety of anti-MRSA cephalosporin with those of vancomycin-based regimens in treating adult patients with ABSSSIs were included. The primary and secondary outcomes were clinical response at the test-of-cure assessments and risk of adverse events (AEs), respectively. Eight RCTs were enrolled. The clinical response rate was not significantly different between anti-MRSA cephalosporin and vancomycin-based treatments (odds ratio [OR], 1.05; 95% CI, 0.90–1.23; I2 = 0%). Except for major cutaneous abscesses in which anti-MRSA cephalosporin-based treatment was associated with a lower clinical response rate than vancomycin-based treatment (OR, 0.62; 95% CI, 0.40–0.97; I2 = 0%), other subgroup analyses according to the type of cephalosporin (ceftaroline or ceftobiprole), type of infection, and different pathogens did not show significant differences in clinical response. Anti-MRSA cephalosporin-based treatment was only associated with a higher risk of nausea than vancomycin-based treatment (OR, 1.41; 95% CI, 1.07–1.85; I2 = 0%). In treating ABSSSIs, the clinical efficacy of anti-MRSA cephalosporin is comparable to that of vancomycin-based treatment, except in major cutaneous abscesses. In addition to nausea, anti-MRSA cephalosporin was as tolerable as vancomycin-based treatment.
Molecular Detection, Serotyping, and Antibiotic Resistance of Shiga Toxigenic Escherichia coli Isolated from She-Camels and In-Contact Humans in Egypt
Authors: Diab Mohamed Said , Tarabees Reda , Elnaker Yasser F. , Hadad Ghada A. , Saad Marwa A. , Galbat Salah A. , Albogami Sarah , Hassan Aziza M. , Dawood Mahmoud A. O. , Shaaban Sabah Ibrahim
Published: August 2021

This study aims to determine the prevalence of STEC in she-camels suffering from mastitis in semi-arid regions by using traditional culture methods and then confirming it with Serological and molecular techniques in milk samples, camel feces, as well as human stool samples for human contacts. In addition, an antibiotic susceptibility profile for these isolates was investigation. Mastitic milk samples were taken after California Mastitis Test (CMT) procedure, and fecal samples were taken from she-camels and human stool samples, then cultured using traditional methods to isolate Escherichiacoli. These isolates were initially classified serologically, then an mPCR (Multiplex PCR) was used to determine virulence genes. Finally, both camel and human isolates were tested for antibiotic susceptibility. Out of a total of 180 she-camels, 34 (18.9%) were mastitic (8.3% clinical and 10.6% sub-clinical mastitis), where it was higher in camels bred with other animals. The total presence of E. coli was 21.9, 13.9, and 33.7% in milk, camel feces, and human stool, respectively, whereas the occurrence of STEC from the total E. coli isolates were 36, 16, and 31.4% for milk, camel feces, and stool, respectively. Among the camel isolates, stx1 was the most frequently detected virulence gene, while hlyA was not detected. The most detected virulence gene in human isolates was stx2 (45.5%), followed by stx1. Camel STEC showed resistance to Oxytetracycline only, while human STEC showed multiple drug resistance to Amoxicillin, Gentamycin, and Clindamycin with 81.8, 72.7, and 63.6%, respectively. Breeding camels in semi-arid areas separately from other animals may reduce the risk of infection with some bacteria, including E. coli; in contrast, mixed breeding with other animals contributes a significant risk factor for STEC emergence in camels.
Effects of Fusarium Mycotoxin Exposure on Lipid Peroxidation and Glutathione Redox System in the Liver of Laying Hens
Authors: Kulcsár Szabina , Kövesi Benjámin , Balogh Krisztián , Zándoki Erika , Ancsin Zsolt , Márta Balláné Erdélyi , Mézes Miklós
Published: August 2021

It has been proven by several studies that Fusarium mycotoxins induce oxidative stress in animals, consequently inducing lipid peroxidation, which the glutathione system can neutralize. A short-term (3-day) in vivo feeding trial was performed with laying hens using a double dose of the EU recommendation for mycotoxin contamination (T-2 toxin 0.5 mg/kg feed; deoxynivalenol (DON) 10 mg/kg feed; fumonisin B1 (FB1) 40 mg/kg feed). Some lipid peroxidation and glutathione redox system parameters and gene expression levels were measured in the liver. The results show that FB1 significantly decreased the reduced glutathione (GSH) content and the activity of glutathione peroxidase (GPx) compared to the control and the two other mycotoxin-treated groups on day 3. Lipid peroxidation was affected by all three mycotoxins. Significantly lower values were observed in the case of conjugated dienes for all of the three mycotoxins and malondialdehyde concentration as an effect of DON on day 3. T-2 toxin and DON upregulated the expression of the GPX4 gene. The results show that Fusarium mycotoxins had different effects at the end of the trial. The FB1 exposure caused a decrease in the glutathione redox markers, while DON decreased the formation of malondialdehyde. The results suggest that the Fusarium mycotoxins investigated individually differently activated the antioxidant defense and caused low-level oxidative stress at the dose applied.