bluuebunny/crossref_metadata_2025 huggingface dataset:
PEOPLE-CENTRED DEVELOPMENT: THE CASE OF DEVELOPMENT PROJECTS IN PAPUA INDONESIA DURING THE SPECIAL AUTONOMY SYSTEM
Authors: Hergianasari Putri , As'ad Muhammad Uhaib , Nau Novriest Umbu W.
Published: January 2023

In many developing countries, various development models have been used, but the results are far from expectations. This happens because this ideology only focuses on equitable development by focusing only on economic growth factors. Even so, we can assume developmental deviations are common because when applied in the field, we cannot study them completely thoroughly. However, based on the conditions above, we can take the most optimal approach to formulate an optimal mutually dependent and beneficial relationship between the community and the government as stipulated in legal policy. Therefore, this paper examines how the political economy and the role of the state shape the development of Papua in Special Autonomy System. With FGD data and research from the literature, we use a descriptive-qualitative strategy. According to the findings of the study, the background of economic exploitation in Papua and the sustainability of nature as a production space has a paradoxical relationship, where the result of increasing the economic value of mining activities is conducted by PT. Freeport which is inversely proportional to the loss of green open space. This results in damage to living ecosystems. As a result, the sustainability of the Papuan people's livelihood in the future is threatened. Based on this, the author provides the results of his study as a solution for government policy makers to provide recommendations so that the government prioritizes human-centered development strategies. This study concludes that "capacity building" is needed by humans in order to become the subject of development. With this framework in mind, the people of Papua can optimize development in their area more effectively because the process is carried out through social development that emphasizes education, knowledge, and skills. Keywords: development projects, economic exploitation, people centered development, special autonomy region
INNOVATIVENESS AND COMPETITIVE ADVANTAGE OF SMALL AND MEDIUM-SIZE ENTERPRISES IN KOGI STATE, NIGERIA
Authors: Nafiu Akeem Tunde , Aduku Danlami Joseph , Abah Napoleon Ukwubile
Published: January 2023

This study focused on link innovativeness and Competitive Advantage (CA) of Small and Medium-size Enterprise (SMEs). The study examined the effect of Value Capture Innovation (VCI) on the CA, as well as the effect of VPI on the CA of SMEs in Kogi State. The survey research design was adopted. 255 SMEs were surveyed, but 219 owners/managers eventually became active participants. Multi-stage random sampling technique was adopted. The reliability results showed VCI (α=0.917); and VPI (α=0.776). Multiple Regression analysis was used for testing hypotheses. Descriptive statistics aggregated and characterized the data in a straightforward and clear manner. Finding showed that VCI has significant effect on the CA of SMEs in Kogi State, and that (Value Proposition Innovation (VPI) has significant effect on CA of SMEs. The study concluded that SMEs need to possess innovation capabilities so as to enhance reasonable position in the competitive business environment. The study recommended that SME owners should increase their commitment to VCI so as to achieve sustainable CA for their enterprises, and that SME owners should invest in VPI to create effective medium route towards the achievement of sustainable CA of their enterprises.
Key words: innovative activity, competitive advantage, value capture innovation, value proposition innovation, new customer relationships
Enhanced Anticarcinogenic and Antimicrobial Response of Synthesized Tungsten Oxide Nanoparticles
Authors: Kumari J. , Mangala P.
Published: January 2023

In the present study, we fabricated tungsten trioxide nanoparticles (WO3 NPs) from a tungsten complex [W(C13H10NO)3] of ligand N-salicylideneaniline with tungstic acid as the precursor. Nanoparticles were synthesized using the direct thermal decomposition method. These nanoparticles were evaluated for cytotoxicity influence on human breast cancer MCF7 cell line (adenocarcinoma). The observed results suggested that WO3 can destroy 50 % of viable cells after 24 h of incubation at 37 °C. Based on these results, we concluded that WO3 nanoparticles could be a potential drug carrier candidate against human breast cancer cells based on the amount of the drug. In addition, WO3 nanoparticles exhibited significant antimicrobial and antifungal activity.
Optimization of M/M/2 Queueing Model with Working Vacations
Authors: Gupta S. , Joshi P. K. , Rajeshwari K. N.
Published: January 2023

The paper deals with an M/M/2 Queueing Model with working vacations and reneging of customers due to impatience. The matrix geometric method is used to find the distribution of the number of customers in the system. A cost function is constructed to obtain the optimal value of the service rate to optimize (minimize) the cost function using the Quadratic Fit Search Method (QFSM). Further, the effects on the system's performance measures using numerical analysis and graphical representation are studied.
Gelation of an Organically Crosslinked PHPA Polymer Gel System: An Experimental Study
Authors: Vaishnav M. , Verma N. K.
Published: January 2023

Excessive water production in the oil field is the major difficulty in production for the petroleum industry. Remedial techniques need to be applied to control this excess water production considering the health, safety, and environmental issues and improve the reservoir's economic and productive life. In this study polymer gel system comprising the polymer partially hydrolyzed polyacrylamide (PHPA) and organic cross-linkers (Hydroquinone and Hexamethylene tetramine) were prepared as a water shut-off system to control the excessive production of water in the oil field. The effect of various parameters such as temperature, pH, cross-linker concentration, degree of hydrolysis, and divalent cations on gelation time was investigated using the bottle testing method. The importance of retarders at high temperatures was also evaluated. The gelation temperature was varied from 90 °C to 120 °C to study the effect of different parameters on the gelation time and gel behavior. This study suggests that Partially Hydrolyzed Polyacrylamide (PHPA) with organic cross-linkers can be an effective polymer gel system for water shut-off operations, and with the addition of retarders at high temperature to control gelation time, the performance of the gel can be improved.
Solution of Linear Volterra Integral Equation of Second Kind via Rishi Transform
Authors: Aggarwal S. , Kumar R. , Chandel J.
Published: January 2023

The solution of various problems of engineering and science can easily determined by representing these problems in integral equations. There are numerous analytical and numerical methods which can be used for solving different kinds of integral equations. In this paper, authors used recently developed integral transform “Rishi Transform” for obtaining the analytical solution of linear Volterra integral equation of second kind (LVIESK). For this, the kernel of LVIESK has assumed a convolution type kernel. Five numerical examples are considered for demonstrating the complete procedure of determining the solution. Results of these problems suggest that Rishi transform provides the exact analytical solution of LVIESK without doing complicated calculation work.
A Statistical Overview of Death due to Alcohol Poisoning in the Rajshahi Region
Authors: Uddin Md Kafil , Royhan Zaman Nishat , Sumaiya Shirin , Sadat Md Alvi , Chatterjee Nibedita
Published: January 2023

Introduction: The prevalence of death due to alcohol poisoning is increasing at an alarming rate in Bangladesh. However, there is a lack of actual statistics regarding death cases due to alcohol poisoning in the Rajshahi region. Therefore, this study was designed to explore the recent statistical report of death cases due to alcohol poisoning in the Rajshahi region.

Methods: The Department of Forensic Medicine & Toxicology, Rajshahi Medical College, Rajshahi, Bangladesh, conducted this statistical study, reporting 29 deaths between January 2019 and September 2021. The data was collected from the documents stored in the Department of Forensic Medicine & Toxicology.

Results: This study elucidates that the incidence of death due to alcohol poisoning is increasing over time. Ninety-three percent of victims were male. The maximum number of deaths (34.5%) due to alcohol poisoning was found in people between 21 and 30 years old. The maximum number of victims (27.59%) in the profession were students. Around two-thirds of the deceased were married. Only 24% of victims were other than Islam religion.

Conclusion: As the rate of death due to alcohol poisoning increases over time, it might indicate an increasing number of alcohol consumers. Besides, the lack of consciousness is associated with unwanted death.

TAJ 2022; 35: No-2: 119-124
Effect of Combined Oral Contraceptive Pill on Serum Bilirubin and Alkaline Phosphatase
Authors: Rupa Shamima Nazneen , Begum Bedowra , Jolly Sayeeda Sultana , Kabir Farjana , Akhter Shahnaz , Khan Zahid Hasan , Nath Manik Chandra
Published: January 2023

Background: Combined oral contraceptive is the most known and popular method of contraception. The combined oral contraceptive pill was the first oral contraceptive method and was commercially marketed in 1960. Earlier investigators reported that early oral contraceptive pills had many side effects. Despite the modifications on early OCPs in terms of content and dosage to lessen their side effects, newer contraceptives still have some hepatotoxic effects.  Aim and Objectives: The objective of this study was to investigate the effect of low-dose OCP on S. bilirubin and ALP- one of the most important liver enzymes.

Materials and Methods: This cross-sectional analytical study was conducted on 184 healthy women aged 20-45. Among them, 92 women were OCP users, and 92 were nonusers. BMI-matched non-OCP users women were recruited in the study for comparison of S. bilirubin and ALP. A systematic sampling technique was applied to select each respondent. Data collection was commenced after obtaining ethical clearance from the Ethical Committee and informed consent from the respondents.

Results: The Results showed a significant decrease in serum Alkaline phosphatase among OCP users (p=0.001), but the ALP level was progressively increased with increased duration of OCP use. Serum bilirubin level was within the normal range, but the levels were slightly higher in OCP users but in. OCP users' serum bilirubin levels did not significantly increase with the duration of OCP use (P > 0.05). In summary, OCP users' women are associated with a decreased level of serum Alkaline phosphatase and a slightly increased level of serum bilirubin.

Conclusion: So regular monitoring of S. bilirubin and ALP should be done among OCP users women to avoid many unwanted complications.

TAJ 2022; 35: No-2: 133-141
Expediente
Authors: Paubrasilia Revista
Published: January 2023

Expediente da revista Paubrasilia. Ano 2023. Publicação contínua.
ANALISIS PERBANDINGAN POTENSI KEBANGKRUTAN PERUSAHAAN MANUFAKTUR PERIODE 2020 DENGAN MODEL ALTMAN, SPRINGATE, DAN ZMIJEWSKI
Authors:   Universitas Katolik Widya Mandala Surabaya Kampus Kota Madiun, Sari Heny Endah , Ariyan Vivi ,   Universitas Katolik Widya Mandala Surabaya Kampus Kota Madiun
Published: January 2023

Penelitian ini bertujuan untuk mengetahui perbedaan antara model Altman, Springate, dan Zmijewski, pada perusahaan manufaktur yang terdaftar di BEI serta untuk mengetahui model prediksi yang paling akurat dari ketiga model. Penelitian ini menggunakan data sekunder berupa laporan keuangan periode 2020. Teknik pengambilan sampel yang digunakan adalah purposive sampling dengan total 131 sampel. Alat analisis yang digunakan adalah uji Kruskal-Wallis dengan bantuan program Microsoft Excel dan SPSS 22. Hasil perhitungan ketiga model prediksi menunjukka bahwa terdapat beberapa perusahaan yang diprediksi mengalami kebangkrutan. Berdasarkan hasil uji Kruskal-Wallis dapat diketahui bahwa terdapat perbedaan antara ketiga model. Hasil penelitian ini menujukkan bahwa model Zmijewski adalah model prediksi kebangkrutan yang memiliki tingkat akurasi tertinggi dalam memprediksi kebangkrutan perusahaan manufaktur periode 2020 dengan tingkat akurasi sebesar 73%.
Differential response of seabird species to warm- and cold-water events in a heterogeneous cross-shelf environment in the Gulf of Alaska
Authors: Cushing DA , Kuletz KJ , Sousa L , Day RH , Danielson SL , Labunski EA , Hopcroft RR
Published: January 2023

We used seabird surveys and concurrent oceanographic observations in the Northern Gulf of Alaska during spring 1998-2019 to evaluate how seabirds responded to temperature variability, including a protracted marine heatwave, in a highly heterogeneous ecosystem. We examined temporally changing distributions of seabirds along the Seward Line, a 220 km transect across the shelf and slope, and evaluated relationships between water-mass properties and seabird abundance. Environmental factors associated with abundance include depth, water-column temperature and salinity, and surface-current velocities. Environmental responses of alcids and gulls contrasted with those of procellariiform (tubenose) seabirds, and their trajectories suggest a possible shift in community composition under future climate warming. Changes in seabird distribution and abundance associated with a shift from cold to warm conditions were especially pronounced over the middle- and outer-shelf domains, which are transitional between coastal and oceanic water masses. The abundance of tubenoses increased during and after the heatwave, whereas alcids and gulls shifted inshore, exhibited reproductive failures, and experienced mass mortalities due to starvation. Tubenoses appear well-adapted to periods of lower productivity during warming events because of their flight efficiency, allowing them to search widely to locate prey patches. In contrast, alcids, which forage by diving and have energetically expensive flight, appear sensitive to such conditions.
Limited long-term movement and slow growth of the sea cucumber Pearsonothuria graeffei
Authors: Hammond AR , Purcell SW
Published: January 2023

Sea cucumbers are heavily exploited worldwide, yet data are lacking on animal mobility and life-history parameters for fishery management and conservation planning. This study assessed movement and growth rates for a medium-sized holothuroid,Pearsonothuria graeffei, harvested throughout the Indo-Pacific. We used photographic mark-recapture to track long-term movements and growth for this species over 2 yr. Recapture rates were 67-72%. Movement rates averaged 9 m yr-1, and many individuals were found in aggregations and recaptured there in 2 successive years. Growth was highly variable; small animals (<700 g) tended to gain weight while large animals (>700 g) tended to lose weight. Some individuals lost weight and then regained weight, while others gained weight and later lost it. Growth models estimated thatP. graeffeiapproach their average maximum weight (769 g) in 7-12 yr and are slow-growing (growth coefficient = 0.17). Natural mortality(M; 0.48 yr-1) was low, and estimated longevity was 18 yr.P. graeffeiexhibits traits that heighten its vulnerability to overfishing: aggregation behaviour, low mobility, slow growth, a long lifespan and lowM. The site fidelity and low mobility infer that a system of small reserves would effectively protect breeding populations and that emigration to new sites is very limited. This study provides the first published evidence from natural habitats that holothuroids can lose and later regain weight. Our empirical findings suggest that small- to medium-sized holothuroids might be slower growing and longer lived than previously believed, imploring a more conservative approach to conservation policy.
PAR2: The Cornerstone of Pancreatic Diseases
Authors: SUHAJ P , OLEJAR T , MATEJ R
Published: January 2023

It has been 30 years since the first member of the protease-activated receptor (PAR) family was discovered. This was followed by the discovery of three other receptors, including PAR2. PAR2 is a G protein-coupled receptor activated by trypsin site-specific proteolysis. The process starts with serine proteases acting between arginine and serine, creating an N-terminus that functions as a tethered ligand that binds, after a conformational change, to the second extracellular loop of the receptor, leading to activation of G-proteins. The physiological and pathological functions of this ubiquitous receptor are still elusive. This review focuses on PAR2 activation and its distribution under physiological and pathological conditions, with a particular focus on the pancreas, a significant producer of trypsin, which is the prototype activator of the receptor. The role in acute or chronic pancreatitis, pancreatic cancer, and diabetes mellitus will be highlighted.
DÜZELTME: Karbon ve azotun sabit izotoplarının geçmiş beslenme alışkanlıkları ve geçim uygulamalarını yeniden yapılandırmak için kullanımı
Authors: IRVINE Benjamin , ÖZDEMİR Kameray
Published: January 2023

Tarihi ve arkeolojik topluluklarda beslenme geleneksel olarak etnografik, yazılı kayıtlar, arkeozoolojik ve arkeobotanik kalıntılar ve benzeri kaynaklar kullanılarak yeniden oluşturulmakla birlikte bu veri kaynakları bize yalnızca hangi kaynakların mevcut olduğunu söyleyebilir. Bununla birlikte, sabit izotop analizleri, tüketilen gıdaların geniş kategorilerinin doğrudan bir ölçümünü sağlar. İnsan ve hayvan kemiğinden özütlenen kolajenin sabit karbon ve azot izotop bileşimi, geçmiş insan topluluklarının beslenme alışkanlıklarını, geçim stratejilerindeki değişimi, göçü, ürün ve hayvan yönetimlerindeki değişiklikleri, topluluk içinde zamana, yaşa, cinsiyete veya gömü geleneğine göre beslenme varyasyonunu gözlemlemek ve sütten kesme süreci belirleyebilmek için kullanılır. Türkiye'de, sabit izotopların arkeolojik ve tarihi materyallere uygulanması nispeten geç başlamış ve ilk çalışma 2003 yılında yapılmıştır. Gelecekte, farklı bölgelerden ve zaman periyotlarından daha fazla sayıda ve daha büyük örnek setlerini analiz ederek bilgimizi ve anlayışımızı geliştirebilir ve ilerletebilir, meta veri analizi için daha büyük bir izotop veri seti oluşturabilir ve bireyler, yerleşimler, dönemler ve bölgeler arasında karşılaştırmalı çalışmalar yapabiliriz.
Nad leksikom Evanđelja iz Dovolje: doprinos proučavanju tekstovnoleksičkoj razini rukopisa
Authors: Ramić-Kunić Erma
Published: January 2023

The subject of this work is the textual-lexical level of the Gospel from Dovolja (hereinafter Dov.), a Bosnian Church Slavonic manuscript from the beginning of the 15th century. The main characteristic of this manuscript is its linguistic variety, which is especially evident at the textual and lexical level. Some parts of the manuscript are a reflection of the archaic Cyrilo-Method tradition, while others have been rejuvenated by pre-Slavisms. The paper tries to show how many templates were used in transcribing Dov., and where are the boundaries of those templates. In this sense, the conducted research shows that two main and one secondary template were used in transcribing Dov. The boundary of the first main template is from the beginning of the preserved text Ev. according to Matthew to the third chapter of Ev. according to Marc. It belongs to the Preslav tradition (T2). The second template includes the text from Mc. 3:1 to the end of the preserved text Ev. according to Luke, and is a reflection of the early Cyrilo-Method tradition (T1). Within the second template, the scribe also reaches for an innovative template of type T2 (from Lk. 9:22 to approximately Lk. 10:25). That template could be considered secondary because it includes two incomplete heads of Ev. according to Luke.
Дистрибуција силазних акцената ван првога слога у речима странога (и домаћега) порекла у српском језику
Authors: Stojanović Milena
Published: January 2023

The paper analyses accents outside the first syllable in words of foreign (and domestic) origin using a research in three different environments by survey and interview. The subjects of the research were people from Belgrade (urban environment), village Tometino Polje (near Divčibare) and Požega (small town near Užice). The aim was what extent the standard is obeyed. It was concluded that Belgrade keeps a long-falling accent after the first styllable, but not postaccentual lenght. This is not the case in Požega and Tometino Polje. People there, in the genitive plural of polysyllabic words of domestic origin keep the model long-lasting accent and two postaccentual lengths and follow the standard to a lesser extent (Tometino Polje). Тhe paper also analyses the role linguistic experts, media and school have in this field through the discussion with subjects. The results show that subjects are aware of a huge influence they have, but they agree that standard is not sufficiently obeyed.
Dinámica de la productividad manufacturera en la frontera norte mexicana, regional y por estados: 1993-2018
Authors: Félix Armenta Jimmy , León Arias Adrián De
Published: January 2023

The objective of this article is to describe the performance of the total productivity of the manufacturing factors in the Northern border region of Mexico during the period 1993-2018. The methodological approach is focused on Solow´s Residual and Harberger’s Sunrise/Sunset diagrams to identify the contributions of each of the states. The main findings of the research indicate significant increases in the sources of growth for the region. In addition, the region’s progress is diversified among the entities, with Nuevo León being the most prominent. It is concluded that the northern border region has become the largest pole of job creation in the country’s manufacturing sector, although it has been limited in terms of total factor productivity. This makes it necessary to develop intraregional policies with specific measures that improve aggregate productivity in each state.
Fluctuaciones en el precio y demanda de gasolina en la frontera norte de México
Authors: Ibarra Salazar Jorge , Sotres Cervantes Lida Karina , Morales Erika
Published: January 2023

The objective of the article is to estimate the price elasticity of the demand for gasoline in Mexico’s Northern border based on applying monthly data of Mexican regions from 1997 to 2015. The results reveal that the demand for gasoline at the border is less inelastic than inland. A database is provided that includes more observations and regional economic variables compared to previous studies. It is concluded that beyond the economic effects of gasoline-related tourism, the competition faced by gas stations on the Northern border influences the price elasticity of demand. This confirms the importance of gasoline tourism in this region of Mexico, as has been recognized by federal and municipal authorities.
Compromised osteogenic effect of exosomes internalized by senescent bone marrow stem cells via endocytoses involving clathrin, macropinocytosis and caveolae
Authors: Qi Lei , Ge Weiwen , Pan Cancan , Jiang Weidong , Lin Dan , Zhang Lei
Published: January 2023

Stem cell senescence leads to progressive functional declines and disrupts the physiological homeostasis of bone environment. Stem cell-derived exosomes are emerging as promising therapeutical approaches to treat diverse aging-related osseous diseases. Herein, a previously reported osteoinductive exosome (OI-exo) was applied as a therapeutic agent for bone repair in aging individuals and its internalization mechanisms in senescent bone marrow stem cells (BMSCs) were explored. The results demonstrated that OI-exos derived from young BMSCs could partially rescue the proliferation, osteogenic differentiation and alleviate aging phenotypes in vitro. OI-exo-delivered hierarchical mesoporous bioactive glass (MBG) scaffold effectively promote in vivo bone formation in aging rat cranial defect model. However, the osteogenic effects of OI-exo both in vitro and in vivo were compromised in senescent individuals and for aging BMSCs compared to younger ones. This study revealed that non-senescent BMSCs internalized exosomes exclusively via clathrin-mediated endocytosis, while senescent BMSCs additionally evoked macropinocytosis and caveolae-mediated endocytosis to mediate the internalization of exosomes. The alteration of endocytic manner of senescent BMSCs and the involvement of macropinocytosis might be responsible for the compromised effects of therapeutical exosomes. The phenomena discovered in this study could also be extended to other scenarios where drugs or treatments exerted compromised effects in aging individuals. The influence of endocytic manner, avoidance of macropinocytosis-related negative effects should be taken into considerations in future therapeutic design for aging populations.
Separation, purification, and crystallization of 1,5-pentanediamine hydrochloride from fermentation broth by cation resin
Authors: Li Hui , Chen Xu , Tang Yibo , Yang Yue , He Feng , Wang Xin , Li Ganlu , Chen Kequan , Ouyang Pingkai , Yang Yuning
Published: January 2023

1,5-Pentanediamine hydrochloride (PDAH) was an important raw material for the preparation of bio-based pentamethylene diisocyanate (PDI). PDI has shown excellent properties in the application of adhesives and thermosetting polyurethane. In this study, PDAH was recovered from 1,5-pentanediamine (PDA) fermentation broth using a cation exchange resin and purified by crystallization. D152 was selected as the most suitable resin for purifying PDAH. The effects of solution pH, initial temperature, concentration of PDA, and adsorption time were studied by the static adsorption method. The equilibrium adsorption data were well fitted to Langmiur, Freundlich, and Temkin-Pyzhev adsorption isotherms. The adsorption free energy, enthalpy, and entropy were calculated. The experimental data were well described by the pseudo first-order kinetics model. The dynamic experiment in the fixed bed column showed that under optimal conditions, the adsorption capacity reached 96.45 mg g−1, and the recovery proportion of the effective section reached 80.16%. In addition, the crystallization of the PDAH solution obtained by elution proved that the crystal product quality of resin eluting solution was highest. Thus, our research will contribute to the industrial scale-up of the separation of PDAH.
Development of lacrimal gland organoids from iPSC derived multizonal ocular cells
Authors: Asal Melis , Koçak Gamze , Sarı Vedat , Reçber Tuba , Nemutlu Emirhan , Utine Canan Aslı , Güven Sinan
Published: January 2023

Lacrimal gland plays a vital role in maintaining the health and function of the ocular surface. Dysfunction of the gland leads to disruption of ocular surface homeostasis and can lead to severe outcomes. Approaches evolving through regenerative medicine have recently gained importance to restore the function of the gland. Using human induced pluripotent stem cells (iPSCs), we generated functional in vitro lacrimal gland organoids by adopting the multi zonal ocular differentiation approach. We differentiated human iPSCs and confirmed commitment to neuro ectodermal lineage. Then we identified emergence of mesenchymal and epithelial lacrimal gland progenitor cells by the third week of differentiation. Differentiated progenitors underwent branching morphogenesis in the following weeks, typical of lacrimal gland development. We were able to confirm the presence of lacrimal gland specific acinar, ductal, and myoepithelial cells and structures during weeks 4–7. Further on, we demonstrated the role of miR-205 in regulation of the lacrimal gland organoid development by monitoring miR-205 and FGF10 mRNA levels throughout the differentiation process. In addition, we assessed the functionality of the organoids using the β-Hexosaminidase assay, confirming the secretory function of lacrimal organoids. Finally, metabolomics analysis revealed a shift from amino acid metabolism to lipid metabolism in differentiated organoids. These functional, tear proteins secreting human lacrimal gland organoids harbor a great potential for the improvement of existing treatment options of lacrimal gland dysfunction and can serve as a platform to study human lacrimal gland development and morphogenesis.
Very small embryonic-like stem cells have the potential to win the three-front war on tissue damage, cancer, and aging
Authors: Bhartiya Deepa , Jha Nitu , Tripathi Anish , Tripathi Ashish
Published: January 2023

The concept of dedifferentiation and reprogramming of mature somatic cells holds much promise for the three-front “war” against tissue damage, cancer, and aging. It was hoped that reprogramming human somatic cells into the induced pluripotent state, along with the use of embryonic stem cells, would transform regenerative medicine. However, despite global efforts, clinical applications remain a distant dream, due to associated factors such as genomic instability, tumorigenicity, immunogenicity, and heterogeneity. Meanwhile, the expression of embryonic (pluripotent) markers in multiple cancers has baffled the scientific community, and it has been suggested that somatic cells dedifferentiate and “reprogram” into the pluripotent state in vivo to initiate cancer. It has also been suggested that aging can be reversed by partial reprogramming in vivo. However, better methods are needed; using vectors or Yamanaka factors in vivo, for example, is dangerous, and many potential anti-aging therapies carry the same risks as those using induced pluripotent cells, as described above. The present perspective examines the potential of endogenous, pluripotent very small embryonic-like stem cells (VSELs). These cells are naturally present in multiple tissues; they routinely replace diseased tissue and ensure regeneration to maintain life-long homeostasis, and they have the ability to differentiate into adult counterparts. Recent evidence suggests that cancers initiate due to the selective expansion of epigenetically altered VSELs and their blocked differentiation. Furthermore, VSEL numbers have been directly linked to lifespan in studies of long- and short-lived transgenic mice, and VSEL dysfunction has been found in the ovaries of aged mice. To conclude, a greater interest in VSELs, with their potential to address all three fronts of this war, could be the “light at the end of the tunnel.”
Harshening stem cell research and precision medicine: The states of human pluripotent cells stem cell repository diversity, and racial and sex differences in transcriptomes
Authors: Nguyen Thong Ba , Lac Quan , Abdi Lovina , Banerjee Dipanjan , Deng Youping , Zhang Yiqiang
Published: January 2023

In vitro investigation on human development, disease modeling, and drug discovery has been empowered by human induced pluripotent stem cell (hiPSC) technologies that form the foundation of precision medicine. Race and sex genetic backgrounds have become a major focus of many diseases modeling and drug response evaluation in the pharmaceutical industry. Here, we gathered data from major stem cell repositories to analyze the diversity with respect to ethnicity, sex, and disease types; and we also analyzed public datasets to unravel transcriptomics differences between samples of different ethnicities and sexes. We found a lack of diversity despite the large sample size of human induced pluripotent stem cells. In the ethnic comparison, the White group made up the majority of the banked hiPSCs. Similarly, for the organ/disease type and sex comparisons, the neural and male hiPSCs accounted for the majority of currently available hiPSCs. Bulk RNA-seq and single-cell transcriptomic analysis coupled with Machine Learning and Network Analysis revealed panels of gene features differently expressed in healthy hiPSCs and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) of different races and sexes. The data highlights the current ethnic and sex inequality in stem cell research and demonstrates the molecular biological diversity of hiPSCs and cardiomyocytes from different races and genders. We postulate that future efforts in stem cell biology, regenerative and precision medicine should be guided towards an inclusive, diverse repository reflecting the prevalence of diseases across racial and ethnic groups and the sexes, important for both common and rare disease modeling, drug screening, and cell therapeutics.
Fundamentals to therapeutics: Epigenetic modulation of CD8+ T Cell exhaustion in the tumor microenvironment
Authors: Blake Maja K. , O’Connell Patrick , Aldhamen Yasser A.
Published: January 2023

In the setting of chronic antigen exposure in the tumor microenvironment (TME), cytotoxic CD8+ T cells (CTLs) lose their immune surveillance capabilities and ability to clear tumor cells as a result of their differentiation into terminally exhausted CD8+ T cells. Immune checkpoint blockade (ICB) therapies reinvigorate exhausted CD8+ T cells by targeting specific inhibitory receptors, thus promoting their cytolytic activity towards tumor cells. Despite exciting results with ICB therapies, many patients with solid tumors still fail to respond to such therapies and patients who initially respond can develop resistance. Recently, through new sequencing technologies such as the assay for transposase-accessible chromatin with sequencing (ATAC-seq), epigenetics has been appreciated as a contributing factor that enforces T cell differentiation toward exhaustion in the TME. Importantly, specific epigenetic alterations and epigenetic factors have been found to control CD8+ T cell exhaustion phenotypes. In this review, we will explain the background of T cell differentiation and various exhaustion states and discuss how epigenetics play an important role in these processes. Then we will outline specific epigenetic changes and certain epigenetic and transcription factors that are known to contribute to CD8+ T cell exhaustion. We will also discuss the most recent methodologies that are used to study and discover such epigenetic modulations. Finally, we will explain how epigenetic reprogramming is a promising approach that might facilitate the development of novel exhausted T cell-targeting immunotherapies.
The role of RNA-binding proteins in orchestrating germline development in Caenorhabditis elegans
Authors: Albarqi Mennatallah M. Y. , Ryder Sean P.
Published: January 2023

RNA passed from parents to progeny controls several aspects of early development. The germline of the free-living nematode Caenorhabditis elegans contains many families of evolutionarily conserved RNA-binding proteins (RBPs) that target the untranslated regions of mRNA transcripts to regulate their translation and stability. In this review, we summarize what is known about the binding specificity of C. elegans germline RNA-binding proteins and the mechanisms of mRNA regulation that contribute to their function. We examine the emerging role of miRNAs in translational regulation of germline and embryo development. We also provide an overview of current technology that can be used to address the gaps in our understanding of RBP regulation of mRNAs. Finally, we present a hypothetical model wherein multiple 3′UTR-mediated regulatory processes contribute to pattern formation in the germline to ensure the proper and timely localization of germline proteins and thus a functional reproductive system.
Sustainable production of biofuels and bioderivatives from aquaculture and marine waste
Authors: Alvarado-Ramírez Lynette , Santiesteban-Romero Berenice , Poss Guillaume , Sosa-Hernández Juan Eduardo , Iqbal Hafiz M. N. , Parra-Saldívar Roberto , Bonaccorso Alfredo D. , Melchor-Martínez Elda M.
Published: January 2023

The annual global fish production reached a record 178 million tonnes in 2020, which continues to increase. Today, 49% of the total fish is harvested from aquaculture, which is forecasted to reach 60% of the total fish produced by 2030. Considering that the wastes of fishing industries represent up to 75% of the whole organisms, the fish industry is generating a large amount of waste which is being neglected in most parts of the world. This negligence can be traced to the ridicule of the value of this resource as well as the many difficulties related to its valorisation. In addition, the massive expansion of the aquaculture industry is generating significant environmental consequences, including chemical and biological pollution, disease outbreaks that increase the fish mortality rate, unsustainable feeds, competition for coastal space, and an increase in the macroalgal blooms due to anthropogenic stressors, leading to a negative socio-economic and environmental impact. The establishment of integrated multi-trophic aquaculture (IMTA) has received increasing attention due to the environmental benefits of using waste products and transforming them into valuable products. There is a need to integrate and implement new technologies able to valorise the waste generated from the fish and aquaculture industry making the aquaculture sector and the fish industry more sustainable through the development of a circular economy scheme. This review wants to provide an overview of several approaches to valorise marine waste (e.g., dead fish, algae waste from marine and aquaculture, fish waste), by their transformation into biofuels (biomethane, biohydrogen, biodiesel, green diesel, bioethanol, or biomethanol) and recovering biomolecules such as proteins (collagen, fish hydrolysate protein), polysaccharides (chitosan, chitin, carrageenan, ulvan, alginate, fucoidan, and laminarin) and biosurfactants.
Silver-promoted solid-phase guanidinylation enables the first synthesis of arginine glycosylated Samoamide A cyclopeptide analogue
Authors: Liang Bingxin , Li Rong , Li Linji , Tang Ming , Li Xiang , Su Chunli , Liao Hongli
Published: January 2023

Cyclization and glycosylation serve as effective approaches for enhancing the drug properties of peptides. Distinct from typical glycosylation, atypical arginine N-glycosylation has drawn increasing attention due to its fundamental role in various cellular procedures and signaling pathways. We previously developed a robust strategy for constructing arginine N-glycosylated peptides characterized by silver-promoted solid-phase guanidinylation. Modeled after cyclic octapeptide Samoamide A, an antitumor peptide composed of eight hydrophobic amino acids extracted from cyanobacteria, herein we first performed arginine scanning to determine an optimal position for replacement with arginine. Consequently, the first synthesis of arginine glycosylated Samoamide A cyclopeptide analogue was described combining solid-phase glycosylation with solution-phase cyclization. The resultant SA-HH-TT displayed enhanced water solubility compared with the non-glycosylated SA-HH-TT. Notably, our method provides a universal strategy for synthesizing arginine N-glycosylated cyclopeptides.
Highly effective removal of nickel ions from wastewater by calcium-iron layered double hydroxide
Authors: Li Ning , Yuan Mingjie , Lu Sheng , Xiong Xiaoli , Xie Zhigang , Liu Yongsheng , Guan Wei
Published: January 2023

Water pollution due to heavy metals has become a universal environmental problem. Ni(II) is a common heavy metal ion in polluted wastewater, which has high toxicity and carcinogenicity. In this study, the structure of a calcium-iron layered double hydroxide (Ca-Fe-LDHs) was synthesized and characterized by FTIR, XRD, SEM and XPS. Then, Ni(II) ion was effectively removed by Ca-Fe-LDHs and its mechanism for this materials was described. The maximum adsorption capacity of Ni(II) for Ca-Fe-LDHs was 418.9 mg‧g−1 when the initial concentration of Ni(II) was 1 g/L. The adsorption and removal of Ni(II) by Ca-Fe-LDHs was attributed to the action of hydroxyl groups on the hydrotalcite, generating surface capture. Ni(OH)2)0.75(H2O)0.16(NiCO3)0.09, Ni(OH)2, NiO, NiSO4 and other precipitates were generated on its surface. And a small amount of Ni-Fe-LDHs was generated through isomorphic transition before hydrolysis. Therefore, surface capture and isomorphic transition enhanced the removal efficiency of Ni(II) with Ca-Fe-LDHs, making Ca-Fe-LDHs as a potential material for effective removal of Ni(II).
In-situ construction of Zr-based metal-organic framework core-shell heterostructure for photocatalytic degradation of organic pollutants
Authors: Abdel Aziz Yasmeen S. , Sanad Moustafa M. S. , Abdelhameed Reda M. , Zaki Ayman H.
Published: January 2023

Photocatalysis is an eco-friendly promising approach to the degradation of textile dyes. The majority of reported studies involved remediation of dyes with an initial concentration ≤50 mg/L, which was away from the existing values in textile wastewater. Herein, a simple solvothermal route was utilized to synthesize CoFe2O4@UiO-66 core-shell heterojunction photocatalyst for the first time. The photocatalytic performance of the as-synthesized catalysts was assessed through the photodegradation of methylene blue (MB) and methyl orange (MO) dyes at an initial concentration (100 mg/L). Under simulated solar irradiation, improved photocatalytic performance was accomplished by as-obtained CoFe2O4@UiO-66 heterojunction compared to bare UiO-66 and CoFe2O4. The overall removal efficiency of dyes (100 mg/L) over CoFe2O4@UiO-66 (50 mg/L) reached >60% within 180 min. The optical and photoelectrochemical measurements showed an enhanced visible light absorption capacity as well as effective interfacial charge separation and transfer over CoFe2O4@UiO-66, emphasizing the successful construction of heterojunction. The degradation mechanism was further explored, which revealed the contribution of holes (h+), superoxide (•O2−), and hydroxyl (•OH) radicals in the degradation process, however, h+ were the predominant reactive species. This work might open up new insights for designing MOF-based core-shell heterostructured photocatalysts for the remediation of industrial organic pollutants.
Emergence of plasmid-mediated colistin resistance mcr-3.5 gene in Citrobacter amalonaticus and Citrobacter sedlakii isolated from healthy individual in Thailand
Authors: Phuadraksa Thanawat , Wichit Sineewanlaya , Songtawee Napat , Tantimavanich Srisurang , Isarankura-Na-Ayudhya Chartchalerm , Yainoy Sakda
Published: January 2023

Citrobacterspp. are Gram-negative bacteria commonly found in environments and intestinal tracts of humans and animals. They are generally susceptible to third-generation cephalosporins, carbapenems and colistin. However, several antibiotic resistant genes have been increasingly reported inCitrobacterspp., which leads to the postulation thatCitrobacterspp. could potentially be a reservoir for spreading of antimicrobial resistant genes. In this study, we characterized two colistin-resistantCitrobacterspp. isolated from the feces of a healthy individual in Thailand. Based on MALDI-TOF and ribosomal multilocus sequence typing, both strains were identified asCitrobacter sedlakiiandCitrobacter amalonaticus. Genomic analysis and S1-nuclease pulsed field gel electrophoresis/DNA hybridization revealed thatCitrobacter sedlakiiandCitrobacter amalonaticusharboredmcr-3.5gene on pSY_CS01 and pSY_CA01 plasmids, respectively. Both plasmids belonged to IncFII(pCoo) replicon type, contained the same genetic context (Tn3-IS1-ΔTnAs2-mcr-3.5-dgkA-IS91) and exhibited high transferring frequencies ranging from 1.03×10-4- 4.6×10-4CFU/recipient cellEscherichia coliJ53. Colistin-MICs of transconjugants increased ≥ 16-fold suggesting thatmcr-3.5on these plasmids can be expressed in other species. However, besidemcr, other major antimicrobial resistant determinants in multidrug resistant Enterobacterales were not found in these two isolates. These findings indicate thatmcrgene continued to evolve in the absence of antibiotics selective pressure. Our results also support the hypothesis thatCitrobactercould be a reservoir for spreading of antimicrobial resistant genes. To the best of our knowledge, this is the first report that discovered human-derivedCitrobacterspp. that harboredmcrbut no other major antimicrobial resistant determinants. Also, this is the first report that described the presence ofmcrgene inC. sedlakiiandmcr-3inC. amalonaticus.
Trypanosoma cruzi-specific CD8+ T cells and other immunological hallmarks in chronic Chagas cardiomyopathy: Two decades of research
Authors: Puerta Concepción J. , Cuellar Adriana , Lasso Paola , Mateus Jose , Gonzalez John M.
Published: January 2023

Trypanosoma cruzi, the causal agent of Chagas disease, has coexisted with humans for thousands of years. Therefore, the parasite has developed several mechanisms of antigenic variability that has allowed it to live inside the cells and evade the host immune response. Since T. cruzi displays an intracellular cycle-stage, our research team focused on providing insights into the CD8+ T cells immune response in chronic Chagas cardiomyopathy. We began our work in the 2000s studying parasite antigens that induce natural immune responses such as the KMP11 protein and TcTLE, its N-terminal derived peptide. Different approaches allowed us to reveal TcTLE peptide as a promiscuous CD8+ T cell epitope, able of inducing multifunctional cellular immune responses and eliciting a humoral response capable of decreasing parasite movement and infective capacity. Next, we demonstrated that as the disease progresses, total CD8+ T cells display a dysfunctional state characterized by a prolonged hyper-activation state along with an increase of inhibitory receptors (2B4, CD160, PD-1, TIM-3, CTLA-4) expression, an increase of specific terminal effector T cells (TTE), a decrease of proliferative capacity, a decrease of stem cell memory (TSCM) frequency, and a decrease of CD28 and CD3ζ expression. Thus, parasite-specific CD8+ T cells undergo clonal exhaustion, distinguished by an increase in late-differentiated cells, a mono-functional response, and enhanced expression of inhibitory receptors. Finally, it was found that anti-parasitic treatment induces an improved CD8+ T cell response in asymptomatic individuals, and a mouse animal model led us to establish a correlation between the quality of the CD8+ T cell responses and the outcome of chronic infection. In the future, using OMICs strategies, the identification of the specific cellular signals involved in disease progression will provide an invaluable resource for discovering new biomarkers of progression or new vaccine and immunotherapy strategies. Also, the inclusion of the TcTLE peptide in the rational design of epitope-based vaccines, the development of immunotherapy strategies using TSCM or the blocking of inhibitory receptors, and the use of the CD8+ T cell response quality to follow treatments, immunotherapies or vaccines, all are alternatives than could be explored in the fight against Chagas disease.