bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrating Technological and Educational Collaborations: Enhancing Leadership and Participation in STEM Fields
Authors: Toolo Lineo
Published: January 2024

This study investigates the advancement of underrepresented groups in leadership roles within the fields of Science, Technology, Engineering, and Mathematics (STEM), areas traditionally dominated by their male counterparts. Through a convergent sequential mixed method, data was collected using 105 questionnaires and six semi-structured interviews involving students, lecturers, government officials, and university admissions administrators in the STEM disciplines. A concurrent triangulation strategy was applied for simultaneous quantitative and qualitative data analysis, utilizing MS Excel for the numerical data and thematic analysis for the narrative information. The research also examined statistical documents to assess the enrollment disparity among underrepresented groups and the presence of specific development programs in universities aimed at addressing this imbalance. Findings suggest that targeted and culturally informed collaborative efforts can effectively encourage the ascent of underrepresented demographics into STEM leadership roles in South African universities. The implications of the study are broad, given that the research spanned two distinct universities, implying that the strategies identified could inform actions across different educational institutions to foster inclusivity and equality in STEM leadership.
Needs, Motivations, and Abilities: Exploring the Perspectives of Science High School Educators in Performing and Writing Research
Authors: Galdonez Dominic Patric
Published: January 2024

Education is a constantly evolving field, driven by the increasing demand for innovative teaching methods. Teachers, often seen as the cornerstone of education, assume a multifaceted role that extends beyond the classroom. They actively engage in educational research, contributing significantly to the advancement of teaching and learning. This study aimed to collect, analyze, and comprehend the perceptions of teachers at the Philippine Science High School-Ilocos Region Campus in conducting and writing meaningful research. Utilizing a quantitative research approach, the study includes twenty-five (25) teachers from the Philippine Science High School-Ilocos Region Campus as respondents. A researcher-developed survey questionnaire, designed based on existing literature, serves as the primary data collection tool. Key findings from this research reveal that: teachers tend to hold a relatively negative perception of research-related factors within their school environment; teachers maintain a positive stance toward research in their professional roles; teachers are intrinsically motivated by research in their professional development; teachers recognize the presence of research-related difficulties within their professional roles; teachers exhibit a strong aptitude for planning research-related activities; teachers demonstrate impressive writing skills in the context of research. In summary, this study sheds light on the perceptions and experiences of teachers engaged in research activities at the Philippine Science High School-Ilocos Region Campus. It highlights the nuanced dynamics of their involvement, from mixed perceptions of research support to their unwavering motivation and commendable skills in planning and writing research papers. This research provides valuable insights for educators and institutions seeking to enhance research engagement and productivity among their teaching staff.
Carbon quantum dots in bioimaging and biomedicines
Authors: Das Surya , Mondal Somnath , Ghosh Dhiman
Published: January 2024

Carbon quantum dots (CQDs) are gaining a lot more attention than traditional semiconductor quantum dots owing to their intrinsic fluorescence property, chemical inertness, biocompatibility, non-toxicity, and simple and inexpensive synthetic route of preparation. These properties allow CQDs to be utilized for a broad range of applications in various fields of scientific research including biomedical sciences, particularly in bioimaging and biomedicines. CQDs are a promising choice for advanced nanomaterials research for bioimaging and biomedicines owing to their unique chemical, physical, and optical properties. CQDs doped with hetero atom, or polymer composite materials are extremely advantageous for biochemical, biological, and biomedical applications since they are easy to prepare, biocompatible, and have beneficial properties. This type of CQD is highly useful in phototherapy, gene therapy, medication delivery, and bioimaging. This review explores the applications of CQDs in bioimaging and biomedicine, highlighting recent advancements and future possibilities to increase interest in their numerous advantages for therapeutic applications.
Aconitine and its derivatives: bioactivities, structure-activity relationships and preliminary molecular mechanisms
Authors: Zhao Pengyu , Tian Ye , Geng Yuefei , Zeng Chenjuan , Ma Xiuying , Kang Jie , Lu Lin , Zhang Xin , Tang Bo , Geng Funeng
Published: January 2024

Aconitine (AC), which is the primary bioactive diterpene alkaloid derived from Aconitum L plants, have attracted considerable interest due to its unique structural feature. Additionally, AC demonstrates a range of biological activities, such as its ability to enhance cardiac function, inhibit tumor growth, reduce inflammation, and provide analgesic effects. However, the structure-activity relationships of AC are remain unclear. A clear understanding of these relationships is indeed critical in developing effective biomedical applications with AC. In line with these challenges, this paper summarized the structural characteristics of AC and relevant functional and bioactive properties and the structure-activity relationships presented in biomedical applications. The primary temporal scope of this review was established as the period spanning from 2010 to 2023. Subsequently, the objective of this review was to provide a comprehensive understanding of the specific action mechanism of AC, while also exploring potential novel applications of AC derivatives in the biomedical field, drawing upon their structural characteristics. In conclusion, this review has provided a comprehensive analysis of the challenges and prospects associated with AC in the elucidation of structure-bioactivity relationships. Furthermore, the importance of exploring modern biotechnology approaches to enhance the potential biomedical applications of AC has been emphasized.
Integrating computational methods guided the discovery of phytochemicals as potential Pin1 inhibitors for cancer: pharmacophore modeling, molecular docking, MM-GBSA calculations and molecular dynamics studies
Authors: Alzain Abdulrahim A. , Elbadwi Fatima A. , Shoaib Tagyedeen H. , Sherif Asmaa E. , Osman Wadah , Ashour Ahmed , Mohamed Gamal A. , Ibrahim Sabrin R. M. , Roh Eun Joo , Hassan Ahmed H. E.
Published: January 2024

Pin1 is a pivotal player in interactions with a diverse array of phosphorylated proteins closely linked to critical processes such as carcinogenesis and tumor suppression. Its axial role in cancer initiation and progression, coupled with its overexpression and activation in various cancers render it a potential candidate for the development of targeted therapeutics. While several known Pin1 inhibitors possess favorable enzymatic profiles, their cellular efficacy often falls short. Consequently, the pursuit of novel Pin1 inhibitors has gained considerable attention in the field of medicinal chemistry. In this study, we employed the Phase tool from Schrödinger to construct a structure-based pharmacophore model. Subsequently, 449,008 natural products (NPs) from the SN3 database underwent screening to identify compounds sharing pharmacophoric features with the native ligand. This resulted in 650 compounds, which then underwent molecular docking and binding free energy calculations. Among them, SN0021307, SN0449787 and SN0079231 showed better docking scores with values of −9.891, −7.579 and −7.097 kcal/mol, respectively than the reference compound (−6.064 kcal/mol). Also, SN0021307, SN0449787 and SN0079231 exhibited lower free binding energies (−57.12, −49.81 and −46.05 kcal/mol, respectively) than the reference ligand (−37.75 kcal/mol). Based on these studies, SN0021307, SN0449787, and SN0079231 showed better binding affinity that the reference compound. Further the validation of these findings, molecular dynamics simulations confirmed the stability of the ligand-receptor complex for 100 ns with RMSD ranging from 0.6 to 1.8 Å. Based on these promising results, these three phytochemicals emerge as promising lead compounds warranting comprehensive biological screening in future investigations. These compounds hold great potential for further exploration regarding their efficacy and safety as Pin1 inhibitors, which could usher in new avenues for combating cancer.
Red recombination enables a wide variety of markerless manipulation of porcine epidemic diarrhea virus genome to generate recombinant virus
Authors: Pan Shuonan , Mou Chunxiao , Chen Zhenhai
Published: January 2024

Porcine epidemic diarrhea virus (PEDV) is a member of the genera Alphacoronavirus that has been associated with acute watery diarrhea and vomiting in swine. Unfortunately, no effective vaccines and antiviral drugs for PEDV are currently available. Reverse genetics systems are crucial tools for these researches. Here, a PEDV full-length cDNA clone was constructed. Furtherly, three PEDV reporter virus plasmids containing red fluorescent protein (RFP), Nano luciferase (Nluc), or green fluorescence protein (GFP) were generated using Red recombination with the GS1783 E. coli strain. These reporter-expressing recombinant (r) PEDVs showed similar growth properties to the rPEDV, and the foreign genes were stable to culture up to P9 in Vero cells. Using the Nluc-expressing rPEDV, the replication of PEDV was easily quantified, and a platform for rapid anti-PEDV drug screening was constructed. Among the three drugs, Bergenin, Umifenovir hydrochloride (Arbidol), and Ganoderma lucidum triterpenoids (GLTs), we found that GLTs inhibited PEDV replication mainly after the stage of virus “Entry”. Overall, this study will broaden insight into the method for manipulating the PEDV genome and provide a powerful tool for screening anti-PEDV agents.
The pediatric gut bacteriome and virome in response to SARS-CoV-2 infection
Authors: Piazzesi Antonia , Pane Stefania , Del Chierico Federica , Romani Lorenza , Campana Andrea , Palma Paolo , Putignani Lorenza
Published: January 2024

Introduction

Since the beginning of the SARS-CoV-2 pandemic in early 2020, it has been apparent that children were partially protected from both infection and the more severe forms of the disease. Many different mechanisms have been proposed to explain this phenomenon, including children’s frequent exposure to other upper respiratory infections and vaccines, and which inflammatory cytokines they are more likely to produce in response to infection. Furthermore, given the presence of SARS-CoV-2 in the intestine and its ability to infect enterocytes, combined with the well described immunomodulatory capabilities of the microbiome, another potential contributing factor may be the presence of certain protective microbial members of the gut microbiota (GM).

Methods

We performed shotgun metagenomic sequencing and profiled both the bacteriome and virome of the GM of pediatric SARS-CoV-2 patients compared to healthy, age-matched subjects.

Results

We found that, while pediatric patients do share some pro-inflammatory microbial signatures with adult patients, they also possess a distinct microbial signature of protective bacteria previously found to be negatively correlated with SARS-CoV-2 infectivity and COVID-19 severity. COVID-19 was also associated with higher fecal Cytomegalovirus load, and with shifts in the relative abundances of bacteriophages in the GM. Furthermore, we address how the preventative treatment of COVID-19 patients with antibiotics, a common practice especially in the early days of the pandemic, affected the bacteriome and virome, as well as the abundances of antimicrobial resistance and virulence genes in these patients.

Discussion

To our knowledge, this is the first study to address the bacteriome, virome, and resistome of pediatric patients in response to COVID-19 and to preventative antibiotics use.
Isobavachalcone exhibits antifungal and antibiofilm effects against C. albicans by disrupting cell wall/membrane integrity and inducing apoptosis and autophagy
Authors: Qian Weidong , Lu Jiaxing , Gao Chang , Liu Qiming , Yao Wendi , Wang Ting , Wang Xiaobin , Wang Zhifeng
Published: January 2024

Isobavachalcone (IBC) is a natural flavonoid with multiple pharmacological properties. This study aimed to evaluate the efficacy of IBC against planktonic growth and biofilms of Candida albicans (C. albicans) and the mechanisms underlying its antifungal action. The cell membrane integrity, cell metabolic viability, and cell morphology of C. albicans treated with IBC were evaluated using CLSM and FESEM analyses. Crystal violet staining, CLSM, and FESEM were used to assess the inhibition of biofilm formation, as well as dispersal and killing effects of IBC on mature biofilms. RNA-seq combined with apoptosis and autophagy assays was used to examine the mechanisms underlying the antifungal action of IBC. IBC exhibited excellent antifungal activity with 8 μg/mL of MIC for C. albicans. IBC disrupted the cell membrane integrity, and inhibited biofilm formation. IBC dispersed mature biofilms and damaged biofilm cells of C. albicans at 32 μg/mL. Moreover, IBC induced apoptosis and autophagy-associated cell death of C. albicans. The RNA-seq analysis revealed upregulation or downregulation of key genes involved in cell wall synthesis (Wsc1 and Fks1), ergosterol biosynthesis (Erg3, and Erg11), apoptisis (Hsp90 and Aif1), as well as autophagy pathways (Atg8, Atg13, and Atg17), and so forth, in response to IBC, as evidenced by the experiment-based phenotypic analysis. These results suggest that IBC inhibits C. albicans growth by disrupting the cell wall/membrane, caused by the altered expression of genes associated with β-1,3-glucan and ergosterol biosynthesis. IBC induces apoptosis and autophagy-associated cell death by upregulating the expression of Hsp90, and altering autophagy-related genes involved in the formation of the Atg1 complex and the pre-autophagosomal structure. Together, our findings provide important insights into the potential multifunctional mechanism of action of IBC.
Diabetic peripheral neuropathy: pathogenetic mechanisms and treatment
Authors: Zhu Jinxi , Hu Ziyan , Luo Yifan , Liu Yinuo , Luo Wei , Du Xiaohong , Luo Zhenzhong , Hu Jialing , Peng Shengliang
Published: January 2024

Diabetic peripheral neuropathy (DPN) refers to the development of peripheral nerve dysfunction in patients with diabetes when other causes are excluded. Diabetic distal symmetric polyneuropathy (DSPN) is the most representative form of DPN. As one of the most common complications of diabetes, its prevalence increases with the duration of diabetes. 10-15% of newly diagnosed T2DM patients have DSPN, and the prevalence can exceed 50% in patients with diabetes for more than 10 years. Bilateral limb pain, numbness, and paresthesia are the most common clinical manifestations in patients with DPN, and in severe cases, foot ulcers can occur, even leading to amputation. The etiology and pathogenesis of diabetic neuropathy are not yet completely clarified, but hyperglycemia, disorders of lipid metabolism, and abnormalities in insulin signaling pathways are currently considered to be the initiating factors for a range of pathophysiological changes in DPN. In the presence of abnormal metabolic factors, the normal structure and function of the entire peripheral nervous system are disrupted, including myelinated and unmyelinated nerve axons, perikaryon, neurovascular, and glial cells. In addition, abnormalities in the insulin signaling pathway will inhibit neural axon repair and promote apoptosis of damaged cells. Here, we will discuss recent advances in the study of DPN mechanisms, including oxidative stress pathways, mechanisms of microvascular damage, mechanisms of damage to insulin receptor signaling pathways, and other potential mechanisms associated with neuroinflammation, mitochondrial dysfunction, and cellular oxidative damage. Identifying the contributions from each pathway to neuropathy and the associations between them may help us to further explore more targeted screening and treatment interventions.
Modified tibial cortex transverse transport for diabetic foot ulcers with Wagner grade ≥ II: a study of 98 patients
Authors: Liu Junpeng , Yao Xingchen , Xu Ziyu , Wu Yue , Pei Fuchun , Zhang Lin , Li Meng , Shi Ming , Du Xinru , Zhao Hui
Published: January 2024

Background

Diabetic foot ulcers constitute a substantial healthcare burden on a global scale and present challenges in achieving healing. Our objective was to assess the efficacy of modified tibial cortex transverse transport surgery in managing refractory diabetic foot ulcers.

Methods

We retrospectively analyzed clinical data from 98 patients suffering from diabetic foot ulcers classified as Wagner grade ≥II who were admitted to our medical facility between January 2020 and June 2022. All the patients were treated by modified tibial cortex transverse transport surgery, wherein the osteotomy scope was reduced to two rectangular bone windows measuring 1.5cm × 1.5cm each. Record the patient’s general information and ulcer healing time; ulcer area, ankle-brachial index, WIFi classification, and visual analogue scale before and 3 months following the surgical intervention.

Results

The average duration of diabetes of 98 patients with diabetic foot ulcer was 20.22 ± 8.02 years, 52 patients had more than one toe gangrene on admission. The postoperative wound healing rate was 95.83% and the average healing time was 53.18 ± 20.18 days. The patients showed significant improvement in ankle-brachial index, WIFi classification, and visual analogue scale at 3 months postoperatively compared to preoperatively, with statistically significant differences (P< 0.05). Eight patients experienced complications, and the incidence of complications was 8.16%. Throughout the follow-up period, there were no instances of ulcer recurrence noted.

Conclusion

Modified tibial cortex transverse transport surgery demonstrates effectiveness in the management of diabetic foot ulcers by enhancing lower limb microcirculation and facilitating the process of wound healing.
Forensic analysis and sequence variation of 133 STRs in the Hakka population
Authors: Feng Yuhang , Zhao Yutao , Lu Xiaoyu , Li Haiyan , Zhao Kai , Shi Meisen , Wen Shaoqing
Published: January 2024

Introduction: Short Tandem Repeats (STRs) are highly valuable genetic markers in forensic science. However, the conventional PCR-CE technique has limitations, and the emergence of massively parallel sequencing (MPS) technology presents new opportunities for STR analysis. Yet, there is limited research on Chinese population diversity using MPS.

Methods: In this study, we obtained genotype data for 52 A-STRs and 81 Y-STRs from the Hakka population in Meizhou, Guangdong, China, using the Forensic Analysis System Multiplecues SetB Kit on the MGISEQ-2000 platform.

Results: Our findings demonstrate that these 133 STRs are highly efficient for forensic applications within the Meizhou Hakka population. Statistical analysis revealed Hobs values ranging from 0.61306 to 0.91083 and Hexp values ranging from 0.59156 to 0.91497 for A-STRs based on length polymorphism. For sequence polymorphism, Hobs values ranged from 0.61306 to 0.94586, and Hexp values fluctuated between 0.59156 and 0.94487. The CPE values were 1-5.0779620E-21 and 1-3.257436E-24 for length and sequence polymorphism, respectively, while the CPD values were 1-1.727007E-59 and 1-5.517015E-66, respectively. Among the 80 Y-STR loci, the HD values for length and sequence polymorphism were 0.99764282 and 0.99894195, respectively. The HMP values stood at 0.00418102 and 0.00288427, respectively, and the DC values were 0.75502742 and 0.83363803, respectively. For the 52 A-STR loci, we identified 554 and 989 distinct alleles based on length and sequence polymorphisms, respectively. For the 81 Y-STR loci, 464 and 652 unique alleles were detected at the length and sequence level, respectively. Population genetic analysis revealed that the Meizhou Hakka population has a close kinship relationship with the Asian populations THI and KOR based on length polymorphism data of A-STRs. Conversely, based on length polymorphism data of Y-STRs, the Meizhou Hakka population has the closest kinship relationship with the Henan Han population.

Discussion: Overall, the variation information of repeat region sequences significantly enhances the forensic identification efficacy of STR genetic markers, providing an essential database for forensic individual and paternity testing in this region. Additionally, the data generated by our study will serve as a vital resource for research into the genetic structure and historical origins of the Meizhou Hakka population.
Improving French bean yield potential through induced mutagenesis using EMS and SA
Authors: Laskar Rafiul Amin , Dowarah Bhaskar , Tamang Dilip , Das Sangeeta , Borah Protiva , Raina Aamir
Published: January 2024

Introduction

French bean (Phaseolus vulgaris L.) holds global significance as one of the most consumed legumes, with commercial value surpassing that of all other legume crops combined. In India, the consumption of French beans has grown steadily, especially in the North Eastern region, driven by heightened consumer interest in its nutritional benefits. Considering these factors, we initiated an induced mutagenesis program to enhance the genetic diversity of locally grown French bean genotypes, traditionally cultivated for their superior adaptability.

Methods

To achieve this, we initiated an induced mutagenesis program. Seeds from the village seed stock were subjected to treatments with varying doses of ethyl methane sulfonate (EMS) ranging from 0.1% to 0.4% and sodium azide (SA) from 0.1% to 0.4%. The objective was to increase yield potential and enhance genetic diversity.

Results

The treatment with EMS and SA led to a non-specific, dosage-independent reduction in biophysiological characteristics in French bean mutants. Notably, the 0.4% SA treatment significantly inhibited germination and fertility, causing a decrease in chlorophyll (10.02 mg. g-1 FW) and carotenoid (1.57 mg. g-1 FW) levels. This suggests a disruption in genes associated with chlorophyll and carotenoid synthesis. However, in the M2 generation, the mutagenic treatments substantially improved yield and associated traits. The highest pod yield per plant was recorded at 79.50 gm for the 0.2% EMS treatment. A character association study revealed strong correlations (0.217 to 0.995) between pod yield and other agronomic traits.

Discussion

The results indicate that selecting mutants based on these traits in populations treated with EMS and SA can significantly increase crop yield. The 0.2% SA and 0.2% EMS M2 mutant populations exhibited the highest induced variability, making them ideal for selecting higher-yielding mutant lines for further breeding generations. The increased yields in these mutant lines, derived from a local cultivar, show promise for meeting the growing demand for French bean production through their widespread cultivation.
Modulatory role of nitric oxide in wound healing of potato tubers
Authors: Dogramaci Munevver , Sarkar Dipayan , Lulai Edward C.
Published: January 2024

Introduction

Wounding of potato (Solanum tuberosum L.) tubers affects the postharvest storage qualities and marketability. To mitigate wound-related losses, it is necessary to accelerate wound healing (WH) responses of potato tubers. While role of nitric oxide (NO) in healing of wounded biological tissues is well known, its impact on WH responses of potato tubers has not been examined thoroughly. The aim of this study was to elucidate the potential modulatory role of NO in WH response of potato tubers by determining the activity of key enzymes associated with NO biosynthesis.

Methods

Using a model wounding system, tuber tissue discs were extracted from mini tubers of cv. Russet Burbank to examine their WH responses. Tuber discs were treated with NO related chemicals, such as NO scavenger, nitric oxide synthase (NOS) inhibitor, and NO donors. The effect of these treatments on in vitro production of NO, activity of nitrate reductase, NOS, and phenylalanine ammonia-lyase were determined. The accumulation of suberin polyphenolics (SPP) in wounded parenchyma cells, an indicator of early suberization process, was analyzed histologically.

Results

Treatment of tuber tissues with the higher dose of an NO scavenger (2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) at the time of wounding completely ceased SPP accumulation between 0 h to 3 d after wounding. Increased production of NO and enhanced activity of NOS were also observed immediately after wounding of the tuber tissues. The results suggest that NO is a key biological modulator in WH responses of potato tubers and could be optimized as a potential exogenous treatment to counter wound-related losses.
Immune-related cardiovascular toxicities of PD-1/PD-L1 inhibitors in solid tumors: an updated systematic review and meta-analysis
Authors: Zhang Chi , Wei Fengtao , Ma Wenhan , Zhang Jingbo
Published: January 2024

Purpose

The objective of this study was to investigate the risk of cardiovascular toxicities related to PD-1/PD-L1 inhibitors in solid tumors.

Methods

A literature search was performed following the participants, interventions, comparisons, outcomes, and study design (PICOS) principles, and the study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data analysis was conducted using Review Manager version 5.4.

Results

This meta-analysis included 69 randomized controlled trials (RCTs) divided into five groups based on the treatment regimens: PD-1/PD-L1 + chemotherapy versus chemotherapy, PD-1/PD-L1 versus chemotherapy, PD-1/PD-L1 versus placebo, PD-1/PD-L1 + CTLA-4 versus PD-1/PD-L1 and PD-1/PD-L1 + CTLA-4 versus chemotherapy. Compared to chemotherapy treatment alone, PD-1/PD-L1 +chemotherapy significantly increased the risk of hypertension [all-grade (OR = 1.27, 95% CI [1.05, 1.53], p = 0.01); grade 3–5 (OR = 1.36, 95% CI [1.04, 1.79], p = 0.03)], hypotension [all-grade (OR = 2.03, 95% CI [1.19, 3.45], p = 0.009); grade 3–5 (OR = 3.60, 95% CI [1.22, 10.60], p = 0.02)], arrhythmia [all-grade (OR = 1.53, 95% CI [1.02, 2.30], p = 0.04); grade 3–5 (OR = 2.91, 95% CI [1.33, 6.39], p = 0.008)] and myocarditis [all-grade (OR = 2.42, 95% CI [1.06, 5.54], p = 0.04)]. The risk of all-grade hypotension (OR = 2.87, 95% CI [1.26, 6.55], p = 0.01) and all-grade arrhythmia (OR = 2.03, 95% CI [1.13, 3.64], p = 0.02) significantly increased when treated with PD-1/PD-L1 inhibitors compared to the placebo. The risks of cardiovascular toxicities are significantly higher with PD-1+CTLA-4 compared to PD-1 alone (OR = 2.02, 95% CI [1.12, 3.66], p = 0.02).

Conclusion

PD-1/PD-L1 inhibitor leads to an increased risk of cardiovascular toxicities, especially hypertension, hypotension, arrhythmia, and myocarditis.
Roles of ubiquitin-specific proteases in inflammatory diseases
Authors: Chen Rui , Zhang Hui , Li Linke , Li Jinsheng , Xie Jiang , Weng Jie , Tan Huan , Liu Yanjun , Guo Tailin , Wang Mengyuan
Published: January 2024

Ubiquitin-specific proteases (USPs), as one of the deubiquitinating enzymes (DUBs) families, regulate the fate of proteins and signaling pathway transduction by removing ubiquitin chains from the target proteins. USPs are essential for the modulation of a variety of physiological processes, such as DNA repair, cell metabolism and differentiation, epigenetic modulations as well as protein stability. Recently, extensive research has demonstrated that USPs exert a significant impact on innate and adaptive immune reactions, metabolic syndromes, inflammatory disorders, and infection via post-translational modification processes. This review summarizes the important roles of the USPs in the onset and progression of inflammatory diseases, including periodontitis, pneumonia, atherosclerosis, inflammatory bowel disease, sepsis, hepatitis, diabetes, and obesity. Moreover, we highlight a comprehensive overview of the pathogenesis of USPs in these inflammatory diseases as well as post-translational modifications in the inflammatory responses and pave the way for future prospect of targeted therapies in these inflammatory diseases.
Transcriptional profile of human thymus reveals IGFBP5 is correlated with age-related thymic involution
Authors: Yang Xiaojing , Chen Xichan , Wang Wei , Qu Siming , Lai Binbin , Zhang Ji , Chen Jian , Han Chao , Tian Yi , Xiao Yingbin , Gao Weiwu , Wu Yuzhang
Published: January 2024

Thymus is the main immune organ which is responsible for the production of self-tolerant and functional T cells, but it shrinks rapidly with age after birth. Although studies have researched thymus development and involution in mouse, the critical regulators that arise with age in human thymus remain unclear. We collected public human single-cell transcriptomic sequencing (scRNA-seq) datasets containing 350,678 cells from 36 samples, integrated them as a cell atlas of human thymus. Clinical samples were collected and experiments were performed for validation. We found early thymocyte-specific signaling and regulons which played roles in thymocyte migration, proliferation, apoptosis and differentiation. Nevertheless, signaling patterns including number, strength and path completely changed during aging, Transcription factors (FOXC1, MXI1, KLF9, NFIL3) and their target gene, IGFBP5, were resolved and up-regulated in aging thymus and involved in promoting epithelial-mesenchymal transition (EMT), responding to steroid and adipogenesis process of thymic epithelial cell (TECs). Furthermore, we validated that IGFBP5 protein increased at TECs and Hassall’s corpuscle in both human and mouse aging thymus and knockdown of IGFBP5 significantly increased the expression of proliferation-related genes in thymocytes. Collectively, we systematically explored cell-cell communications and regulons of early thymocytes as well as age-related differences in human thymus by using both bioinformatic and experimental verification, indicating IGFBP5 as a functional marker of thymic involution and providing new insights into the mechanisms of thymus involution.
Protective effects and mechanisms of ellagic acid on intestinal injury in piglets infected with porcine epidemic diarrhea virus
Authors: Song Zhuan , Deng Cuifang , Chen Qinyin , Zhao Shengnan , Li Peng , Wu Tao , Hou Yongqing , Yi Dan
Published: January 2024

The present study was conducted to decipher the protection effects of ellagic acid (EA) on piglets infected with porcine epidemic diarrhea virus (PEDV). Thirty 7-day-old piglets were randomly assigned to three treatment groups: control, PEDV, and EA + PEDV groups. After a 3-day period of adaption, piglets in the EA + PEDV group were orally administered with 20 mg/kg·BW EA during days 4-11 of the trial. On day 8, piglets were orally administered with PEDV at a dose of 106 TCID50 (50% tissue culture infectious dose) per pig. Additionally, intestinal porcine epithelial (IPEC-1) cells infected with PEDV were used to investigate the anti-PEDV effect of EA in vitro. The results showed that EA at a dose of 10-40 μmol/L increased the viability of PEDV-infected IPEC-1 cells, and EA administration mitigated intestinal edema in piglets challenged with PEDV. Further studies indicated that EA treatment significantly increased the proportion of white blood cells in blood and concentrations of IL-6, IL-1β, and IL-10 in the serum, but decreased the TNF-α content and gene expression of IL-6, IL-1β, TNF-α, and CXCL2 in the jejunum. Moreover, EA intervention considerably elevated the activity of total superoxide dismutase (T-SOD), but decreased the H2O2 concentration in the ileum of piglets. Importantly, EA suppressed the increased expression of antiviral-related genes and proteins (including MXI, ISG15, HSP70, and p-IRF7) induced by PEDV challenge in the jejunum. Furthermore, PEDV infection increased the protein abundance of p-JAK2 and p-STAT3, which were further enhanced by EA supplementation. In conclusion, our results revealed that EA could promote the restoration of intestinal homeostasis by regulating the interferon pathway that was interrelated with the activation of JAK2/STAT3 signaling. These findings provide theoretical basis for the use of EA as a therapy targeting PEDV infection in piglets.
An Fc-modified monoclonal antibody as novel treatment option for pancreatic cancer
Authors: Lutz Martina S. , Wang Kevin , Jung Gundram , Salih Helmut R. , Hagelstein Ilona
Published: January 2024

Pancreatic cancer is a highly lethal disease with limited treatment options. Hence, there is a considerable medical need for novel treatment strategies. Monoclonal antibodies (mAbs) have significantly improved cancer therapy, primarily due to their ability to stimulate antibody-dependent cellular cytotoxicity (ADCC), which plays a crucial role in their therapeutic efficacy. As a result, significant effort has been focused on improving this critical function by engineering mAbs with Fc regions that have increased affinity for the Fc receptor CD16 expressed on natural killer (NK) cells, the major cell population that mediates ADCC in humans. Here we report on the preclinical characterization of a mAb directed to the target antigen B7-H3 (CD276) containing an Fc part with the amino acid substitutions S239D/I332E to increase affinity for CD16 (B7-H3-SDIE) for the treatment of pancreatic cancer. B7-H3 (CD276) is highly expressed in many tumor entities, whereas expression on healthy tissues is more limited. Our findings confirm high expression of B7-H3 on pancreatic cancer cells. Furthermore, our study shows that B7-H3-SDIE effectively activates NK cells against pancreatic cancer cells in an antigen-dependent manner, as demonstrated by the analysis of NK cell activation, degranulation and cytokine release. The activation of NK cells resulted in significant tumor cell lysis in both short-term and long-term cytotoxicity assays. In conclusion, B7-H3-SDIE constitutes a promising agent for the treatment of pancreatic cancer.
Defining the “Correlate(s) of Protection” to tick-borne encephalitis vaccination and infection – key points and outstanding questions
Authors: Ackermann-Gäumann Rahel , Lang Phung , Zens Kyra D.
Published: January 2024

Tick-borne Encephalitis (TBE) is a severe disease of the Central Nervous System (CNS) caused by the tick-borne encephalitis virus (TBEV). The generation of protective immunity after TBEV infection or TBE vaccination relies on the integrated responses of many distinct cell types at distinct physical locations. While long-lasting memory immune responses, in particular, form the basis for the correlates of protection against many diseases, these correlates of protection have not yet been clearly defined for TBE. This review addresses the immune control of TBEV infection and responses to TBE vaccination. Potential correlates of protection and the durability of protection against disease are discussed, along with outstanding questions in the field and possible areas for future research.
Mapping interaction quality for nursing and medical students in primary care placement in municipal emergency care units: a systematic observational study
Authors: Giske Solveig , Gamlem Siv M. , Kvangarsnes Marit , Landstad Bodil J. , Hole Torstein , Dahl Berit Misund
Published: January 2024

Introduction

Primary care placement for nursing and medical students is vital for developing the competence to accommodate the increasing number of patients with multimorbid and complex conditions. Prior studies have suggested that interaction quality in primary care placement empowers learning. However, research mapping interaction quality in primary care placements in municipal emergency care units is lacking. This study aimed to systematically map interaction quality for nursing and medical students in primary care placement in two municipal emergency care units.

Materials and methods

This study adopted a systematic descriptive observational design. Systematic observations (n = 201 cycles) of eight nursing students (n = 103 cycles) and six medical students (n = 98 cycles) were used to map interaction quality across six learning situations between March and May 2019. Observations were coded using the Classroom Assessment Scoring System-Secondary (CLASS-S). Data were analyzed using descriptive statistics and Spearman correlations.

Results

Interaction quality is described in three domains: (I) emotional support, (II) framework for learning, and (III) instructional support, and the overall measure, student engagement. The results indicated middle-quality interactions in the emotional and instructional support domains and high quality in the framework for learning domain and student engagement. Correlations exhibited similar patterns and ranged from non-significant to strong correlations.

Conclusion

The interaction qualities indicated a generally positive and supportive learning environment contributing to nursing and medical students’ learning and active participation in work tasks related to their professional roles. Thus, this new form for primary care placement for nursing and medical students in the municipal emergency care units was found to be a positive learning arena. These results may enhance nursing and medical education programs in countries with similar health services and education. Health education, supervisors, peers, and others contributing to students’ learning should recognize which interaction qualities may affect learning and how to improve quality, thus affecting supervisors’ approach to training students. While the CLASS-S showed potential for mapping interaction qualities for nursing and medical students in primary care placement in municipal emergency care units, further studies are needed to validate the CLASS-S for use in clinical placement settings.
Sex-specific bacterial microbiome variation in octopus vulgaris skin
Authors: Rodríguez-Barreto Deiene , Sanz-González Juan Carlos , Martín M. Virginia , Arrieta Jesús M. , Almansa Eduardo
Published: January 2024

Growing knowledge of the host-microbiota of vertebrates has shown the prevalence of sex-specific differences in the microbiome. However, there are virtually no studies assessing sex-associated variation in the microbiome of cephalopods. Here we assess sex-specific variation in the common octopus (Octopus vulgaris) skin microbiome using amplicon sequencing targeting the V4 hypervariable region of prokaryote 16S rRNA genes. Skin and mantle-associated mucus was collected from wild adult individuals of common Octopus (Octopus vulgaris) (9 males and 7 females of similar size). There were no significant differences in the alpha diversity of microbial communities associated with skin or mantle mucosa between sexes. However, our results clearly indicate that adult octopus males and females have a distinct microbial community composition in both skin and mantle associated mucus communities, with female microbiome being dominated by Firmicutes (48.1%), while that of males contained a majority of Proteobacteria (60.5%), with Firmicutes representing only 3.30%, not finding significant differentiation in the microbial communities between the tissues explored. The dominance of different taxa in the skin ofO. vulgarisfemales and males (e.g., Mycoplasmatales andLactococcusin females and Rhizobiales and Rhodobacteriales in males) suggests a sex-specific symbiosis in which those microbes benefit from easy access to distinct substrates present in female and male skin, respectively. Given the lack of differences in size between specimens of both sexes in this study, we hypothesize differences in hormone profile, as well as behavioral or ecological differences between sexes in the wild, as the main drivers of microbiome differentiation between sexes. Most knowledge of cephalopod microbiota is limited to the digestive tract and the reproductive system. However, cephalopod skin is an organ with a plethora of functions. This is a first attempt to characterize cephalopod skin microbiota and determine sex influence on it.
From transients to permanent residents: the existence of obligate aerobic microorganisms in the goat rumen
Authors: Wang Rongjiao , Huang Dan , Chen Changguo , Song Dingzhou , Peng Hongen , He Min , Huang Xiujun , Huang Zhonghua , Wang Bin , Lan Hai , Tang Ping
Published: January 2024

The rumen serves as a complex ecosystem, harboring diverse microbial communities that play crucial ecological roles. Because previous studies have predominantly focused on anaerobic microorganisms, limited attention has been given to aerobic microorganisms in the goat rumen. This study aims to explore the diversity of aerobic microorganisms in the rumen and understand their niche and ecological roles. Rumen fluid samples were collected from 6 goats at different time points post-morning feeding. pH, NH3-N, and volatile fatty acid (TVFA) concentrations were measured, while In vitro cultivation of aerobic microorganisms was performed using PDA medium. Internal Transcribed Spacer (ITS) and 16S sequencing unveiled microbial diversity within the rumen fluid samples. Evidence of obligate aerobic microorganisms in the goat rumen suggests their potential contribution to ecological functionalities. Significantly, certain aerobic microorganisms exhibited correlations with TVFA levels, implying their involvement in TVFA metabolism. This study provides evidence of the existence and potential ecological roles of obligate aerobic microorganisms in the goat rumen. The findings underscore the significance of comprehensively deciphering goat rumen microbial communities and their interactions, with aerobes regarded as permanent residents rather than transients. These insights form a solid foundation for advancing our understanding of the intricate interplay between goat and their aerobic microorganisms in the rumen.
History of concussion and lowered heart rate variability at rest beyond symptom recovery: a systematic review and meta-analysis
Authors: Wesolowski Eric , Ahmed Zubair , Di Pietro Valentina
Published: January 2024

Introduction

Concussion is a growing concern in worldwide sporting culture. Heart rate variability (HRV) is closely tied with autonomic nervous system (ANS) deficits that arise from a concussion. The objective of this review was to determine if a history of concussion (HOC) can impact HRV values in the time-domain in individuals at rest. This review works to add to the literature surrounding HRV testing and if it can be used to check for brain vulnerabilities beyond the recovery of concussion symptoms.

Materials and methods

The systematic review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) method. A computer based systematic review scanned articles dating from 1996 to June 2023 through PubMed, Cochrane Library, Google Scholar, and EMBASE databases. A risk of bias assessment was conducted using the ROBINS-E tool. The average difference in time between heartbeats (MeanNN), the standard deviation of the differences (SDNN), and the root mean squared of the successive intervals (RMSSD) were measured.

Results

Six total studies were found that fit the inclusion criteria including a total of 242 participants (133 without HOC, 109 with HOC). The average age of the control group was 23.3 ± 8.2, while the average age of the history of TBI group was 25.4 ± 9.7, with no significant difference between the groups (p = 0.202). Four of the studies reported no significant difference in any of the three measures, while two of the studies reported significant difference for all three measures. The meta-analysis was conducted and found that MeanNN (p = 0.03) and RMSSD (p = 0.04) reached statistical significance, while SDNN did not (p = 0.11).

Conclusion

The results of this meta-analysis showed significant difference in two of the three HRV time-domain parameters evaluated. It demonstrates that there can be lowered HRV values that expand beyond the recovery of symptoms, reflecting an extensive period of ANS susceptibility after a concussion. This may be an important variable in determining an athlete’s return to play (RTP). Lack of homogenous study populations and testing methods introduces potential for bias and confounding factors, such as gender or age. Future studies should focus on baseline tests to compare individuals to themselves rather than matched controls.
12-week melatonin administration had no effect on diabetes risk markers and fat intake in overweight women night workers
Authors: de Sousa Carlos Alberto Rodrigues , Nogueira Luciana Fidalgo , Cipolla-Neto José , Moreno Claudia Roberta de Castro , Marqueze Elaine Cristina
Published: January 2024

Introduction

Interactions between circadian clocks and key mediators of chronic low-grade inflammation associated with fat consumption may be important in maintaining metabolic homeostasis and may pose a risk for the development of obesity-associated comorbidities, especially type 2 diabetes (T2DM).

Objective

The aims of the present study were to evaluate the effects of melatonin administration on diabetes risk markers according to dietary lipid profile (pro-inflammatory versus anti-inflammatory) in excessive weight night workers, and to determine the effect of administration on fat consumption profile.

Methods

A randomized, controlled, double-blind, crossover clinical trial involving 27 nursing professionals working permanent night shifts under a 12×36-hour system. The melatonin group (12 weeks) used synthetic melatonin (3 mg) only on days off and between shifts, while the placebo group (12 weeks) was instructed to take a placebo, also on days off and between shifts. For inflammatory characteristics, participants were divided into pro-inflammatory (saturated fats, trans fats and cholesterol) and anti-inflammatory (monounsaturated, polyunsaturated fats and EPA + DHA) groups according to fatty acid determinations. At baseline and at the end of each phase, blood glucose, insulin, glycosylated hemoglobin plasma concentrations were collected, and HOMA-IR was calculated.

Conclusion

Melatonin administration for 12 weeks had no effect on T2DM risk markers according to dietary lipid profile (pro-inflammatory or anti-inflammatory potential) in excessive weight night workers. Among the limitations of the study include the fact that the low dose may have influenced the results expected in the hypothesis, and individual adaptations to night work were not evaluated. The insights discussed are important for future research investigating the influence of melatonin and fats considered anti- or pro-inflammatory on glucose and insulin homeostasis related to night work.