Mn-Fe dual metal-organic framework based on trimesic acid as a high-performance electrode for lithium metal batteries.

A novel Mn-Fe dual metal-organic framework (Mn-Fe-BTC DMOF) was synthesized via a one-step hydrothermal method and employed as a cathode material in lithium metal batteries. The Mn-Fe-BTC DMOF exhibited a high initial capacity (1385 mA h g-1) and after 100 cycles (687 mA h g-1), demonstrating its potential for high-performance energy storage devices.

Assessing Heavy Metal Contamination in Commonly Used Fertilizers for Polyculture Fish Ponds and Its Implications for Human Health: A Comprehensive Investigation.

Over-fertilizing fish ponds can cause pollution, introducing heavy metals into the food chain and posing health risks. The present study investigated the incidence of heavy metals (Pb, Cu, Cd, and Cr) in commonly applied fertilizers, including nitrogen, phosphorus and potassium (NPK), triple superphosphate (TSP), and di-ammonium phosphate (DAP), and their association with heavy metals in water, sediment, and cultured fish species (Catla catla, Labeo rohita, and Cyprinus carpio) in polyculture fish ponds. The study was conducted over 4 months, with four groups in triplicates: control (no fertilizer), group 1 (NPK), group 2 (TSP), and group 3 (DAP). Heavy metal analysis was carried out using atomic absorption spectrophotometry before and after fertilizer application. Significantly (p < 0.05) higher levels of heavy metals were observed in water and sediment after applying fertilizers, with the most pronounced results in group 3 (DAP) followed by group 2 (TSP). The concentration of heavy metals was significantly (p < 0.05) higher in group 3 (DAP) fertilizers compared to other groups. Compared to the control, the concentration and bioaccumulation of heavy metals were significantly (p < 0.05) higher in the fertilizer-applied groups, with notably higher levels in group 3 (DAP). Cluster analysis and the correlation matrix did not show any significant association between the heavy metals and the fertilizers, indicating a complex interplay between the biotic and abiotic factors of the system. The health index (HI) value was < 1 in fish muscles of all studied groups, indicating the fish are safe for consumption. The study recommends monitoring and regulating fertilizer use, especially DAP, to prevent heavy metal contamination, and exploring sustainable alternatives to minimize environmental and health risks.

Comparison of perceived stress and oral health status using perceived stress scale and DMFT index between healthy, undiagnosed hypertensive, and known hypertensive dental patients.

Subtle and asymptomatic nature of high blood pressure results in increase in mortality and morbidity. Dentists may play a vital role in identifying patients with suspected hypertension who are not yet diagnosed to refer them timely to physicians for diagnosis and management of the condition. The aim of this study was to compare the oral health status using decayed, missing, filled teeth (DMFT) index and perceived stress score using perceived stress scale (PSS-10) between systemically healthy dental patients, and patients with undiagnosed and known hypertension attending dental out-patient department of Combined Military Hospital (CMH) Lahore Medical College & Institute of Dentistry, Lahore, Pakistan. It is a cross-sectional descriptive study in which 108 patients participated selected through purposive sampling method, 36 in each group. According to Kruskal Wallis H test, there were significant associations seen among the three groups with age (p < 0.001), DMFT (p < 0.001), and PSS-10 scores (p = 0.003). According to Spearman's matrix correlations, moderate positive correlations were observed between mean arterial pressure (MAP) and DMFT (r = 0.46, p < 0.001), and MAP and age (r = 0.38, p = 0.001), DMFT and PSS-10 (r = 0.47, p < 0.001), and DMFT and age (r = 0.33, p = 0.004) in healthy and patients with undiagnosed hypertension. It may be concluded that patients with raised blood pressure have higher perceived stress and deteriorated oral health.

Developing lifestyle intervention program for pre-hypertensive patients; consensus building using a modified Delphi approach.

BACKGROUND: Prehypertension is a preclinical state of hypertension which leads to an increased likelihood of coronary heart disease, myocardial infarction, cerebrovascular disease as well as target organ damage. Addressing pre-hypertension through early lifestyle interventions is crucial to mitigating these detrimental effects and improving long-term health outcomes. So, the main objective of this study is to develop a lifestyle intervention program (LSIP) for the management of prehypertension using consensus building approach. METHODS: It was a three round online modified Delphi study with 70 members panellists. All panellists had an experience of prehypertension either as patients (n = 30) or professionals (n = 40). Round 1 included initial recommendations developed from a previous systematic review and metanalysis, which were rated by panellists for their importance on a 5-point Likert scale. Panellists could also suggest additional items in the Round 1. Round 2 and 3 included all items from the Round 1 with new items suggested by the panellists. Data was analysed descriptively using SPSS version 29. All items receiving at least 70% of all respondents combined rating of 'Important' and 'Very Important' in Round 3 were included in the final set of recommendations. RESULTS: Fifty-one panellists (80.9%) (patients = 25, professionals = 26) completed Round 3. Twenty-six recommendation items were included in the Round 1. Twenty new items were added in Round 2 with 46 total items in Round 2 and 3. Thirty-five of these items reached consensus in Round 3. The final set of recommendation comprised of 15 educational. 10 dietary, and 10 exercise recommendations. CONCLUSION: This modified Delphi study developed a comprehensive LSIP for the prevention of prehypertension, incorporating a holistic approach with educational, dietary, and exercise components aimed at the general population. Previously established standards of care (SOC) for managing prehypertension varied significantly and often provided fragmented guidance particularly on physical activity and education. This preventive model offers a novel and scalable approach for early intervention in prehypertension, potentially reducing reliance on medications and improving long-term health outcomes.

Caregivers' expectations of their non-verbal autistic children in rural KwaZulu-Natal.

BACKGROUND:  Caregiver expectations have been shown to impact child outcomes. There is limited research regarding caregivers of non-verbal autistic children in rural South Africa. Autistic individuals form part of a larger environment, which they influence and which impacts them. Caregivers form part of this environment. OBJECTIVES:  This study aims to explore caregivers' expectations of communication, education, social implications and intervention for their non-verbal autistic child in rural KwaZulu-Natal (KZN). METHOD:  Bronfenbrenner's ecological and bioecological systems theory framed the study and allowed the child's interaction with their environment to be understood through the use of a qualitative study design via interviews. Eleven caregivers (pilot study: n = 1 and main study: n = 10) of non-verbal autistic children were selected and interviewed. Data were analysed thematically. RESULTS:  Caregivers had varied expectations. Grandparents were often the primary caregivers (microsystem). Relationships within the mesosystem (caregiver and therapist) and caregiver's understanding affected their feelings and expectations that changed over time (chronosystem). Education was the predominant expectation. The study highlighted limited resources (schools) within the exosystem. Caregivers reported both support and judgement from their communities. CONCLUSION:  There is a need for public awareness, caregiver counselling and autism support groups in rural KZN and more specialised education options in order to improve caregivers' expectations.Contribution: This study contributes to the limited literature in the field of autism in South Africa, more specifically the rural context and communication disorders.

Optimization and pharmacological evaluation of phytochemical-rich Cuscuta reflexa seed extract for its efficacy against chlorpyrifos-induced hepatotoxicity in murine models.

The popular organophosphorus (OP) compound chlorpyrifos (CP) has recently gained significant attention due to its health risks, particularly among farmers exposed to OP pesticides. This study aimed to evaluate the acute toxicity of Cuscuta reflexa seed extract (CRSE) and its efficacy of mitigating the adverse effects of CP in albino male mice. For acute toxicity analysis, the first group was served as the control group, while the second group was received CRSE (200 mg/kg/bw) on the first day of the 14-day experiment. For hepatotoxicity analysis, the first group was the control group, the second group (vehicle control) received corn oil (CO) (2 mL/kg/bw), the third group was given CP (20 mg/kg/bw) dissolved in corn oil and the fourth group was given CP (20 mg/kg/bw) along-with CRSE (200 mg/kg/bw) orally via gavage once daily for 21 days. The acute toxicity examination revealed no statistically significant differences between the CRSE-treated and control groups in serum biochemical indicators and histopathological analyses of various organs, suggesting that CRSE as safe at a dosage of 200 mg/kg/bw, with an oral LD50 in mice higher than 200 mg/kg. The hepatotoxicity study demonstrated that the CP administration resulted in liver damage and oxidative stress, while CRSE acted as an antioxidant and attenuated the signs of oxidative stress in liver damage. Hence, a promising therapeutic approach for lowering CP hepatotoxicity is co-treatment with CRSE.

A case-control study investigating cardiovascular health in maintenance hemodialysis patients through oxidative stress biomarkers and carotid artery intima-media thickness.

INTRODUCTION: Chronic kidney disease (CKD) is a major risk factor for the development of cardiovascular disease (CVD), and it is the leading cause of morbidity and mortality in end-stage renal disease (ESRD) patients receiving maintenance hemodialysis (MHD).

Sex prediction according to digital analysis of the morphological characteristics of maxillary posterior teeth in a Pakistani population.

Objective: Researchers have examined several dental characteristics to identify differences in tooth morphology between males and females in various populations. Nevertheless, no research has been undertaken to ascertain sexual dimorphism and develop a sex prediction model by using the groove pattern, cusp number and occlusal pattern in any population group. Therefore, this study accessed the sexual differences and the ability to predict sex according to these characteristics of maxillary teeth in the Pakistani community. Method: A total of 130 dental casts were selected (65 each from males and females). Digital images of the occlusal surface of the maxillary first premolar, second premolar and first molar were captured with a Canon Powershot A2200 14.1 MP digital camera with 4× optical zoom. Cusp number, groove pattern and occlusal pattern were recorded for each tooth type. Data were analysed with chi-square tests and logistic regression analysis. Results: The groove pattern and occlusal pattern of the maxillary first premolar and first molar showed significant sexual dimorphism (p < 0.05). The cusp number of the maxillary first molar also displayed a statistically significant difference between males and females (p < 0.05). The sex prediction accuracy was 76.7% for the training samples and 70% for the test samples. Conclusion: We observed significant sexual dimorphism in the groove pattern and the occlusal pattern of the maxillary first premolar and maxillary first molar teeth, as well as the cusp number of the maxillary first molar teeth. The prediction model demonstrated good accuracy, at 76.7%, and hence can be used for sex prediction in the Pakistani population.

Molecular characterization of Peste des petits ruminants virus (PPRV) in sheep and goats and risk factors associated with it in selected districts of Khyber Pakhtunkhwa-Pakistan.

BACKGROUND: Peste des Petits Ruminants (PPR) is an economically significant transboundary viral disease of sheep and goats caused by the PPRV virus, affecting annual losses of 1.45-2.10 billion US dollars globally. We designed the current study to evaluate the positive cases, molecular characterization, phylogenetic analysis, and risk factors correlated with the disease in various districts of Khyber Pakhtunkhwa, Pakistan, with the aim of contributing to these strategies. METHODS AND RESULTS: A total of 384 samples from three selected districts, i.e., Peshawar, Charsadda and Chitral (n = 128 each), were collected, and the virus was investigated by using the sandwich ELISA, while the N gene of the virus was used as a target for molecular detection via RT-PCR. The confirmed samples were then sequenced, and phylogenetic analysis was performed. According to our findings, the highest positive cases was found in district Peshawar (50.87%), followed by Charsadda and Chitral (24.56%), respectively, while risk factor analysis showed that certain categories, such as species, sex, and age less than two years, have higher risk (P < 0.05) in contrast to their respective categories. Furthermore, sequencing and phylogenetic analysis of representative samples showed that the PPRV strains in the current study clustered in lineage IV, which is circulating in the small ruminant population of Asia, the Middle East, and African countries. Comparative residue analysis highlighted the mutation by representing 242 variable sites out of 371 locations. CONCLUSIONS: PPRV has foremost importance in Pakistan because the virus was detected in a considerable number of samples, and most of which were sourced from subsidiary areas where veterinary services are not prioritized.

Comparison of TC-325 Hemostatic Powder with Standard Endoscopic Treatments for Malignancy-Related Upper Gastrointestinal Bleeding: Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: TC-325 powder has been successfully used in the management of malignancy-related upper gastrointestinal bleeding (UGIB) with favorable results. We conducted a meta-analysis of randomized controlled trials (RCTs) comparing TC-325 hemostatic powder with standard endoscopic treatments in the management of malignancy-related UGIB. METHODS: Several databases were reviewed from inception to May 02, 2024 to identify RCTs comparing TC-325 and standard endoscopic treatments for the management of malignancy-related UGIB. Our outcomes of interest were immediate hemostasis, 30-day rebleeding, length of hospital stay, need for surgery, need for angiographic embolization, and all-cause mortality. We calculated pooled risk ratio (RR) with 95% confidence intervals (CI) for categorical variables and mean difference (MD) with 95% CI for continuous variables. We used a random effect model to analyze the data and heterogeneity was assessed by I2 statistic. RESULTS: Four RCTs with 227 patients were included. We found that, the rate of immediate hemostasis was significantly higher in the TC-325 group compared to the standard therapy group, RR (95% CI): 1.48 (1.26, 1.74). There was no significant difference in 30-day rebleeding between the groups RR (95% CI): 0.52 (0.15, 1.76). We found no significant difference in other outcomes between groups such as the need for angiographic embolization, all-cause mortality, length of hospital stay, and need for surgery. CONCLUSIONS: We found that, TC-325 hemostatic powder was superior to standard endoscopic treatments in achieving immediate hemostasis in patients with malignancy-related UGIB.

Clinical prognostication in acute necrotizing encephalopathy of childhood: the role of magnetic resonance imaging severity assessment.

BACKGROUND: Acute necrotizing encephalopathy of childhood is a unique entity with bilateral gray and white matter involvement. OBJECTIVE: The aim of this study is to explore whether the severity of findings on imaging scans is indicative of the prognosis and clinical outcomes for pediatric patients with acute necrotizing encephalopathy. MATERIALS AND METHODS: A retrospective cross-sectional study was conducted on 42 patients diagnosed with acute necrotizing encephalopathy. A severity score based on MR imaging was computed for each patient, utilizing a point system determined by the existence of factors such as hemorrhage, cavitation, enhancement, diffusion restriction, and lesion location. The scoring was categorized into mild, moderate, and severe. Clinical outcomes were determined at the time of discharge and at follow-ups as mild disability, moderate disability, severe disability, and death according to the modified Rankin Scale. Associations were determined by Fisher's exact test, chi-square test, and one-way ANOVA. RESULTS: The study included 21 boys and 21 girls with a mean age of 71.5 months. A statistically significant connection (P=0.027) was found between the severity score from MR imaging and the clinical outcome. A statistically significant relationship was also observed between diffusion restriction (P=0.008), cerebellar involvement (P=0.048), and an unfavorable clinical outcome. Additionally, individuals who experienced shock exhibited a correlation with adverse outcomes (P=0.01). CONCLUSION: In predicting the outcome of acute necrotizing encephalopathy, cerebellar involvement and presence of diffusion restriction were associated with worse clinical outcomes in our study. Developing a comprehensive MR-based severity score is crucial for improving diagnostic accuracy and patient outcomes. Our findings underscore the importance of including diffusion restriction and cerebellar involvement in the scoring system.

Comparison of light microscopy and digital microscopy for learning oral pathology practicals among second year dental students.

Background/purpose: Previous studies have shown that digital microscopy is an indispensable tool for teaching oral pathology laboratory course. Despite this, our institute relies solely on recommended/reference book images for oral pathology practicals, neglecting both light and digital microscopy methods. Gathering students' feedback on these methods is essential before considering digital microscopy as part of the oral pathology curriculum. Therefore, this study aimed to compare the usefulness of light and digital microscopy among second-year dental students. Materials and methods: The study was conducted from December 6 to December 7, 2023, in the Department of Oral Pathology, Dr. Ishrat-ul-Ibad Khan Institute of Oral Health Sciences, Dow University of Health Sciences. The study involved the selection of five cases from the oral pathology course, followed by feedback on students' diagnostic skills, learning impact and acceptance rate of light and digital microscopy using an online questionnaire. Mann-Whitney U test was used to compare students' responses and P-value < 0.05 was set as statistically significant. Results: There was a statistically significant difference in diagnostic scores between light microscopy and digital microscopy (P < 0.05). Statistically significant differences favoring digital microscopy were observed in various aspects, including interpreting variations, diagnosis, time efficiency, and image clarity. Conclusion: Although diagnostic scores were lower, digital microscopy was perceived as a useful method for enhancing diagnostic skills among dental students. Both light microscopy and digital microscopy are viable options for oral pathology practicals, however, digital microscopy was preferred by students due to its time efficiency and clear image quality.

Fabrication, Characterization, and Performance Evaluation of Thermally Stable [5,6]-Fused Bicyclic Energetic Materials.

In recent decades, there has been considerable interest in investigating advanced energetic materials characterized by high stability and favorable energetic properties. Nevertheless, reconciling the conflicting balance between high energy and the insensitivity of such materials through traditional approaches, which involve integrating fuel frameworks and oxidizing groups into an organic molecule, presents significant challenges. In this study, we employed a promising method to fabricate high-energy-density materials (HEDMs) through the intermolecular assembly of variously substituted purines with a high-energy oxidant. Purines are abundant in nature and are readily available. A series of advanced energetic materials with a good balance between energy and sensitivity were prepared by the simple and effective self-assembly of purines with high-energy oxidants. Notably, these compounds exhibit incredibly improved crystal densities (1.80-2.00 g·cm-3) and good detonation performance (D: 7072-8358 m·s-1; P: 19.82-34.56 GPa). In comparison to RDX, these self-assembled energetic materials exhibit reduced mechanical sensitivities and enhanced thermal stabilities. Compounds 1-5 demonstrate both high energy and low sensitivity, indicating that self-assembly represents a straightforward and effective approach for developing advanced energetic materials with a balanced combination of energy and safety. Moreover, this study offers an avenue for synthesizing energetic materials based on naturally occurring compounds assembled through intermolecular attractions, thereby achieving a balance between energy and sensitivity along with versatile functionality.

A Voice-Activated Device Exercise and Social Engagement Program for Older Adult-Care Partner Dyads: Pilot Clinical Trial and Focus Group Study Evaluating the Feasibility, Use, and Estimated Functional Impact of EngAGE.

BACKGROUND: Maintaining exercise is essential for healthy aging but difficult to sustain. EngAGE is a socially motivated exercise program delivered over a voice-activated device that targets older adult-care partner dyads. OBJECTIVE: This 10-week pilot study aimed to assess EngAGE feasibility and use, obtain user experience feedback, and estimate potential impact on function. METHODS: In total, 10 older adults aged ≥65 years were recruited from an independent living residence together with their self-identified care partners. EngAGE delivered National Institute on Aging Go4Life exercises to older adults daily, while care partners received progress reports and prompts to send encouraging messages that were read aloud by the device to the older adult. Older adults' use was tracked, and physical function was assessed at baseline and follow-up. Follow-up focus group data provided qualitative feedback. RESULTS: On average, participants completed 393.7 individual exercises over the 10-week intervention period or 39.4 exercises/wk (range 48-492, median 431, IQR 384-481, SD 112.4) without injury and used EngAGE on an average of 41 of 70 days or 4.1 d/wk (range 7-66, median 51, IQR 23-56, and SD 21.2 days). Mean grip strength increased nonsignificantly by 1.3 kg (preintervention mean 26.3 kg, SD 11.0; postintervention mean 27.6 kg, SD 11.6; P=.34), and 4 of 10 participants improved by a minimal clinically important difference (MCID) of 2.5 kg. Further, the time for 5-repeated chair stands significantly reduced by 2.3 seconds (preintervention mean 12, SD 3.6 s; postintervention mean 9.7, SD 2.7 s; P=.02), and 3 of 9 participants improved by an MCID of -2.3 seconds. Furthermore, 3-meter usual walk performance was brisk at baseline (mean 2.1, SD 0.4 s) and decreased by 0.1 seconds (postintervention 2, SD 0.4 s; P=.13), although 5 of 9 participants improved by a MCID of 0.05 m/s. Qualitative results showed perceived benefits, favored program features, and areas for improvement. CONCLUSIONS: We present a pilot study of a new voice-activated device application customized to older adult users that may serve as a guide to other technology development for older adults. Our pilot study served to further refine the application and to inform a larger trial testing EngAGE's impact on functional outcomes, a necessary step for developing evidence-based technology tools.

Leadership competencies for dentists: What do undergraduate students think?

Dentists face difficult situations and challenges every day, but undergraduate dental students in Pakistan are not formally taught leadership skills or assessed for these skills. This study aims to explore the perception of undergraduate dental students on various leadership competencies. A multi-institutional cross-sectional observational study was conducted on undergraduate students in five institutions by using universal sampling technique. Students were asked to self-assess various leadership competencies for dentists based on 15 competencies using a validated questionnaire utilizing Likert scale response format. Responses to these items were presented as frequency and percentage. The overall scores were presented in mean and standard deviation and median and interquartile range. The differences in median scores of all items of the questionnaire between male and female students were determined with Mann Whitney U tests. The year-wise differences in the median of all response items of the questionnaire were determined using Kruskal Wallis H test. A total of 750 students, of which 570 (76%) were females and 180 (24%) were males, participated in the study. Most of the students (n = 708, 94.4%) did not attended any leadership course or workshop in the last five years. Majority of the students perceived that their leadership competencies were fair to excellent. Empathy was perceived as 'excellent' by the majority of the students (n = 294, 39.2%). Majority of the students (n = 319, 42.5%) perceived that their 'authenticity' skills were 'good'. Statistically significant differences were reported between male and female students in most of the leadership skills including 'compassion', 'advocacy skills', 'inquiry skills', 'empathy', 'integrity', 'ability to build trust with others', 'managing conflict', 'leading groups/teams', 'dealing with difficult personalities', and 'likelihood to exercise leadership during a crisis' (p < 0.05). There were also significant differences in the median item scores in 13 out of 15 leadership domains and the year of study (p < 0.05). The study identified the perceptions of students regarding different leadership competencies. It gives indications that which leadership competencies need to be incorporated, promoted, and enhanced in leadership curriculum to make them effective dental practitioners and leaders in future. Incorporating these targeted leadership courses into the curriculum can provide participants with the opportunity to refine their existing leadership strengths and develop a well-rounded set of competencies essential for making a significant contribution in their chosen fields.

Impact of the circular economy on ecological footprint: evidence from Germany.

The circular economy practices contribute to sustainable development by maximising efficiency, utilising renewable resources, extending product lifespans, and implementing waste reduction strategies. This study investigates the individual impacts of four sources of the circular economy on the ecological footprint in Germany, a country that is among the pioneers in establishing a comprehensive roadmap for the circular economy. The four sources examined are renewable energy consumption (REC), recycling, reuse, and repair of materials. Using time series data from 1990 to 2021, the study employed the dynamic autoregressive distributed lag (ARDL) simulation technique and also applied kernel-based linear regression (KRLS) to test the robustness of the results. The findings revealed that reuse practices significantly reduce the ecological footprint in both the short and long run. REC and repair also substantially decrease the ecological footprint, as shown by the simulation analysis. Conversely, while recycling is generally considered crucial for minimising environmental impact, in this study, it was found to contribute to environmental degradation. This paradox may be attributed to the nascent state of the recycling industry and data limitations. The results from KRLS confirm the findings of the dynamic ARDL. It is recommended that policymakers develop measures that are appropriate, efficient, and targeted to enhance the role of each source of the circular economy in reducing the ecological footprint in Germany. The major limitation of the study is its reliance on the indirect measures of circular economy attributed to the non-availability of data on direct measures.

Mechanistic target of rapamycin (mTOR) pathway in Sertoli cells regulates age-dependent changes in sperm DNA methylation.

Over the past several decades, a trend toward delayed childbirth has led to increases in parental age at the time of conception. Sperm epigenome undergoes age-dependent changes increasing risks of adverse conditions in offspring conceived by fathers of advanced age. The mechanism(s) linking paternal age with epigenetic changes in sperm remain unknown. The sperm epigenome is shaped in a compartment protected by the blood-testes barrier (BTB) known to deteriorate with age. Permeability of the BTB is regulated by the balance of two mTOR complexes in Sertoli cells where mTOR complex 1 (mTORC1) promotes the opening of the BTB and mTOR complex 2 (mTORC2) promotes its integrity. We hypothesized that this balance is also responsible for age-dependent changes in the sperm epigenome. To test this hypothesis, we analyzed reproductive outcomes, including sperm DNA methylation in transgenic mice with Sertoli cell-specific suppression of mTORC1 (Rptor KO) or mTORC2 (Rictor KO). mTORC2 suppression accelerated aging of the sperm DNA methylome and resulted in a reproductive phenotype concordant with older age, including decreased testes weight and sperm counts, and increased percent of morphologically abnormal spermatozoa and mitochondrial DNA copy number. Suppression of mTORC1 resulted in the shift of DNA methylome in sperm opposite to the shift associated with physiological aging - sperm DNA methylome rejuvenation and mild changes in sperm parameters. These results demonstrate for the first time that the balance of mTOR complexes in Sertoli cells regulates the rate of sperm epigenetic aging. Thus, mTOR pathway in Sertoli cells may be used as a novel target of therapeutic interventions to rejuvenate the sperm epigenome in advanced-age fathers.

Role of Interleukins in Pancreatic Cancer: A Literature Review.

PURPOSE: This review article summarizes the pathophysiological aspects of interleukins (ILs) including IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, and IL-10 in pancreatic cancer (PC). METHODS: Science Direct, PubMed, and Google Scholar were used for the literature review. The search was conducted until August 12, 2024, and particular keywords such as "Pancreatic Cancer," "Interleukins," "Pathophysiological Aspects," "Immunosuppression," "Invasiveness," and "Metastasis" were used. Focusing on interleukins related to pancreatic cancer, 61 original studies were included: 32 studies for human patients, 16 studies for animal models, and 13 studies for both animal models and human patients. All types of PC were considered. The timeframe of 1991 to 2024 was chosen for clinical studies. RESULTS: In epithelial pancreatic tumors, IL-1 is a major inflammation factor. Serum concentrations of soluble interleukin-2-receptor were considerably greater in patients with PC and chronic pancreatitis than in healthy individuals. In comparison to controls, pancreatic cancer patients had considerably greater levels of macrophage colony-stimulating factor and significantly lower levels of stem cell factor and IL-3. The tissues and cells of pancreatic cancer have higher concentrations of IL-4 receptors. IL-5 has a role in the accumulation of pancreatic fibrosis. For individuals with pancreatic ductal adenocarcinoma (PDAC), a high serum level of IL-6 may be a separate risk factor for the development of widespread liver metastases. PDAC patients' peripheral blood mononuclear cells exhibit a substantial upregulation of IL-7 receptor. The role of IL-8 in the growth and spread of PC in humans. The miR-200a/ß-catenin axis may be the mechanism by which IL-9 stimulates the proliferation and metastasis of PC cells. Blocking IL-10 in the local microenvironment appears to result in a significant reversal of tumor-induced immunosuppression. CONCLUSION: The article concludes that interleukins 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10 played significant roles in the pathogenesis of PC.

Integrating network analysis with differential expression to uncover therapeutic and prognostic biomarkers in esophageal squamous cell carcinoma.

Introduction: Esophageal squamous cell carcinoma (ESCC) accounts for over 90% of all esophageal tumors. However, the molecular mechanism underlying ESCC development and prognosis remains unclear, and there are still no effective molecular biomarkers for diagnosing or predicting the clinical outcome of patients with ESCC. Here, we used bioinformatics analysis to identify potential biomarkers and therapeutic targets for ESCC. Methodology: Differentially expressed genes (DEGs) between ESCC and normal esophageal tissue samples were obtained by comprehensively analyzing publicly available RNA-seq datasets from the TCGA and GTEX. Gene Ontology (GO) annotation and Reactome pathway analysis identified the biological roles of the DEGs. Moreover, the Cytoscape 3.10.1 platform and subsidiary tools such as CytoHubba were used to visualize the DEGs' protein-protein interaction (PPI) network and identify hub genes, Furthermore our results are validated by using Single-cell RNA analysis. Results: Identification of 2524 genes exhibiting altered expression enriched in pathways including keratinization, epidermal cell differentiation, G alpha(s) signaling events, and biological process of cell proliferation and division, extracellular matrix (ECM) disassembly, and muscle function. Moreover, upregulation of hallmarks E2F targets, G2M checkpoints, and TNF signaling. CytoHubba revealed 20 hub genes that had a valuable influence on the progression of ESCC in these patients. Among these, the high expression levels of four genes, CDK1 MAD2L1, PLK1, and TOP2A, were associated with critical dependence for cell survival in ESCC cell lines, as indicated by CRISPR dependency scores, gene expression data, and cell line metadata. We also identify the molecules targeting these essential hub genes, among which GSK461364 is a promising inhibitor of PLK1, BMS265246, and Valrubicin inhibitors of CDK1 and TOP2A, respectively. Moreover, we identified that elevated expression of MMP9 is associated with worse overall survival in ESCC patients, which may serve as potential prognostic biomarker or therapeutic target for ESCC. The single-cell RNA analysis showed MMP9 is highly expressed in myeloid, fibroblast, and epithelial cells, but low in T cells, endothelial cells, and B cells. This suggests MMP9's role in tumor progression and matrix remodeling, highlighting its potential as a prognostic marker and therapeutic target. Discussion: Our study identified key hub genes in ESCC, assessing their potential as therapeutic targets and biomarkers through detailed expression and dependency analyses. Notably, MMP9 emerged as a significant prognostic marker with high expression correlating with poor survival, underscoring its potential for targeted therapy. These findings enhance our understanding of ESCC pathogenesis and highlight promising avenues for treatment.