Evaluation of Anti-Hyperlipidemic Activity of the Seeds Extracts of Ficus carica: In Vitro and In Silico Approaches.

Obesity and hyperlipidemia have become major disorders predominantly causing prevailing cardiovascular diseases and ultimately death. The prolonged use of anti-obesity drugs and statins for reducing obesity and blood lipid levels is leading toward adverse effects of kidneys and muscles, specifically rhabdomyolysis. The objective of this study is to evaluate potential of seeds of Ficus carica against hyperlipidemia. Various extracts and isolated compounds from fig seeds were analyzed and evaluated for their anti-hyperlipidemic potential. Methanol extract and its ethyl acetate fraction showed maximum pancreatic lipase inhibition of 61.93% and 86.45% in comparison to reference drug Orlistat. Four compounds isolated by HPLC-PDA technique were determined as Gallic acid, Catechin, Epicatechin, and Quercetin also showed strong potential to inhibit enzyme pancreatic lipase comparable to Orlistat. These isolated compounds were further analyzed for molecular docking and MM-GBSA studies. Three ligands, namely Quercetin, Epicatechin, and Catechin were found more effective against pancreatic lipase as these possessed docking scores (-9.881, -9.741, -9.410) higher to that of the reference ligand Orlistat (-5.273). The binding free energies of these compounds were -55.03, -56.54, and 60.35 kcal/mol, respectively. The results have shown that Quercetin has the highest binding affinity correlating with the highest inhibition of pancreatic lipase enzyme 1LPB. Hence, it is suggested that seeds of F. carica have promising anti-hyperlipidemic potential and foremost in reducing obesity.

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.

Advance computational tools for multiomics data learning.

The burgeoning field of bioinformatics has seen a surge in computational tools tailored for omics data analysis driven by the heterogeneous and high-dimensional nature of omics data. In biomedical and plant science research multi-omics data has become pivotal for predictive analytics in the era of big data necessitating sophisticated computational methodologies. This review explores a diverse array of computational approaches which play crucial role in processing, normalizing, integrating, and analyzing omics data. Notable methods such similarity-based methods, network-based approaches, correlation-based methods, Bayesian methods, fusion-based methods and multivariate techniques among others are discussed in detail, each offering unique functionalities to address the complexities of multi-omics data. Furthermore, this review underscores the significance of computational tools in advancing our understanding of data and their transformative impact on research.

Investigation of the toxicity and safety concerns of transgenic maize seeds expressing immunogenic F and HN protein genes against Newcastle disease virus.

Introduction: The presented study investigated the potential toxicity and safety concerns associated with transgenic maize seeds expressing immunogenic F and HN protein genes against Newcastle disease virus (NDV). Methodology: The experiment involved feeding Sprague-Dawley rats with transgenic maize seeds formulated into standard diets at levels of 30% (w/w) for a duration of 90 days. The rats were divided into three groups, with 10 rats per group. We assessed various parameters including overall appearance, feed consumption, body weight, organ weight, hematological parameters, serum chemistry, and histopathology. Results: The results of these assessments were compared between the control group and the treatment groups. The study findings revealed that there were no significant differences between the control and treatment groups in terms of overall appearance, feed consumption, body weight, organ weight, hematological parameters, serum chemistry, microscopic histopathology, and gross appearance of tissues. These observations suggest that the consumption of transgenic maize seeds did not lead to any treatment-related adverse effects or toxicological issues. Furthermore, the transgenic maize seeds were found to be nutritionally equivalent to their non-transgenic counterpart. Conclusion: Overall, no physiological, pathological, or molecular toxicity was observed in the Rats fed with transgenic feed.However, it is important to note that this study focused specifically on the parameters measured and the outcomes observed in Sprague-Dawley rats, and further research and studies are necessary to fully evaluate the safety and potential applications of transgenic edible vaccines in humans or other animals.

Metabolic Phenotyping of Healthy and Diseased Human RPE Cells.

Purpose: Metabolic defects in the retinal pigment epithelium (RPE) underlie many retinal degenerative diseases. This study aims to identify the nutrient requirements of healthy and diseased human RPE cells. Methods: We profiled nutrient use of various human RPE cells, including differentiated and dedifferentiated fetal RPE (fRPE), induced pluripotent stem cell-derived RPE (iPSC RPE), Sorsby fundus dystrophy (SFD) patient-derived iPSC RPE, CRISPR-corrected isogenic SFD (cSFD) iPSC RPE, and ARPE-19 cell lines using Biolog Phenotype MicroArray Assays. Results: Differentiated fRPE cells and healthy iPSC RPE cells can use 51 and 48 nutrients respectively, including sugars, intermediates from glycolysis and tricarboxylic acid (TCA) cycle, fatty acids, ketone bodies, amino acids, and dipeptides. However, when fRPE cells lose their epithelial phenotype through dedifferentiation, nutrient use becomes restricted to 17 nutrients, primarily sugar and glutamine-related amino acids. SFD RPE cells can use 37 nutrients; however, compared to cSFD RPE and healthy iPSC RPE, they are unable to use lactate, some TCA cycle intermediates, and short-chain fatty acids. Nonetheless, they show increased use of branch-chain amino acids (BCAAs) and BCAA-containing dipeptides. Dedifferentiated ARPE-19 cells grown in traditional culture media cannot use lactate and ketone bodies. In contrast, nicotinamide supplementation promotes differentiation toward an epithelial phenotype, restoring the ability to use these nutrients. Conclusions: Epithelial phenotype confers metabolic flexibility to healthy RPE for using various nutrients. SFD RPE cells have reduced metabolic flexibility, relying on the oxidation of BCAAs. Our findings highlight the potentially important roles of nutrient availability and use in RPE differentiation and diseases.

Impact of gated FDG PET/CT on the staging of patients with suspected or proven newly diagnosed advanced epithelial ovarian, fallopian tube, and primary peritoneal cancer: results from a non-randomized, phase II clinical trial.

OBJECTIVE: Imaging for staging ovarian cancer is important to determine the extent of disease. The primary objective of this study was to compare gated 18F-fluorodeoxyglucose positron emission tomography coupled with computed tomography (FDG PET/CT) and standard CT scan with intravenous contrast to diagnose thoracic involvement in patients with advanced ovarian cancer prior to treatment. The secondary objective was to estimate changes in the International Federation of Gynecology and Obstetrics (FIGO) stage and clinical management resulting from gated PET/CT. METHODS: The IMAGE trial is a non-randomized phase II clinical trial comparing standard CT scanning with gated PET/CT in diagnosing thoracic involvement in a non-selected group of patients with suspected ovarian cancer on a contrast CT scan. Three sets of PET images were obtained comprising an ungated 2 min whole body image, a static 7.5 min image of the upper abdomen and thorax, and a gated end-expiratory image over the upper abdomen and thorax. Images were evaluated for specificity, sensitivity, diagnostic accuracy, and the proportion of patients with changes in FIGO stage and subsequent clinical management was compared between imaging techniques. RESULTS: A total of 84 patients were enrolled based on a standard CT scan, 67 of whom were eligible for gated PET/CT scans. Diagnostic accuracy with gated PET/CT was more than 80% for lesions in lung, liver, extra-abdominal sites, and pleura, but less than 50% for extra-abdominal lymph nodes. Compared with CT scan at baseline, 46% of patients who had 7.5 min gated PET/CT had disease upstaged from stage III to IV, and 8% had disease downstaged from stage IV to III. However, this led to a change of management in only 5% of patients. CONCLUSIONS: Gated PET/CT enables upstaging; however, in our institution it altered clinical management only in a minority of patients. TRIAL REGISTRATION NUMBER: NCT02258165.

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.

FL-DSFA: Securing RPL-Based IoT Networks against Selective Forwarding Attacks Using Federated Learning.

The Internet of Things (IoT) is a significant technological advancement that allows for seamless device integration and data flow. The development of the IoT has led to the emergence of several solutions in various sectors. However, rapid popularization also has its challenges, and one of the most serious challenges is the security of the IoT. Security is a major concern, particularly routing attacks in the core network, which may cause severe damage due to information loss. Routing Protocol for Low-Power and Lossy Networks (RPL), a routing protocol used for IoT devices, is faced with selective forwarding attacks. In this paper, we present a federated learning-based detection technique for detecting selective forwarding attacks, termed FL-DSFA. A lightweight model involving the IoT Routing Attack Dataset (IRAD), which comprises Hello Flood (HF), Decreased Rank (DR), and Version Number (VN), is used in this technique to increase the detection efficiency. The attacks on IoT threaten the security of the IoT system since they mainly focus on essential elements of RPL. The components include control messages, routing topologies, repair procedures, and resources within sensor networks. Binary classification approaches have been used to assess the training efficiency of the proposed model. The training step includes the implementation of machine learning algorithms, including logistic regression (LR), K-nearest neighbors (KNN), support vector machine (SVM), and naive Bayes (NB). The comparative analysis illustrates that this study, with SVM and KNN classifiers, exhibits the highest accuracy during training and achieves the most efficient runtime performance. The proposed system demonstrates exceptional performance, achieving a prediction precision of 97.50%, an accuracy of 95%, a recall rate of 98.33%, and an F1 score of 97.01%. It outperforms the current leading research in this field, with its classification results, scalability, and enhanced privacy.

Cardiac manifestations and outcomes of COVID-19 vaccine-associated myocarditis in the young in the USA: longitudinal results from the Myocarditis After COVID Vaccination (MACiV) multicenter study.

Background: We aimed to study the clinical characteristics, myocardial injury, and longitudinal outcomes of COVID-19 vaccine-associated myocarditis (C-VAM). Methods: In this longitudinal retrospective observational cohort multicenter study across 38 hospitals in the United States, 333 patients with C-VAM were compared with 100 patients with multisystem inflammatory syndrome in children (MIS-C). We included patients ≤30 years of age with a clinical diagnosis of acute myocarditis after COVID-19 vaccination based on clinical presentation, abnormal biomarkers and/or cardiovascular imaging findings. Demographics, past medical history, hospital course, biochemistry results, cardiovascular imaging, and follow-up information from April 2021 to November 2022 were collected. The primary outcome was presence of myocardial injury as evidenced by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging. Findings: Patients with C-VAM were predominantly white (67%) adolescent males (91%, 15.7 ± 2.8 years). Their initial clinical course was more likely to be mild (80% vs. 23%, p < 0.001) and cardiac dysfunction was less common (17% vs. 68%, p < 0.0001), compared to MIS-C. In contrast, LGE on CMR was more prevalent in C-VAM (82% vs. 16%, p < 0.001). The probability of LGE was higher in males (OR 3.28 [95% CI: 0.99, 10.6, p = 0.052]), in older patients (>15 years, OR 2.74 [95% CI: 1.28, 5.83, p = 0.009]) and when C-VAM occurred after the first or second dose as compared to the third dose of mRNA vaccine. Mid-term clinical outcomes of C-VAM at a median follow-up of 178 days (IQR 114-285 days) were reassuring. No cardiac deaths or heart transplantations were reported until the time of submission of this report. LGE persisted in 60% of the patients at follow up. Interpretation: Myocardial injury at initial presentation and its persistence at follow up, despite a mild initial course and favorable mid-term clinical outcome, warrants continued clinical surveillance and long-term studies in affected patients with C-VAM. Funding: The U.S. Food and Drug Administration.

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.

Chromoblastomycosis: A Single Centre Clinical Laboratory Experience of Seven Years (2016-2022) and Literature Review From Pakistan.

BACKGROUND: Chromoblastomycosis (CBM) is a chronic infection of skin and subcutaneous tissue. CBM cases have been reported in local literature from Pakistan with heterogenous demographic, diagnostic and therapeutic information. The objective of this study is to share the experience of CBM from a large tertiary care hospital laboratory in Pakistan. METHOD: This was a retrospective observational study. Histopathology and microbiology data of suspected CBM between 2016 and 2022 was retrieved. Patients' demographics, site of involvement, histopathological findings and positive microbiology cultures were assessed. Literature search on Google Scholar, PubMed and PakMediNet was done between 1990 and 2023 with multiple terms. RESULT: A total of 16 CBM cases were identified; 14 were histopathology positive and two were both histopathology and culture positive. The median age was 21 years, and 11 patients were male. The predominant site was lower extremities followed by the face. Severe acanthosis, hyperkeratosis and granuloma with sclerotic bodies were observed in all histopathology slides. Alternaria spp. and Phialophora spp. were isolated from two culture-positive cases. A total of nine cases of CBM were reported from Pakistan in PubMed non-indexed journal. CONCLUSION: CBM is not a commonly thought of disease when evaluating skin lesions in Pakistan. A high index of suspicion when assessing patients who may have a history of trauma, exposure to soil and suggestive lesions is reasonable. An integrated approach between clinicians, histopathologist and microbiologist is required to do early identification and therapeutic interventions.

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.

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.

Assessing disintegration effectiveness: A thorough evaluation using the SeDeM-ODT expert system for doxylamine succinate orodispersible formulation.

BACKGROUND: The SeDeM-ODT expert system is designed to assess the suitability of the pharmaceutical ingredients for their conversion into an orodispersible formulation by direct compression. The tool can be utilized to select the most appropriate excipients that improve the compressibility and buccodispersibility of the formulation. OBJECTIVE: This study aimed to utilize the SeDeM-ODT expert system to evaluate the performance of superdisintegrants and select an appropriate superdisntegrant for Doxylamine Succinate orodispersible formulation. METHOD: The SeDeM-ODT expert system scrutinized the excipients to develop an orodispersible Doxylamine Succinate formulation. Among the 15 parameters of the tool, some of them were determined through experimental work, while the remaining were calculated through the experimental values of other parameters. The central composite design approach was used for formulation development. The prepared powder blends were compressed using the direct compression method and evaluated for different parameters (hardness, thickness, diameter, friability, weight variation, water absorption ratio, wetting time, and disintegration time). RESULTS: The results of the SeDeM-ODT expert system were correlated with the values obtained by the post-compression tests. The Crospovidone formulation (F7) was found to be an optimized formulation as it disintegrated quickly compared with the other formulations containing other superdisintegtrants. The results perfectly endorsed the SeDeM-ODT expert system evaluation, as Crospovidone showed the highest IGCB value of 6.396. CONCLUSION: The study observed the effectiveness of the expert system in accurately examining the performance of disintegrating agents. The study observed the effectiveness of the expert system in accurately examining the performance of disintegrating agents. The assessment proved Crospovidone to produce quicker disintegration in Doxylamine Succinate orodispersible formulation.

Childhood trauma distribution and behavioural problems among Pakistani adolescents.

BACKGROUND: Childhood trauma adversely impacts adolescents, and consequently, they develop behavioural problems. Understanding the distribution of childhood traumas and their association with behavioural problems among adolescents is paramount for the preventive efforts. AIM/OBJECTIVE: The present research aimed to investigate this association among adolescents. METHODS: This association was investigated among adolescents (N = 200) between 12 and 18 years. Childhood Trauma Questionnaire and Strength and Difficulty Questionnaire was used to assess the distribution of trauma and internalizing and externalizing behavioural problems among adolescents through purposive and convenience sampling technique. RESULTS: The findings across trauma distribution indicated higher distribution of childhood abuse and neglect across males as compared to females. Males further significantly scored higher on sexual abuse and emotional neglect. Apparently, a large number of adolescents experienced all five sub types of childhood traumas (sexual abuse, emotional abuse, physical abuse, emotional and physical neglect). Additionally, across the severity continuum of childhood traumas, male scored higher on the severe to extreme continuum for all subtypes except physical abuse, where females scored higher. Lastly, logistic regression analysis indicated higher peer problems among those adolescents who have experienced all types of childhood traumas. CONCLUSION: These findings could be beneficial for intervention-based programs and policies to help trauma-exposed adolescents cope with their lives.

Factor XII signaling via uPAR-integrin ß1 axis promotes tubular senescence in diabetic kidney disease.

Coagulation factor XII (FXII) conveys various functions as an active protease that promotes thrombosis and inflammation, and as a zymogen via surface receptors like urokinase-type plasminogen activator receptor (uPAR). While plasma levels of FXII are increased in diabetes mellitus and diabetic kidney disease (DKD), a pathogenic role of FXII in DKD remains unknown. Here we show that FXII is locally expressed in kidney tubular cells and that urinary FXII correlates with kidney dysfunction in DKD patients. F12-deficient mice (F12-/-) are protected from hyperglycemia-induced kidney injury. Mechanistically, FXII interacts with uPAR on tubular cells promoting integrin ß1-dependent signaling. This signaling axis induces oxidative stress, persistent DNA damage and senescence. Blocking uPAR or integrin ß1 ameliorates FXII-induced tubular cell injury. Our findings demonstrate that FXII-uPAR-integrin ß1 signaling on tubular cells drives senescence. These findings imply previously undescribed diagnostic and therapeutic approaches to detect or treat DKD and possibly other senescence-associated diseases.

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.

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.

Functional genomics and taxonomic insights into heavy metal tolerant novel bacterium Brevibacterium metallidurans sp. nov. NCCP-602T isolated from tannery effluent in Pakistan.

The strain designated NCCP-602T was isolated from tannery effluent, and displayed aerobic, gram-positive, rod-shaped cells that were characterized by oxidase negative, catalase positive, and non-motile features. The most favourable growth conditions were observed at a temperature of 30°C, pH 7.0, and NaCl concentration of 1% (w/v). It tolerated heavy metals at high concentrations of chromium (3600 ppm), copper (3300 ppm), cadmium (3000 ppm), arsenic (1200 ppm) and lead (1500 ppm). The results of phylogenetic analysis, derived from sequences of the 16S rRNA gene, indicated the position of strain NCCP-602T within genus Brevibacterium and showed that it was closely related to Brevibacterium ammoniilyticum JCM 17537T. Strain NCCP-602 T formed a robust branch that was clearly separate from closely related taxa. A comparison of 16S rRNA gene sequence similarity and dDDH values between the closely related type strains and strain NCCP-602T provided additional evidence supporting the classification of strain NCCP-602T as a distinct novel genospecies. The polar lipid profile included diphosphatidylglycerol, glycolipid, phospholipids and amino lipids. MK-7 and MK-8 were found as the respiratory quinones, while anteiso-C15:0, iso-C15:0, iso-C16:0, iso-C17:0, and anteiso-C17:0 were identified as the predominant cellular fatty acids (> 10%). Considering the convergence of phylogenetic, phenotypic, chemotaxonomic, and genotypic traits, it is suggested that strain NCCP-602 T be classified as a distinct species Brevibacterium metallidurans sp. nov. within genus Brevibacterium with type strain NCCP-602T (JCM 18882T = CGMCC1.62055T).