Browse Articles

DNA damage modulates sleep drive in basal cnidarians with divergent chronotypes

Association between blink-related anterior segment dynamics and intraocular pressure

Ancestral pattern of the <i>Xenopus</i> germ cell cyst: From the germ stem cells to the oocytes and nurse cells

Atomically dispersed Pd-Mn dual-metal doped CeO2 nanorods for efficient methane oxychlorination

Knowledge, practices, and influencing factors of tracheostomy care among nurses in Northwest Amhara Hospitals, Ethiopia (2024)

L-lactic acid enhances type I interferon immune response and inhibits virus infection by promoting IRF9 L-lactylation

Lysine lactylation is a crucial posttranslational modification (PTM) that regulates protein function. Here, this study revealed that L-lactic acid promotes host immune response and inhibits viral infection by inducing Interferon Regulatory Factor 9 (IRF9) L-lactylation. We first found L-lactylation modification (L-Kla) of IRF9 mediated by AARS1. Further studies demonstrated that IRF9 L-lactylation potentiates type I interferon (IFN-I) signaling by promoting IRF9–STAT2 interaction, thereby boosting antiviral immune response. Intriguingly, L-lactic acid exhibits dual effects on viral infection: L-lactic acid exhibits antiviral effects at physiological and moderately elevated levels but proviral effects at high levels. Furthermore, we found that the viruses can achieve immune evasion by promoting SIRT1-mediated delactylation of IRF9. Interestingly, we uncovered that metformin promotes IRF9 L-lactylation by both accumulating lactic acid and disrupting virus-induced IRF9–SIRT1 interaction. These findings renew the understanding of the roles of lactic acid in antiviral immune response and determine metformin’s immunomodulatory effects on antiviral immunity through regulating IRF9 L-lactylation.

Retrospective cohort study of hepatitis B immunization strategy effects in Beijing across 30 years

GC-MS metabolite profiling and multi-target Docking analysis of Calotropis procera and Euphorbia tirucalli stem extracts for cytotoxicity and antioxidant activity

Dosa: A method to covalently barcode proteins for high-throughput biochemistry

Deep mutational scanning couples a protein’s activity to DNA sequencing for high-throughput assessment of the effects of all single amino acid substitutions, but it largely uses indirect assays, like cell proliferation, as proxy for protein activity. Here, we covalently link variant proteins in vivo to an RNA barcode by fusing them to Escherichia coli tRNA (m 5 U 54 ) methyltransferase TrmA (E358Q). This methyltransferase mutant forms a covalent bond with a tRNA T-arm stem-loop sequence, which we embed in an RNA along with a unique barcode. Following cell lysis, variant proteins are separated in vitro according to their biochemical properties and identified by sequencing their covalently linked barcodes. The in vitro assays can be carried out in highly denaturing conditions, such as 8 M urea, due to the covalent RNA–protein linkage. We use this method, Dosa, to analyze a large pool of FLAG epitope variants for binding to an anti-FLAG–antibody, to profile substrate variants for their cleavage by enteropeptidase and human rhinovirus 3C protease, and to measure the solubility of several hundred Aβ(1-42) variants. This method should be amenable to numerous biochemical assays with proteins produced in E. coli or mammalian cells.

Lithospheric models supported by the Caribbean and Levant examples help rethink transpression at plate boundaries

Evaluation of deflagration fracturing effect based on the HJC constitutive model

Dynamic decrosslinking enables self-healing, reprocessability, and upcycling in polyurethane networks

Both emissions and ageing altered brown carbon aerosols in the East Asian outflow

Shouldering the challenge of deciphering avian palate evolution

Modulation of PDX1 gene expression and glycemic control by Citrullus lanatus in experimental type 2 diabetes

Abstract Diabetes mellitus is a major global health burden characterized by hyperglycemia, oxidative stress, and progressive pancreatic β-cell dysfunction. Despite the availability of conventional therapies, the need for safer and more effective alternatives persists. Citrullus lanatus (African watermelon) is a fruit rich in bioactive compounds with reported antihyperglycemic and antioxidant properties. This study investigated the modulatory effects of C. lanatus juice on pancreatic and duodenal homeobox 1 (PDX1) gene expression and glycemic control in fortified-diet-fed streptozotocin-induced diabetic Wistar rats. Thirty-six rats weighing 90–110 g, were randomized into six groups: normal control (NMC), diabetic control (DBC), metformin-treated diabetic rats (DBM, 500 mg/kg), and diabetic rats treated with C. lanatus juice at 200 mg/kg (DBCL1), 500 mg/kg (DBCL2), and 1000 mg/kg (DBCL3). Animals were pre-fed either normal or fortified diets prior to diabetes induction with streptozotocin (35 mg/kg). Following 14 days of treatment, blood and pancreatic tissues were analyzed for glycemic, antioxidant, and molecular parameters. C. lanatus juice significantly ( p  &lt; 0.05) reduced fasting blood glucose in a dose-dependent manner, with the greatest effect observed in DBCL3. Antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase) were significantly increased, while malondialdehyde levels were reduced in all treated groups. Notably, PDX1 gene expression was markedly upregulated ( p  &lt; 0.05) in C. lanatus -treated rats, accompanied by improved insulin, C-peptide, and HDL levels. These findings suggest that C. lanatus juice exerts antidiabetic effects that are associated with increased PDX1 mRNA expression, improved glycemic control, and reduced oxidative stress, supporting a potential role for transcriptional modulation of β-cell function, highlighting its potential as a functional dietary intervention for type 2 diabetes management.

Tetraspanin TSP-12 and SUP-17/ADAM10 exhibit cell type–specific codependence for trafficking through the Golgi

A subset of the four-pass transmembrane proteins called C8 tetraspanins (TspanC8) can bind and promote the cell surface localization of ADAM10 (A Disintegrin and Metalloproteinase 10). ADAM10 is a conserved transmembrane metalloprotease essential for metazoan embryonic development and human health. However, the in vivo functional relationships between C8 tetraspanins and ADAM10 are not fully understood. Caenorhabditis elegans has two paralogous tetraspanins, TSP-12 and TSP-14, that resemble the mammalian TspanC8 proteins. We have previously shown that TSP-12/TspanC8 can bind SUP-17/ADAM10 and promote its cell surface localization in early embryos. In this study, we identified the specific step in the secretory pathway where TSP-12–SUP-17 interaction is needed. We found that TSP-12 and SUP-17 share a mutually dependent, yet cell type– and developmental stage–specific relationship in their Golgi trafficking itinerary. In the early embryo, TSP-12 and SUP-17 depend on each other for their transit through the Golgi. However, only SUP-17 is required for proper Golgi trafficking of TSP-12 in the developing oocytes. We further showed that the ER accumulation of SUP-17 in embryos lacking TSP-12 is mediated by the Retention in Endoplasmic Reticulum 1 protein RER-1. These findings, combined with our previous work showing that TSP-12 and TSP-14 function redundantly in endosomes for the recycling of the type II receptor of the BMP signaling pathway, showcase the dynamic and versatile functions of TSP-12 in membrane trafficking in specific cellular contexts. They further highlight the importance of dissecting the functional relationships between TspanC8 proteins and ADAM10 in vivo.

Validity of the International Fitness Scale (IFIS) and its associations with cardiometabolic health and body composition in adults with type 2 diabetes: A cross-sectional study

Aims To assess the validity of the International Fitness Scale (IFIS) for evaluating cardiorespiratory fitness compared to the 6-minute walk test (6MWT) (criterion validity) and to examine associations with cardiometabolic and body composition outcomes (construct validity). Methods A cross-sectional analysis was conducted on 282 adults with type 2 diabetes mellitus (T2DM) (mean age 63.6 ± 8.1 years, 37.9% women). Self-reported fitness was assessed using IFIS, including overall, cardiorespiratory, muscular, speed-agility and flexibility scores. Objective cardiorespiratory fitness was assessed using the 6MWT. Associations with 6MWT, cardiometabolic (i.e., cardiovascular health score, metabolic dysfunction-associated steatotic liver disease [MASLD], high-sensitivity C-reactive protein) and body composition outcomes (i.e., body mass index [BMI], visceral adipose tissue volume, thigh fat-free muscle volume) were analyzed using ANCOVA (adjusted by sex and age) and ROC curves, compared using DeLong tests. Results Both IFIS overall and IFIS cardiorespiratory showed graded associations with 6MWT (p &lt; 0.001 for ANCOVA models). For discriminating performance below the population-predicted mean 6MWT distance, IFIS cardiorespiratory showed an AUC of 0.615 (95% CI: 0.552–0.678). Apart from IFIS muscular, IFIS scores were significantly associated with all cardiometabolic and body composition outcomes, with ROC analyses showing at least similar predictive performance for IFIS overall and cardiorespiratory fitness scores compared to 6MWT. Notably, IFIS overall outperformed the 6MWT for predicting poor cardiovascular health (AUCs: 0.678 [95% CI: 0.618–0.737] versus 0.586 [95% CI: 0.517–0.654]) and MASLD (AUCs: 0.630 [95% CI: 0.563–0.696] versus 0.519 [95% CI: 0.443–0.595]). Conclusion This study supports that IFIS may be a practical tool for adults with T2DM, showing evidence of criterion validity via graded association with 6MWT performance, and construct validity via significant associations with cardiometabolic and body composition outcomes. Although its ability to discriminate impaired functional capacity was limited, IFIS may serve as a feasible alternative for fitness assessment when objective testing is not possible in primary care.

Human factors in yachting tourism accidents: an integrated human factors classification framework with statistical and network analysis

Performance of glomerular filtration rate equations using serum creatinine in children with congenital anomalies of the kidney and urinary tract

Introduction Congenital anomalies of the kidney and urinary tract (CAKUT) are a significant cause of pediatric morbidity and mortality, often leading to chronic kidney disease (CKD). Accurate glomerular filtration rate (GFR) assessment is crucial for effective management, but a gold-standard pediatric GFR estimation formula remains elusive. This study compared the bedside Schwartz, Chronic Kidney Disease in Children (CKiD-U25) creatinine, and European Kidney Function Consortium (EKFC) creatinine-based equations against measured GFR (mGFR) using technetium-99m-diethylenetriaminepentaacetic acid (Tc-99mDTPA) clearance. Methods Data were collected from 276 children with CAKUT at Dr. Soetomo Academic General Hospital. Estimated GFR (eGFR) was calculated using the bedside Schwartz, CKiD-U25, and EKFC equations. mGFR was determined using Tc-99mDTPA clearance, considered the gold standard. Correlation (Spearman rs), bias, and accuracy (P30, percentage of eGFR within 30% of mGFR) were assessed. Subgroup analysis was performed for children older than two years. Results Both equations correlated significantly with mGFR (bedside Schwartz: r = 0.793; CKiD-U25: r = 0,793; EKFC: r = 0.745, p &lt; 0.0001). However, the bedside Schwartz systematically underestimated mGFR (bias: −21.7 mL/min/1.73 m²), while the EKFC overestimated (bias: 17 mL/min/1.73 m², p &lt; 0.0001). In children &gt;2 years, correlations strengthened (bedside Schwartz: r = 0.804; EKFC: r = 0.835, p &lt; 0.0001), with the EKFC demonstrating more accuracy (P30: 90.1%) compared to the bedside Schwartz CKiD-U25 creatinine (75% and 75%, respectively) Conclusion These findings suggest the both bedside Schwartz and EKFC could be a reliable tool for GFR estimation in this pediatric CAKUT population.

Interplay between resting heart rate variability, daily affective dynamics and mental health difficulties in autistic youths

Abstract Repeated exposure to external stressors could lead to altered autonomic functioning, contributing to difficulties in emotion regulation and the development of mental health difficulties. This pathway is important to investigate in autistic youths who are vulnerable to develop stress-related mental health difficulties. We investigated the interplay between resting heart rate variability (HRV), fluctuations of daily affects over time (daily affective dynamics) and mental health symptoms (internalizing, externalizing and social anxiety symptoms) in 27 autistic (M age =17.66) and 24 non-autistic (M age =19.86) adolescents and young adults. Resting HRV was collected using a mobile electrocardiogram. Ecological Momentary Assessment assessed daily affective dynamics (affective instability and affective reactivity to stress). Mental health symptoms were assessed with questionnaires. Resting HRV did not differ significantly between the groups. HRV was not directly associated with mental health symptoms in analyses corrected for multiple comparisons, but affective reactivity to stress mediated the association between HRV and internalizing symptoms. Finally, differences emerged in the relationship between HRV and daily affective dynamics between autistic and non-autistic individuals. Our results suggest that increased stress reactivity may be a mechanism linking altered autonomic functioning to mental health difficulties, offering important insights for targeting clinical interventions.