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Female mice grow testes after this single DNA tweak
Study on water flooding sweep characteristics of horizontal-vertical combined well pattern in offshore heavy oil reservoirs
Cryo-EM structure of the SRI-HtrI complex reveals the cytoplasmic coupling in an archaeal phototaxis system
The Physicochemical Synergy Effect of Nanosecond Pulsed Electric Fields (nsPEF) and cisplatin on reversing chemoresistance of bladder cancer
Nanosecond Pulsed Electric Field (nsPEF) is an intense electrical pulse technology with ultra-short duration (nanoseconds), capable of generating electric field intensities up to several kV/cm. By inducing irreversible electroporation for tumor tissue ablation, nsPEF triggers apoptosis in cancer cells, stimulates anti-tumor immune responses, and enhances exogenous gene transfection. As a primarily non-thermal technique, it offers advantages such as minimal tissue damage, high targeting efficiency, short treatment duration, and compatibility with other therapies. Currently demonstrating broad application potential in cancer treatment. Urothelial Bladder Carcinoma (UBC), accounting for over 90% of bladder cancers, originates from the transitional epithelium of the bladder’s urothelium and represents the most common malignant tumor in the urinary system. Cisplatin (CDDP), a key chemotherapeutic agent for UBC, is particularly effective for recurrent or advanced-stage patients. However, repeated use often leads to drug resistance. This study investigates the cytotoxic effects of nsPEF on UBC cells and its inhibitory mechanisms against drug-resistant UBC. Through sustained gradient concentration induction of CDDP, we successfully established drug-resistant cell lines T24/CDDP and TCC/CDDP. After treatment with nsPEF on parental cell lines (T24, TCC) and their drug-resistant variants (T24/CDDP, TCC/CDDP), all cells exhibited time-and dose-dependent sensitivity. Western blot analysis revealed that the basal expression of γ-H2AX was significantly reduced in the drug-resistant cells (T24/CDDP, TCC/CDDP), while nsPEF treatment significantly upregulated its expression. In vivo experiments further demonstrated that nsPEF exhibited significant antitumor efficacy against tumor-bearing mice from T24/CDDP. Overall, nsPEF effectively induces apoptosis in T24, TCC, and their drug-resistant variants, with particularly potent effects on drug-resistant UBC cells. This enhanced effect may be attributed to nsPEF-induced more severe DNA damage in drug-resistant cells, as manifested by elevated γ-H2AX expression.. This study provides experimental evidence for applying nsPEF to overcome chemotherapy resistance in UBC.
Home-Based Care for Hypertension in Rural South Africa
BMSC-derived exosomal ANTXR1 inhibits erythroid differentiation by suppressing the TLR4/MyD88/NF-κB signaling pathway
The genomic impact of population connectivity and decline in Africa’s elephants
Abstract African elephants are keystone species facing severe declines due to the ivory trade and habitat loss. To investigate the genomic consequences, we analyze 232 high-coverage genomes from 17 African countries in the first continent-wide genomic analysis treating savanna ( Loxodonta africana ) and forest ( L. cyclotis ) elephants as distinct species. We find a deep divergence between species, with forest elephants showing higher heterozygosity and historically larger effective population sizes, while savanna elephants exhibit greater inbreeding and genetic load. Surprisingly, we detect widespread introgression of trace forest ancestry across savanna populations, suggesting a complex history of hybridization. Within species, historically high mobility promoted genetic connectivity, though we identify signs of human-induced isolation and drift in peripheral populations. Our findings highlight gene flow as a key force in African elephant evolution and underscore the urgency of understanding the impact of accelerating habitat fragmentation in these ecosystem engineers.
Editorial Note: The residual rate of HPV and the recurrence rate of CIN after LEEP with negative margins: A meta-analysis
Sudden Cardiac Arrest in Athletes
The E3 ubiquitin ligase mechanism specifying targeted microRNA degradation
Abstract MicroRNAs (miRNAs) associate with Argonaute (AGO) proteins to form complexes that down-regulate target RNAs, including messenger RNAs from most human genes 1–3 . Within each complex, the miRNA pairs to target RNAs, and AGO provides effector function while also protecting the miRNA from cellular nucleases 2–5 . Although much is known about miRNA-directed gene regulation, less is known about how miRNAs themselves are regulated. One pathway that regulates miRNAs involves unusual targets called ‘trigger’ RNAs, which reverse the canonical regulatory logic and instead down-regulate miRNAs 6–9 . This target-directed miRNA degradation (TDMD) is thought to require a cullin–RING E3 ligase because it depends on the cullin protein CUL3 and other ubiquitylation components, including the BC-box protein ZSWIM8 (refs. 10,11 ). ZSWIM8 is required for murine perinatal viability and for destabilization of most short-lived miRNAs, which suggests biological importance of TDMD 11–13 . Here, biochemical and cellular assays establish AGO binding and polyubiquitylation by the ZSWIM8–CUL3 E3 ligase as the key regulatory steps of TDMD, and thereby define a unique cullin–RING E3 ligase class. Cryogenic electron microscopy analyses show ZSWIM8 recognizing distinct AGO and RNA conformations shaped by pairing of the miRNA to the trigger. Specificity of AGO ubiquitylation is established through generalizable RNA–RNA, RNA–protein and protein–protein interactions. The substrate features recognized by the E3 ligase do not conform to a conventional degron 14,15 but instead establish a two-RNA-factor authentication mechanism for specifying a protein ubiquitylation substrate.
Class-adaptive oracle-free metamorphic test case prioritization framework for vision-based deep neural networks
Filaments of light dynamically isolate a single attosecond pulse
Behavioural and Social Drivers (BeSD) of COVID-19 vaccination for children: A cross-sectional study of parental vaccine confidence and intent in Mysore, India
Background India rolled out COVID-19 vaccinations for adults in January 2021 and children aged 12–18 in early 2022. A 2021 survey indicated that 63% of Indian parents were willing to vaccinate their children against COVID-19, with few studies examining vaccine hesitancy and acceptability. The the Behavioral and Social Drivers of Vaccination (BeSD) framework helps demonstrate which factors may affect vaccination uptake. Our study examined parents’ intentions-to-vaccinate their children below 18 years of age against COVID-19 in Mysore, India and their decision-making process using the BeSD framework. Methods From November 2021 to May 2022, 506 parents/guardians of children below 18 years of age living in Mysore district, India were consented and interviewed by phone or face-to-face. We assessed their own COVID-19 vaccination status, vaccine confidence (Vaccine Confidence Index), intention-to-vaccinate their child against COVID-19, and other factors affecting vaccination such as demographic variables. Multivariable ordinal logistic regression was conducted to examine the association of influencing factors based on the literature and BeSD framework using Stata version 16.1. Intention-to-vaccinate was presented as odds ratios (OR) with associated 95% confidence intervals (95%CI). Results The majority (91.3%) of the 506 participants fully trusted COVID-19 vaccines for their children. The same number (91.3%) had been fully vaccinated themselves, and 78.3% reported being (very) likely to vaccinate their children against COVID-19. Vaccine-hesitant and vaccine-confident groups were not significantly different socio-demographically. As parental age increased, parents had higher odds to express intention-to-vaccinate their child (OR: 1.04, 95%CI: 1.01–1.08). Parents from urban Mysore had lower odds to vaccinate their child compared to those from rural areas (OR: 0.53, 95%CI: 0.35–0.82). Conclusion Most parents expressed vaccine confidence and intention-to-vaccinate their child against COVID-19. Exploring decision-making processes among parents is a crucial strategy to ensure effective implementation of vaccination programs.
Hepatic Pseudoprogression after Treatment with Nectin-4–Targeted Antibody–Drug Conjugate
Combination of irreversible and calcium electroporation to overcome heterogeneity-associated incomplete ablation in the pancreas
Publisher Correction: A “paradox of progress” shapes the social determinants of infectious diseases in Vietnam, 1975–2025
Parental, pregnancy and neonatal characteristics during the perinatal period as potential risk factors for childhood cancer: FeToxCancer case-control study
Childhood cancer aetiology is poorly understood and is considered to originate in utero and early postnatal life. In this study, we investigated perinatal characteristics as potential risk factors by performing a population-based case-control study, including 1340 cancer cases diagnosed < 19y and born between 1989–2021 in southern Sweden, and 13400 controls matched by sex, year, and municipality of birth. Perinatal characteristics were obtained from seven national registries. Cox regression was used to examine the associations between perinatal characteristics and the risk of overall childhood cancer, leukaemia, CNS tumours, lymphoma, and other cancer types combined (OCT). Large for gestational age was associated with a higher risk of overall cancer (HR, 95%CI: 1.32, 1.02–1.69) and leukaemia (HR, 95%CI: 1.58, 1.01–2.5), while a 5-min Apgar score <7 indicated a higher risk of OCT (HR, 95%CI: 2.16, 1.12–4.15). Mechanical ventilation during neonatal care was associated with a higher risk of overall cancer (HR, 95%CI: 1.88, 1.39–2.53) and OCT (HR, 95%CI: 2.09, 1.19–3.39). The aforementioned characteristics were associated with up to a threefold increased risk among children diagnosed before six months of age compared to those diagnosed later. Additionally, maternal obesity was associated with a higher risk of CNS tumours (HR, 95%CI: 1.51, 1.04–2.21) and lymphoma (HR, 95%CI: 2.26, 1.31–3.88), and maternal underweight with a higher risk of leukaemia (HR, 95%CI: 2.43, 1.40–4.22). Planned caesarean delivery indicated an increased risk of OCT (HR, 95%CI: 1.52, 1.04–2.22). Our findings identify several perinatal characteristics associated with childhood cancer risk, highlighting the perinatal period as an important window for future etiological research.