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Net widening of Southern California beaches
Abstract Human impacts from dams reduce river sediment fluxes and are primary causes of coastal erosion worldwide. Here we provide new satellite-derived shoreline observation techniques to examine beach area trends across the diverse coastal settings of California. Contrary to global trends, these data reveal that the most heavily urbanized and dammed region of southern California experienced net beach growth of over 2 million m 2 during 1984-2024. While several beaches experienced severe erosion, overall widening is explained by sufficient sediment supply and concentrated widening from longshore transport captured at coastal structures and in littoral convergence zones. These results indicate that adequate sediment sources exist in this human-modified landscape to mitigate coastal erosion, but that this sediment is not effectively distributed to vulnerable beaches. This highlights the critical role that longshore sediment transport plays in long-term beach trends and illuminates management opportunities for coastal sustainability at the regional scale.
African swine fever outbreaks in German pig holdings – experiences, epidemiological considerations and genome sequences
Abstract Until December 2025, 18 African swine fever outbreaks have occurred in domestic pig holdings in Germany. However, nine of them emerged in western Germany in 2024, representing a separate spatial and temporal cluster. Thus, the current study is limited to the remaining nine outbreaks. We aimed to illustrate the epidemiological background of each of the nine outbreaks. The assessments included the results of the outbreak investigations and of the genome sequencing. This is the first study to provide a detailed overview of these outbreaks and, in particular, to publish the genome sequences involved. In several outbreaks, a connection to the neighboring affected wild boar population was considered likely. The hypotheses were supported by genome sequencing; thus, the study has underscored the benefit of including results of genome sequencing in the evaluation of disease epidemiology. However, outbreaks also occurred on farms without reported cases in wild boar in the vicinity. Similarly, outbreaks were observed in farms with low biosecurity standards but also in farms with very high biosecurity, emphasizing the difficulty to identify a pattern in the outbreaks. Still, it has to be acknowledged that a consistent and sustained compliance with biosecurity measures represents the most important factor in preventing virus introduction.
Population pharmacokinetics model of pyrazinamide to optimize tuberculosis treatment: An interethnic cohort study of diabetes mellitus effect on drug exposure
Diabetes mellitus (DM), a common comorbidity in tuberculosis (TB) patients, can alter the pharmacokinetics (PK) of TB drugs. Additionally, clinical and demographic differences may contribute to interethnic PK variability. However, current WHO-recommended doses for pyrazinamide (PZA) do not account for those factors. We aimed to evaluate factors related to interindividual variability (IIV) and interethnic differences in the PK of PZA between Korean and Indonesian patients with TB. Demographics, clinical characteristics, and PZA concentrations obtained from hospitals in both countries were used for model establishment. Population PK models were developed using the nonlinear mixed-effect method. A Monte Carlo simulation was performed sequentially to evaluate optimal PZA dosing strategies. A one-compartment model with allometric scaling adequately described the PK of PZA. Internal validation of the model showed good performance. No significant interethnic differences in PK parameters were observed. There were 23% and 26% increases in apparent clearance (CL/F) of Indonesian patients with DM (CL/F 3.18 L/h) and Korean patients aged > 60 years with DM (CL/F 3.5). PZA doses of 1000–1250 mg for patients of bodyweight < 40 kg and 1250 mg for older patients with DM in this weight band had a 90% probability of attaining the target AUC 0–24 ≥ 363 mg·h/L These findings indicate that DM strongly influenced IIV, particularly in older patients. We recommend higher PZA doses for patients <40 kg and older patients with DM in this weight band. Our model provides a basis for implementing model-informed precision dosing-based therapeutic drug monitoring in both ethnicities.
A benchmark of expert-level academic questions to assess AI capabilities
AACRNL evolved from virulence factor to epigenetic parasite driving genome expansion in free-living eukaryotes
Optimal operation of multi-carrier energy systems integrated with renewable energy sources and hydrogen storage systems
Outside versus inside the home: Tensions between fathers’ work and parenting responsibilities in Tanzania
Globally, mothers are disproportionately responsible for childcare, while fathers are predominantly viewed as breadwinners. Although recent studies reveal that fathers are becoming more engaged in parenting, little is known about the broader contexts surrounding how fathers allocate their time between parenting, income-generating work, and other daily activities. The objective of this study was to characterize the typical daily schedules from morning to evening among fathers with young children under aged 2 years. Additionally, we aimed to identify the perceived barriers and facilitators influencing fathers’ time spent on parenting. We conducted 60 in-depth interviews (29 fathers and 23 mothers and 8 community stakeholders) and 9 focus group discussions (3 with fathers only, 2 with mothers only, and 4 mixed parent groups) across 4 purposively sampled, peri-urban communities in Mwanza, Tanzania. Among a subsample of 14 fathers, we revisited and conducted follow up in-depth interviews to further obtain retrospective hourly accounts of fathers’ daily time use. Data were analyzed using both deductive and inductive approaches. Overall, fathers spent most daytime hours out of the home engaging in work-related activities, and evenings were often a time when some fathers socialized with peers. Approximately half of fathers reported some involvement in parenting, childcare, or household chores. However, these activities were generally brief and concentrated at specific times of day, such as early mornings before fathers left for work, during lunchtime when men returned home, or on weekends when men spent more time at home. Key barriers to fathers’ time allocation to parenting included patriarchal gender norms that frame childcare as primarily women’s responsibility, poverty, and work-related stress. Facilitators of fathers’ time towards parenting included greater autonomy over work schedules and positive attitudes valuing fathers’ nurturing care roles. These findings provide important insights into fathers’ daily routines in this context and the social, cultural, and structural factors that enable or constrain their engagement in parenting. By illuminating men’s time use patterns, this study offers evidence to inform the design of parenting programs that are more responsive to fathers’ schedules and constraints and ultimately promote greater father engagement in childcare.
Plant diversity within communities, not among them, stabilizes grassland productivity across spatial scales
Heritable pulmonary arterial hypertension: new genetic findings and environmental triggers
Abstract Our goal was to identify new environmental or genetic causes in heritable pulmonary arterial hypertension (HPAH) families outside the 18 known diagnostics PAH genes. PAH gene panel sequencing was performed for 47 HPAH families which revealed pathogenic variants in 39 families. Five of the remaining families agreed to whole exome sequencing and to fill in a drug and toxin exposure questionnaire. In Family 1 and 2, mother and daughter with HPAH carried a likely pathogenic variant in the CYBA gene and a variant of uncertain significance in the FKBP1A gene, respectively, following ACMG guidelines. In Family 3, we detected a likely pathogenic variant in the PTGR2 gene. These genes could play part in PAH pathogenesis but further functional analyses are required to corroborate these findings. In the remaining two families, we could not identify any plausible genetic cause. However, a father and son with PAH reported exposure to trichloroethylene, asbestos and tramadol in Family 4. In Family 5, two brothers with pulmonary veno-occlusive disease showed occupational toxin exposure. Thus, our findings indicate that not only a genetic predisposition but also environmental triggers should be investigated for HPAH patients.
Discovery and computational characterization of ZIKV envelope-targeted peptides from a subtractive phage display library
The Zika virus (ZIKV) poses a significant public health threat, and developing highly specific diagnostic and therapeutic agents that can distinguish it from other flaviviruses remains a critical challenge. To address this, we utilized a phage display library with a strategic subtractive panning approach against the ZIKV envelope protein (ZIKV-pE). This method identified eight linear peptides with high binding ability for ZIKV-pE. Enzyme-linked immunosorbent assay (ELISA) confirmed that these peptides recognized ZIKV-pE with statistical significance compared to a bovine serum albumin (BSA) control. To elucidate the binding mechanisms, we performed molecular docking and molecular dynamics (MD) simulations. Computational analysis identified peptides R3Z15, R3Z09, R2Z05, and R3Z02 as the top candidates based on binding free energy calculations. The simulations revealed that these peptides bind specifically to the DIII domain of ZIKV-pE primarily via electrostatic interactions and form stable complexes over 300 ns of MD simulation. Our work identifies specific, high-affinity peptide binders to ZIKV-pE. It provides a structural basis for their selectivity, positioning them as promising candidates for the development of precise ZIKV diagnostics and targeted therapeutics.
Hydrocyclone-enhanced scalable photocatalytic hydrogen generation, from macroscale turbulence to nanoscale reaction dynamics
Influence of structural parameters on the workspace of delta parallel robots and path adaptability optimization for tea fresh leaf sorting applications
Modeling the beating degree of wheat straw biochemical mechanical pulp using multifactorial equations
In traditional pulp beating processes, the “produce-test-adjust” cycle is commonly employed, often resulting in unnecessary consumption of energy and chemicals. To address this issue, this study integrated single-factor experiments with a Plackett-Burman (PB) design to identify three key parameters—refiner gap, KOH dosage, and enzyme dosage—that significantly influence the beating degree of wheat straw biochemical mechanical pulp, selected from ten potential factors. On this basis, the Box-Behnken Design (BBD) response surface methodology (RSM) was employed to establish a quadratic polynomial predictive model between the beating degree and the aforementioned three factors. For this quadratic polynomial predictive model, the coefficient of determination (R²) is 0.9899, the adjusted R² is 0.9768, and the predicted R² is 0.8723. The adjusted R² is close to R², and the predicted R² is close to the adjusted R² with both values being relatively high, indicating the reliability and practicality of the model. The standard deviation is 0.44, the coefficient of variation is 1.13%, and the signal-to-noise ratio of the model reaches 29.2395, suggesting its strong predictive ability and excellent robustness. Methodologically, this study innovatively applied BBD to the prediction of beating degree. Compared with the traditional Central Composite Design (CCD) model, the proposed model does not require extreme operating conditions, and all 17 experimental points fall within a safe operation range. The establishment of this model provides a predictable and controllable optimization tool for the wheat straw bio-pulping process.
Structural basis for selective inhibition of human GABA transporter GAT3
Exceptionally selective voltage-sensor trapping of NaV1.5 channels by Mg-protoporphyrin impairs cancer cell migration
Abstract The human voltage-gated sodium channel hNa V 1.5 is essential for cardiac excitability. Though underrecognized, Na V 1.5 is also expressed in multiple cancers, promoting cell migration and malignancy. hNa V 1.5 is a therapeutic target but limited pharmacological isoform specificity presents a risk of side effects via neuronal and skeletal muscle Na V channels. Here we identify Mg 2+ -protoporphyrin IX (MgPpIX), a Mg-containing tetrapyrrole and intermediate in chlorophyll biosynthesis, as a potent inhibitor of hNa V 1.5 ( IC 50 of 1 nM). The activity profile of various metal protoporphyrins correlates with the electrostatic potential at the metal center of the compounds. MgPpIX is specific to hNa V 1.5, as no inhibition of other hNa V isoforms (hNa V 1.2, 1.4, 1.7, 1.8) was detected. A mutagenesis study and structural modeling reveals that MgPpIX stabilizes the domain-II voltage sensor in the deactivated conformation, with residues E795 and N803 being relevant determinants. MgPpIX also inhibits native Na V channels in breast cancer MDA-MB-231 and colorectal carcinoma SW-480 cell lines, and suppresses cell migration. MgPpIX is an exceptionally potent and specific inhibitor of hNa V 1.5 and may serve as a lead compound in anti-cancer drug development.
Investigation of the drug release modifying property of Pentadesma butyracea gum in diclofenac sodium matrix tablets
Background Natural gums have long served as essential excipients in pharmaceutical formulations, traditionally functioning as binders, disintegrants, suspending agents, and emulsifiers. Their role has expanded to include drug delivery carriers in advanced systems such as matrix formulations, gene therapy, and nanomedicine. Increasing attention has been given to natural gums over synthetic alternatives due to their non-toxicity, biodegradability, affordability, and availability. This study investigated the potential of Pentadesma butyracea gum as a matrix-forming agent for the extended release of diclofenac sodium. Methods The crude gum was harvested from the stem bark of Pentadesma butyracea and purified using ethanol precipitation. Fourier-transform infrared spectroscopy (FTIR) was employed to assess potential interactions between the gum, diclofenac sodium, and other excipients. Matrix tablets (PM01–PM05) containing varying concentrations (15–35% w / w ) of the purified gum were prepared via wet granulation, along with a control batch (PM06) lacking the gum. Additionally, the PM01 formulation was optimised by incorporating xanthan gum at concentrations of 10–20% w / w (PM01A–PM01C). All formulations were assessed for weight and dimensional uniformity, mechanical integrity, drug content, and in vitro release characteristics. Comparative dissolution profiles were assessed against an innovator brand using the similarity (f₂) and difference (f₁) factors. Drug release kinetics and mechanisms were analysed using appropriate mathematical models. Results All batches passed the uniformity of weight and dimensions tests, drug content (99.11–101.87%), friability (0.25–0.79%), hardness (7.74–8.83 Kgf), and tensile strength (1.29–1.49 MPa). The control batch (PM06) failed to meet dissolution criteria, releasing only 60.46% of diclofenac sodium within 45 minutes. In contrast, formulations containing P. butyracea gum exhibited a gradual, concentration-dependent, time-mediated release, with all test batches (PM01–PM05) releasing over 50% of the drug within 45 minutes. Among the optimised formulations, PM01C exhibited a modified release profile, with 19.90 ± 0.508% of the drug released at 2 hours and 100.26 ± 2.118% at 24 hours, consistent with the British Pharmacopoeia standards. The release profile of PM01C was comparable to the reference product (f₂ = 79.35; f₁ = 2.93) and followed zero-order kinetics. PM01A and PM01B exhibited Korsmeyer-Peppas release kinetics. Mechanistically, drug release occurred via non-Fickian diffusion for PM01C and Fickian diffusion for PM01A and PM01B. Conclusion A matrix system comprising 15% w / w P. butyracea gum and ≥ 20% w / w xanthan gum effectively extended the release of diclofenac sodium over 24 hours, demonstrating its potential application in extended-release formulations.
Coordinated gene family evolution shapes the genome of dimorphic Mucorales
Unveiling key genetic loci and candidate genes for brown spot disease resistance in rice based on QTL analysis
Abstract Rice brown spot, a widespread disease caused by the fungus Bipolaris oryzae (teleomorph: Cochliobolus miyabeanus ), significantly diminishes both grain yield and quality. Developing resistant rice cultivars remains the most sustainable and effective strategy for managing this disease. In this study, we conducted quantitative trait locus (QTL) analysis to identify genetic loci and candidate genes associated with brown spot resistance. A mapping population was generated from a cross between the resistant variety ‘Cheongcheong’ and the susceptible variety ‘Nagdong’. Disease evaluations were performed following inoculation with a mixture of six Cochliobolus miyabeanus isolates collected in 2023 to represent current field diversity, and disease severity was assessed seven days post-inoculation using a 0–9 scale. The QTL analysis revealed a new major locus on chromosome 3 linked to brown spot resistance, between markers RM15749 and RM15689. Within this genomic interval, 32 candidate genes were identified using qRT-PCR-based expression profiling. Among them, a gene designated OsRBSq3 ( Os03g0687400 ), encoding a ribosome-inactivating protein family member that plays a role in defense mechanisms against necrotrophic pathogens, exhibited notable differential expression between Cheongcheong and Nagdong. These results provide new insights into the genetic architecture underlying brown spot resistance in rice and highlight OsRBSq3 as a potential target for marker-assisted selection and functional studies.
Differential seedling responses of chickpea varieties to hexavalent chromium (VI) stress under controlled conditions
Hexavalent chromium (Cr VI) contamination infiltration in soil due to industrial activities has become a sever threat to Pakistan’s agricultural productivity. Recent surveys report soil chromium concentrations in agricultural–industrial interfaces of Punjab and Khyber Pakhtunkhwa reaching 100 mg/kg, exceeding the WHO permissible limit (1.5 mg/kg) by more than 50-fold. Chickpea, a widely cultivated crop in Pakistan also faces productivity threats from Cr (VI). This study evaluates the differential seedling responses of two Pakistani chickpea varieties (CM-72 and CM-98) to hexavalent chromium stress (0µM to 100µM) under controlled conditions to address a critical research gap. A fully randomized experimental design (CRD) with five replicates per treatment was utilized, assessing germination metrics, root and shoot lengths, root collar diameter, and biomass over a period of 14 days. Statistical evaluations (ANOVA, Pearson correlation, PCA) indicated substantial varietal differences. Both varieties showed significant (p < 0.05) dose-dependent reductions in germination rates, growth, and biomass; however, CM-72 exhibited greater tolerance. At a concentration of 100 µM Cr VI, CM-72 achieved 90% germination (compared to 80% in CM-98), with moderate declines in root length (39% compared to 77% in CM-98), shoot length (76% compared to 90%), and biomass (34% dry weight loss in comparison to 59% in CM-98). Multivariate analysis revealed strong associations between growth inhibition and chromium stress, with PCA differentiating between structural (root collar diameter) and temporal (germination delay) effects. These results highlight the resilience of CM-72, likely attributable to metabolic and antioxidative adaptations, making it a potential candidate for cultivation in areas contaminated with chromium. The relative tolerance of CM-72 may relate to underlying physiological or biochemical traits that warrant investigation in future studies. This research offers essential insights into the responses of chickpea varieties to Cr VI stress, highlighting the necessity for biochemical and molecular studies to clarify tolerance mechanisms and support sustainable agricultural practices in regions impacted by heavy metals.