Browse Articles

Investigation of the damping characteristics of grouted coal gangue with different particle gradations under multistage triaxial cyclic loading

Respiratory triggered 3D bSSFP MRI enables accurate noninvasive localization of the right adrenal vein confluence in primary aldosteronism

Biodegradable chitosan–gelatin films incorporating Zanthoxylum limonella (Dennst.) Alston essential oil for antibacterial and hemostatic applications

Genotype-by-inhibitor interactions to dissect enterovirus replication

Abstract Replication organelles of positive-sense RNA viruses are essential to virus biology, yet their molecular mechanisms remain poorly defined. While deep mutational scanning (DMS) measures the impact of mutations across viral proteins, it cannot resolve their effects on specific functions. Here, we present a strategy to integrate mutational scanning in the context of specific virus- and host-targeted inhibitors with structural modeling to dissect mechanistic details of Enterovirus replication. Our results reveal key insights into the function of nonstructural proteins in the context of viral replication. We use this approach to clarify the modular architecture of the viral 2 C protein, dissecting the functional partitioning of its ‘virus-facing’ cytoplasmic, enzymatic domain from ‘host-facing’ functions at the membrane-binding domain, revealing evidence for computationally-predicted structural transitions associated with host protein binding. We further show that inhibition of the 3 C protease enriches for mutations in 2 A, highlighting compensatory crosstalk between viral proteases. Finally, targeting host phospholipid synthesis triggers a dose-dependent shift in mutational tolerance in the viral 3 A protein, showing how preference for distinct interaction interfaces with either a host enzyme or its adapter protein varies across inhibitory environments. Our approach, which quantifies the impact of pharmacological probes on viral fitness by comprehensive mutational scanning, creates a virtuous cycle where DMS validates and refines structural predictions that, in turn, serve to contextualize mutational data, all toward a more complete model of positive-sense RNA virus replication.

Valorization of Sargassum wightii through biochar production: development, characterization, and potential applications

A delayed translocation into the endoplasmic reticulum controls the post-translational modifications of PD-L1

Abstract N-terminal signal peptides (SPs) are traditionally considered as drivers of co-translational translocation of newly synthesised proteins into the endoplasmic reticulum (ER). However, growing evidences suggest that proteins with SPs can also undergo post-translational insertion into the ER membrane after synthesis is complete. Recently, an intermediate third mechanism has been uncovered where proteins with marginally hydrophobic or suboptimal SPs are translocated following an initial delay after translation initiation. Here, we show that this “delayed translocation” allows a temporary exposure of the nascent chain to the cytosolic environment, enabling exoplasmic domain modifications by cytosolic enzymes. We report that programmed death ligand-1 (PD-L1) follows this pathway, featuring a suboptimal SP that exposes its extracellular domain to the cytosol, enabling AMPK-dependent regulation of PD-L1 function. Importantly, optimising the SP of PD-L1 eliminates the cytosolic exposure, disrupting PD-L1’s trafficking and maturation, highlighting the physiological importance of the delayed translocation mechanism.

Knowledge stickiness and technological concentration in the AI industry: an empirical study of Chinese cities

Tandem bulk oxygen diffusion and surface reactions in reducible metal oxides control redox cycle dynamics

The proteome study of germinated Puccinia triticina urediniospores reveals a novel effector protein required for virulence

Abstract The obligate biotrophic fungus, Puccinia triticina ( Pt ), is a notorious plant pathogen known for wheat leaf rust disease that devastates global crop production annually. Pathogen-host interactions need to be elucidated, especially the identification of pathogen effectors contributing to virulence. ‘Omics’ strategies are an efficient tool set to study these pathogen-host interactions. No proteome data are available on the germlings stage of Pt , which could highlight proteins involved in the first interaction point between Pt and its host. Here, we have used a proteomics approach on germinated urediniospores of Pt to define the germling proteome. Using two-dimensional gel electrophoresis, 167 spots in the pI range of 4–7 were observed, from which 123 proteins were identified by tandem mass spectrometry. Further in silico characterization revealed that they were predominantly involved in metabolic and cellular processes, with six proteins annotated as candidate effectors. The candidate effector PTTG_06852, hereafter named as virulence factor 1 (PtVF1), was silenced by host-induced gene silencing (HIGS) to investigate its biological function. When the expression of PtVF1 was reduced by 78%, the infection severity was suppressed by 70%. The results demonstrate a significant impairment of virulence upon silencing, which validates PtVF1 as a virulence effector of Pt .

Agonal cell resuscitation strategy to promote tissue repair

Dynamical study of optical soliton solutions to the Lakshmanan-Porsezian-Daniel equation by using $$\phi ^6$$-model expansion approach

Boosting pathology foundation models via few-shot prompt-tuning for rare cancer subtyping

Association between hospital frailty risk score and in-hospital mortality in critically ill patients with sepsis: results from MIMIC-IV database

In situ electron diffraction tomography study of the successive phase transitions in LaTaO4 nanocrystals

Football cybersecurity threat severity prediction using multi-head transformer-based deep learning models

β2 adrenergic receptors orchestrate neutrophil demargination and recruitment to the ischemic heart following myocardial infarction

Prevalence of depressive symptoms and its burden on neurological practice in urban Egypt: a cross-sectional study

Abstract Neurologists, as specialists in a high-stress field, which hold lots of mental and emotional stressors. The complexity of neurological conditions, the extended working hours, and the emotional burden of managing chronic or terminal patients contributes to a stressful work environment. Globally, studies have shown that healthcare professionals, particularly those in specialties of high demand like neurology, are at risk of depression and burnout. This study aims to assess the prevalence of depressive symptoms among neurologists in Egypt. Help identify the risk factors that contribute to these depressive symptoms. A cross-sectional survey was conducted among Egyptian neurologists working in both public and private healthcare institutions. Participants in the study completed the Patient Health Questionnaire-9 (PHQ-9) to assess the severity of depressive symptoms. Data on demographics, job satisfaction, shift duration, workload and overall job satisfaction were also collected and analyzed using descriptive and inferential statistics. Out of 138 neurologists surveyed, nearly half (43.5%) reported moderate to severe depressive symptoms. Those with a prior diagnosis of depression were especially affected—more than 8 in 10 (82.4%, 95% CI 66.2%–91.7%) reported significant symptoms, compared to just over a third (37.5%, 95% CI 28.8%–47.1%) of those without a known history ( p  < 0.001). Higher depression scores were also linked to early career stage and longer working hours. Over half of the neurologists with less than three years of experience (53.1%) and those working more than 80 h per week (56.3%) screened positive for moderate to severe depression. These findings highlight a high burden of depressive symptoms among Egyptian neurologists, particularly those early in their careers or with a prior history of depression, emphasizing the urgent need for targeted mental health interventions and systemic workplace reforms.

Exploring the feasible net-zero transition pathway in China considering energy system flexibility

Abstract Net-zero energy transition is projected to accelerate the replacement of fossil fuels with renewables, leaving system flexibility resources increasingly scarce. Here, we present a sub-annual energy-environment-economy model with endogenous hourly energy demand profiles and power balance dynamics including power dispatch, storage operations and demand-side response that co-optimizes supply- and demand-side flexibility, to map feasible transition pathways for China. The results show that compared with coarser timeslice representative of common modelling practice, sub-annual representation tightening flexibility needs with a high variable renewable energy and high electrification energy system. Results reveal steeper load ramps and frequent evening price strikes, identify increased activities in thermal power, nuclear power, hydrogen production, and energy storage. Accounting for temporal variability in supply and demand, the cost-optimal solution exhibits marginal abatement costs that are over 9% higher, but incorporating demand-side flexibility measures can mitigate cost growth and delineates least-regret portfolios for reliable, affordable decarbonization. Incentives for demand-side response such as load time-shifting and vehicle-to-grid can reduce investment in pumped hydro by 23% and yield more than a threefold cost-benefit ratio. The study highlights enhanced modelling of temporal dynamics within future energy model development and incentive-compatible market mechanism design for dispatchable resource development.

Associations between per- and polyfluoroalkyl substances (PFAS), DNA methylation and gene expression from background exposed Norwegian women (2003–2006)

Abstract Per- and polyfluoroalkyl substances (PFAS) are a large group of widespread synthetic substances associated with several adverse health effects. A potential mechanism underlying these effects is epigenetic modifications, such as DNA methylation. However, evidence on associations between PFAS exposure and DNA methylation among adults is limited, and few studies have investigated the potential influence of PFAS-related methylation changes on gene expression. In this study, we investigated associations between PFAS exposure and DNA methylation in blood. Furthermore, the associations between these methylation differences and gene expression patterns were explored to assess potential functional effects. In addition, associations between PFAS concentrations and estimated white blood cell composition were investigated. This study included women (n = 269) from The Norwegian Women and Health Study (NOWAC), with available blood data on PFAS exposure, DNA methylation, and gene expression. We investigated epigenome-wide associations between PFAS exposure and DNA methylation at individual CpG sites using multivariable linear regression analyses. In a sensitivity analysis, the main models were additionally adjusted for smoking status. Furthermore, we assessed any associations between PFAS exposure and gene expression of genes mapped to CpG sites nominally associated with PFAS, also using multivariable linear regression. Finally, we examined associations between PFAS exposure and estimated white blood cell composition using multivariable linear regression models. Concentrations of PFUnDA were associated with DNA methylation at 21 unique CpG sites, comprising 17 positive and 4 negative associations. Sensitivity analyses did not substantially alter these findings. Furthermore, methylation levels at these sites did not follow a dose-dependent pattern, and the expression of genes mapped to these CpG sites was not significantly associated with exposure levels. No significant associations were observed between other PFAS (PFOA, PFNA, PFHxS, PFHpS, PFOS, and br-PFOS) and DNA methylation or gene expression. Associations between PFHxS, PFHpS, and PFOS with DNA methylation and gene expression were observed at the nominal significance level ( p value < 0.001), but these associations were modest in magnitude, lacked evidence of dose-dependence, and did not remain significant after correction for multiple testing. No statistically significant associations were observed between PFAS exposure and estimated white blood cell composition. Our findings suggest that PFUnDA may influence DNA methylation at specific CpG sites in blood of Norwegian women, though these epigenetic patterns were not accompanied by corresponding patterns in gene expression. Overall, there was limited evidence linking other PFAS to DNA methylation or gene expression.

VGLL4-driven TEAD4 multimerization orchestrates DNA binding and YAP recruitment