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White House proposes vast overhaul of US science funding: what you need to know

In silico investigation of thiazole–semicarbazide hybrids as dual GSK-3β/Tau inhibitors for Alzheimer’s disease

Abstract AD is a widespread and debilitating neurodegenerative disorder, and existing treatments have demonstrated limited efficacy, emphasizing the need for novel therapeutic strategies. This study focused on the design of drug-like molecules with enhanced efficacy and minimized side effects by application of structure-based scaffold hopping and molecular hybridization strategies. Molecular docking was carried out on Glide module; Molecular dynamics simulation of 500 ns was executed employing Desmond and ADMET prediction was achieved by QikProp modules of Schrödinger. Through molecular docking studies targeting the GSK-3β and Tau enzymes, the compounds DVK5 and DVK11 were identified as promising inhibitors, showing favorable interactions within the active sites of these proteins, with docking energies of − 9.863 and – 8.994 kcal/mol , respectively. Molecular dynamics simulations further revealed that the DVK5 and DVK11 complexes exhibited stable interactions within the active sites of GSK-3β and Tau throughout a 500 ns simulation. Additionally, in silico ADMET analysis demonstrated that DVK10 exhibited an excellent human oral absorption rate of 75.175% , outperforming other compounds in the series. These findings strongly suggest the potential of DVK5 and DVK11 as dual inhibitors of GSK-3β and Tau, offering a basis for future drug development studies for the development of new lead compounds for AD treatment.

Orthogonal relay system for efficient CO-to-ethanol electrosynthesis

AIS data-driven MAAC-Stackelberg multi-ship cooperative collision avoidance algorithm

Ship collision avoidance has become a focus issue in maritime navigation. Existing methods often struggle to simultaneously meet the hierarchical decision-making requirements of the International Regulations for Preventing Collisions at Sea (COLREGs), address the dynamic uncertainty of ship risk attitudes, and effectively cope with multi-ship coupling risks. To solve the above problems,this paper proposes an algorithm that combines multi-agent systems with game theory, and integrates ship collision avoidance rules into the reward function design. The algorithm constructs a two-stage framework: the risk attitude perception layer uses a Long Short-Term Memory (LSTM) network to predict the short-term motion states of target ships, and dynamically infers the probability distribution of target ships’ risk attitudes through a Bayesian network combined with historical Automatic Identification System (AIS) data and encounter characteristics. The decision-making execution layer integrates Stackelberg game with the Multi-Agent Actor-Critic (MAAC) algorithm, and embeds COLREGs as rigid constraints into the action space to ensure the compliance of the algorithm. Experimental verification is carried out based on historical AIS data and simulation scenarios. The results show that the proposed algorithm has certain advantages in various key indicators,the collision rate, the COLREGs compliance rate, the trajectory smoothness, and the average risk. Statistical significance tests confirm the robustness and superiority of the algorithm. This study provides a reliable technical scheme for ship collision avoidance strategies in multi-ship waters.

Development and validation of an explainable model for Mycoplasma pneumoniae infection in children

Flipping antimicrobial peptides in the exit tunnel of the bacterial ribosome

Abstract Proline-rich antimicrobial peptides (PrAMPs) kill bacteria by binding in the ribosomal nascent peptide exit tunnel. Type II PrAMPs bind in an orientation matching that of the nascent protein, trap the release factors and arrest ribosomes at stop codons. Conversely, Type I PrAMPs bind in an opposite orientation: their N-terminus invades the peptidyl transferase center arresting translation at start codons. Here, by mining the genome databases, we identify a number of PrAMPs with high sequence similarity to the Type II PrAMP Drosocin. Notably, many of the new PrAMPs do not stall ribosomes at stop codons, but act as Type I PrAMPs arresting translation at start codons. Structural analysis shows that such peptides bind with a Type I orientation. Minimal alterations in the peptide structure can flip the orientation of the PrAMP in the exit tunnel, switching the mechanism of translation inhibition. Altering the mode of binding and action of a PrAMP by only few mutations could be exploited by the host to combat newly emerging bacterial pathogens.

Loneliness and coping strategies in older adults in nursing homes in the Northern region of Malaysia: A mixed-method study

Background Loneliness among institutionalized older adults poses significant health risks, yet remains understudied. A deeper understanding can help shape more compassionate, culturally appropriate, and effective care approaches for the aging demographic. This study aimed to explore the lived experiences of loneliness and the coping mechanisms adopted by older adults residing in institutionalized nursing homes in the Northern region of Malaysia. Methods A mixed-method study was used. A qualitative phenomenological approach was conducted at Rumah Seri Kenangan Taiping, Perak, Malaysia. Participants were selected via purposive sampling. Data collection comprised face-to-face semi-structured interviews. A quantitative approach using the Malay version of the 6-item De Jong Gierveld Loneliness Scale triangulates the methods. Thematic analysis was applied to the interview transcripts using NVivo version 14, and descriptive statistics were performed in SPSS version 27 to analyze loneliness scale scores. Results Twenty-three older adults participated in both qualitative and quantitative analyses. All participants experienced loneliness; 13 respondents were most lonely, with a mean (SD) loneliness score of 4.52 (1.04). Five causes contributing to loneliness were identified: loss of loved ones, health-related issues, socio-economic challenges, socio-cultural changes, and environmental restrictions within the institution. Loneliness impacted participants’ physical health, emotional well-being, and mental health. Coping strategies clustered into three themes: spiritual coping (religious fulfillment and acceptance), strengthening social ties (contact with family, bonding with residents, and visitor interactions), and attention distraction (hobbies, social media use, and participation in institutional activities). Conclusions Loneliness among institutionalized older adults is a multidimensional experience with significant physical and emotional repercussions. However, participants demonstrated resilience through spiritual, social, and behavioral coping strategies. These findings underscore the importance of holistic interventions that enhance emotional support, spiritual well-being, and meaningful engagement to improve the quality of life for older adults living in institutional settings.

Cooperation conflicts with equality when allocating public goods

Human papillomavirus infection and the risk of uveitis: a propensity-score-matched electronic health record study

Closed-loop high-precision two-photon lithography based on a multiplexed single-cavity dual-comb laser

Abstract Two-photon lithography fabricates three-dimensional structures with 100-nanometer resolution; yet its industrial adoption is hindered by poor reproducibility and the need for complex manual tuning processes. While post-fabrication metrology, such as scanning electron microscopy, characterizes final morphologies, it cannot prevent manufacturing errors. Here we show a two-photon lithography platform powered by a single-cavity dual-comb laser that addresses this limitation through real-time correction. During fabrication, one laser comb, after frequency conversion, performs two-photon printing, while the dual-comb system simultaneously performs in-situ phase measurements across the full work field at 360 hertz. By feeding the phase profiles into a dynamic model, the platform automatically modulates printing parameters to correct height errors. We demonstrate this capability through a continuous 14-hour fabrication process to manufacture different millimeter-scale diffractive optical elements with less than 100-nm absolute errors. The resulting devices exhibit superior signal-to-noise ratios, process repeatability, and focus quality. This closed-loop dual-comb platform offers a cost-effective, scalable solution for high-precision, high-yield nanomanufacturing.

The reliability and validity of rehabilitation set of the international classification of functioning, disability, and health in assessing Chinese tumor patients

Background and aim There is currently no comprehensive scale suitable for assessing the rehabilitation progress of Chinese tumor patients. This study aimed to evaluate the psychometric properties of the Rehabilitation Set of the International Classification of Functioning, Disability, and Health for that purpose. Methods The Chinese version of the International Classification of Functioning, Disability, and Health’s Rehabilitation Set (ICF-RS) was used by trained health professionals to assess 1055 Chinese tumor patients. The internal consistency of the responses was assessed in terms of Cronbach’s alpha coefficient. Construct validity was explored through factor analysis. Test-retest reliability, inter-rater reliability, and criterion validity were evaluated using a subset of 121 patients. Criterion validity was quantified by correlating the scores with those generated using the Hospital Anxiety and Depression scale (HADS), the Eastern Cooperative Oncology Group (ECOG) performance status evaluation and the modified Barthel Index (MBI). Results The Cronbach’s alpha for the rehabilitation set’s scores was 0.87, indicating good internal consistency. The test-retest reliability analysis showed that most categories had an intraclass correlation coefficient in excess of 0.75, suggesting good reliability when the rehabilitation set is applied with tumor patients. Inter-rater reliability also demonstrated intraclass correlation greater than 0.75 for most categories. Construct validity was supported by the finding that 18 categories had factor loadings exceeding 0.40. After removing categories with lower factor loadings, the cumulative variance explained increased to 44.6% for the Activity and Participation component and 57.3% for the Body Functions component. Criterion validity was supported by significant associations with established instruments. Specifically, 66.7% (20/30) of the ICF-RS categories correlated significantly with the MBI, with effect sizes (r) ranging from 0.19 to 0.52 (p < 0.05). In contrast, only 10% (3/30) of categories demonstrated significant correlations with the ECOG ratings (ρ = 0.21–0.22, p < 0.05). Furthermore, categories related to emotional functions and psychological demands showed significant correlations with the HADS, with moderate effect sizes (ρ = 0.37–0.41, p < 0.001). Conclusions The Chinese version of the ICF-RS exhibits promising psychometric properties in tumor patients, providing preliminary evidence for its clinical application. It demonstrates good internal consistency, high test-retest reliability and reliable inter-rater consistency. The moderate correlation with MBI ratings and HADS scale scores, along with the distinct factors identified through factor analysis, further supports the instrument’s validity and utility when applied to this population. The data confirm that the ICF-RS is a reliable tool for assessing tumor patients’ functioning and disability. However, the construct validity results recommend further work before the instrument is widely used with tumor patients.

Genetic exploration of the impact of CYP11A1 polymorphisms on the development of PCOS: evidence from a meta-analysis with trial sequential analysis

Abstract Altering CYP11A1 expression due to polymorphisms can increase the likelihood of developing polycystic ovarian syndrome (PCOS). Several CYP11A1 polymorphisms have been extensively studied for their association with PCOS risk, but the findings have been inconsistent. To clarify this association, a meta-analysis was conducted to evaluate the relationship between various CYP11A1 variants and PCOS. A comprehensive literature search was conducted in PubMed/MEDLINE, Web of Science, the Cochrane Library, ScienceDirect, medRxiv, and Google Scholar, up to August 20, 2025. The quality of each article was evaluated using the Newcastle–Ottawa Scale (NOS). Meta-analysis of genetic association was performed by using the MetaGenyo web-based tool, whereas publication bias was examined by Egger’s test. Additionally, trial sequential analysis (TSA) and in silico gene expression analyses were conducted. Benjamini–Hochberg false discovery rate (FDR) correction was applied to control for multiple testing. In the overall population, we found a statistically significant association between the rs4077582 variant and increased PCOS risk in codominant Model 1 (OR = 2.07), codominant Model 2 (OR = 2.12), dominant Model (OR = 2.10), overdominant Model (OR = 1.54), recessive Model (OR = 1.50), and allelic contrast Model (OR = 1.66). These associations remained significant after FDR correction and trim-and-fill adjustment. For rs11632698, codominant 3 (OR = 1.47) and recessive models (OR = 1.57) were significantly linked with PCOS, although TSA indicates that the current evidence remains inconclusive. Trim-and-fill analysis for rs4077582 models showed that small-study effects slightly attenuated the pooled estimates, but the associations remained statistically significant. In contrast, no significant association was detected in the case of the rs6495096, rs4887139, and rs1484215 polymorphisms. This research suggests that the rs4077582 variant of the CYP11A1 gene may increase the risk of PCOS in the overall population. However, given the observational nature of the included studies and the predefined assumptions of TSA, further research on diverse ethnic groups, including functional and longitudinal studies, is needed to confirm this link more conclusively.

Heterogeneity and dynamics of DENV-specific CD8 + T cells in dengue infection

Abstract Dengue virus (DENV) is a major global health threat, with secondary heterotypic infections potentially inducing detrimental memory immune responses. Antigen-specific CD8 + T cells contribute to both protection and pathogenicity, yet how their phenotypic heterogeneity relates to disease severity remains unclear. Here, we performed plate-based single-cell RNA sequencing of circulating DENV-specific CD8 + T cells identified by HLA tetramers loaded with DENV NS3-derived epitopes. Using tetramer binding to peptides corresponding to the currently and serologically inferred dominant previously infecting serotypes, we identify distinct CD8 + T cell subsets associated with disease severity. Asymptomatic dengue is enriched for lower tetramer binding cells with moderate cytotoxic programs, whereas dengue hemorrhagic fever is associated with high tetramer binding CX3CR1 + CD8 + T cells exhibiting enhanced expression of genes related to T cell receptor signaling and cytotoxicity. T cell receptor repertoires are similar among symptomatic cases but displayed temporal dynamics. Overall, DENV NS3-specific CD8 + T cells across disease severity and time are associated with distinct transcriptomic states and T cell receptor features.

Perceptions and experiences of women and providers on barriers and facilitators of quality emergency obstetric and newborn care services in public hospitals of West Shoa Zone, Oromia, Ethiopia: A phenomenological qualitative study

Background Evidence shows that health care delivery is inadequate and poor quality in low- and middle-income countries. Recently, poor quality of health care has been a more significant challenge for reducing maternal and perinatal mortality than insufficient access to health care services. However, data on barriers and facilitators to quality emergency obstetric and newborn care service in Ethiopia are limited. Therefore, this study aims to explore the perceptions and experiences of women and providers on barriers and facilitators of quality emergency obstetric and newborn care services in public hospitals of West Shoa Zone, Ethiopia. Methods A phenomenological qualitative study was conducted in four selected public hospitals of West Shoa Zone from June 01 to July 30 of 2024. A total of sixty-five study participants were purposively selected and interviewed until data saturation. The data were collected through focus group discussions (38 participants), in-depth interviews (12 participants), and key informant interviews (15 participants). The collected data were transcribed verbatim and translated into English language. Finally, MAXQDA software version 24.4.1 was used for thematic data analysis. Results The study findings were categorized into two major themes (i.e., barriers and facilitators) and three sub-themes (factors related to health care facilities, factors related to health care providers, and factors related to clients and the community as a whole). The main identified barriers were a shortage of medical resources and facility infrastructures; insufficient human resources; knowledge and skill gaps of health care providers; inadequate respectful maternity care; a weak client referral system; a lack of updated training; limited community awareness on emergency cases; and inadequate mentoring and supervision activities. In contrast, the major facilitators included the availability of free maternity services, a multidisciplinary team, strong provider commitment and teamwork, establishment of neonatal intensive care units and blood banks, access to ambulances, and community pharmacies. Conclusions This study identified a range of barriers and facilitators influencing the quality of emergency obstetric and newborn care services, encompassing factors related to healthcare facilities, healthcare providers, as well as clients and the whole community. Therefore, all health care facilities and the regional health bureau need to improve the identified barriers and strengthen all facilitators of quality emergency obstetric and newborn care services.

Profiling of extracellular vesicles from primary hepatocytes, organoids, and mash patients identifies cell injury-specific signatures

Abstract Metabolic Dysfunction-Associated Steatohepatitis (MASH) is a severe form of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), traditionally diagnosed via invasive biopsy, underscoring the need for non-invasive alternatives. This study identifies biologically relevant extracellular vesicle (EV) protein signatures associated with MASH using patient serum, primary human hepatocytes (PHH), and human liver organoids (HLO). These complementary models capture distinct aspects of disease progression-circulating EV profiles in patients, hepatic cellular responses in PHH, and multicellular interactions in HLO-providing a comprehensive view of MASH pathophysiology. Using aptamer-based technology, we assayed 6596 proteins from 38 individuals with histological confirmed MASLD and in vitro models. EVs were characterized using nano-flow cytometry, ExoView, and high-resolution microscopy (ONI), with liver-specific markers confirming their origin. Key proteins, including SLC27A5, HP, and CXCL7, were elevated in patient samples, while PHH and HLO models exhibited upregulation of ASGPR1, HP, and CXCL7 under MASH conditions. Proteomic analysis revealed shared pathways across models, with machine learning models achieving AUROC values of 0.97, supporting the diagnostic potential of these protein signatures. This integrative approach advances MASH biomarker discovery by linking localized liver dysfunction with systemic disease mechanisms. These findings highlight clinically relevant EV protein signatures that support the development of non-invasive diagnostics and personalized treatment strategies, including prediction of outcomes for bariatric surgery patients.

MYOD1 mutation drives cancer stem cell pathways and therapy-resistance in spindle cell/sclerosing rhabdomyosarcoma

Abstract Tumor growth and relapse are often driven by cancer stem cells, but self-renewal mechanisms and genetic mutations that elevate their number are not fully understood. Here, we show that recurrent L122R mutation (Leucine to Argine change at amino acid 122) in the DNA-binding site of the Myogenic Differentiation 1 (MYOD1) transcription factor increases cancer stem cell frequency in aggressive Spindle cell/sclerosing rhabdomyosarcoma. MYOD1 L122R also makes tumors resistant to chemotherapy and radiation. Epigenetic analysis reveals that MYOD1 L122R binds MYC-like DNA recognition motifs to activate stem cell programs, while retaining some wild-type function to regulate muscle pathways that drive transformation. Mechanistically, MYOD1 L122R transcriptionally activates Receptor tyrosine kinase-like Orphan Receptor 2 (ROR2) to turn on the non-canonical Wingless/Integrated (WNT) planar cell polarity pathway to increase both cancer stemness and therapy resistance. Targeting ROR2 with antibody-drug conjugates kills MYOD1 L122R -mutated tumor cells, offering therapeutic opportunities. These findings provide insights into how MYOD1 L122R rewires rhabdomyosarcoma to a stem-like state and defines a unique class of oncogenic transcription factors found in aggressive cancers.

A cloud-edge-end collaborative intelligent caching method based on incremental federated learning algorithms

In a cloud-edge-end collaborative system, data generated by terminal devices often contains users’ sensitive information and is constantly generated and changing, leading to potential data privacy leaks in caches. Additionally, due to the inability to promptly capture these dynamic changes and the failure to consider the actual capabilities of nodes, caching strategies become outdated, resulting in reduced cache hit rates and cache imbalance issues. Therefore, this study proposes a cloud-edge-end collaborative intelligent caching method based on an incremental federated learning algorithm. First, the federated learning algorithm is used to aggregate data from terminal devices to the cloud, enabling collaborative data processing while protecting data privacy. Second, incremental learning methods are employed to continuously update terminal data, with the updated data aggregated to the cloud, thereby enabling real-time tracking of data trends and allowing cache strategies to rapidly adapt to dynamic changes in terminal data. Finally, considering the actual capabilities of nodes, the popularity of aggregated data and the weights of edge and terminal nodes are calculated. Data is cached in edge and terminal nodes in descending order of popularity and weight. When cache space is insufficient, data replacement is performed based on the importance of data within nodes, thereby completing intelligent data caching. Experimental results demonstrate that this method achieves good performance in data update aggregation, with high data caching balance and cache hit rates.

Palladium anchored to magnetic silica functionalized with AP groups as a novel and efficient heterogeneous catalyst for C–C coupling reactions

Data-driven concavity engineering for magnetic activation in rigid microspheres

Effectiveness of a home-based exercise program for improving upper limb function in community-dwelling older people: A pragmatic randomized controlled trial

Background Upper limb dysfunction, including shoulder pain, is a major health issue for older people. Exercise is commonly used to treat shoulder disorders. This study aimed to determine the effect of a home-based upper limb exercise program on upper limb function compared to a lower limb exercise program, among community-dwelling people aged 65 years + . Methods A randomized controlled trial was conducted. One group received a home-based exercise program targeting upper limb (UL) strength, mobility and function. The other group received a home-based exercise program targeting lower limb (LL) balance and strength. Both exercise programs were taught at three group-based sessions in weeks 1, 4 and 12 post-randomization. Participants were requested to complete exercises three times per week for 12 months. The primary outcome was UL function, measured with the self-report Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire. Secondary outcomes included shoulder strength and range of motion (ROM), quality of life (QOL) and physical activity. Results 617 participants were randomly assigned to UL (n = 307) or LL (n = 310) groups. Mean age was 73 years, (SD 6.0) and 64% were female. No clinically important or statistically significant between-group difference was detected in UL function (measured by the DASH) at 12 months (mean difference (MD) = 0.99, 95% CI −0.82 to 2.79, p  = 0.283, n  = 462). There were no significant between-group differences in shoulder ROM, most measures of strength, physical activity (device-measured and self-report), QOL and UL function at three and six months. Participants performed the exercises twice per week, averaging 104 exercise sessions (SD 69, median 117, range 0–371) over the 12-month intervention period. Conclusion People aged 65 + can successfully learn and adhere to a home-based exercise program for the UL with instruction provided in a group setting, however this program did not improve UL strength, mobility and function. Considering the increased rates of shoulder dysfunction in older age, more research is needed to determine the optimal exercise protocols for prevention of shoulder dysfunction.