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High strength aluminum alloys are widely used but their strength is reduced as nano-precipitates coarsen rapidly in medium and high temperatures, which greatly limits their application. Single solute segregation layers at precipitate/matrix interfaces are not satisfactory in stabilizing precipitates. Here we obtain multiple interface structures in an Al-Cu-Mg-Ag-Si-Sc alloy including Sc segregation layers, C and L phases as well as a newly discovered χ-AgMg phase, which partially cover the θ′ precipitates. By atomic resolution characterizations and ab initio calculations, such interface structures have been confirmed to synergistically retard coarsening of precipitates. Therefore, the designed alloy shows the good combination of heat resistance and strength among all series of Al alloys, with 97% yield strength retained after thermal exposure, which is as high as 400 MPa. This concept of covering precipitates with multiple interface phases and segregation layers provides an effective strategy for designing other heat resistant materials. Coarsening of precipitates in medium and high temperatures causes reduction in strength of Al alloys. Here, the authors design an Al-Cu-Mg-Ag-Si-Sc alloy with multiple interface structures, showing an excellent combination of strength and heat resistance compared to conventional Al alloys.

To identify potential categories of alarm fatigue among ICU nurses and to explore the differences in characteristics and influencing factors among different categories. Using convenience sampling, 597 ICU nurses from 12 tertiary public hospitals across 8 cities in the Inner Mongolia Autonomous Region of China were recruited from September 2024 to December 2024. A cross-sectional survey was conducted using the General Information Questionnaire, ICU Nurses' Alarm Fatigue Scale, Stanford Presenteeism Scale: Health Status and Employee Productivity, and Nurses' Emotional Labor Scale. Potential profiles of nurse alarm fatigue were analyzed, and the influencing factors of different profiles were explored by univariate analysis and multivariate logistic regression analysis. The median alarm fatigue scale score was 26(IQR = 19.75-31), and the alarm fatigue of ICU nurses could be categorized into low fatigue-robust tolerance group (30.8%), moderate fatigue (54.4%), and high fatigue-negative coping group (14.9%). The regression analyses showed that the number of children, the frequency of night shifts, the health status and employee productivity score, and the emotional labor score were the main factors of the ICU factors influencing different potential categories of nurse alarm fatigue (P < 0.05). ICU nurses alarm in Inner Mongolia exhibited moderate-to-high alarm fatigue with notable subgroup heterogeneity. Nursing managers should implement tailored interventions addressing profile-specific factors, such as workload adjustments and emotional support strategies, to mitigate alarm fatigue.

Liver sinusoidal endothelial cells (LSECs) lose their characteristic fenestrations and become capillarized during the progression of liver fibrosis. Mesenchymal stem cell (MSC) transplantation can reverse this capillarization and reduce fibrosis, but MSC therapy has practical limitations that hinder its clinical use. Here, with the help of artificial intelligence (AI), we show that MSCs secrete a microRNA (miR-325-3p) that helps restore LSEC fenestrations (tiny pores) by modulating their cytoskeleton, effectively reversing capillarization. We further develop a spherical nucleic acid (SNA) nanoparticle carrying miR-325-3p as an alternative to MSC therapy. This SNA specifically enters fibrotic LSECs via the scavenger receptor A (Scara). In three mouse models of liver fibrosis, the SNA treatment restores LSEC fenestrations, reverses capillarization, and significantly reduces fibrosis without adverse effects. Our findings highlight the potential of SNA-based therapy for liver fibrosis, paving the way for targeted nucleic acid treatments directed at LSECs and offering hope for patients. RNAi therapies have potential to treat a range of diseases including liver fibrosis. Here, the authors report on the delivery of miR-325-3p in nucleic acid spheres, which can enter the liver sinusoidal endothelial cells, reversing their capillarisation, treating liver fibrosis in mice.

Background Tibetans are genetically adapted to high-altitude environments. Though many studies have been conducted, the genetic basis of the adaptation remains elusive due to the poor reproducibility for detecting selective signatures in the Tibetan genomes. Results Here, we present whole-genome sequencing (WGS) data of 1001 indigenous Tibetans, covering the major populated areas of the Qinghai–Tibetan Plateau in China. We identify 35 million variants, and more than one-third of them are novel variants. Utilizing the large-scale WGS data, we construct a comprehensive map of allele frequency and linkage disequilibrium and provide a population-specific genome reference panel, referred to as 1KTGP. Moreover, with the use of a combined approach, we redefine the signatures of Darwinian-positive selection in the Tibetan genomes, and we characterize a high-confidence list of 4320 variants and 192 genes that have undergone selection in Tibetans. In particular, we discover four new genes, TMEM132C , ATP13A3 , SANBR , and KHDRBS2 , with strong signals of selection, and they may account for the adaptation of cardio-pulmonary functions in Tibetans. Functional annotation and enrichment analysis indicate that the 192 genes with selective signatures are likely involved in multiple organs and physiological systems, suggesting polygenic and pleiotropic effects. Conclusions Overall, the large-scale Tibetan WGS data and the identified adaptive variants/genes can serve as a valuable resource for future genetic and medical studies of high-altitude populations.

The novel coronavirus (2019-nCoV) infection caused pneumonia. we retrospectively analyzed the virus presence in the pharyngeal swab, blood, and the anal swab detected by real-time PCR in the clinical lab. Unexpectedly, the 2109-nCoV RNA was readily detected in the blood (6 of 57 patients) and the anal swabs (11 of 28 patients). Importantly, all of the 6 patients with detectable viral RNA in the blood cohort progressed to severe symptom stage, indicating a strong correlation of serum viral RNA with the disease severity (p-value = 0.0001). Meanwhile, 8 of the 11 patients with annal swab virus-positive was in severe clinical stage. However, the concentration of viral RNA in the anal swab (Ct value = 24 + 39) was higher than in the blood (Ct value = 34 + 39) from patient 2, suggesting that the virus might replicate in the digestive tract. Altogether, our results confirmed the presence of virus RNA in extra-pulmonary sites.

Dengue is prevalent in tropical and subtropical regions. As an arbovirus disease, it is mainly transmitted by Aedes aegypti and Aedes albopictus . According to the previous studies, temperature is closely related to the survival of Aedes mosquitoes, the proliferation of dengue virus (DENV) and the vector competence of Aedes to transmit DENV. This review describes the correlations between temperature and dengue epidemics, and explores the potential reasons including the distribution and development of Aedes mosquitoes, the structure of DENV, and the vector competence of Aedes mosquitoes. In addition, the immune and metabolic mechanism are discussed on how temperature affects the vector competence of Aedes mosquitoes to transmit DENV.

Major depressive disorder (MDD) is characterized by persistent low mood and anhedonia. Mitochondrial dysfunction is linked to MDD, but the mechanisms are unclear. In this study, transcriptomic analysis of MDD patients’ peripheral blood found three key genes: TFAM , SURF1 , and NDUFB9 . Single-cell transcriptomic analysis of the prefrontal cortex (PFC) in MDD patients identified seven cell types. Analysis showed strong interactions between excitatory and inhibitory neurons in the PFC, with the three genes mainly in inhibitory neurons and NDUFB9 having the highest expression. We then established a chronic unpredictable mild stress (CUMS) mouse model. CUMS exposure induced depressive-like behaviors in mice, as evidenced by decreased sucrose preference, increased immobility time in the forced swim, and reduced activity and frequency of entries into the central area in the open field. Moreover, CUMS-exposed mice exhibited mitochondrial dysfunction in the prefrontal cortex (PFC). Notably, the expressions of TFAM, SURF1, and NDUFB9 were decreased in the PFC of CUMS mice, with the most significant decrease observed in NDUFB9. Subsequently, the overexpression of NDUFB9 in CUMS-treated mice significantly alleviated depressive-like behaviors, restored mitochondrial function and reduced the death of inhibitory neurons. It also enhanced mitophagy by PINK1/Parkin pathway. Inhibiting autophagy and mitophagy confirmed mitophagy’s pivotal role in NDUFB9-mediated restoration. Co-IP and protein half-life assays revealed that NDUFB9 stabilizes PINK1, thereby promoting mitophagy. In conclusion, our findings reveal a novel role of NDUFB9 on alleviating depression-like behavior by enhancing mitophagy, suggesting that targeting NDUFB9 could offer a promising therapeutic strategy for MDD.

Similar to two other lethal coronaviruses, SARS‐CoV and MERS‐CoV, SARS‐CoV‐2 induces excessive and aberrant host immune responses that are always accompanied by cytokine storms (CS) and subsequent ALI or even ARDS, resulting in multiple organ failure and death. 2 Even in patients who were treated in intensive care units for CS, persistent inflammation led to serious sequelae of lung fibrosis, causing lung dysfunction and reduced quality of life. 3 Although corticosteroid given to reverse catabolism in critical illness decreased the mortality after SARS and MERS infection, the clinical application of corticosteroid has been restricted in COVID‐19, considering its delay in virus clearance and complications in survivors. To alleviate acute respiratory disease and reverse pulmonary fibrosis in intensive‐care SARS‐CoV‐2‐infected patients, three curative properties of MSCs have emerged (Figure 1): (a) directly inducing the apoptosis of activated T cells to relieve the aberrant and excessive immune responses, (b) homing toward specific injuries of lung to maintain homeostasis as well as promote regeneration, and (c) releasing cytokines to diminish inflammation and extracellular vesicles (EVs) to stimulate tissue reparation. 1 Notably, it has been proved that MSC‐released cytokines can potently inhibit neutrophil intravasation and enhance the differentiation of macrophages. 5,6 Moreover, these MSC‐released EVs can deliver microRNA, mRNA, DNA, proteins, and metabolites into host cells in specific injuries of the lung to promote lung repair as well as regeneration and restore lung function. 1 1 FIGURE. Potential mechanism of MSCs in the treatment of severe COVID‐19 As the continuing epidemic threat of SARS‐CoV‐2 to global health and the fast‐growing number of fatalities, advancing new therapeutic development becomes central or primary to minimize the death and sequelae from SARS‐CoV‐2 infection. [...]MSCs should be considered as a potential treatment for these critical patients.

Neuron reconstruction is a critical step in quantifying neuronal structures from imaging data. Advances in molecular labeling techniques and optical imaging technologies have spurred extensive research into the patterns of long-range neuronal projections. However, mapping these projections incurs significant costs, as large-scale reconstruction of individual axonal arbors remains time-consuming. In this study, we present a dataset comprising axon imaging volumes along with corresponding annotations to facilitate the evaluation and development of axon reconstruction algorithms. This dataset, derived from 11 mouse brain samples imaged using fluorescence micro-optical sectioning tomography, contains carefully selected 852 volume images sized at 192 × 192 × 192 voxels. These images exhibit substantial variations in terms of axon density, image intensity, and signal-to-noise ratios, even within localized regions. Conventional methods often struggle when processing such complex data. To address these challenges, we propose a distance field-supervised segmentation network designed to enhance image signals effectively. Our results demonstrate significantly improved axon detection rates across both state-of-the-art and traditional methodologies. The released dataset and benchmark algorithm provide a data foundation for advancing novel axon reconstruction methods and are valuable for accelerating the reconstruction of long-range axonal projections.

Talaromycosis is a life-threatening fungal disease commonly seen in patients with acquired immunodeficiency syndrome (AIDS), which is endemic in Southern China and Southeast countries. The diagnostic methods available for talaromycosis are relatively time-consuming and yield a high mortality. Therefore, early diagnosis of talaromycosis is extremely important. We aimed to determine a potential method for assisting in its early diagnosis. A total of 283 patients with AIDS admitted to our hospital were prospectively included in this cross-sectional study and divided into those with Talaromyces marneffei (TSM group, n = 93) and those without Talaromyces marneffei (non-TSM group, n = 190). The diagnostic accuracy of the Mp1p enzyme immunoassay (EIA), galactomannan (GM) assay, and blood culture performed within 3 days of hospitalisation were evaluated, using talaromycosis confirmed by culture and/or pathology as the gold standard. The positivity rates in the Mp1p EIA, GM assay, and blood culture were 72%, 64.5%, and 81.7%, respectively, in the TSM group. The sensitivity, specificity, and positive and negative predictive values of the Mp1p EIA were 72.0% (67/93), 96.8% (184/190), 91.8% (67/73), and 87.6% (184/210), respectively. The Mp1p EIA showed a substantial agreement with the gold standard (kappa: 0.729) and superiority to the GM assay (kappa: 0.603); it also showed a superior diagnostic accuracy in the patients with CD4+ counts of < 50 cells/µL compared to those with CD4+ counts ranged from 50–100 cells/µL. The Mp1p EIA has the advantage of assisting in the early diagnosis of talaromycosis in patients with AIDS, especially those with low CD4+ counts.