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Musculoskeletal diseases affect over 100 million people globally and are a leading cause of severe, prolonged pain, and disability. Recognized as a clinical emergency, prompt and accurate diagnosis of musculoskeletal disorders is crucial, as delayed identification poses the risk of amputation for patients, and in severe cases, can result in life-threatening conditions such as bone cancer. In this paper, a hybrid model HRD (Human-Resnet50-Densenet121) based on deep learning and human participation is proposed to efficiently identify disease features by classifying X-ray images. Feasibility testing of the model was conducted using the MURA dataset, with metrics such as accuracy, recall rate, F1-score, ROC curve, Cohen's kappa, and AUC values employed for evaluation. Experimental results indicate that, in terms of model accuracy, the hybrid model constructed through a combination strategy surpassed the accuracy of any individual model by more than 4%. The model achieved a peak accuracy of 88.81%, a maximum recall rate of 94%, and the highest F1-score value of 87%, all surpassing those of any single model. The hybrid model demonstrates excellent generalization performance and classification accuracy. [ABSTRACT FROM AUTHOR]

Soil pathogens play important roles in shaping soil microbial diversity and controlling ecosystem functions. Though climate and local environmental factors and their influences on fungal pathogen communities have been examined separately, few studies explore the relative contributions of these factors. This is particularly crucial in eco‐fragile regions, which are more sensitive to environmental changes. Herein we investigated the diversity and community structure of putative soil fungal pathogens in cold and dry grasslands on the Tibetan Plateau, using high‐throughput sequencing. The results showed that steppe soils had the highest diversity of all pathogens and plant pathogens; contrastingly, meadow soils had the highest animal pathogen diversity. Structural equation modelling revealed that climate, plant, and soil had similar levels of influence on putative soil fungal pathogen diversity, with total effects ranging from 52% to 59% (all p < 0.001), with precipitation exhibiting a stronger direct effect than plant and soil factors. Putative soil fungal pathogen community structure gradually changed with desert, steppe, and meadow, and was primarily controlled by the interactions of climate, plant, and soil factors rather than by distinct factors individually. This finding contrasts with most studies of soil bacterial and fungal community structure, which generally report dominant roles of individual environmental factors. [ABSTRACT FROM AUTHOR]

Testosterone (TS) is an important androgen drug and a precursor of steroid drug synthesis. Ketoreductase 2 (KR-2) (GenBank accession no. ABP64403.1) is observed to stereo-selectively catalyze the bioreduction of 4-androstene-3,17-dione (4-AD) to testosterone and contribute to the regeneration of NADH using isopropanol as a co-substrate. The Km value of KR-2 was 2.22 mmol/L with 4-AD, and the optimal pH was 6.5–7.0. The enzyme is stable and demonstrates relatively high-level enzyme activity at 40 °C. Acetone significantly inhibits this activity. This inhibition was overcome using an intermittent vacuum during the reaction process. Finally, the amount of TS reached 65.42 g/L after a 52 h reaction with 65.8 g/L 4-AD, 10% isopropanol, and 2 g/L β–NAD+ at 40 °C, with a conversion rate of 98.73%. A total of 6.15 g of TS was obtained from 6.58 g of 4-AD after the reaction and purification; the HPLC purity was 99.82%, and the overall yield was 92.81%. This enzyme provides a promising route for the green biosynthesis of testosterone for industrial applications. [ABSTRACT FROM AUTHOR]

Background: The nutrient-absorbing villi of small intestines are renewed and repaired by intestinal stem cells (ISCs), which reside in a well-organized crypt structure. Genetic studies have shown that Wnt molecules secreted by telocytes, Gli1+ stromal cells, and epithelial cells are required for ISC proliferation and villus homeostasis. Intestinal stromal cells are heterogeneous and single-cell profiling has divided them into telocytes/subepithelial myofibroblasts, myocytes, pericytes, trophocytes, and Pdgfralow stromal cells. Yet, the niche function of these stromal populations remains incompletely understood. Results: We show here that a Twist2 stromal lineage, which constitutes the Pdgfralow stromal cell and trophocyte subpopulations, maintains the crypt structure to provide an inflammation-restricting niche for regenerating ISCs. Ablating Twist2 lineage cells or deletion of one Wntless allele in these cells disturbs the crypt structure and impairs villus homeostasis. Upon radiation, Wntless haplo-deficiency caused decreased production of anti-microbial peptides and increased inflammation, leading to defective ISC proliferation and crypt regeneration, which were partially rescued by eradication of commensal bacteria. In addition, we show that Wnts secreted by Acta2+ subpopulations also play a role in crypt regeneration but not homeostasis. Conclusions: These findings suggest that ISCs may require different niches for villus homeostasis and regeneration and that the Twist2 lineage cells may help to maintain a microbe-restricted environment to allow ISC-mediated crypt regeneration. [ABSTRACT FROM AUTHOR]

The electrocatalytic reduction of CO2 to high value‐added chemicals is one of the effective technologies to achieve the goal of carbon neutralization. However, highly selective production of hydrocarbon via electrochemical conversion of CO2 still has great challenges. Herein, a unique CuO phase composition is constructed that consists of rectangular nanoflakes possessing crystalline/amorphous structures by the facile strategy. Crystalline CuO square nanoblocks are confined in amorphous nanoflakes and form crystalline/amorphous hybrid phase. The results of electrocatalytic CO2 reduction demonstrate that this crystalline/amorphous CuO material exhibits superior CO2 conversion ability with ethylene Faradaic efficiency of 58.3 % at −1.08 V vs. RHE, which is ascribed to nanoflake structures and fast electron transfer on the crystalline/amorphous interfaces because of superior conductivity of amorphous CuO. The present research provides an effective route to reconstruct novel crystalline/amorphous interfaces of CuO for catalysis applications. [ABSTRACT FROM AUTHOR]

To improve their competitiveness, companies should acquire the latest software systems. However, many small or medium‐sized companies might not be able to afford a proper software acquisition process without the resource and technical support essential for acquiring the right software system. This article proposes a meta‐process, software acquisition with an external agent (SAEA), that includes a new industry role, external agent, to substitute for that support. SAEA will significantly reduce the cost of the software acquisition process. For implementing SAEA, the authors also introduce composition trees as a modelling language to collect, integrate, and compare all software requirements from different stakeholders and to identify issues during the software acquisition process. Finally, a real industry case study, for which this process has been successfully implemented, has been provided to illustrate our approach. [ABSTRACT FROM AUTHOR]

Molybdenum carbide possessing a Pt‐like d‐band electronic structure is considered as one of potential candidates of electrocatalysts and it shows intrinsic catalytic property. However, a high carbonizing temperature easily leads to the coalescence of nanoparticles (NPs). Here, we propose a simple sol‐gel route to achieve high dispersity of carbide NPs by designing a Mo‐involved xerogel. The results show that molybdenum carbide NPs are dispersed and anchored on the nitrogen‐doped carbon nanosheets (Mo2C@NC). Ultrathin carbon layers resemble graphene and the network structures act as a support of carbide NPs, which can hinder NPs' coalescence effectively. Nanpoparticles cross‐coupled on network‐structure nanosheets display the grid shapes. Electrochemical studies indicate that Mo2C@NC material exhibits outstanding hydrogen evolution performance in alkaline electrolyte. [ABSTRACT FROM AUTHOR]

Leveraging stromal cells: Reducing the activation of proinflammatory signaling pathways has been shown to have therapeutic effects in animal models and in patients with inflammatory bowel disease (IBD). However, a substantial proportion of patients do not respond to available therapies. Here, Gao et al. investigated the endogenous immune mechanisms activated in IBD to identify potential therapeutic targets. The authors identified a population of stromal cells marked by Twist2 that suppresses inflammation in animal models of IBD by producing and suppressing inflammatory M1 macrophage polarization. In patients, they identified an inverse correlation between severity of disease and stromal cell Cox2 expression. Targeting this endogenous signaling might be an effective strategy to reduce inflammation in IBD. Inflammatory bowel disease (IBD) affects 0.3% of the global population, yet the etiology remains poorly understood. Anti-inflammation therapy has shown great success, but only 60% of patients with IBD benefit from it, indicating that new targets are needed. Here, we report the discovery of an intrinsic counter regulatory mechanism in colitis pathogenesis that may be targeted for IBD treatment. In response to microbial invasion, resident Vimentin+ stromal cells, connective tissue cells genetically marked by Twist2, are activated during the propagation phase of the disease, but not during initiation and resolution phases, and become a primary source of prostaglandin E2 (PGE2). PGE2 induction requires a nuclear factor κB–independent, TLR4-p38MAPK-Cox2 pathway activation. Ablation of each of the pathway genes, but not Rela or Tgfb1, in Twist2 cells enhanced M1 macrophage polarization and granulocyte/T helper 1 (TH1)/TH17 infiltration and aggravated colitis development. PGE2 administration ameliorated colitis in mouse models with defective PGE2 production but not in animals with normal PGE2 induction. Analysis of clinical samples and public domain data revealed increased expression of Cox2, the rate-limiting enzyme of PGE2 biosynthesis, in inflamed tissues, and especially in colon Vimentin+Twist2+ stromal cells, in about 60% of patients with active Crohn's disease or ulcerative colitis. Moreover, Cox2 protein expression was negatively correlated with disease severity, suggesting an involvement of stromal cells in IBD pathogenesis. Thus, the study uncovers an active immune pathway in colitic inflammation that may be targeted to treat patients with IBD with defects in PGE2 production. [ABSTRACT FROM AUTHOR]

Accumulating evidence show that Poly C Binding Protein 1 (PCBP1) is deleted in distinct types of tumors as a novel tumor suppressor, but its tumor suppression mechanism remains elusive. Here, we firstly describe that downregulation of PCBP1 is significantly associated with clinical ovarian tumor progression. Mechanistically, PCBP1 overexpression affects various autophagy-related genes expression at various expression levels to attenuate the intrinsic cell autophagy, including the autophagy-initiating ULK, ATG12, ATG7 as well as the bona fide marker of autophagosome, LC3B. Accordingly, knockdown of the endogenous PCBP1 in turn enhances autophagy and less cell death. Meanwhile, PCBP1 upregulates p62/SQSTM1 via inhibition p62/SQSTM1 autophagolysome and proteasome degradation as well as its mRNA stability, consequently accompanying with the caspase 3 or 8 activation for tumor cell apoptosis. Importantly, clinical ovary cancer sample analysis consistently validates the relevance of PCBP1 expression to both p62/SQSTM1 and caspase-8 to overall survival, and indicates PCBP1 may be a master player to repress tumor initiation. Taken together, our results uncover the tumorigenic mechanism of PCBP1 depletion and suggest that inhibition of tumor cell autophagy with autophagic inhibitors could be an effective therapeutical strategy for PCBP1-deficient tumor. [ABSTRACT FROM AUTHOR]

Inflammation is a key regulator in the progression of atherosclerosis (AS) which extremely affects people's health. Secoisolariciresinol diglucoside (SDG), a plant lignan, is relevant to angiogenesis and cardioprotection against ischemia-reperfusion injury and improves vascular disorders. However, the effect of SDG on cardiovascular disorder is not clear. In the present study, we aimed to investigate the effects of SDG on lipopolysaccharide- (LPS-) stimulated Human Umbilical Vein Endothelial Cells (HUVECs) and elucidate the underlying mechanism. The LPS-stimulated HUVEC cellular model was established. The cell viability, the cell tube formation activity, the nitric oxide (NO) release, the levels of inflammatory cytokine interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), the activation of nuclear factor kappa-B (NF-κB) pathway, and the expression of protein kinase B (Akt) were determined using Cell Counting Kit-8, cell tube-formation assay, western blotting, and enzyme-linked immunosorbent assay. Our results revealed that SDG reduces the angiogenic capacity of HUVECs and inhibited LPS-mediated HUVEC injury and apoptosis. In addition, SDG increased NO release and decreased the levels of IL-1β, IL-6, and TNF-α in LPS-treated HUVECs. Meanwhile, SDG inhibited the NF-κB pathway and downregulated Akt expression in LPS-induced HUVECs. Our results indicated that SDG relieves LPS-mediated HUVEC injury by inhibiting the NF-κB pathway which is partly dependent on the disruption of Akt activation. Therefore, SDG exerts its cytoprotective effects in the context of LPS-treated HUVECs via regulation of the Akt/IκB/NF-κB pathway and may be a potential treatment drug for cardiovascular disease. [ABSTRACT FROM AUTHOR]

The transport properties of the solid electrolyte interphase (SEI) play an important role in the charging and discharging process of lithium-ion batteries (LIBs). We used nonequilibrium molecular dynamics (NEMD) simulation to mimic the lithium permeability of SEI films with different chemical compositions, thicknesses and densities. We found the order of permeability to be Li2CO3 > LiF > compound > Li2O > LiOH. Permeability is likely more affected by the binding energy between the lithium ions and the SEI atoms than by structural qualities such as surface area and porosity. The density profiles indicate lithium ions tend to accumulate on the SEI–vacuum interface when the film is less permeable. The transport process does not satisfy Einstein's diffusion equation, thereby revealing the nonequilibrium nature. The relationship between the chemical compositions, densities, thicknesses and permeabilities of each film is expressed by an empirical equation, which can be used to quickly predict the transport properties of SEI films. [ABSTRACT FROM AUTHOR]

Local defect structures play significant roles on material properties, but they are seriously neglected in the design, synthesis, and development of highly efficient TiO2‐based visible light catalysts (VLCs). Here, we take anatase TiO2 nanocrystals that contain (Ti3+, N3−) ions and have the complicated chemical formula of (Ti1-x4+Tix3+)(O2-y-z2-Ny3- □z) as an example, and point out that the formation of Ti3+‐VO‐2Ti4+‐N3− local defect clusters is a key missing step for significantly enhancing VLC properties of host TiO2 nanocrystals. Experimental and theoretical investigations also demonstrate the emergent behaviors of these intentionally introduced defect clusters for developing highly efficient VLCs. This research thus not only provides highly efficient visible light catalysts for various practical applications but also addresses the significance of local defect structures on modifying material properties. Defect‐clusters‐driven: Local defect structure could determine or create material properties since it could change a local chemical environment and subsequently mediate the electronic state density of materials. Here, we demonstrate that the deliberate design and formation of Ti3+‐VO‐2Ti4+‐N3− defect clusters in TiO2 anatase nanocrystals would drive the highly efficient visible light catalytic decomposition of organic contaminates. This research thus not only presents a defect‐engineering route to design/develop highly efficient visible light catalysts but also highlights the significance of local defect structures on modifying material properties. [ABSTRACT FROM AUTHOR]

Better understanding of the colloidal behaviors of nanomaterials impacted by aquatic chemistry parameters is needed for appropriate evaluation of the environmental risks posed by nanomaterials in natural waters. In the study, the colloidal stability of Fe 3 O 4 magnetic nanoparticles (Fe-MNPs) was evaluated over a range of chemistry characteristics [e.g., pH, dissolved organic matter (DOM), salt types, cationic strength] in six synthetic water samples. The findings from the synthetic water samples were further examined with eight “real world” environmental water samples. Our results demonstrated that DOM fraction, humic acid (HA), promoted suspension of Fe-MNPs more by hydrophobic interactions in addition to ligand exchange and electrostatic effects compared with fulvic acid (FA). Capability of cations to increase aggregation of Fe-MNPs were in the order of Ca 2+  > Mg 2+ >> Na + because of their different degrees of bridging complexation with DOM molecules on particle surfaces. As a key parameter for indicating Fe-MNPs colloidal stability, Zeta (ζ) potentials of Fe-MNPs in these waters samples were well correlated to (R 2  = 0.880, P  < 0.001) the contents, types and adsorption forms of DOM and cations. However, several other factors could also affect the hydrodynamic diameter (HDD) of Fe-MNPs in the “real world” environmental waters. It assumed that ampholytic-DOM molecules such as amino acid- and protein-like molecules caused great aggregation of Fe-MNPs. These findings would be helpful for better understanding and evaluating the colloidal behaviors of nanomaterials when they released into natural water environment, thus could shed light on developing relevant pollution control strategies. [ABSTRACT FROM AUTHOR]

To utilize Si nanostructures as photocathode for high-efficiency solar water splitting, a catalyst with low cost and high activity is inevitable to modify Si. In this study, employing the electrochemical deposition method, the surfaces of Si nanowire arrays were decorated with a novel non-noble metal electrocatalyst, Mo 4 O 11 . The morphology, chemical composition and structure of the as-synthesized Si/Mo 4 O 11 nanowire arrays were characterized in details. As photocathodes for photoelectrochemical water splitting, the Si/Mo 4 O 11 nanowire arrays exhibited more positive turn-on potential and larger photocurrent compared to Si nanowire arrays. The results demonstrate that the Si/Mo 4 O 11 nanowire arrays could be a promising candidate for solar water splitting. [ABSTRACT FROM AUTHOR]