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Abstract Objective The aim of this study is to assess the use of machine learning methodologies in the diagnosis of endometriosis (EM). Methods This study included a total of 106 patients with EM and 203 patients with non-EM conditions (like simple cysts and simple uterine fibroids), all admitted to the Shunyi Women’s and Children’s Hospital of Beijing Children’s Hospital between January 2017 and September 2022. All participants were free of comorbidities and their diagnoses were confirmed via postoperative pathology. Comparative analysis was conducted between the EM and non-EM groups. Baseline data were assessed, including white blood cell count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, mean platelet volume, hemoglobin, carbohydrate antigen 125 (CA125), carbohydrate antigen 199, coagulation parameters, and other serologic indicators. An optimal predictive model was developed using an artificial intelligence algorithm to determine the presence of EM. The objective is to provide new insights for the clinical diagnosis and treatment of EM. Results The random forest algorithm demonstrated superior performance when compared to decision trees, LogitBoost, artificial neural networks, naïve Bayes, support vector machines, and linear regression in machine learning methods. Combining CA125 with the NLR yielded a better prediction of EM than using CA125 alone when applying the random forest algorithm. The accuracy of predicting EM with CA125 combined with NLR was 78.16%, with a sensitivity of 86.21% and an area under the curve (AUC) of 0.85 (P

In general, the Ti–6.5Al–2Zr–1Mo–1V (TA15) components fabricated via laser powder bed fusion (L-PBF) exhibit high strength and low ductility. Herein, we report a novel approach to enhance the comprehensive mechanical properties of L-PBF TA15 alloy by adjusting the laser power. Samples processed using the optimal laser power exhibit a grid structure of alternating wide and narrow prior-β grains (PBGs), the inside of which is composed of a fully martensitic microstructure. The paper discusses in detail the alterations in the microstructure of samples processed at both low and high laser powers, clarifying the relationship between microstructure and mechanical properties. Thinner martensite contributes to higher strength, while a homogenous microstructure improves ductility. These findings provide valuable insights for controlling microstructure and achieving strength-ductility synergy in L-PBF additive manufacturing of titanium alloys.

Abstract Au@Pt nanozyme, a bimetallic core–shell structure Au and Pt nanoparticle, has attracted significant attention due to its excellent catalytic activity and stability. Here, we propose that Au@Pt improves glucose tolerance and reduces TG after four weeks administration. The transcriptomic analysis of mouse liver tissues treated with Au@Pt nanozyme showed changes in genes related to glucose and lipid metabolism signaling pathways, including glycolysis/gluconeogenesis, pyruvate metabolism, PPAR signaling, and insulin signaling. Moreover, analysis of fecal samples from mice treated with Au@Pt nanozyme showed significant changes in the abundance of beneficial gut microbiota such as Dubosiella, Parvibacter, Enterorhabdus, Monoglobus, Lachnospiraceae_UCG-008, Lachnospiraceae_UCG-006, Lachnospiraceae_UCG-001, and Christensenellaceae_R-7_group. Combined multi-omics correlation analyses revealed that the modulation of glucose and lipid metabolism by Au@Pt was strongly correlated with changes in hepatic gene expression profiles as well as changes in gut microbial profiles. Overall, our integrated multi-omics analysis demonstrated that Au@Pt nanozyme could modulate glucose and lipid metabolism by regulating the expression of key genes in the liver and altering the composition of gut microbiota, providing new insights into the potential applications of Au@Pt nanozyme in the treatment of metabolic disorder. Graphical Abstract

Abstract Background Prostate cancer (PCa) stands as the second most prevalent malignancy impacting male health, and the disease’s evolutionary course presents formidable challenges in the context of patient treatment and prognostic management. Charged multivesicular body protein 4 C (CHMP4C) participates in the development of several cancers by regulating cell cycle functions. However, the role of CHMP4C in prostate cancer remains unclear. Methods In terms of bioinformatics, multiple PCa datasets were employed to scrutinize the expression of CHMP4C. Survival analysis coupled with a nomogram approach was employed to probe into the prognostic significance of CHMP4C. Gene set enrichment analysis (GSEA) was conducted to interrogate the functional implications of CHMP4C. In terms of cellular experimentation, the verification of RNA and protein expression levels was executed through the utilization of qRT-PCR and Western blotting. Upon the establishment of a cell line featuring stable CHMP4C knockdown, a battery of assays, including Cell Counting Kit-8 (CCK-8), wound healing, Transwell, and flow cytometry, were employed to discern the impact of CHMP4C on the proliferation, migration, invasion, and cell cycle function of PCa cells. Results The expression of CHMP4C exhibited upregulation in both PCa cells and tissues, and patients demonstrating elevated CHMP4C expression levels experienced a notably inferior prognosis. The nomogram, constructed using CHMP4C along with clinicopathological features, demonstrated a commendable capacity for prognostic prediction. CHMP4C knockdown significantly inhibited the proliferation, migration, and invasion of PCa cells (LNcaP and PC3). CHMP4C could impact the advancement of the PCa cell cycle, and its expression might be regulated by berberine. Divergent CHMP4C expression among PCa patients could induce alterations in immune cell infiltration and gene mutation frequency. Conclusions Our findings suggest that CHMP4C might be a prognostic biomarker in PCa, potentially offering novel perspectives for the advancement of precision therapy for PCa.

Abstract. Background:. Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid (GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development. Methods:. We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 (E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib. Results:. GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment. Conclusions:. GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.

This study aimed to compare the diagnostic efficacy of dynamic contrast-enhanced computed tomography (CT), dynamic contrast-enhanced Magnetic Resonance Imaging (MRI) and their combination in diagnosing adrenal tumors. 68 patients with adrenal tumors admitted to the hospital from December 2019 to December 2020 were selected. MRI and CT plain scans were performed on all patients, as well as dynamic contrast-enhanced imaging. As the gold standard for evaluating diagnostic efficacy, dynamic contrast-enhanced CT, dynamic contrast-enhanced MRI, and their combination were compared with pathological examination results. To compare diagnostic method differences, receiver operating characteristic (ROC) curves were plotted. MRI contour rates at each delay point were significantly higher in adenoma patients than non-adenoma patients (p < 0.05). CT contour rates at each delay point were also significantly higher in adenoma patients than non-adenoma patients (p < 0.05). The sensitivity, accuracy and negative predictive value of the combined diagnostic examination were significantly higher than individual examinations (p < 0.05). Based on ROC curve analysis, dynamic contrast-enhanced MRI, dynamic contrast-enhanced CT, and the combined diagnostic had an area under the curve (AUC) of 0.818 (95% Confidence Interval (CI): 0.696–0.940), 0.827 (95% CI: 0.706–0.949), and 0.908 (95% CI: 0.769–1.019), respectively. The combined diagnosis showed the largest AUC with significant differences (p < 0.05). The overall model quality analysis showed that the model values of single and combined indicators were greater than 0.5, and the highest value of the combined index was 0.80. In summary, the combination of dynamic-enhanced CT and dynamic-enhanced MRI is more effective at diagnosing adrenal tumors than either technique alone. Combination diagnoses can assist in diagnosing and treating adrenal tumors with high clinical application value.

Abstract In practice, simultaneous impact localization and time history reconstruction can hardly be achieved, due to the ill-posed and under-determined problems induced by the constrained and harsh measuring conditions. Although $$\ell_{1}$$ ℓ 1 regularization can be used to obtain sparse solutions, it tends to underestimate solution amplitudes as a biased estimator. To address this issue, a novel impact force identification method with $$\ell_{p}$$ ℓ p regularization is proposed in this paper, using the alternating direction method of multipliers (ADMM). By decomposing the complex primal problem into sub-problems solvable in parallel via proximal operators, ADMM can address the challenge effectively. To mitigate the sensitivity to regularization parameters, an adaptive regularization parameter is derived based on the K-sparsity strategy. Then, an ADMM-based sparse regularization method is developed, which is capable of handling $$\ell_{p}$$ ℓ p regularization with arbitrary p values using adaptively-updated parameters. The effectiveness and performance of the proposed method are validated on an aircraft skin-like composite structure. Additionally, an investigation into the optimal p value for achieving high-accuracy solutions via $$\ell_{p}$$ ℓ p regularization is conducted. It turns out that $$\ell_{0.6}$$ ℓ 0.6 regularization consistently yields sparser and more accurate solutions for impact force identification compared to the classic $$\ell_{1}$$ ℓ 1 regularization method. The impact force identification method proposed in this paper can simultaneously reconstruct impact time history with high accuracy and accurately localize the impact using an under-determined sensor configuration.

Abstract Melatonin (MT) is a key regulator in plants’ response to leaf senescence induced by aging or various abiotic stresses. Here, we demonstrated that darkness and leaf aging enhance endogenous MT levels by upregulating key genes involved in MT synthesis. Additionally, exogenous MT application significantly mitigated leaf senescence induced by darkness and leaf aging in tomato plants, leading to higher chlorophyll content and maximum photochemical efficiency (Fv/Fm) compared to the control. Using Solanum lycopersicum L. tryptophan decarboxylase (SlTDC)-overexpressed and -knockout transgenic tomato seedlings, we found that SlTDC overexpression increased endogenous MT content and suppressed mRNA levels of chlorophyll degradation-related genes: pheophorbide a oxygenase (PAO), pheophytinase (PPH), and non-yellow coloring1 like (NOL). Furthermore, SlTDC overexpression alleviated photosystem II complex (PSII) photoinhibition, increased ribulose-1,5-bisphosphate carboxylase (Rubisco) and Rubisco activase (RCA) activities and mRNA levels, and maintained higher photosynthetic efficiency in leaves under darkness and in leaves aged over 35 d compared to wild-type plants. Conversely, SlTDC knockout accelerated darkness- or leaf aging-induced leaf senescence in tomatoes. Our findings suggest that MT application or SlTDC overexpression can effectively alleviate leaf senescence by regulating photosynthesis in tomato plants.

Abstract Lung cancer is a leading cause of cancer-related mortality globally, with a dismal 5-year survival rate, particularly for Lung Adenocarcinoma (LUAD). Mechanical changes within the tumor microenvironment, such as extracellular matrix (ECM) remodeling and fibroblast activity, play pivotal roles in cancer progression and metastasis. However, the specific impact of the basement membrane (BM) on the mechanical characteristics of LUAD remains unclear. This study aims to identify BM genes influencing internal mechanical stress in tumors, elucidating their effects on LUAD metastasis and therapy resistance, and exploring strategies to counteract these effects. Using Matrigel overlay and Transwell assays, we found that mechanical stress, mimicked by matrix application, augmented LUAD cell migration and invasion, correlating with ECM alterations and activation of the epithelial-mesenchymal transition (EMT) pathway. Employing machine learning, we developed the SVM_Score model based on relevant BM genes, which accurately predicted LUAD patient prognosis and EMT propensity across multiple datasets. Lower SVM_Scores were associated with worse survival outcomes, elevated cancer-related pathways, increased Tumor Mutation Burden, and higher internal mechanical stress in LUAD tissues. Notably, the SVM_Score was closely linked to COL5A1 expression in myofibroblasts, a key marker of mechanical stress. High COL5A1 expression from myofibroblasts promoted tumor invasiveness and EMT pathway activation in LUAD cells. Additionally, treatment with Sorafenib, which targets COL5A1 secretion, attenuated the tumor-promoting effects of myofibroblast-derived COL5A1, inhibiting LUAD cell proliferation, migration, and enhancing chemosensitivity. In conclusion, this study elucidates the complex interplay between mechanical stress, ECM alterations, and LUAD progression. The SVM_Score emerges as a robust prognostic tool reflecting tumor mechanical characteristics, while Sorafenib intervention targeting COL5A1 secretion presents a promising therapeutic strategy to mitigate LUAD aggressiveness. These findings deepen our understanding of the biomechanical aspects of LUAD and offer insights for future research and clinical applications.

Abstract Background Photodegradation of plant litter plays a pivotal role in the global carbon (C) cycle. In temperate forest ecosystems, the exposure of plant litter to solar radiation can be significantly altered by changes in autumn phenology and snow cover due to climatic change. How this will affect litter decomposition and nutrient dynamic interacting with forest canopy structure (understorey vs. gaps) is uncertain. In the present study, we conducted a field experiment using leaf litter of early-fall deciduous Betula platyphylla (Asian white birch) and late-fall deciduous Quercus mongolica (Mongolian oak) to explore the effect of change in autumn solar radiation on dynamics of litter decomposition in a gap and understorey of a temperate mixed forest. Results Exposure to the full-spectrum of not only significantly increased the loss of mass, C, and lignin, but also modified N loss through both immobilization and mineralization during the initial decomposition during autumn canopy opening, irrespective of canopy structure and litter species. These effects were mainly driven by the blue-green spectral region of sunlight. Short-term photodegradation by autumn solar radiation had a positive legacy effect on the later decomposition particularly in the forest gap, increasing mass loss by 16% and 19% for Asian white birch and Mongolia oak, respectively. Conclusions Our results suggest that earlier autumn leaf-fall phenology and/or later snow cover due to land-use or climate change would increase the exposure of plant organic matter to solar radiation, and accelerate ecosystem processes, C and nutrient cycling in temperate forest ecosystems. The study provides a reference for predictive research on carbon cycling under the background of global climate change.

Abstract Background As the population ages, senior care for older adults in China has become increasingly important and has attracted the attention of both government and society. This study aimed to explore preferences and influencing factors related to senior care among older Chinese adults and thus propose effective and targeted strategies for the development of a comprehensive care system for older adults in the aging Chinese population. Methods Data were obtained from a cross-sectional survey conducted in sixteen communities or villages in Jiangsu Province, China, from July to September 2021. Guided by the Andersen Behavioral Model, multivariate logistic regression was conducted to identify factors associated with preferences for senior care arrangements. Results A total of 870 respondents were included in the study, 60.11% of whom preferred receiving care in their own homes, while only 13.68% chose residential care facilities (RCFs). For predisposing factors, rural respondents preferred receiving care in their own homes compared to urban respondents (children’s home: OR = 0.55, P 1, P

Polysaccharides are one of the main constituents of Cordyceps cicadae (C. cicadae), and they show various biological activities. In the present study, C. cicadae fruiting bodies were used as raw materials to extract polysaccharides using an aqueous two-phase system, along with cellulase and pectinase, aiming to provide references for the further development, utilization, and in-depth research of C. cicadae polysaccharides. Effects of cellulase and pectinase addition amounts and (NH4)2SO4 and polyethylene glycol (PEG) mass fractions on the polysaccharide-extraction rates were analyzed by single-factor experiments. The conditions for C. cicadae polysaccharide extraction were optimized by response-surface methodology, and the antioxidant, hypoglycemic, and hypolipidemic properties of the polysaccharides were evaluated in vitro. The optimal conditions for C. cicadae polysaccharide extraction were as follows: Cellulase addition amount 2.01%, pectinase addition amount 2.07%, (NH4)2SO4 mass fraction 17.72%, and PEG mass fraction 20.87%, the polysaccharide-extraction rate reached 25.34% under these conditions. When the C. cicadae polysaccharide concentration was 1.0~5.0 mg/mL, the maximum Fe2+-chelating and ABTS+ radical-clearance abilities were 16.33%±1.68% and 17.38%±3.07%, respectively. The determination of total reducing power showed that the maximum absorbance of C. cicadae polysaccharides was 0.53±0.005. The maximum inhibitory rates of C. cicadae polysaccharides for α-amylase and α-glucosidase activities were 30.96%±4.53% and 49.40%±1.30% respectively, the maximum adsorption rates of C. cicadae polysaccharides for sodium cholate, sodium taurocholate, and cholesterol were 47.24%±1.89%, 44.88%±0.82%, and 70.19%±2.54% respectively. The results indicated that C. cicadae polysaccharides demonstrate effective antioxidant, hypoglycemic, and hypolipidemic abilities in vitro. This study will provide a theoretical basis for developing C. cicadae polysaccharide-related products, especially for clinical applications.

Abstract Background Metabolic reprogramming contributes to bladder cancer development. This study aimed to understand the role of SLC7A5 in bladder cancer. Methods We systematically analyzed the correlation between SLC7A5 and bladder cancer through various approaches, including bioinformatics, western blotting, cell cycle analysis, cell proliferation assays, and invasion experiments. We also investigated the immunological features within the tumor microenvironment (TME), encompassing cancer immune cycles, immune modulators, immune checkpoints, tumor-infiltrating immune cells (TIIC), T cell inflammation scores, and treatment responses. Additionally, for a comprehensive assessment of the expression patterns and immunological roles of SLC7A5, pan-cancer analysis was performed using cancer genomics datasets. Results SLC7A5 was associated with adverse prognosis in bladder cancer patients, activating the Wnt pathway and promoting bladder cancer cell cycle progression, proliferation, migration, and invasion. Based on the evidence that SLC7A5 positively correlated with immunomodulators, TIIC, the cancer immune cycle, immune checkpoint and T cell inflammation scores, we also found that SLC7A5 was associated with the inflammatory tumor immune microenvironment. EGFR-targeted therapy, cancer immunotherapy, and radiation therapy were effective for patients with high SLC7A5 expression in bladder cancer. Low SLC7A5 patients were, however, sensitive to targeted therapies and anti-angiogenic therapy, such as blocking β-catenin network, PPAR-γ and FGFR3 signaling. Anti-SLC7A5 combined with cancer immunotherapy may have greater effectiveness than either therapy alone. Furthermore, we observed specific overexpression of SLC7A5 in TME of various cancers. Conclusion SLC7A5 can predict therapeutic response to immunotherapy, radiotherapy and chemotherapy in bladder cancer patients. Targeting SLC7A5 in combination with immunotherapy may be a potentially appropriate treatment option.

Abstract Purpose The duration of type 2 diabetes mellitus (T2DM) and blood glucose levels have a significant impact on the development of T2DM complications. However, currently known risk factors are not good predictors of the onset or progression of diabetic retinopathy (DR). Therefore, we aimed to investigate the differences in the serum lipid composition in patients with T2DM, without and with DR, and search for potential serological indicators associated with the development of DR. Methods A total of 622 patients with T2DM hospitalized in the Department of Endocrinology of the First Affiliated Hospital of Xi’an JiaoTong University were selected as the discovery set. One-to-one case–control matching was performed according to the traditional risk factors for DR (i.e., age, duration of diabetes, HbA1c level, and hypertension). All cases with comorbid chronic kidney disease were excluded to eliminate confounding factors. A total of 42 pairs were successfully matched. T2DM patients with DR (DR group) were the case group, and T2DM patients without DR (NDR group) served as control subjects. Ultra-performance liquid chromatography–mass spectrometry (LC–MS/MS) was used for untargeted lipidomics analysis on serum, and a partial least squares discriminant analysis (PLS-DA) model was established to screen differential lipid molecules based on variable importance in the projection (VIP) > 1. An additional 531 T2DM patients were selected as the validation set. Next, 1:1 propensity score matching (PSM) was performed for the traditional risk factors for DR, and a combined 95 pairings in the NDR and DR groups were successfully matched. The screened differential lipid molecules were validated by multiple reaction monitoring (MRM) quantification based on mass spectrometry. Results The discovery set showed no differences in traditional risk factors associated with the development of DR (i.e., age, disease duration, HbA1c, blood pressure, and glomerular filtration rate). In the DR group compared with the NDR group, the levels of three ceramides (Cer) and seven sphingomyelins (SM) were significantly lower, and one phosphatidylcholine (PC), two lysophosphatidylcholines (LPC), and two SMs were significantly higher. Furthermore, evaluation of these 15 differential lipid molecules in the validation sample set showed that three Cer and SM(d18:1/24:1) molecules were substantially lower in the DR group. After excluding other confounding factors (e.g., sex, BMI, lipid-lowering drug therapy, and lipid levels), multifactorial logistic regression analysis revealed that a lower abundance of two ceramides, i.e., Cer(d18:0/22:0) and Cer(d18:0/24:0), was an independent risk factor for the occurrence of DR in T2DM patients. Conclusion Disturbances in lipid metabolism are closely associated with the occurrence of DR in patients with T2DM, especially in ceramides. Our study revealed for the first time that Cer(d18:0/22:0) and Cer(d18:0/24:0) might be potential serological markers for the diagnosis of DR occurrence in T2DM patients, providing new ideas for the early diagnosis of DR.

Abstract Nanozyme, characterized by outstanding and inherent enzyme-mimicking properties, have emerged as highly promising alternatives to natural enzymes owning to their exceptional attributes such as regulation of oxidative stress, convenient storage, adjustable catalytic activities, remarkable stability, and effortless scalability for large-scale production. Given the potent regulatory function of nanozymes on oxidative stress and coupled with the fact that reactive oxygen species (ROS) play a vital role in the occurrence and exacerbation of metabolic diseases, nanozyme offer a unique perspective for therapy through multifunctional activities, achieving essential results in the treatment of metabolic diseases by directly scavenging excess ROS or regulating pathologically related molecules. The rational design strategies, nanozyme-enabled therapeutic mechanisms at the cellular level, and the therapies of nanozyme for several typical metabolic diseases and underlying mechanisms are discussed, mainly including obesity, diabetes, cardiovascular disease, diabetic wound healing, and others. Finally, the pharmacokinetics, safety analysis, challenges, and outlooks for the application of nanozyme are also presented. This review will provide some instructive perspectives on nanozyme and promote the development of enzyme-mimicking strategies in metabolic disease therapy. Graphical Abstract

【Objective】The digitization of agriculture and rural areas is considered to be a crucial element in promoting rural revitalization and enhancing agricultural construction, significantly contributing to the increase of farmers' income. The study aims to develop an comprehensive framework for evaluating the digitization of agriculture and rural areas, empirically investigating its effectiveness in income increase and clarifying the action mechanisms. Additionally, it provides policyoriented insights to alleviate the challenges of the "digital divide" and to advance the sophisticated development of the digital economy in agricultural and rural areas.【Methods】The panel data from 31 provinces (region) in China from 2011-2020 was selected, and the Entropy-Weighted TOPSIS Method was applied for assessing the level of digitalization in agriculture and rural areas. The fixed and mediation effects were utilized to investigate the influence and mechanisms of digitalization on farmers'income increase. A threshold model was employed to explore the threshold effects between the digitalization and the increase of farmers' income.【Results】(1) Digitalization in agriculture and rural areas significantly enhances farmers' income; with a 1% increase in digitalization level corresponding to an average income increase of 57.4 CNY for farmers. The positive effect is more pronounced in the eastern regions, while it appears to be inhibitory in the central regions and less evident in promoting income in the western regions, indicating the presence of a "digital divide". (2) Digitalization in agriculture and rural areas contributes to farmers' income increase through multiple channels: fostering diversification of farmers' occupations, accelerating land circulation, enhancing the probability of farmers obtaining financing, and promoting the sales of agricultural products. (3) Digital inclusive finance exhibits significant dual threshold effects between digitalization in agriculture and rural areas and farmers' income increase, with the first threshold value at 33.401 and the second at 148.370. As the threshold interval increases, the impact of digitalization on farmers' income increase demonstrates a "positive U-shaped" relationship, showing as initially inhibitory and subsequently promotive.【Conclusion】Digitalization in agriculture and rural areas effectively facilitates income increase for farmers, however, the challenges of the "digital divide" persist. Consequently, it proposes policy implications such as enhancing digital infrastructure, providing training and education in agricultural digitalization, promoting the development of rural digital inclusive finance, and formulating region-specific digital development strategies to further augment farmers' income.

Abstract Background Androgenic alopecia (AGA) is the most common type of hair loss in men, and there are many studies on the treatment of hair loss by platelet‐rich plasma (PRP). The human scalp contains a huge microbiome, but its role in the process of hair loss remains unclear, and the relationship between PRP and the microbiome needs further study. Therefore, the purpose of this study was to investigate the effect of PRP treatment on scalp microbiota composition. Methods We performed PRP treatment on 14 patients with AGA, observed their clinical efficacy, and collected scalp swab samples before and after treatment. The scalp microflora of AGA patients before and after treatment was characterized by amplifying the V3‐V4 region of the 16 s RNA gene and sequencing for bacterial identification. Results The results showed that PRP was effective in the treatment of AGA patients, and the hair growth increased significantly. The results of relative abundance analysis of microbiota showed that after treatment, g_Cutibacterium increased and g_Staphylococcus decreased, which played a stable role in scalp microbiota. In addition, g_Lawsonella decreased, indicating that the scalp oil production decreased after treatment. Conclusions The findings suggest that PRP may play a role in treating AGA through scalp microbiome rebalancing.

Anthocyanins play crucial roles in pollen protection and pollinator attraction in flowering plants. However, the mechanisms underlying flower color determination and whether floral anthocyanin regulators participate in other processes remain largely unresolved in soybeans (Glycine max). In this study, we investigated the genetic components and mechanisms governing anthocyanin biosynthesis in soybean flowers. Molecular and genetic studies have characterized two antagonistic regulators, the positive activator GmMYBA3 and the negative repressor GmMYBR1, that modulate the gene expression of anthocyanin biosynthesis in soybean flowers. Further findings revealed a regulatory interplay between GmMYBA3 and GmMYBR1 bridged by GmTT8a, highlighting the complexity of anthocyanin regulation in different soybean organs. Exploration of additional soybean cultivars demonstrated the universality of GmMYBA3 and GmMYBR1 in regulating floral anthocyanin biosynthesis- related genes, with GmF3′5′H identified as a crucial determinant of white flower color. This study provides a molecular mechanism underlying soybean flower color determination, paving the way for the molecular modification of soybean flowers to probably enhance their resistance to abiotic stresses and attractiveness to pollinators.

Chicken is an important food animal worldwide and plays an important role in human life by providing meat and eggs. Despite recent significant advances in gut microbiome studies, a comprehensive study of chicken gut bacterial, archaeal, and viral genomes remains unavailable. In this study, we constructed a chicken multi-kingdom microbiome catalog (CMKMC), including 18,201 bacterial, 225 archaeal, and 33,411 viral genomes, and annotated over 6,076,006 protein-coding genes by integrating 135 chicken gut metagenomes and publicly available metagenome-assembled genomes (MAGs) from ten countries. We found that 812 and 240 MAGs in our dataset were putative novel species and genera, respectively, far beyond what was previously reported. The newly unclassified MAGs were predominant in Phyla Firmicutes_A (n = 263), followed by Firmicutes (n = 126), Bacteroidota (n = 121), and Proteobacteria (n = 87). Most of the classified species-level viral operational taxonomic units belong to Caudovirales. Approximately, 63.24 % of chicken gut viromes are predicted to infect two or more hosts, including complete circular viruses. Moreover, we found that diverse auxiliary metabolic genes and antibiotic resistance genes were carried by viruses. Together, our CMKMC provides the largest integrated MAGs and viral genomes from the chicken gut to date, functional insights into the chicken gastrointestinal tract microbiota, and paves the way for microbial interventions for better chicken health and productivity.

Abstract Background The aged people who live in nursing home are predicted to keep growing in the following decades. There are both quantitative imbalance and structural imbalance in the utilization of nursing homes in China. This study aimed to analyze old people’s preference for nursing homes and help the government optimize resource allocation. Methods A discrete choice experiment (DCE) was conducted and six attributes of nursing homes including monthly fee, distance from home, geographical location, medical facilities, environment of nursing homes and nursing staff were determined. Respondents were recruited from Nantong and Yangzhou city, China. In each city, two communities or villages were randomly selected. In each community/village, about 65 old people were randomly selected. Analysis was conducted using mixed logit regression models to determine preferences for potential attributes. Results A total of 233 old people were included in the analysis. The findings indicated that all six attributes were statistically significant factors for participants. “Professional nursing staff” was the most important characteristic to participants, followed by “Medical facilities”. Compared with female, the males preferred professional nursing staff (β = 2.939 vs. β = 2.643, P

Abstract REBCO has been used extensively as coated conductors applied to superconducting magnets due to its exceptional superconducting properties. As a REBCO superconductor, YbBa2Cu3O7−y (Yb123) has a low melting temperature, making it suitable for use as an intermediate medium connector while preparing the superconducting joint. However, there is still uncertainty about the formation mechanism of Yb123 and the synthesis of this superconductor has not been fully understood. Therefore, this study systematically investigated the phase transformation process of Yb123 during heat treatment in flowing oxygen. The results indicated that Yb123 sample with the highest phase purity could be obtained by annealing at 927 °C or 937 °C but not in between, respectively. Furthermore, a quantitative phase analysis revealed that the sample annealed at 937 °C had a phase purity greater than 80 wt%. Additionally, a strong c-axis texture was observed in the bulk Yb123 superconductor prepared at 937 °C. Meanwhile, the superconducting results revealed that the bulk sample’s Tc was 89.9 K, and its self-field critical current densities at 4.2 K and 77 K were 1.3 × 105 A/cm2 and 5.0 × 103 A/cm2, respectively. Based on the results mentioned above, the phase transformation process and formation mechanism of Yb123 in flowing oxygen were elaborated.

Abstract Background Oral leukoplakia (OLK) is a prevalent precancerous lesion with limited non-pharmacological treatment options. Surgery and various lasers are the mainstay of treatment; however, their relative efficacy and optimal choice remain unclear. This first network meta-analysis compared the effects of different lasers and surgical excision on post-treatment recurrence and comfort in OLK patients. Methods We searched four databases for relevant randomized controlled trials (RCTs) up to April 2023. The primary outcome was post-treatment recurrence, and secondary outcomes included intraoperative hemorrhage and postoperative pain scores. The Cochrane Risk of Bias tool was used to assess the study quality. Meta-analysis and network meta-analysis were employed to determine efficacy and identify the optimal intervention. Results A total of 11 RCTs including 917 patients and 1138 lesions were included. Er,Cr:YSGG laser treatment showed significantly lower recurrence rates compared to CO2 laser (OR: 0.04; 95% CI: 0.01–0.18), CO2 laser with margin extension (OR: 0.06; 95% CI: 0.01–0.60), Er:YAG laser (OR: 0.10; 95% CI: 0.03–0.37), electrocautery (OR: 0.03; 95% CI: 0.00–0.18), and standard care (OR: 0.08; 95% CI: 0.02–0.33). Er,Cr:YSGG laser also ranked the best for reducing recurrence, followed by standard care and CO2 laser combined with photodynamic therapy (PDT). Er:YAG and Er:Cr:YSGG lasers minimized bleeding and pain, respectively. None of the interventions caused severe adverse effects. Conclusion For non-homogeneous OLK, Er:YAG, Er:Cr:YSGG, and CO2 laser combined with PDT offer promising alternatives to surgical excision, potentially reducing recurrence and improving patient comfort. Further high-quality RCTs are necessary to confirm these findings and determine the optimal laser–PDT combination for OLK treatment.

Background This study was conducted to determine optimal predictive ability of National Institutes of Health Stroke Scale (NIHSS) measurements at baseline, 24 hours, and change from baseline to 24 hours after thrombolysis on functional recovery in patients with acute ischemic stroke who participated in the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study). Methods and Results ENCHANTED was an international, multicenter, 2×2 quasifactorial, prospective, randomized open trial of low‐dose versus standard‐dose intravenous alteplase and intensive versus guideline‐recommended blood pressure lowering in thrombolysis‐eligible patients with acute ischemic stroke. Absolute (baseline minus 24 hours) and percentage (absolute change/baseline × 100) changes in NIHSS scores were calculated. Receiver operating characteristic curve analyses assessed performance of different NIHSS measurements on 90‐day favorable functional recovery (modified Rankin Scale [mRS] score 0–2) and excellent functional recovery (mRS score 0–1). Youden index was used to identify optimal predictor cutoff points. A total of 4410 patients in the ENCHANTED trial were enrolled. The 24‐hour NIHSS score had the highest discriminative ability for predicting favorable 90‐day functional recovery (mRS score 0–2; area under the curve 0.866 versus 0.755, 0.689, 0.764; P

The strain designated as Y139T is a novel Gram-stain-negative, aerobic, and non-motile bacterium, was isolated from a soil sample in McClain County, Oklahoma, United States. The cells of strain Y139T were a rod-shaped, with the width of 0.4–0.7 μm and the length of 1.5–2.0 μm. Growth occurred at 20–37°C (optimum, 30°C), pH 5.5–9.5 (optimum, pH 7.0), and 0–1.0% NaCl (w/v) (optimum, 0%). The polar lipid profiles included phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidyldimethylethanolamine, and an unidentified lipid. The major fatty acids included C16:0, iso-C14:0, and C16:1ω9c. Menaquinone-9 (MK-9) was recognized as the only respiratory quinone. Strain Y139T showed the highest 16S rRNA gene sequence similarity to Luteolibacter flavescens MCCC 1K03193T (98.3%). Phylogenetic analysis positioned it within the genus Luteolibacter. The draft genome of strain Y139T consisted of 7,106,054 bp, and contained 5,715 open reading frames (ORFs), including 5,656 coding sequences (CDSs) and 59 RNA genes. The genomic DNA G + C content was found to be 62.5%. Comparing strain Y139T with L. flavescens MCCC 1K03193T and Luteolibacter arcticus CCTCC AB 2014275T, the average nucleotide identity (ANI) values were 80.6 and 82.1%, respectively. Following phylogenetic, physiological, biochemical, and chemotaxonomic analyses, a novel species within the genus Luteolibacter, designated as Luteolibacter soli sp. nov., was proposed for strain Y139T, which was also assigned as the type strain (=KCTC 92644T = MCCC 1H01451T). Further analysis of core genes across 9 Luteolibacter species uncovered significant genomic divergence, particularly in those related to cofactor, vitamin, and energy metabolism. Analysis of biogeographic distribution suggested that lake and soil were the main habitats for the genus Luteolibacter. Additionally, the genus Luteolibacter was sensitive to climate warming and precipitation.

Background: It has been demonstrated that aberrant androgen receptor (AR) signaling contributes to the pathogenesis of prostate cancer (PCa). To date, the most efficacious strategy for the treatment of PCa remains to target the AR signaling axis. However, numerous PCa patients still face the issue of overtreatment or undertreatment. The establishment of a precise risk prediction model is urgently needed to distinguish patients with high-risk and select appropriate treatment modalities. Methods: In this study, a consensus AR regulatory gene-related signature (ARS) was developed by integrating a total of 101 algorithm combinations of 10 machine learning algorithms. We evaluated the value of ARS in predicting patient prognosis and the therapeutic effects of the various treatments. Additionally, we conducted a screening of therapeutic targets and agents for high-risk patients, followed by the verification in vitro and in vivo. Results: ARS was an independent risk factor for biochemical recurrence and distant metastasis in PCa patients. The enhanced and consistent prognostic predictive capability of ARS across various platforms was confirmed when compared with 44 previously published signatures. More importantly, PCa patients in the ARShigh group benefit more from PARP inhibitors and immunotherapy, while chemotherapy, radiotherapy, and AR-targeted therapy are more effective for ARSlow patients. The results of in silico screening suggest that AURKB could potentially serve as a promising therapeutic target for ARShigh patients. Conclusions: Collectively, this prediction model based on AR regulatory genes holds great clinical translational potential to solve the dilemma of treatment choice and identify potential novel therapeutic targets in PCa.

ABSTRACT The Changle goose (CLG), a Chinese indigenous breed, is celebrated for its adaptability, rapid growth, and premium meat quality. Despite its agricultural value, the exploration of its genomic attributes has been scant. Our study entailed whole‐genome resequencing of 303 geese across CLG and five other Chinese breeds, revealing distinct genetic diversity metrics. We discovered significant migration events from Xingguo gray goose to CLG and minor gene flow between them. We identified genomic regions through selective sweep analysis, correlating with CLG's unique traits. An elevated inbreeding coefficient in CLG, alongside reduced heterozygosity and rare single nucleotide polymorphisms (RSNPs), suggests a narrowed genetic diversity. Genomic regions related to reproduction, meat quality, and growth were identified, with the GATA3 gene showing strong selection signals for meat quality. A non‐synonymous mutation in the Sloc2a1 gene, which is associated with reproductive traits in the CLG, exhibited significant differences in allelic frequency. The roles of CD82, CDH8, and PRKAB1 in growth and development, alongside FABP4, FAF1, ESR1, and AKAP12 in reproduction, were highlighted. Additionally, Cdkal1 and Mfsd14a may influence meat quality. This comprehensive genetic analysis underpins the unique genetic makeup of CLG, providing a basis for its conservation and informed breeding strategies.

Background: The presence of fibrotic interstitial lung disease (ILD) is relatively common in patients with emphysema. This has been designated combined pulmonary fibrosis and emphysema (CPFE). CPFE had worse prognosis than emphysema alone. Krebs von den Lungen-6 (KL-6) levels as a biomarker of alveolar type 2 epithelial cell injury, which is widely used to identify the presence of ILD, whether it can differentiate CPFE from COPD remains unknown. Methods: 259 patients from Xiangya Hospital with diagnosis of COPD, with or without ILD, and who had KL-6 tests were recruited for this retrospective analysis. Recorded data included demographic information, comorbidities, inflammatory biomarkers. Results of CT and pulmonary function tests were collected one week before or after KL-6 measurements. Results: Among 259 patients, 52 patients were diagnosed with CPFE. The mean age was 67.39 ± 8.14 yeas. CPFE patients had higher ratio of rheumatic diseases (21.2 % vs 7.2 %, P = 0.003). CPFE patients exhibited higher values of FEV1 (1.97 vs 1.57, P = 0.002) and FEV1/FVC ratio (69.46 vs 57.64, P

BackgroundEarlier observational studies have demonstrated a correlation between glioma and the risk of neurodegenerative diseases (NDs), but the causality and direction of their associations remain unclear. The objective of this study was to ascertain the causal link between glioma and NDs using Mendelian randomization (MR) methodology.MethodsGenome-wide association study (GWAS) data were used in a two-sample bi-directional MR analysis. From the largest meta-analysis GWAS, encompassing 18,169 controls and 12,488 cases, summary statistics data on gliomas was extracted. Summarized statistics for NDs, including Alzheimer’s disease (AD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD) were obtained from the GWAS of European ancestry. Inverse variance weighted (IVW) method was elected as the core MR approach with weighted median (WM) method and MR-Egger method as complementary methods. In addition, sensitivity analyses were performed. A Bonferroni correction was used to correct the results.ResultsGenetically predicted glioma had been related to decreased risk of AD. Specifically, for all glioma (IVW: OR = 0.93, 95% CI = 0.90–0.96, p = 4.88 × 10−6) and glioblastoma (GBM) (IVW: OR = 0.93, 95% CI = 0.91–0.95, p = 5.11 × 10−9). We also found that genetically predicted all glioma has a suggestive causative association with MS (IVW: OR = 0.90, 95% CI = 0.81–1.00, p = 0.045). There was no evidence of causal association between glioma and ALS or PD. According to the results of reverse MR analysis, no discernible causal connection of NDs was found on glioma. Sensitivity analyses validated the robustness of the above associations.ConclusionWe report evidence in support of potential causal associations of different glioma subtypes with AD and MS. More studies are required to uncover the underlying mechanisms of these findings.

Abstract Background The gut microbiota is recognized as a regulator of brain development and behavioral outcomes during childhood. Nonetheless, associations between the gut microbiota and behavior are often inconsistent among studies in humans, perhaps because many host-microbe relationships vary widely between individuals. This study aims to stratify children based on their gut microbiota composition (i.e., clusters) and to identify novel gut microbiome cluster-specific associations between the stool metabolomic pathways and child behavioral outcomes. Methods Stool samples were collected from a community sample of 248 typically developing children (3–5 years). The gut microbiota was analyzed using 16S sequencing while LC-MS/MS was used for untargeted metabolomics. Parent-reported behavioral outcomes (i.e., Adaptive Skills, Internalizing, Externalizing, Behavioral Symptoms, Developmental Social Disorders) were assessed using the Behavior Assessment System for Children (BASC-2). Children were grouped based on their gut microbiota composition using the Dirichlet multinomial method, after which differences in the metabolome and behavioral outcomes were investigated. Results Four different gut microbiota clusters were identified, where the cluster enriched in both Bacteroides and Bifidobacterium (Ba2) had the most distinct stool metabolome. The cluster characterized by high Bifidobacterium abundance (Bif), as well as cluster Ba2, were associated with lower Adaptive Skill scores and its subcomponent Social Skills. Cluster Ba2 also had significantly lower stool histidine to urocanate turnover, which in turn was associated with lower Social Skill scores in a cluster-dependent manner. Finally, cluster Ba2 had increased levels of compounds involved in Galactose metabolism (i.e., stachyose, raffinose, alpha-D-glucose), where alpha-D-glucose was associated with the Adaptive Skill subcomponent Daily Living scores (i.e., ability to perform basic everyday tasks) in a cluster-dependent manner. Conclusions These data show novel associations between the gut microbiota, its metabolites, and behavioral outcomes in typically developing preschool-aged children. Our results support the concept that cluster-based groupings could be used to develop more personalized interventions to support child behavioral outcomes. Video Abstract

Abstract Background The optimal timing of thoracic radiotherapy (TRT) in driver‐gene‐negative metastatic non‐small cell lung cancer (mNSCLC) patients was retrospectively investigated based on survival and safety profile. Methods The efficacy and safety data of driver‐gene‐negative mNSCLC patients treated with TRT during maintenance after first‐line therapy was collected. Patients whose primary tumor and metastatic lesions remained no progression during maintenance and then received TRT were categorized as the NP (no progression) group, while patients who experienced slow progression during maintenance without reaching progressive disease and then received TRT were categorized as the SP (slow progression) group. The efficacy and adverse events of TRT were analyzed. Results In total, 149 driver‐gene‐negative mNSCLC patients treated with TRT during maintenance were enrolled into the study, with 119 in the NP group and 30 in the SP group. After a median follow‐up of 30.83 (range: 26.62–35.04) months, the median progression‐free survival (PFS) in the NP group was 11.13 versus 9.53 months in the SP group (HR 0.599, p = 0.017). The median overall survival (OS) in the NP group was 32.27 versus 25.57 months in the SP group (HR 0.637, p = 0.088). The median PFS after radiotherapy (rPFS) was 6.33 versus 3.90 months (HR 0.288, p 0.05). Conclusion The addition of TRT during the pre‐emptive no progression phase was associated with a significantly longer PFS than during the delayed slow progression phase and had an acceptable safety profile. Our results might support the earlier initiation of TRT after induction therapy for some patients with driver‐gene‐negative mNSCLC.

Abstract Background Although hepatitis B virus (HBV) infection is a major risk factor for hepatic cancer, the majority of HBV carriers do not develop this lethal disease. Additional molecular alterations are thus implicated in the process of liver tumorigenesis. Since phosphatase and tensin homolog (PTEN) is decreased in approximately half of liver cancers, we investigated the significance of PTEN deficiency in HBV-related hepatocarcinogenesis. Methods HBV-positive human liver cancer tissues were checked for PTEN expression. Transgenic HBV, Alb-Cre and Pten fl/fl mice were inter-crossed to generate WT, HBV, Pten −/− and HBV; Pten −/− mice. Immunoblotting, histological analysis and qRT-PCR were used to study these livers. Gp73 −/− mice were then mated with HBV; Pten −/− mice to illustrate the role of hepatic tumor biomarker golgi membrane protein 73 (GP73)/ golgi membrane protein 1 (GOLM1) in hepatic oncogenesis. Results Pten deletion and HBV transgene synergistically aggravated liver injury, inflammation, fibrosis and development of mixed hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). GP73 was augmented in HBV; Pten −/− livers. Knockout of GP73 blunted the synergistic effect of deficient Pten and transgenic HBV on liver injury, inflammation, fibrosis and cancer development. Conclusions This mixed HCC-ICC mouse model mimics liver cancer patients harboring HBV infection and PTEN/AKT signaling pathway alteration. Targeting GP73 is a promising therapeutic strategy for cancer patients with HBV infection and PTEN alteration.

In this work, the Mg97Y2Zn (at%) alloys have been processed by the rotary-die (RD) ECAP technique under different temperature or pass conditions to tailor the microstructure and mechanical properties. The results reveal that the DRX ratio (VDRX) increases with the increase of ECAP pass or temperature, weakening the texture intensity. The refinement of DRXed grains saturates after 9 passes of ECAP at 350 °C, while the size of DRXed grains (dDRX) monotonically decreases with the reduction of temperature from 400 °C to 300 °C in the case of the same pass number (9P). The combination of fine dDRX, large VDRX, and directionally arranged LPSO phases along the extrusion direction endows the 350 °C–9P alloy with the optimum strength and ductility synergy, exhibiting the tensile yield strength (TYS) of 267 MPa, ultimate tensile strength (UTS) of 318 MPa, and elongation of 10.3%. However, the larger VDRX, weaker texture, less low-angle grain boundaries combine to improve the elongation (14.7%) of the 400 °C–9P alloy at the expense of the TYS (231 MPa) and UTS (303 MPa). This paper provides useful information to optimize the RD-ECAP parameters for the fabrication of high-performance Mg97Y2Zn alloys.

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system is an acquired immune system of many bacteria and archaea, comprising CRISPR loci, Cas genes, and its associated proteins. This system can recognize exogenous DNA and utilize the Cas9 protein's nuclease activity to break DNA double-strand and to achieve base insertion or deletion by subsequent DNA repair. In recent years, multiple laboratory and clinical studies have revealed the therapeutic role of the CRISPR/Cas9 system in neurological diseases. This article reviews the CRISPR/Cas9-mediated gene editing technology and its potential for clinical application against neurological diseases.

Background and objective Lung cancer is a leading cause of cancer-related deaths. Non-small cell lung cancer (NSCLC) is the most common pathological subtype, with adenocarcinoma being the predominant type. FAT atypical cadherin 1 (FAT1) is a receptor-like protein with a high frequency of mutations in lung adenocarcinoma. The protein encoded by FAT1 plays a crucial role in processes such as cell adhesion, proliferation, and differentiation. This study aims to investigate the expression of FAT1 in lung adenocarcinoma and its relationship with immune infiltration. Methods Gene expression levels and relevant clinical information of 513 lung adenocarcinoma samples and 397 adjacent lung samples were obtained through The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data. The mRNA expression levels of the FAT1 gene in lung adenocarcinoma tissues were analyzed, along with its association with the prognosis of lung adenocarcinoma patients. Pathway enrichment analysis was conducted to explore the signaling pathways regulated by the FAT1 gene. Immunoblotting was used to detect the differential expression of FAT1 in lung epithelial cells and various lung cancer cell lines, while immunohistochemistry was employed to assess FAT1 expression in lung cancer and adjacent tissues. Results FAT1 gene mutations were identified in 14% of lung adenocarcinoma patients. TCGA database data revealed significantly higher FAT1 mRNA expression in lung adenocarcinoma tissues compared to adjacent lung tissues. Kaplan-Meier analysis indicated lower survival rates in lung adenocarcinoma patients with higher FAT gene expression. Pathway enrichment analysis suggested the involvement of FAT1 in tumor development pathways, and its expression was closely associated with immune cell infiltration. Immunohistochemical validation demonstrated significantly higher expression of FAT1 in cancer tissues compared to adjacent lung tissues. Conclusion FAT1 mRNA is highly expressed in lung adenocarcinoma tissues, and elevated FAT1 mRNA expression is associated with poor prognosis in lung adenocarcinoma patients. FAT1 may serve as a potential biomarker for lung cancer.

Abstract Background Oculocutaneous albinism (OCA) is a group of rare genetic disorders characterized by a reduced or complete lack of melanin in the skin, hair, and eyes. Patients present with colorless retina, pale pink iris, and pupil, and fear of light. The skin, eyebrows, hair, and other body hair are white or yellowish-white. These conditions are caused by mutations in specific genes necessary for the production of melanin. OCA is divided into eight clinical types (OCA1-8), each with different clinical phenotypes and potential genetic factors. This study aimed to identify the genetic causes of non-syndromic OCA in a Chinese Han family. Methods We performed a comprehensive clinical examination of family members, screened for mutation loci using whole exome sequencing (WES) technology, and predicted mutations using In silico tools. Results The patient’s clinical manifestations were white skin, yellow hair, a few freckles on the cheeks and bridge of the nose, decreased vision, blue iris, poorly defined optic disk borders, pigmentation of the fundus being insufficient, and significant vascular exposure. The WES test results indicate that the patient has compound heterozygous mutations in the OCA2 gene (c.1258G > A (p.G420R), c.1441G > A (p.A481T), and c.2267-2 A > C), respectively, originating from her parents. Among them, c.1258G > A (p.G420R) is a de novo mutation with pathogenic. Our analysis suggests that compound heterozygous mutations in the OCA2 gene are the primary cause of the disease in this patient. Conclusions The widespread application of next-generation sequencing technologies such as WES in clinical practice can effectively replace conventional detection methods and assist in the diagnosis of clinical diseases more quickly and accurately. The newly discovered c.1258G > A (p.G420R) mutation can update and expand the gene mutation spectrum of OCA2-type albinism.

Abstract With the advancement of adversarial techniques for malicious code, malevolent attackers have propagated numerous malicious code variants through shell coding and code obfuscation. Addressing the current issues of insufficient accuracy and efficiency in malicious code classification methods based on deep learning, this paper introduces a detection strategy for malicious code, uniting Convolutional Neural Networks (CNNs) and Transformers. This approach utilizes deep neural architecture, incorporating a novel fusion module to reparametrize the structure, which mitigates memory access costs by eliminating residual connections within the network. Simultaneously, overparametrization during linear training time and significant kernel convolution techniques are employed to enhance network precision. In the data preprocessing stage, a pixel-based image size normalization algorithm and data augmentation techniques are utilized to remedy the loss of texture information in the malicious code image scaling process and class imbalance in the dataset, thereby enhancing essential feature expression and alleviating model overfitting. Empirical evidence substantiates this method has improved accuracy and the most recent malicious code detection technologies.

Abstract As an emerging business model, merchants are selling surplus food in blind boxes, which provides new opportunities for reducing waste and promoting sustainable development. Surplus food blind boxes, however, have not been extensively researched in terms of design and marketing strategies. Therefore, we are examining how to increase consumers’ purchase intention regarding surplus food blind boxes as well as the relationship between purchase intention, continuous intention, and recommendation intention. In this paper, two studies are conducted. As part of study 1, We used factor analysis to explore the reasons that influence consumers to purchase. In study 2, we utilized structural equation modeling to examine the impact of purchase intention on continuous intention and recommendation intention. Results indicate that food quality, perceived sustainability, and conspicuous consumption are the most important positive factors. The most important negative factors are perceived food risk, resistance to sales techniques, taste anxiety, and inadequate marketing strategies. Based on our findings, we constructed a path relationship between purchase intention, continuous intention, and recommendation intention. The purchase intention of the surplus food blind box users directly influences the recommendation intention and the continuous intention, while the recommendation intention indirectly influences the continuous intention. This study did not demonstrate that gender had a moderating effect. Meanwhile, it provides a reference for the actual marketing management of surplus food blind box merchants.

Abstract Solid‐state high voltage high repetitive pulse generators have a broad prospect in various applications. The high power and high‐frequency operation of the pulse generator suffer from the massive heat dissipation problem, which limits the improvement of the output parameters and even affects the lifetime. This article focuses on heat management technology for high voltage high repetitive pulse generators. Firstly, the typical circuit topology of the high repetitive pulse generators was summarised. From the perspective of different application requirements, the demands of the heat management design were concluded. Moreover, the heat generation characteristics and difficulties of solid‐state high voltage high repetitive pulse generators were analysed. Then, the different state‐of‐art cooling techniques were reviewed, and their applicability and limitations for the high voltage high repetitive generators were discussed. Finally, a flow chart for heat management design was given.

Abstract Background The COVID-19 pandemic is a persistent global threat to public health. As for the emerging variants of SARS-CoV-2, it is necessary to develop vaccines that can induce broader immune responses, particularly vaccines with weak cellular immunity. Methods In this study, we generated a double-layered N-S1 protein nanoparticle (N-S1 PNp) that was formed by desolvating N protein into a protein nanoparticle as the core and crosslinking S1 protein onto the core surface against SARS-CoV-2. Results Vaccination with N-S1 PNp elicited robust humoral and vigorous cellular immune responses specific to SARS-CoV-2 in mice. Compared to soluble protein groups, the N-S1 PNp induced a higher level of humoral response, as evidenced by the ability of S1-specific antibodies to block hACE2 receptor binding and neutralize pseudovirus. Critically, N-S1 PNp induced Th1-biased, long-lasting, and cross-neutralizing antibodies, which neutralized the variants of SARS-CoV-2 with minimal loss of activity. N-S1 PNp induced strong responses of CD4+ and CD8+ T cells, mDCs, Tfh cells, and GCs B cells in spleens. Conclusions These results demonstrate that N-S1 PNp vaccination is a practical approach for promoting protection, which has the potential to counteract the waning immune responses against SARS-CoV-2 variants and confer broad efficacy against future new variants. This study provides a new idea for the design of next-generation SARS-CoV-2 vaccines based on the B and T cells response coordination. Graphical Abstract Steps involved in the preparation of double-layered N-S1 protein nanoparticle vaccines and experimental design performed in combating virus infection. After intramuscular immunization of mice, the double-layered N-S1 protein nanovaccine could effectively promote the maturation of antigen-presenting and mature dendritic cells, robust broad-spectrum neutralizing antibody production, cytokines secretion, robust mDC, Tfh cell, and GCs B cell responses induction, T-cell memory formation and durable antibody responses, and unique global transcriptome characteristics, thus achieving a robust cellular immunity and broad antibody responses against SARS-CoV-2 based on the B and T cells response coordination

Abstract Cichoric acid (CA), a natural phenolic compound found in many plants, has been reported to have antioxidant, anti‐inflammatory, hypoglycemic, and other effects. The aim of this study was to determine the potential role and underlying mechanisms of CA in isoproterenol (ISO)‐induced myocardial fibrosis (MF). The MF model was induced by subcutaneous ISO injection in mice. Blood and heart tissue were collected for examination. Hematoxylin and eosin staining and Masson's trichrome staining were used to evaluate the histopathological changes and collagen deposition. The production of reactive oxygen species markers was observed by fluorescence microscopy, the degree of cardiomyocyte microstructure injury was observed by transmission electron microscope, and oxidative stress factors were detected by kit method, and the effect of CA on inflammatory factors was detected by ELISA. The expression levels of collagen proteins and signaling pathways were further investigated by western blotting. The results showed that CA inhibited the expression of ISO‐induced proinflammatory factors (TNF‐α, IL‐1β, and IL‐18) and proteins (HK1, NLRP3, caspase‐1, cleaved‐caspase‐1, and ASC), and regulated the expression of apoptotic factors (caspase‐3, cleaved‐caspase‐3, Bax, and Bcl‐2). The results indicated that CA may regulate the HK1/NLRP3 inflammasome pathway by inhibiting HK1 expression and play a protective role in MF.

In this study, a novel two-stage vacuum distillation method was proposed to refine crude indium to prepare refined indium. Low-temperature distillation (1223K, holding time of 3h) and high-temperature distillation (1473K, holding time of 5h) were conducted under a system pressure of 7 × 10−3Pa to successfully purify crude indium (99 wt%) to refined indium (99.995 wt%). This strategy can replace the traditional electrolytic process for the clean production of refined indium and achieve the goals of environmental protection. The vapor-liquid equilibrium (VLE) values of indium-based binary alloys were calculated using the molecular interaction volume model (MIVM), and a VLE phase diagram was drawn. Optimal temperatures of 1173K for low-temperature and 1373K for high-temperature distillation were determined based on the VLE phase diagram, and good purification was achieved. Moreover, this study reveals the migration distribution pattern of typical impurity elements (e.g., Tl and Sn) in crude indium in the low and high-temperature distillation sections, further improving the refining effect. Notably, the combination of MIVM simulations and experiments can obtain optimal experimental parameters for segmental vacuum distillation and further help to avoid the waste of raw materials and energy caused by pre-experiments, realizing the clean and efficient production of refined indium.

New energy sources are transforming the automotive market. This shift has also expanded the possibilities for in-vehicle interaction. Through a literature review, this study categorizes the in-vehicle interaction activities into three types: driving tasks, comfort tasks, and entertainment tasks. This study conducted empirical survey of 377 users to understand their preferences of in-vehicle interaction input methods inside new energy vehicles. The results show that gender, educational level, income, driver's license type and driving experience have significant influence on the perception and preference of the in-vehicle interaction input methods. However, age and experience with new energy vehicle didn't show significant results. The findings of this study can assist manufacturers in developing targeted solutions and meeting the personalized needs of users in future vehicle market segments.

Mercury (Hg) contamination poses a global threat to the environment, given its elevated ecotoxicity. Herein, we employed the lepidopteran model insect, silkworm (Bombyx mori), to systematically investigate the toxic effects of Hg-stress across its growth and development, histomorphology, antioxidant enzyme activities, and transcriptome responses. High doses of Hg exposure induced evident poisoning symptoms, markedly impeding the growth of silkworm larvae and escalating mortality in a dose-dependent manner. Under Hg exposure, the histomorphology of both the midgut and fat body exhibited impairments. Carboxylesterase (CarE) activity was increased in both midgut and fat body tissues responding to Hg treatment. Conversely, glutathione S-transferase (GST) levels increased in the fat body but decreased in the midgut. The transcriptomic analysis revealed that the response induced by Hg stress involved multiple metabolism processes. Significantly differently expressed genes (DEGs) exhibited strong associations with oxidative phosphorylation, nutrient metabolisms, insect hormone biosynthesis, lysosome, ribosome biogenesis in eukaryotes, and ribosome pathways in the midgut or the fat body. The findings implied that exposure to Hg might induce the oxidative stress response, attempting to compensate for impaired metabolism. Concurrently, disruptions in nutrient metabolism and insect hormone activity might hinder growth and development, leading to immune dysfunction in silkworms. These insights significantly advance our theoretical understanding of the potential mechanisms underlying Hg toxicity in invertebrate organisms.

Oral biofilm is the leading cause of dental caries, which is difficult to completely eradicate because of the complicated biofilm structure. What's more, the hypoxia environment of biofilm and low water-solubility of conventional photosensitizers severely restrict the therapeutic effect of photodynamic therapy (PDT) for biofilm. Although conventional photosensitizers could be loaded in nanocarriers, it has reduced PDT effect because of aggregation-caused quenching (ACQ) phenomenon. In this study, we fabricated an oxygen self-sufficient nanodroplet (PFC/TPA@FNDs), which was composed of fluorinated-polymer (FP), perfluorocarbons (PFC) and an aggregation-induced emission (AIE) photosensitizer (Triphenylamine, TPA), to eradicate oral bacterial biofilm and whiten tooth. Fluorinated-polymer was synthesized by polymerizing (Dimethylamino)ethyl methacrylate, fluorinated monomer and 1-nonanol monomer. The nanodroplets could be protonated and behave strong positive charge under bacterial biofilm acid environment promoting nanodroplets deeply penetrating biofilm. More importantly, the nanodroplets had extremely high PFC and oxygen loading efficacy because of the hydrophobic affinity between fluorinated-polymer and PFC to relieve the hypoxia environment and enhance PDT effect. Additionally, compared with conventional ACQ photosensitizers loaded system, PFC/TPA@FNDs could behave superior PDT effect to ablate oral bacterial biofilm under light irradiation due to the unique AIE effect. In vivo caries animal model proved the nanodroplets could reduce dental caries area without damaging tooth structure. Ex vivo tooth whitening assay also confirmed the nanodroplets had similar tooth whitening ability compared with commercial tooth whitener H2O2, while did not disrupt the surface microstructure of tooth. This oxygen self-sufficient nanodroplet provides an alternative visual angle for oral biofilm eradication in biomedicine.

Summary: The liver X receptor (LXR) is considered a therapeutic target for atherosclerosis treatment, but synthetic LXR agonists generally also cause hepatic steatosis and hypertriglyceridemia. Desmosterol, a final intermediate in cholesterol biosynthesis, has been identified as a selective LXR ligand that suppresses inflammation without inducing lipogenesis. Δ24-Dehydrocholesterol reductase (DHCR24) converts desmosterol into cholesterol, and we previously showed that the DHCR24 inhibitor SH42 increases desmosterol to activate LXR and attenuate experimental peritonitis and metabolic dysfunction-associated steatotic liver disease. Here, we aimed to evaluate the effect of SH42 on atherosclerosis development in APOE∗3-Leiden.CETP mice and low-density lipoproteins (LDL) receptor knockout mice, models for lipid- and inflammation-driven atherosclerosis, respectively. In both models, SH42 increased desmosterol without affecting plasma lipids. While reducing liver lipids in APOE∗3-Leiden.CETP mice, and regulating populations of circulating monocytes in LDL receptor knockout mice, SH42 did not attenuate atherosclerosis in either model.

The soil seed bank plays a key role in vegetation resilience under environmental disturbances, and is especially important for the restoration of degraded vegetation. However, the responsive dynamics of the soil seed bank to animal grazing and its potential in the restoration of grazing degraded steppe grassland remain unclear. Here we examined the changes in plant species diversity and density in both the soil seed bank and the aboveground vegetation of a natural grassland along an experimental gradient of four grazing intensities (nil, light, moderate and heavy grazing) in an adaptive grazing management system that ensures grassland residual cover was always above a certain criteria. The grassland is a typical steppe dominated by Leymus chinensis, Stipa grandis, and Cleistogenes squarrosa in central Inner Mongolia, China. We found that (i) plant species richness and density of the seed bank in the top 10 cm soil layer increased with grazing intensity, though the density of the seed bank in the top 5 cm soil layer showed an decrease. (ii) Moderate and heavy grazing significantly decreased the density of perennial but increased annual and biennial plants in the top 5 cm soil layer, which dominate the changes in the top 10 cm soil layer. (iii) Plant species richness and density in the aboveground vegetation also increased with grazing intensity, so did the similarity between the species composition of the soil seed bank and aboveground vegetation in the top 10 cm. The increase in the richness and density of annual and biennial species dominated the responsive changes to grazing of the soil seed bank and aboveground vegetation in the studied grassland. Our results provide a reference basis for grazing management in the region from the perspective of the soil seed bank, and suggest that the adaptive grazing system with grassland residual height controlled above a criterion benefits to the soil seed bank thus the re-generation of vegetation.

ObjectiveTo determine the genetic causes of monogenic inherited diseases in a couple using clinical whole exome sequencing (WES) and advise on their reproductive choices.MethodsWES was applied to a couple seeking reproductive advice, the female with short stature and the male with congenital cataracts.Results(1) The woman exhibited a 13.8 Kb heterozygous deletion at chrX: 591590–605428 (hg19). This region corresponds to exons 2–6 of the short-stature homeobox-containing (SHOX) gene (NM000451). Associated diseases involving the SHOX gene range from severe Leri–Weill dyschondrosteosis to mild nonspecific short stature. Meanwhile, further validation using a quantitative reverse transcription polymerase chain reaction assay confirmed the heterozygous deletion of the SHOX gene in the proband, as well as other family members with similar clinical characteristics (the proband’s mother, aunt, and cousin). Multiple pathogenic reports of this variant have been included in the HGMD database. Per the American College of Medical Genetics and Genomics (ACMG) classification criteria, this deletion is classified as pathogenic. (2) For the male patient, a heterozygous variant was detected in the CRYBB3 gene: NM004076: c.226G>A (p.Gly76R). Variants in the CRYBB3 gene can cause Cataract 22 (OMIM: 609741). At present, this variant locus is not included in databases such as the gnomAD, while both SIFT and PolyPhen2 deem this locus ‘damaging’. Moreover, further validation by Sanger sequencing confirmed that the variant was inherited from the male patient’s mother, who also had cataracts. According to ACMG standards and guidelines, the c.226G>A (p.Gly76Arg) variant in the CRYBB3 gene is classified as having ‘uncertain significance’.ConclusionWES identified pathogenic variants in both individuals, suggesting a 25% chance of a healthy child naturally. Third-generation assisted reproductive techniques are recommended to minimize the risk of affected offspring.

Background This study aimed to investigate the perinatal factors and early neonatal outcomes of abnormal birth weight (ABW) in Hangzhou, China from 2015 to 2021.Methods A retrospective cohort study was designed to analyse the data of 76 847 newborns, in which the case groups included 3042 cases of low birth weight (LBW) and 2941 cases of fetal macrosomia (MAC), and 70 864 cases of normal weight were as the reference group.Results The incidence of LBW and MAC was 3.96% and 3.83% in Hangzhou, China from 2015 to 2021. Prematurity (7 days, fetal anomalies, caesarean section, pregnancy complications, maternal coinfection with pathogens and summer births would be correlated with the incidence of LBW (ORs=43.50, 7.60, 2.09, 1.89, 1.57, 1.28, 1.19 and 1.18, all p41 weeks), scarred uterus, anterior vaginal incision and gravidity ≥2 were correlated with decreased incidence of LBW, with ORs of 0.05, 0.54, 0.65 and 0.80. Moreover, caesarean delivery, post-term pregnancy (> 41 weeks), parity ≥1, lateral vaginal incision, gravidity ≥2, hospitalisation >7 days, winter births and pregnancy complications also have association with the incidence of MAC (ORs=3.92, 2.73, 2.19, 1.87, 1.22, 1.20, 1.17 and 1.13, all p7 days are associated with the odds of LBW and MAC, however, factors such as pregnancy with scarred uterus relate to the decrease of ABW. Close monitoring and intervention during pregnancy are essential to reduce the occurrence of ABW.

Abstract Targeting cancer‐specific metabolic processes is a promising therapeutic strategy. Here, this work uses a compound library that directly inhibits metabolic enzymes to screen the potential metabolic targets in lung adenocarcinoma (LUAD). SHIN1, the specific inhibitor of serine hydroxymethyltransferase 1/2 (SHMT1/2), has a highly specific inhibitory effect on LUAD cells, and this effect depends mainly on the overexpression of SHMT2. This work clarifies that mitogen‐activated protein kinase 1 (MAPK1)‐mediated phosphorylation at Ser90 is the key mechanism underlying SHMT2 upregulation in LUAD and that this phosphorylation stabilizes SHMT2 by reducing STIP1 homology and U‐box containing protein 1 (STUB1)‐mediated ubiquitination and degradation. SHMT2‐Ser90 dephosphorylation decreases S‐adenosylmethionine levels in LUAD cells, resulting in reduced N6‐methyladenosine (m6A) levels in global RNAs without affecting total protein or DNA methylation. Methylated RNA immunoprecipitation sequencing (MeRIP‐Seq) and RNA sequencing (RNA‐Seq) analyses further demonstrate that SHMT2‐Ser90 dephosphorylation accelerates the RNA degradation of oncogenic genes by reducing m6A modification, leading to the inhibition of tumorigenesis. Overall, this study elucidates a new regulatory mechanism of SHMT2 during oncogenesis and provides a theoretical basis for targeting SHMT2 as a therapeutic target in LUAD.

Objective To evaluate the effectiveness of standardised antiretroviral therapy (ART) among different HIV subtypes in people living with HIV/AIDS (PLWHA), and to screen the best ART regimen for this patient population.Design A retrospective cohort study was performed, and PLWHA residing in Huzhou, China, between 2018 and 2020, were enrolled.Setting and participants Data from 625 patients, who were newly diagnosed with HIV/AIDS in the AIDS Prevention and Control Information System in Huzhou between 2018 and 2020, were reviewed.Analysis and outcome measures Data regarding demographic characteristics and laboratory investigation results were collected. Immune system recovery was used to assess the effectiveness of ART, and an increased percentage of CD4+ T lymphocyte counts >30% after receiving ART for >1 year was determined as immunopositive. A multiple logistic regression model was used to comprehensively quantify the association between PLWHA immunological response status and virus subtype. In addition, the joint association between different subtypes and treatment regimens on immunological response status was investigated.Results Among 326 enrolled PLWHA with circulating recombinant forms (CRFs) CRF01_AE, CRF07_BC and other HIV/AIDS subtypes, the percentages of immunopositivity were 74.0%, 65.6% and 69.6%, respectively. According to multivariate logistic regression models, there was no difference in the immunological response between patients with CRF01_AE, CRF07_BC and other subtypes of HIV/AIDS who underwent ART (CRF07_BC: adjusted OR (aOR) (95% CI) = 0.8 (0.4 to 1.4); other subtypes: aOR (95% CI) = 1.2 (0.6 to 2.3)). There was no evidence of an obvious joint association between HIV subtypes and ART regimens on immunological response.Conclusions Standardised ART was beneficial to all PLWHA, regardless of HIV subtypes, although it was more effective, to some extent, in PLWHA with CRF01_AE.