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Abstract Background TFE3 rearranged renal cell carcinoma (TFE3 rRCC), classified as a distinct entity of RCCs, exhibits aggressive biological behavior and possesses unique metabolic characteristics. In the present study, TFE3 rRCC with high expression of TFE3 fusion proteins was employed to investigate the features of lipid metabolism and its underlying mechanism in cancer progression. Methods Fluorescence microscope and flow cytometry were employed to detect lipid droplets (LDs). GPO-PAP method and Oil Red O staining were used to quantify triacylglycerol levels. The data for bioinformatics analysis were sourced from GEO and iProX. The biological roles of TFE3 and LAMP2A were investigated by CCK8 assay, EdU staining, seahorse, transwell assay, colony, and sphere formation assay. The regulatory mechanisms involving TFE3, LAMP2A and Hsc70 were investigated using western blotting, immunohistochemistry, qRT-PCR, luciferase assays, Co-IP techniques, and ChIP analyses. Results The level of LDs accumulation in TFE3 rRCC was relatively low, and the knockdown of TFE3 led to an increase in LDs accumulation while inhibiting tumor progression. The underlying mechanism revealed that TFE3 fusion proteins inhibited the biosynthesis of LDs within the endoplasmic reticulum by promoting the degradation of DGAT1 and DGAT2 via autophagy. Furthermore, TFE3 fusion proteins upregulated LAMP2A, thereby enhancing chaperone-mediated autophagy pathways. The process facilitated the degradation of LDs and promoted oxidative metabolism of long-chain fatty acids in mitochondria. Conclusions TFE3 fusion proteins facilitated the progression of TFE3 rRCC through enhancing the degradation of LDs via chaperone-mediated lipophagy. LAMP2A could serve as a novel potential prognostic biomarker and therapeutic targets.

To study the axial static buckling performance of square cross-section aluminum foam-filled galvanized steel tubes, 40 specimens were tested in four groups. The axial buckling loads and buckling modes of aluminum foam-filled galvanized steel tubes were investigated. The effects of parameters such as aluminum foam density, length-to-width ratio, and steel tube thickness on the average and maximum buckling loads and buckling modes of aluminum foam-filled galvanized steel tubes were explored. The test results showed that the addition of aluminum foam increased the stiffness of the outer galvanized steel tube, changing the buckling mode from symmetric to asymmetric, with a noticeable increase in the number of buckling wrinkles. The average and maximum buckling loads increased with the increase in the relative density of the aluminum foam and the thickness of the outer steel tube. The maximum crushing loads of galvanized steel tubes with thicknesses of 1.5 mm and 2 mm are 1.7 and 3.6 times that of a galvanized steel tube with a thickness of 1 mm, respectively. In contrast, the maximum crushing loads of foam aluminum-filled galvanized steel tubes with thicknesses of 1.5 mm and 2 mm are 2.3 and 3.7 times that of a foam aluminum-filled galvanized steel tube with a thickness of 1 mm, respectively. After the galvanized steel tube is filled with aluminum foam, the foam filler can significantly enhance the bearing capacity and stiffness of the structure, and improve the impact resistance of the structure. Considering the interaction effect between the outer steel tube and the filled aluminum foam, theoretical analyses were conducted on the average and maximum buckling loads of aluminum foam-filled steel tubes, and the theoretical calculation results matched well with the experimental results.

Purpose: This Mendelian randomization (MR) analysis study aimed to investigate the genetic causal relationship between non-thyroidal autoimmune diseases (ADs) and Graves' ophthalmopathy (GO). Materials: Single nucleotide polymorphisms (SNPs) associated with inflammatory bowel disease (IBD), multiple sclerosis (MS), psoriasis vulgaris (PV), type 1 diabetes (T1D), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA) were obtained from the IEU Open genome-wide association studies (GWAS) database, GWAS data for GO were obtained from the FinnGen database. Bidirectional MR analysis was conducted using inverse variance weighted (IVW) method, weighted median (WM) method and MR-Egger test. Cochran's Q statistic was used to assess the heterogeneity between SNP estimates. MR-Egger regression was used to evaluate horizontal pleiotropy and MR pleiotropy residual sum and outlier (MR-PRESSO) test was used to detect the outliers. Results: For non-thyroidal ADs, the forward MR results using the IVM method showed that T1D (OR ​= ​1.259, 95%CI: 1.026–1.5465, P ​= ​0.028) and SLE (OR ​= ​1.807, 95%CI: 1.229–2.655, P ​= ​0.003) were correlated with the risk of GO at the genetic level, while there was no evidence showing that IBD, MS, PV and RA were correlated with GO. In the reverse MR study, there was a significant increase in the risk of developing T1D in GO (OR ​= ​1.135, 95%CI: 1.018–1.265, P ​= ​0.022), but pleiotropy and heterogeneity existed. Conclusions: In the European population, there is strong genetic evidence that patients with T1D and SLE have a higher risk of developing GO, whereas the effect of GO on ADs is unclear.

Abstract A standardized representation and sharing of crop disease and pest data is crucial for enhancing crop yields, especially in China, which features vast cultivation areas and complex agricultural ecosystems. A knowledge graph for crop diseases and pests, acting as a repository of entities and relationships, is crucial conceptually for achieving unified data management. However, there is currently a lack of knowledge graphs specifically designed for this field. In this paper, we propose CropDP-KG, a knowledge graph for crop diseases and pests in China, which leverages natural language processing techniques to analyze data from the Chinese crop diseases and pests image-text database. CropDP-KG covers relevant information on crop diseases and pests in China, featuring 8 primary entities such as diseases, symptoms, and crops, and is organized into 7 relationships such as primary occurrence locations, affected parts and suitable temperature. In total, it includes 13,840 entities and 21,961 relationships. In the case studies presented in this research, we also show a versatile application of CropDP, namely a knowledge service system, and have released its codebase under an open-source license. The content of this paper provides a guide for users to build their own knowledge graphs, aiming to help them effectively reuse and extend the knowledge graphs they create.

Abstract Little is known about how exclusive e-cigarette use affects exosomal microRNA (miRNA) expression, which is crucial in inflammation and disease processes like cancer. We compared exosomal miRNA profiles between exclusive e-cigarette users and non-users. We used plasma samples from 15 exclusive e-cigarette users and 15 non-users from the Population Assessment of Tobacco and Health (PATH) Wave 1 study (2013–2014) and sequenced miRNAs with Illumina NextSeq 500/550. We performed differential analyses using DESeq2 in R/Bioconductor, adjusting for race, and conducted gene enrichment analyses on target genes regulated by significant miRNAs. Further, molecular-based techniques using the miRNA mimics and inhibitors were applied for the validation of the expressions of the miRNAs in vitro. We identified four miRNAs that were upregulated in exclusive e-cigarette users compared to non-users: hsa-miR-100-5p, hsa-miR-125a-5p, hsa-miR-125b-5p, and hsa-miR-99a-5p, after adjusting for the confounding effects of race. However, none of the miRNAs remained statistically significant after controlling for the false discovery rate (FDR) at 5%. Subgroup analysis of White participants only identified four miRNAs (hsa-miR-100-5p, hsa-miR-125b-5p, hsa-miR-200b-3p, and hsa-miR-99a-5p) that were also upregulated in e-cigarette users with one miRNA hsa-miR-200b-3p remaining statistical significance after controlling for the FDR at 5%. GO enrichment analysis showed that these miRNAs are involved in processes like transcription regulation and cellular protein modification. KEGG pathway analysis indicated their involvement in cancer pathways, including small cell lung cancer, renal cell carcinoma, and signaling pathways (neurotrophin, ErbB, PI3K-Akt, FoxO, Hippo, MAPK, TGF-beta). Overexpression of hsa-miR-125b-5p promoted DNA damage in bronchial epithelial cells. These findings suggest an elevation of carcinogenic cellular signaling pathways in exclusive e-cigarette users.

Abstract Kaposi's sarcoma-associated herpesvirus (KSHV) infection can cause a variety of tumors and is one of the leading causes of death in acquired immune deficiency syndrome (AIDS) patients. As a small molecule antiviral drug, ganciclovir (GCV) can be used for anti-KSHV treatment. However, GCV has non-specific action and toxic side effects in vivo, and how to make it safer and more effective against KSHV is still a great challenge. By encapsulating GCV into metal–organic skeleton material zeolitic imidazolate framework-8 (ZIF-8) and further modification of hyaluronic acid (HA), the nanomedical delivery system of GCV (HA/GCV@ZIF-8) has been developed for efficient GCV delivery and targeted anti-KSHV treatment. The modification of HA leads to the targeted binding of the nanocomplex with the overexpressed CD44 receptors in tumor cell membranes, resulting in the increased accumulation and cellular uptake of GCV. Exploiting the decomposition property of ZIF-8 under acidic conditions, the nanocomplex exhibits pH-responsive drug release in slightly acidic tumor environment. In addition, HA/GCV@ZIF-8 not only suppresses expression of KSHV pathogenic genes with less drug dose, but also inhibits the ability of cell proliferation and migration. In vivo anti-tumor results showed that HA/GCV@ZIF-8 accumulated in tumor cells and effectively inhibited tumor growth. The results open a gate for the targeted anti-KSHV treatment. Graphical Abstract

Abstract Several hydroxysteroid dehydrogenase 17-beta 13 variants have previously been identified as protective against metabolic dysfunction-associated steatohepatitis (MASH) fibrosis, ballooning and inflammation, and as such this target holds significant therapeutic potential. However, over 5 years later, the function of 17B-HSD13 remains unknown. Structure-aided design enables the development of potent and selective sulfonamide-based 17B-HSD13 inhibitors. In order to probe their inhibitory potency in endogenous expression systems like primary human hepatocytes, inhibitors are transformed into synthetic surrogate substrates with distinct selectivity advantages over substrates previously published. Their application to cells endogenously expressing 17B-HSD13 enables quantitative measures of enzymatic inhibition in primary human hepatocytes which has never been reported to date. Application to multiple cellular systems expressing the protective human variants reveals that the most prevalent IsoD variant maintains NAD-dependent catalytic activity towards some but not all substrates, contradicting reports that the truncation results in loss-of-function.

Abstract As the main form of global rural decline, the impact of rural population loss on the overall level and trend of rural multifunction is still unclear. Thus, it is crucial to reveal the characteristics and influencing factors of rural multifunction changes in depopulation areas which is important to actively deal with depopulation and promote sustainable development in rural areas. Based on an evaluation of rural multifunctionality from 2000 to 2020, the spatial statistical analysis method and a geographical model were used to reveal the declining characteristics of rural multifunction in the depopulation area, as well as the effects of the influencing factors in the whole region and under various population size areas. The results show that demographic changes had a significant impact on rural multifunction development. Compared to areas with population growth, the weakening of rural multifunctionality was more likely to occur in counties with depopulation. The negative impact of population shrinkage on rural multifunction development was shown in our results as an inverted “U” shape. In the process of demographic shrinkage, the dominant factors affecting rural multifunctionality in the whole region tended to be diversified, but the population urbanization rate was always the main factor. Among regions with different population sizes, natural factors played important roles in the development of rural multifunction, and depopulation enhanced the impact of economic factors. The interaction effect of natural, social, and economic factors was stronger than that of a single factor in rural multifunction. In the process of depopulation, the interaction effect was more and more polarized. The interaction effect of economic and natural factors enhanced, but which was the most stable in mid-population-size areas. Thus, to alleviate rural decline and realize rural revitalization, the trend of demographic change should be given attention to keep a moderate population size, as well as we should actively deal with the impact of population shrinkage on rural multifunction according to different stages of population shrinkage.

Abstract The zinc-activated channel (ZAC) is an atypical mammalian cys-loop receptor (CLR) that is activated by zinc ions and protons, allowing cations to pass through. The molecular mechanism that ligands use to activate ZAC remains elusive. Here, we present three cryo-electron microscopy reconstructions of human ZAC (hZAC) under different conditions. These three hZAC structures display highly similar conformations to one another, forming symmetrical homo-pentamers with a central ion-conduction pore. The hZAC protomer comprises an extracellular domain (ECD) and a transmembrane domain (TMD), sharing more structural similarity with anion-permeable CLRs, such as glycine receptors and type A γ-aminobutyric acid receptors. Notably, hZAC possesses a distinctive C-tail that establishes a disulfide bond with the loop M2-M3 in the TMD and occupies what is typically the canonical neurotransmitter orthosteric site in other mammalian CLRs. Moreover, the tip of the cys-loop creates an unprecedented orthosteric site in hZAC. The binding of Zn2+ triggers a conformational shift in the cys-loop, which presumably prompts the loop M2-M3 to move and open the channel gate. This study sheds light on the assembly of the channel, its structural features, and the process of signal transduction in hZAC.

Abstract Background In thyroid-associated ophthalmopathy (TAO), orbital decompression is a critical surgical approach for functional and aesthetic reasons. Meanwhile, the presence of surgical complications, especially the new onset of primary gaze diplopia, also influences postoperative patient satisfaction. This research investigates the effectiveness and potential risks associated with different orbital decompression in patients with TAO. Methods Systematic searches were conducted to identify pertinent studies from PubMed, Embase, and the Cochrane Library databases. The search was completed on October 11, 2023. And after retrieval, the publication dates of the articles included in the analysis ranged from January 1, 2008, to February 22, 2023. The overall postoperative outcomes were determined using random-effects meta-analyses with corresponding 95% confidence intervals (CI). A network meta-analysis was performed to integrate both direct and indirect evidence. The primary outcomes were defined as the status of exophthalmos and the new onset of primary gaze diplopia. Results From 1,538 identified records, 87 studies were selected, encompassing 5102 patients and 8,779 procedures. The studies reported varying degrees of exophthalmos reduction based on different surgical techniques: -3.46 mm (95% CI -3.76 to -3.15 mm) for fat removal orbital decompression, -4.02 mm (95% CI -5.14 to -2.89 mm) for the medial wall technique, -3.89 mm (95% CI -4.22 to -3.55 mm) for the lateral wall technique, -5.23 mm (95% CI -5.69 to -4.77 mm) for the balanced wall technique, -3.91 mm (95% CI -4.37 to -3.46 mm) for the infero-medial wall technique, and − 5.80 mm (95% CI -6.47 to -5.13 mm) for the three-wall technique. The incidence of new-onset primary gaze diplopia was reported in 31 studies involving 214 out of 2001 patients, resulting in a weighted proportion of 0.11 (95% CI 0.06–0.14). Notably, the lowest rates were associated with the lateral approach and fat removal orbital decompression, with pooled proportion (95% CI) rates of 3% (1–6) and 3% (2–4), respectively, suggesting that these two techniques may be more effective in preventing the occurrence of this complication during the postoperative period. Conclusions This meta-analysis establishes that orbital decompression is a beneficial and safe surgical approach. While this study enhances the evidence hierarchy for orbital decompression in treating TAO, it requires further validation through larger, prospective, and randomized studies with long-term follow-up periods.

Abstract To meet the demand for high‐quality healthcare services, data trading can effectively promote the circulation of medical data and improve the level of healthcare services. To address the existing problems of data regulation difficulties and data privacy leakage in medical data trading, a trusted and regulated data trading scheme based on blockchain and zero‐knowledge proof is proposed. In this scheme, a regulatory institution is introduced to control the issuance of authorized tokens and ensure the controllability of data sharing activities. The blockchain takes over the task of generating public parameters to reduce the computational overhead of the system. Based on homomorphic proxy re‐encryption technology, users can perform data analysis in the cloud to ensure data security. Smart contracts and zero‐knowledge proof technology can automatically verify the validity of data to protect the rights and interests of data users; at the same time, efficient consensus algorithms can also increase the rate of transactions processed by the blockchain system. Finally, as the security and performance analysis shows, the scheme in this paper has better security, higher efficiency and more comprehensive functions.

Abstract Objective This study aims to analyze factors associated with the missed diagnosis of high-grade squamous intraepithelial lesions (HSIL+) in patients initially diagnosed with low-grade squamous intraepithelial lesions (LSIL) through colposcopic biopsy and to develop a predictive model for assessing the risk of missed HSIL+. Methods We conducted a retrospective analysis of 505 patients who underwent loop electrical excision procedure (LEEP) following an LSIL diagnosis by colposcopic biopsy. Logistic regression was used to identify demographic and pathological parameters associated with missed diagnoses of HSIL+. Additionally, several machine learning methods were employed to construct and assess the performance of the risk prediction models. Results The overall rate of missed diagnoses for HSIL+ was 15.2%. Independent risk factors identified were HPV16/18 infection (OR 2.071; 95% CI 1.039–4.127; p = 0.039), TCT ≥ ASC-H (OR 4.147; 95% CI 1.392–12.355; p = 0.011), TZ3 (OR 1.966; 95% CI 1.003–3.853; p = 0.049) and Colposcopic impression G2 (OR 3.627; 95% CI 1.350–9.743; p = 0.011). Among the models tested, the Decision Tree algorithm demonstrated superior performance with an accuracy of 94.7%, sensitivity of 80.0%, specificity of 96.9%, and an area under the curve (AUC) of 0.936 in the validation set. Conclusion Key independent risk factors for the missed diagnosis of HSIL in patients with LSIL include HPV16/18 infection, TCT ≥ ASC-H, TZ3, and colposcopic impression G2. The Decision Tree model offers a cost-effective, reliable, and clinically valuable tool for accurately predicting the risk of missed diagnosis of HSIL+, facilitating early intervention and management.

Abstract Traditional education systems obscure the diverse interconnections inherent within subject knowledge, thus failing to meet the current demand for personalized and adaptive learning experiences. Recent advances have explored various relation extraction techniques to construct educational knowledge graphs that integrate dispersed subject knowledge into a unified framework. However, educational conceptual entities are far more abstract and intricate compared to their real-world equivalents, and these techniques primarily focus on static knowledge, overlooking the dynamic nature of knowledge in practical learning and application scenarios. To address these issues, we propose a Prompt-based framework with dynamic Update mechanism for educational Relation Extraction (PURE). This framework embraces a prompt-tuning strategy and employs a more appropriate MacBERT-large model to encode the instances wrapped by prompt templates. Furthermore, we construct an instance-relation database that serves as an external knowledge base of our framework. A dynamic instance-relation update mechanism is proposed to refine the database, thus enhancing the accuracy of PURE in predicting new triples. We conduct experiments on a Data Structure course relation extraction dataset and three public datasets. The experimental results demonstrate that PURE achieves significant improvements and outperforms several state-of-the-art baselines in efficiency of extraction and utilization of educational information. Comparable performance is achieved even in more complex biomedical relation extraction, validating its robustness and applicability to other domains.

Rejuvenation presents a promising way to improve the plasticity of metallic glasses. How modulating the degree of rejuvenation of metallic glasses remains a challenging issue. Here, based on the molecular dynamics simulation, we investigate the evolution of the structural and mechanical properties of a binary Al75Mg25 metallic glass and successfully realized the rejuvenation modulation through the multiple recovery annealing treatment. A range of samples with different degrees of rejuvenation were obtained by successive multiple recovery annealing process. According to our calculations, we found that the degree of rejuvenation is highly correlated with the Al-centered clusters. Microstructural analyses show that a higher degree of rejuvenation is concomitant with less 1551 index of Honeycutt-Andersen indices and a lower content of in terms of Voronoi Tessellation analysis. Moreover, our calculated results demonstrate that the samples with the aging initial state show a higher degree of rejuvenation as compared to the samples with the rejuvenated initial state. This can be attributed to that there are more icosahedral clusters, which are more likely to change to other types of clusters with low local fivefold symmetry in the aged samples during the subsequent high-temperature annealing process. Our work confirms that proper multiple (no more than three times) recovery annealing treatment can increase the degree of rejuvenation of metallic glasses and can offer a better understanding of the effect of rejuvenation on the microstructures and mechanical properties of metallic glasses.

Fast and non-destructive analysis of material defect is a crucial demand for semiconductor devices. Herein, we are devoted to exploring a solar-cell defect analysis method based on machine learning of the modulated transient photovoltage (m-TPV) measurement. The perturbation photovoltage generation and decay mechanism of the solar cell is firstly clarified for this study. High-throughput electrical transient simulations are further carried out to establish a database containing millions of m-TPV curves. This database is subsequently used to train an artificial neural network to correlate the m-TPV and defect properties of the perovskite solar cell. A Back Propagation neural network has been screened out and applied to provide a multiple parameter defect analysis of the cell. This analysis reveals that in a practical solar cell, compared to the defect density, the charge capturing cross-section plays a more critical role in influencing the charge recombination properties. We believe this defect analysis approach will play a more important and diverse role for solar cell studies.

Abstract The low resolution of spatial transcriptomics data necessitates additional information for optimal use. We developed scDOT, which combines spatial transcriptomics and single cell RNA sequencing to improve the ability to reconstruct single cell resolved spatial maps and identify senescent cells. scDOT integrates optimal transport and expression deconvolution to learn non-linear couplings between cells and spots and to infer cell placements. Application of scDOT to lung spatial transcriptomics data improves on prior methods and allows the identification of the spatial organization of senescent cells, their neighboring cells and novel genes involved in cell-cell interactions that may be driving senescence.

Abstract Bartonella are vector-borne gram-negative facultative intracellular bacteria that can infect a wide spectrum of mammals, and are recognized as emerging human pathogens. This study aimed to investigate the prevalence and molecular characteristics of Bartonella infections in small mammals within the Qinghai Menyuan section of Qilian Mountain National Park, China. Small mammals were captured, and the liver, spleen and kidney were collected for Bartonella detection and identification using a combination of real-time PCR targeting the transfer-mRNA (ssrA) gene and followed by sequencing of the citrate synthase (gltA) gene. A total of 52 rodents were captured, and 36 rodents were positive for Bartonella, with a positivity rate of 69.23% (36/52). Bartonella was detected in Cricetulus longicaudatus, Microtus oeconomus, Mus musculus, and Ochotona cansus. The positivity rate was significantly different in the different habitats. Two Bartonella species were observed, including Bartonella grahamii and Bartonella heixiaziensis, and B. grahamii was the dominant epidemic strain in this area. Phylogenetic analysis showed that B. grahamii mainly clustered into two clusters, which were closely related to the Apodemus isolates from China and Japan and the local plateau pika isolates, respectively. In addition, genetic polymorphism analysis showed that B. grahamii had high genetic diversity, and its haplotype had certain regional differences and host specificity. Overall, high prevalence of Bartonella in small mammals in the Qinghai Menyuan section of Qilian Mountain National Park. B. grahamii is the dominant strain with high genetic diversity and potential pathogenicity to humans, and corresponding control measures should be considered.

Abstract Background Peer support is a promising and significant way for people living with HIV (PLWH) to improve their health outcomes. Matching PLWH with HIV peer volunteers can effectively stimulate and mobilize the function of peer support in health management. We develop the online platform Aspark, which features a precision matching function for PLWH and volunteers. This protocol provides a comprehensive overview of the randomized controlled trial design based on Aspark. Method A parallel randomized controlled trial using block randomization will be conducted at the Beijing YouAn Home of Loving Care. The intervention group (n = 70) will have access to all 12 features of Aspark, including precise volunteer matching, health management tools, drug interaction queries, and medication reminders. The control group (n = 70) will have access to two features of informational support on Aspark. The outcomes of both groups will be evaluated at baseline and at 3, 6, 9, and 12 months after platform registration. The primary outcome is perceived social support. The secondary outcomes include mental symptoms, quality of life, self-efficacy, medication adherence, and health behaviors. Linear mixed models or generalized linear mixed models will be applied to test the intervention effects. Discussion The Aspark trial is a randomized controlled trial designed to examine the influence of a mobile health (mHealth) application that integrates peer support and precision matching to strengthen social support for PLWH in China. This trial has the potential to significantly enhance social support for PLWH while also optimizing the delivery of peer support services and fully mobilizing the role of peer support in the overall health management of PLWH. Trial registration Clinical registration number: ChiCTR2300077454.

Abstract The Hydrogel wound dressing with good rewarming property, anti‐freezing property, and adhesion property has important practical significance in medical care for the first and second grade frostbite. The ears, hands, mouth, and nose of field workers on duty and training high cold region are prone to frostbite due to long‐term exposure to in severe cold. Therefore, rapid rewarming of wound surface is the key to the treatment of frostbite. In this paper, antifreeze and rewarming are achieved by photothermal conversion materials and quaternary ammonium salts. Herein, the PAM/CS/MXene30/Betaine5/AgNPs200(PCM30B5A200) hydrogel based on chitosan (CS) and acrylamide (AM) is designed and fabricated by thermally initiated free radical polymerization. The dressing has excellent rewarming properties, anti‐freezing properties, tensile properties, repeatable self‐adhesion and antibacterial properties. In this system, hydrogels are mainly cross‐linked by hydrogen bonds between CS and AM. Betaine is added to the material to make the hydrogel have good freeze‐resistance and flexibility at −24 °C, and can be combined with AgNPs and MXene, to achieve a triple antibacterial. The PCM30B5A200 hydrogel reached the rewarming temperature of 40.5 °C at 9 min. PCM30B5A200 multifunctional hydrogels have good application value in the first and second grade frostbite wounds.

Summary: Background: To date, comprehensive data on the distribution of chronic kidney disease (CKD), the most prevalent comorbidity in diabetes, among Chinese adults with diabetes is lacking. Additionally, research gaps exist in understanding the association between CKD and cardiovascular health (CVH), an integrated indicator of lifestyle and metabolic control, within a nationwide sample of Chinese adults with diabetes. Methods: A nationally community-based cross-sectional survey was conducted in 2018–2020. 58,560 residents diagnosed with diabetes aged 18–74 years nationwide were invited to participate, and 52,000 participants with complete CKD data were included in this study. CKD was identified by the presence of albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g) and/or decreased estimated glomerular filtration rate (eGFR,

BuShao Tiaozhi Capsule (BSTZC), a novel drug in China, has been used to treat hyperlipidemia (HLP) in clinical practice for many years. Despite our previous studies suggesting that BSTZC can treat HLP, there is a lack of a rapid and systematic method to explore its active components. Therefore, in this study, we aimed to investigate the active components and mechanisms of BSTZC in treating HLP by integrating serum pharmacology, pharmacokinetics, network analysis, and experimental validation. We first established UPLC fingerprints, calibrated 23 common peaks, and identified 13 common peaks, and the similarity was greater than 0.99 for 10 batches. A total of nine metabolites from BSTZC were identified in serum and considered as PK markers. The pharmacokinetic parameters of the PK markers were compared between the control group and the model group through the pharmacokinetics study to determine the dynamic changes of representative components in rats. Compared with the control group, the Cmax and AUC0→t of OXY, IVT, IVL, and KPF-3-G were significantly higher (P< 0.05); the AUC0→∞ of OXY, PN, and IVT was significantly higher (P< 0.05); and the t1/2 of IVT, SA, and KPF-3-G was significantly different (P< 0.05). In vivo experiments showed that BSTZC and its active components could effectively alleviate lipid metabolism disorders and liver injury, with obvious lipid-lowering effects. Further studies showed that BSTZC alleviated HLP by inhibiting the PI3K/Akt signaling pathway, which was consistent with the results of the network analysis study. Our results revealed the active components and mechanisms of BSTZC in the treatment of HLP, which could provide useful information to guide the clinical application of BSTZC.

Ardisia gigantifolia is a critically endangered medicinal plant endemic to China and only 77 wild individuals were found at present. To provide detailed information for selecting its restoration habitats, plantlets of this species were transplanted into four sites with different habitats, including two current sites (GLQ and HK) with extant populations, one historical site (NX) and one site (BG) outside its historical range but near the existing range. The survival, growth and physiological performance of transplanted plantlets and habitat characters were compared among the four sites, and the population structure and physiological traits of wild individuals were compared among the two extant populations. The results revealed that relative irradiance would be the main factor influencing the photosynthesis and growth of transplanted plantlets. Transplanted plantlets at NX presented the best overall performance in survival, growth and physiology, and presented better physiological performance than wild seedlings at the two current sites, revealing that NX was the optimal habitat for reintroduction of A. gigantifolia. Compared to NX, severe shading at GLQ and HK resulted in the decrease of light energy utilization efficiency and growth parameters. Wild seedlings at GLQ exhibited significantly lower light energy utilization efficiency but significantly higher malondialdehyde content than those at HK, which would explain the lower proportion of young individuals and the smaller growth trend in the GLQ population.

IntroductionHematopoietic stem cell transplantation (HSCT) and chemotherapy are considered potentially curative options for post-remission therapy in acute myeloid leukemia (AML). However, the comparative effectiveness of these approaches in favorable- and intermediate-risk AML remains unclear and requires further investigation.MethodsIn this retrospective study, 111 patients diagnosed with de novo favorable- and intermediate-risk AML, categorized according to the ELN 2022 guidelines, were investigated to compare outcomes following autologous HSCT (auto-HSCT), matched sibling donor HSCT (MSD-HSCT), and chemotherapy. Through propensity score matching for disease status before HSCT, 42 cases in first complete remission were selected for each of the auto-HSCT group and the MSD-HSCT group. Additionally, 27 cases in the chemotherapy group, excluding patients with early relapse or death, were included for comparison.ResultsIn the overall population, the 3-year overall survival (OS) rates were 85.7%, 83.1%, and 70.4% (p = 0.043), while the disease-free survival (DFS) rates were 78.6%, 83.2%, and 57.1% (p = 0.002) in the auto-HSCT, MSD-HSCT, and chemotherapy groups, respectively. Notably, both auto-HSCT and MSD-HSCT demonstrated significantly improved DFS compared to chemotherapy in patients with favorable-risk AML. Multivariate analysis further revealed that chemotherapy was significantly associated with inferior DFS compared to auto-HSCT (HR=2.82; 95% CI, 1.26–6.32, p=0.012), while DFS was similar between the MSD-HSCT and auto-HSCT groups (HR=0.80; 95% CI, 0.31–2.09, p=0.645).DiscussionThe findings suggested the advantages of both MSD-HSCT and auto-HSCT over chemotherapy as post-remission therapy for AML patients with favorable and intermediate risk. Further research is needed to support these conclusions.

Abstract Background Idiopathic pulmonary fibrosis (IPF) is an age-related disease featured with abnormal fibrotic response and compromised lung function. Cellular senescence is now considered as an essential driving mechanism for IPF. Given the poor knowledge of the mechanisms underpinning IPF progression, understanding the cellular processes and molecular pathways is critical for developing effective therapies of IPF. Methods Lung fibrosis was induced using bleomycin in C57BL/6 mice. Cellular senescence was measured by immunofluorescence. The effects of FGF-4 on fibroblast activation markers and signaling molecules were assessed with western blot and qPCR. Results We demonstrated elevated abundance of senescent mesenchymal stem cells (MSCs) in IPF lung tissues, which was tightly correlated with the severity of pulmonary fibrosis in vivo. In addition, senescent MSCs could effectively induce the phenotype of pulmonary fibrosis both in vitro and in vivo. To further confirm how senescent MSCs regulate IPF progression, we demonstrate that FGF-4 is significantly elevated in senescent MSCs, which can induce the activation of pulmonary fibroblasts. In vitro, FGF-4 can activate Wnt signaling in a FOXM1-dependent manner. Inhibition of FOXM1 via thiostrepton effectively impairs FGF-4-induced activation of pulmonary fibroblast and dramatically suppresses the development of pulmonary fibrosis. Conclusion These findings reveal that FGF-4 plays a crucial role in senescent MSCs-mediated pulmonary fibrogenesis, and suggests that strategies aimed at deletion of senescent MSCs or blocking the FGF-4/FOXM1 axis could be effective in the therapy of IPF.

Promoting the construction of a healthy China requires enhancing awareness of the primary responsibility for health and developing a new pattern of active health. However, active health currently faces practical issues such as insufficient transition from passive health management and a lack of long-term driving mechanisms. Starting from the practice of projects such as health banks, this article introduces the concept of health savings into active health management. Through the goal-framing theory, it systematically analyzes the functional characteristics of health savings, the long-term health motivation driving path, and the formation path of the long-term mechanism of active health. It provides empirical insights for enriching the connotation and extension of active health. At the same time, suggestions are put forward to enrich the selection of health savings functions, adapt to residents' health security needs, improve the level of information technology application, and formulate progressive strategies.

Abstract Background There is a high incidence of cervical cancer in Xinjiang. Genetic variation in human papillomavirus may increase its ability to invade, spread, and escape host immune response. Methods HPV16 genome was sequenced for 90 positive samples of HPV16 infection. Sequences of the E4, E5 and L2 genes were analysed to reveal sequence variation of HPV16 in Xinjiang and the distribution of variation among the positive samples of HPV16 infection. Results Eighty-one of the 90 samples of HPV16 infection showed variation in HPV16 E4 gene with 18 nucleotide variation sites, of which 8 sites were synonymous variations and 11 missense variations. 90 samples of HPV16 infection showed variation in HPV16 E5 and L2 genes with 16 nucleotide variation sites (6 synonymous, 11 missense variations) in the E5 gene and 100 nucleotide variation sites in L2 gene (37 synonymous, 67 missense variations). The frequency of HPV16 L2 gene missense variations G3377A, G3599A, G3703A, and G3757A was higher in the case groups than in the control groups. Conclusions Phylogenetic tree analysis showed that 87 samples were European strains, 3 cases were Asian strains, there were no other variations, and G4181A was related to Asian strains. HPV16 L2 gene missense variations G3377A, G3599A, G3703A, and G3757A were significantly more frequent in the case groups than in the control groups.

Abstract Background Most Chinese joint entity and relation extraction tasks in medicine involve numerous nested entities, overlapping relations, and other challenging extraction issues. In response to these problems, some traditional methods decompose the joint extraction task into multiple steps or multiple modules, resulting in local dependency in the meantime. Methods To alleviate this issue, we propose a joint extraction model of Chinese medical entities and relations based on RoBERTa and single-module global pointer, namely RSGP, which formulates joint extraction as a global pointer linking problem. Considering the uniqueness of Chinese language structure, we introduce the RoBERTa-wwm pre-trained language model at the encoding layer to obtain a better embedding representation. Then, we represent the input sentence as a third-order tensor and score each position in the tensor to prepare for the subsequent process of decoding the triples. In the end, we design a novel single-module global pointer decoding approach to alleviate the generation of redundant information. Specifically, we analyze the decoding process of single character entities individually, improving the time and space performance of RSGP to some extent. Results In order to verify the effectiveness of our model in extracting Chinese medical entities and relations, we carry out the experiments on the public dataset, CMeIE. Experimental results show that RSGP performs significantly better on the joint extraction of Chinese medical entities and relations, and achieves state-of-the-art results compared with baseline models. Conclusion The proposed RSGP can effectively extract entities and relations from Chinese medical texts and help to realize the structure of Chinese medical texts, so as to provide high-quality data support for the construction of Chinese medical knowledge graphs.

Periocular basal cell carcinoma (pBCC) is the most common malignancy in the periocular region, characterized by local aggressiveness, high incidence, and significant recurrence rates. While surgery is the primary treatment option, achieving complete lesion removal can be challenging due to the sensitive anatomy of this area and associated cosmetic considerations. Recent advancements in photodynamic therapy (PDT) have demonstrated promising efficacy and cosmetic outcomes for superficial BCC, offering alternatives to traditional treatments. However, PDT's effectiveness is often limited by the penetration depth of photosensitizers, particularly for deep tumors. To address these challenges, we developed a regimen that combines palliative surgery with immediate PDT for pBCC cases with inadequate or positive surgical margins. This integrated approach aims to overcome the penetration limitations of PDT while enhancing tumor clearance and preserving cosmetic outcomes. We report on three cases where all patients achieved complete clinical remission, with satisfactory cosmetic results and no recurrence observed during follow-up periods ranging from 12 to 23 months. Our findings suggest that palliative surgical resection, in conjunction with PDT, represents an effective treatment strategy for pBCC. This approach is particularly valuable when standard surgical margins cannot be achieved, especially considering the importance of cosmetic healing.

BackgroundPrevious microbiological investigations have demonstrated a significant correlation between Corynebacterium kroppenstedtii complex (CKC) infection and mastitis. Recent studies have confirmed the existence of the CKC, with Corynebacterium parakroppenstedtii (C. parakroppenstedtii) identified as the primary infectious agent. Examining the incidence of CKC in cases of severe non-lactational mastitis, alongside the clinical characteristics of infected patients, as well as evaluating the drug sensitivity testing protocols for CKC, can provide a more robust foundation for the diagnosis and treatment of CKC infections.MethodsData regarding the diagnosis and treatment of non-nursing patients with severe mastitis who underwent surgical intervention were extracted from the hospital’s electronic medical record system. Additionally, drug susceptibility tests were conducted on 15 strains of CKC isolated from mammary abscesses as well as DSM 44385 model strains. The effects of β-NAD and Tween80 (TW80) on the antibiotic susceptibility test by AGAR dilution and micro broth dilution were analyzed.ResultsIn this study, C. parakroppenstedtii accounted for 80% (12/15) of the isolates, while Corynebacterium pseudokroppenstedtii made up 13.3% (2/15), and Corynebacterium kroppenstedtii was identified in only 6.7% (1/15) of the cases. There were significant differences in age at first delivery (p < 0.001), prolactin (p < 0.001), CRP (p < 0.05), WBC (p < 0.05), and NEUT (p < 0.05) between CKC positive group and CKC negative group. In the AGAR dilution test, the addition of β-NAD only caused acceptable differences in penicillin G and ciprofloxacin but did not affect 12 antibiotics. There are 14 drugs with good coincidence rates (92.9%) in the micro broth dilution method and agar dilution method without the addition of β-NAD. The addition of 0.05% (v/v) TW80 resulted in all strains being resistant to penicillin G. Daptomycin is not suitable for the micro broth dilution method.ConclusionElderly primiparas with high prolactin levels have a higher risk of CKC infection. The micro broth dilution method is not applicable for EUCAST drug susceptibility testing for CKC and there is no suitable drug susceptibility evaluation procedure for daptomycin against CKC.

BackgroundNicotine is a highly addictive agent in tobacco products. On June 21, 2022, the US Food and Drug Administration (FDA) announced a plan to propose a rule to establish a maximum nicotine level in cigarettes and other combusted tobacco products. ObjectiveThis study aimed to understand public perception and discussion of very low nicotine content (VLNC) on Twitter (rebranded as X in July 2023). MethodsFrom December 12, 2021, to January 1, 2023, we collected Twitter data using relevant keywords such as “vln,” “low nicotine,” and “reduced nicotine.” After a series of preprocessing steps (such as removing duplicates, retweets, and commercial tweets), we identified 3270 unique noncommercial tweets related to VLNC. We used an inductive method to assess the public perception and discussion of VLNC on Twitter. To establish a codebook, we randomly selected 300 tweets for hand-coding, including the attitudes (positive, neutral, and negative) toward VLNC (including its proposed rule) and major topics (13 topics). The Cohen κ statistic between the 2 human coders reached over 70%, indicating a substantial interrater agreement. The rest of the tweets were single-coded according to the codebook. ResultsWe observed a significant peak in the discussion of VLNC on Twitter within 4 days of the FDA’s announcement of the proposed rule on June 21, 2022. The proportion of tweets with a negative attitude toward VLNC was significantly lower than those with a positive attitude, 24.5% (801/3270) versus 37.09% (1213/3270) with P

BackgroundFrailty, particularly cognitive frailty, is an escalating public health issue. Cognitive frailty is defined by the simultaneous presence of physical frailty and cognitive impairment, without a confirmed diagnosis of dementia, and has become a significant geriatric syndrome. This study aimed to explore the association between chronic pain and the risk of cognitive frailty.MethodsWe utilized data from two waves (2011 and 2015) of the China Health and Retirement Longitudinal Study (CHARLS), conducting both cross-sectional and longitudinal analyses involving 17,705 Chinese adults aged 45 years and older. Chronic pain was defined as pain reported at both time points. Cognitive function was evaluated using a questionnaire adapted from the Telephone Interview for Cognitive Status. The frailty index (FI) was derived from a 30-item assessment. Cognitive frailty was characterized by the co-occurrence of cognitive impairment and physical frailty.ResultsAmong the 14,285 participants, 5.39% exhibited cognitive frailty at baseline. Both cross-sectional and longitudinal analyses indicated that individuals suffering from chronic pain faced a higher likelihood of developing cognitive frailty compared to those without pain. After adjusting for potential confounders, multivariate models also indicated a higher odds of cognitive frailty for participants with chronic pain.ConclusionChronic pain is significantly associated with an elevated risk of cognitive frailty among middle-aged and elderly individuals. These findings highlight the importance of managing chronic pain to mitigate the risk of cognitive frailty, thereby potentially enhancing the quality of life for the aging population and alleviating the economic burden on families and society.

Candida albicans is an opportunistic fungal pathogen known for surviving in various nutrient-limited conditions within the host and causing infections. Our prior research revealed that Hfl1p, an archaeal histone-like or Hap5-like protein, is linked to mitochondrial ATP generation and yeast-hyphae morphogenesis. However, the specific roles of Hfl1p in these virulence behaviours, through its function in the CBF/NF-Y complex or as a DNA polymerase II subunit, remain unclear. This study explores Hfl1p’s diverse functions in energy metabolism and morphogenesis. By combining proteomic analysis and phenotypic evaluations of the hfl1Δ/hfl1Δ mutant with ChIP data, we found that Hfl1p significantly impacts mitochondrial DNA-encoded CI subunits, the tricarboxylic acid (TCA) cycle, and morphogenetic pathways. This influence occurs either independently or alongside other transcription factors recognizing a conserved DNA motif (TAXXTAATTA). These findings emphasize Hfl1p’s critical role in linking carbon metabolism and mitochondrial respiration to the yeast-to-filamentous form transition, enhancing our understanding of C. albicans’ metabolic adaptability during morphological transition, an important pathogenic trait of this fungus. This could help identify therapeutic targets by disrupting the relationship between energy metabolism and cell morphology in C. albicans.

Knowledge about the impact craters on rocky planets is crucial for understanding the evolutionary history of the universe. Compared to traditional visual interpretation, deep learning approaches have improved the efficiency of crater detection. However, single-source data and divergent data quality limit the accuracy of crater detection. In this study, we focus on valuable features in multi-modal remote sensing data from Chang’e lunar exploration mission and propose an Attention-based Dual-branch Segmentation Network (ADSNet). First, we use ADSNet to extract the multi-modal features via a dual-branch encoder. Second, we introduce a novel attention for data fusion where the features from the auxiliary modality are weighted by a scoring function and then being fused with those from the primary modality. After fusion, the features are transferred to the decoder through skip connection. Lastly, high-accuracy crater detection is achieved based on the learned multi-modal data features through semantic segmentation. Our results demonstrate that ADSNet outperforms other baseline models in many metrics such as IoU and F1 score. ADSNet is an effective approach to leverage multi-modal remote sensing data in geomorphological feature detection on rocky planets in general.

ABSTRACT Bartonella grahamii is one of the most prevalent Bartonella species in wild rodents and has been associated with human cases of neuroretinitis. The structure and distribution of genomic diversity in natural B. grahamii is largely unexplored. Here, we have applied a comprehensive population genomic and phylogenomic analysis to 172 strains of B. grahamii to unravel the genetic differences and influencing factors that shape its populations. The findings reveal a remarkable genomic diversity within the species, primarily in the form of single- nucleotide polymorphisms. The open pangenome of B. grahamii indicates a dynamic genomic evolution influenced by its ecological niche. Whole-genome data allowed us to decompose B. grahamii diversity into six phylogroups, each characterized by a unique “mosaic pattern” of hosts and biogeographic regions. This suggests a complex interplay between host specificity and biogeography. In addition, our study suggests a possible origin of European strains from Asian lineages, and host factors have a more significant impact on the genetic differentiation of B. grahamii than geographical factors. These insights contribute to understanding the evolutionary history of this pathogen and provide a foundation for future epidemiological research and public health strategies.IMPORTANCEBartonella grahamii has been reported worldwide and shown to infect humans. Up to now, an effective transmission route of B. grahamii to humans has not been confirmed. The genetic evolution of B. grahamii and the relationship between B. grahamii and its host need to be further studied. The factors driving the genetic diversity of B. grahamii are still controversial. The results showed that the European isolates shared a common ancestor with the Chinese isolates. Host factors were shown to play an important role in driving the genetic diversity of B. grahamii. When host factors were fixed, geographic barriers drove B. grahamii microevolution. Our study emphasizes the importance of characterizing isolate genomes derived from hosts and geographical locations and provides a new reference for the origin of B. grahamii.

BackgroundUnderstanding public opinions about emerging tobacco products is important to inform future interventions and regulatory decisions. Heated tobacco products (HTPs) are an emerging tobacco product category promoted by the tobacco industry as a “better alternative” to combustible cigarettes. Philip Morris International’s IQOS is leading the global HTP market and recently has been subject to important policy events, including the US Food and Drug Administration’s (FDA) modified-risk tobacco product (MRTP) authorization (July 2020) and the US import ban (November 2021). Although limited in their legal implications outside the United States, these policy events have been quoted in global news outlets and Philip Morris International’s promotional communications, showing how they may potentially impact global tobacco regulation. Given the impending return of IQOS to the US market, understanding how the policy events were received through social media discourse will provide valuable insights to inform global tobacco control policy. ObjectiveThis study aims to examine HTP-related social media discourse around important policy events. MethodsWe analyzed HTP-related posts on Twitter during the time period that included IQOS’s MRTP authorization in the United States and the US import ban, examining personal testimonial, news/information, and direct marketing/retail tweets separately. We also examined how the tweets discussed health and policy. A total of 10,454 public English tweets (posted from June 2020 to December 2021) were collected using HTP-related keywords. We randomly sampled 2796 (26.7%) tweets and conducted a content analysis. We used pairwise co-occurrence analyses to evaluate connections across themes. ResultsTweet volumes peaked around IQOS-related policy events. Among all tweets, personal testimonials were the most common (1613/2796, 57.7%), followed by news/information (862/2796, 30.8%) and direct marketing/retail (321/2796, 11%). Among personal testimonials, more tweets were positive (495/1613, 30.7%) than negative (372/1613, 23.1%), often comparing the health risks of HTPs with cigarettes (402/1613, 24.9%) or vaping products (252/1613, 15.6%). Approximately 10% (31/321) of the direct marketing/retail tweets promoted international delivery, suggesting cross-border promotion. More than a quarter of tweets (809/2796, 28.9%) discussed US and global policy, including misinterpretation about IQOS being a “safer” tobacco product after the US FDA’s MRTP authorization. Neutral testimonials mentioning the IQOS brand (634/1613, 39.3%) and discussing policy (378/1613, 23.4%) showed the largest pairwise co-occurrence. ConclusionsResults suggest the need for careful communication about the meaning of MRTP authorizations and relative risks of tobacco products. Many tweets expressed HTP-favorable opinions referring to reduced health risks, even though the US FDA has denied marketing of the HTP with reduced risk claims. The popularity of social media as an information source with global reach poses unique challenges in health communication and health policies. While many countries restrict tobacco marketing via the web, our results suggest that retailers may circumvent such regulations by operating overseas.

Human genetic studies show that loss of function mutations in 17-Beta hydroxysteroid dehydrogenase (HSD17β13) are associated with protection from non-alcoholic steatohepatitis (NASH). As a result, therapies that reduce HSD17β13 are being pursued for the treatment of NASH. However, inconsistent effects on steatosis, inflammation, and fibrosis pathogenesis have been reported in murine Hsd17b13 knockdown or knockout models. To clarify whether murine Hsd17b13 loss regulates liver damage and fibrosis, we characterized Hsd17b13 knockout mice subjected to pro-NASH diets or pro-inflammatory chemical-induced liver injury. There were no effects of Hsd17b13 loss on liver injury, inflammation, fibrosis, or lipids after 28 weeks on the Gubra-Amylin NASH (GAN) diet or 12 weeks on a 45% choline-deficient high-fat diet (CDAHFD). However, AAV-mediated re-expression of murine Hsd17b13 in KO mice increased liver macrophage abundance in both sexes fed the 45% CDAHFD. In contrast, there was a modest reduction in liver fibrosis, but not lipids or inflammation within Hsd17b13 null female, but not male, mice after 12 weeks of a 60% CDAHFD compared to WT littermates. Fibrosis and the abundance of liver macrophages were increased in Hsd17b13 KO females upon adenoviral re-expression of mouse HSD17β13, but this was not reflected in inflammatory markers. Additionally, we found minimal differences in liver injury, lipids, or inflammatory and fibrotic markers 48 h after acute CCl4 exposure. In summary, murine Hsd17b13 loss has modest diet- and sex-specific effects on liver fibrosis which contrasts with human genetic studies. This suggests a disconnect between the biological function of HSD17β13 in mice and humans.

Background Gynecological cancers (GC) pose a severe threat to the health and safety of women’s lives, and organoids, as in-vitro research models, have demonstrated significant advantages in simulating tissue characteristics and drug screening. In recent years, there has been a rapid increase in research outcomes related to organoids in GC. However, there has been no bibliometric study concerning.Methods Publications related to GC and organoids from 2010-2023 were retrieved from the Web of Science Core Collection (WoSCC). We conducted a bibliometric analysis and visualization using CiteSpace, VOSviewer, and the Bibliometrix R Package. This analysis included the spatiotemporal distribution, author, sources, references, and keywords.Results A total of 333 publications were included. The number of annual publications indicated an explosive phase of development since 2019. The USA was the most important country in terms of cooperation, publication output, citation and centrality. University of California system ranked first in productivity among institutions, and HIPPO Y is the most relevant author in the research field. CANCERS published the most documents, and NATURE is the most cited sources. Analysis of Keywords and References, it is possible to establish the trend, and find the hotspots in the research field.Conclusion This bibliometric analysis delineated global landscapes and progress trends in GC organoids research. This study emphasized that organoids can effectively replicate the original tissue or tumors, providing a good in-vitro model for research on tumor-related mechanisms and showing significant advantages in drug screening and efficacy clinical prediction. Additionally, as preclinical models, they provide compelling evidence for personalized therapy and prediction of patient drug responses.

ABSTRACT Objectives Glioblastoma multiforme (GBM) is considered the most assailant subtype of gliomas, presenting a formidable obstacle because of its inherent resistance to temozolomide (TMZ). This study aimed to characterize the function of lncRNA NEAT1 in facilitating the advancement of gliomas. Methods The expression level of NEAT1 in glioma tissues and cells was detected by qRT‐PCR. RNA interference experiment, cell proliferation assay, FITC/PI detection assay, immunoblotting, bioinformatics prediction, a double luciferase reporter gene assay, RNA immunoprecipitation (RIP) assay, SLDT assay and correlation analysis of clinical samples were performed to explore the regulatory effects of NEAT1, miR‐454‐3p and Cx43 and their role in malignant progression of GBM. The role of NEAT1 in vivo was investigated by an intracranial tumor formation experiment in mice. Results The results showed that recurring gliomas displayed elevated levels of NEAT1 compared to primary gliomas. The suppression of NEAT1 led to a restoration of sensitivity in GBM cells to TMZ. NEAT1 functioned as a competitive endogenous RNA against miR‐454‐3p. Connexin 43 was identified as a miR‐454‐3p target. NEAT1 was found to regulate gap junctional intercellular communication by modulating Connexin 43, thereby impacting the response of GBM cells to TMZ chemotherapy. Downregulation of NEAT1 resulted in enhanced chemosensitivity to TMZ and extended the survival of mice. Conclusions Overall, these results indicated that the NEAT1/miR‐454‐3p/Connexin 43 pathway influences GBM cell response to TMZ and could offer a potential new strategy for treating GBM.

Abstract Background The mortality of pneumonia in older adults surpasses that of other populations, especially with the prevalence of coronavirus disease 2019 (COVID-19). Under the influence of multiple factors, a series of geriatric syndromes brought on by age is one of the main reasons for the poor prognosis of pneumonia. This study attempts to analyze the impact of geriatric syndrome on the prognosis of pneumonia. Methods This is a prospective cross-sectional study. Patients over 65 years old with COVID-19 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative community-acquired pneumonia (SN-CAP) were included in the research. General characteristics, laboratory tests, length of stay (LOS), and comprehensive geriatric assessment (CGA) were collected. Multivariate regression analysis to determine the independent predictors of the severity, mortality, and LOS of COVID-19. At the same time, the enrolled subjects were divided into three categories by clustering analysis of 10 CGA indicators, and their clinical characteristics and prognoses were analyzed. Results A total of 792 subjects were included in the study, including 204 subjects of SN-CAP (25.8%) and 588 subjects (74.2%) of COVID-19. There was no significant difference between non-severe COVID-19 and SN-CAP regarding mortality, LOS, and CGA (P > 0.05), while severe COVID-19 is significantly higher than both (P

Abstract Objective To identify the risk factors of cervical high-grade squamous intraepithelial lesion(HSIL) complicated with occult cervical cancer and standardize the management of initial treatment for HSIL. Method The clinical data of patients who underwent total hysterectomy directly due to HSIL in the obstetrics and gynecology department of two tertiary hospitals and three secondary hospitals from 2018 to 2023 were collected. Their general characteristics, pathological parameters and survival status were analyzed. Logistic regression model was used to analyze the correlation between clinical parameters and postoperative pathological upgrading. Result 1. Among the 314 patients with HSIL who underwent total hysterectomy directly, 73.2% were from primary hospitals. 2. 25 patients (7.9%) were pathologically upgraded to cervical cancer, all of which were early invasive cancer. 3. Up to now, there was no recurrence or death in the 25 patients with early-stage invasive cancer, and the median follow-up period was 21 months(range 2–59 months). 4. Glandular involvement(OR 3.968; 95%CI 1.244–12.662) and lesion range ≥ 3 quadrants (OR 6.527; 95% CI 1.78–23.931), HPV 16/18 infection (OR 5.382; 95%CI 1.947–14.872), TCT ≥ ASC-H (OR 4.719; 95%CI 1.892–11.766) were independent risk factors that affected the upgrading of postoperative pathology. 5. The area under the curve (AUC) calculated by the Logistic regression model was 0.840, indicating that the predictive value was good. Conclusion There is a risk of occult cervical cancer in patients with HSIL. Glandular involvement, Lesion range ≥ 3 quadrants, HPV 16/18 infection and TCT ≥ ASC-H are independent risk factors for HSIL combined with occult cervical cancer. The prognosis of biopsy-proved HSIL patients who underwent extrafascial hysterectomy and unexpected early invasive cancer was later identified on specimen may be good.

Abstract Charge loss at grain boundaries of kesterite Cu2ZnSn(S, Se)4 polycrystalline absorbers is an important cause limiting the performance of this emerging thin-film solar cell. Herein, we report a Pd element assisted reaction strategy to suppress atomic vacancy defects in GB regions. The Pd, on one hand in the form of PdSe x compounds, can heterogeneously cover the GBs of the absorber film, suppressing Sn and Se volatilization loss and the formation of their vacancy defects (i.e. VSn and VSe), and on the other hand, in the form of Pd(II)/Pd(IV) redox shuttle, can assist the capture and exchange of Se atoms, thus contributing to eliminating the already-existing VSe defects within GBs. These collective effects have effectively reduced charge recombination loss and enhanced p-type characteristics of the kesterite absorber. As a result, high-performance kesterite solar cells with a total-area efficiency of 14.5% (certified at 14.3%) have been achieved.

Bartter syndrome (BS) is a rare, inherited salt-losing renal tubular disorder characterized by secondary hyperaldosteronism, hypokalemia, hypochloremia, metabolic alkalosis, and low-to-normal blood pressure. Classic BS, or BS Type 3, the most common subtype in the Asian population, is caused by a molecular defect in ClC-Kb, a voltage-gated chloride channel in renal tubules, due to CLCNKB gene mutation. Because the onset of BS is more common in children than in adults, the diagnosis, treatment outcomes, genotype/phenotype association, and follow-up of adult-onset BS Type 3 are limited. This case report describes the findings in a 20-year-old man who was admitted with hypokalemic paralysis, with clinical manifestations were similar to those of Gitelman syndrome (GS); however, the patient was later diagnosed to have BS Type 3 through genetic testing (NM_000085.4 (CLCNKB): c.1052G>T). A literature review showed that no homozygous mutations have been reported to date. After 5 years of treatment and follow-up, we found that this genotype requires high levels of potassium and is prone to urinary protein and metabolic syndrome. Distinguishing adult-onset BS from GS is challenging in clinical practice. However, genetic diagnosis can help solve this problem effectively, and genotypes play a guiding role in treatment planning.

Abstract Aneuploidy is a hallmark of cancers, but the role of aneuploidy-related genes in lung adenocarcinoma (LUAD) and their prognostic value remain elusive. Gene expression and copy number variation (CNV) data were enrolled from TCGA and GEO database. Consistency clustering analysis was performed for molecular cluster. Tumor microenvironment was assessed by the xCell and ESTIMATE algorithm. Limma package was used for selecting differentially expressed genes (DEGs). LASSO and stepwise multivariate Cox regression analysis were used to establish an aneuploidy-related riskscore (ARS) signature. GDSC database was conducted to predict drug sensitivity. A nomogram was designed by rms R package. TCGA-LUAD patients were stratified into 3 clusters based on CNV data. The C1 cluster displayed the optimal survival advantage and highest inflammatory infiltration. Based on integrated intersecting DEGs, we constructed a 6-gene ARS model, which showed effective prediction for patient’s survival. Drug sensitivity test predicted possible sensitive drugs in two risk groups. Additionally, the nomogram exhibited great predictive clinical treatment benefits. We established a 6-gene aneuploidy-related signature that could effectively predict the survival and therapy for LUAD patients. Additionally, the ARS model and nomogram could offer guidance for the preoperative estimation and postoperative therapy of LUAD.

In view of the application status and technical challenges of steel–wood composite joints in architecture, this paper proposes an innovative connection technology to solve issues such as susceptibility to pry-out at beam–column joints and low load-bearing capacity and to provide various reinforcement methods in order to meet the different structural requirements and economic benefits. By designing and manufacturing four groups of beam–column joint specimens with different reinforcement methods, including no reinforcement, structural adhesive and angle steel reinforcement, 4 mm thick steel sleeve reinforcement, and 6 mm thick steel sleeve reinforcement, monotonic loading tests and finite element simulations were carried out, respectively. This research found that unreinforced specimens and structural adhesive angle steel-reinforced joints exhibited obvious mortise and tenon compression deformation and, moreover, tenon pulling phenomena at load values of approximately 2 kN and 2.6 kN, respectively. However, the joint reinforced by a steel sleeve showed a significant improvement in the tenon pulling phenomenon and demonstrated excellent initial stiffness characteristics. The failure mode of the steel sleeve-reinforced joints is primarily characterized by the propagation of cracks at the edges of the steel plate and the tearing of the wood, but the overall structure remains intact. The initial rotational stiffness of the joints reinforced with angle steel and self-tapping screws, the joints reinforced with 4 mm thick steel sleeves, and the joints reinforced with 6 mm thick steel sleeves are 3.96, 6.99, and 13.62 times that of the pure wooden joints, while the ultimate bending moments are 1.97, 7.11, and 7.39 times, respectively. Using finite element software to simulate four groups of joints to observe their stress changes, the areas with high stress in the joints without sleeve reinforcement are mainly located at the upper and lower ends of the tenon, where the compressive stress at the upper edge of the tenon and the tensile stress at the lower flange are both distributed along the grain direction of the beam. The stress on the column sleeve of the joints reinforced with steel sleeves and bolts is relatively low, while the areas with high strain in the beam sleeve are mainly concentrated on the side with the welded stiffeners and its surroundings; the strain around the bolt holes is also quite noticeable.

BackgroundThe Omnibus Budget Bill, known as H. R. 2471, passed through Congress on March 10, 2022, and was eventually signed by President Biden on March 15, 2022. This bill amended the Federal Food, Drug, and Cosmetic Act granting the Food and Drug Administration (FDA) regulatory authority over synthetic nicotine. ObjectiveThis study aims to examine the public perceptions of the Omnibus Bill that regulates synthetic nicotine products as tobacco products on Twitter (rebranded as X). MethodsThrough the X streaming application programming interface, we collected and identified 964 tweets related to the Omnibus Bill on synthetic nicotine between March 8, 2022, and April 13, 2022. The longitudinal trend was used to examine the discussions related to the bill over time. An inductive method was used for the content analysis of related tweets. By hand-coding 200 randomly selected tweets by 2 human coders respectively with high interrater reliability, the codebook was developed for relevance, major topics, and attitude to the bill, which was used to single-code the rest of the tweets. ResultsBetween March 8, 2022, and April 13, 2022, we identified 964 tweets related to the Omnibus Bill regulating synthetic nicotine. Our longitudinal trend analysis showed a spike in the number of tweets related to the bill during the immediate period following the bill’s introduction, with roughly half of the tweets identified being posted between March 8 and 11, 2022. A majority of the tweets (497/964, 51.56%) had a negative sentiment toward the bill, while a much smaller percentage of tweets (164/964, 17.01%) had a positive sentiment toward the bill. Around 31.43% (303/964) of all tweets were categorized as objective news or questions about the bill. The most popular topic for opposing the bill was users believing that this bill would lead users back to smoking (145/497, 29.18%), followed by negative implications for small vape businesses (122/497, 24.55%) and government or FDA mistrust (94/497, 18.91%). The most popular topic for supporting the bill was that this bill would take a dangerous tobacco product targeted at teens off the market (94/164, 57.32%). ConclusionsWe observed a more negative sentiment toward the bill on X, largely due to users believing it would lead users back to smoking and negatively impact small vape businesses. This study provides insight into public perceptions and discussions of this bill on X and adds valuable information for future regulations on alternative nicotine products.

Background: Chromoblastomycosis (CMB) is a chronic granulomatous fungal infection that affect the skin and subcutaneous tissues. It is clinically problematic due to limited treatment options, low cure rates, and high rates of relapse. This underscores the necessity for innovative treatment approaches. In this study, potassium iodide (KI) combined with Methylene Blue (MB) mediated antimicrobial photodynamic therapy (PDT) were assessed in the treatment of Fonsecaea monophora (F. monophora) both in vitro and in vivo. And the underlying mechanism that contributes to the efficacy of this treatment approach was investigated. Methods: In vitro experiments were conducted using different combinations and concentrations of MB, KI, and 660 nm light (60 mW/cm2) to inhibit F. monophora. The study was carried out using colony-forming unit (CFU) counts and scanning electron microscopy (SEM). The production of singlet oxygen (1O2), free iodine (I2), hydrogen peroxide (H2O2), and superoxide anion during the KI combined MB-mediated antimicrobial PDT process was also detected. In vivo experiments were developed using a Balb/c mouse paw infection model with F. monophora and treated with PBS, 10 mM KI, 2 mM MB +100 J/cm² and 10 mM KI+2 mM MB +100 J/cm² respectively. Inflammatory swelling, fungal load and histopathological analyses of the mouse footpads were assessed. Results: KI enhanced the killing effect of MB-mediated antimicrobial PDT on the conidial spores of F. monophora at the cell and infected animal model level. During the process, the main antimicrobial agents in KI combined with MB- mediated antimicrobial PDT could produce stronger toxic active species including free I2 and H2O2. Conclusion: KI combined with MB-mediated antimicrobial PDT could be an effective adjunct therapy for treating CBM.

IntroductionGlobal climate change (CC) significantly impacts sustainable food systems and the agricultural sector, primarily through increasing adverse weather events. This study aims to explore the adaptation strategies farmers use to address these challenges and evaluate the effectiveness of climate-smart agricultural (CSA) practices on food performance.MethodsWe collected data from 720 crop farmers located in three provinces of Pakistan using a random sampling method. To address potential biases, this study employed the endogenous switching regression (ESR) model. This model effectively addresses endogeneity and selection bias by considering both observable and unobservable characteristics.ResultsStudy findings indicate that CSA practices substantially enhance net farm returns, reduce volatility, and mitigate downside risks. The analysis also highlights key features affecting the acceptance of CSA practices, including higher education, age, climate information, and availability of agricultural extension services.DiscussionThese insights are essential for policymakers, offering a framework for informed decision-making to tackle CC’s effects on food production, improve living standards, and enhance global food security.

Objectives: To evaluate the neutralizing antibody (NAb) levels against the SARS-CoV-2 Omicron variants BF.7, BQ.1, BQ.1.1, XBB.1, and XBB.1.5 after vaccination and natural infection. Methods: The NAbs against the different viral strains of 490 individuals with SARS-CoV-2 and 187 without SARS-CoV-2 in the Beijing COVID-19 outbreak during December 2022 to January 2023 were analyzed. Results: In uninfected individuals, limited levels of NAbs were produced against the prototype and variant strains after two doses vaccine but significantly increased after three or four doses of the vaccine. The infected individuals had high NAbs levels against the BF.7, BQ.1, and BQ.1.1 variants and moderate NAbs levels against the XBB.1 and XBB.1.5 variants. The highest NAbs levels were observed after two inoculation doses. The third and fourth doses vaccine did not result in a significant increase the NAbs levels. After the last dose of vaccination, the NAbs levels peaked at 12 months for the prototype and BF.7 and between 6 to 12 months for the BQ.1, BQ.1.1, XBB.1, and XBB.1.5 variants. Conclusions: The immune response decreases as the virus mutates. If booster vaccination is considered necessary, it is suggested for at least 6 months after infection.

ABSTRACT In this study, we investigated the prevalence of Bartonella in deer from Qilian County, Qinghai Province, China. Blood samples were collected from 69 red deer, 40 white-lipped deer, and 27 sika deer. The detection of Bartonella spp. has been conducted. The overall prevalence of Bartonella was 33.6% (46/135). Species-specific prevalence was 50.72% in red deer (35/69), 20.00% in white-lipped deer (8/40), and 11.11% in sika deer (3/27). There were significant differences in the prevalence rates among the different species of deer. The amplicon sequence comparison revealed a high homology of the ruminant-associated Bartonella spp. Nanopore sequencing further confirmed the results. Bartonella reads were presented in each of the qPCR-positive samples. Phylogenetic analysis indicated that the Bartonella sequences detected in deer blood were closely related to ruminant-borne Bartonella spp. In summary, we reported the Bartonella prevalence of different deer species in Qinghai, and there were at least one species of ruminant-associated Bartonella, B. schoenbuchensis.IMPORTANCEThis is the first report about Bartonella infections in the deer population from China. We found that there were two species of Bartonella and an unidentified species of Bartonella among the unculturing strains carried by these deer populations. We first used Nanopore sequencing to detect Bartonella from deer blood samples and indicated that Nanopore sequencing is beneficial to detect pathogens due to its advantage of real-time and high sensitivity.