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Abstract Background Health-related quality of life is a multi-dimensional concept that involves individual’s perceived physical and mental health, social relationships, and environment. Family members are the primary caregivers of people living with schizophrenia in China, the quality of life of caregiver of people living with schizophrenia is generally poorer, which may indirectly affect the quality of life of the people with schizophrenia. Methods We conducted a comprehensive survey on quality of life in caregivers of people living with schizophrenia based on the Schizophrenia-specific cohort in the Less-developed Multi-ethnic Region of Southwest China to validate the accessibility and effectiveness of the schizophrenia family care model at the family level, caregivers of people living with schizophrenia were selected as participants in Baoshan City, Yunnan Province from September 2022 to March 2023, quality of life, family burden of disease, sociodemographic and behavioral information of participants were collected. Results Domain scores for physical, psychological, social relationships, and environment of quality of life were 13.50 ± 2.61, 12.67 ± 2.40, 13.64 ± 2.32, and 12.46 ± 1.76 respectively. In our study, we found that gender, age, education level, personal monthly income, history of smoking and alcohol consumption, subjective sleep quality, relation to the patient, degree of self-care and the number of relapses in patient all influence 1 to 4 domains of quality of life for caregivers, stratified analysis was conducted to minimize the effect of gender on the results, we still found that history of smoking could positively predict the score of psychological domain and history of alcohol consumption could positively predict the score of social relationships domain. Canonical correlation analysis showed that the ‘impact on family interaction’ in family burden of disease was most closely related to quality of life. Conclusion Building harmonious family relationships can help improve the quality of life for caregivers of People living with schizophrenia.

The supply-side advancement in the transportation modes may bring a new mobility paradigm in the proximate future because consumers in the era of autonomous vehicles (AVs) would be able to choose from a variety of modes of transportation that would be likely to co-exist, including private AVs, conventional automobiles, and shared mobility services. Accordingly, research on the demand response is needed since it can provide insights on who would use and how the market would react to these emerging modes, which helps develop a more solid long-term transportation planning. Thus, this study conducted nationwide stated choice experiments in the U.S. and employed the Mixed Logit (MXL) model. Combined with market share summary, parameter estimation, and marginal effect estimates, this study offered several notable findings and implications. For instance, descriptive statistics underscored a significant propensity for private and shared AVs, with approximately 24% of respondents indicating their intention to use these modes, while shared mobility services garnered less than 10% of the market share. However, conventional personal cars retained their dominance, with around 50% of respondents favoring this mode in the AV era. Moreover, parameter estimation of the MXL model indicates that trip purposes, alternative-specific characteristics, individual features, transportation-related factors, and attitudinal factors significantly and differently influence the outcome probability of choosing a certain mode. Furthermore, marginal effects estimated from the model suggest that the potential users of AVs and SAVs seem to be more cost-conscious than drivers of a personal car, while SAV users are slightly less cost-sensitive than AV users. These findings underscore the need for adaptive policies that cater to the diverse preferences and behaviors of future mobility consumers, ensuring the development of sustainable and equitable transportation systems.

Abstract In the realm of cancer research, the tumor microenvironment (TME) plays a crucial role in tumor initiation and progression, shaped by complex interactions between cancer cells and surrounding non-cancerous cells. Cytokines, as essential immunomodulatory agents, are secreted by various cellular constituents within the TME, including immune cells, cancer-associated fibroblasts, and cancer cells themselves. These cytokines facilitate intricate communication networks that significantly influence tumor initiation, progression, metastasis, and immune suppression. Pyroptosis contributes to TME remodeling by promoting the release of pro-inflammatory cytokines and sustaining chronic inflammation, impacting processes such as immune escape and angiogenesis. However, challenges remain due to the complex interplay among cytokines, pyroptosis, and the TME, along with the dual effects of pyroptosis on cancer progression and therapy-related complications like cytokine release syndrome. Unraveling these complexities could facilitate strategies that balance inflammatory responses while minimizing tissue damage during therapy. This review delves into the complex crosstalk between cytokines, pyroptosis, and the TME, elucidating their contribution to tumor progression and metastasis. By synthesizing emerging therapeutic targets and innovative technologies concerning TME, this review aims to provide novel insights that could enhance treatment outcomes for cancer patients.

The complete mitochondrial genome of Culex hutchinsoni Barraud, 1924 was reported with 15,586 bp long. It contained 37 annotated genes and the control region, which is consistent with other mosquitoes. Most PCGs used typical ATN as start codons, while some special start codons were also used (i.e. TCG for COX1, TTG for ND1, GTG for ND5). Most PCGs terminated with TAA as well as some PCGs (COX1, COX2, COX3, ND3, ND4 and CYTB) terminated with TA-tRNA or T-tRNA. Cx. (Lophoceraomyia) was recovered as the sister group to Cx. (Culex), while Cx. hutchinsoni was recovered within the species group of Cx. pipiens.

Abstract Hepatocellular carcinoma (HCC) cells, along with multiple nonmalignant stromal cells, such as fibroblasts, endothelial cells and immune cells, comprise an intricate cellular ecosystem, undergo dynamic phenotypic changes and present complicated cellular interactions, thus synergistically facilitating HCC initiation and progression and leading to treatment resistance. Clarifying the heterogeneity, cell plasticity and complexity of the cellular ecosystem of HCC will be highly beneficial for understanding HCC development and identifying novel therapeutic targets. Single-cell RNA sequencing (scRNA-seq) refers to profiling the transcriptome at single-cell resolution, and the development of scRNA-seq technology and analysis algorithms has greatly promoted the analysis of cell composition, cell subpopulation heterogeneity, development trajectory and cell-to-cell interactions in cell populations. In this review, we systematically summarized and discussed scRNA-seq in treatment-naive primary HCC and revealed the global cell composition of HCC; the widespread molecular heterogeneity of HCC cells; the molecular subtypes of fibroblasts; the cell composition, functional states and development trajectory of immune cells; and the frequent interactions between different cell types to systematically draw the landscape of the cellular ecosystem of primary HCC.

Abstract Sorafenib, a first-line therapeutic option for advanced hepatocellular carcinoma (HCC), faces a formidable challenge in the form of emerging resistance. Recently, the oncogene DDX11 antisense RNA 1 (DDX11-AS1) has been implicated in various cancers, including HCC. However, its role in sorafenib resistance remains unknown. Our findings reveal that DDX11-AS1 is upregulated in sorafenib-resistant HCC cells, contributing to their resistance by suppressing ferroptosis. Further investigation elucidated the mechanism by which DDX11-AS1 activates the antioxidant Nrf2-Keap1 pathway. By interacting with Nrf2 and hindering its association with Keap1, DDX11-AS1 enhances the stability and nuclear translocation of Nrf2. In summary, our study unveils the potent role of DDX11-AS1 as an enhancer of sorafenib resistance, inhibiting sorafenib-induced ferroptosis through the activation of the Nrf2-Keap1 pathway in HCC. These findings offer a promising therapeutic strategy to overcome resistance and effectively treat HCC.

Abstract Understanding the interface between nanomaterials and lipoproteins is crucial for gaining insights into their impact on lipoprotein structure and lipid metabolism. Here, we use graphene oxide (GOs) nanosheets as a controlled carbon nanomaterial model to study how surface properties influence lipoprotein corona formation and show that GOs have strong binding affinity with low-density lipoprotein (LDL). We use advanced techniques including X-ray reflectivity, circular dichroism, and molecular simulations to explore the interfacial interactions between GOs and LDL. Specifically, hydrophobic GOs preferentially associate with LDL’s lipid components, whereas hydrophilic GOs tend to bind with apolipoproteins. Furthermore, these GOs distinctly modulate a variety of lipid metabolism pathways, including LDL recognition, uptake, hydrolysis, efflux, and lipid droplet formation. This study underscores the importance of structure analysis at the nano-biomolecule interface, emphasizing how nanomaterials’ surface properties critically influence cellular lipid metabolism. These insights will inspire the design and application of future biocompatible nanomaterials and nanomedicines.

Abstract Background Clinical trials have shown that immunotherapy based on Vγ9Vδ2 T cells (Vδ2 T cells) is safe and well-tolerated for various cancers including cervical cancer (CC), but its overall treatment efficacy remains limited. Therefore, exploring the mechanisms underlying the suboptimal efficacy of Vδ2 T cell-based cancer immunotherapy is crucial for enabling its successful clinical translation. Methods Tumor samples from CC patients and CC cell line-derived xenograft (CDX) mice were analyzed using flow cytometry to examine the exhausted phenotype of tumor-infiltrating Vδ2 T cells. The interrelationship between BTN3A1 expression and Vδ2 T cells in CC, along with their correlation with patient prognosis, was analyzed using data from The Cancer Genome Atlas (TCGA) database. CC cell lines with BTN3A1 knockout (KO) and overexpression (OE) were constructed through lentivirus transduction, which were then co-cultured with expanded Vδ2 T cells, followed by detecting the function of Vδ2 T cells using flow cytometry. The pathways and transcription factors (TFs) related to BTN3A1-induced Vδ2 T cells exhaustion and the factors affecting BTN3A1 expression were identified by RNA-seq analysis, which was confirmed by flow cytometry, Western Blot, and gene manipulation. Results Tumor-infiltrating Vδ2 T cells exhibited an exhausted phenotype in both CC patients and CDX mice. BTN3A1 expressed in CC is highly enhancing exhaustion markers, while reducing the secretion of effector molecules in Vδ2 T cells. Blocking TCR or knocking down nuclear receptor subfamily 4 group A (NR4A) 2/3 can reverse BTN3A1-induced exhaustion in Vδ2 T cells. On the other hand, IFN-γ secreted by Vδ2 T cells promoted the expression of BTN3A1 and PD-L1. Conclusions Through binding γδ TCRs, BTN3A1 expressed on tumor cells, which is induced by IFN-γ, can promote Vδ2 T cells to upregulate the expression of TFs NR4A2/3, thereby affecting their activation and expression of exhaustion-related molecules in the tumor microenvironment (TME). Therefore, targeting BTN3A1 might overcome the immunosuppressive effect of the TME on Vδ2 T cells in CC.

Abstract This study proposes a smart grid model named “GridOptiPredict”, which aims to achieve efficient analysis and processing of power system data through deep fusion of deep learning and graph neural network, so as to improve the intelligent level and overall efficiency of power grid operation. The model integrates three core functions of load forecasting, power grid state sensing and resource optimization into one, forming a closely connected and complementary framework. Through carefully designed experimental scheme, the practical value and effectiveness of “Grid OptiPredict” model are fully verified from three aspects: accuracy of load forecasting, sensitivity of power grid state sensing and efficiency of resource allocation strategy. Experimental results show that the model has significant advantages in prediction accuracy, model stability and robustness, resource optimization, security, information security, social and economic benefits and user experience.

Abstract The purpose of this study was to compare the predictive value of different lymph node staging systems and to develop an optimal prognostic nomogram for predicting distant metastasis in pancreatic ductal adenocarcinoma (PDAC). Our study involved 6364 patients selected from the Surveillance, Epidemiology, and End Results (SEER) database and 126 patients from China. Independent risk factors for distant metastasis were screened by univariate and multivariate logistic regression analyses, and a model-based comparison of different lymph node staging systems was conducted. Furthermore, we developed a nomogram for predicting distant metastasis using the optimal performance lymph node staging system. The lymph node ratio (LNR), log odds of positive lymph nodes (LODDS), age, primary site, grade, tumor size, American Joint Committee on Cancer (AJCC) 7th Edition T stage, and radiotherapy recipient status were significant predictors of distant metastasis in PDAC patients. The model with the LODDS was a better fit than the model with the LNR. We developed a nomogram model based on LODDS and six clinical parameters. The area under the curve (AUC) and concordance index (C-index) of 0.753 indicated that this model satisfied the discrimination criteria. Kaplan–Meier curves indicate a significant difference in OS among patients with different metastasis risks. LODDS seems to have a superior ability to predict distant metastasis in PDAC patients compared with the AJCC 8th Edition N stage, PLN and LNR staging systems. Moreover, we developed a nomogram model for predicting distant metastasis. Clinicians can use the model to detect patients at high risk of distant metastasis and to make further clinical decisions.

The rapid development of the global economy and population growth are accompanied by the production of numerous waste textiles. This leads to a waste of limited resources and serious environmental pollution problems caused by improper disposal. The rational recycling of wasted textiles and their transformation into high-value-added emerging products, such as smart wearable devices, is fascinating. Here, we propose a novel roadmap for turning waste cotton fabrics into three-dimensional elastic fiber-based thermoelectric aerogels by a one-step lyophilization process with decoupled self-powered temperature–compression strain dual-parameter sensing properties. The thermoelectric aerogel exhibits a fast compression response time of 0.2 s, a relatively high Seebeck coefficient of 43 μV·K−1, and an ultralow thermal conductivity of less than 0.04 W·m−1·K−1. The cross-linking of trimethoxy(methyl)silane (MTMS) and cellulose endowed the aerogel with excellent elasticity, allowing it to be used as a compressive strain sensor for guessing games and facial expression recognition. In addition, based on the thermoelectric effect, the aerogel can perform temperature detection and differentiation in self-powered mode with the output thermal voltage as the stimulus signal. Furthermore, the wearable system, prepared by connecting the aerogel-prepared array device with a wireless transmission module, allows for temperature alerts in a mobile phone application without signal interference due to the compressive strains generated during gripping. Hence, our strategy is significant for reducing global environmental pollution and provides a revelatory path for transforming waste textiles into high-value-added smart wearable devices.

ABSTRACT Background The incidence rate and mortality of cervical cancer rank the fourth in the global female cancer. N6‐methyladenosine (m6A) always plays an important role in tumor progression, and fat mass and obesity‐associated gene (FTO) works as the m6A demethylase. Aims Our study aimed to narrate the biological function and potential mechanisms for FTO in cervical cancer malignancy. Materials & Methods We analyzed potential clinical value of FTO in cervical cancer patients. The relative protein levels of FTO in cervical cancerous tissue and paracancerous tissue were verified by IHC. After changing the FTO expression level by lentivirus transfection, the proliferation and metastasis ability of cervical cancer cells were detected both in vitro and in vivo. Further, Merip‐seq and Merip‐qPCR are used to profile m6A transcriptome‐wide. Finally, western blot were performed to identify the regulatory mechanism. Results Based on TCGA‐CESC cohort and GEO dataset, FTO expression levels in HPV‐positive cancer patients were significantly higher than those in HPV‐negative cancer patients and could predict advanced FIGO stage. The protein level of FTO in cervical cancerous tissue was higher than that in paracancerous tissue. Functional assays indicated that FTO promoted the proliferation, migration and invasion of cervical cancer cells both in vitro and in vivo. The Merip‐seq and Merip‐qPCR evoked that relative PIK3R3 m6A level was significantly increased after FTO knockdown, which effected the activation of FoxO pathway. After knocking down FTO, upregulation of PIK3R3 can restore the malignancy of cervical cancer. Conclusion All in all, these data suggest a vital role for FTO in occurrence and development of cervical cancer.

As one of the three major food crops in the world, maize plays a significant role in alleviating the food crisis. Maize stalk rot can reduce maize yield and mechanical harvesting efficiency. In addition, mycotoxins such as Deoxynivalenol (DON) and Zearalenone (ZEN) produced by maize stalk rot pathogens can also harm livestock and human health. Maize stalk rot is an infection of the whole growth period, and there are no effective control measures at present. Therefore, it is of great significant to study the pathogenesis and control mechanism of stalk rot from multiple perspectives. In the present study, root and rhizosphere soil of disease-resistant inbred line Y853 and disease-susceptible inbred line Q478 were collected at the dough stage (R4) and maturity stage (R6) of maize, respectively. The effects of resistant/susceptible inbred line on soil microorganisms were analyzed by amplicon sequences and metabolomics. The results showed that there was different microbial community composition from different inbred lines in different growth stages. Specifically, the abundance of Arthrobacter, Streptomyces and Bacillus in R4 rhizosphere soil was higher than that of R6, while the rhizosphere fungal composition of LR853 was significantly different from that of the other three compartments. Co-occurrence network analysis showed that the pathogen Fusarium had the highest degree centrality and closeness centrality in the DR478. Moreover, metabolomics analysis showed that four main metabolic pathways were significantly enriched, and 15 metabolites were upgrade in resistant inbred line. Furthermore, microbes, especially fungi, also were related to these 15 metabolites. Our results revealed that maize resistance to stalk rot is closely related to root-associated microbiota and rhizospheric metabolites, which would be a new perspective of phytopathogenic biocontrol.

In this study, 34 deep eutectic solvents (DESs) were successfully prepared for the extraction of proanthocyanidin from Rhodiolae Crenulatae Radix et Rhizomes. The extraction process was optimized using single factor exploration and Box-Behnken design-response surface analysis. The extraction rate was significantly improved when the molar ratio of choline chloride to 1,3-propanediol was 1:3.5 and the water content was 30% (V/V) in DESs. AB-8 macroporous resin and ethyl acetate were used for separation and refining, and the oligomer-rich proanthocyanidin components were eventually obtained. The ultraviolet (UV) and infrared (IR) spectra showed that the proanthocyanidins were mainly composed of catechin and epicatechin. To further clarify the chemical composition of proanthocyanidin, an ion scan list containing 156 proanthocyanidins precursors was obtained by constructing a proanthocyanidins structural library and mass defect filtering (MDF) algorithm, combined with the full mass spectrometry (MS)/dd-MS2 scan mode that turns on the “if idle pick others” function. By using ultra-high performance liquid chromatography and high-resolution MS (UHPLC/HRMS), the analysis used both targeted and non-targeted methods to detect proanthocyanidins. Finally, 50 oligomeric proanthocyanidin (OPC) compounds were identified, including 7 monomers, 22 dimers, 20 trimers, and 1 tetramer, most of which were procyanidins of proanthocyanidins (84%), and a small amount of prodelphinidin (14%) and other types of proanthocyanidins (2%), which enabled the systematic characterization of proanthocyanidin components from Rhodiolae Crenulatae Radix et Rhizomes. Meanwhile, the comparison with the grape seeds OPCs standard (United States Pharmacopeia) revealed that the proanthocyanidins in Rhodiolae Crenulatae Radix et Rhizomes were more abundant, suggesting that the proanthocyanidins in Rhodiolae Crenulatae Radix et Rhizomes has promising applications.

Background:Polygonum multiflorum shows dual hepatoprotective and hepatotoxic effects. The bioactive components responsible for these effects are unknown. This study investigates whether cis-2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (cis-TSG), a stilbene glycoside, has hepatoprotective and/or hepatotoxic effects in a liver injury model.Methods: C57BL/6J mice were administered α-naphthylisothiocyanate (ANIT) to induce cholestasis, followed by treatment with cis-TSG. Hepatoprotective and hepatotoxic effects were assessed using serum biomarkers, liver histology, and metabolomic and lipidomic profiling. Transcriptomic analysis were conducted to explore gene expression changes associated with lipid and bile acid metabolism, inflammation, and oxidative stress.Results and Discussion: ANIT administration caused significant liver injury, evident from elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and dysregulated lipid metabolism. cis-TSG treatment markedly reduced ALT and AST levels, normalized lipid profiles, and ameliorated liver damage, as seen histologically. Metabolomic and lipidomic analyses revealed that cis-TSG influenced key pathways, notably glycerophospholipid metabolism, sphingolipid metabolism, and bile acid biosynthesis. The treatment with cis-TSG increased monounsaturated and polyunsaturated fatty acids (MUFAs and PUFAs), enhancing peroxisome proliferator-activated receptor alpha (PPARα) activity. Transcriptomic data confirmed these findings, showing the downregulation of genes linked to lipid metabolism, inflammation, and oxidative stress in the cis-TSG-treated group. The findings suggest that cis-TSG has a hepatoprotective effect through modulation of lipid metabolism and PPARα activation.

Facing rising maritime security threats, this study presents T-MOEA/D, a sophisticated evolutionary algorithm enhancing UUVs’ capabilities in mine detection and neutralization. The algorithm tackles the multi-objective challenge by balancing time and energy, integrating user preferences into its optimization process. It leverages genetic operators such as dual chromosome encoding and partially mapped crossover to evolve efficient solutions, outperforming T-NSGA-II and T-NSGA-III in hypervolume and operational time. The UUV, directed by T-MOEA/D, navigates to operational areas and employs StyleGAN and YOLOv9 for accurate mine perception, crucial for executing mine countermeasure tasks. The system’s effectiveness is confirmed through Unity3D simulations and real-world tests, demonstrating its practicality and reliability. The study’s findings offer strategic guidance for planning large-scale mine countermeasure missions with multiple UUVs, ensuring operational efficiency and safety in complex underwater environments. The Pareto optimal solutions align with user preferences, reflecting a tailored approach to mine countermeasure missions.

Abstract Fractures of the contralateral hip may easily occur in elderly patients after an initial hip fracture. The aim of this study was to investigate the clinical characteristics and major predisposing risk factors of contralateral hip fracture after initial hip fracture in the elderly, to provide a clinical basis for preventing contralateral hip fracture. The data of 1586 patients who had sustained first or second hip fractures and had been surgically treated in our department were retrospectively analyzed. Potential predictive factors for contralateral hip fracture and descriptive statistics associated with surgery (such as blood loss, operation time, and length of hospital stay) were recorded. Of these patients, 133 (8.4%) suffered contralateral hip fracture. The rates of contralateral fracture after femoral neck and intertrochanteric fracture were 5.4% and 10.7% respectively (P

This is an article in the field of mineral processing engineering. The opper polymetallic ore in a high-altitude mining area in Xizang has a high oxidation rate and complex ore properties. In order to make full, efficient and comprehensive use of mineral resources, this article analyzes and studies the mineral properties and characteristics of the raw ore based on theory and practical experience. Finally, the flotation process with JM-1 sulfide agent, ZJ-1 collector, copper, lead and zinc mixed flotation of "sulfur before oxygen" as the key technology is determined. At the condition that the copper oxidation rate of the raw ore is 38.58%, the mixed concentrate grade sum of lead and zinc is 41.17%, and the recovery of copper, lead and zinc is 58.74%, 80.71% and 70.82%, respectively, after two roughing, three cleaning and two scavenging processes, which greatly improves the utilization effect and technical level of dressing. It also provides technical support and favorable basis for the improvement and innovation of mineral processing technology in the later stage.

Abstract The authors investigated the ingredient detection technique of silicone rubber based on the Terahertz spectrum. For this purpose, 18 diverse high‐temperature vulcanised silicone rubber (HTVSR) formulations were customised, 8 of which are used as calibration set while the rest 10 as prediction set. Based on the Beer‐Lambert Law, the partial‐least‐square (PLS) regression model and the least‐squares support‐vector machines (LS‐SVM) regression model were used to yield the relationships between the absorption spectrums and the content percentages of polydimethylsiloxane (PDMS), alumina trihydrate (ATH), and silica in HTVSR. The results showed that for the formulations tested, the prediction accuracy of all three main ingredients by the PLS regression model could be improved by changing the spectrum range from 0.2–4 to 0.5–2 THz. If the data were pre‐processed by the Savitzky–Golay smoothing method or multiplicative scatter correction method, the prediction accuracy of PDMS could be further enhanced. However, this would lead to a slight decrease in the prediction accuracy of ATH. For the LS‐SVM regression model, the radial basis function (RBF) kernel and the linear kernel were studied. It was found that the prediction accuracy of both kernels was better than that of the PLS regression model. With the LS‐SVM regression model using the RBF kernel, the correlated coefficients of PDMS and ATH in the prediction set could be up to 0.9915 and 0.9742, respectively.

Abstract Background The use of stem cell-derived exosomes (Exos) as therapeutic vehicles is receiving increasing attention. Exosome administration has several advantages over cell transplantation, thus making exosomes promising candidates for large-scale clinical implementation and commercialization. However, exosome extraction and purification efficiencies are relatively low, and therapeutic heterogeneity is high due to differences in culture conditions and cell viability. Therefore, in this study, we investigated a priming procedure to enhance the production and therapeutic effects of exosomes from human umbilical cord mesenchymal stem cells (hucMSCs). After preconditioning hucMSCs with agonists/inhibitors that target the Wnt/β-catenin pathway, we assessed both the production of exosomes and the therapeutic efficacy of the optimized exosomes in the context of diabetic wound healing, hoping to provide a safer, more stable and more effective option for clinical application. Results The Wnt signalling pathway agonist CHIR99021 increased exosome production by 1.5-fold without causing obvious changes in the characteristics of the hucMSCs or the size of the exosome particles. Further studies showed that CHIR99021 promoted the production of exosomes by facilitating exocytosis. This process was partly mediated by SNAP25. To further explore whether CHIR99021 changed the cargo that was loaded into the exosomes and its therapeutic effects, we performed proteomic and transcriptomic analyses of exosomes from primed and control hucMSCs. The results showed that CHIR99021 significantly upregulated the expression of proteins that are associated with cell migration and wound healing. Animal experiments confirmed that, compared to control hucMSC-derived exosomes, CHIR99021-pretreated hucMSC-derived exosomes (CHIR-Exos) significantly accelerated wound healing in diabetic mice, enhanced local collagen deposition, promoted angiogenesis, and reduced chronic inflammation. Subsequent in vitro experiments confirmed that the CHIR-Exos promoted wound healing by facilitating cell migration, inhibiting oxidative stress-induced apoptosis, and preventing cell cycle arrest. Conclusions The Wnt agonist CHIR99021 significantly increased exosome secretion by hucMSCs, which was partly mediated by SNAP25. Notably, CHIR99021 treatment also significantly increased the exosomal levels of proteins that are associated with wound healing and cell migration, resulting in enhanced acceleration of wound healing. All of these results suggested that pretreatment of hucMSCs with CHIR99021 not only promoted exosome production but also improved the exosome therapeutic efficacy, thus providing a promising option for large-scale clinical implementation and commercialization. Graphical Abstract

Based on the Dali I section of the Central Yunnan Diversion Dali Tunnel Project, an indoor model test of TBM traversing faulted geological conditions under high ground stress was carried out using the self-developed miniature TBM tunneling integrated test system to study the impact of faulting on the stability of TBM tunnels under high ground stress, analyze and summarize the change of stress and strain in the surrounding rock of the tunnel and the tunnel damage phenomenon, and reveal the disaster-causing mechanism of faulted geological jamming. The research results show that the TBM tunneling process first produces cracks in the surrounding rock at the upper part of the tunnel, and then a small drop in the vault when the TBM bores into the intersection of the two materials. The pressure on the surrounding rock in front of the palm face is mainly in the range of 0.43D～0.50D (D is the diameter of the hole), with the maximum increase of 1.19 times in the pressure on the surrounding rock. The internal rock displacement above the tunnel vault has four distinct phases of change with TBM tunneling. The closer the upper surrounding rock is to the tunnel contour line, the greater the deformation. When TBM passes through the fault interface, the deformation rate of the surrounding rock is the highest. The impact range on the internal displacement of the surrounding rock is mainly within 1.21D in front of the palm and 1.50D above it. The impact range of the fault is about 1.73H (H is the horizontal projection length of the fault interface), which is mainly caused by the loose sliding of the surrounding rock above the fault interface, and it is also easy to cause TBM jamming, Therefore, it is advisable to carry out advanced treatment at the fault interface during construction to reduce the risk of TBM operation.

Abstract Background Lung adenocarcinoma (LUAD) is a non-small cell carcinoma. Ribonuclease/angiogenin inhibitor 1 (RNH1) exerts multiple roles in virous cancers. E2F1 is a critical transcription factor involved in the LUAD development. Here, we analyze the expression of RNH1 in LUAD patients, investigate the biological function of RNH1 in LUAD, and demonstrate its potential mechanisms through E2F1 in LUAD. Methods In the present study, we presented the expression of RNH1 in LUAD based on the database and confirmed it by western blot detection of RNH1 in human LUAD tissues. Lentiviral infection was constructed to silence or overexpress RNH1 in NCI-H1395 and NCI-H1437 cells. We assess the role of RNH1 on proliferation in LUAD cells by MTT assay, colony formation assays, and cell cycle detection. Hoechst staining and flow cytometry were used to evaluate the effects of RNH1 on apoptosis of LUAD cells. The function of RNH1 in invasion and migration was investigated by Transwell assay. Dual luciferase assay, ChIP detection, and pull-down assay were conducted to explore the association of E2F1 in the maintenance of RNH1 expression and function. The regulation of E2F1 on the functions of RNH1 in LUAD cells was explored. Mouse experiments were performed to confirm the in-vivo role of RNH1 in LUAD. mRNA sequencing indicated that RNH1 overexpression altered the expression profile of LUAD cells. Results RNH1 expression in LUAD tissues of patients was presented in this work. Importantly, RNH1 knockdown improved the proliferation, migration and invasion abilities of cells and RNH1 overexpression produced the opposite effects. Dual luciferase assay proved that E2F1 bound to the RNH1 promoter (-1064 ∼ -1054, -1514 ∼ -1504) to reduce the transcriptional activity of RNH1. ChIP assay indicated that E2F1 DNA was enriched at the RNH1 promoter (-1148 ∼ -943, -1628 ∼ -1423). Pull-down assays also showed the association between E2F1 and RNH1 promoter (-1148 ∼ -943). E2F1 overexpression contributed to the malignant behavior of LUAD cells, while RNH1 overexpression reversed it. High-throughput sequencing showed that RNH1 overexpression induced multiple genes expression changes, thereby modulating LUAD-related processes. Conclusion Our study demonstrates that binding of E2F1 to the RNH1 promoter may lead to inhibition of RNH1 expression and thus promoting the development of LUAD.

Abstract The burgeoning need for extensive data processing has sparked enthusiasm for the development of a novel optical logic gate platform. In this study, junction field‐effect phototransistors based on molybdenum disulfide/Germanium (MoS2/Ge) heterojunctions are constructed as optical logic units. This device demonstrates a positive photoresponse that is attributed to the photoconductivity effect occurring upon irradiation with visible (Vis) light. Under the illumination of near‐infrared (NIR) optics with wavelengths within the communication band, the device shows a negative photoresponse, which is associated with the interlayer Coulomb interactions. The current state of the device can be effectively modulated as different logical states by precisely tuning the wavelength and power density of the optical. Within a 3 × 3 MoS2/Ge phototransistor array, five essentially all‐optical logic gates (“AND,” “OR,” “NAND,” “NOT,” and “NOR”) can be achieved in every signal unit. Furthermore, three complex all‐optical logical operations are demonstrated by integrating two MoS2/Ge phototransistors in series. Compared to electronic designs, these all‐optical logic devices offer a significant reduction in transistor number, with savings of 50–94% when implementing the above‐mentioned functions. These results present opportunities for the development of photonic chips with low power consumption, high fidelity, and large volumes.

Summary: Sensing is a critical function of artificial cells; however, this is challenging to realize using bottom-up approaches. Here, we present a protocol for building protocell membranes that sense cues important for redox biochemistry and signaling by combining synthetic phospholipids and natural lipids. We detail procedures for building giant unilamellar vesicles as protocell models that fluoresce in response to the biologically significant redox agents peroxynitrite, hydrogen peroxide, and hydrogen sulfide.For complete details on the use and execution of this protocol, please refer to (i) Gutierrez and Aggarwal et al.1 as well as (ii) Erguven and Wang et al.2 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

ABSTRACT Objective: Tibial plateau fractures are common intra-articular fractures that pose classification and treatment challenges for orthopedic surgeons. Objective: This study examines the value of 3D printing for classifying and planning surgery for complex tibial plateau fractures. Methods: We reviewed 54 complex tibial plateau fractures treated at our hospital from January 2017 to January 2019. Patients underwent preoperative spiral CT scans, with DICOM data processed using Mimics software. 3D printing technology created accurate 1:1 scale models of the fractures. These models helped subdivide the fractures into seven types based on the tibial plateau's geometric planes. Surgical approaches and simulated operations, including fracture reduction and plate placement, were planned using these models. Results: The 3D models accurately depicted the direction and extent of fracture displacement and plateau collapse. They facilitated the preoperative planning, allowing for precise reconstruction strategies and matching intraoperative details with the pre-printed models. Post-surgery, the anatomical structure of the tibial plateau was significantly improved in all 54 cases. Conclusion: 3D printing effectively aids in the classification and preoperative planning of complex tibial plateau fractures, enhancing surgical outcomes and anatomical restoration. Level of Evidence IV, Prospective Study.

As the second part of the investigation on vibration characteristics of ± 800 kV converter transformers, this part focuses on load conditions. A full-load thermal stability test is carried out on 12 YY and YD converter transformers in a converter station. Vibration, voltage, current, and other important information are collected by online monitoring devices. Vibration amplitude, vibration spectrum, dominant frequency, vibration power ratio of frequency band, vibration power entropy, and odd–even harmonic ratio under different load conditions are calculated and studied to evaluate the vibration state. Theoretical analyses of winding electromagnetic force and vibration acceleration are carried out and results show that the harmonic currents make the dominant frequency shift to 300 Hz or 400 Hz. Most vibration characteristics are sensitive to load rate changes. The odd–even harmonic ratio is sensitive to filter disconnection and reconnection. The results of this study reveal the vibration regularity and corresponding mechanism and can contribute to further study on vibration assessment of ± 800 kV converter transformers under load conditions.

For lack of study on the vibration characteristics of converter transformers, this paper studied the vibration signal analysis method and investigated the vibration characteristics of converter transformers during the commissioning of a ±800 kV converter station. The study comprised two parts including no-load and load conditions. In Part I, converter transformers are under no-load conditions. Vibration data are collected under conditions of no-load closing, no-load voltage rise with converters, and no-load voltage rise with DC lines. The vibration characteristics and mechanisms are studied based on the collected data. Several different vibration characteristics are introduced. Vibration power entropy, vibration total harmonic distortion, and recurrence rate are calculated under no-load conditions. Results show that vibration amplitude, vibration total harmonic distortion, and recurrence rate are sensitive to no-load closing. Vibration power entropy is sensitive to no-load voltage rise with DC lines. All these vibration characteristics are sensitive to converter unlocking. These characteristics show different and significant changes under different no-load conditions. Thus, it is vital to choose appropriate vibration characteristics when assessing the vibration state of converter transformers under different operating conditions. The study examines the vibration characteristics’ physical meanings and their changing mechanisms. It also summarizes distribution intervals and typical values of vibration characteristics. This research reveals the vibration regularity and corresponding mechanism. It provides a reference for vibration state assessment and early fault detection of ±800 kV converter transformers under no-load conditions.

BackgroundObservational data posits a correlation between reproductive traits and nonalcoholic fatty liver disease (NAFLD), but their causal inference is still unclear. This investigation seeks to elucidate the causal influence of reproductive traits on NAFLD and determine the intervening role of health condition and socioeconomic status in these connections.MethodsUtilizing a Mendelian Randomization (MR) approach, this research leveraged a comprehensive dataset from the Genome-wide Association Study (GWAS) database. The study incorporated body mass index, major depression, educational level, household income and Townsend deprivation index as intermediary variables. Initially, a bidirectional two-sample MR study was conducted to explore the genetic associations between reproductive traits and NAFLD. Then, two-step MR analyses were implemented to quantify the extent of mediation by these indicators. The weighted inverse variance method was the primary analytical approach, complemented by several sensitivity analyses to affirm the robustness of the MR assumptions. Finally, these findings were validated in the FinnGen research.ResultsThe bidirectional MR analysis indicated that earlier reproductive traits (age at menarche, age at first sexual intercourse, and age at first birth) were associated with an elevated risk of NAFLD, absent any evidence of the reverse relationship. Body mass index accounted for 35.64% of the association between premature menarche and NAFLD. Additionally, body mass index, major depression, educational level and household income mediated 41.65%, 14.35%, 37.88%, and 18.59% of the connection between early sexual intercourse and NAFLD, respectively. Similarly, these same variables elucidated 36.36%, 15.58%, 41.56%, and 22.73% of the correlation between younger age at first birth and NAFLD.ConclusionOur study elucidated the causal relationships between reproductive traits and NAFLD. Potential underlying mechanisms may involve factors such as body mass index, major depression, educational attainment and household income.

Abstract As a distributed learning paradigm, federated learning is supposed to protect data privacy without exchanging users’ local data. Even so, the gradient inversion attack, in which the adversary can reconstruct the original data from shared training gradients, has been widely deemed as a severe threat. Nevertheless, most existing researches are confined to impractical assumptions and narrow range of applications. To mitigate these shortcomings, we propose a comprehensive framework for gradient inversion attack, with well-designed algorithms for image and label reconstruction. For image reconstruction, we fully utilize the generative image prior, which derives from wide-used generative models, to improve the reconstructed results, by additional means of iterative optimization on mixed spaces and gradient-free optimizer. For label reconstruction, we design an adaptive recovery algorithm regarding real data distribution, which can adjust previous attacks to more complex scenarios. Moreover, we incorporate a gradient approximation method to efficiently fit our attack for FedAvg scenario. We empirically verify our attack framework using benchmark datasets and ablation studies, considering loose assumptions and complicated circumstances. We hope this work can greatly reveal the necessity of privacy protection in federated learning, while urge more effective and robust defense mechanisms.

Abstract Despite that surgical resection is widely regarded as the most effective approach to the treatment of liver cancer, its safety and efficacy upon centrally located hepatocellular carcinoma (HCC) remain unsatisfactory. In consequence, seeking an integrated treatment, like combined with adjuvant radiotherapy, to enhance the prognosis of patients is of critical importance. By recruiting patients undergoing surgical resection for centrally located HCC ranging from June 2015 to 2020, they were divided into liver resection combined with adjuvant radiotherapy (LR + RT) and mere liver resection (LR) groups. The calculation of propensity score and model of Cox proportional hazards regression were utilized. 193 patients were recruited in aggregation, containing 88 ones undergoing LR + RT, while 105 handled with LR. RT was verified to be an independent factor of prognosis for relapse (HR 0.60). In propensity-score analyses, significant association existed between adjuvant radiotherapy and better disease-free survival (DFS) (Matched, HR 0.60; Adjustment of propensity score, HR 0.60; Inverse probability weighting, HR 0.63). The difference of DFS was apparent within two groups (p value = 0.022), and RT significantly down-regulated early relapse (p value

Abstract A key factor limiting the development of silicone rubber insulating materials is their short service life in harsh operating environments. The establishment of a self‐healing system is desired to improve the long‐term operational performance of silicone rubber and effectively extend its service life. In this study, poly(urea‐formaldehyde) microcapsules containing polydimethylsiloxane healing agents are prepared and a dual‐component microcapsule self‐healing system for silicone rubber material is established and optimised. In addition, the key factors affecting the self‐healing performance (such as microcapsule size, rupture rate, and microcapsule doping amount) are investigated. It is found that when SYLGARDTM 184 is used as the healing agent and matrix, with a 4:6 (A:B) doping ratio of dual‐component microcapsules and 20 phr doping amount, the self‐healing efficiency is approximately 51%. Furthermore, increasing the microcapsule rupture rate and the interface strength between the healing agent and the matrix can effectively improve the self‐healing performance. The relationships between key factors and self‐healing performance are theoretically revealed. Based on the relationships, the microcapsule self‐healing system can be appropriately designed. The results of this paper can provide a reference for the development of long‐life silicone rubber insulating materials.

Flexible thermoelectric materials play an important role in smart wearables, such as wearable power generation, self-powered sensing, and personal thermal management. However, with the rapid development of Internet of Things (IoT) and artificial intelligence (AI), higher standards for comfort, multifunctionality, and sustainable operation of wearable electronics have been proposed, and it remains challenging to meet all the requirements of currently reported thermoelectric devices. Herein, we present a multifunctional, wearable, and wireless sensing system based on a thermoelectric knitted fabric with over 600 mm·s−1 air permeability and a stretchability of 120%. The device coupled with a wireless transmission system realizes self-powered monitoring of human respiration through an mobile phone application (APP). Furthermore, an integrated thermoelectric system was designed to combine photothermal conversion and passive radiative cooling, enabling the characteristics of being powered by solar-driven in-plane temperature differences and monitoring outdoor sunlight intensity through the APP. Additionally, we decoupled the complex signals of resistance and thermal voltage during deformation under solar irradiation based on the anisotropy of the knitted fabrics to enable the device to monitor and optimize the outdoor physical activity of the athlete via the APP. This novel thermoelectric fabric-based wearable and wireless sensing platform has promising applications in next-generation smart textiles.

Introduction: Human papillomavirus (HPV) integration can induce gene expression dysregulation by destroying higher-order chromatin structure in cervical cancer. Objectives: We established a 13q22 site-specific HPV16 gene knock-in cell model to interrogate the changes in chromatin structure at the initial stages of host cell malignant transformation. Methods: We designed a CRISPR-Cas9 system with sgRNA targeting 13q22 site and constructed the HPV16 gene donor. Cells were cotransfected, screened, and fluorescence sorted. The whole genome sequencing (WGS) was used to confirm the precise HPV16 gene integration site. Western blot and qRT-PCR were used to measure gene expression. In vitro and in vivo analysis were performed to estimate the tumorigenic potential of the HPV16 knock-in cell model. Combined Hi-C, chromatin immunoprecipitation and RNA sequencing analyses revealed correlations between chromatin structure and gene expression. We performed a coimmunoprecipitation assay with anti-PIBF1 antibody to identify endogenous interacting proteins. In vivo analysis was used to determine the role of PIBF1 in the tumor growth of cervical cancer cells. Results: We successfully established a 13q22 site-specific HPV16 gene knock-in cell model. We found that HPV integration promoted cell proliferation, invasion and stratified growth in vitro, and monoclonal proliferation in vivo. HPV integration divided the affected topologically associated domain (TAD) into two smaller domains, and the progesterone-induced blocking factor 1 (PIBF1) gene near the integration site was upregulated, although PIBF1 was not enriched at the domain boundary by CUT-Tag signal analysis. Moreover, PIBF1 was found to interact with the cohesin complex off chromatin to reduce contact domain formation by disrupting the cohesin ring-shaped structure, causing dysregulation of tumorigenesis-related genes. Xenograft experiments determined the role of PIBF1 in the proliferation in cervical cancer cells. Conclusion: We highlight that PIBF1, a potential chromatin structure regulatory protein, is activated by HPV integration, which provides new insights into HPV integration-driven cervical carcinogenesis.

Monkeypox (mpox) outbreak in 2022 has caused more than 91,000 cases, has spread to 115 countries, regions, and territories, and has thus attracted much attention. The stability of poxvirus particles in the environment is recognized as an important factor in determining their transmission. However, few studies have investigated the persistence of poxviruses on material surfaces under various environmental conditions, and their sensitivity to biocides. Here, we systematically measured the stability of vaccinia virus (VACV) under different environmental conditions and sensitivity to inactivation methods via plaque assay, quantitative real-time polymerase chain reaction (qPCR), and Gaussia luciferase (G-luciferase) reporter system. The results show that VACV is stable on the surface of stainless steel, glass, clothing, plastic, towel, A4 paper, and tissue and persists much longer at 4 °C and −20 °C, but is effectively inactivated by ultraviolet (UV) irradiation, heat treatment, and chemical reagents. Our study raises the awareness of long persistence of poxviruses in the environment and provides a simple solution to inactivate poxviruses using common disinfectants, which is expected to help the control and prevention of mpox virus and future poxvirus outbreaks.