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[Introduction] The widespread adoption of electric vehicles (EVs) enhances environmental sustainability during travel, yet it simultaneously elevates strain on the mains supply. To assess the impact of EV charging on the power grid, a specialized charging load calculation method is developed for large EV cluster on the basis of the Monte Carlo method. [Method] In this approach, EVs were categorized into six groups based on their usage: private EVs, electric buses, electric taxis, online ride-hailing EVs, official EVs, and logistics EVs. Typical battery performance parameters for each group were identified, and probability models were established to characterize the variability in their travel and charging patterns. By integrating group scale forecasts, daily charging schedules for each group were simulated through random sampling. Subsequently, the daily charging load for each group was calculated, culminating in the total charging load for the EV cluster through an aggregation method. [Result] The EV cluster in a southern province in 2030 was taken as the simulation case. [Conclusion] The case analysis reveals that the proposed approach can provide the daily charging load of various EV groups and the entire EV cluster. Furthermore, among all types of EVs, electric buses have the highest peak charging load at 4 639.5 MW, followed by that of private EVs (not higher than 70% of the electric buses' peak load), and electric taxis have the lowest peak charging load. The charging peak of the entire EV cluster occurs between 19:00 and 23:00 at night, and the peak load can reach 10.0927 GW.

The processing body (P-Body) is a membrane-less organelle with stress-resistant functions. Under stress conditions, cells preferentially translate mRNA that favors the stress response, resulting in a large number of transcripts unfavorable to the stress response in the cytoplasm. These non-translating mRNAs aggregate with specific proteins to form P-Bodies, where they are either stored or degraded. The protein composition of P-Bodies varies depending on cell type, developmental stage, and external environmental conditions. This review primarily elucidates the protein composition in plants and the assembly of P-Bodies, and focuses on the mechanisms by which various proteins within the P-Bodies of plants regulate mRNA decapping, degradation, translational repression, and storage at the post-transcriptional level in response to ethylene signaling and abiotic stresses such as drought, high salinity, or extreme temperatures. This overview provides insights into the role of the P-Body in plant abiotic stress responses.

Artificial intelligence (AI)-enabled technology has the potential to expand access to high-quality health information and health care services. Learning how diverse users interact with technology enables improvements to the AI model and the user interface, maximizing its potential benefit for a greater number of people. This narrative describes how technology developers, academic researchers, and representatives from a community-based organization collaborated to conduct a community-centered project on emerging health technologies. Our project team comprised representatives from Stanford Medicine, Google, and Santa Clara Family Health Plan’s Blanca Alvarado Community Resource Center. We aimed to understand the usability and acceptability of an AI-driven dermatology tool among East San Jose, California, community members. Specifically, our objectives were as follows: to test a model for cross-sector research of AI-based health technology; to determine the utility of the tool in an ethnically and age-diverse population; to obtain in-depth user experience feedback from participants recruited during community events; to offer free skin health consultations; and to provide resources for receiving follow-up care. We describe a collaborative approach in which each party contributed expertise: knowledge of the community from the community health partner, clinical expertise from the academic research institution, and software and AI expertise from the technology company. Through an iterative process, we identified important community needs, including technological, language, and privacy support. Our approach allowed us to recruit and engage a diverse cohort of participants, over 70% of whom preferred a language other than English. We distill learnings from planning and executing this case study that may help other collaborators bridge the gap between academia, industry, and community in AI health care innovation.

Abstract While KRAS mutation is the leading cause of low survival rates in lung cancer bone metastasis patients, effective treatments are still lacking. Here, we identified homeobox C10 (HOXC10) as a lynchpin in pan-KRAS-mutant lung cancer bone metastasis. Through RNA-seq approach and patient tissue studies, we demonstrated that HOXC10 expression was dramatically increased. Genetic depletion of HOXC10 preferentially impeded cell proliferation and migration in vitro. The bioluminescence imaging and micro-CT results demonstrated that inhibition of HOXC10 significantly reduced bone metastasis of KRAS-mutant lung cancer in vivo. Mechanistically, the transcription factor HOXC10 activated NOD1/ERK signaling pathway to reprogram epithelial-mesenchymal transition (EMT) and bone microenvironment by activating the NOD1 promoter. Strikingly, inhibition of HOXC10 in combination with STAT3 inhibitor was effective against KRAS-mutant lung cancer bone metastasis by triggering ferroptosis. Taken together, these findings reveal that HOXC10 effectively alleviates pan-KRAS-mutant lung cancer with bone metastasis in the NOD1/ERK axis-dependent manner, and support further development of an effective combinatorial strategy for this kind of disease.

Detecting relations between entities across multiple sentences in a document, referred to as document-level relation extraction, poses a challenge in natural language processing. Graph networks have gained widespread application for their ability to capture long-range contextual dependencies in documents. However, previous studies have often been limited to using only two to three types of nodes to construct document graphs. This leads to insufficient utilization of the rich information within the documents and inadequate aggregation of contextual information. Additionally, relevant relationship labels often co-occur in documents, yet existing methods rarely model the dependencies of relationship labels. In this paper, we propose the Interaction and Fusion of Rich Textual Information Network (IFRTIN) that simultaneously considers multiple types of nodes. First, we utilize the structural, syntactic, and discourse information in the document to construct a document graph, capturing global dependency relationships. Next, we design a regularizer to encourage the model to capture dependencies of relationship labels. Furthermore, we design an Adaptive Encouraging Loss, which encourages well-classified instances to contribute more to the overall loss, thereby enhancing the effectiveness of the model. Experimental results demonstrate that our approach achieves a significant improvement on three document-level relation extraction datasets. Specifically, IFRTIN outperforms existing models by achieving an F1 score improvement of 0.67% on Dataset DocRED, 1.2% on Dataset CDR, and 1.3% on Dataset GDA. These results highlight the effectiveness of our approach in leveraging rich textual information and modeling label dependencies for document-level relation extraction.

Abstract Infections caused by pathogenic Escherichia coli are a serious threat to human health, while conventional antibiotic susceptibility tests (AST) have a long turn-around time, and rapid antibiotic susceptibility methods are urgently needed to save lives in the clinic, reduce antibiotic misuse and prevent emergence of antibiotic-resistant bacteria. We optimized and validated the feasibility of a novel rapid AST based on SYBR Green I and Propidium Iodide (SGPI-AST) for E. coli drug susceptibility test. A total of 112 clinical isolates of E. coli were collected and four antibiotics (ceftriaxone, cefoxitin, imipenem, meropenem) were selected for testing. Bacterial survival rate of E. coli was remarkably linearly correlated with S value at different OD600 values. After optimizing the antibiotic concentrations, the sensitivity and specificity of SGPI-AST reached 100%/100%, 97.8%/100%, 100%/100% and 98.4%/99% for ceftriaxone, cefoxitin, imipenem and meropenem, respectively, and the corresponding concordances of the SGPI-AST with conventional AST were 1.000, 0.980, 1.000 and 0.979, respectively. The SGPI-AST can rapidly and accurately determine the susceptibility of E. coli clinical isolates to multiple antibiotics in 60 min, and has the potential to be applied to guide the precise selection of antibiotics for clinical management of infections caused by pathogenic E. coli.

Abstract In recent years, research on organ-on-a-chip technology has been flourishing, particularly for drug screening and disease model development. Fibroblasts and vascular endothelial cells engage in crosstalk through paracrine signaling and direct cell–cell contact, which is essential for the normal development and function of the heart. Therefore, to faithfully recapitulate cardiac function, it is imperative to incorporate fibroblasts and vascular endothelial cells into a heart-on-a-chip model. Here, we report the development of a human heart-on-a-chip composed of induced pluripotent stem cell (iPSC)-derived cardiomyocytes, fibroblasts, and vascular endothelial cells. Vascular endothelial cells cultured on microfluidic channels responded to the flow of culture medium mimicking blood flow by orienting themselves parallel to the flow direction, akin to in vivo vascular alignment in response to blood flow. Furthermore, the flow of culture medium promoted integrity among vascular endothelial cells, as evidenced by CD31 staining and lower apparent permeability. The tri-culture condition of iPSC-derived cardiomyocytes, fibroblasts, and vascular endothelial cells resulted in higher expression of the ventricular cardiomyocyte marker IRX4 and increased contractility compared to the bi-culture condition with iPSC-derived cardiomyocytes and fibroblasts alone. Such tri-culture-derived cardiac tissues exhibited cardiac responses similar to in vivo hearts, including an increase in heart rate upon noradrenaline administration. In summary, we have achieved the development of a heart-on-a-chip composed of cardiomyocytes, fibroblasts, and vascular endothelial cells that mimics in vivo cardiac behavior.

Abstract Earthquake-induced rock landslides in the eastern mountains of the Tibetan Plateau, especially landslides with weak interlayers pose a significant threat to major construction projects. Prestressed anchor cable is one of the main reinforcement methods of rock slopes. This paper combines shaking table model tests and numerical simulation to study the reinforcement effect and dynamic response characteristics of prestressed anchor cables applied to rock slopes with weak interlayers under strong earthquakes. The research results show that prestressed anchor cables can effectively reinforce slopes with weak interlayers. A small cable inclination, a small spacing and a high prestress are recommended in the seismic reinforcement design of prestressed anchor cable. In addition, the characteristics of slope progressive damage and prestress loss under the earthquake are found by the shaking table test. The results have been applied in hazard prevention and control of rock slopes on the Chengdu-Lanzhou Railway at the eastern Qinghai-Tibet Plateau.

Context The use of traditional Chinese medicine (TCM) for breast cancer patients inhibits tumor cell growth and proliferation, alleviates adverse reactions, and inhibits tumor recurrence and metastasis post-surgery. An assessment of its historical efficacy and an examination of the latest research trends are imperative to thoroughly leverage the potential of TCM for breast cancer treatment.Objective This study analyzes the published literature on TCM for breast cancer treatment using bibliometric analysis to determine the current state, identify hot spots, and discern trends, providing insight into research in this field.Methods TCM-based breast cancer treatment publications between 2003 and 2022 were retrieved from the Web of Science, China National Knowledge Infrastructure, Wanfang, and Duxiu databases. Visual analysis was performed using VOSviewer (V1.6.19) and CiteSpace (V6.3.R1) software. Examined metrics included the annual publication count, literature and journal, national and institutional contributions, author co-occurrence, keyword co-occurrence, keywords timeline, and keywords with citation bursts in this research field.Results and conclusion A total of 1080 English publications and 2617 Chinese publications were included in the analysis. China was the leading contributor of publications. High-frequency keywords such as ‘apoptosis’, ‘expression’, ‘in vivo’, ‘chemotherapy’, ‘triple-negative breast cancer’, and ‘lymphedema’ were identified from English and Chinese publications; ‘epithelial mesenchymal transition’ and ‘network pharmacology’ emerged as hotspots. The development of modern science, technology, and in-depth research can result in broader prospects for the research and application of TCM in breast cancer treatment, resulting in more effective solutions for the treatment of breast cancer and other malignant tumors.

Abstract Multiple Sclerosis (MS) is a heterogeneous inflammatory and neurodegenerative disease with an unpredictable course towards progressive disability. Treating progressive MS is challenging due to limited insights into the underlying mechanisms. We examined the molecular changes associated with primary progressive MS (PPMS) using a cross-tissue (blood and post-mortem brain) and multilayered data (genetic, epigenetic, transcriptomic) from independent cohorts. In PPMS, we found hypermethylation of the 1q21.1 locus, controlled by PPMS-specific genetic variations and influencing the expression of proximal genes (CHD1L, PRKAB2) in the brain. Evidence from reporter assay and CRISPR/dCas9 experiments supports a causal link between methylation and expression and correlation network analysis further implicates these genes in PPMS brain processes. Knock-down of CHD1L in human iPSC-derived neurons and knock-out of chd1l in zebrafish led to developmental and functional deficits of neurons. Thus, several lines of evidence suggest a distinct genetic-epigenetic-transcriptional interplay in the 1q21.1 locus potentially contributing to PPMS pathogenesis.

Abstract Background Hyperglycemia is a rapidly increasing risk factor for cancer mortality worldwide. However, the dose‒response relationship between glucose levels and all-cause mortality in cancer survivors is still uncertain. Methods We enrolled 4,491 cancer survivors (weighted population 19,465,739) from the 1999–2019 National Health and Nutrition Examination Survey (NHANES). Cancer survivors were defined based on the question of whether they had ever been diagnosed with cancer by a doctor or a health professional. Hemoglobin A1c (HbA1c) was selected in this study as a stable marker of glucose level. Mortality was ascertained by linkage to National Death Index records until December 31, 2019. Cox proportional hazard, Kaplan‒Meier survival curves and Restricted cubic spline regression models were used to evaluate the associations between HbA1c and all-cause mortality risk in cancer survivors. Results In NHANES, after adjusting for confounders, HbA1c had an independent nonlinear association with increased all-cause mortality in cancer survivors (nonlinear P value

Camellia fascicularis has important ornamental, medicinal, and food value. It also has tremendous potential for exploiting bioactivities. However, the bioactivities of secondary metabolites in C. fascicularis have not been reported. The structures of compounds were determined by spectral analysis and nuclear magnetic resonance (NMR) combined with the available literature on secondary metabolites of C. fascicularis leaves. In this study, 15 compounds were identified, including 5 flavonoids (1–5), a galactosylglycerol derivative (6), a terpenoid (7), 4 lignans (8–11), and 4 phenolic acids (12–15). Compounds 6–7 and 9–12 were isolated from the genus Camellia for the first time. The remaining compounds were also isolated from C. fascicularis for the first time. Evaluation of antioxidant and antimicrobial activities revealed that compounds 5 and 8–11 exhibited stronger antioxidant activity than the positive drug ascorbic acid, while compounds 7, 13, and 15 showed similar activity to ascorbic acid. The minimum inhibitory concentration (MIC) of antibacterial activity for compounds 5, 7, 9, 11, and 13 against Pseudomonas aeruginosa was comparable to that of the positive control drug tetracycline at a concentration of 62.50 µg/mL; other secondary metabolites inhibited Escherichia coli and Staphylococcus aureus at concentrations ranging from 125–250 µg/mL.

Polyester-cotton fabrics (PTCO) have excellent properties and are ubiquitous in daily life, but their serious flammability brings great safety hazards to people's lives. This study used phenylphosphonic acid (PPOA) and urea as raw materials to prepare a flame retardant named POU. PTCO/POU was prepared by the pad-dry-cure technique, and the performance was compared with that of PTCO/PPOA, revealing many interesting phenomena. Based on the gas phase and condensed phase flame-retardant mechanism brought by P/N synergy, PTCO/POU had better flame retardancy than PTCO/PPOA did. The damaged length was 6.7 cm, and the limiting oxygen index (LOI) value was 30.1%. The char residues after burning were complete and denser with a higher degree of graphitization. Thermogravimetric analysis showed that POU can significantly reduce the Rmax of PTCO, and improve its thermal stability in high temperature zones. The CCT results showed that PTCO/POU had the longest time to ignition and the smallest fire growth index, which was of great significance for reducing fire risk. The TG-FTIR results showed that the volatile products of PTCO/POU were greatly reduced, and during the burning process, NH3 was produced to dilute the concentration of combustible gases. In addition, PTCO/POU also had better whiteness performance than PTCO/PPOA did. This work greatly improved the flame retardancy of PTCO in a simple way and expanded its application prospects.

Abstract In this study, a shaking table test was conducted on long-short composite anti-slide piles, the development process and dynamic response of cracks in a pile-supported slope were observed, and the failure mechanism of the slope was explored. The experiment showed that the failure of the pile-supported slope under an earthquake was a gradual process; cracks first occur at the top of the slope, where the support action of the piles was weak. As the input seismic action increased, cracks developed downwards along the slope. Owing to the support effect of the long-short anti-slide composite piles, the transmission path of the cracks changed, and the cracks developed along the top of the composite piles, ultimately leading to overtop failure. When cracks appeared on the slope or near final failure, the acceleration response law of the supported slope undergone a sudden change, which was an important indicator of slope instability. The distribution of dynamic soil stress on the pile body was greatly affected by the input peak ground acceleration, and the maximum bending moment of the long-short composite anti-slide piles was located near the weak interlayer.

Abstract Background Transposable elements play a critical role in maintaining genome architecture during neurodevelopment. Short Interspersed Nuclear Elements (SINEs), a major subtype of transposable elements, are known to harbor binding sites for the CCCTC-binding factor (CTCF) and pivotal in orchestrating chromatin organization. However, the regulatory mechanisms controlling the activity of SINEs in the developing brain remains elusive. Results In our study, we conduct a comprehensive genome-wide epigenetic analysis in mouse neural precursor cells using ATAC-seq, ChIP-seq, whole genome bisulfite sequencing, in situ Hi-C, and RNA-seq. Our findings reveal that the SET domain bifurcated histone lysine methyltransferase 1 (SETDB1)-mediated H3K9me3, in conjunction with DNA methylation, restricts chromatin accessibility on a selective subset of SINEs in neural precursor cells. Mechanistically, loss of Setdb1 increases CTCF access to these SINE elements and contributes to chromatin loop reorganization. Moreover, de novo loop formation contributes to differential gene expression, including the dysregulation of genes enriched in mitotic pathways. This leads to the disruptions of cell proliferation in the embryonic brain after genetic ablation of Setdb1 both in vitro and in vivo. Conclusions In summary, our study sheds light on the epigenetic regulation of SINEs in mouse neural precursor cells, suggesting their role in maintaining chromatin organization and cell proliferation during neurodevelopment.

Abstract Photothermal therapy (PTT) is a promising cancer treatment method due to its ability to induce tumor-specific T cell responses and enhance therapeutic outcomes. However, incomplete PTT can leave residual tumors that often lead to new metastases and decreased patient survival in clinical scenarios. This is primarily due to the release of ATP, a damage-associated molecular pattern that quickly transforms into the immunosuppressive metabolite adenosine by CD39, prevalent in the tumor microenvironment, thus promoting tumor immune evasion. This study presents a photothermal nanomedicine fabricated by electrostatic adsorption among the Fe-doped polydiaminopyridine (Fe-PDAP), indocyanine green (ICG), and CD39 inhibitor sodium polyoxotungstate (POM-1). The constructed Fe-PDAP@ICG@POM-1 (FIP) can induce tumor PTT and immunogenic cell death when exposed to a near-infrared laser. Significantly, it can inhibit the ATP-adenosine pathway by dual-directional immunometabolic regulation, resulting in increased ATP levels and decreased adenosine synthesis, which ultimately reverses the immunosuppressive microenvironment and increases the susceptibility of immune checkpoint blockade (aPD-1) therapy. With the aid of aPD-1, the dual-directional immunometabolic regulation strategy mediated by FIP can effectively suppress/eradicate primary and distant tumors and evoke long-term solid immunological memory. This study presents an immunometabolic control strategy to offer a salvage option for treating residual tumors following incomplete PTT.

Abstract Traditional quarter‐wavelength parallel‐line couplers (QWPLC) in microstrip form suffer heavily in low directivity because of unbalanced even‐mode and odd‐mode phase velocities. Related schemes to improve directivity lead to complex structures and large dimensions. This study derives and validates an iterative synthesis method to design a high‐directivity microstrip coupler adopting a symmetric stepped‐impedance microstrip coupled line (SSIMCL). Given that the even‐mode and odd‐mode effective dielectric constants (EDCs) vary with the characteristic impedances, the authors take the EDCs of traditional QWPLC as the initial values for an SSIMCL, and the characteristic impedances and EDCs can be computed and converged in several iterations, resulting in good phase delay balance and high coupler directivity. A 20‐dB microstrip coupler working at 1 GHz with high directivity is designed, fabricated, and measured. The obtained maximum directivity is 47 dB and approximately 1 GHz, while the relative bandwidth with a directivity higher than 20 dB and a return loss better than 20 dB is larger than 70%. The novel microstrip coupler also features a compact, simple structure shorter than λg/4.

Abstract Background Diabetes is a common chronic metabolic disease. The progression of the disease promotes vascular inflammation and the formation of atherosclerosis, leading to cardiovascular disease. The coronary artery perivascular adipose tissue attenuation index based on CCTA is a new noninvasive imaging biomarker that reflects the spatial changes in perivascular adipose tissue attenuation in CCTA images and the inflammation around the coronary arteries. In this study, a radiomics approach is proposed to extract a large number of image features from CCTA in a high-throughput manner and combined with clinical diagnostic data to explore the predictive ability of vascular perivascular adipose imaging data based on CCTA for coronary heart disease in diabetic patients. Methods R language was used for statistical analysis to screen the variables with significant differences. A presegmentation model was used for CCTA vessel segmentation, and the pericoronary adipose region was screened out. PyRadiomics was used to calculate the radiomics features of pericoronary adipose tissue, and SVM, DT and RF were used to model and analyze the clinical data and radiomics data. Model performance was evaluated using indicators such as PPV, FPR, AAC, and ROC. Results The results indicate that there are significant differences in age, blood pressure, and some biochemical indicators between diabetes patients with and without coronary heart disease. Among 1037 calculated radiomic parameters, 18.3% showed significant differences in imaging omics features. Three modeling methods were used to analyze different combinations of clinical information, internal vascular radiomics information and pericoronary vascular fat radiomics information. The results showed that the dataset of full data had the highest ACC values under different machine learning models. The support vector machine method showed the best specificity, sensitivity, and accuracy for this dataset. Conclusions In this study, the clinical data and pericoronary radiomics data of CCTA were fused to predict the occurrence of coronary heart disease in diabetic patients. This provides information for the early detection of coronary heart disease in patients with diabetes and allows for timely intervention and treatment.

Hyperlipidemia is a prevalent chronic metabolic disease that severely affects human health. Currently, commonly used clinical therapeutic drugs are prone to drug dependence and toxic side effects. Dietary intervention for treating chronic metabolic diseases has received widespread attention. Rosa sterilis is a characteristic fruit tree in China whose fruits are rich in flavonoids, which have been shown to have a therapeutic effect on hyperlipidemia; however, their exact molecular mechanism of action remains unclear. Therefore, this study aimed to investigate the therapeutic effects of R. sterilis total flavonoid extract (RS) on hyperlipidemia and its possible mechanisms. A hyperlipidemic zebrafish model was established using egg yolk powder and then treated with RS to observe changes in the integral optical density in the tail vessels. Network pharmacology and molecular docking were used to investigate the potential mechanism of action of RS for the treatment of hyperlipidemia. The results showed that RS exhibited favorable hypolipidemic effects on zebrafish in the concentration range of 3.0–30.0 μg/mL in a dose-dependent manner. Topological and molecular docking analyses identified HSP90AA1, PPARA, and MMP9 as key targets for hypolipidemic effects, which were exerted mainly through lipolytic regulation of adipocytes and lipids; pathway analysis revealed enrichment in atherosclerosis, chemical carcinogenic-receptor activation pathways in cancers, and proteoglycans in prostate cancer and other cancers. Mover, chinensinaphthol possessed higher content and better target binding ability, which suggested that chinensinaphthol might be an important component of RS with hypolipidemic active function. These findings provide a direction for further research on RS interventions for the treatment of hyperlipidemia.

In this study, slow strain rate test (SSRT), X-ray photoelectron spectroscopy (XPS), electrochemical impedance spectroscopy (EIS), and scanning electron microscopy (SEM) were used to investigate the stress corrosion behavior of 316L austenitic stainless steel in 50 wt% NaOH solution at 100 °C. In addition, the electrochemical properties of the material were characterized using the EIS technique, and the composition of the corrosion product film was analyzed by XPS. Results show that the mechanical properties of materials deteriorate as the strain rate decreases in the stress corrosion test. However, when the applied strain rate is less than a certain strain rate, the deterioration of mechanical properties tends to be stable. Moreover, appropriate equivalent circuit models are fitted for the stress corrosion behavior of 316L austenitic stainless steel in hot NaOH solution, which can be used to analyze the stress corrosion behavior under various working conditions.

Abstract In the process of conservation mounting, starch paste made from wheat flour is the glue of choice to paste reinforcing strips and backing papers, often Xuan paper, for mending and decorating aged and damaged paper-based Chinese artworks. To keep objects intact and select appropriate conservation materials, this research explored the applicability of near-infrared (NIR) spectroscopy coupled with multivariate analysis for the characterization of contemporary unsized Xuan paper with and without starch. In particular, partial least squares (PLS) regression was used to predict the degree of polymerization (DP) of the paper, i.e., one of the most important properties of paper materials, and principal component analysis (PCA) was used to detect starch and to distinguish between papers with different amounts of starch. Using 12 contemporary unsized Xuan papers, the NIR-PLS method for DP prediction was validated, and the best-performed model was generated using the logarithmic transformation of DP−1 as a response variable, with root mean square error of prediction (RMSEP) of DP 128. The NIR-PCA method was also found to be applicable to separate starch-free papers and papers treated with starch, and the results indicate that the higher the content of starch, the better PCA classification performs. This research provides supporting data for the non-destructive characterization of Xuan paper-based objects and differentiates between Xuan paper before and after treatment with starch.

Abstract Background The key to enhancing the efficacy of antagonistic regimens in pregnancy is to better synchronize follicular growth during cycles of controlled ovarian stimulation (COS), especially in patients with diminished ovarian reserve (DOR). During in vitro fertilization-embryo transfer (IVF-ET) treatment, luteal phase estrogen pretreatment may enhance follicular development synchronization and yield of mature oocytes. However, the effect of estrogen pretreatment in DOR patients with elevated basal follicle-stimulating hormone (FSH) levels has not been well studied. Methods We retrospectively analyzed the clinical data of patients with elevated basal FSH levels and DOR (401 cycles) who underwent IVF/intracytoplasmic monosperm injection (ICSI)-assisted conception. Both groups were treated with a flexible gonadotropin-releasing hormone (GnRH) antagonist regimen and were further divided into two groups according to whether they received luteal estrogen pretreatment. There were 79 patients in the estrogen pretreatment group and 322 patients in the control group. On the second day of the menstrual cycle, gonadotropin (Gn) stimulation of the ovaries was initiated. The general characteristics, clinical, biological parameters and outcomes of the two groups were compared. Results The basic profiles of the two groups were similar (P > 0.05). More patients in the pretreatment group showed FSH rebound after gonadotropin (Gn) initiation, resulting in a significantly higher number of Gn days and total Gn than those in the control group (P 0.05). Conclusions The use of luteal phase estrogen pretreatment in patients with elevated basal FSH combined with DOR resulted in high FSH levels after the release of negative feedback, which was detrimental to early follicular growth, did not increase the follicular output rate, may have increased the use and duration of controlled ovarian stimulation drugs, and did not increase the number of eggs gained or improve clinical outcomes.

Abstract Background The maintenance of mitochondrial homeostasis is critical for tumor initiation and malignant progression because it increases tumor cell survival and growth. The molecular events controlling mitochondrial integrity that facilitate the development of hepatocellular carcinoma (HCC) remain unclear. Here, we report that UBX domain-containing protein 1 (UBXN1) hyperactivation is essential for mitochondrial homeostasis and liver tumorigenesis. Methods Oncogene-induced mouse liver tumor models were generated with the Sleeping Beauty (SB) transposon delivery system. Assessment of HCC cell growth in vivo and in vitro, including tumour formation, colony formation, TUNEL and FACS assays, was conducted to determine the effects of UBXN1 on HCC cells, as well as the involvement of the UBXN1-prohibitin (PHB) interaction in mitochondrial function. Coimmunoprecipitation (Co-IP) was used to assess the interaction between UBXN1 and PHB. Liver hepatocellular carcinoma (LIHC) datasets and HCC patient samples were used to assess the expression of UBXN1. Results UBXN1 expression is commonly upregulated in human HCCs and mouse liver tumors and is associated with poor overall survival in HCC patients. UBXN1 facilitates the growth of human HCC cells and promotes mouse liver tumorigenesis driven by the NRas/c-Myc or c-Myc/shp53 combination. UBXN1 interacts with the inner mitochondrial membrane protein PHB and sustains PHB expression. UBXN1 inhibition triggers mitochondrial damage and liver tumor cell apoptosis. Conclusions UBXN1 interacts with PHB and promotes mitochondrial homeostasis during liver tumorigenesis.

Abstract Background Despite the existence of several Randomized Controlled Trials (RCTs) investigating Low-Dose Computed Tomography (LDCT) as a guide in lung biopsies, conclusive findings remain elusive. To address this contention, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of LDCT-guided lung biopsies. Methods A comprehensive search across major databases identified RCTs comparing the effectiveness of LDCT-guided with Standard-Dose Computed Tomography (SDCT)-guided lung biopsies. Subsequently, we utilized a random-effects model meta-analysis to assess diagnostic accuracy, radiation dose, operation duration, and clinical complications associated with these procedures. Results Out of 292 scrutinized studies, six RCTs representing 922 patients were included in the final analysis. Results indicated the differences between the LDCT and SDCT groups were not different with statistical significance in terms of diagnostic accuracy rates (Intent-to-Treat (ITT) populations: Relative Risk (RR) 1.01, 95% Confidence interval [CI] 0.97–1.06, p = 0.61; Per-Protocol (PP) populations: RR 1.01, 95% CI 0.98–1.04, p = 0.46), incidence of pneumothorax (RR 1.00, 95% CI 0.75–1.35, p = 0.98), incidence of hemoptysis (RR 0.95, 95% CI 0.63–1.43, p = 0.80), and operation duration (minutes) (Mean Differences [MD] -0.34, 95% CI -1.67-0.99, p = 0.61). Notably, LDCT group demonstrated a lower radiation dose (mGy·cm) with statistical significance (MD -188.62, 95% CI -273.90 to -103.34, p

Abstract Background We previously conducted a case-control study and found that exposure to electronic screen before nocturnal sleep was associated with hypertensive disorders in pregnancy (HDP). Hence, we carried out this cohort study aiming to identify the effects of screen exposure time on the incidence rate and severity of HDP. Methods A retrospective cohort study was conducted from January 2022 and July 2022 from three hospitals in Wuxi and Changzhou cities. A total of 732 women were recruited and the information included socio-demographic characteristics, screen exposure and outcomes. Generalized estimating equations and binary non-conditional logistic models were applied to multivariate analysis, calculating the odds ratios (ORs) and 95% confidence intervals (CIs) of screen exposure time. Results The duration order of total screen time was smartphone > computer > television, while the duration order of screen time before nocturnal sleep was smartphone > television > computer. Multivariate analyses showed that the susceptibility of HDP among women who exposed to television before nocturnal sleep was 81.5% percent higher than those not exposed (P = 0.018, OR[95%CI] = 1.815[1.106–2.981]). In addition, total daily exposure time of television in the third trimester of pregnancy significantly increased the severity of HDP (P = 0.021, OR[95%CI] = 3.641[1.213–10.927]). Conclusions Based on this preliminary study, we would suggest that pregnant women do not watch television before nocturnal sleep. While in the third trimester of pregnancy, total exposure time of television should be limited. Investigations from other areas and experimental studies should be conducted to verify the conclusion.

Abstract Background Osteosarcoma (OS) is the most common primary malignant bone tumor and is highly prone to metastasis. OS can metastasize to the lymph node (LN) through the lymphatics, and the metastasis of tumor cells reestablishes the immune landscape of the LN, which is conducive to the growth of tumor cells. However, the mechanism of LN metastasis of osteosarcoma and remodeling of the metastatic lymph node (MLN) microenvironment is not clear. Methods Single-cell RNA sequencing of 18 samples from paracancerous, primary tumor, and lymph nodes was performed. Then, new signaling axes closely related to metastasis were identified using bioinformatics, in vitro experiments, and immunohistochemistry. The mechanism of remodeling of the LN microenvironment in tumor cells was investigated by integrating single-cell and spatial transcriptomics. Results From 18 single-cell sequencing samples, we obtained 117,964 cells. The pseudotime analysis revealed that osteoblast(OB) cells may follow a differentiation path from paracancerous tissue (PC) → primary tumor (PT) → MLN or from PC → PT, during the process of LN metastasis. Next, in combination of bioinformatics, in vitro and in vivo experiments, and immunohistochemistry, we determined that ETS2/IBSP, a new signal axis, might promote LN metastasis. Finally, single-cell and spatial dissection uncovered that OS cells could reshape the microenvironment of LN by interacting with various cell components, such as myeloid, cancer-associated fibroblasts (CAFs), and NK/T cells. Conclusions Collectively, our research revealed a new molecular mechanism of LN metastasis and clarified how OS cells influenced the LN microenvironment, which might provide new insight for blocking LN metastasis.

Abstract Diabetic foot ulcer (DFU) is a serious complication of diabetic patients which negatively affects their foot health. This study aimed to estimate the role and mechanism of the miR‐200 family in DNA damage of diabetic wound healing. Human foreskin fibroblasts (HFF‐1 cells) were stimulated with high glucose (HG). Db/db mice were utilized to conduct the DFU in vivo model. Cell viability was evaluated using 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide assays. Superoxide dismutase activity was determined using detection kits. Reactive oxygen species determination was conducted via dichlorodihydrofluorescein‐diacetate assays. Enzyme‐linked immunosorbent assay was used to evaluate 8‐oxo‐7,8‐dihydro‐2′deoxyguanosine levels. Genes and protein expression were analyzed by quantitative real‐time polymerase chain reaction, western blotting, or immunohistochemical analyses. Luciferase reporter gene and RNA immunoprecipitation assays determined the interaction with miR‐200a/b/c‐3p and GLI family zinc finger protein 2 (GLI2) or ataxia telangiectasia mutated (ATM) kinase. HG repressed cell proliferation and DNA damage repair, promoted miR‐200a/b/c‐3p expression, and suppressed ATM and GLI2. MiR‐200a/b/c‐3p inhibition ameliorated HG‐induced cell proliferation and DNA damage repair repression. MiR‐200a/b/c‐3p targeted ATM. Then, the silenced ATM reversed the miR‐200a/b/c‐3p inhibition‐mediated alleviative effects under HG. Next, GLI2 overexpression alleviated the HG‐induced cell proliferation and DNA damage repair inhibition via miR‐200a/b/c‐3p. MiR‐200a/b/c‐3p inhibition significantly promoted DNA damage repair and wound healing in DFU mice. GLI2 promoted cell proliferation and DNA damage repair by regulating the miR‐200/ATM axis to enhance diabetic wound healing in DFU.

Abstract Background and aims Patients undergoing maintenance hemodialysis (MHD) experience increased mortality and cardiovascular disease (CVD) risks; however, the potential connection between pinch strength (PS) and the prognosis of these patients remains unknown. Consequently, this study aimed to comprehensively assess the influence of PS and handgrip strength (HGS) on both survival and cardiovascular events (CVE) in patients undergoing MHD. Methods Data were gathered from patients undergoing MHD at the Hemodialysis Center of Guangzhou Red Cross Hospital in March 2021. We performed a retrospective follow-up spanning 24 months, with death serving as the primary endpoint for observation and CVE as the secondary endpoint. Multifactorial Cox regression analysis, Kaplan–Meier survival curves, trend tests, and restricted cubic spline were applied to explore the association. Results During a 24-month follow-up, data were collected from 140 patients undergoing MHD with an average age of 66.71 ± 12.61 years. Among them, 52 (37.14%) experienced mortality, whereas 36 (40.00%) had CVE without baseline CVD. Kaplan–Meier survival curves demonstrated better survival rates and reduced CVE risk for patients in the second, third, and fourth quartiles compared with those in the first quartile for PS. Adjusted analyses in different models revealed higher PS levels were independently associated with all-cause mortality (major model, model 4, HR, 0.78; 95% CI, 0.64–0.95) but not with CVE risk (unadjusted HR, 0.90; 95% CI, 0.77–1.05). Compared with lower quartile PS levels, higher PS levels significantly reduced all-cause mortality (HR, 0.31; 95% CI, 0.10–1.02), and this trend remained consistent (P for trend = 0.021). Finally, the restricted cubic spline method using different models showed a linear relationship between PS and all-cause mortality (P > 0.05), when PS exceeded 4.99 kg, the all-cause mortality of MHD patients significantly decreased. Conclusions PS was independently associated with all-cause mortality but not with CVE in patients undergoing MHD.

In the field of ophthalmology, orbital fat prolapse under the upper eyelid is less recognized than subconjunctival orbital fat prolapse. Despite its occasional occurrence in clinical practice, this condition is often inadequately understood and incorrectly classified due to its subtle manifestations and the limited number of focused studies. Typically affecting young patients, the prolapse is located subcutaneously in the mid-upper eyelid, resulting in a pseudo-occlusion. This study aims to investigate this specific ocular anomaly, we delineate the clinical presentations, surgical interventions, and differential diagnoses of this condition through three representative cases, proposing its classification as a distinct disease entity named Upper Eyelid Subcutaneous Orbital Fat Prolapse (UESOFP).

This paper studies how to integrate the smart charging of large-scale electric vehicles (EVs) into the generation and storage expansion planning (GSEP), while analyzing the impact of smart charging on the GSEP of a real power system in south China. For this purpose, a random simulation-based method is first developed to provide the tractable formulations of the adjustable charging load and reserve provision from EVs. This method avoids the unrealistic assumption that EVs drive and charge every day, which often exists in prior relevant approaches. Based on the random simulation, this paper proposes a novel GSEP optimization model which incorporates the weekly adjustable charging load of EVs. In the proposed model, the total charging load of EVs can be co-optimized with the investment and operational decisions of various generation and storage units. This GSEP model is applied to a provincial power system in south China. The numerical results show that the implementation of smart charging can significantly alter the decisions of GSEP. As the participation rate of smart charging improves from 0% to 90%, there is an additional 1,800 MW installation in wind and solar power, while the need to build new batteries is noticeably reduced; also, depending on the level of EV uptake, the annualized total system cost decreases by 5.11%–7.57%, and the curtailment of wind and solar power is reduced by 10.34%–19.64%. Besides, numerical tests reveal that the traditional assumption that EVs drive and charge every day can mislead the evaluation of adjustable charging load and overestimate the daily charging power peak by averagely 24.72%.

BackgroundCardiac lipid metabolism reprogramming is recognized as a critical pathological factor in the progression of chronic heart failure (CHF). The therapeutic potential of digilanid C and electroacupuncture stimulation (ES) in enhancing lipid metabolism and cardiac function has been established. However, the optimal synergistic regulatory strategies of these interventions on cardiac lipid metabolism have yet to be elucidated.MethodsThis study aimed to comprehensively evaluate the impact of a digilanid C-ES combination on cardiac steatosis remodeling in CHF. Assessments were conducted across various dimensions, including myocardial oxygen consumption, mitochondrial function, and lipid metabolism. Additionally, we sought to uncover the underlying neuromolecular mechanisms.ResultsOur findings, at both molecular and morphological levels, indicated that the synergistic application of digilanid C and ES significantly inhibited myocardial fibrosis and steatosis. This combination therapy facilitated the repair of cardiac neuro-vascular uncoupling and induced a reprogramming of lipid metabolism. Notably, the digilanid C-ES combination ameliorated cardiomyocyte apoptosis and enhanced mitochondrial biogenesis in CHF, leading to a restructured energy supply pattern. Cardiac immunofluorescence analyses revealed the aggregation of cardiac glial cells (CGCs) at sites of abnormal neurovascular coupling, a response to cardiac lipid degeneration. This was accompanied by a marked reduction in the abnormally elevated expression of interleukin 6 (IL-6) and glutamatergic signaling, which correlated with the severity of cardiac steatosis and the aberrant activation of CGCs. The combined therapy was found to activate the Janus kinase 1 (JAK1)/signal transducer and activator of transcription 3 (STAT3) pathway, effectively attenuated lipid accumulation and over-recruitment of CGCs and deprivation of glutamatergic nerves.ConclusionThese findings underscore the potential of digilanid C and ES combination therapy as a novel approach to modulate the complex interplay between neurovascular dynamics and metabolic dysregulation in CHF.

BackgroundThere is a lack of evidence regarding the effectiveness of empowerment healthy education for caregivers of Alzheimer’s patients.ObjectiveTo explore the effectiveness of the intervention of health education guided by empowerment theory on dementia knowledge, caregiving readiness, positive caregiving emotions, anxiety, and depression in informal Alzheimer’s disease caregivers.DesignA single-blinded, randomized controlled trial.SettingA teaching hospital in Tianjin, China.ParticipantsEighty caregivers of Alzheimer’s disease patients.MethodsParticipants were recruited from the hospital and randomly assigned to either experimental or control group. The experimental group underwent a 12-weeks, one-to-one intervention of six session lasting 45–60 min each. The control group received conventional health education. Outcome measures included dementia knowledge, caregiver readiness (primary outcomes), positive caregiving emotions, anxiety, and depression (secondary outcomes).ResultsAfter 12 weeks, the intervention group exhibited significantly higher levels of dementia knowledge, caregiver readiness, and positive caregiving emotions compared with the control group. Furthermore, levels of hospitalization-related anxiety and depression were lower in the intervention group. All study results of this study showed statistically significant differences (p

Pathogenic microorganisms with antibiotic resistance genes (ARGs) pose a serious threat to public health and soil ecology. Although new drugs and available antibacterial materials can kill ARG carriers but accidentally kill beneficial microorganisms. Therefore, the rapid enrichment and separation of ARGs and their carriers from soil is becoming an important strategy for controlling the diffusion of ARGs. Hydroxamate siderophore (HDS) has gained widespread attentions for its involvement in trace element transfer among microorganisms in the soil environment, we thus explored an in-situ trapping-enrichment method for ARGs and their carriers via a small molecular HDS secreted by Pseudomonas fluorescens HMP01. In this study, we demonstrate that HDS significantly in-situ traps and enriches certain ARGs, including chloramphenicol, MLS, rifamycin, and tetracycline resistance genes in the soil environment. The enrichment efficiencies were 1473-fold, 38-fold, 17-fold, and 5-fold, respectively, higher than those in the control group. Specifically, the primary enriched ARGs were rpoB, mphL, catB2, and tetA(60), and Bacillus, Rhizobium, Rossellomorea, and Agrobacterium were hosts for these ARGs. This enrichment was caused by the upregulation of chemotaxis genes (e.g., cheW, cheC, and cheD) and rapid biofilm formation within the enriched bacterial population. Notably, representative ARGs such as cat, macB, and rpoB were significantly reduced by 36%, 85.7%, and 72%, respectively, in the paddy soil after HDS enrichment. Our research sheds light on the potential application of siderophore as a rapping agent for the eco-friendly reduction of ARGs and their carriers in soil environments.

Background Gastric intestinal metaplasia(GIM) is an independent risk factor for GC, however, its pathogenesis is still unclear. Ferroptosis is a new type of programmed cell death, which may be involved in the process of GIM. The purpose of this study was to analyze the expression of ferroptosis-related genes (FRGs) in GIM tissues and to explore the relationship between ferroptosis and GIM. Method The results of GIM tissue full transcriptome sequencing were downloaded from Gene Expression Omnibus(GEO) database. R software (V4.2.0) and R packages were used for screening and enrichment analysis of differentially expressed genes(DEGs). The key genes were screened by least absolute shrinkage and selection operator(LASSO) and support vector machine-recursive feature elimination(SVM-RFE) algorithm. Receiver operating characteristic(ROC) curve was used to evaluate the diagnostic efficacy of key genes in GIM. Clinical samples were used to further validate hub genes. Results A total of 12 differentially expressed ferroptosis-related genes (DEFRGs) were identified. Using two machine learning algorithms, GOT1, ALDH3A2, ACSF2 and SESN2 were identified as key genes. The area under ROC curve (AUC) of GOT1, ALDH3A2, ACSF2 and SESN2 in the training set were 0.906, 0.955, 0.899 and 0.962 respectively, and the AUC in the verification set were 0.776, 0.676, 0.773 and 0.880, respectively. Clinical samples verified the differential expression of GOT1, ACSF2, and SESN2 in GIM. Conclusion We found that there was a significant correlation between ferroptosis and GIM. GOT1, ACSF2 and SESN2 can be used as diagnostic markers to effectively identify GIM.

IntroductionAmong cultivated tea plants (Camellia sinensis), only four mitogenomes for C. sinensis var. assamica (CSA) have been reported so far but none for C. sinensis var. sinensis (CSS). Here, two mitogenomes of CSS (CSSDHP and CSSRG) have been sequenced and assembled.MethodsUsing a combination of Illumina and Nanopore data for the first time. Comparison between CSS and CSA mitogenomes revealed a huge heterogeneity.ResultsThe number of the repetitive sequences was proportional to the mitogenome size and the repetitive sequences dominated the intracellular gene transfer segments (accounting for 88.7%- 92.8% of the total length). Predictive RNA editing analysis revealed that there might be significant editing in NADH dehydrogenase subunit transcripts. Codon preference analysis showed a tendency to favor A/T bases and T was used more frequently at the third base of the codon. ENc plots analysis showed that the natural selection play an important role in shaping the codon usage bias, and Ka/Ks ratios analysis indicated Nad1 and Sdh3 genes may have undergone positive selection. Further, phylogenetic analysis shows that six C. sinensis clustered together, with the CSA and CSS forming two distinct branches, suggesting two different evolutionary pathway.DiscussionAltogether, this investigation provided an insight into evolution and phylogeny relationship of C. sinensis mitogenome, thereby enhancing comprehension of the evolutionary patterns within C. sinensis species.

Summary: Our understanding of human fetal cerebellum development during the late second trimester, a critical period for the generation of astrocytes, oligodendrocytes, and unipolar brush cells (UBCs), remains limited. Here, we performed single-cell RNA sequencing (scRNA-seq) in human fetal cerebellum samples from gestational weeks (GWs) 18–25. We find that proliferating UBC progenitors distribute in the subventricular zone of the rhombic lip (RLSVZ) near white matter (WM), forming a layer structure. We also delineate two trajectories from astrogenic radial glia (ARGs) to Bergmann glial progenitors (BGPs) and recognize oligodendrogenic radial glia (ORGs) as one source of primitive oligodendrocyte progenitor cells (PriOPCs). Additionally, our scRNA-seq analysis of the trisomy 21 fetal cerebellum at this stage reveals abnormal upregulated genes in pathways such as the cell adhesion pathway and focal adhesion pathway, which potentially promote neuronal differentiation. Overall, our research provides valuable insights into normal and abnormal development of the human fetal cerebellum.

Abstract Constructing composite solid electrolytes (CSEs) integrating the merits of inorganic and organic components is a promising approach to developing high‐performance all‐solid‐state lithium metal batteries (ASSLMBs). CSEs are now capable of achieving homogeneous and fast Li‐ion flux, but how to escape the trade‐off between mechanical modulus and adhesion is still a challenge. Herein, a strategy to address this issue is proposed, that is, intercalating highly conductive, homogeneous, and viscous‐fluid ionic conductors into robust coordination laminar framework to construct laminar solid electrolyte with homogeneous and fast Li‐ion conduction (LSE‐HFC). A 9 µm‐thick LSH‐HFC, in which poly(ethylene oxide)/succinonitrile is adsorbed by coordination laminar framework with metal–organic framework nanosheets as building blocks, is used here as an example to determine the validity. The Li‐ion transfer mechanism is verified and works across the entire LSE‐HFC, which facilitates homogeneous Li‐ion flux and low migration energy barriers, endowing LSE‐HFC with high ionic conductivity of 5.62 × 10−4 S cm−1 and Li‐ion transference number of 0.78 at 25 °C. Combining the outstanding mechanical strength against punctures and the enhanced adhesion force with electrodes, LSE‐HFC harvests uniform Li plating/stripping behavior. These enable the realization of high‐energy‐density ASSLMBs with excellent cycling stability when being assembled as LiFePO4/Li and LiNi0.6Mn0.2Co0.2O2/Li cells.

Purpose: This study aimed to assess the stress distribution in pulpotomized primary molars with different types of restorative materials using 3D-finite element analysis (FEA), and provide valuable insights into the selection and application of restorative materials, with the ultimate goal of reducing the risk of pulpotomy failure and protecting residual dental tissue. Methods: Four 3D models of pulpotomized primary molars with different restorative materials according to the material and its elastic modulus were analysed: resin composite, stainless steel crowns (SSCs), prefabricated zirconia crowns and endocrowns. The food layer was also designed before vertical and bucco-lingual forces were applied to simulate physiological masticatory conditions. The results were obtained by colorimetric graphs of the von Mises stresses (VMS) in the restoration and tooth remnant. The maximum shear stress on the bonding interfaces and pressure stress on the Mineral trioxide aggregate (MTA)-pulp interfaces were recorded. Results: The results of the 3D-FEA showed that all restorative materials generated stresses and strains on the tooth structure after pulpotomy. In the resin composite group, the marginal enamel exhibited the highest stress peaks. In the zirconia crown and SSC groups, there was a concentration of stress at the dentin-restoration margin. The shear stress concentrations were mainly at the adhesive margins, with lower levels around endocrowns compared to other groups. MTA in the resin composite group experienced more VMS than in the other group. The resin composite group also generated relatively higher pressure stress values at the MTA-pulp interface compared to the other groups. Significance: In the model of primary teeth following pulpotomy, the three types of restorations covering the occlusal surface can effectively reduce the stress on pulp capping materials under occlusal loads, thereby potentially decreasing the risk of pulpotomy failure. In addition, the group of endocrowns demonstrated reduced stress at the bonding interface and in the stress concentration zone near the dentist-restoration edge, making them more effective at protecting residual dental tissue.

Histone methylation can affect chromosome structure and binding to other proteins, depending on the type of amino acid being modified and the number of methyl groups added, this modification may promote transcription of genes (H3K4me2, H3K4me3, and H3K79me3) or reduce transcription of genes (H3K9me2, H3K9me3, H3K27me2, H3K27me3, and H4K20me3). In addition, advances in tumor immunotherapy have shown that histone methylation as a type of protein post-translational modification is also involved in the proliferation, activation and metabolic reprogramming of immune cells in the tumor microenvironment. These post-translational modifications of proteins play a crucial role in regulating immune escape from tumors and immunotherapy. Lysine methyltransferases are important components of the post-translational histone methylation modification pathway. Lysine methyltransferase 2C (KMT2C), also known as MLL3, is a member of the lysine methyltransferase family, which mediates the methylation modification of histone 3 lysine 4 (H3K4), participates in the methylation of many histone proteins, and regulates a number of signaling pathways such as EMT, p53, Myc, DNA damage repair and other pathways. Studies of KMT2C have found that it is aberrantly expressed in many diseases, mainly tumors and hematological disorders. It can also inhibit the onset and progression of these diseases. Therefore, KMT2C may serve as a promising target for tumor immunotherapy for certain diseases. Here, we provide an overview of the structure of KMT2C, disease mechanisms, and diseases associated with KMT2C, and discuss related challenges.

Summary: Background: In non-high-risk individuals, risk-category-based atherosclerotic cardiovascular disease (ASCVD) screening strategies may be more cost-effective than one-size-fits-all approaches. However, current decisions are constrained by a lack of research evidence. We aimed to explore appropriate risk-category-based screening interval strategies for non-high-risk individuals in ASCVD primary prevention in the Chinese population. Methods: We used data from 28,624 participants in the China Kadoorie Biobank (CKB) who had completed at least two field surveys. The risk assessment tools were the 10-year ASCVD risk prediction models developed based on the CKB cohort. We constructed multistate Markov models to model disease progression and estimate transition probabilities between different risk categories. The total person-years spent unidentified in the high-risk state over a 10-year period were calculated for each screening interval protocol. We also estimated the number of ASCVD events prevented, quality-adjusted life years (QALYs) gained, and costs saved when compared to the 3-yearly screening protocol. Findings: When compared to the uniform 3-yearly protocol, most risk-category-based screening interval protocols would identify more high-risk individuals timely, thus preventing more ASCVD events and gaining QALYs. A few of them would reduce total health-care costs. The protocol, which used 6-year, 3-year, and 2-year screening intervals for low-risk, intermediate-low-risk, and intermediate-high risk individuals, was optimal, and would reduce the person-years spent unidentified in the high-risk category by 17.9% (95% CI: 13.1%–21.9%), thus preventing an estimated 113 thousand (95% CI: 83–138) hard ASCVD events for Chinese adults aged 30–79 over a 10-year period. When using a lower cost of statin therapy, more screening protocols would gain QALYs while saving costs. Interpretation: For the primary prevention of ASCVD, risk-category-based screening protocols outperformed the one-size-fits-all approach in the Chinese population. Funding: This work was supported by National Natural Science Foundation of China (82192904, 82388102, 82192900) and grants (2023YFC2509400) from the National Key R&D Program of China. The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up is supported by grants from the UK Wellcome Trust (212946/Z/18/Z, 202922/Z/16/Z, 104085/Z/14/Z, 088158/Z/09/Z), grants (2016YFC0900500) from the National Key R&D Program of China, National Natural Science Foundation of China (81390540, 91846303, 81941018), and Chinese Ministry of Science and Technology (2011BAI09B01).

In the context of the formidable challenge posed by global climate change, achieving high-quality and sustainable economic development has become a topic of widespread concern. Since the signing of the Kyoto Protocol, nations worldwide have actively engaged in the fight against climate change. As the largest emitter of greenhouse gases globally, China has introduced a series of low-carbon policies to attain its sustainability goals. Based on the panel data of 31 provinces in China from 2005 to 2019, this paper investigates the spatial spillover effects of the carbon Emission Trading Scheme (ETS) on the industrial structure upgrading and its transmission mechanisms by constructing spatial econometric models and a multiple mediation effect model. The results indicate that ETS exerts a promotional effect on industrial structure upgrading within policy pilot regions. However, in the peripheral areas outside the pilot regions, there exists a negative spillover effect, and the inhibitory effect is stronger than the promotional effect. Moreover, consumer upgrading and technological innovation emerge as two major pathways through which ETS stimulates the upgrading of industrial structures. Results from two sets of heterogeneity tests reveal that the impact of low-carbon policies on industrial structure upgrading is most pronounced in the eastern regions and areas characterized by high pollution.

Abstract Motivation Drug combination therapies have shown promise in clinical cancer treatments. However, it is hard to experimentally identify all drug combinations for synergistic interaction even with high-throughput screening due to the vast space of potential combinations. Although a number of computational methods for drug synergy prediction have proven successful in narrowing down this space, fusing drug pairs and cell line features effectively still lacks study, hindering current algorithms from understanding the complex interaction between drugs and cell lines. Results In this paper, we proposed a Permutable feature fusion network for Drug-Drug Synergy prediction, named PermuteDDS. PermuteDDS takes multiple representations of drugs and cell lines as input and employs a permutable fusion mechanism to combine drug and cell line features. In experiments, PermuteDDS exhibits state-of-the-art performance on two benchmark data sets. Additionally, the results on independent test set grouped by different tissues reveal that PermuteDDS has good generalization performance. We believed that PermuteDDS is an effective and valuable tool for identifying synergistic drug combinations. It is publicly available at https://github.com/littlewei-lazy/PermuteDDS . Scientific contribution First, this paper proposes a permutable feature fusion network for predicting drug synergy termed PermuteDDS, which extract diverse information from multiple drug representations and cell line representations. Second, the permutable fusion mechanism combine the drug and cell line features by integrating information of different channels, enabling the utilization of complex relationships between drugs and cell lines. Third, comparative and ablation experiments provide evidence of the efficacy of PermuteDDS in predicting drug-drug synergy.

Abstract Background Pelvic floor myofascial pain is one of the pelvic floor dysfunction diseases disturbing women after delivery. There is a lack of objective standardization for the diagnosis of pelvic floor myofascial pain due to the various symptoms and the dependence on the palpating evaluation. Ultrasound imaging has the advantages of safety, simplicity, economy and high resolution, which makes it an ideal tool for the assistant diagnosis of pelvic floor myofascial pain and evaluation after treatment. Methods This is a retrospective case-control study including women accepting evaluation of pelvic floor function at 6 weeks to 1 year postpartum. They were divided into pelvic floor myofascial pain group and normal control group. A BCL 10–5 biplane transducer was applied to observed their puborectalis. The length, minimum width, area, deficiency, deficiency length, deficiency width, deficiency area, rate of deficiency area, local thickening,angle between the tendinous arch of levator ani muscle and puborectalis of corresponding puborectalis in different groups were observed and measured. Results A total of 220 postpartum women participated in the study, with 77 in the pelvic floor myofascial pain group and 143 in the normal control group. The Intraclass correlation coefficient value was over 0.750, and Kappa ranged from 0.600 to 0.800. puborectalis deficiency (adjusted odds ratio = 11.625, 95% confidence interval = 4.557–29.658) and focal thickening (adjusted odds ratio = 16.891, 95% confidence interval = 1.819–156.805) were significantly associated with higher odds of having postpartum pelvic floor myofascial pain. Grayscale or the angle between the arch tendineus levator ani and puborectalis measurements on the pain side tended to be smaller than on the non-pain side in patients with unilateral puborectalis or iliococcygeus pain (P

Abstract Background To date, the extended Morrow procedure is considered the gold standard treatment for patients with obstructive hypertrophic cardiomyopathy who experience severe symptoms and are unresponsive to medication treatment. We therefore aimed to perform transapical intramyocardial septal microwave ablation to reduce the thickness of the interventricular septum myocardium in a minimally invasive method. Methods Fourteen swine were divided to form either a microwave ablation group (n = 7) or a sham group (n = 7). In the microwave ablation group, a transapical microwave antenna was inserted into the septum to ablate each myocardial segment at 40 W for 1 min, while in the sham group, the same operation was performed but without power output. We used echocardiography, electrocardiogram, during the operation. And added computerized tomography, cardiac nuclear magnetic resonance during follow-up. Results Segment hypokinesis was observed in all swine immediately following ablation. Compared with the sham group, the thickness of ablated segments in the ablation group decreased significantly 1 month post-operation (ablation group, 5.53 ± 1.00 mm vs. 8.03 ± 1.15 mm, respectively, P

Abstract Renal involvement is common in monoclonal gammopathy (MG); however, the same patient may have both MG and non-paraprotein-associated renal damage. Accordingly, distinguishing the cause of renal damage is necessary because of the different clinical characteristics and associated treatments. In this multicenter retrospective cohort study, we described the clinicopathological characteristics and prognosis of 703 patients with MG and renal damage in central China. Patients were classified as having MG of renal significance (MGRS), MG of undetermined significance (MGUS), or hematological malignancy. 260 (36.98%), 259 (36.84%), and 184 (26.17%) had MGRS, MGUS, and hematological malignancies, respectively. Amyloidosis was the leading pattern of MGRS (74.23%), followed by thrombotic microangiopathy (8.85%) and monoclonal immunoglobulin deposition disease (8.46%). Membranous nephropathy was the leading diagnosis of MGUS (39.38%). Renal pathological findings of patients with hematological malignancies included paraprotein-associated lesions (84.78%) and non-paraprotein-associated lesions (15.22%). The presence of nephrotic syndrome and an abnormal free light chain (FLC) ratio were independently associated with MGRS. The overall survival was better in patients with MGUS than in those with MGRS or hematological malignancies.

In this paper, in order to realize the predefined-time control of -dimensional chaotic systems with disturbance and uncertainty, a disturbance observer and sliding mode control method were presented. A sliding manifold was designed for ensuring that when the error system runs on it, the tracking error was stable within a predefined time. A sliding mode controller was developed which enabled the dynamical system to reach the sliding surface within a predefined time. The total expected convergence time can be acquired through presetting two predefined-time parameters. The results demonstrated the feasibility of the proposed control method.

Abstract P. ginseng is a precious traditional Chinese functional food, which is used for both medicinal and food purposes, and has various effects such as immunomodulation, anti-tumor and anti-oxidation. The growth year of P. ginseng has an important impact on its medicinal and economic values. Fast and nondestructive identification of the growth year of P. ginseng is crucial for its quality evaluation. In this paper, we propose a FC-CNN network that incorporates spectral and spatial features of hyperspectral images to characterize P. ginseng from different growth years. The importance ranking of the spectra was obtained using the random forest method for optimal band selection. Based on the hyperspectral reflectance data of P. ginseng after radiometric calibration and the images of the best five VNIR bands and five SWIR bands selected, the year-by-year identification of P. ginseng age and its identification experiments for food and medicinal purposes were conducted, and the FC-CNN network and its FCNN and CNN branch networks were tested and compared in terms of their effectiveness in the identification of P. ginseng growth years. It has been experimentally verified that the best year-by-year recognition was achieved by utilizing images from five visible and near-infrared important bands and all spectral curves, and the recognition accuracy of food and medicinal use reached 100%. The FC-CNN network is significantly better than its branching model in the effect of edible and medicinal identification. The results show that for P. ginseng growth year identification, VNIR images have much more useful information than SWIR images. Meanwhile, the FC-CNN network utilizing the spectral and spatial features of hyperspectral images is an effective method for the identification of P. ginseng growth year.

Objective: To understand and highlight the differences in clinical, demographic, and image quality characteristics between patient-taken (PAT) and clinic-taken (CLIN) photographs of skin conditions. Patients and Methods: This retrospective study applied logistic regression to data from 2500 deidentified cases in Stanford Health Care’s eConsult system, from November 2015 to January 2021. Cases with undiagnosable or multiple conditions or cases with both patient and clinician image sources were excluded, leaving 628 PAT cases and 1719 CLIN cases. Demographic characteristic factors, such as age and sex were self-reported, whereas anatomic location, estimated skin type, clinical signs and symptoms, condition duration, and condition frequency were summarized from patient health records. Image quality variables such as blur, lighting issues and whether the image contained skin, hair, or nails were estimated through a deep learning model. Results: Factors that were positively associated with CLIN photographs, post-2020 were as follows: age 60 years or older, darker skin types (eFST V/VI), and presence of skin growths. By contrast, factors that were positively associated with PAT photographs include conditions appearing intermittently, cases with blurry photographs, photographs with substantial nonskin (or nail/hair) regions and cases with more than 3 photographs. Within the PAT cohort, older age was associated with blurry photographs. Conclusion: There are various demographic, clinical, and image quality characteristic differences between PAT and CLIN photographs of skin concerns. The demographic characteristic differences present important considerations for improving digital literacy or access, whereas the image quality differences point to the need for improved patient education and better image capture workflows, particularly among elderly patients.

Abstract Tertiary lymphoid structures (TLSs) have been associated with favorable immunotherapy responses and prognosis in various cancers. Despite their significance, their quantification using multiplex immunohistochemistry (mIHC) staining of T and B lymphocytes remains labor-intensive, limiting its clinical utility. To address this challenge, we curated a dataset from matched mIHC and H&E whole-slide images (WSIs) and developed a deep learning model for automated segmentation of TLSs. The model achieved Dice coefficients of 0.91 on the internal test set and 0.866 on the external validation set, along with intersection over union (IoU) scores of 0.819 and 0.787, respectively. The TLS ratio, defined as the segmented TLS area over the total tissue area, correlated with B lymphocyte levels and the expression of CXCL13, a chemokine associated with TLS formation, in 6140 patients spanning 16 tumor types from The Cancer Genome Atlas (TCGA). The prognostic models for overall survival indicated that the inclusion of the TLS ratio with TNM staging significantly enhanced the models’ discriminative ability, outperforming the traditional models that solely incorporated TNM staging, in 10 out of 15 TCGA tumor types. Furthermore, when applied to biopsied treatment-naïve tumor samples, higher TLS ratios predicted a positive immunotherapy response across multiple cohorts, including specific therapies for esophageal squamous cell carcinoma, non-small cell lung cancer, and stomach adenocarcinoma. In conclusion, our deep learning-based approach offers an automated and reproducible method for TLS segmentation and quantification, highlighting its potential in predicting immunotherapy response and informing cancer prognosis.

Abstract Electric vehicles (EVs) charging swapping stations (CSSs), as well as multi‐functional integrated charging and swapping facilities (CSFs), have become important to reduce the impact of e‐mobility on the electric power distribution system. This paper presents a coordinated planning optimization strategy for CSSs/CSFs and active distribution networks (AND) that includes distributed generation. The approach is based on the application of a specifically developed spatial‐temporal load forecasting method of both plug‐in EVs (PEVs) and swapping EVs (SEVs). The approach is formulated as a mathematical programming optimization model that provides the location and sizing of new CSSs, the best active distribution network topology, the required distributed generation, and substation capacities. The developed model is solved using CPLEX, and its characteristics and performances are evaluated through a realistic case study.