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Abstract The electrocatalytic reduction of CO2 to CO is slowed by the energy cost of the hydrogenation step that yields adsorbed *COOH intermediate. Here, we report a hydrogen radical (H•)-transfer mechanism that aids this hydrogenation step, enabled by constructing Ni-partnered hetero-diatomic pairs, and thereby greatly enhancing CO2-to-CO conversion kinetics. The partner metal to the Ni (denoted as M) catalyzes the Volmer step of the water/proton reduction to generate adsorbed *H, turning to H•, which reduces CO2 to carboxyl radicals (•COOH). The Ni partner then subsequently adsorbs the •COOH in an exothermic reaction, negating the usual high energy-penalty for the electrochemical hydrogenation of CO2. Tuning the H adsorption strength of the M site (with Cd, Pt, or Pd) allows for the optimization of H• formation, culminating in a markedly improved CO2 reduction rate toward CO production, offering 97.1% faradaic efficiency (FE) in aqueous electrolyte and up to 100.0% FE in an ionic liquid solution.

Abstract Single‐atom catalysts (SACs), featuring highly uniform active sites, tunable coordination environments, and synergistic effects with support, have emerged as one of the most efficient catalysts for various reactions, particularly for electrochemical CO2 reduction (ECR). However, the scalability of SACs is restricted due to the limited choice of available support and problems that emerge when preparing SACs by thermal deposition. Here, an in situ reconstruction method for preparing SACs is developed with a variety of atomic sites, including nickel, cadmium, cobalt, and magnesium. Driven by electricity, different oxygen‐containing metal precursors, such as MOF‐74 and metal oxides, are directly atomized onto nitrogen‐doped carbon (NC) supports, yielding SACs with variable metal active sites and coordination structures. The electrochemical force facilitates the in situ generation of bonds between the metal and the supports without the need for additional complex steps. A series of MNxOy (M denotes metal) SACs on NC have been synthesized and utilized for ECR. Among these, NiNxOy SACs using Ni‐MOF‐74 as a metal precursor exhibit excellent ECR performance. This universal and general SAC synthesis strategy at room temperature is simpler than most reported synthesis methods to date, providing practical guidance for the design of the next generation of high‐performance SACs.

Abstract Aged livers have shown aggravated liver ischemia and reperfusion (IR) injury. Timely efferocytosis of apoptotic cells is a key mechanism for avoiding excessive inflammation and tissue injury. Here, we investigated the alteration of efferocytosis by aged macrophages and its role in regulating macrophage STING (stimulator of interferon genes) signaling and liver IR injury. Aged and young mice were subjected to liver partial IR model. Liver injury and inflammation were measured. Efferocytosis by aged macrophages and the underlying regulatory mechanism were analyzed as well. Aged macrophages exhibited impaired efferocytosis with decreased MerTK (c-mer proto-oncogene tyrosine kinase) activation, which was reversed by treatment of the MerTK CRISPR activation plasmid. Increased MerTK cleavage by ADAM17 (a disintegrin and metalloproteinase 17) due to enhanced ROS (reactive oxygen species) levels contributed to defective efferocytosis by aged macrophages. MerTK activation by suppressing ADAM17 or ROS improved aged macrophage efferocytosis, leading to reduced inflammatory liver injury. Moreover, increased apoptotic hepatocytes, DNA accumulation, and macrophage STING activation were observed in aged ischemic livers. Improvement in efferocytosis by aged macrophages via MerTK activation suppressed STING activation and inflammatory liver injury. Our study demonstrates that aging suppresses MerTK- mediated macrophage efferocytosis to promote macrophage STING activation and inflammatory liver IR injury, suggesting a new mechanism and potential therapy to promote inflammation resolution and efferocytosis in aged livers.

Conclusions: This research delved into the mechanisms by which the macrophage ATG16L1 signal influences inflammatory signaling, hepatocyte apoptosis, and activation of HSCs in liver fibrosis. Consequently, it offers theoretical substantiation and an experimental groundwork for the identification of biological targets for therapeutic intervention in liver fibrosis.

Abstract Mixed-lineage kinase domain-like protein (MLKL)-mediated necroptosis has been implicated in aggravating liver ischemia and reperfusion (IR) injury. However, the precise role and mechanism of MLKL in regulating oxidative DNA damage of hepatocytes and subsequent activation of macrophage stimulator of interferon genes (STING) signaling remains unclear. In this study, we investigated the role of MLKL in regulating the interplay between hepatocyte injury and macrophage pro-inflammatory responses during liver IR injury. We found that IR increased MLKL expression in liver tissues of wild type (WT) mice. MLKL knockout (KO) attenuated liver IR injury and suppressed the activation of cGAS-STING signaling in intrahepatic macrophages, which was abrogated by STING activation with its agonist. Mechanistically, IR induced oxidative DNA damage in hepatocytes, leading to cGAS-STING activation in macrophages, which was suppressed by MLKL KO. Moreover, increased PTEN-induced kinase 1 (PINK1)-mediated mitophagy contributed to reduced oxidative DNA damage in hepatocytes and subsequent decreased activation of STING signaling in macrophages in MLKL KO mice. Our findings demonstrated a non-canonical role of MLKL in the pathogenesis of liver IR. MLKL deficiency significantly promoted PINK1-mediated mitophagy activation to inhibit oxidative DNA damage in hepatocytes, which in turn suppressed macrophage cGAS-STING activation and inflammatory liver IR injury.

Circulating tumor DNA (ctDNA) is a critical biomarker not only important for the early detection of tumors but also invaluable for personalized treatments. Currently ctDNA detection relies on sequencing. Here, a platform termed three-dimensional-coded interlocked DNA rings (3D-coded ID rings) was created for multiplexed ctDNA identification. The ID rings provide a ctDNA recognition ring that is physically interlocked with a reporter ring. The specific binding of ctDNA to the recognition ring initiates target-responsive cutting via a restriction endonuclease; the cutting then triggers rolling circle amplification on the reporter ring. The signals are further integrated with internal 3D codes for multiplexed readouts. ctDNAs from non-invasive clinical specimens including plasma, feces, and urine were detected and validated at a sensitivity much higher than those obtained through sequencing. This 3D-coded ID ring platform can detect any multiple DNA fragments simultaneously without sequencing. We envision that our platform will facilitate the implementation of future personalized/precision medicine.

Background and aims Macrophage innate immune response plays an important role in tumorigenesis. However, the role and mechanism of macrophage STING signaling in modulating tumor microenvironment to suppress tumor growth at secondary sites remains largely unclear.Methods STING expression was assessed in liver samples from patients with colorectal cancer (CRC) liver metastasis. Global or myeloid stimulator of interferon gene (STING)-deficient mice, myeloid NOD-like receptor protein 3 (NLRP3)-deficient mice, and wild-type (WT) mice were subjected to a mouse model of CRC liver metastasis by intrasplenic injection of murine colon carcinoma cells (MC38). Liver non-parenchymal cells including macrophages and natural killer (NK) cells were isolated for flow cytometry analysis. Bone marrow-derived macrophages pretreated with MC38 were co-cultured with splenic NK cells for in vitro studies.Results Significant activation of STING signaling were detected in adjacent and tumor tissues and intrahepatic macrophages. Global or myeloid STING-deficient mice had exacerbated CRC liver metastasis and shorten survival, with decreased intrahepatic infiltration and impaired antitumor function of NK cells. Depletion of NK cells in WT animals increased their metastatic burden, while no significant effects were observed in myeloid STING-deficient mice. STING activation contributed to the secretion of interleukin (IL)-18 and IL-1β by macrophages, which optimized antitumor activity of NK cells by promoting the expression of 4-1BBL in macrophages and 4-1BB in NK cells, respectively. Moreover, MC38 treatment activated macrophage NLRP3 signaling, which was inhibited by STING depletion. Myeloid NLRP3 deficiency increased tumor burden and suppressed activation of NK cells. NLRP3 activation by its agonist effectively suppressed CRC liver metastasis in myeloid SITNG-deficient mice.Conclusions We demonstrated that STING signaling promoted NLRP3-mediated IL-18 and IL-1β production of macrophages to optimize the antitumor function of NK cells via the co-stimulation signaling of 4-1BBL/4-1BB.

Gastric cancer (GC) is the fifth most common cancer in the world and a serious threat to human health. Due to its high morbidity and mortality, a simple, rapid and accurate early screening method for GC is urgently needed. In this study, the potential of Raman spectroscopy combined with different machine learning methods was explored to distinguish serum samples from GC patients and healthy controls. Serum Raman spectra were collected from 109 patients with GC (including 35 in stage I, 14 in stage II, 35 in stage III, and 25 in stage IV) and 104 healthy volunteers matched for age, presenting for a routine physical examination. We analyzed the difference in serum metabolism between GC patients and healthy people through a comparative study of the average Raman spectra of the two groups. Four machine learning methods, one-dimensional convolutional neural network, random forest, support vector machine, and K-nearest neighbor were used to explore identifying two sets of Raman spectral data. The classification model was established by using 70% of the data as a training set and 30% as a test set. Using unseen data to test the model, the RF model yielded an accuracy of 92.8%, and the sensitivity and specificity were 94.7% and 90.8%. The performance of the RF model was further confirmed by the receiver operating characteristic (ROC) curve, with an area under the curve (AUC) of 0.9199. This exploratory work shows that serum Raman spectroscopy combined with RF has great potential in the machine-assisted classification of GC, and is expected to provide a non-destructive and convenient technology for the screening of GC patients.

The demand for rapid and accurate identification of microorganisms is growing due to considerable importance in all areas related to public health and safety. Here, we demonstrate a rapid and label-free strategy for the identification of microorganisms by integrating terahertz-attenuated total reflection (THz-ATR) spectroscopy with an automated recognition method based on multi-classifier voting. Our results show that 13 standard microbial strains can be classified into three different groups of microorganisms (Gram-positive bacteria, Gram-negative bacteria, and fungi) by THz-ATR spectroscopy. To detect clinical microbial strains with better differentiation that accounts for their greater sample heterogeneity, an automated recognition algorithm is proposed based on multi-classifier voting. It uses three types of machine learning classifiers to identify five different groups of clinical microbial strains. The results demonstrate that common microorganisms, once time-consuming to distinguish by traditional microbial identification methods, can be rapidly and accurately recognized using THz-ATR spectra in minutes. The proposed automatic recognition method is optimized by a spectroscopic feature selection algorithm designed to identify the optimal diagnostic indicator, and the combination of different machine learning classifiers with a voting scheme. The total diagnostic accuracy reaches 80.77% (as high as 99.6% for Enterococcus faecalis) for 1123 isolates from clinical samples of sputum, blood, urine, and feces. This strategy demonstrates that THz spectroscopy integrated with an automatic recognition method based on multi-classifier voting significantly improves the accuracy of spectral analysis, thereby presenting a new method for true label-free identification of clinical microorganisms with high efficiency.

In order to reveal the influence of the pull-out rate on the load-bearing properties of the coal–rock combined anchor body, the mechanical properties and failure characteristics of a coal–rock combined anchor body under different pull-out rates (10, 20, 30, 40, 50 mm/min) were studied using the pull-out test and theoretical analysis. The results show that the bearing capacity of the bolt on the coal–rock combined anchor body improves under a dynamic load, but the load-bearing properties of the coal–rock combined anchor body are different from those of the full rock (coal) anchor body. With the increase in the pull-out rate, the maximum pull-out load of the bolt on the coal–rock combined anchor body increases first, then decreases, and finally tends to be stable. Under the condition of a low drawing rate, the bearing capacity of the coal–rock combined anchor system can be greatly improved, but when the pull-out rate exceeds 20 mm/min, the bearing capacity of the anchor system is reduced. The debonding process of the anchoring section of the coal–rock combined anchor body gradually expands from the beginning section of the anchor to the bottom of the borehole. The coal–rock combined anchor body undergoes time differential development of cracks, and the failure of the coal and rock mass occurs at different times. Its failure process can be divided into three stages: (1) the coal anchor and rock anchor act together; (2) the rock anchor acts alone; and (3) the coal anchor and rock anchor have residual action.

Abstract Aims Left ventricular hypertrophy (LVH) is frequently detected via echocardiography in individuals with Fabry disease (FD), sometimes leading to confusion with hypertrophic cardiomyopathy (HCM) of other aetiologies. Considering this diagnosis challenge, FD should be included in the list of differential diagnosis for patients presenting with LVH. To address this concern, we conducted a prospective screening study in China, using dried blood spot (DBS) testing, to evaluate patients with unexplained LVH. Methods Our study was designed as a nationwide, multicentre prospective investigation. A total of 1015 patients from 55 different centres who were diagnosed with LVH by echocardiography were screened in the study from September 2022 to December 2023. Demographic information, biochemistry data, echocardiography parameters and clinical observations were meticulously collected from all participants. The DBS method was used to assess α‐galactosidase A (α‐Gal A) activity in males and both α‐Gal A and globotriaosylsphingosine (lyso‐Gb3) levels in females. Results The final screening population included 906 patients (589 males, 65%) with LVH, characterized by a mean maximal myocardial thickness of 14.8 ± 4.6 mm and an average age of 56.9 ± 17.2 years. In total, 43 patients (38 males, 5 females) exhibited low α‐Gal A activity measurement (1.1 ng/mL). Among these patients, eight individuals (7 males and 1 female) were genetically confirmed to harbour pathogenic GLA mutations, resulting in a total prevalence of 0.88%. Compared with patients without FD, patients with FD tended to have proteinuria (75% vs. 21.2%, P = 0.001), family history of HCM (37.5% vs. 2.3%, P T) and c.547+3A>G, were deemed potentially pathogenic. Subsequent familial validation post‐diagnosis identified an additional 14 confirmed cases. Conclusions This pioneering screening study for FD among Chinese patients with unexplained LVH using DBS measurement, revealed an FD detection rate of 0.88%. Our findings confirmed that the combined measurement of lyso‐Gb3 and α‐Gal A activity is beneficial for primary screening of FD in patients with LVH. Given the availability of efficacious therapies and the value of cascade screening in extended families, early detection of FD in LVH patients is clinically important.

Abstract Aims Limited literature shows the existence of sex differences in the long‐term prognosis of heart failure (HF) patients with frailty. In this study, whether sex differences exist in the impact of frailty on death from cardiovascular causes in patients with HF was investigated by conducting a retrospective cohort study. Methods and results Data from the National Health and Nutrition Examination Survey (NHANES) study (2009–2018) were used to conduct a retrospective cohort study of 958 participants with HF. Patients were grouped based on sex and frailty index (FI). The relationship between death from cardiovascular causes and baseline frailty was assessed by Cox proportional hazard analysis and the Kaplan–Meier (K‐M) plot. The study population had an age of 67.3 ± 12.3. Among them, around 54.5% were male. A median follow‐up of 3.6 years was performed. After that, females who died from cardiovascular causes exhibited higher baseline FI values, while males did not show this trend (P

Abstract Quartz is one of the most abundant minerals in shales, occurring predominantly in three forms: biogenic quartz (BQ), detrital quartz (DQ) and clay-transformed quartz (CTQ). The content of quartz is typically correlated with the fracability of shale gas reservoirs. However, the origins of quartz and its influence on mechanical properties remain not fully elucidated. To address this gap, this study examines shale samples from LM1-LM8 graptolite zones in well W202 of the Weiyuan shale gas field, the Sichuan Basin as the research object. After systematic analysis of organic geochemistry, mineral composition, cathodoluminescence observation, major/trace elements, and log interpretation and calculation of shale mechanical parameters, the genetic mechanism of quartz was analyzed and the percentage of quartz of different origins and the influence on rock mechanical properties were evaluated quantitatively. The results indicate that the three types of quartz (BQ, DQ and CTQ) were variably present in the Longmaxi shale across different graptolite zones. The LM1-LM3 graptolite zones exhibit the highest abundance of BQ, with contents ranging from 58.3 to 79.6%, with an average of 65.7%. DQ predominates in the LM4-LM5 and LM6-LM8 graptolite zones, with average contents of 38.7% and 34.9%, respectively. The BQ content is marginally higher in the LM4-LM5 zone compared to the LM6-LM8 zone, averaging 12.7% and 6.1%, respectively. The three types of quartz exert a dual influence on Young’s modulus, and a single linear effect on Poisson’s ratio. An increase BQ content correlates with a decreased in Poisson’s ratio, whereas increased contents of DQ and CTQ correlate with an increased Poisson’s ratio. With the highest Young’s modulus and the lowest Poisson’s ratio, the LM1-LM3 shale is the most favorable interval for hydraulic fracturing. Furthermore, BQ is positively correlated with the Brittleness index (BI), whereas the contents of DQ and CTQ are negatively correlated with BI. When the quartz content falls between 52% and 85%, the ratio of DQ to BQ is optimal for fracture development coinciding with high BI values, which are most conducive to fracturing stimulation.

Abstract Background High-quality goatskins are valuable byproducts usually produced by indigenous goat breeds with poorer production performance in Asia and Africa. However, the genetic and molecular mechanisms underpinning goatskin’s biomechanical properties (e.g., tensile strength) remain elusive. Mechanistic exploration of these traits could greatly aid the genetic improvement and genetic resource conservation of native breeds in these regions. To fulfill this purpose, we collected skin tissues from three goat breeds: Huai goat (HG), a Chinese native variety producing high-quality goatskins; Yudong meat goat (YDMG), a crossbreed of HG and Boer goat; Henan dairy goat (HNDG), a dairy goat breed. Results Scanning electronic microscopy analysis of skin tissues found that the collagen fiber diameters, collagen fibril diameters, and crimps significantly differed among the three goat breeds; however, collagen fibril diameters are similar in HG and HNDG. A sum of 230, 775, and 86 differentially expressed genes (DEGs) were identified from YDMG versus HNDG, HG versus HNDG, and YDMG versus HG, respectively. Functional enrichment analysis suggested that signaling pathways involved in fatty acid, retinol, steroid metabolisms, and GO items related to the physical properties of the skin (e.g., collagen-containing extracellular matrix) are significantly overrepresented in DEGs identified from meat versus dairy goats. Furthermore, 106 DEGs (e.g., COL1A1, COL1A2, and SPARC) showed specific expression patterns in HG and YDMG versus HNDG. Items about biophysical features of skin (e.g., extracellular matrix organization and ECM proteoglycans) are markedly enriched. Protein-protein interaction analysis suggested that two growth factors (IGF1 and PDGFD) are latent collagen and other ECM protein expression modulators. Conclusion Ultrastructural analysis of goat skin tissues suggested that collagen fibril diameter is not a major factor affecting goatskin quality. Transcriptomic profiles unveiled core genes and associated biological processes potentially involved in regulating goatskin quality. These discoveries shined new light on deeper understanding the mechanisms of hide-related traits in goat and other livestock.

Recognition of ship traffic patterns can provide insights into the rules of navigation, maneuvering, and collision avoidance for ships at sea. This is essential for ensuring safe navigation at sea and improving navigational efficiency. With the popularization of the Automatic Identification System (AIS), numerous studies utilized ship trajectories to identify maritime traffic patterns. However, the current research focuses on the spatiotemporal behavioral feature clustering of ship trajectory points or segments while lacking consideration for multiple factors that influence ship behavior, such as ship static and maritime geospatial features, resulting in insufficient precision in ship traffic pattern recognition. This study proposes a ship traffic pattern recognition method that considers multi-attribute trajectory similarity (STPMTS), which considers ship static feature, dynamic feature, port geospatial feature, as well as semantic relationships between these features. First, A ship trajectory reconstruction method based on grid compression was introduced to eliminate redundant data and enhance the efficiency of trajectory similarity measurements. Subsequently, to quantify the degree of similarity of ship trajectories, a trajectory similarity measurement method is proposed that combines ship static and dynamic information with port geospatial features. Furthermore, trajectory clustering with hierarchical methods was applied based on the trajectory similarity matrix for dividing trajectories into different clusters. The quality of the similarity measurement results was evaluated by quality criterion to recognize the optimal number of ship traffic patterns. Finally, the effectiveness of the proposed method was verified using actual port ship trajectory data from the Tianjin Port of China, ranging from September to November 2016. Compared with other methods, the proposed method exhibits significant advantages in identifying traffic patterns of ships entering and leaving the port in terms of geometric features, dynamic features, and adherence to navigation rules. This study could serve as an inspiration for a comprehensive exploration of maritime transportation knowledge from multiple perspectives.

This study employs a data-driven methodology that embeds the principle of dimensional invariance into an artificial neural network to automatically identify dominant dimensionless quantities in the penetration of rod projectiles into semi-infinite metal targets from experimental measurements. The derived mathematical expressions of dimensionless quantities are simplified by the examination of the exponent matrix and coupling relationships between feature variables. As a physics-based dimension reduction methodology, this way reduces high-dimensional parameter spaces to descriptions involving only a few physically interpretable dimensionless quantities in penetrating cases. Then the relative importance of various dimensionless feature variables on the penetration efficiencies for four impacting conditions is evaluated through feature selection engineering. The results indicate that the selected critical dimensionless feature variables by this synergistic method, without referring to the complex theoretical equations and aiding in the detailed knowledge of penetration mechanics, are in accordance with those reported in the reference. Lastly, the determined dimensionless quantities can be efficiently applied to conduct semi-empirical analysis for the specific penetrating case, and the reliability of regression functions is validated.

Objective: To determine the efficacy and safety of the Yinmei Kuijie decoction combined with 5-aminosalicylic acid (5-ASA) in treating mildly to moderately active ulcerative colitis (UC) under real-world conditions. Methods: This multicenter, prospective, non-randomized, observational study will be conducted in real-world settings. A total of 204 eligible patients will be consecutively enrolled in the study. Patients in the combination treatment group will receive Yinmei Kuijie decoction in combination with 5-ASA, whereas those in the control group will be treated with 5-ASA alone. The primary endpoint will be a clinical response at week 12, defined as a ≥3 point and ≥30% reduction from baseline in the Mayo total score with ≥1 reduction in rectal bleeding or rectal bleeding score = 0 or 1. Secondary efficacy endpoints at week 12 will include health-related quality of life, mucosal healing, and inflammation indicators. Conclusion: The results of this study may provide evidence of the efficacy and safety of Yinmei Kuijie decoction combined with 5-ASA in treating patients with mildly to moderately active UC under real-world principles. The results will provide a basis for further confirmatory studies on the efficacy of Yinmei Kuijie decoction.

Abstract Methylation quantitative trait loci (meQTLs) quantify the effects of genetic variants on DNA methylation levels. However, most published studies utilize bulk methylation datasets composed of different cell types and limit our understanding of cell-type-specific methylation regulation. We propose a hierarchical Bayesian interaction (HBI) model to infer cell-type-specific meQTLs, which integrates a large-scale bulk methylation data and a small-scale cell-type-specific methylation data. Through simulations, we show that HBI enhances the estimation of cell-type-specific meQTLs. In real data analyses, we demonstrate that HBI can further improve the functional annotation of genetic variants and identify biologically relevant cell types for complex traits.

Current methods synthetic aperture radar–automatic target recognition (SAR–ATR) research methods still struggle with overfitting due to small amounts of training data, as well as black-box opacity and high computational requirements. Unmanned aerial vehicles, as the mainstream means of acquiring SAR data, place higher requirements on ATR algorithms due to their flexible maneuvering characteristics. This article starts by studying the electromagnetic (EM) backscattering mechanism and the physical properties of SAR. We construct a heterogeneous graph for the first time to fully exploit both the EM scattering information of the target components and their interactions. Moreover, the multilevel multihead attention mechanism is introduced to the graph net to learn features from various topological structure levels. Additionally, we include a convolutional neural network based feature extraction net to replenish intuitive visual features. The above two nets form the lightweight dual-stream framework (LDSF). LDSF uses a feature fusion subnetwork to adaptively fuse the dual-stream features to maximize the final classification performance. The experiments use two more rigorous evaluation protocols on MSTAR and OpenSARShip, namely, once-for-all and less-for-more, which can rigorously assess the efficacy and generalization capability of the algorithms. The superiority of LDSF is verified.

A new species of the genus Digitivalva Gaedike, 1970 from Japan, D. bella Zhang, Yagi & Hirowatari, sp. nov., is described. The host plant of this species is identified as Carpesium divaricatum Sieb. & Zucc. (Asteraceae). Larvae of this species pupate beneath the host tissue; this habit is for the first time reported for the genus Digitivalva in Japan. Adult specimens with male and female genitalia and pupae are illustrated and described in detail. Although the wing markings differ, the new species is considered closely related to D. arnicella (Heyden, 1863) from Europe, with which it shares similar biological and morphological features.

Abstract Background Anxiety and depression often co-occur, exhibiting high comorbidity, with their trends evolving over time. However, the specific pathways through which comorbid symptoms of anxiety and depression evolve and interact remain unclear. To investigate these questions, this study employed Network Analysis (NA) and Longitudinal Network Analysis (LNA) to explore the central symptoms of anxiety and depression, as well as the temporal evolution of these central symptoms. Methods The study focused on 606 high school students who were not in their final year in Shandong of China, with assessments conducted from March to September 2022. The bootnet package in R was used for establishing NA and LNA models, as well as for conducting accuracy analysis and node stability analysis. Results The results of the NA indicated that adolescent highly susceptible to anxiety and depression. And uncontrollable worry was a common central symptom, while irritability emerged as a central bridging symptom across all three NAs. The LNA results revealed that suicidal ideation and worthlessness were key central symptoms in the LNA. Furthermore, worthlessness played a pivotal role in the developmental pathway of “suicidal ideation → worthlessness → anxiety and uncontrollable worry.” A reduction in suicidal ideation was associated with decreased severity in other symptoms. Conclusions The findings suggest that adolescent anxiety and depression are in a state of vulnerability, and that irritability, worthlessness, and suicidal ideation are potential targets for interventions to address adolescent anxiety and depression.

Abstract Traditional substrate cultivation is now a routine practice in vegetable facility breeding. However, finding renewable substrates that can replace traditional substrates is urgent in today’s production. In this study, we used the ‘Pindstrup’ substrate as control and two types of composite substrates made from fermented corn straw (i.e. 0–3 and 3–5 mm) to identify appropriate substrate conditions for tomato seedling growth under winter greenhouse conditions. Seedling growth potential related data and substrate water content related data were tested to carry out data-oriented support. Since the single physiological data cannot well explain the mechanism of tomato seedlings under winter greenhouse condition, transcriptomic analysis of tomato root and leaf tissues were conducted to provide theoretical basis. The physiological data of tomato seedlings and substrate showed that compared with 0–3 mm and Pindstrup substrate, tomato seedlings planted in 3–5 mm had stronger growth potential and stronger water retention, and were more suitable for planting tomato seedlings. Transcriptome analysis revealed a greater number of DEGs between the Pindstrup and the 3–5 mm. The genes in this group contribute to tomato growth as well as tomato stress response mechanisms, such as ABA-related genes, hormone-related genes and some TFs. The simulation network mechanism diagram adds evidence to the above conclusions. Overall, these results demonstrate the potential benefits of using the fermented corn straw of 3–5 mm for growing tomato seedlings and present a novel method of utilizing corn straw.

Abstract Diabetes mellitus (DM) is a chronic metabolic disease that is highly susceptible to kidney injury. Di’ao XinXueKang capsules (DXXK) is a novel Chinese herbal medicine that has been used in clinical trials for the therapy of DM and kidney disease, but the underlying pharmacological mechanism remains unclear. This study aims to integrate network pharmacology, molecular docking and in vivo experiments to explore the potential mechanisms of DXXK in the treatment of diabetic kidney injury. The chemical constituents of DXXK were extracted from the ETCM and Batman-TCM databases, and then evaluated for their pharmacological activity via the Swiss ADME platform. Multiple disease databases were searched and integrated for DM-related targets. Overlapping targets were then collected to construct a protein–protein interaction (PPI) network. KEGG and GO enrichment analyses were performed based on the Metascape database, and molecular docking was performed using AutoDock Vina software. The main components in DXXK were analyzed by HPLC. The results of network pharmacology and molecular docking were validated in an animal model of DM induced by the combination of a high-fat diet (HFD) and streptozotocin (STZ). We screened and obtained 7 ingredients and identified dioscin, protodioscin, and pseudoprotodioscin as the major components of DXXK by HPLC. A total of 2,216 DM-related pathogenic genes were obtained from DrugBank, GeneCards, OMIM, and DisGeNET databases. KEGG and GO enrichment analyses indicated that the TGF-beta signaling pathway is a critical pathway associated with DM therapy. Molecular docking revealed that the ingredients in DXXK bind to the pivotal targets TGFβ1, Smad2, and Smad3. In diabetic mice, we found that DXXK alleviated diabetic symptoms, lowered blood glucose, improved insulin tolerance, and modulated lipid metabolism. Furthermore, DXXK attenuated renal lesions and fibrosis by downregulating TGFβ1, Smad2, and Smad3. Collectively, our results suggest that DXXK has the potential to regulate glucolipid metabolism in DM, and it may serve as a viable therapeutic option for renoprotection by inhibiting of the TGF-β1/Smad2/3 pathway.

Abstract With the continuous development of robot-assisted technology, Robot-assisted Laparoscopic Partial Nephrectomy (RALPN) has gradually become an optional method for the treatment of Hemorrhage secondary to angiomyolipoma (HSA). However, there are rare clinical reports of the primary RALPN for HSA. Therefore, this research aims to evaluate the efficacy and safety of primary RALPN for HSA. Fourteen patients(six males and eight females), aged 14–56 years, underwent primary RALPN for HSA and were retrospectively analyzed from 2015 to 2023. The initial blood routine examination revealed decreased hemoglobin in all patients, and Contrast-enhanced computed tomography (CT) indicated retroperitoneal hematoma. After correcting shock and electrolyte imbalance through fluid therapy and medical treatment, all primary RALPN procedures were performed with transabdominal access on the side of the Hemorrhage. After tumor resection and hematoma removal with a monopolar Curved Scissor, the absorbable barbed suture was performed for inner and outer running stitches, respectively. Patient demographic information, perioperative characteristics, and functional outcomes were collected and analyzed. The initial tumor size of fourteen patients ranged from 57 to 145 mm, and the RENAL ranged from 7 to 11. All of the HSA was controlled, and primary RALPN was successful. The operating time it was ranged from 105 to 265 min. Postoperatively, one patient exhibited chylous drainage (Clavien-Dindo II), and another patient developed pleural effusion (Clavien-Dindo III). No postoperative transfusion and Digital Subtraction Angiography (DSA) highly selective embolization of the bleeding vessel was needed. No patients developed urinoma or urinary fistula. Within the follow-up period, the overall complications were manageable. Primary RALPN is a safe and effective procedure for HSA, which may be considered an alternative to selective renal artery embolization.

Abstract Purpose To assess the associations of muscle strength, measure by grip strength and relative grip strength (grip strength divided by body weight), on the allostatic load (AL) index in adolescent boys and girls. Methods A total of 1,323 students were recruited (boys = 776, girls = 547). Data on general demographic characteristics, anthropometric indicators, grip strength, blood pressure, pulse rate, and biological samples were collected. A 20-indicator-based AL index (using the AL1, AL2, and AL3 calculation methods) was used as the dependent variable. Multiple linear regression models were used to evaluate the association between grip strength, relative grip strength, and AL. All analyses were stratified by sex. Results The mean age of the participants was 14.17 ± 1.45 years. Overall, the linear regression model adjusting for demografic characteristics showed that greater grip strength was associated with higher AL1 scores (R 2 = 10.1%, β = 0.096, P

Abstract Background History-taking is an essential clinical competency for qualified doctors. The limitations of the standardized patient (SP) in taking history can be addressed by the virtual standardized patient (VSP). This paper investigates the accuracy of virtual standardized patient simulators and evaluates the applicability of the improved system’s accuracy for diagnostic teaching support and performance assessment. Methods Data from the application of VSP to medical residents and students were gathered for this prospective study. In a human–machine collaboration mode, students completed exams involving taking SP histories while VSP provided real-time scoring. Every participant had VSP and SP scores. Lastly, using the voice and text records as a guide, the technicians will adjust the system’s intention recognition accuracy and speech recognition accuracy. Results The research revealed significant differences in scoring across several iterations of VSP and SP (p

Abstract The combination of ASC22, an anti-PD-L1 antibody potentially enhancing HIV-specific immunity and chidamide, a HIV latency reversal agent, may serve as a strategy for antiretroviral therapy-free virological control for HIV. People living with HIV, having achieved virological suppression, were enrolled to receive ASC22 and chidamide treatment in addition to their antiretroviral therapy. Participants were monitored over 24 weeks to measure changes in viral dynamics and the function of HIV-specific CD8+ T cells (NCT05129189). 15 participants completed the study. At week 8, CA HIV RNA levels showed a significant increase from baseline, and the values returned to baseline after discontinuing ASC22 and chidamide. The total HIV DNA was only transiently increased at week 4 (P = 0.014). In contrast, integrated HIV DNA did not significantly differ from baseline. Increases in the proportions of effector memory CD4+ and CD8+ T cells (TEM) were observed from baseline to week 24 (P = 0.034 and P = 0.002, respectively). The combination treatment did not succeed in enhancing the function of HIV Gag/Pol- specific CD8+ T cells. Nevertheless, at week 8, a negative correlation was identified between the proportions of HIV Gag-specific TEM cells and alterations in integrated DNA in the T cell function improved group (P = 0.042 and P = 0.034, respectively). Nine adverse events were solicited, all of which were graded 1 and resolved spontaneously. The combined treatment of ASC22 and chidamide was demonstrated to be well-tolerated and effective in activating latent HIV reservoirs. Further investigations are warranted in the context of analytic treatment interruption.

Abstract Mitochondria are essential organelles that play critical roles in energy metabolism, apoptosis and various cellular processes. Accumulating evidence suggests that mitochondria are also involved in cancer development and progression. The mitochondrial unfolded protein response (UPRmt) is a complex cellular process that is activated when the protein-folding capacity of the mitochondria is overwhelmed. The core machinery of UPRmt includes upstream regulatory factors, mitochondrial chaperones and proteases. These components work together to eliminate misfolded proteins, increase protein-folding capacity, and restore mitochondrial function. Recent studies have shown that UPRmt is dysregulated in various cancers and contributes to tumor initiation, growth, metastasis, and therapeutic resistance. Considering the pivotal role of the UPRmt in oncogenesis, numerous compounds and synthetic drugs targeting UPRmt-related components induce cancer cell death and suppress tumor growth. In this review, we comprehensively summarize recent studies on the molecular mechanisms of UPRmt activation in C. elegans and mammals and elucidate the conceptual framework, functional aspects, and implications of the UPRmt for cancer therapy. In summary, we paint a developmental landscape of the UPRmt in different types of cancer and offer valuable insights for the development of novel cancer treatment strategies by targeting the UPRmt.