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Since the economic reform and opening up, the exploitation of mineral resources has made significant contributions to the economic development of China. However, due to the non-renewable nature of most mineral resources, a considerable number of mines are facing resource depletion and closure. How to develop and utilize the positive environmental effects left by these mines will become a crucial support for extending the mining industry value chain, ensuring green and low-carbon energy development, and achieving China’s strategic goals of “carbon peak” and “carbon neutrality”. To scientifically develop environmentally positive resources in mines, this study focused on four categories of goals in the development and utilization of positive environmental effects in mines: resources, energy, popular science and entertainment, and ecological carbon sinks. Based on the “Supply - Demand - Development” (SDD) constraint combination of mining supply ontology characteristics, specific market demands, and development and utilization conditions, a comprehensive evaluation constraint system was developed, consisting of 6 first-level constraints and 38 second-level constraints of corresponding attributes. Following the principles of goal-oriented development and utilization, a single-goal evaluation index set with 18 implementation items was constructed. Also, a single-goal suitability evaluation model was built which introduced the triangular fuzzy numbers to determine the index weights, and classified suitability into “suitable, more suitable, more difficult and difficult” based on suitability indices. Furthermore, considering the systematic complexity of the positive effects development and utilization of the mine environment, the logical relationships between the development and utilization objectives were analyzed. In addition, a multi-goal linear evaluation theory was proposed based on the comprehensive optimal concept of economic, ecological and social benefits. By solving through the ideal point method or single-goal linear programming solution, the comprehensive optimal solution or the most suitable set for the positive effects development and utilization of the mine environment was obtained. Finally, from the perspectives of national strategy, social needs, watershed ecology, and positive effect market development, the study provides some insights into the significant implications of the implementation and systematic evaluation of mine environmental positive effects development and utilization.

Aiming at the real problems such as the occurrence of coal and gas outburst and based on the hypothesis of comprehensive action of coal and gas outburst, a method of gas hydration and solidification to prevent coal and gas outburst is proposed. The core of this method is to solidify the gas in coal seam to form gas hydrate, which can not only reduce the gas pressure, but also improve the coal strength, so as to reduce or eliminate the risk of coal and gas outburst. Based on the idea of “coal and gas outburst prevention using hydrate”, the test of gas hydrate formation in coal and the in-situ test of the mechanical property-permeability of gas hydrate bearing coal have been performed, with the numerical modeling technique of the triaxial compression of the gas hydrate bearing coal proposed. The techniques are implemented by comprehensively applying the methods of theoretical analysis, development of testing equipment, indoor test and numerical analysis. In terms of coal and gas outburst prevention, the thermodynamic and kinetic conditions of gas hydrate formation are its theoretical basis, the stable storage of gas hydrate is its technical precondition, and the reduction of gas pressure and the improvement of mechanical properties are its key measures. This paper focuses on the cross mechanics related to the gas hydrate bearing coal. The results show that: ① the theoretical framework of gas solidification technology by the hydrate method for outburst prevention has been initially formed, and the meso-mechanism of improving the mechanical characteristics of coal before and after gas hydration has been preliminarily explored by means of the numerical simulation. ② At present, it has been confirmed that the hydrate formation in coal can not only reduce the gas pressure, but also improve its mechanical properties. High saturation can obviously improve the peak strength of coal. ③ Gas hydrate formation experiences three stages: rapid, slow and stable stage. Additionally, the formation of hydrate will cause the gas seepage channel in the coal to be blocked, resulting in a decrease in its permeability. ④ High gas pressure and high CH4 concentration not only help to increase the saturation but also delay hydrate decomposition, which is conducive to the stable existence of the hydrate. However, a large number of repetitive experiments are still needed to verify the reliability of the method to build up a generalized database. By analyzing current research findings, the limitations and challenges that still exist are discussed, with further research interests pointed out.

Abstract Microfluidic flowmeters are a powerful and highly accurate tool, enabling precise monitoring and measurements of flows of gases and fluids in a range of applications. Here we proposed and experimentally demonstrated a whispering gallery modes flowmeter composed of a liquid crystal-filled nested capillary. Whispering gallery modes are excited by a tapered fiber coupled perpendicularly to the nested capillary. The air flowing through the capillary cools it down, which leads to a temperature-induced change of the refractive index of the nematic liquid crystals. This change in turn leads to a spectral shift of the whispering gallery modes resonances, which can be linked to the airflow rate in the capillary. The temperature change in the liquid crystals was simulated considering the heat transfer between the liquid crystals and airflow in the capillary, which indicated that the liquid crystals temperature decreases in a nonlinear manner with the increase of the airflow rate. A flowmeter with the maximum sensitivity of 0.3423 nm·min·mL−1 in the flowrate range from 0 to 2.52 nm·min·mL−1 and a resolution of 5.72 pm was demonstrated in our experiment. The proposed sensor provides a platform for whispering gallery modes flowmeters and offers the advantages of good stability, high sensitivity, and miniature size.

Abstract This study aims to develop a clinical diagnostic model for assessing the need for initial abdominal surgery in patients diagnosed with Crohn's disease (CD) and create a nomogram to facilitate clinical decision-making. A total of 164 surgical CD patients and 230 control CD patients were included in this retrospective analysis. Least Absolute Shrinkage and Selection Operator (Lasso) regression and binomial logistic regression were employed to select clinical variables. The 394 CD patients were randomly allocated to a training set and a validation set in a 7:3 ratio. The filtered variables were used to establish a diagnostic model and nomogram in the training set, subsequently validated in the testing set. Decision Curve Analysis (DCA) and clinical impact curve were constructed to validate the clinical applicability of the model. Binomial logistic regression analysis identified seven clinical variables with a p-value less than 0.01, including Biomarker (B), Waist-to-Height Ratio (WHtR), Intestinal obstruction, Albumin (ALB), Crohn's Disease Activity Index (CDAI), Myocardial Flow Index (MFI), and C-reactive protein (CRP). These variables were utilized to establish the diagnostic model. Calibration curves showed good alignment, with a C-index of 0.996 in the training set and 0.990 in the testing set. DCA and clinical impact curve demonstrated that the diagnostic model had good clinical efficiency and could provide clinical benefits. A validated diagnostic model for determining the timing of the first abdominal operation in CD patients was established and evaluated, showing high discriminative ability, calibration, and clinical efficiency. It can be utilized by clinicians to assess the optimal timing for transitioning CD patients from medical treatment to surgical intervention, providing valuable references for individualized treatment decisions for CD patients.

Abstract The high-frequency pulse flow, equivalent to the natural frequency of rocks, is generated by a self-excited oscillating cavity to achieve resonance rock-breaking. The flow field and oscillating mechanism of the self-excited oscillating cavity were simulated using the large eddy simulation method of Computational Fluid Dynamics (CFD). A field-scale testing apparatus was developed to investigate the impulse characteristics and verify the simulation results. The results show that the fluid at the outlet at the tool is deflected due to the pulse oscillation of the fluid. The size and shape of low-pressure vortices constantly change, leading to periodic changes in fluid impedance within the oscillating cavity. The impulse frequency reaches its highest point when the length–diameter ratio is 0.67. As the length–diameter ratio increases, the tool pressure loss also increases. Regarding the cavity thickness, the impulse frequency of the oscillating cavity initially decreases, then increases, and finally decreases again. Moreover, both the impulse frequency and pressure loss increase with an increase in displacement. The numerical simulation findings align with the experimental results, thus confirming the validity of the theoretical model. This research provides theoretical guidance for the practical application of resonance rock-breaking technology.

Abstract The blue and white porcelain produced in Jingdezhen during China’s Yuan Dynasty is an outstanding cultural heritage of ceramic art that has attracted wide attention for its identification. However, the traditional visual identification method is susceptible to misjudgment, thermoluminescence dating damages the samples, and the methods based on chemical analysis are limited by the accuracy and specificity of the elemental features. In this paper, we address the identification challenge by using machine learning techniques combined with portable X-ray Fluorescence Spectrometer (pXRF) analysis. We collect a large dataset of chemical compositions of Yuan blue and white porcelain from Jingdezhen using pXRF, and propose a graph anomaly detection method based on gradient attention map (GRAM) to identify the porcelain from different dynasties. We treat the porcelain produced in the Yuan dynasty as normal samples and those from other dynasties as abnormal samples. For GRAM, we merely train the variational graph autoencoder (VGAE) model with normal graphs and then use its encoder to extract graph features and compute the anomaly scores by utilizing the GRAM of the graph representations with respect to the node feature embeddings. Finally, we compare GRAM with state-of-the-art graph anomaly detection techniques and show that it achieves superior performance.

Abstract Background Cayratia albifolia C.L.Li (CAC), commonly known as “Jiao-Mei-Gu” in China, has been extensively utilized by the Dong minority for several millennia to effectively alleviate symptoms associated with autoimmune diseases. CAC extract is believed to possess significant anti-inflammatory properties within the context of Dong medicine. However, an in-depth understanding of the specific pharmaceutical effects and underlying mechanisms through which CAC extract acts against rheumatoid arthritis (RA) has yet to be established. Methods Twenty-four Sprague–Dawley rats were divided into four groups, with six rats in each group. To induce the collagen-induced arthritis (CIA) model, the rats underwent a process of double immunization with collagen and adjuvant. CAC extract (100 mg/kg) was orally administered to rats. The anti-RA effects were evaluated in CIA rats by arthritis score, hind paw volume and histopathology analysis. Pull-down assay was conducted to identify the potential targets of CAC extract from RAW264.7 macrophage lysates. Moreover, mechanism studies of CAC extract were performed by immunofluorescence assays, real-time PCR and Western blot. Results CAC extract was found to obviously down-regulate hind paw volume of CIA rats, with diminished inflammation response and damage. 177 targets were identified from CAC extract by MS-based pull-down assay. Bioinformatics analysis found that these targets were mainly enriched in macrophage activation and neutrophils extracellular traps (NETs). Additionally, we reported that CAC extract owned significant anti-inflammatory activity by regulating PI3K-Akt-mTOR signal pathway, and inhibited NETosis in response to PMA. Conclusions We clarified that CAC extract significantly attenuated RA by inactivating macrophage and reducing NETosis via a multi-targets regulation. Graphical Abstract

The effects of projectile/target impedance matching and projectile shape on energy, momentum transfer and projectile melting during collisions are investigated by numerical simulation. By comparing the computation results with the experimental results, the correctness of the calculation and the statistical method of momentum transfer coefficient is verified. Different shapes of aluminum, copper and heavy tungsten alloy projectiles striking aluminum, basalt, and pumice target for impacts up to 10 km/s are simulated. The influence mechanism of the shape of the projectile and projectile/target density on the momentum transfer was obtained. With an increase in projectile density and length-diameter ratio, the energy transfer time between the projectile and targets is prolonged. The projectile decelerates slowly, resulting in a larger cratering depth. The energy consumed by the projectile in the excavation stage increased, resulting in lower mass-velocity of ejecta and momentum transfer coefficient. The numerical simulation results demonstrated that for different projectile/target combinations, the higher the wave impedance of the projectile, the higher the initial phase transition velocity and the smaller the mass of phase transition. The results can provide theoretical guidance for kinetic impactor design and material selection.

Flexible photodetector is crucial for the intelligent industrial applications. However, the optical-sensitive materials are usually grown in a high temperature and then transferred onto the flexible substrate. This paper reported a directly fabricated flexible photodetector based on TiO2-doped Graphene Nanosheets Embedded Carbon (GNEC)film. An Electron Cyclotron Resonance (ECR) system was employed to in-situ deposit TiO2-doped GNEC film on a polyimide substrate, which were subsequently sensitized with N719 dye to fabricate the TiO2@GNEC photodetector. The GNEC film contains vertically aligned Graphene Nanosheets (GNs), which exhibit high-density edge states. The edge states suppress the recombination rate of photo-generated electron-hole pairs, thereby significantly enhancing the photo-responsive performance. The photodetector demonstrates a high photo responsivity of 0.82 mA/W and a response time of 1.93 seconds. Due to the in-situ manufacturing capabilities of the ECR system, which avoids defects from secondary material transfers, the photodetector array exhibits excellent consistency and achieves clear recognition of light patterns in both flat and bent states.

This paper aims to establish a model that can reasonably reflect the mechanical properties of coal containing gas under different water content and confining pressure conditions. Firstly, the stress-strain characteristics of coal containing gas under different water content and confining pressure conditions are analyzed based on triaxial tests. Afterwards, this paper obtains the Duncan-Chang model parameters by combining the Duncan-Chang model and Janbu formula. Moreover, it establishes the fitting formulas of initial elastic modulus failure stress and various influencing factors, and conducts an improved Duncan-Chang model to characterize the deformation law of coal containing gas under different stress levels. Finally, this paper verifies the improved model and evaluate the accuracy of the mode. The results show that the increase of water content is an important reason for the dynamic change of coal model parameters of coal containing gas. The prediction curve of the improved model is in good agreement with the actual test curve, and the improved model can accurately reflect the stress-strain characteristics of coal containing gas under different confining pressures and water contents.

Abstract To analyze the relationship between macro and meso parameters of the gas hydrate bearing coal (GHBC) and to calibrate the meso-parameters, the numerical tests were conducted to simulate the laboratory triaxial compression tests by PFC3D, with the parallel bond model employed as the particle contact constitutive model. First, twenty simulation tests were conducted to quantify the relationship between the macro–meso parameters. Then, nine orthogonal simulation tests were performed using four meso-mechanical parameters in a three-level to evaluate the sensitivity of the meso-mechanical parameters. Furthermore, the calibration method of the meso-parameters were then proposed. Finally, the contact force chain, the contact force and the contact number were examined to investigate the saturation effect on the meso-mechanical behavior of GHBC. The results show that: (1) The elastic modulus linearly increases with the bonding stiffness ratio and the friction coefficient while exponentially increasing with the normal bonding strength and the bonding radius coefficient. The failure strength increases exponentially with the increase of the friction coefficient, the normal bonding strength and the bonding radius coefficient, and remains constant with the increase of bond stiffness ratio; (2) The friction coefficient and the bond radius coefficient are most sensitive to the elastic modulus and the failure strength; (3) The number of the force chains, the contact force, and the bond strength between particles will increase with the increase of the hydrate saturation, which leads to the larger failure strength.

Remote sensing image semantic segmentation methods have become the main approach for extracting cropland information. However, in the mountainous regions of southwestern China, croplands exhibit narrow and fragmented shapes, as well as complex planting patterns, making it difficult for traditional semantic segmentation methods to accurately delineate fine-grained cropland boundaries. To address these challenges, a multiattention Transformer network named MATNet is proposed in this paper, for fine-grained extraction of cropland at the parcel level in complex scenes. MATNet built upon the fusion of CNN encoder and Transformer decoder. In the encoder, spatial and channel reconstruction units are introduced, reducing information redundancy in the convolutional layers. The Transformer decoder incorporates multiple attention mechanisms, this design feature enhances the attention window's perception of local content and improves the model's ability to extract features from fine-grained cropland parcels through optimized computationnal al location. Taking the experimental results of the Dali cropland dataset as an illustration, MATNet achieved the highest values across five evaluation metrics, including mIoU. Specifically, the Recall, F1, and mIoU scores were 94.68%, 94.69%, and 89.92%, respectively. Compared with six other advanced models, MATNet consistently performed best in terms of extracting fine-grained cropland parcels.

Background Dysregulated circular RNAs (circRNAs) are involved in osteoarthritis (OA) progression.Objective We aimed to explore the effect of hsa_circ_0044719 (circTRIM25) on the ferroptosis of chondrocytes.Methods Chondrocytes were treated with interleukin (IL)-1β to generate cell model. Cellular behaviours were measured using cell counting kit-8, enzyme-linked immunosorbent assay, relevant kits, propidium iodide staining, and immunofluorescence assay. Quantitative real-time polymerase chain reaction was performed to examine the expression of circTRIM25, miR-138-5p, and cAMP responsive element binding protein 1 (CREB1), and their interactions were assessed using luciferase reporter analysis and RNA pull-down assay.Results CircTRIM25 was upregulated in OA tissues and IL-1β-stimulated chondrocytes. Knockdown of circTRIM25 facilitated the viability and suppressed ferroptosis and inflammation of IL-1β-induced cells. CircTRIM25 served as a sponge of miR-138-5p, which directly targets CREB1. Downregulation of miR-138-5p abrogated the effect induced by knockdown of circTRIM25. Furthermore, enforced CREB1 reversed the miR-138-5p induced effect. Moreover, knockdown of circTRIM25 attenuated cartilage injury in vivo.Conclusion Silencing of circTRIM25 inhibited ferroptosis of chondrocytes via the miR-138-5p/CREB axis and thus attenuated OA progression.

AbstractCatheter-related bloodstream infection (CRBSI) has become the bacterial infection of special concern considerably causing the prolonged hospitalization and the delayed clinical treatment. In this paper, silver nanoparticles (AgNPs) were stabilized in sodium polyethylene sulfonate (PVS) solution (PVS-Ag). Amphiphilic bio-carbon particles (ACPs) were synthesized from S. cerevisiae cells and employed as the matrix. Chitosan (CS) modification on ACPs (ACPs-CS) facilitated the PVS-Ag grafting with stability and efficiency. Results of morphologic analysis indicated that CS and PVS-Ag modification distinctly changed the morphological-structural properties of the ACPs surface. Surface potentials of ACPs, ACPs-CS and the obtained functionalized bio-carbon material (ACPs-CS-PVS-Ag) were −38.0 mV, +36.1 mV and −53.1 mV, respectively, revealing that the anionic groups enriched on the PVS-Ag surface had largely consumed the amino groups around the surface of ACPs-CS. Results from X-ray photoelectron spectroscopy (XPS) and thermogravimetric analysis (TGA) further demonstrated that AgNPs had successfully attached to the ACPs-CS surface. The anionic amphiphiles (ACPs-CS-PVS-Ag) exerted high blood-compatibility and bio-safety, especially the broad-spectrum antibacterial property at the microgram scale. In conclusion, the ACPs-CS-PVS-Ag assembly has potential value in the development of biomedical devices and/or implants for the safe-and-effective elimination of bacterial infections.

AbstractBackgrounds The role of O-GlcNAc transferase (OGT)-induced O-linked N-acetylglucosaminylation (O-GlcNAcylation) has been reported in multiple human diseases. However, its specific functions in osteoarthritis (OA) progression remain undetermined.Objective This study focused on the target proteins of OGT-induced O-GlcNAcylation in OA and the specific functional mechanism.Methods The levels of total O-GlcNAc and OGT were measured in both in vitro and in vivo OA models using western blot. The effects of OGT knockout on OA progression were detected through Safranin O staining, immunohistochemical staining and OARSI score evaluation. The effects of OGT silencing on LPS-induced chondrocyte injury were assessed by performing loss-of function assays. Co-immunoprecipitation (co-IP) was conducted to verify the effect of OGT-induced O-GlcNAcylation on the interaction between NEK7 and NLRP3. The role of OGT in modulating the O-GlcNAcylation and phosphorylation levels of NEK7 was analysed using western blot.Results The OGT-indued O-GlcNAcylation level was increased in both in vitro and in vivo OA models. Knockout of OGT mitigated OA progression in model mice. Additionally, silencing of OGT suppressed LPS-induced chondrocyte pyroptosis. Moreover, silencing of OGT inhibited the O-GlcNAcylation and enhanced the phosphorylation of NEK7 at S260 site, thereby blocking the binding of NEK7 with NLRP3.Conclusion OGT-induced NEK7 O-GlcNAcylation promotes OA progression by promoting chondrocyte pyroptosis via the suppressing interaction between NEK7 and NLRP3.

AbstractExtensive mining of mineral resources in the mountainous areas of southwestern China has caused frequent occurrences of landslides, threatening social and economic development. Therefore, further research on the formation mechanism of such landslides is urgently investigated. Using detailed geological investigations, a numerical simulation, and related theoretical analysis reveal the dynamic triggering mechanism, influencing factors, and mechanical evolution model of the Jianshanying landslide under the coupled action of heavy rainfall and mine blasting vibrations. Results showed the following: First, rainfall of about 5 days, which nearly saturated the slope, and nearly 3 blasting cycles (peak horizontal and vertical velocities of 0.3375 and 0.1573 cm/s, respectively) executed close to it were the main controlling factors inducing the landslide. Second, the macroscopic deformation of the slope manifested obvious subsidence and tipping, and the maximum vertical and horizontal displacements of the slope shoulder reached 13.466 and 2.961 m, respectively. Third, the critical failure of the slope occurred at 15 s in the dynamic analysis, and its subsequent responses involved disintegration and fragmentation, debris flow, scraping of the sliding bed, and self-stabilized accumulation. Finally, its mechanical evolution model was divided into the subsidence stage and the shear-tension stage. These results provide technical support for early identification and risk management of geological hazards in mines in southwestern China.

Background: Cognitive dysfunction, encompassing perioperative psychological distress and cognitive impairment, is a prevalent postoperative complication within the elderly population, and in severe cases, it may lead to dementia. Building upon our prior research that unveiled a connection between postoperative mood fluctuations and cognitive dysfunction with the phosphorylation of P38, this present investigation aims to delve deeper into the involvement of the P38 MAPK/NLRP3 pathway in perioperative neurocognitive disorders (PND) in an abdominal exploratory laparotomy (AEL) aged mice model. Methods: C57BL/6 mice (male, 18-month-old) underwent AEL with 3 % anesthesia. Then, inhibitors targeting P38 MAPK (SB202190, 1 mg/kg) and GSK3β (TWS119, 10 mg/kg) were administered multiple times daily for 7 days post-surgery. The NLRP3-cKO AEL and WT AEL groups only underwent the AEL procedure. Behavioral assessments, including the open field test (OFT), novel object recognition (NOR), force swimming test (FST), and fear conditioning (FC), were initiated on postoperative day 14. Additionally, mice designated for neuroelectrophysiological monitoring had electrodes implanted on day 14 before surgery and underwent novel object recognition while their local field potential (LFP) was concurrently recorded on postoperative day 14. Lastly, after they were euthanasized, pathological analysis and western blot were performed. Results: SB202190, TWS119, and astrocyte-conditional knockout NLRP3 all ameliorated the cognitive impairment behaviors induced by AEL in mice and increased mean theta power during novel location exploration. However, it is worth noting that SB202190 may exacerbate postoperative depressive and anxiety-like behaviors in mice, while TWS119 may induce impulsive behaviors. Conclusions: Our study suggests that anesthesia and surgical procedures induce alterations in mood and cognition, which may be intricately linked to the P38 MAPK/NLRP3 pathway.

Abstract Objectives EGFR‐tyrosine kinase inhibitor (TKI) is used to treat recurrent and metastatic nasopharyngeal carcinoma (rmNPC). This meta‐analysis aims to study the efficacy and safety of EGFR‐TKI in treating patients with rmNPC. Methods We conducted a systematic search of PubMed, Embase, and Web of Science up to November 2023, and included literature that met the criteria. We extracted objective response rate (ORR), disease control rate (DCR), median progression‐free survival (mPFS), median overall survival (mOS), and adverse reaction‐related events and performed meta‐analysis using Stata 14.0. Results A total of nine articles were included. The summary results showed that the ORR for patients treated with EGFR‐TKI for rmNPC was 38% (95% CI = 27%–49%), the DCR was 71% (95% CI = 61%–80%), the mPFS was 6.29 months (95% CI = 5.22–7.35), and the mOS was 15.94 months (95% CI = 14.68–17.20). The most common grade 3–4 adverse reaction events in these patients were mucositis, nasopharyngeal necrosis, and oral ulceration. We found an incidence rate of 49% (95% CI = 38%–61%) for grade 3–4 adverse events (AEs). The anti‐PD1 combined with TKI treatment method is more effective than the EGFR‐TKI alone for treating rmNPC. Conclusion The study shows that EGFR‐TKI has good efficacy in treating rmNPC but does not translate into survival benefits and owns a high incidence of grade 3–4 AEs. More RCT trials are needed in the future to verify the efficacy of anti‐PD1 combined with TKI treatment method.

BackgroundIn recent years, the prevalence of obesity has continued to increase as a global health concern. Numerous epidemiological studies have confirmed the long-term effects of exposure to ambient air pollutant particulate matter 2.5 (PM2.5) on obesity, but their relationship remains ambiguous.MethodsUtilizing large-scale publicly available genome-wide association studies (GWAS), we conducted univariate and multivariate Mendelian randomization (MR) analyses to assess the causal effect of PM2.5 exposure on obesity and its related indicators. The primary outcome given for both univariate MR (UVMR) and multivariate MR (MVMR) is the estimation utilizing the inverse variance weighted (IVW) method. The weighted median, MR-Egger, and maximum likelihood techniques were employed for UVMR, while the MVMR-Lasso method was applied for MVMR in the supplementary analyses. In addition, we conducted a series of thorough sensitivity studies to determine the accuracy of our MR findings.ResultsThe UVMR analysis demonstrated a significant association between PM2.5 exposure and an increased risk of obesity, as indicated by the IVW model (odds ratio [OR]: 6.427; 95% confidence interval [CI]: 1.881–21.968; PFDR = 0.005). Additionally, PM2.5 concentrations were positively associated with fat distribution metrics, including visceral adipose tissue (VAT) (OR: 1.861; 95% CI: 1.244–2.776; PFDR = 0.004), particularly pancreatic fat (OR: 3.499; 95% CI: 2.092–5.855; PFDR =1.28E-05), and abdominal subcutaneous adipose tissue (ASAT) volume (OR: 1.773; 95% CI: 1.106–2.841; PFDR = 0.019). Furthermore, PM2.5 exposure correlated positively with markers of glucose and lipid metabolism, specifically triglycerides (TG) (OR: 19.959; 95% CI: 1.269–3.022; PFDR = 0.004) and glycated hemoglobin (HbA1c) (OR: 2.462; 95% CI: 1.34–4.649; PFDR = 0.007). Finally, a significant negative association was observed between PM2.5 concentrations and levels of the novel obesity-related biomarker fibroblast growth factor 21 (FGF-21) (OR: 0.148; 95% CI: 0.025–0.89; PFDR = 0.037). After adjusting for confounding factors, including external smoke exposure, physical activity, educational attainment (EA), participation in sports clubs or gym leisure activities, and Townsend deprivation index at recruitment (TDI), the MVMR analysis revealed that PM2.5 levels maintained significant associations with pancreatic fat, HbA1c, and FGF-21.ConclusionOur MR study demonstrates conclusively that higher PM2.5 concentrations are associated with an increased risk of obesity-related indicators such as pancreatic fat content, HbA1c, and FGF-21. The potential mechanisms require additional investigation.

BackgroundWe aimed to evaluate the efficacy, safety, and immunogenicity of a SARS-CoV-2 mRNA vaccine (Omicron BA.5) LVRNA012 given as the booster in immunized but SARS-CoV-2 infection-free adults in China.MethodsThis is a single-center, randomized, double-blind, placebo-controlled phase 3 clinical trial enrolling healthy adult participants (≥18 years) who had completed two or three doses of inactivated COVID-19 vaccines at least 6 months before, in Bengbu, Anhui province, China. Eligible participants were randomly assigned (1:1) to receive a booster intramuscular vaccination with an LVRNA012 vaccine (100ug) or placebo. The primary endpoint was the protective efficacy of a booster dose of the LVRNA012 vaccine or placebo against symptomatic COVID-19 of any severity 14 days after vaccination. Laboratory-confirmed COVID-19 infections were identified from 14 days to 180 days after intervention, with active surveillance for symptomatic illness 8 times per month between 7 to 90 days and at least once per month between 90 to 180 days after intervention.Results2615 participants were recruited and randomly assigned in a 1:1 ratio to either the vaccine group (1308) or the placebo group (1307). A total of 141 individuals (46 in the LVRNA012 group and 95 in the placebo group) developed symptomatic COVID-19 infection 14 days after the booster immunization, showing a vaccine efficacy of 51.9% (95% CI, 31.3% to 66.4%). Most infections were detected 90 days after intervention during a period when XBB was prevalent in the community. Adverse reactions were reported by 64% of participants after the LVRNA012 vaccination, but most of them were mild or moderate. The booster vaccination with the LVRNA012 mRNA vaccine could significantly enhance neutralizing antibody titers against the Omicron variant XBB.1.5 (GMT 132.3 [99.8, 175.4]) than did those in the placebo group (GMT 12.5 [8.4, 18.7]) at day 14 for the previously immunized individuals.ConclusionThe LVRNA012 mRNA vaccine is immunogenic, and shows robust efficacy in preventing COVID-19 during the omicron-predominate period.Clinical trial registrationClinicalTrials.gov, identifier NCT05745545.

This study examined the applicability of indocyanine green (ICG) fluorescence imaging to assist the laparoscopic resection of retroperitoneal tumors in pediatric patients via an abdominal approach. Conducted prospectively at the Guangzhou Women and Children's Medical Center from May to September 2023, the research included three pediatric cases, for whom laparoscopic retroperitoneal tumor resections were performed utilizing ICG fluorescence imaging. In each case, ICG was intravenously administered (0.3 mg/kg) prior to surgery, enabling the visualization of vital vascular structures through real-time fluorescence imaging. The trocar's placement was guided by a “four-hole” technique from the healthy side in a 70-degree lateral decubitus position. The operations were accomplished successfully without any complications. Pathological analysis of the patients identified one case of Wilms tumor of the embryonal type, one ganglioneuroblastoma of the mature type without N-MYC gene amplification, and one mature cystic teratoma. The findings suggest that with careful patient selection and skilled surgical execution, the utilization of ICG fluorescence imaging in the laparoscopic resection of retroperitoneal tumors is both safe and effective in children. This approach significantly improves the visualization of critical blood vessels, thus enhancing surgical safety.

BackgroundThis study aimed to compare the clinical outcomes of Zero-P and ROI-C devices applied to anterior cervical discectomy and fusion (ACDF) surgery of cervical degenerative disc disease (CDDD).MethodsFrom January 2020 and December 2020, 56 patients with CDDD who underwent ACDF using Zero-P or ROI-C were included in this retrospective study. The outcomes included visual analogue scale (VAS) score, Japanese Orthopedic Association (JOA) score, neck disability index (NDI) score, Cobb angle, dysphagia, and bone fusion rate. Dysphagia was assessed using the Bazaz grading system. The comparison of outcomes between the two groups was based on the 2-year follow-up time point, which was defined as the last follow-up visit.ResultsThe Zero-P group included 16 males and 14 females, with a mean age of 56.2 (range, 35–65) years. The ROI-C group included 11 males and 15 females, with a mean age of 57.4 (range, 36–67) years. There was no significant difference in gender and mean age between the two groups. There were no significant differences in VAS score, JOA score, NDI score, Cobb angle, dysphagia, and bone fusion rate between two groups at the last follow up visit. In the Zero-P group, the duration of surgeries involving C3–4 or C6–7 segments was significantly longer than those including C4–5 or C5–6 segments (135.0 ± 19.0 vs. 105.6 ± 17.5 min, P 0.05). The Cobb angle in the last follow-up visit in the Zero-P group (24.4 ± 4.5°) was significantly higher than that in the ROI-C group (18.1 ± 2.3°) (P

Background: Immunotherapy has changed the treatment landscape for lung cancer. This study aims to construct a tumor mutation-related model that combines long non-coding RNA (lncRNA) expression levels and tumor mutation levels in tumor genomes to detect the possibilities of the lncRNA signature as an indicator for predicting the prognosis and response to immunotherapy in lung adenocarcinoma (LUAD). Methods: We downloaded the tumor mutation profiles and RNA-seq expression database of LUAD from The Cancer Genome Atlas (TCGA). Differentially expressed lncRNAs were extracted based on the cumulative number of mutations. Cox regression analyses were used to identify the prognostic lncRNA signature, and the prognostic value of the five selected lncRNAs was validated by using survival analysis and the receiver operating characteristic (ROC) curve. We used qPCR to validate the expression of five selected lncRNAs between human lung epithelial and human lung adenocarcinoma cell lines. The ImmuCellAI, immunophenoscore (IPS) scores and Tumor Immune Dysfunction and Exclusion (TIDE) analyses were used to predict the response to immunotherapy for this mutation related lncRNA signature. Results: A total of 162 lncRNAs were detected among the differentially expressed lncRNAs between the Tumor mutational burden (TMB)-high group and the TMB-low group. Then, five lncRNAs (PLAC4, LINC01116, LINC02163, MIR223HG, FAM83A-AS1) were identified as tumor mutation-related candidates for constructing the prognostic prediction model. Kaplan‒Meier curves showed that the overall survival of the low-risk group was significantly better than that of the high-risk group, and the results of the GSE50081 set were consistent. The expression levels of PD1, PD-L1 and CTLA4 in the low-risk group were higher than those in the high-risk group. The IPS scores and TIDE scores of patients in the low-risk group were significantly higher than those in the high-risk group. Conclusion: Our findings demonstrated that the five lncRNAs (PLAC4, LINC01116, LINC02163, MIR223HG, FAM83A-AS1) were identified as candidates for constructing the tumor mutation-related model which may serve as an indicator of tumor mutation levels and have important implications for predicting the response to immunotherapy in LUAD.

Abstract CTCF plays an important role in 3D genome organization by adjusting the strength of chromatin insulation at TAD boundaries, where clustered CBS (CTCF-binding site) elements are often arranged in a tandem array with a complex divergent or convergent orientation. Here, using Pcdh and HOXD loci as a paradigm, we look into the clustered CTCF TAD boundaries and find that, counterintuitively, outward-oriented CBS elements are crucial for inward enhancer-promoter interactions as well as for gene regulation. Specifically, by combinatorial deletions of a series of putative enhancer elements in mice in vivo or CBS elements in cultured cells in vitro, in conjunction with chromosome conformation capture and RNA-seq analyses, we show that deletions of outward-oriented CBS elements weaken the strength of long-distance intra-TAD promoter-enhancer interactions and enhancer activation of target genes. Our data highlight the crucial role of outward-oriented CBS elements within the clustered CTCF TAD boundaries in developmental gene regulation and have interesting implications on the organization principles of clustered CTCF sites within TAD boundaries.

Abstract Background Recent studies have shown that, owning to its cohesive cleavage, Cas9-mediated CRISPR gene editing outcomes at junctions of chromosomal rearrangements or DNA-fragment editing are precise and predictable; however, the underlying mechanisms are poorly understood due to lack of suitable assay system and analysis tool. Results Here we developed a customized computer program to take account of staggered or cohesive Cas9 cleavage and to rapidly process large volumes of junctional sequencing reads from chromosomal rearrangements or DNA-fragment editing, including DNA-fragment inversions, duplications, and deletions. We also established a sensitive assay system using HPRT1 and DCK as reporters for cell growth during DNA-fragment editing by Cas9 with dual sgRNAs and found prominent large resections or long deletions at junctions of chromosomal rearrangements. In addition, we found that knockdown of PolQ (encoding Polθ polymerase), which has a prominent role in theta-mediated end joining (TMEJ) or microhomology-mediated end joining (MMEJ), results in increased large resections but decreased small deletions. We also found that the mechanisms for generating small deletions of 1bp and >1bp during DNA-fragment editing are different with regard to their opposite dependencies on Polθ and Polλ (encoded by the PolL gene). Specifically, Polθ suppresses 1bp deletions but promotes >1bp deletions, whereas Polλ promotes 1bp deletions but suppresses >1bp deletions. Finally, we found that Polλ is the main DNA polymerase responsible for fill-in of the 5′ overhangs of staggered Cas9 cleavage ends. Conclusions These findings contribute to our understanding of the molecular mechanisms of CRISPR/Cas9-mediated DNA-fragment editing and have important implications for controllable, precise, and predictable gene editing.

Highlights Alkyl-tailored Y-SMAs named YR-SeNF series with near-infrared absorption, different molecular crystallinity and self-assembly abilities are developed. The related organic solar cells (OSCs) with an active layer processed from halogen-free solvents and spin-coating-free technologies achieve a ~ 19% efficiency. Ternary OSCs offer a robust operating stability under MPP tracking and well-keep > 80% of the initial efficiency for even over 400 h.

Abstract Objective: To determine if customer purchases at small food stores are associated with healthfulness of the diet as approximated by skin carotenoids. Design: This is a cross-sectional survey of customers in small food stores regarding demographics and food purchases. Food and beverage purchases were classified as ‘healthy’ or ‘non-healthy’ and ‘carotenoid’ v. ‘non-carotenoid’ using a systematic classification scheme. Fruit and vegetable intake was objectively assessed using a non-invasive device to measure skin carotenoids. Associations between variables of interest were examined using Pearson’s correlation coefficients, t tests and multiple linear regression analyses. Setting: Twenty-two small food retail stores in rural (n 7 stores) and urban (n 15) areas of North Carolina. Participants: Customers of small food stores Results: Of study participants (n 1086), 55·1 % were male, 60·0 % were African American/Black and 4·2 % were Hispanic, with a mean age of 43·5 years. Overall, 36 % purchased at least one healthy item, and 7·6 % of participants purchased a carotenoid-containing food/beverage. Healthy foods and beverages purchased included produce, lean meats, 100 % juices, plain popcorn, plain nuts, milk and yogurt. Unhealthy items included non-100 % juices, crackers, chips, candy, cakes and donuts. Purchase of a healthy or carotenoid-containing item was positively associated with skin carotenoid scores (P = 0·002 and 0·006, respectively). Conclusions: A relatively small proportion of customers purchased any healthy or carotenoid-containing foods and beverages, and those who did purchase healthy options had higher skin carotenoid scores. Future research should confirm these findings in different populations.

The central and western coal resources have the highest degree of enrichment and superior development conditions in China. With the improvement of mining efficiency, the disturbance of high-intensity and large-mining-height mining mode to groundwater system also increases. In particular, the groundwater in the aquifer outside the disturbance range of the water-conducting fracture zone gradually participates in the mine water inflow process during the coal mining. Such mode leads to a series of problems such as large deviation of mine water inflow prediction, inaccurate evaluation of water inflow risk and unclear water hazard prevention measures, which brings great hidden risks to the current mine water hazard prevention and control. In this paper, a derivative mode of dynamic water inrush is summarized. With the coal mining, the evolution of groundwater system caused by overburden failure will induce new disaster sources, resulting in different forms of water inrush. Its connotation is to change the basis of defining the derivative dynamic water inrush model from the traditional static analysis before mining to the dynamic evaluation considering the change in the whole mining cycle. The derived dynamic water inrush model of the mine can be preliminarily divided into three categories, namely, “skylight leakage type”, “bed separation disaster type” and “channel permeability increase type”. This paper mainly discusses the derivative dynamic water inrush mode of “skylight leakage type”. Taking the Shanxi Yushen mining area, a shallow buried coal seam mining area with high strength and large mining height, as an example, the disaster-pregnant conditions of “skylight supply type” derivative disasters are discussed in depth. Through supplementary analysis of water-richness and hydraulic connection strength of indirect water-filled aquifer, the comprehensive evaluation of water inrush risk in roof aquifer is achieved, and the evaluation method system of disaster derivative model is put forward. Through the transformation of mining mode, the active prevention and control system is constructed. A passive prevention and control system is constructed by multi-objective advance drainage before mining and local grouting after mining. By further refining the mine water inrush disaster model, optimizing the evaluation system and establishing comprehensive prevention and control technology, it provides a scientific basis for the protection of groundwater resources and safe low-carbon mining in ecologically fragile areas.

Abstract Background The morbidity and mortality of community-acquired pneumonia (CAP) remain high among infectious diseases. It was reported that angiopoietin-like 4 (ANGPTL4) could be a diagnostic biomarker and a therapeutic target for pneumonia. This study aimed to develop a more objective, specific, accurate, and individualized scoring system to predict the severity of CAP. Methods Totally, 31 non-severe community-acquired pneumonia (nsCAP) patients and 14 severe community-acquired pneumonia (sCAP) patients were enrolled in this study. The CURB-65 and pneumonia severity index (PSI) scores were calculated from the clinical data. Serum ANGPTL4 level was measured by enzyme-linked immunosorbent assay (ELISA). After screening factors by univariate analysis and receiver operating characteristic (ROC) curve analysis, multivariate logistic regression analysis of ANGPTL4 expression level and other risk factors was performed, and a nomogram was developed to predict the severity of CAP. This nomogram was further internally validated by bootstrap resampling with 1000 replications through the area under the ROC curve (AUC), the calibration curve, and the decision curve analysis (DCA). Finally, the prediction performance of the new nomogram model, CURB-65 score, and PSI score was compared by AUC, net reclassification index (NRI), and integrated discrimination improvement (IDI). Results A nomogram for predicting the severity of CAP was developed using three factors (C-reactive protein (CRP), procalcitonin (PCT), and ANGPTL4). According to the internal validation, the nomogram showed a great discrimination capability with an AUC of 0.910. The Hosmer–Lemeshow test and the approximately fitting calibration curve suggested a satisfactory accuracy of prediction. The results of DCA exhibited a great net benefit. The AUC values of CURB-65 score, PSI score, and the new prediction model were 0.857, 0.912, and 0.940, respectively. NRI comparing the new model with CURB-65 score was found to be statistically significant (NRI = 0.834, P

Abstract Background Compared to traditional fetal heart rate monitoring (FHR) for the outpatients in clinic, remote FHR monitoring shows real-time assessment of fetal wellbeing at home. The clinical function of remote FHR monitoring in pregnant wome in outpatient is still unclear. Objective To explore the feasibility of remote FHR self-monitoring in singleton pregnant women from southern China. Study design This prospective cohort study was conducted at one tertiary center in southern China. Pregnant women used a mobile cardiotocogram device to measure the FHR at least once a week until delivery in the remote group. For the control group, pregnant women underwent traditional FHR monitoring once a week in the outpatient clinic. The rate of cesarean section, risk of postpartum hemorrhage and adverse neonatal outcomes were compared between the two groups. All the pregnant women completed a questionnaire survey to evaluate their acquisition of remote FHR self-monitoring. Results Approximately 500 women were recruited in the remote FHR self-monitoring group (remote group), and 567 women were recruited in the traditional FHR monitoring group (control group). The women in the remote FHR monitoring group were more likely to be nulliparous (P

The sub-lakes of Poyang Lake have significant ecological value. To date, the diazotrophs in sub-lakes are unknown. Moreover, no study has simultaneously focused on diazotrophic communities in the water and sediment in natural freshwater ecosystems. In this study, we investigated the diazotrophic alpha diversity, structure, abundance, molecular ecological network, and community assembly mechanism in the water and sediment of sub-lakes using Illumina MiSeq sequencing and a quantitative polymerase chain reaction assay. The results showed that the sediment had a greater diversity of diazotrophs than the water. Proteobacteria and Spirochaetes were the dominant diazotrophic phyla in the water, whereas Proteobacteria was the dominant diazotrophic phylum in the sediment. There were significant differences in the composition of diazotrophic communities between the water and sediment. The sediment had a more complex co-occurrence network of diazotrophs than the water. Deterministic processes dominate the community assembly of diazotrophs in both the water and sediment of the sub-lakes, and the relative role of deterministic processes was stronger for sediment than water. Our study is the first to reveal the differences in the diazotrophic communities between the water and sediment in natural freshwater ecosystems and provides the fundamental scientific datasets for understanding the nitrogen fixation process in sub-lakes.