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Understanding the historical groundwater recharge process and its influencing factors is crucial for effectively managing regional groundwater resources amidst future climate change. However, the availability of high-resolution hydroclimate archives remains severely limited. In this study, we used a 59 m chloride profile within the unsaturated loess zone to reconstruct the potential groundwater recharge (PGR) records spanning 273 years in a near-humid area on the Loess Plateau. Spectral analysis was employed to identify the principal influencing factors on PGR across various time scales. The reconstructed hydrological records revealed three wet periods and four dry periods from 1745 to 2007 AD, with PGR rates ranging from 66.7 to 222.4 mm yr−1 during wet periods and 20.0 to 66.7 mm yr−1 during dry periods. In addition, spectral analysis indicated multiple cycles, ranging from 2.1 to 50.0 years, within the PGR history. Temperature, precipitation, and sunspot activity emerged as the key factors governing the rate of PGR over the 3-year, 7-year, and 11-year time scales, respectively, highlighting the combined influence of solar activity and climate on the PGR process. These findings enhance our understanding of groundwater recharge and environmental climate dynamics in the near-humid loess unsaturated zone and other regions exhibiting similar hydroclimatic conditions.

A crucial challenge faced by noninvasive imaging through strongly scattering media is overcoming background light interference. Polarization-based anti-scattering methods can eliminate background light interference, but fail to utilize speckle images that do not contain unscattered object light for object reconstruction. Although speckle correlation imaging (SCI) methods can utilize speckle images for object reconstruction, it is difficult to achieve stable high-quality reconstruction and overcome background light interference using these methods. In this study, we propose a polarized-speckle deviation imaging (PSDI) method to overcome background light interference and achieve high-quality imaging through strongly scattering media. PSDI utilizes the bispectrum and autocorrelation of polarized speckle image deviations to reconstruct the Fourier phase and amplitude spectra of the object image, respectively. Experimental results show that when the background light is polarized and unpolarized, PSDI can achieve stable high-fidelity reconstruction of a polarized object when the signal-to-background ratio (SBR) is lower than −7 dB and −9 dB, respectively. PSDI bridges the gap between imaging with strongly scattered light and overcoming strong background light interference, and is expected to find widespread applications in fields such as biomedical imaging, astronomical observation, underwater imaging, and remote sensing.

Previous control methods developed by our research team cannot satisfy the high accuracy requirements of unmanned surface vessel (USV) path-tracking during bathymetric mapping because of the excessive overshoot and slow convergence speed. For this reason, this study developed an adaptive fuzzy integral-derivative line-of-sight (AFIDLOS) method for USV path-tracking control. Integral and derivative terms were added to counteract the effect of the sideslip angle with which the USV could be quickly guided to converge to the planned path for bathymetric mapping. To obtain high accuracy of the look-ahead distance, a fuzzy control method was proposed. The proposed method was verified using simulations and outdoor experiments. The results demonstrate that the AFIDLOS method can reduce the overshoot by 79.85%, shorten the settling time by 55.32% in simulation experiments, reduce the average cross-track error by 10.91% and can ensure a 30% overlap of neighboring strips of bathymetric LiDAR outdoor mapping when compared with the traditional guidance law.

Four new species of jelly fungi were described from northeastern China based on morphological and molecular evidence. These new species were classified into the four genera Sirobasidium (Sirobasidium jilinense), Calocera (Calocera velutina), Dacrymyces (Dacrymyces jauensis), and Dacryopinax (Dacryopinax manghanensis). Maximum likelihood and Bayesian analyses were performed using a combined nuc rDNA internal transcribed spacer region (ITS) and nuc 28S rDNA (nrLSU) dataset for the construction of phylogenetic trees. Morphological descriptions, line illustrations, and the ecological habits of these new species are provided.

The integration of visual algorithms with infrared imaging technology has become an effective tool for industrial gas leak detection. However, existing research has mostly focused on simple scenarios where a gas plume is clearly visible, with limited studies on detecting gas in complex scenes where target contours are blurred and contrast is low. This paper uses a cooled mid-wave infrared (MWIR) system to provide high sensitivity and fast response imaging and proposes the MWIRGas-YOLO network for detecting gas leaks in mid-wave infrared imaging. This network effectively detects low-contrast gas leakage and segments the gas plume within the scene. In MWIRGas-YOLO, it utilizes the global attention mechanism (GAM) to fully focus on gas plume targets during feature fusion, adds a small target detection layer to enhance information on small-sized targets, and employs transfer learning of similar features from visible light smoke to provide the model with prior knowledge of infrared gas features. Using a cooled mid-wave infrared imager to collect gas leak images, the experimental results show that the proposed algorithm significantly improves the performance over the original model. The segment mean average precision reached 96.1% (mAP50) and 47.6% (mAP50:95), respectively, outperforming the other mainstream algorithms. This can provide an effective reference for research on infrared imaging for gas leak detection.

As an important mechanism in the post-transcriptional regulation of eukaryotic gene expression, alternative polyadenylation (APA) plays a key role in biological processes such as cell proliferation and differentiation. However, the role and dynamic pattern of APA during Litopenaeus vannamei metamorphosis are poorly understood. Here, RNA-seq data covering from the embryo to the maturation (16 time points) of L. vannamei were utilized. We identified 247 differentially expressed APA events between early and adult stages, and through fuzzy mean clustering analysis, we discovered five dynamic APA patterns. Among them, the gradual elongation of the 3′UTR is the major APA pattern that changes over time, and its genes are enriched in the pathways of protein and energy metabolism. Finally, we constructed mRNA-miRNA and PPI networks and detected several central miRNAs that may regulate L. vannamei development. Our results revealed the complex APA mechanisms in L. vannamei metamorphosis, shedding new light on post-transcriptional regulation of crustacean metamorphosis.

Introduction Pulmonary vein isolation (PVI) is the cornerstone of radiofrequency (RF) ablation for atrial fibrillation (AF). However, a single ablation strategy does not always achieve the desired therapeutic effect in all patients with persistent AF, and individualised strategies are required for different clinical characteristics.Methods and analysis This study aimed to determine the optimal catheter ablation strategy for persistent AF by comparing the efficacy of PVI and BCXL (BC: big circles encircling pulmonary vein isolation; XL: unfixed number of lines based on the left atrial substrate). The BCXL-AF study (clinical trial no. ChiCTR2200067081) was designed as a prospective, randomised, parallel-controlled, single-blinded clinical trial. Overall, 400 patients with persistent AF were randomised in a 1:1 ratio into PVI-only and BCXL-individualised ablation groups. Patients randomised to the individualised ablation group will be further categorised into risk strata according to their clinical condition using the actual ablation method determined by the strata. Seven postoperative visits were conducted from discharge to 24 months of age. The primary observation endpoint will be the incidence of atrial tachyarrhythmia (including AF, atrial flutter and atrial tachycardia with a duration of ≥30 s) without using antiarrhythmic drugs after a blank period of 3 months following a single ablation procedure. The BCXL-AF study will assess an optimal approach for persistent AF RF ablation and evaluate the effectiveness of individualised RF ablation strategies in reducing the recurrence rate of AF.Ethics and dissemination The study protocol was reviewed, and ethical approval was obtained from the Army Medical University Human Ethics Committee (approval number: 2022-484-01). All the participants provided written informed consent. This study was conducted according to the principles of the Declaration of Helsinki and its amendments. The results of this study will be disseminated through manuscript publication and conference presentations.Trial registration number ChiCTR2200067081.

Abstract is missing (Short communication)

Urothelial carcinoma (UC) is a prevalent malignant tumor involving the urinary system. Although there are various treatment modalities, including surgery, chemotherapy, and immune checkpoint inhibitor (ICI) therapy, some patients experience disease recurrence and metastasis with poor prognosis and dismal long-term survival. Antibody–drug conjugates (ADCs), which combine the targeting ability of antibody drugs with the cytotoxicity of chemotherapeutic drugs, have recently emerged as a prominent research focus in the development of individualized precision cancer therapy. Although ADCs have improved the overall response rate in patients with UC, their effectiveness remains limited. Currently, ADC-based combination therapies, particularly ADC combined with ICIs, have demonstrated promising efficacy. This combination approach has advanced the treatment of UC, exhibiting the potential to become the standard first-line therapy for advanced UC in the future. This article reviewed clinical trials involving ADC-based combination therapy for UC and discussed the possible challenges and future perspectives to provide guidance for the clinical treatment of UC.

The original coarse spatial resolution of Gravity Recovery and Climate Experiment (GRACE) data limits its application in small and medium-scale areas. The study proposes a novel random forest-based GRACE drought index (NRFGDI) to enhance the spatial resolution of drought monitoring, which is applied to central Yunnan. We first employed the random forest (RF) algorithm to improve the spatial resolution of GRACE-derived terrestrial water storage anomaly (TWSA) to 0.1°, then established the NRFGDI based on the downscaled TWSA. Subsequently, the NRFGDI was verified using traditional drought indexes, including the standardized precipitation evapotranspiration index (SPEI) and the self-calibrating Palmer drought severity index (sc-PDSI), along with the 2009/2010 Bulletin of Flood and Drought Disasters in China. The NRFGDI not only captures drought characteristics, but also offers finer spatial resolution. The study provides an effective means for medium to small-scale drought monitoring, thereby making valuable contributions to decision-making processes concerning droughts in central Yunnan.

BackgroundBletilla striata (Thunb.) Reichb.f. (B. striata) is a traditional Chinese medicinal herb. B. striata polysaccharides (BSP), stilbenes and 2-isobutyl malic acid glucosoxy-benzyl ester compounds are the main active ingredients in B. striata. However, there is limited report on the changes of medicinal components and their biosynthesis regulation mechanisms in the tubers of B. striata at different stages.MethodThe tubers of B. striata were collected during the flowering period, fruiting period, and harvest period to determine the total polysaccharide content using the phenol sulfuric acid method. The changes in secondary metabolites in the tubers at these stages were analyzed by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS), and transcriptomics was conducted for further exploration of their biosynthetic pathways.ResultThe BSP content gradually increases from the flowering period to the fruiting period as the tubers develop, reaching its peak, but subsequently decreases at harvest time, which may be associated with the germination of B. striata buds in later stage. A total of 294 compounds were identified in this study. Among them, a majority of the compounds, such as 2-isobutyl malate gluconoxy-benzyl ester, exhibited high content during the fruit stage, while stilbenes like coelonin, 3'-O-methylbatatasin III, and blestriarene A accumulated during the harvesting period. The transcriptome data also revealed a substantial number of differentially expressed genes at various stages, providing a partial explanation for the complex changes in metabolites. We observed a correspondence between the expression pattern of GDP-Man biosynthesis-related enzyme genes and cumulative changes in BSP. And identified a positive correlation between 9 transcription factors and genes associated with polysaccharide biosynthesis, while 5 transcription factors were positively correlated with accumulation of 2-isobutyl malate gluconoxy-benzyl ester compounds and 5 transcription factors exhibited negative correlated with stilbene accumulation.ConclusionIt is imperative to determine the appropriate harvesting period based on the specific requirements of different active ingredients and the accumulation patterns of their metabolites. Considering the involvement of multiple transcription factors in the biosynthesis and accumulation of its active ingredients, a comprehensive investigation into the specific regulatory mechanisms that facilitate high-quality cultivation of B. striata is imperative.

Colon cancer is increasing worldwide and is commonly regarded as hormone independent, yet recent reports have implicated sex hormones in its development. Nevertheless, the role of hormones from the hypothalamus–hypophysis axis in colitis-associated colorectal cancer (CAC) remains uncertain. In this study, we observed a significant reduction in the expression of the oxytocin receptor (OXTR) in colon samples from both patient with colitis and patient with CAC. To investigate further, we generated mice with an intestinal-epithelium-cell-specific knockout of OXTR. These mice exhibited markedly increased susceptibility to dextran-sulfate-sodium-induced colitis and dextran sulfate sodium/azoxymethane-induced CAC compared to wild-type mice. Our findings indicate that OXTR depletion impaired the inner mucus of the colon epithelium. Mechanistically, oxytocin was found to regulate Mucin 2 maturation through β1-3-N-acetylglucosaminyltransferase 7 (B3GNT7)-mediated fucosylation. Interestingly, we observed a positive correlation between B3GNT7 expression and OXTR expression in human colitis and CAC colon samples. Moreover, the simultaneous activations of OXTR and fucosylation by l-fucose significantly alleviated tumor burden. Hence, our study unveils oxytocin’s promising potential as an affordable and effective therapeutic intervention for individuals affected by colitis and CAC.

AimsTo explore the causal relationship between ulcerative colitis (UC) and male infertility using Mendelian randomization method with single nucleotide polymorphism (SNP) as the instrumental variables.MethodsGenetic loci closely associated with UC were extracted as instrumental variables and male infertility was the outcome variable in pooled data from the gene-wide association study (GWAS),which was derived from European ethnic groups. The UC data(ebi-a-GCST003045) contained a total sample size of 27432 individuals and 110944 SNPs, and the male infertility data(finn-b-N14_MALEINFERT) contained a total sample size of 73479 individuals and 16377329 SNPs. The SNPs highly correlated with UC were screened from ebi-a-GCST003045(P0.8,replacing the missing SNPs with SNPs with high linkage, and deleting SNPs without substitution sites) were extracted. MR analysis was performed using MR-Egger regression, the weighted median and the inverse-variance weighted (IVW) respectively, and the causal relationship between UC and male infertility was evaluated by OR and 95% CI, and the Egger-intercept method was used to test for horizontal multiplicity, and the sensitivity analysis was performed using "leave-one-out method". Finally, we used Bayesian Weighted Mendelian Randomization (BWMR) approach to test the results of MR study.ResultsA total of 86 SNPs were included as IVs, with OR and 95% CI of 1.095(0.820~1.462)、1.059(0.899~1.248)、1.125(1.002~1.264) for MR-Egger, the weighted median and IVW results respectively, and P value of less than 0.05 for IVW, indicating that a causal relationship between UC and male infertility was causally related. The results of MR analysis combined with BWMR analysis also showed positive genetic causal relationship between UC and male infertility.MR-Egger regression showed an intercept of -2.21×10-3 with a standard error of 0.006 and P = 0.751, there was no horizontal pleiotropy for the IVs of exposure factors. Heterogeneity tests showed no heterogeneity and the results of the "leave-one-out" sensitivity analysis were stable.ConclusionThere is a causal association between UC and male infertility, which increases the risk of developing male infertility.

The real-time monitoring on the risk status of the vehicle and its driver can provide the assistance for the early detection and blocking control of single-vehicle accidents. However, complex risk coupling relationship is one of the main features of single-vehicle accidents with high mortality rate. On the basis of investigating the coupling effect among multi-risk factors and establishing a safety management database throughout the life cycle of vehicles, single-vehicle driving risk network (SVDRN) with a three-level threshold was developed, and its topology features were analyzed to assessment the importance of nodes. To avoid the one-sidedness of single indicator, the multi-attribute comprehensive evaluation model was applied to measure the comprehensive effect of characteristic indicators for nodes importance. A algorithm for real-time monitoring of vehicle driving risk status was proposed to identify key risk chains. The result revealed that improper operation, speeding, loss of vehicle control and inefficient driver management were the sequence of top four risk factors in the comprehensive evaluation result of nodes importance (mean value = 0.185, SD = 0.119). There were minor differences of 0.017 in the node importance among environmental factors, among which non-standard road alignment had the larger value. The improper operation and non-standard road alignment were the highest combination correlation of factors affecting road safety, with the support of 51.81% and the confidence of 69.35%. This identification algorithm of key risk chains that combines node importance and its risk state threshold can effectively determine the high-frequency risk transmission paths and risk factors through multi-vehicle test, providing a basis for centralization management of transport enterprises.

The macrovascular complications of diabetes cause high mortality and disability in patients with type 2 diabetes mellitus (T2DM). The inflammatory response of vascular smooth muscle cell (VSMC) runs through its pathophysiological process. Salvianolic acid B (Sal B) exhibits beneficial effects on the cardiovascular system. However, its role and mechanism in diabetic vascular inflammatory response remain unclear. In this study, we found that Sal B reduced vascular inflammation in diabetic mice and high glucose- (HG-) induced VSMC inflammation. Subsequently, we found that Sal B reduced HG-induced VSMC inflammation by downregulating FOXO1. Furthermore, miR-486a-5p expression was obviously reduced in HG-treated VSMC. Sal B attenuated HG-induced VSMC inflammation by upregulating miR-486a-5p. Loss- and gain-of-function experiments had proven that the transfection of the miR-486a-5p mimic inhibited HG-induced VSMC inflammation whereas that of the miR-486a-5p inhibitor promoted HG-induced VSMC inflammation, thereby leading to the amelioration of vascular inflammation in the diabetic mice. Furthermore, studies had shown that miR-486a-5p inhibited FOXO1 expression by directly targeting its 3′-UTR. In conclusion, Sal B alleviates the inflammatory response of VSMC by upregulating miR-486a-5p and aggravating its inhibition of FOXO1 expression. Sal B exerts a significant anti-inflammatory effect in HG-induced VSMC inflammation by modulating the miR-486a-5p/FOXO1 axis.

This study introduces a variable-stiffness pneumatic bending actuator to enhance the stiffness of flexible robots. The bending actuator combines the working principles of a pneumatic drive, a wedge structure, and particle blockage. It enables one-dimensional, bidirectional bending motion and offers pose-maintenance capabilities. The approach to variable-stiffness is both driven and antagonistic. Stiffness in both bending and opposite directions is nonlinearly correlated with air pressure values. Specifically, at 0.5 MPa of air pressure, the stiffness in the bending direction increases to 6.1 times the initial stiffness. At 0.15 MPa, the stiffness in the opposite direction is 2.1 times the initial value. When air pressure is greater than 0.15 MPa, the stiffness incrementally increases due to the wedge impedance force. A driven variable-stiffness control is simple and suitable for applications with a constant load direction, while the antagonistic approach is more suitable for occasions where the load direction changes during movement.

Similar to parent polycyclic aromatic hydrocarbons (PPAHs), substituted PAHs (SPAHs) are prevalent in the environment and harmful to humans. However, they have not received much attention. This study investigated the occurrence, distribution, and sources of 10 PPAHs and 15 SPAHs in soil, water, and indoor and outdoor PM2.5 and dust in high-exposure areas (EAH) near industrial parks and low-exposure areas (EAL) far from industrial parks. PAH pollution in all media was more severe in the EAH than in the EAL. All SPAHs were detected in this study, with alkylated and oxygenated PAHs being predominant. Additionally, 3-OH-BaP and 1-OH-Pyr were detected in all dust samples in this study, and 6-N-Chr, a compound with carcinogenicity 10 times higher than that of BaP, was detected at high levels in all tap water samples. According to the indoor-outdoor ratio, PAHs in indoor PM2.5 in the EAH mainly originated from indoor pollution sources; however, those in the EAL were simultaneously affected by indoor-outdoor air exchange and indoor sources. Most target PAHs tended to deposit from air to dust, and this tendency was significantly negatively associated with the octanol-air partitioning coefficient of PAHs. SPAHs in the environment are primarily derived from the petroleum industry and the mixed combustion of gasoline, biomass, and coal. The toxicity equivalence factors of SPAHs were predicted using QSAR models to assess their lifetime carcinogenic risk (ILCR). The ILCRtotal from PAHs for adults in the EAH was >10−4. Though the levels of 6-N-Chr and 1-Me-Pyr in the environment were markedly lower than those of PPAHs, their ILCRs from PM2.5 inhalation and dermal contact with water exceeded 10−6. This study is significant for recognizing and controlling the health risks associated with SPAHs in humans.

Study region: Changwu Tableland, Chinese Loess Plateau Study focus: Soil water status and water demand are two important factors to influence root water uptake (RWU) patterns, but the mechanisms involved in deep-rooted plants remain unknown. This study addresses this knowledge gap by investigating diurnal variations in RWU patterns for two different-aged apple orchards (7 vs. 19 years) on the Chinese Loess Plateau (CLP). We achieved this by inputting measured plant and soil information into a physical-based numerical RWU model. New hydrological insights for the region: The results showed that the 19-year-old orchard exhibits distinct characteristics compared to the 7-year-old orchard. Specifically, the 19-year-old orchard had less deep soil water content, resulting in lower matric potential and hydraulic conductance. In contrast to cropland soil water, the cumulative deep soil water (>2 m) deficits were 17.6 and 1108.3 mm in the 7-year-old and 19-year-old orchards, respectively. Despite the 19-year-old orchard having 67% of its fine roots below 5 m soil depth, their contribution ratio to total RWU was only 30–40%, indicating less available deep soil water for the older orchard.Sap flow and leaf water potential had bell-shaped diurnal variations, leading to shifting soil water contributions to RWU in the 7-year-old and 19-year-old orchards. These changes were particularly evident when soil water potential in the root zone was heterogeneous, resulting in contrasting RWU patterns during different water demand periods. Notably, the 7-year-old orchard exhibited less water contribution from deep 2–5 m layer and enriched xylem water isotopes at midday with high water demand, while the 19-year-old orchard had more water contribution from deep 5–21.6 m layer and depleted xylem water isotopes. These contrasting RWU variations shed light on the profound impact of orchard age on deep RWU patterns, especially under the varying water demand conditions after CLP afforestation.

Miniaturization of supercapacitors offers an attractive route to the fabrication of portable and wearable electronic devices, but still suffers from limited areal capacity. Herein, we utilize a facile stamping approach to fabricate flexible paper-based micro-supercapacitors that are based on the ternary composite containing polyaniline (PANI) as patterned interdigital electrode materials. The ternary composites are composed of PANI, metal-organic frameworks derived from porous carbon (C800) and low-oxidized graphene (LGE). Benefiting from the synergy of C800 and LGE, the electrical conductivity and capacitance retention of PANI composites were enhanced, obviously. The resultant composites displayed high areal capacitance of 162 mF cm−2, remarkable energy density of 24.9 μWh·cm−2, 90 % capacitance over thousands of charge-discharge cycles and excellent stability against bending even at large angles.

ABSTRACTThis study aimed to conduct a bibliometric analysis in the field of bladder cancer (BC) immunotherapy, and explore the research trends, hotspots and frontiers from 2000 to 2022. VOSviewer software was used to analyze the collaborative relationships between authors, institutions, countries/regions, and journals through citation, co-authorship, and co-citation analysis, to identify research hotspots and frontiers in this field. Researchers based in the United States of America have published a total of 627 papers with 27,308 citations. Indeed, the USA ranked first among the top 10 most active countries and showed the most extensive collaboration with other countries. The University of Texas MD Anderson CANC CTR has published 58 articles, making it the top most institution in terms of published articles and active collaborative research. Kamat AM and Lamm DL were the most active and co-cited authors with 28 papers and 980 co-citations, respectively. Chang Yuan and Xu le were the most active collaborative authors with a total link strength of 195. The J UROLOGY was the most active and frequently co-cited journal, with 100 papers and 6,668 co-citations. Studies of BC immunotherapy can be broadly classified into three categories: “basic research”, “clinical trial”, and “prognosis”. Our findings provide an overview of the research priorities and future directions of BC immunotherapy. Tumor microenvironment and immune checkpoint inhibitors (ICIs) of BC, as well as the combination of ICIs with other drugs, may become the main direction of future research.

AbstractBackground Limited studies are available concerning on the earlier identification of AKI with sepsis. The aim of the study was to identify the risk factors of AKI early which depended on the timing onset and progression of AKI and investigate the effects of timing onset and progression of AKI on clinical outcomes.Methods Patients who developed sepsis during their first 48-h admission to ICU were included. The primary outcome was major adverse kidney events (MAKE) consisted of all-cause mortality, RRT-dependence, or an inability to recover to 1.5 times of the baseline creatinine value up to 30 days. We determined MAKE and in-hospital mortality by multivariable logistic regression and explored the risk factors of early persistent-AKI. C statistics were used to evaluate model fit.Results 58.7% sepsis patients developed AKI. According to the timing onset and progression of AKI, Early transient-AKI, early persistent-AKI, late transient-AKI, late persistent-AKI were identified. Clinical outcomes were quite different among subgroups. Early persistent-AKI had 3.0-fold (OR 3.04, 95% CI 1.61 − 4.62) risk of MAKE and 2.6-fold (OR 2.60, 95%CI 1.72 − 3.76) risk of in-hospital mortality increased compared with the late transients-AKI. Older age, underweight, obese, faster heart rate, lower MAP, platelet, hematocrit, pH and energy intake during the first 24 h on ICU admission could well predict the early persistent-AKI in patients with sepsis.Conclusion Four AKI subphenotypes were identified based on the timing onset and progression of AKI. Early persistent-AKI showed higher risk of major adverse kidney events and in-hospital mortality.Trial registration This study was registered in the Chinese Clinical Trials Registry (www.chictr.org/cn) under registration number ChiCTR-ECH-13003934.

Abstract Background Temporomandibular joint disorders (TMD) is the most common non-dental pain complaint in the maxillofacial region, which presents a variety of symptoms and signs, including temporomandibular joints (TMJ) and masticatory muscle pain, joint noise, tinnitus, headaches, irregular or restricted mandibular function, masticatory difficulty, and restricted mouth opening. When comes to the relationship between obesity and TMD, it has remained controversial and inconsistent, therefore, we first conducted this meta-analysis to estimate the unclear relationship between obesity and TMD. Methods Searches were conducted in PubMed, Web of Science, Embase, and Cochrane Library. Subjects were divided into five groups according to BMI level in this study, including the normal weight group: 18.5 ≤ BMI

Abstract Background Lotus corniculatus is a widely distributed perennial legume whose great adaptability to different environments and resistance to barrenness make it an excellent forage and ecological restoration plant. However, its molecular genetics and genomic relationships among populations are yet to be uncovered. Result Here we report on a genomic variation map from worldwide 272 L. corniculatus accessions by genome resequencing. Our analysis suggests that L. corniculatus accessions have high genetic diversity and could be further divided into three subgroups, with the genetic diversity centers were located in Transcaucasia. Several candidate genes and SNP site associated with CNglcs content and growth traits were identified by genome-wide associated study (GWAS). A non-synonymous in LjMTR was responsible for the decreased expression of CNglcs synthesis genes and LjZCD was verified to positively regulate CNglcs synthesis gene CYP79D3. The LjZCB and an SNP in LjZCA promoter were confirmed to be involved in plant growth. Conclusion This study provided a large number of genomic resources and described genetic relationship and population structure among different accessions. Moreover, we attempt to provide insights into the molecular studies and breeding of CNglcs and growth traits in L. corniculatus.

Abstract Background In colorectal cancer (CRC), the normal tissue adjacent to tumor (NAT) communicates actively with the tumor. Adult stem cells from the colon play a crucial role in the development of the colonic epithelium. In the tumor microenvironment, however, it is unclear what changes have occurred in colonic stem cells derived from NAT. Methods Using an intestinal stem cell culture system, we cultured colonic cells from NAT and paired CRC tissue, as well as cells from healthy tissue (HLT). Clonogenicity and differentiation ability were used to compare the function of clones from NAT, HLT and CRC tissues. RNA high-throughput sequencing of these clones was used to identify the molecular characteristics of NAT-derived clones. Coculture of clones from HLT and CRC was used to assess molecular changes. Results We found that the morphological characteristics, clonogenic ability, and differentiation ability of NAT-derived clones were consistent with those of HLT-derived clones. However, NAT-derived clones changed at the molecular level. A number of genes were specifically activated in NAT. NAT-derived clones enriched pathways related to inflammation and fibrosis, including epithelial mesenchymal transition (EMT) pathway and TGF-beta signaling pathway. Our results also confirmed that NAT-derived clones could recruit fibroblasts in mice. In addition, HLT-derived clones showed high expression of FOSB when cocultured with tumor cells. Conclusions Our results demonstrate that colonic stem cells from NAT in the tumor microenvironment undergo changes at the molecular level, and these molecular characteristics can be maintained in vitro, which can induce fibrosis and an inflammatory response. Video Abstract

Abstract Background Previous studies have shown inconsistent findings regarding the association of light to moderate alcohol consumption with cause-specific mortality. Therefore, this study sought to examine the prospective association of alcohol consumption with all-cause and cause-specific mortality in the US population. Methods This was a population-based cohort study of adults aged 18 years or older in the National Health Interview Survey (1997 to 2014) with linkage to the National Death Index records through December 31, 2019. Self-reported alcohol consumption was categorized into seven groups (lifetime abstainers; former infrequent or regular drinkers; and current infrequent, light, moderate, or heavy drinkers). The main outcome was all-cause and cause-specific mortality. Results During an average follow-up of 12.65 years, among the 918,529 participants (mean age 46.1 years; 48.0% male), 141,512 adults died from all causes, 43,979 from cardiovascular disease (CVD), 33,222 from cancer, 8246 from chronic lower respiratory tract diseases, 5572 from accidents (unintentional injuries), 4776 from Alzheimer’s disease, 4845 from diabetes mellitus, 2815 from influenza and pneumonia, and 2692 from nephritis, nephrotic syndrome, or nephrosis. Compared with lifetime abstainers, current infrequent, light, or moderate drinkers were at a lower risk of mortality from all causes [infrequent—hazard ratio: 0.87; 95% confidence interval: 0.84 to 0.90; light: 0.77; 0.75 to 0.79; moderate 0.82; 0.80 to 0.85], CVD, chronic lower respiratory tract diseases, Alzheimer’s disease, and influenza and pneumonia. Also, light or moderate drinkers were associated with lower risk of mortality from diabetes mellitus and nephritis, nephrotic syndrome, or nephrosis. In contrast, heavy drinkers had a significantly higher risk of mortality from all causes, cancer, and accidents (unintentional injuries). Furthermore, binge drinking ≥ 1 day/week was associated with a higher risk of mortality from all causes (1.15; 1.09 to 1.22), cancer (1.22; 1.10 to 1.35), and accidents (unintentional injuries) (1.39; 1.11 to 1.74). Conclusions Infrequent, light, and moderate alcohol consumption were inversely associated with mortality from all causes, CVD, chronic lower respiratory tract diseases, Alzheimer’s disease, and influenza and pneumonia. Light or moderate alcohol consumption might also have a beneficial effect on mortality from diabetes mellitus and nephritis, nephrotic syndrome, or nephrosis. However, heavy or binge had a higher risk of all-cause, cancer, and accidents (unintentional injuries) mortality.

Abstract By 31 May 2022, original/Alpha, Delta and Omicron strains induced 101 outbreaks of COVID-19 in mainland China. Most outbreaks were cleared by combining non-pharmaceutical interventions (NPIs) with vaccines, but continuous virus variations challenged the dynamic zero-case policy (DZCP), posing questions of what are the prerequisites and threshold levels for success? And what are the independent effects of vaccination in each outbreak? Using a modified classic infectious disease dynamic model and an iterative relationship for new infections per day, the effectiveness of vaccines and NPIs was deduced, from which the independent effectiveness of vaccines was derived. There was a negative correlation between vaccination coverage rates and virus transmission. For the Delta strain, a 61.8% increase in the vaccination rate (VR) reduced the control reproduction number (CRN) by about 27%. For the Omicron strain, a 20.43% increase in VR, including booster shots, reduced the CRN by 42.16%. The implementation speed of NPIs against the original/Alpha strain was faster than the virus’s transmission speed, and vaccines significantly accelerated the DZCP against the Delta strain. The CRN ( $${R}_{c1}$$ R c 1 ) during the exponential growth phase and the peak time and intensity of NPIs were key factors affecting a comprehensive theoretical threshold condition for DZCP success, illustrated by contour diagrams for the CRN under different conditions. The DZCP maintained the $${R}_{c1}$$ R c 1 of 101 outbreaks below the safe threshold level, but the strength of NPIs was close to saturation especially for Omicron, and there was little room for improvement. Only by curbing the rise in the early stage and shortening the exponential growth period could clearing be achieved quickly. Strengthening China's vaccine immune barrier can improve China's ability to prevent and control epidemics and provide greater scope for the selection and adjustment of NPIs. Otherwise, there will be rapid rises in infection rates and an extremely high peak and huge pressure on the healthcare system, and a potential increase in excess mortality.

We investigated the magnitude–frequency relationship and decay pattern of an aftershock sequence using data from the 2008 Wenchuan earthquake. We analyzed the spatial variations in aftershock activity parameters b and p. The calculated b-value of the aftershock sequence is 0.89 ± 0.02, which is relatively small, probably owing to the absence of small earthquakes in the aftershock catalog. The p-value, indicating the decay rate of aftershock activity, is 1.05 ± 0.02, which is normal. The decay pattern of the Wenchuan aftershock sequence agrees well with the modified Omori law. The b-value of the aftershock sequence mainly spatially varies between 0.6 and 1.2, and the p-value varies between 0.6 and 1.8. Although the physical significance of the spatial variations in b- and p-values has not been clearly defined, in this study, the physical significance of the b-value is mainly related to changes in stress, P-wave velocity, and the density of media in the earthquake area, and that in the p-value is associated with the fault slip amount during the mainshock; the b- and p-values show a strong linear correlation. After the mainshock, stress decreased and increased in areas with large and small b-values, respectively; the regions with large and small b-values were associated with low and high P-wave velocities, respectively. The subsurface media experienced relatively high and low apparent velocities in areas with small and large b-values, respectively. The amount of fault slip was small and large in regions with small and large p-values, respectively, exhibiting a linear correlation between the fault slip amount and p-value. The results indicate that the spatial variations in the b- and p-values were related to the physical properties of the media in the earthquake area and focal earthquake mechanism.

Event cameras are bio-inspired neuromorphic sensors that have emerged in recent years, with advantages such as high temporal resolutions, high dynamic ranges, low latency, and low power consumption. Event cameras can be used to build event-based imaging polarimeters, overcoming the limited frame rates and low dynamic ranges of existing systems. Since events cannot provide absolute brightness intensity in different angles of polarization (AoPs), degree of linear polarization (DoLP) recovery in non-division-of-time (non-DoT) event-based imaging polarimeters is an ill-posed problem. Thus, we need a data-driven deep learning approach. Deep learning requires large amounts of data for training, and constructing a dataset for event-based non-DoT imaging polarimeters requires significant resources, scenarios, and time. We propose a method for generating datasets using simulated polarization distributions from existing red–green–blue images. Combined with event simulator V2E, the proposed method can easily construct large datasets for network training. We also propose an end-to-end event-based DoLP recovery network to solve the problem of DoLP recovery using event-based non-DoT imaging polarimeters. Finally, we construct a division-of-time event-based imaging polarimeter simulating an event-based four-channel non-DoT imaging polarimeter. Using real-world polarization events and DoLP ground truths, we demonstrate the effectiveness of the proposed simulation method and network.

Carbon-sequestering microorganisms play an important role in the carbon cycle of wetland ecosystems. However, the response mechanism of carbon-sequestering microbial communities to wetland type changes and their relationship with soil carbon remain unclear. To explore these differences and identify the main influencing factors, this study selected marsh wetlands, river wetlands and lakeside wetlands around Qinghai Lake as research subjects. High-throughput sequencing was employed to analyze the functional gene cbbM of carbon-sequestering microorganisms. The results revealed that the alpha diversity of cbbM carbon-sequestering microorganisms mirrored the trend in total carbon content, with the highest diversity observed in marsh wetlands and the lowest in lakeside wetlands. The dominant bacterial phylum was Proteobacteria, with prevalent genera including Thiothrix, Acidithiobacillus, and Thiodictyon. Acidithiobacillus served as a biomarker in lakeside wetlands, while two other genera were indicative of marsh wetlands. The hierarchical partitioning analysis indicated that the diversity of cbbM carbon-fixing microorganisms was primarily influenced by the total nitrogen content, while the community structure was significantly affected by the soil total carbon content. Moreover, an increased soil temperature and humidity were found to favor the carbon fixation processes of Thiomicrospira, Thiomonas, Polaromonas, and Acidithiobacillus. In summary, changes in wetland types seriously affected the characteristics of cbbM carbon sequestration in microbial communities, and a warm and humid climate may be conducive to wetland carbon sequestration.

Every late autumn, fluttering poplar leaves scatter throughout the campus and city streets. In this work, poplar leaves were used as the raw material, while H3PO4 and KOH were used as activators and urea was used as the nitrogen source to prepare biomass based-activated carbons (ACs) to capture CO2. The pore structures, functional groups and morphology, and desorption performance of the prepared ACs were characterized; the CO2 adsorption, regeneration, and kinetics were also evaluated. The results showed that H3PO4 and urea obviously promoted the development of pore structures and pyrrole nitrogen (N–5), while KOH and urea were more conductive to the formation of hydroxyl (–OH) and ether (C–O) functional groups. At optimal operating conditions, the CO2 adsorption capacity of H3PO4– and KOH–activated poplar leaves after urea treatment reached 4.07 and 3.85 mmol/g, respectively, at room temperature; both showed stable regenerative behaviour after ten adsorption–desorption cycles.

Background: Warfarin has become the first choice for anticoagulation in patients who need lifelong anticoagulation due to its clinical efficacy and low price. However, the anticoagulant effect of warfarin is affected by many drugs, foods, etc. accompanied by a high risk of bleeding and embolism. The Vitamin K epoxide reductase complex 1 (VKORC1) and Cytochrome P450 2C9 (CYP2C9) genotypic variation can influence the therapeutic dose of warfarin. However, it is not clear whether there is a correlation between warfarin dose and liver function, kidney function and metabolic markers such as uric acid (UA) in patients with different genotypes. We performed a single-center retrospective cohort study to evaluate the factors affecting warfarin dose and to establish a dose conversion model for warfarin patients undergoing heart valve replacement. Methods: We studied 343 patients with a mechanical heart valve replacement, compared the doses of warfarin in patients with different warfarin-related genotypes (CYP2C9 and VKORC1), and analyzed the correlation between liver function, kidney function, UA and other metabolic markers and warfarin dose in patients with different genotypes following heart valve replacement. Results: Genotype analysis showed that 72.01% of patients had CYP2C9*1/*1 and VKORC1 mutant AA genotypes. Univariate regression analysis revealed that the warfarin maintenance dose was significantly correlated with gender, age, body surface area (BSA), UA and genotype. There was no correlation with liver or kidney function. Multiple linear regression analysis showed that BSA, genotype and UA were the independent factors influencing warfarin dose. Conclusions: There is a significant correlation between UA content and warfarin dose in patients with heart valve replacement genotypes CYP2C9*1/*1/VKORC1(GA+GG), CYP2C9*1/*1/VKORC1AA and CYP2C9*1/*1/VKORC1AA.

Soil health is seriously threatened by the overuse of chemical fertilizers in agricultural management. Biogas slurry is often seen as an organic fertilizer resource that is rich in nutrients, and its use has the goal of lowering the amount of chemical fertilizers used while preserving crop yields and soil health. However, the application of continuous biogas slurry has not yet been studied for its long-term impact on soil nutrients and microbial communities in a rotation system of annual ryegrass-silage maize (Zea mays). This study aimed to investigate the impacts on the chemical properties and microbial community of farmland soils to which chemical fertilizer (NPK) (225 kg ha−1), biogas slurry (150 t ha−1), and a combination (49.5 t ha−1 biogas slurry + 150 kg ha−1 chemical fertilizer) were applied for five years. The results indicated that compared to the control group, the long-term application of biogas slurry significantly increased the SOC, TN, AP, and AK values by 45.93%, 39.52%, 174.73%, and 161.54%, respectively; it neutralized acidic soil and increased the soil pH. TN, SOC, pH, and AP are all important environmental factors that influence the structural composition of the soil’s bacterial and fungal communities. Chemical fertilizer application significantly increased the diversity of the bacterial community. Variation was observed in the composition of soil bacterial and fungal communities among the different treatments. The structure and diversity of soil microbes are affected by different methods of fertilization; the application of biogas slurry not only increases the contents of soil nutrients but also regulates the soil’s bacterial and fungal community structures. Therefore, biogas slurry can serve as a sustainable management measure and offers an alternative to the application of chemical fertilizers for sustainable intensification.

Glycosylation, a dynamic modification prevalent in viruses and higher eukaryotes, is principally regulated by uridine diphosphate (UDP)-glycosyltransferases (UGTs) in plants. Although UGTs are involved in plant defense responses, their responses to most pathogens, especially plant viruses, remain unclear. Here, we aimed to identify UGTs in the whole genome of Nicotiana benthamiana (N. benthamiana) and to analyze their function in Chinese wheat mosaic virus (CWMV) infection. A total of 147 NbUGTs were identified in N. benthamiana. To conduct a phylogenetic analysis, the UGT protein sequences of N. benthamiana and Arabidopsis thaliana were aligned. The gene structure and conserved motifs of the UGTs were also analyzed. Additionally, the physicochemical properties and predictable subcellular localization were examined in detail. Analysis of cis-acting elements in the putative promoter revealed that NbUGTs were involved in temperature, defense, and hormone responses. The expression levels of 20 NbUGTs containing defense-related cis-acting elements were assessed in CWMV-infected N. benthamiana, revealing a significant upregulation of 8 NbUGTs. Subcellular localization analysis of three NbUGTs (NbUGT12, NbUGT16 and NbUGT17) revealed their predominant localization in the cytoplasm of N. benthamiana leaves, and NbUGT12 was also distributed in the chloroplasts. CWMV infection did not alter the subcellular localization of NbUGT12, NbUGT16, and NbUGT17. Transient overexpression of NbUGT12, NbUGT16, and NbUGT17 enhanced CWMV infection, whereas the knockdown of NbUGT12, NbUGT16 and NbUGT17 inhibited CWMV infection in N. benthamiana. These NbUGTs could serve as potential susceptibility genes to facilitate CWMV infection. Overall, the findings throw light on the evolution and function of NbUGTs.

Global demand for underground gas storage (UGS) is steadily increasing, with the limestone-based UGS system situated in the Sichuan Basin of China gathering considerable interest in recent years. However, studies focusing on the fundamental mechanisms of the injection-production process in these systems are limited. Moreover, existing studies utilizing physical experimental methods frequently fall short in effectively visualizing micro-flow or incorporating real core samples from the reservoir. To address these gaps, we performed a coreflood experiment, integrating micro-Computed Tomography (CT) scanning to investigate mechanisms of fluid flow and storage capacity during the injection and production cycles in limestone reservoirs. Our approach involved utilizing core plugs with artificially engraved fracture-vuggy structures, which mimic the characteristics of the reservoir. Micro-CT scans were performed to visualize the microscopic changes in fractured-vuggy structures and the distribution of irreducible water during each cycle. This study reveals that increased cycles correspondingly affect gas storage capacity, particularly by expanding it in relative larger vuggy structures while reducing it in finer fissure network structures. The amount of irreducible water decreases after injection-production cycles, likely being expelled alongside the extracted dry gas. This plays a critical role in expanding the storage capacity in larger vuggy systems. Conversely, there is a decrease in storage capacity within fissure network systems, as the irreducible water is replaced by gas. This leads to a reduction in the opening force of the fine conduit. The dense matrix has a very limited effect on the flow mechanism and its influence on storage capacity. Overall, these findings offer practical insights for optimizing injection and production strategies in limestone UGS systems within the Sichuan Basin, contributing to a deeper understanding and efficient utilization of this vital infrastructure.

The purple-leaf phenotype in pak choi is due to the accumulation of anthocyanin. The main regulated genes are unclear. The gene controlling the purple-leaf phenotype was mapped on A03 using BSA-seq, but the candidate interval was not further narrowed with InDel markers. Based on our previous study, we hypothesized that the candidate gene that regulates purple leaves in pak choi may also be the Dark_Pur gene from B. juncea. Using the Dark_Pur-1 marker to identify P1, P2, F1, and F2, it was confirmed that the purple trait in purple-leaf pak choi was controlled by the Dark_Pur gene from B. juncea through distant hybridization. A DNA segment of approximately 514 Kb containing the Dark_Pur gene was reintroduced into pak choi from B. juncea. Meanwhile, a new purple pak choi germplasm line was created with green pak choi × purple B. juncea via distant hybridization, which proved that distant hybridization is an effective method for creating new germplasms. Furthermore, the purple-leaf phenotypes of 20 pak choi varieties were identified, and the purple-leaf traits of all lines were derived from B. juncea via distant hybridization. At present, few studies have focused on the background of the purple trait in pak choi; however, in this study, our results suggest that there is a high probability that the purple trait in pak choi may be completely derived from purple B. juncea via distant hybridization. This study also lays a good foundation for research on the creation of new germplasms through distant hybridization among the Brassica species.

Artemisia japonica Thunb. has been used as a traditional Chinese medicine and a vegetable for thousands of years in China. However, there are few reports on the chemical composition and biological activity of its leaves. Thus, this study aimed to evaluate the chemical composition, antioxidant and anti-inflammatory effects of water extracts of A. japonica leaves and their underlying mechanisms. A total of 48 compounds were identified in the water extract using UPLC-QTOF-MS2 analysis, with phenolic acids, particularly chlorogenic acid compounds, being the predominant components. The ethyl acetate fraction (EAF) contained most of the total phenolic content (385.4217 mg GAE/g) and displayed superior antioxidant capacity with the IC50DPPH•, IC50ABTS•+, and OD0.5reducing power at 10.987 μg/mL, 43.630 μg/mL and 26.883 μg/mL, respectively. Furthermore, EAF demonstrated potent antioxidant and anti-inflammatory effects in LPS-induced RAW264.7 cells by upregulating the Nrf2/HO-1 signal pathway. These findings highlight that A. japonica leaves possess remarkable abilities to mitigate inflammation and oxidative stress, suggesting their potential utilization as medicinal agents and food additives for promoting human health.

In the knowledge economy era, innovation has become a key emphasis for urban competitions. This paper constructs a theoretical research framework that integrates the basic understandings, influencing factors and ensuing results of intercity innovative competition relations. On the basis of data from the general programs of the National Natural Science Foundation of China from 2005 to 2019, this paper constructs intercity innovative competition relations in China, analyses their spatial distribution and quantitative characteristics, and quantitatively investigates the impact of urban innovation capacity and multidimensional proximity (e.g., geographical proximity, institutional proximity and cognitive proximity) on intercity innovative competition relations through a negative binomial model. The study obtained the following findings: (1) In terms of the overall intercity innovative competition relations, the intensity of China’s intercity innovative competition relations gradually increased from 2005 to 2019, with a spatial clustering towards cities with high administrative ranks (e.g., municipalities directly under the central government, sub-provincial cities and provincial capitals); Beijing is always at the centre of innovative competition relations, but its standing has slightly slipped in recent years. (2) From the perspective of disciplines, cities can become benchmarks in particular fields of innovative competitions by competing according to their disciplinary strengths; intercity innovative competition relations in China vary across various academic disciplines. (3) In terms of influencing factors, urban innovation capacity has significant positive effects on intercity innovative competition relations; geographical proximity, institutional proximity and cognitive proximity all have significant positive effects on innovative competition relations; and interactions occur between multidimensional proximities, including a complementary effect between geographical proximity and institutional proximity, a substitutive effect between cognitive proximity and geographical proximity, and a substitutive effect between cognitive proximity and institutional proximity.

HIV infection remains a serious global public health problem. Although current drug treatment is effective and can reduce plasma viral loads below the level of detection, it cannot eradicate the virus. The reasons for the low virus persistence despite long-term therapy have not been fully elucidated. In addition, multiple HIV infection, i.e., infection of a cell by multiple viruses, is common and can facilitate viral recombination and mutations, evading the immune system and conferring resistance to drug treatment. The mechanisms for multiple HIV infection formation and their respective contributions remain unclear. To answer these questions, we developed a mathematical modeling framework that encompasses cell-free viral infection and cell-to-cell spread. We fit sub-models that only have one transmission route and the full model containing both to the multi-infection data from HIV-infected patients, and show that the multi-infection data can only be reproduced if these two transmission routes are both considered. Computer simulations with the best-fitting parameter values indicate that cell-to-cell spread leads to the majority of multiple infection and also accounts for the majority of overall infection. Sensitivity analysis shows that cell-to-cell spread has reduced susceptibility to treatment and may explain low HIV persistence. Taken together, this work indicates that cell-to-cell spread plays a crucial role in the development of HIV multi-infection and low HIV persistence despite long-term therapy, and therefore has important implications for understanding HIV pathogenesis and developing more effective treatment strategies to control or even eliminate the disease.

Abstract The immunologically “cold” microenvironment of triple negative breast cancer results in resistance to current immunotherapy. Here, we reveal the immunoadjuvant property of gas therapy with cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway activation to augment aggregation-induced emission (AIE)-active luminogen (AIEgen)-based photoimmunotherapy. A virus-mimicking hollow mesoporous tetrasulfide-doped organosilica is developed for co-encapsulation of AIEgen and manganese carbonyl to fabricate gas nanoadjuvant. As tetra-sulfide bonds are responsive to intratumoral glutathione, the gas nanoadjuvant achieves tumor-specific drug release, promotes photodynamic therapy, and produces hydrogen sulfide (H2S). Upon near-infrared laser irradiation, the AIEgen-mediated phototherapy triggers the burst of carbon monoxide (CO)/Mn2+. Both H2S and CO can destroy mitochondrial integrity to induce leakage of mitochondrial DNA into the cytoplasm, serving as gas immunoadjuvants to activate cGAS-STING pathway. Meanwhile, Mn2+ can sensitize cGAS to augment STING-mediated type I interferon production. Consequently, the gas nanoadjuvant potentiates photoimmunotherapy of poorly immunogenic breast tumors in female mice.

Abstract Diabetic nephropathy (DN) is one of the serious chronic microvascular complications of diabetes, and leads to the increased morbidity and mortality in diabetic patients. Gasdermin E (GSDME)-dependent pyroptosis signaling pathway plays important roles in a variety of physiological and pathological processes. However, its role and mechanism in DN are still unclear. In this study, we established a rat DN model by intraperitoneal injection of streptozotocin (STZ) successfully. Structural and functional disorders in the kidney were exhibited on the 12th week after STZ injection; the expressions of caspase-3 and GSDME at protein level in renal cortex were significantly up-regulated. At the 20th week, GSDME-N increased significantly, accompanied by the upregulation of caspase-1 in renal cortex and the release of mature IL-1β (mIL-1β) in serum. Furthermore, we found the protein levels of GSDME, caspase-3, caspase-1 and IL-1β were all increased in HK2 and HBZY-1 cells under high-glucose conditions. We also found that the expression of GSDME-N significantly decreased when caspase-3 was knockdown. In contrast, knockdown of GSDME has no effect on caspase-3. Interestingly, either caspase-3, caspase-1 or GSDME knockdown reduced the release of mIL-1β. Finally, injection of adeno-associated virus (AAV) 9-shGSDME into the rat kidney reduced kidney damage and renal cell pyroptosis in comparison with wild-type diabetic rats. These results indicated that the activation of caspase-1 induced IL-1β maturation, and the activation of caspase-3 mediated cleavage of GSDME responsible for the formation of plasma membrane pore, followed by cytoplasmic release of mIL-1β. Overall, we identified a pro-pyroptosis role for GSDME in DN, which does provide an important basis for clinical therapeutic studies.

Abstract Background Postoperative adjuvant chemotherapy (AC) is now well-accepted as standard for high-risk stage II and stage III colorectal cancer (CRC) patients, however the optimal time to initiate AC remains elusive. Methods A comprehensive literature search was performed using the PubMed and Embase databases. The Hazard ratio (HR) with the corresponding 95% confidence interval (CI) was used as an effect measure to evaluate primary endpoints. All analyses were conducted using Stata software version 12.0 with the Random-effects model. Results A total of 30 studies were included in our study. Upon comparison on overall survival (OS), we identified that delaying the initiation of AC for > 8 weeks after operation was significantly associated with poor OS (HR: 1.37; 95% CI: 1.27—1.48; P 8 weeks was not undermined by subgroup analysis based on region, tumor site, sample size and study quality. No obvious differences were observed in survival between AC within 5–8 weeks and ≤ 4 weeks (HR: 1.03; 95% CI: 0.96 -1.10; P = 0.46). Moreover, two studies both highlighted that the survival benefit of AC was still statistically significant when AC was applied 5–6 months after surgery compared with the non-chemotherapy group. Conclusions Delaying the initiation of AC for > 8 weeks after surgery was significantly associated with poor OS. AC started within 8 weeks after surgery brought more benefits to CRC patients. There were no obvious differences in survival benefits between AC within 5–8 weeks and ≤ 4 weeks. Compared to patients not receiving AC after surgery, a delay of approximately 5–6 months was still useful to improve prognosis.

Abstract Background The prognosis of patients with previously treated advanced gastric or gastroesophageal junction (GEJ) cancer remains poor. Given the robust development of immunotherapy and targeted therapy during the last decades, we aimed to investigate if the combination of traditional second-line chemotherapy with sintilimab and apatinib could bring survival benefits for these patients. Methods In this single-center, single-arm, phase II trial, patients with previously treated advanced gastric or GEJ adenocarcinoma received specific dose level of intravenous paclitaxel or irinotecan (investigator’s choice), 200 mg intravenous sintilimab on day 1, and 250 mg oral apatinib once daily continuously in each cycle until disease progression, intolerable toxicity, or withdrawal of consent. The primary endpoints were objective response rate and progression-free survival. The secondary endpoints were mainly overall survival and safety. Results From May 2019 to May 2021, 30 patients were enrolled. At the data cutoff date (March 19, 2022), the median follow-up duration was 12.3 months and 53.6% (95% CI, 33.9–72.5%) patients achieved objective response. The median progression-free survival and overall survival were 8.5 months (95% CI, 5.4–11.5) and 12.5 months (95% CI, 3.7–21.3), respectively. Grade 3–4 adverse events included hematological toxicities, elevated alanine aminotransferase, elevated aspartate aminotransferase, elevated alkaline phosphatase, elevated gamma-glutamyl transpeptidase, hyperbilirubinemia and proteinuria. The most frequent grade 3–4 adverse event was neutropenia (13.3%). No serious treatment-related adverse events or treatment-related deaths occurred. Conclusion Sintilimab plus apatinib and chemotherapy demonstrates promising anti-tumor activity with manageable safety profile in patients with previously treated advanced gastric or GEJ cancer. Trial registration ClinicalTrials.gov: NCT05025033, 27/08/2021.

Abstract Background Breast cancer is a serious threat to female health, and its incidence varies with education level (EL). In the present study, the association between EL and the risk of developing female breast cancer was investigated. Methods From May 2006 to December 2007, 20,400 observation subjects in Kailuan Cohort received questionnaires and were subjected to clinical examinations for data collection on baseline population characteristics, height, weight, lifestyle and past disease history. Then, these participants were followed up with from the date of recruitment to December 31, 2019. Cox proportional risk regression models were used to analyse the association between EL and the risk of developing female breast cancer. Results The cumulative follow-up period of 20,129 observation subjects that meet the inclusion criteria of this study was 254,386.72 person-years, and the median follow-up time was 12.96 years. During the follow-up period, 279 cases of breast cancer were diagnosed. In comparison with the low EL group, the risk of developing breast cancer was significantly higher in the medium (hazard ratio [HR] (95% confidence interval [CI]) = 2.23 (1.12–4.64)] and high [HRs (95% CI) = 2.52 (1.12–5.70)] EL group. Conclusion An increased risk of breast cancer was associated with a higher EL, and some certain factors, such as alcohol use and hormone therapy, may play a mediating role.

Objective: The scarfskin and scarcocarp of 16 batches of Citrus medica L. var. sarcodactylis Swingle were collected as the research objects to find out the differences between scarfskin and scarcocarp. Methods: The fingerprints of scarfskin and scarcocarp of Citrus medica L. var. sarcodactylis Swingle were established by HPLC, and the content of multicomponents was determined respectively. Result: Eight common peaks were picked up in scarcocarp, 18 in scarfskin, and six constituents were identified as scopoletin, scoparone, hesperidin, diosimin, 5,7-dimethoxy coumarin and bergapten. The similarity evaluation system for chromatographic fingerprint of traditional Chinese medicine was employed for similarity analysis. The scarfskin and scarcocarp of Citrus medica L. var. sarcodactylis Swingle in Leshan City had good similarity with their respective reference fingerprints, both greater than 0.90. The similarity between the scarfskin and scarcocarp of the same batch of Citrus medica L. var. sarcodactylis Swingle was very low, only 0.10 to 0.35. On this basis, the contents of six identified components were determined. In the scarfskin of Citrus medica L. var. sarcodactylis Swingle six components were detected, and the contents of 5,7-dimethoxy coumarin and diosimin were higher. But the contents of hesperidin and diosimin in the scarcocarp were higher, and the other four components were not detected. Conclusion: Through HPLC fingerprint and quantitative analysis of multiple components, it was found that there were significant differences in composition and content between scarfskin and scarcocarp. With these characteristics, the scarfskin and scarcocarp of Citrus medica L. var. sarcodactylis Swingle could be used in different fields to maximize the use of resources. At the same time, the established method could be used for quality control of Citrus medica L. var. sarcodactylis Swingle, and would provide technical support for rational and efficient development and utilization of Citrus medica L. var. sarcodactylis Swingle resources.

This study aimed to explored the association between depressive symptoms and infertility among U.S. women, and the effect of serum calcium on this association. We used data from the National Health and Nutrition Examination Survey (2013–2018), relating to women aged 20–45 years. Depressive symptoms were determined using the nine-item Patient Health Questionnaire (PHQ-9 scores ≥10), and interview data were used to identify self-reported infertility. Of 2708 women (mean age: 32.7 ± 7.5 years), 274 were depressed and 12.0 % self-reported being “ever-infertile.” Depressive symptoms were associated with infertility in multivariable logistic regression (OR, 1.62; 95 % CI, 1.11–2.38). Depressive symptoms were associated with infertility among participants who were obese (OR, 1.68; 95 % CI, 1.03–2.74), had not received psychological counseling (OR, 1.60; 95 % CI, 1.03–2.50), were antidepressant users (OR 3.22; 95 % CI, 1.15–9.00), and had high serum calcium levels (OR, 2.05; 95 % CI, 1.25–3.35). A significant interaction between serum calcium and depression was observed for infertility (P = .038, interaction likelihood ratio test). In sensitivity analyses, the association between depressive symptoms and infertility remained after excluding women aged ≥35 years (OR, 1.87; 95 % CI, 1.08–3.23), lowering the cut-off for PHQ-9 scores (≥5) (OR, 1.48; 95 % CI, 1.12–1.96), excluding women with some gynecological diseases (OR, 1.63; 95 % CI, 1.07–2.49), and using inverse probability of treatment weighting (OR, 1.64; 95 % CI, 1.17–2.31). Conclusion: Our findings indicate that depression is associated with infertility among U.S. women and serum calcium may have an effect on the association. Interventions such as serum calcium reduction, weight management and psychosocial counseling for infertility treatment in individuals with depression may be integrated into routine clinical practice. Additionally, more caution could be exercised when using antidepressants.

Accurately assessing isotope information on water sources and mixtures is essential for determining root water uptake (RWU) patterns. This study investigates the impact of rooting depth and cryogenic vacuum extraction (CVE) on the isotopic composition of deep soil water and RWU patterns in a 19-year-old apple orchard on China’s Loess Plateau. We used a Bayesian mixing model (MixSIAR) to analyze corrected isotopic data from soil and xylem water samples collected at different depths, ranging from 3 m to 21.6 m. Our findings reveal a progressive decline in the isotopic composition of deep soil water by 0.63‰ m–1, which decreased deep soil water contributions to transpiration by 1–12% at different rooting depths. The xylem and soil water isotopes became more enriched after correction, with xylem water isotopes closer to the soil water isotope line and water isotopes enriched in the shallow soil layer. Consequently, the contributions of shallow soil water to transpiration increased after xylem water isotope correction but decreased after soil water isotope correction. Monthly averages of these ratios decreased by 12.8% or increased by 8.4%, respectively. After correcting for both soil and xylem water isotopes, the average contributions of shallow soil water increased by 7.4% each month, while those of deep soil water were not consistent. Our findings suggest that rooting depth and CVE have a greater impact on seasonal contribution ratios but a comparatively milder influence on seasonal patterns. This delineation is important for accurately quantifying plant water use strategies.

BackgroundSince abnormal aerobic glycolysis was first identified in cancer cells, many studies have focused on its mechanisms. The purpose of this study was to analyze the global research status of the Warburg effect in cancer using bibliometrics.MethodsArticles published from 01 January 2013 to 31 December 2022 (n=2,067) were retrieved from the Web of Science core collection database and analyzed using VOSviewer and CiteSpace software.ResultsOver the past decade, there was an overall increase in the number of annual publications. China was the most productive country with 790 articles, while the United States received the most citations, with 25,657 citations in total. Oncotarget was the most productive and most cited journal, with 99 articles and 4,191 citations, respectively. International cooperation was common, with the USA cooperating most with other countries. Lactate metabolism, citrate production, and non-coding RNAs related to the Warburg effect have received increasing attention in cancer research. These areas may become future research trends.ConclusionThe study findings help summarize the research status and hotspots of the Warburg effect cancer, and will inform subsequent research.