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Background: The homologous recombination deficiency (HRD) score serves as a promising biomarker to identify patients who are eligible for treatment with PARP inhibitors (PARPi). Previous studies have suggested a 3-biomarker Genomic Instability Score (GIS) threshold of ≥ 42 as a valid biomarker to predict response to PARPi in patients with ovarian cancer and breast cancer. However, the GIS threshold for prostate cancer (PCa) is still lacking. Here, we conducted an exploratory analysis to investigate an appropriate HRD score threshold and to evaluate its ability to predict response to PARPi in PCa patients. Methods: A total of 181 patients with metastatic castration-resistant PCa were included in this study. Tumor tissue specimens were collected for targeted next-generation sequencing for homologous recombination repair (HRR) genes and copy number variation (CNV) analysis. The HRD score was calculated based on over 50,000 single-nucleotide polymorphisms (SNP) distributed across the human genome, incorporating three SNP-based assays: loss of heterozygosity, telomeric allelic imbalance, and large-scale state transition. The HRD score threshold was set at the last 5th percentile of the HRD scores in our cohort of known HRR-deficient tumors. The relationship between the HRD score and the efficacy in 16 patients of our cohort who received PARPi treatment were retrospectively analyzed. Results: Genomic testing was succeeded in 162 patients. In our cohort, 61 patients (37.7%) had HRR mutations (HRRm). BRCA mutations occurred in 15 patients (9.3%). The median HRD score was 4 (ranged from 0 to 57) in the total cohort, which is much lower than that in breast and ovarian cancers. Patients who harbored HRRm and BRCA or TP53 mutations had higher HRD scores. CNV occured more frequently in patients with HRRm. The last 5th percentile of HRD scores was 43 in the HRR-mutant cohort and consequently HRD high was defined as HRD scores ≥43. In the 16 patients who received PARPi in our cohort, 4 patients with a high HRD score achieved an objective response rate (ORR) of 100% while 12 patients with a low HRD score achieved an ORR of 8.3%. Progression-free survival (PFS) in HRD high patients was longer compared to HRD low patients, regardless of HRRm. Conclusions: A HRD score threshold of 43 was established and preliminarily validated to predict the efficacy of PARPi in this study. Future studies are needed to further verify this threshold.

Multifunctional therapeutics have emerged as a solution to the constraints imposed by drugs with singular or insufficient therapeutic effects. The primary challenge is to integrate diverse pharmacophores within a single-molecule framework. To address this, we introduced DeepSA, a novel edit-based generative framework that utilizes deep simulated annealing for the modification of articaine, a well-known local anesthetic. DeepSA integrates deep neural networks into metaheuristics, effectively constraining molecular space during compound generation. This framework employs a sophisticated objective function that accounts for scaffold preservation, anti-inflammatory properties, and covalent constraints. Through a sequence of local editing to navigate the molecular space, DeepSA successfully identified AT-17, a derivative exhibiting potent analgesic properties and significant anti-inflammatory activity in various animal models. Mechanistic insights into AT-17 revealed its dual mode of action: selective inhibition of NaV1.7 and 1.8 channels, contributing to its prolonged local anesthetic effects, and suppression of inflammatory mediators via modulation of the NLRP3 inflammasome pathway. These findings not only highlight the efficacy of AT-17 as a multifunctional drug candidate but also highlight the potential of DeepSA in facilitating AI-enhanced drug discovery, particularly within stringent chemical constraints.

RNA-binding proteins (RBPs) are key post-transcriptional regulators, and the malfunctions of RBP-RNA binding lead to diverse human diseases. However, prediction of RBP binding sites is largely based on RNA sequence features, whereas in vivo RNA structural features based on high-throughput sequencing are rarely incorporated. Here, we designed a deep bimodal information fusion network called DeepFusion for unraveling protein-RNA interactions by incorporating structural features derived from DMS-seq data. DeepFusion integrates two sub-models to extract local motif-like information and long-term context information. We show that DeepFusion performs best compared with other cutting-edge methods with only sequence inputs on two datasets. DeepFusion’s performance is further improved with bimodal input after adding in vivo DMS-seq structural features. Furthermore, DeepFusion can be used for analyzing RNA degradation, demonstrating significantly different RBP-binding scores in genes with slow degradation rates versus those with rapid degradation rates. DeepFusion thus provides enhanced abilities for further analysis of functional RNAs. DeepFusion’s code and data are available at http://bioinfo.org/deepfusion/.

Background: Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by multi-organ involvement and the presence of autoantibodies, pathogenic factors that can serve as diagnostic biomarkers. The current research has been focusing on exploring specific autoantigens with clinical relevance for SLE subtypes. In line with this objective, this study investigated potential antigenic targets associated with specific phenotypes in SLE by leveraging an omics-based approach combined with immunoassay techniques. Methods: A transcriptomic analysis was conducted in a cohort of 70 SLE patients to identify genes significantly correlated to the relevant phenotype. Epitope mapping and sequence analysis techniques were used to predict autoantigens, and the corresponding antibodies were subsequently quantified by enzyme-linked immunosorbent assay (ELISA) and validated by Western blot. Results: Transcriptomic data analysis revealed a group of hub genes exhibiting a significant correlation with the neuropsychiatric phenotype and a positive relationship with platelets. Subsequent epitope prediction for the corresponding proteins highlighted vasodilator-stimulated phosphoprotein (VASP) as a potential autoantigen. Moreover, ELISA and immunoblotting confirmed that the anti-VASP antibody present in the serum was significantly elevated in SLE patients with neuropsychiatric involvement and positively associated with demyelination. Conclusion: VASP harbors autoantigenic epitopes associated with neuropsychiatric phenotype, especially the demyelination symptom in SLE, and its antibodies may serve as promising biomarkers in this disease.

Summary: Mesenchymal stem cells (MSCs) are heterogeneous in morphology and transcriptome, resulting in varying therapeutic outcomes. In this study, we found that 3D spheroid culture of heterogeneous MSCs, which have undergone conventional 2D monolayer culture for 5–6 passages, synchronized the cells into a uniform cell population with dramatically reduced cell size, and considerably increased levels of immunosuppressive genes and growth factors. Single-cell RNA sequencing (scRNA-seq) analysis of the cells revealed that 3D MSCs consisted of 2 major cell subpopulations and both expressed high levels of immunosuppressive factors, compared to 6 subpopulations in 2D MSCs. In addition, 3D MSCs showed a greater suppressive effect on T cells. Moreover, intravenous infusion of a large dose of 3D MSCs prior to imiquimod (IMQ) treatment significantly improved psoriatic lesion. Thus, our results indicate that 3D spheroid culture reprograms heterogeneous MSCs into a uniform immunosuppressive phenotype and promises a novel therapeutic potential for inflammatory diseases.

Reversible data hiding (RDH) algorithms have been extensively employed in the field of copyright protection and information dissemination. Among various RDH algorithms, the multiple histogram modification (MHM) algorithm has attracted significant attention because of its capability to generate high-quality marked images. In previous MHM methods, the prediction error histograms were mostly generated in a fixed way. Recently, clustering algorithms automatically classify prediction errors into multiple classes, which enhances the similarity among prediction errors within the same class. However, the design of features and the determination of clustering numbers are crucial in clustering algorithms. Traditional algorithms utilize the same features and fix the number of clusters (e.g., empirically generate 16 classes), which may limit the performance due to the lack of adaptivity. To address these limitations, an adaptive initial feature selection scheme and a clustering number optimization scheme based on the Fuzzy C-Means (FCM) clustering algorithm are proposed in this paper. The superiority of the proposed scheme over other state-of-the-art schemes is verified by experimental results.

ABSTRACT: The freezability of chicken spermatozoa is low, therefore, effective cryoprotectants is desiderated. Antifreeze proteins (AFPs) are widely found in cold-tolerant species and help them to survive in freezing environments. This study was the first to evaluate the effects of different concentrations of plant-originated antifreeze glycoprotein (AFGP) (0, 0.1, 1, and 5 μg/mL) on post-thawed sperm motion characteristics, morphology, mitochondrial function, antioxidant activity, and fertilizing potential in chickens. Results showed that the total motility of 0.1 to 1 μg/mL AFGP groups were significantly higher than those of the 5 μg/mL AFGP group (P < 0.05). The post-thawed sperm viability of 0.1 μg/mL AFGP group was significantly higher than any of test groups (P < 0.05). Higher abnormal morphology rate of post-thawed sperm was observed in the control group (0 μg/mL AFGP) than in the 0.1, 1, and 5 μg/mL AFGP groups (P < 0.05). The concentrations of malondialdehyde (MDA) decreased gradually with the increase of AFGP concentration. ATP was significantly higher in the 0.1 and 1 μg/mL AFGP groups than those of control and any of test groups (P < 0.05). The 0.1 to 1 μg/mL AFGP groups had increased mitochondrial membrane potential (MMP) level (P > 0.05). The 0.1 μg/mL AFGP group had the highest average fertility (61.36%) compared with control group (57.02%) and any of test groups of chickens at 31 wk of age, and the 1 μg/mL AFGP group had the highest average fertility (37.72%) compared with control group (21.73%) and any of test groups of chickens at 65 wk of age. In conclusion, the results from this study suggest lower concentration of AFGP (0.1–1 μg/mL) showed positive effect for sperm function. This study inspires the continuous evaluation and seeking right way of adopting different kinds of AFPs in rooster semen cryopreservation.

Antibiotic resistance is an escalating global health concern, exacerbated by the pervasive presence of antibiotic resistance genes (ARGs) in natural environments. The Yangtze River, the world's third-longest river, traversing areas with intense human activities, presents a unique ecosystem for studying the impact of these genes on human health. Here, we explored ARGs in the Yangtze River, examining 204 samples from six distinct habitats of approximately 6000 km of the river, including free-living and particle-associated settings, surface and bottom sediments, and surface and bottom bank soils. Employing shotgun sequencing, we generated an average of 13.69 Gb reads per sample. Our findings revealed a significantly higher abundance and diversity of ARGs in water-borne bacteria compared to other habitats. A notable pattern of resistome coalescence was observed within similar habitat types. In addition, we developed a framework for ranking the risk of ARG and a corresponding method for calculating the risk index. Applying them, we identified water-borne bacteria as the highest contributors to health risks, and noted an increase in ARG risks in particle-associated bacteria correlating with heightened anthropogenic activities. Further analysis using a weighted ARG risk index pinpointed the Chengdu–Chongqing and Yangtze River Delta urban agglomerations as regions of elevated health risk. These insights provide a critical new perspective on ARG health risk assessment, highlighting the urgent need for strategies to mitigate the impact of ARGs on human health and to preserve the ecological and economic sustainability of the Yangtze River for future human use.

An optimized Affinity Selection-Mass Spectrometry (AS-MS) workflow has been developed for the efficient identification of potent USP1 inhibitors. USP1 was immobilized on agarose beads, ensuring low small molecule retention, efficient protein capture, and protein stability. The binding affinity of 49 compounds to USP1 was evaluated using the optimized AS-MS method, calculating binding index (BI) values for each compound. Biochemical inhibition assays validated the AS-MS results, revealing a potential correlation between higher BI values and lower IC50 values. This optimized workflow enables rapid identification of high-quality USP1 inhibitor hits, facilitating structure-activity relationship studies and accelerating the discovery of potential cancer therapeutics.

Brain development is a highly complex process regulated by numerous genes at the molecular and cellular levels. Brain tissue exhibits serial microstructural changes during the development process. High-resolution diffusion magnetic resonance imaging (dMRI) affords a unique opportunity to probe these changes in the developing brain non-destructively. In this study, we acquired multi-shell dMRI datasets at 32 µm isotropic resolution to investigate the tissue microstructure alterations, which we believe to be the highest spatial resolution dMRI datasets obtained for postnatal mouse brains. We adapted the Allen Developing Mouse Brain Atlas (ADMBA) to integrate quantitative MRI metrics and spatial transcriptomics. Diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), and neurite orientation dispersion and density imaging (NODDI) metrics were used to quantify brain development at different postnatal days. We demonstrated that the differential evolutions of fiber orientation distributions contribute to the distinct development patterns in white matter (WM) and gray matter (GM). Furthermore, the genes enriched in the nervous system that regulate brain structure and function were expressed in spatial correlation with age-matched dMRI. This study is the first one providing high-resolution dMRI, including DTI, DKI, and NODDI models, to trace mouse brain microstructural changes in WM and GM during postnatal development. This study also highlighted the genotype-phenotype correlation of spatial transcriptomics and dMRI, which may improve our understanding of brain microstructure changes at the molecular level.

Natural environments play a crucial role in transmission of antimicrobial resistance (AMR). Development of methods to manage antibiotic resistance genes (ARGs) in natural environments are usually limited to the laboratory or field scale, partially due to the complex dynamics of transmission between different environmental compartments. Here, we conducted a nine-year longitudinal profiling of ARGs at a watershed scale, and provide evidence that restrictions on livestock farms near water bodies significantly reduced riverine ARG abundance. Substantial reductions were revealed in the relative abundance of genes conferring resistance to aminoglycosides (42%), MLSB (36%), multidrug (55%), tetracyclines (53%), and other gene categories (59%). Additionally, improvements in water quality were observed, with distinct changes in concentrations of dissolved reactive phosphorus, ammonium, nitrite, pH, and dissolved oxygen. Antibiotic residues and other pharmaceuticals and personal care products (PPCPs) maintain at a similarly low level. Microbial source tracking demonstrates a significant decrease in swine fecal indicators, while human fecal pollution remains unchanged. These results suggest that the reduction in ARGs was due to a substantial reduction in input of antibiotic resistant bacteria and genes from animal excreta. Our findings highlight the watershed as a living laboratory for understanding the dynamics of AMR, and for evaluating the efficacy of environmental regulations, with implications for reducing environmental risks associated with AMR on a global scale.

Summary: Cleaner heating policies aim to reduce air pollution and may bring about health benefits to individuals. Based on a fixed-effect model focusing on Beijing, this study found that after the onset of air pollution, daily clinic visits, hospitalization days, and hospitalization expenses increased several days after the occurrence of air pollution. These hospitalization changes were observed in males and females and three different age groups. A difference-in-differences (DID) model was constructed to identify the influences of cleaner heating policies on health consequences. The study revealed that the policy positively affects health outcomes, with an average decrease of 3.28 thousand clinic visits for all diseases. The total hospitalization days and expenses tend to decrease by 0.22 thousand days and 0.34 million CNY (Chinese Yuan), respectively. Furthermore, implementing the policy significantly reduced the number of daily clinic visits for respiratory diseases, asthma, stroke, diabetes, and chronic obstructive pulmonary diseases (COPDs).

In reinforced concrete structures, the interface between old and new concrete is commonplace in precast splices, repairs, and construction joints, and is vital for structural integrity. While extensive research has been conducted on the mechanical bonding properties of interfaces between new and old concrete, there remains a notable gap in understanding the shear behavior under various interfacial treatments. To investigate the influence of interface preparation methods and surface roughness on the shear performance of new-to-old concrete interface, direct shear tests were conducted on Z-shaped specimens. The surface roughness of the initially cast specimens was measured using 3D laser scanning, and the interface morphology was observed by scanning electron microscopy. A comprehensive analysis of comparison between calculated and experimental shear strength values was conducted on 243 sets of direct shear test data. Results revealed that the surface roughness of the specimens ranged from 0.13–3.69 mm, with voids of 0.5–10 μm width present in the bond interfaces. Two failure modes, namely cohesion and adhesion, were identified in the aggregates on the bond interfaces. Within a specific range, the shear strength of bond interfaces increased with an increase in surface roughness. Additionally, bond interfaces with the same roughness but different surface process methods exhibited varying shear bearing capacities. Furthermore, the formula for calculating the shear strength of bond interfaces based on different surface preparation processes and segmented roughness was developed.

Objectives: Frailty is an age-related syndrome associated with poor health outcomes. Studies in developed countries indicate that the dietary inflammatory index (DII) and dietary total antioxidant capacity (DTAC) are important dietary factors influencing the risk of frailty in older adults. However, few studies have explored the association between DII, DTAC, and frailty among older Chinese adults. The objective of the current study was to examine whether DII and DTAC were associated with pre-frailty or frailty among older Chinese adults. Design: A cross-sectional study. Setting: Community-based. Participants: We included 6414 participants aged ≥60 years. Measurements: Dietary intake was assessed using a validated food frequency questionnaire (FFQ). The DII and energy-adjusted DII (E-DII) were calculated using food parameters. DTAC was estimated using two widely adopted antioxidant scores: DTAC based on ferric reducing antioxidant power and dietary antioxidant quality score (DAQS) obtained from vitamins (vitamins A, C, and E) and minerals (zinc and selenium) with antioxidant functions. Frailty was assessed using the frailty index (FI) calculated from 28 health-related deficits. Individuals were classified as robust (FI ≤ 0.10), pre-frailty (FI > 0.10 to

Background: Postoperative complications in aging patients remain a significant cause of increased costs, hospital length of stay, and patient distress. Although alterations in energy metabolism have been closely linked to aging process and surgery, it is still unclear whether metabolic changes during surgery is associated with postoperative complications in elderly patients. This study was conducted to investigate whether metabolic changes during surgery predicts postoperative complications in elderly patients. Methods: We conducted a prospective single-center observational cohort study. 244 adults (aged ≥65 years) who were scheduled for elective major non-cardiac surgery were recruited. Blood samples for each patient were taken before and after surgery. All patients were randomly divided into two groups (122 in each group), then oxygen consumption rate (OCR) or extracellular acidification rate (ECAR) was measured on isolated monocytes in each group. Results: 14 of 110 (12.7%) patients went through OCR measurement and 15 of 122 patients (12.3%) went through ECAR measurement experienced moderate to severe complications. Overall, there was an intensification of glycolysis in monocytes after surgery. Among all variables, only the change (preoperative -postoperative) of glycolytic reserve (GR)/glycolysis (G) and GR/non-glycolytic acidification (NG) were predictors of moderate to severe complications (AUC = 0.70; 95% CI, 0.56–0.81; P = 0.019 and AUC = 0.67; 95% CI, 0.55–0.80; P = 0.031). Decreased postoperative GR/G were associated with worse postoperative complications (RR = 9.08; 95% CI, 1.23–66.81; P = 0.024). Conclusions: Compared with mitochondria function, the change of glycolytic function in monocyte was more valuable in predicting postoperative complications after major abdominal surgery. Our study gave us a new insight into identifying patients at high risk in aging patients.

Aim:This study aims to identify suitable candidates for axillary sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) among clinical N2 (cN2) triple-negative (TN) or HER2 positive (HER2+）breast cancer patients following neoadjuvant therapy（NAT）.Background: Despite the substantial axillary burden in cN2 breast cancer patients, high pathological response rates can be achieved with NAT in TN or HER2+ subtypes, thus enabling potential downstaging of axillary surgery.Methods: A retrospective analysis was conducted on data from the CSBrS-012 study, screening 709 patients with initial cN2, either HER2+ or TN subtype, from January 1, 2010 to December 31, 2020. The correlation between axillary pathologic complete response (pCR) (yPN0) and breast pCR was examined.Results: Among the 177 cN2 patients who achieved breast pCR through NAT, 138 (78.0 %) also achieved axillary pCR. However, in the 532 initial clinical N2 patients who did not achieve breast pCR, residual axillary lymph node metastasis persisted in 77.4 % (412/532) of cases. The relative risk of residual axillary lymph node metastasis in patients who did not achieve breast pCR was 12.4 (8.1–19.1), compared to those who did achieve breast pCR, P

Aim: The study aimed to explore the relationship between urate deposition and surrounding atherosclerotic plaques, and to confirm the contribution of urate deposition to the development of coronary atherosclerosis. Methods and results: The present study employed Dual-energy CT (DECT) material separation technology through calcium score scan to access the presence of MSU crystal deposition in coronary atherosclerotic plaques in patients with clinically suspected coronary heart diseases undergoing DECT. DECT showed that among 872 patients, 441 had plaques in coronary arteries; the incidence of plaque was 50.6 %. The patients were divided in the atherosclerotic plaque vs. non-plaque groups. There were significant differences in age, sex, blood pressure, blood glucose, serum creatinine, and history of gout and hyperuricemia between the plaque and non-plaque groups (all P

Background: Anemia seriously affects the health and quality of life of the older adult population and may be influenced by various types of environmental metal exposure. Current studies on metals and anemia are mainly limited to single metals, and the association between polymetals and their mixtures and anemia remains unclear. Methods: We determined 11 urinary metal concentrations and hemoglobin levels in 3781 participants. Binary logistic regression and restricted cubic spline (RCS) model were used to estimate the association of individual metals with anemia. We used Bayesian kernel machine regression (BKMR) and Quantile g-computation (Q-g) regression to assess the overall association between metal mixtures and anemia and identify the major contributing elements. Stratified analyses were used to explore the association of different metals with anemia in different populations. Results: In a single-metal model, nine urinary metals significantly associated with anemia. RCS analysis further showed that the association of arsenic (As) and copper (Cu) with anemia was linear, while cobalt, molybdenum, thallium, and zinc were non-linear. The BKMR model revealed a significant positive association between the concentration of metal mixtures and anemia. Combined Q-g regression analysis suggested that metals such as Cu, As, and tellurium (Te) were positively associated with anemia, with Te as the most significant contributor. Stratified analyses showed that the association of different metals with anemia varied among people of different sexes, obesity levels, lifestyle habits, and blood pressure levels. Conclusions: Multiple metals are associated with anemia in the older adult population. A significant positive association was observed between metal mixture concentrations and anemia, with Te being the most important factor. The association between urinary metal concentrations and anemia is more sensitive in the non-hypertensive populations.

Background: Continuous light exposure increases sympathetic excitation in rats, leading to hypertension, left ventricular hypertrophy, and fibrosis. This study was aimed to investigate whether continuous light exposure causes destabilization of vital signs and gut microbiota (GM) in Sprague Dawley (SD) rats and whether clonidine hydrochloride (CH), a central sympathetic depressant drug, could prevent these changes. Methods: Eight-week-old male SD rats were divided into three groups with different interventions for 14 weeks: control group (CG), 2-mL pure water gavaged daily while on a normal 12-h light/dark cycle; continuous illumination group (CI), 2-mL pure water gavaged daily while receiving continuous exposure to light (300 lx); and drug administration group (DA), CH (10 μg/kg) gavaged daily while receiving continuous exposure to light (300 lx). Results: The results showed that blood pressure, heart rate, and body weight were significantly higher in the CI group than in the CG and DA groups (P Prevotella (genus level) > Prevotellaceae_bacterium (species level) were enriched in the CI group. The Muribaculaceae family was more abundant in the CG group than in the CI group. Conclusion: Sympathetic nerve inhibition restored the abnormal vital signs and GM changes under continuous light exposure.

Colorectal cancer is a common malignancy with significant rates of morbidity and mortality. A number of factors, including the tumor microenvironment, chemokines, the inflammatory response, have an impact on the development of colorectal cancer. A critical component of the tumor microenvironment is chemokines. Various cell subsets are attracted to the tumor microenvironment through interactions with chemokine receptors. These cells have varying effects on the development of the tumor and the effectiveness of treatment. Additionally, chemokines can participate in inflammatory processes and have effects that are either pro- or anti-tumor. Chemokines can be exploited as targets for medication resistance and treatment in colorectal cancer. In this review, we discuss the expression of chemokines and chemokine receptors, and their relationship with immune cells in the tumor microenvironment. At the same time, we also collect and discuss the significance of chemokines and chemokine receptors in colorectal cancer progression, and their potential as molecular targets for CRC treatment.

In carbonate soils, soil inorganic carbon (SIC) dissolves and releases CO2 due to exogenous application of nitrogen fertilizer, which makes the soil an important carbon source. Application of the nitrification inhibitor 3,4-dimethylpyrazole phosphate (DMPP) is likely to be an effective measure to alleviate SIC dissolution. A 5-year field experiment was conducted to observe SIC dynamics under three treatments: No N fertilizer (CK), N fertilizer (NF), and N fertilizer combined with DMPP (N + NI). Soil samples were collected from 0 to 20, 20–40, 40–60, 60–80, and 80–100 cm in depth, and soil organic carbon (SOC), SIC, total carbon (TC), total nitrogen (TN), and carbon isotope composition (δ13C) of the soil were analyzed. The proportion of pedogenic carbonate (PIC) in SIC was estimated using an isotopic mass balance equation. Results showed that: (1) compared with the application of N only, DMPP had no significant effect on SOC content and δ13CSOC in the 0–100 cm soil profile; (2) the application of N fertilizer significantly reduced the SIC content by 10.0 g·kg−1 (58.3 %) in the 0–80 cm soil profile. In the 0–20, 20–40, and 60–80 cm soil layers, the SIC content was reduced by 2.9, 1.9, and 3.8 g·kg−1, respectively. However, the SIC content significantly increased by 3.2 g·kg−1 (58.9 %) in the 80–100 cm soil layer. DMPP application significantly increased the SIC content in the 0–20 and 20–40 cm soil layers by 1.3 g·kg−1 (50.9 %) and 1.2 g·kg−1 (48.2 %), respectively; (3) DMPP combined with N significantly alleviated PIC dissolution in the 0–40 cm soil layers and increased PIC stock in 0–100 cm soil by 6.2 Mg·ha−1 (64.6 %). Applying DMPP to farmland soil containing carbonate significantly alleviated the dissolution of N fertilizer on PIC, which may decrease CO2 emissions in the field.

Introduction: Gastric cancer (GC)is the third leading cause of cancer-related deaths in China and immunotherapy emerging as a revolutionary treatment for GC recently. Tumor mutational burden (TMB) is a predictive biomarker of immunotherapy in multiple cancers. However, the prognostic significance and subtype of TMB in GC is not fully understood. Objectives: This study aims to evaluate the prognostic value of TMB in Chinese GC and further classify TMB-high GC (GCTMB-H) patients combing with mutational signatures. Methods: Genomic profiling of 435 cancer-gene panel was performed using 206 GC samples from Chinese people. Actionable genetic alterations were compared across all the samples to generate actionable subtyping. The prognostic value of TMB in Chinese GC was evaluated. Mutational signatures were analyzed on TMB-H subtype to stratify the prognosis of TMB. Transcriptomic analysis was applied to compare the distributed immunocytes among different subtypes. Results: 88.3% (182/206) of GC samples had at least one mutation, while 45.1% (93/206) had at least one somatic copy number alteration (SCNA). 29.6% (61/206) of GC samples were TMB-H, including 13 MSI-H and 48 MSS tumors. According to distinct genetic alteration profiles of 69 actionable genes, we classified GC samples into eight molecular subtypes, including TMB-H, ERBB2 amplified, ATM mutated, BRCA2 mutated, CDKN2A/B deleted, PI3KCA mutated, KRAS mutated, and less-mutated subtype. TMB-H subtype presented a remarkable immune-activated phenotype as determined by transcriptomic analysis that was further validated in the TCGA GC cohort. GCTMB-H patients exhibited significantly better survival (P = 0.047). But Signature 1-high GCTMB-H patients had relatively worse prognosis (P = 0.0209, HR = 2.571) than Signature 1-low GCTMB-H patients from Chinese GC cohort, also validated in TCGA GC cohort, presenting highly activated carbohydrate, fatty acid or lipid metabolism. Conclusion: The Signature 1-high GCTMB-H could be a marker of poor prognosis and is associated with metabolism disorder.

Introduction: Male infertility is a multifactorial pathological condition and may be a harbinger of future health. Phthalates are ubiquitous environmental contaminants that have been implicated in the global decline in male fertility. Among them, di-(2-ethylhexyl) phthalate (DEHP) is the most prevalently used. Lycopene (LYC) is a possible preventive and therapeutic agent for male infertility owing to its antioxidant properties. The blood-testis barrier (BTB) is formed between Sertoli cells where it creates a unique microenvironment for spermatogenesis. Objectives: We hypothesize that phthalate caused male infertility and LYC plays an important role in phthalate-induced male fertility disorders. Methods: Hematoxylin-eosin (H&E) staining, ultrastructure observation, and fluorescence microscopy were used to examine the morphological changes. RNA-Seq, and western blotting were conducted to detect gene and protein levels. Routine testing for sperm morphology and sperm-egg binding assay were conducted to examine the morphological structure and function of sperm. Cell scratch assay and transepithelial electrical resistance (TER) were used to detect cell migration capacity and barrier integrity. Results: In vivo experiments, we showed that LYC prevented DEHP-induced impairment of BTB integrity, which provided a guarantee for the smooth progress of spermatogenesis. LYC improved DEHP-induced change in sperm parameters and fertilization ability. Subsequent in vitro experiments, LYC alleviated MEHP-induced disruption of intercellular junctions in mouse Spermatogonia cells (GC-1 cells) and mouse Sertoli cells (TM4 cells). In MEHP-induced BTB impairment models of Sertoli cells, treatment with LYC or overexpressing connexin-43 (Cx43) promoted cell migration capacity and normalized BTB integrity. Cx43 knockdown inhibited cell migration capacity and perturbed BTB reassembly in LYC preventing DEHP-induced BTB impairment. Conclusion: Our study provides evidence for the role of LYC in phthalates-induced spermatogenic disorders and points to Cx43 as a potential target for male fertility.

The properties of steel are affected by the non-metallic inclusions. It is critical to control the morphology of inclusions for producing the high-quality steel. However, due to the morphology of inclusions is complex and diverse, it is difficult to reveal the real morphology of inclusions by using the traditional two-dimensional (2D) observation method, and making it hard to quantitatively analyze the size and morphology of inclusions. In this study, the three-dimensional (3D) morphology of the alumina clusters in steel samples was observed by using the X-ray Micro-CT in the beamline of BL16U2 at Shanghai Synchrotron Radiation Facility (SSRF). Avizo software was used to reconstruct the 3D morphology of the alumina clusters, which intuitively shows the actual morphology of alumina clusters. The accuracy of 2D and 3D observation methods is discussed based on the stereological analysis of individual alumina cluster. A series of parameters were defined to characterize the morphological characteristics of the alumina clusters based the 3D observation. The fractal theory was introduced to quantitatively describe the morphological of alumina clusters. In the current study, the 2D fractal dimension of alumina clusters was determined as 1.64. The complexity of 3D morphology of alumina clusters was analyzed by 3D fractal dimension and shape factor. The current work provides an effective method for quantitative description of the morphology and spatial distribution of inclusions, which provides an important reference for effective control of alumina inclusions.

With the advancement of China’s “carbon neutrality” process, the carbon emission quotas of various types of users have gradually tightened, “carbon responsibility” has attracted widespread attention, and the “high/low carbon area” is divided from the perspective of the user side, and the analysis of “carbon responsibility” is conducive to building a flexible and reasonable response mechanism that promotes carbon reduction demand, and revitalizes the carbon reduction potential of the user side. Based on the theory of carbon emission flow, considering the generator output power transfer distribution factor, The emergence of the proportional sharing principle and electrical dissection theory solves the problem of load-side electricity consumption sources. The emerging carbon emission stream theory, which is both applicable to power systems and consistent with the proportional sharing principle, is used as a basis to further delineate high/low carbon areas. By tracing from the load side to the power side, we can determine the power consumption attributes of the load side, differentiate between high-carbon and low-carbon power users, divide the typical areas of high-carbon and low-carbon power, the levy carbon tax on high-carbon power, change the power consumption habits of the load side to achieve effective demand response, and complete the low-carbon planning of the power system from the load side. the carbon emission flow distribution factor model is established, a method of dividing the high and low carbon area of the power system is proposed, and the effectiveness of the proposed method is verified by the IEEE30 node system.

Aqueous Zn-organic batteries (AZOBs) stand out in the family of aqueous Zn devices due to high theoretical capacity, tunable structures, sustainable resources, and low cost of organic hosts. However, the development of advanced AZOBs faces numerous issues and challenges, including, poor conductivity, low actual capacity, serve molecular dissolution, and unsatisfying energy density. Herein, we summarize an overview of various organic materials as the inserted ion hosts. In addition to categorizing organic compounds based on their functional groups, this report also covers the latest developments in organic cathodes and their energy storage mechanisms. Furthermore, strategies for advanced Zn-organic devices are suggested with regard to structural design and important battery metrics. Moreover, challenges and perspectives are finally discussed from the point of view of full batteries. We hope this review can provide a valuable evaluation of commercial Zn-organic batteries and spur new insights toward a greener energy world.

Reversible data hiding (RDH) has been generally utilized in copyright protection and content integrity authentication for multimedia. In general, many typical RDH schemes are based on grayscale images. Considering that color images are widely employed in daily life, color image based RDH should be significantly concerned. Recently, color image based RDH is rare and those schemes are mostly empirically designed, which means that embedding capacity is manually allocated between different channels (such as RGB channels). In addition, most existing algorithms only focus on designing effective prediction methods to utilize the correlation in each channel, which means that the correlation between different channels is insufficiently employed and thus the algorithm performance is limited. Therefore, in this paper, the correlation between those different channels is sufficiently considered and an adaptive capacity allocation framework is proposed instead of empirical schemes. Moreover, the construction of a new synchronous histogram associated with the above-mentioned capacity allocation algorithm is proposed to further improve its performance. Experimental results demonstrate the superiority of the proposed scheme compared with other state-of-the-art ones.

Oxidative stress (OS) plays a pivotal role in the pathogenesis of spinal cord injury (SCI), yet its underlying mechanisms remain elusive. In this study, we explored the OS phenotype in a rat model of SCI. Subsequently, comprehensive bioinformatic analyses were conducted on microarray data pertaining to SCI (GSE45006). Notably, KEGG enrichment analysis revealed a pronounced enrichment of pivotal pathways, namely MAPK, FoxO, Apoptosis, NF-κB, TNF, HIF-1, and Chemokine across distinct phases of SCI. Furthermore, GO enrichment analysis highlighted the significance of biological processes including response to hypoxia, response to decrease oxygen levels, response to reactive oxygen species, cellular response to oxidative stress, reactive oxygen species metabolic process, and regulation of neuron death in the context of OS following SCI. Notably, our study underscores the prominence of nine genes, namely Itgb1, Itgam, Fn1, Icam1, Cd44, Cxcr4, Ptprc, Tlr4, and Tlr2 as OS key genes in SCI, consistently expressed in both the acute phase (1, 3, 7 days) and sub-acute phase (14 days). Subsequently, the relative mRNA expression of these key genes in different time points (1, 3, 7, 14 days) post-SCI. Finally, leveraging the DsigDB database, we predicted ten potential compounds potentially targeting OS and facilitating the repair of SCI, thus providing novel insights into the mechanisms underlying OS and identifying potential therapeutic targets for SCI.

Acquired aplastic anemia (AA) is a bone marrow failure (BMF) disease, characterized by fatty bone marrow (BM) and BM hypocellularity resulted from auto-immune dysregulated T cells-mediated destruction of BM haemopoietic stem cells (HPSC). The objective of this study was to investigate potential therapeutic effect of irisin, a molecule involved in adipose tissue transition, on AA mouse model. Our results showed that the concentration of irisin in serum was lower in AA patients than in healthy controls, suggesting a role of irisin in the pathogenesis of AA. In the AA mice, irisin administration prolonged the survival rate, prevented or attenuated peripheral pancytopenia, and preserved HPSC in the BM. Moreover, irisin also markedly reduced BM adipogenesis. In vitro results showed that irisin increased both cell proliferation and colony numbers of HPSC. Furthermore, our results demonstrated that irisin upregulated the expression of mitochondrial ATPase Inhibitory Factor 1 (IF1) in HPSC, inhibited the activation of mitochondrial fission protein (DRP1) and enhanced aerobic glycolysis. Taken together, our findings indicate novel roles of irisin in the pathogenesis of AA, and in the protection of HPSC through stimulation of proliferation and regulation of mitochondria function, which provides a proof-of-concept for the application of irisin in AA therapy.

Cardiovascular risk models developed may have limitations when applied to rural Chinese. This study validated and compared the Framingham Risk Score (FRS) and Prediction for Atherosclerotic Cardiovascular Disease Risk in China (PAR) models in predicting 10-year risk of coronary heart disease (CHD) in a rural cohort in Ningxia, China from 2008 to 2019. The FRS and PAR models were validated by estimating predicted events, C index, calibration χ2 and plots. 1381 adults without CHD at baseline were followed up for 9.75 years on average. 168 CHD cases were observed. The FRS and PAR underestimated CHD events by 22 % and 46 % for the total population, while overestimated for males by 152 % and 78 %, respectively. The C index was slightly higher for PAR than FRS. Both models showed weak calibration with chi-square values above 20 (p

The purpose of this work was to investigate the deterioration mechanism of an optimized Al2O3–MgO refractory castable during industrial trials. After structural optimization, the average corrosion rate of every cycle deceased to 0.29 mm/cycle from 0.46 mm/cycle. Corroded microstructure of the optimized Al2O3–MgAl2O4 refractory castable after server 195 cycles was explored. It was indicated that the structural optimization led to an approximate 36% improvement in corrosion resistance than that of comparison one. An adhered slag layer comprising of (Fe, Mg)Al2O4 spinel was observed on the refractory's surface. Iron beans and iron/manganese oxides mainly occurred in the reaction layer, and several penetrating cracks occurred at the corroded interface which would cause potential structural spalling for refractory lining. Based on the observed microstructural characteristics, a corrosion mechanism of refractory lining in a commercial ladle was proposed.

Background: In the past, multiple studies have offered incremental evidence that indicates that competitive endogenous RNA (ceRNA) regulatory networks are involved in tumor growth and present novel therapeutic targets. Herein, we investigated the impact of thymidine kinase 1 (TK1)-related ceRNA networks on the prognosis of non-small cell lung cancer (NSCLC). Methods: TK1 expression data in NSCLC and normal tissue samples were retrieved from the Cancer Genome Atlas (TCGA) database and were then compared. Thereafter, the findings of the immunohistochemical staining experiments and clinical follow-up data derived from patients with NSCLC were used for conducting prognostic analysis. The starBase database was searched to determine TK1-targeted microRNAs and long non-coding RNAs, and clinical data from TCGA were used for survival analysis to construct a ceRNA network associated with TK1 expression and prognosis. Finally, the roles played by methylation and immunity in the prognosis and treatment of NSCLC were analyzed. Results: Our findings revealed that the cancer tissues expressed significantly higher TK1 levels than normal tissues, and the follow-up clinical data revealed that the prognosis was generally worse in the high-expression patients than in the low-expression patients. In addition, clinical data collected from the starBase and TCGA databases showed that the LINC00665/has-let-7b-5p/TK1 network could influence the growth and prognosis of NSCLC. It was also noted that the TK1 methylation site was correlated with the prognosis of NSCLC, and immunoprognostic analysis further indicated that patients with higher TK1 expression levels displayed a worse prognosis. Conclusion: When the regulatory network of LINC00665/has-let-7b-5p/TK1 was assessed, it was observed that elevated TK1 levels may affect the prognosis of NSCLC. Therefore, it could be considered a prognostic biomarker and a probable therapeutic target for predicting NSCLC prognosis.

Zinc (Zn) is considered as one of the heavy metal pollutants in soil affecting agriculture. Salicylic acid (SA) is an important phytohormone that can mitigate effects against various abiotic stresses in plants, however, its exploration to improve Zn stress tolerance in alfalfa plants is still elusive. Thus, in the present study, exogenous SA treatment was conducted on alfalfa plants under Zn stress. The effects of exogenous SA on the physiological effects of alfalfa plants and the expression levels related genes were studied. This study tested the biomass, relative water content, chlorophyll levels, photosynthetic capacity, proline and soluble sugar contents, detected the activity of antioxidant enzymes (such as peroxidase and superoxide dismutase), glutathione biosynthesis, and endogenous SA levels, and quantified the genes associated with the antioxidant system and glutathione metabolism-mediated Zn stress. The results showed that exogenous SA could elevate the physiological adaptability of alfalfa plants through enhancing photosynthesis, proline and soluble sugar levels, stimulating antioxidant system and glutathione metabolism, and inducing the transcription level of related genes, thereby diminishing oxidative stress, inhibiting excessive Zn accumulation of alfalfa plants, increasing tolerance to Zn stress, and reducing the toxicity of Zn. Collectively, the application of SA alleviates Zn toxicity in alfalfa plants. The findings gave first insights into the regulatory mechanism of the Zn stress tolerance of alfalfa by exogenous SA and this might have positive implications for managing other plants which are suffering Zn stress.

A complex and vast biological network regulates all biological functions in the human body in a sophisticated manner, and abnormalities in this network can lead to disease and even cancer. The construction of a high-quality human molecular interaction network is possible with the development of experimental techniques that facilitate the interpretation of the mechanisms of drug treatment for cancer. We collected 11 molecular interaction databases based on experimental sources and constructed a human protein-protein interaction (PPI) network and a human transcriptional regulatory network (HTRN). A random walk-based graph embedding method was used to calculate the diffusion profiles of drugs and cancers, and a pipeline was constructed by using five similarity comparison metrics combined with a rank aggregation algorithm, which can be implemented for drug screening and biomarker gene prediction. Taking NSCLC as an example, curcumin was identified as a potentially promising anticancer drug from 5450 natural small molecules, and combined with differentially expressed genes, survival analysis, and topological ranking, we obtained BIRC5 (survivin), which is both a biomarker for NSCLC and a key target for curcumin. Finally, the binding mode of curcumin and survivin was explored using molecular docking. This work has a guiding significance for antitumor drug screening and the identification of tumor markers.

Gastric cancer is a malignant tumor with high mortality and high incidence. This study aims to explore the function and molecular mechanism of Cortactin on gastric cancer progression in vitro and in vivo. A bioinformatics analysis from TCGA displayed that Cortactin was highly expressed in gastric cancer samples, and patients with a high Cortactin level had a worse survival rate. Subsequently, we investigated the specific mechanism of action of A in gastric cancer by collecting patient samples for immunohistochemistry, WB, qRT-PCR, cell transfection, cell invasion and metastasis, and constructing tumor xenografts in nude mice. Overexpression of Cortactin inhibited apoptosis and enhanced cellular proliferation and mobility in AGS cells, while those activities were reversed by the knockdown of MMP2 or MMP9. Conversely, the deletion of Cortactin induced apoptosis and suppressed cell growth and metastasis in SGC7901 cells, whereas those behaviors were inhibited by overexpression of MMP2 or MMP9. Additionally, the ERK pathway was activated by Cortactin upregulation. In vivo studies presented that overexpression of Cortactin promoted tumor growth, increased Ki67 expression, and reduced caspase 3 expression, which was reversed by ERK inhibitor treatment. In conclusion, Cortactin acted as an oncogene in gastric cancer and exerted its function by ERK/MMP2/MMP9 signaling pathway.

Colorectal cancer (CRC) is one of the most common digestive diseases worldwide. It has steadily ascended to the top three cancers in terms of incidence and mortality. The primary cause is the inability to diagnose it at an early stage. Therefore, early detection and diagnosis are essential for colorectal cancer prevention. Although there are now various methods for CRC early detection, in addition to recent developments in surgical and multimodal therapy, the poor prognosis and late detection of CRC still remain significant. Thus, it is important to investigate novel technologies and biomarkers to improve the sensitization and specification of CRC diagnosis. Here, we present some common methods and biomarkers for early detection and diagnosis of CRC, we hope this review will encourage the adoption of screening programs and the clinical use of these potential molecules as biomarkers for CRC early detection and prognosis.

Steel slag powder (SSP) was selected as an inorganic micro powder filler instead of limestone powder (LSP) to prepare asphalt mastic in this paper. Firstly, the microscopic characteristics of SSP and LSP such as particle size distribution, surface morphology, phase composition and chemical composition were characterized by laser particle size analyzer, scanning electron microscopy (SEM), X-ray diffraction (XRD) analyzer, and X-ray fluorescence (XRF) analyzer. Then, the composition and content of chemical functional groups of asphalt mastics were studied by fourier transform infrared spectrometer (FTIR). Finally, the effect of SSP on the creep and fatigue properties of asphalt mastics was investigated via multiple stress creep recovery (MSCR) and time scanning experiments using a dynamic shear rheometer (DSR). The results showed that the addition of SSP as mineral filler instead of LSP to asphalt binder enhanced the deformation resistance and the fatigue life of the asphalt mastics.The complex shear modulus of asphalt mastics show an increase trend with an increase in the SSP content. Compared with LSP asphalt mastic, the complex shear modulus of SSP asphalt mastic ( SSP content 30 %, 50 %, 100 %) increased by 84.9 %, 118.0 % and 256.1 %, respectively. From the perspective of structural design and material selection, the fatigue life NDER corresponding to the cumulative dissipative energy rate(DER) is recommended to analyze the fatigue life of asphalt mastics.The results of the MSCR and time scanning experiments demonstrated that the use of a combination of SSP and LSP as filler could be an effective approach for comprehensive utilization of steel slag in asphalt mixture.

Metabolic-associated fatty liver disease (MAFLD), which is previously known as non-alcoholic fatty liver disease (NAFLD), represents a major health concern worldwide with limited therapy. Here, we provide evidence that ferroptosis, a novel form of regulated cell death characterized by iron-driven lipid peroxidation, was comprehensively activated in liver tissues from MAFLD patients. The canonical-GPX4 (cGPX4), which is the most important negative controller of ferroptosis, is downregulated at protein but not mRNA level. Interestingly, a non-canonical GPX4 transcript-variant is induced (inducible-GPX4, iGPX4) in MAFLD condition. The high fat-fructose/sucrose diet (HFFD) and methionine/choline-deficient diet (MCD)-induced MAFLD pathologies, including hepatocellular ballooning, steatohepatitis and fibrosis, were attenuated and aggravated, respectively, in cGPX4-and iGPX4-knockin mice. cGPX4 and iGPX4 isoforms also displayed opposing effects on oxidative stress and ferroptosis in hepatocytes. Knockdown of iGPX4 by siRNA alleviated lipid stress, ferroptosis and cell injury. Mechanistically, the triggered iGPX4 interacts with cGPX4 to facilitate the transformation of cGPX4 from enzymatic-active monomer to enzymatic-inactive oligomers upon lipid stress, and thus promotes ferroptosis. Co-immunoprecipitation and nano LC–MS/MS analyses confirmed the interaction between iGPX4 and cGPX4. Our results reveal a detrimental role of non-canonical GPX4 isoform in ferroptosis, and indicate selectively targeting iGPX4 may be a promising therapeutic strategy for MAFLD.

To improve the accuracy of the evaluation of the equivalent inertia of a power system, a method for evaluating the equivalent inertia level of a power system based on an intelligent optimization algorithm is proposed. The proposed method constructs the objective function based on different degrees of system perturbation, ignores the frequency characteristics of the load, constructs the objective function with the generator swing equation, solves the inertia time constant of each generator using the intelligent optimization algorithm, and then evaluates the equivalent inertia of the whole system, eliminates the influence of inconsistent frequency change rate under perturbation on the system equivalent inertia evaluation, and thus obtains a more accurate system equivalent inertia evaluation, experimental result shows the evaluation accuracy can be improved by 10.79% and 3.48% respectively compared with other two comparison method.

ABSTRACT: Cronobacter sakazakii is a food-borne pathogen that is resistant to a variety of environmental stress conditions. It can survive in harsh environments. We studied the effects of silver nanoparticles (AgNP) on the environmental tolerance and biofilm formation of C. sakazakii. First, we determined the minimum inhibitory concentration (MIC) of AgNP to C. sakazakii and determined the growth curve of C. sakazakii treated with different concentrations of AgNP by using the plate counting method. After determining the sub-inhibition concentrations (SIC) of AgNP on C. sakazakii, we studied the effects of AgNP on the resistance of C. sakazakii to heat, desiccation, osmotic pressure, and acid. The antibiofilm activity of AgNP was also studied. Finally, real-time quantitative PCR was used to analyze the transcription levels of 16 genes related to the environmental tolerance of C. sakazakii. The SIC of AgNP significantly reduced the survival rate of C. sakazakii under various environmental stress conditions. The results showed that AgNP at 0.625 and 1.25 μg/mL significantly inhibited the formation of C. sakazakii biofilms. The expression levels of most genes were significantly downregulated in C. sakazakii cells treated with 0.625 and 1.25 μg/mL AgNP. Therefore, AgNP may reduce the environmental tolerance of C. sakazakii by inhibiting the expression of genes related to stress tolerance. Moreover, AgNP inhibited the production of ATP in C. sakazakii cells and the formation of C. sakazakii biofilms. Our research provides a theoretical basis for the application of AgNP in food packaging, bactericidal coatings, and other fields.

Corilagin, a polyphenolic tannic acid compound, showed significant anti-inflammatory activity in atherosclerotic mice. The present study aimed to evaluate the effect and mechanism of corilagin in atherosclerosis by in vivo, in vitro and in molecular docking strategies analysis. An atherosclerotic model was established by feeding ApoE−/− mice a high-fat diet. Murine RAW264.7 macrophages were cultured and induced with lipopolysaccharide (LPS). Treatment with corilagin had a marked inhibitory effect on the plaque area and lipid accumulation in atherosclerotic mice. Corilagin decreased the expression of iNOS and promoted the expression of CD206 in aortic plaque, as well as inhibited the production of proinflammatory factors in HFD-fed ApoE−/− mice and LPS-induced RAW264.6 cell. Corilagin also obviously inhibited the expression of TLR4, reduced the phosphorylation of the JNK, the protein expressions of p38 and NF-κB pathway. In addition, corilagin markedly diminished the nuclear translocation of NF-κBp65. Similarly, molecular docking study suggested that hydrogen bonds were detected between the corilagin and the five proteins (TLR4, Myd88, p65, P38, and JNK) with a significant “CDOCKER energy”. These results showed that the antiatherosclerotic effect of corilagin against M1 macrophage polarization and inflammation via suppression the activation of TLR4-NFκB/MAPK signaling pathway. Therefore, corilagin could be a promising lead compound to develop drugs for the treatment of atherosclerosis.

In January 2022, we received ant specimens collected from three field colonies from Shantou City, Guangdong Province, China. They were identified as the little fire ant, Wasmannia auropunctata, through morphological and molecular analyses. Wasmannia auropunctata is listed as one of the 100 most dangerous invasive species by the International Union for Conservation of Nature (IUCN) and has spread from its native range in South America to every continent except Antarctica. DNA analysis of mitochondrial cytochrome c oxidase subunit I (COI) in nine specimens of W. auropunctata found that they had a close genetic relationship with specimens from Argentina. This study represents the first formal record of the establishment of W. auropunctata outdoor in Chinese mainland. However, the invasion stage and occurrence degree of W. auropunctata in China are not clear to date. The implementation of quarantine measures, investigation of the occurrence and distribution, and development of monitoring and control strategies are needed to actively respond to the threat posed by this highly invasive ant.

Background/purpose: Mechanical stress plays a vital role in osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Cyclic mechanical stress may up-regulate reactive oxygen species (ROS) level. N-acetylcysteine (NAC) possesses powerful antioxidant capacity. However, it is undefined the impact of NAC on osteogenic differentiation stimulated by cyclic mechanical stress in PDLSCs. The aim of our research was to study the effect of NAC on PDLSCs during osteogenic differentiation under cyclic mechanical stress. Materials and methods: The expression levels of osteogenesis markers were used to examine the osteogenic differentiation of PDLSCs. ROS production were measured by flow cytometry. The levels of reduced glutathione (GSH) and oxidized glutathione (GSSG) were analyzed. We also examined the changes of alveolar bone and periodontal ligament (PDL) tissues in orthodontic rats by micro-computed tomography (micro-CT) system and immunohistochemistry (IHC) staining. The nuclear factor erythroid-2-related factor-2 (Nrf2) expression was examined. Results: NAC could enhance the osteogenic differentiation and up-regulate the GSH level as well as the ratio of GSH/GSSG, while down-regulate ROS generation and Nrf2 expression induced by cyclic mechanical stress in PDLSCs. NAC had beneficial effects on the microstructure of alveolar bone and enhanced the expression levels of osteogenesis markers, such as alkaline phosphatase (ALP) and collagen type 1 (COL1) in PDL in orthodontic rats at the tension side. Conclusion: NAC could improve the osteogenic differentiation stimulated by cyclic mechanical stress in PDLSCs and in orthodontic rats, suggesting a potential therapeutic approach for alveolar bone remodeling in orthodontics.

The distribution of antibiotic resistance genes (ARGs) in water sources potentially threatens drinking water safety. However, the sources of antibiotic resistome in groundwater are still under-investigated. Here, we evaluated the profiles of antibiotic resistome in peri-urban groundwater and its associated water sources (river and mountain spring) to characterize the antibiotic resistome from natural water sources on groundwater resistome. A total of 261 antibiotic resistome were detected in groundwater, mountain spring, and river samples. The relative abundances of ARGs and mobile genetic elements (MGEs) were significantly higher in the river samples than in spring water and groundwater samples. The resistome profiles were similar between groundwater and spring water but differed from the river samples. According to source tracking results, the groundwater resistome was likely to be derived from springs (28.0%−50.0%) and rivers (28.6%−48.6%), which share the same trend for the source tracking of bacterial communities. Bacterial α-diversity, bacterial β-diversity, and MGEs directly or indirectly affected the ARGs in groundwater samples. Although the abundance of groundwater resistome was not elevated by river and spring water, groundwater resistomes were diverse and may be derived from both river and spring water. We highlight the importance of groundwater resistome and its association with potential water sources, providing a better understanding and basis for the effective control of the ARG proliferation and dissemination in groundwater from exogenous water bodies in the future.

Building heights are one of the crucial data for comprehending the functions of urban systems. Employing optical remote sensing imagery, the shadow-based method is one of the most promising methods which have been proposed for estimating building height. However, the existing shadow-based studies for building height estimation are restricted to a small area due to the lack of building height annotations and ignorance of building azimuth variations. The Ice, Cloud, and Land Elevation Satellite-2 (ICESat-2) allows large-scale building height retrieval in the along-track direction and thus can be taken as ground truth building height annotations to support the shadow-based algorithms for large-scale building height extraction. Here, we proposed an approach for extracting building height by combining Google Earth Satellite (GES) images and ICESat-2 photons. Building and shadow instances were first extracted using a U-Net deep learning framework. Based on the building height annotations retrieved from ICESat-2 photons, an improved shadow-based building height estimation model by minimizing the global error across all sample buildings was developed. A typical urban area located in the city center of Shanghai, China with an area of around 90 km2 was selected to validate the proposed method. In total 15,966 buildings were successfully extracted and the results indicated that the estimated building heights have high accuracy with an absolute mean error of 4.08 m. Moreover, the proposed method shows a better performance compared to the existing shadow-based method and existing building height datasets. The method holds great potential for large-scale building-level height retrieval which contributes to further studies of urban morphologies.

The two-dimensional (2D) Zn-MOF-NH2/Cu heterojunctions were prepared via in situ photodeposition of Cu NPs on the surface of 2D Zn-MOF-NH2. The 2D Zn-MOF-NH2/Cu (1 wt%) heterojunction exhibited the excellent photocatalytic activity with a CO production rate of 0.76 μmol/h under irradiation of full spectrum light only using H2O as a hole sacrificial agent, which is 16.2 and 2.7 times that of bulk Zn-MOF-NH2 and 2D Zn-MOF-NH2 nanosheets, respectively. This work provides an insight into design of a highly efficient 2D MOFs-based photocatalysts in catalytic CO2 reduction.

As zoonotic pathogens are threatening public health globally, the virulence factor genes (VFGs) they carry underlie latent risk in the environment. However, profiling VFGs in the environment is still in its infancy due to lack of efficient and reliable quantification tools. Here, we developed a novel high-throughput qPCR (HT-qPCR) chip, termed as VFG-Chip, to comprehensively quantify the abundances of targeted VFGs in the environment. A total of 96 VFGs from four bacterial pathogens including Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, and Salmonella enterica were targeted by 120 primer pairs, which were involved in encoding five types of virulence factors (VFs) like toxin, adherence, secretion system, immune evasion/invasion, and iron uptake. The specificity of VFG-Chip was both verified computationally and experimentally, with high identity of amplicon sequencing and melting curves analysis proving its robust capability. The VFG-Chip also displayed high sensitivity (by plasmid serial dilution test) and amplification efficiency averaging 97.7%. We successfully applied the VFG-Chip to profile the distribution of VFGs along a wastewater treatment system with 69 VFGs detected in total. Overall, the VFG-Chip provides a robust tool for comprehensively quantifying VFGs in the environment, and thus provides novel information in assessing the health risks of zoonotic pathogens in the environment.

The global rate of human male infertility is rising at an alarming rate owing to environmental and lifestyle changes. Phthalates are the most hazardous chemical additives in plastics and have an apparently negative impact on the function of male reproductive system. Ferroptosis is a recently described form of iron-dependent cell death and has been linked to several diseases. Transferrin receptor (TfRC), a specific ferroptosis marker, is a universal iron importer for all cells using extracellular transferrin. We aim to investigate the potential involvement of ferroptosis during male reproductive toxicity, and provide means for drawing conclusions on the effect of ferroptosis in phthalates-induced male reproductive disease. In this study, we found that di (2-ethylhexyl) phthalate (DEHP) triggered blood-testis barrier (BTB) dysfunction in the mouse testicular tissues. DEHP also induced mitochondrial morphological changes and lipid peroxidation, which are manifestations of ferroptosis. As the primary metabolite of DEHP, mono-2-ethylhexyl phthalate (MEHP) induced ferroptosis by inhibiting glutathione defense network and increasing lipid peroxidation. TfRC knockdown blocked MEHP-induced ferroptosis by decreasing mitochondrial and intracellular levels of Fe2+. Our findings indicate that TfRC can regulate Sertoli cell ferroptosis and therefore is a novel therapeutic molecule for reproductive disorders in male patients with infertility.

Primary Progressive Aphasia (PPA) is a neurodegenerative disorder primarily affecting language functions. Neuromodulatory techniques (e.g., transcranial direct current stimulation, active-tDCS) and behavioral (speech-language) therapy have shown promising results in treating speech and language deficits in PPA patients. One mechanism of active-tDCS efficacy is through modulation of network functional connectivity (FC). It remains unknown how biological sex influences FC and active-tDCS or language treatment(s). In the current study, we compared sex differences, induced by active-tDCS and language therapy alone, in the default mode and language networks, acquired during resting-state fMRI in 36 PPA patients. Using a novel statistical method, the covariate-assisted-principal-regression (CAPs) technique, we found sex and age differences in FC changes following active-tDCS. In the default mode network (DMN): (1) men (in both conditions) showed greater FC in DMN than women. (2) men who received active-tDCS showed greater FC in the DMN than men who received language-treatment only. In the language network: (1) women who received active-tDCS showed significantly greater FC across the language network than women who received sham-tDCS. As age increases, regardless of sex and treatment condition, FC in language regions decreases. The current findings suggest active-tDCS treatment in PPA alters network-specific FC in a sex-dependent manner.