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ABSTRACTBackground Methionine adenosyl transferase II alpha (MAT2A) is the key enzyme to transform methionine into S-adenosylmethionine (SAM), the main methylgroup donor involved in the methylation. The purpose of our study wasto explore whether MAT2A-mediated methionine metabolism affected theexpression of inflammatory cytokines in human gingival fibroblasts(hGFs).Methods Both healthy and inflamed human gingiva were collected. HGFs werecultured and treated with P. gingivalis, with or without MAT2Ainhibitor (PF9366), small interference RNA (siRNA), or extrinsic SAMpretreatment. The levels of inflammatory cytokines were detected byreal-time PCR, western blotting, and ELISA. SAM levels were detectedby ELISA. The nuclear factor-kappa B (NF-κB) and mitogen-activatedprotein kinase (MAPK) pathway was explored by western blotting.Results The expression of MAT2A was increased in the inflamed tissues. P.gingivalis infection promoted the expression of MAT2A and SAM inhGFs. Meanwhile, PF9366 and MAT2A-knockdown significantly decreasedexpression of inflammatory cytokines and SAM production. PF9366inhibited activation of NF-κB/MAPK pathway in P. gingivalis-treatedhGFs.Conclusions MAT2A-mediated methionine metabolism promoted P. gingivalis-inducedinflammation in hGFs. Targeting MAT2A may provide a novel therapeuticmethod for modulating periodontitis.

Triple-negative breast cancer (TNBC) is a challenging subtype with unclear biological mechanisms. Recently, the transcription factor androgen receptor (AR) and its regulation of the DLGAP5 gene have gained attention in TNBC pathogenesis. In this study, we found a positive correlation between high AR expression and TNBC cell proliferation and growth. Furthermore, we confirmed DLGAP5 as a critical downstream regulator of AR with high expression in TNBC tissues. Knockdown of DLGAP5 significantly inhibited TNBC cell proliferation, migration, and invasion. AR was observed to directly bind to the DLGAP5 promoter, enhancing its transcriptional activity and suppressing the activation of the p53 signaling pathway. In vivo experiments further validated that downregulation of AR or DLGAP5 inhibited tumor growth and enhanced CD8+ T cell infiltration. This study highlights the crucial roles of AR and DLGAP5 in TNBC growth and immune cell infiltration. Taken together, AR inhibits the p53 signaling pathway by promoting DLGAP5 expression, thereby impacting CD8+ T cell infiltration in TNBC.

Background: While hepatocellular carcinoma (HCC) represents a highly heterogeneous disease with variable oncogenesis mechanisms and biological features, little is understood about differences in distant metastasis (DM) and prognosis between early-onset and late-onset HCC. This study defined early-onset disease as cancer diagnosed at age younger than 50 years and aimed to present a comprehensive analysis to characterize these disparities based on age. Methods: Information of HCC patients was retrospectively collected from the SEER database and our hospital. Patient demographics, tumor characteristics, and survival were compared between the two groups. A 1:1 propensity score matching (PSM) was adopted to adjust confounding factors. Logistic and cox analysis were utilized to explore risk factors of DM and prognosis, respectively. Besides, the survival differences were assessed by the Kaplan–Meier curve and log-rank test. Results: In total, 19187 HCC patients obtained from the SEER database and 129 HCC patients obtained from our own center were enrolled. Among 19187 patients with HCC, 3376 were identified in the matched cohort, including 1688 early-onset patients and 1688 late-onset patients. Compared with late-onset HCC, early-onset HCC was more likely to occur in female (25.2% vs. 22.9%, P = 0.030), have large tumors (>10.0 cm, 24.1% vs. 14.6%, P = 0.000), harbor poorly differentiated/undifferentiated cancers (17.0% vs. 14.0%, P = 0.003), present advanced clinical stage (T3+T4, 33.7% vs. 28.5%; N1, 9.2% vs. 6.7%; P = 0.000), and develop DM (13.0% vs. 9.5%, P = 0.000). After adjustment for confounders by PSM, we discovered that early-onset HCC remained an independent risk factor for DM. However, combined with Kaplan–Meier curve and cox analysis, early-onset HCC was an independent favorable predictor of survival. We validated these data on an independent cohort from our hospital. Conclusion: In this population-based study, despite developing DM more frequently, early-onset HCC exhibited a superior prognosis than late-onset HCC. Nevertheless, further research is warranted to understand the underlying aetiologic basis for the disparities.

Abstract Objectives The regulatory mechanisms of GCN5 (General control non‐repressed protein5) in the osteogenic differentiation of mesenchymal stem cells (MSCs) in periodontitis are still unclear. The purpose of this review focuses on the regulating roles of GCN5 in bone metabolism and periodontitis, discusses the potential molecular mechanism and provides targets and new ideas for the treatment of periodontitis. Material and Methods The integrative review methodology was used. Data sources include PubMed, Cochrane Library, and additional sources. Results MSCs play an important role in the osteogenesis balance of periodontal tissue. Periodontal ligament stem cells (PDLSCs) from periodontitis patients exhibited defective osteogenic differentiation capacities. Histone acetylation is important in regulating the differentiation of different types of MSCs cells and is closely related to the reduced osteogenic differentiation of PDLSCs. GCN5, one of the first histone acetyltransferase linked to gene transcriptional activation, participates in many biological processes of mesenchymal stem cells. Downregulation of GCN5 expression and lack of GCN5 caused decreased osteogenic differentiation of PDLSCs. Intercellular information exchange may be an important way for MSCs to exert their regulatory and therapeutic functions. Conclusions GCN5 affects the function of cell metabolism‐related genes by regulating the acetylation status of histones or non‐histones, thereby regulating some important progress of MSCs such as PDLSCs' osteogenic differentiation and BMCS osteogenic differentiation.

Abstract Time-averaged shear-wave velocity to 30 m (V S30) is commonly used in ground motion models as a parameter for evaluating site effects. This study used a collection of boreholes in Beijing, Tianjin, Guangxi, Guangdong, and three other municipalities and provinces, which were divided into three regions with reference to the seismic ground motion parameter zonation map of China, to establish V S30 prediction models based on terrain categories. Regional effects were verified by comparing morphometric parameter (topographic slope, surface texture, and local convexity) thresholds and terrain classification maps obtained from global digital elevation model (DEM) data and regional DEM data of the three regions. Additionally, V S30 prediction models for the three regions using both types of terrain classification maps were established and analyzed comparatively to provide credible regional V S30 models for China. Through analysis of the correlations between the measured V S30 values and the predicted V S30 values, calculation of the mean squared error and mean absolute percentage error in each region, and with consideration of the geological characteristics of the boreholes, the V S30 prediction models based on terrain classification maps from regional data were finally applied in developing regional V S30 models for China. Intercomparison of the V S30 prediction models for the three regions indicated that subregional consideration is necessary in terrain classification. Finally, a spatial analysis method adopting inverse distance weighting of the residuals was used to update the initial V S30 models. The developed V S30 models could be used both in developing regional ground motion models and in the construction of earthquake disaster scenarios. Graphical Abstract

This study aimed to conduct a meta-analysis to investigate whether short-term exposure to fine (PM2.5) and coarse (PM10) particulate matter was associated with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) hospitalization, emergency room visit, and outpatient visit at different lag values. PubMed, Embase, and the Cochrane Library were searched for relevant papers published up to March 2021. For studies reporting results per 1-µg/m3 increase in PM2.5, the results were recalculated as per 10-µg/m3 increase. We manually calculated the RRs for these two studies and transferred the RRs to estimate 10 µg/m3 increases in PM2.5. Automation tools were initially used to remove ineligible studies. Two reviewers independently screened the remaining records and retrieved reports. Twenty-six studies (28 datasets; 7,018,419 patients) were included. There was a significant association between PM2.5 and AECOPD events on lag0 (ES = 1.01, 95%CI: 1.01-1.02, p

Abstract Background Liver metastases are a major contributor to the poor immunotherapy response in colorectal cancer patients. However, the distinctions in the immune microenvironment between primary tumors and liver metastases are poorly characterized. The goal of this study was to compare the expression profile of multiple immune cells to further analyze the similarities and differences between the microenvironments of liver metastases and the primary tumor. Methods Tissues from 17 patients with colorectal cancer who underwent resection of primary and liver metastases was analyzed using multispectral immunofluorescence. The expression of multiple immune cells (CD8, Foxp3, CD68, CD163, CD20, CD11c, CD66b, CD56, PD-L1, INF-γ, Ki67 and VEGFR-2) in the tumor center (TC), tumor invasive front (

The rice leaf folder, Cnaphalocrocis medinalis (Lepidoptera: Pyralidae), is a notorious pest of rice in Asia. The larvae and adults of C. medinalis utilize specialized chemosensory systems to adapt to different environmental odors and physiological behaviors. However, the differences in chemosensory genes between the olfactory organs of these two different developmental stages remain unclear. Here, we conducted a transcriptome analysis of larvae heads, male antennae, and female antennae in C. medinalis and identified 131 putative chemosensory genes, including 32 OBPs (8 novel OBPs), 23 CSPs (2 novel CSPs), 55 ORs (17 novel ORs), 19 IRs (5 novel IRs) and 2 SNMPs. Comparisons between larvae and adults of C. medinalis by transcriptome and RT-qPCR analysis revealed that the number and expression of chemosensory genes in larval heads were less than that of adult antennae. Only 17 chemosensory genes (7 OBPs and 10 CSPs) were specifically or preferentially expressed in the larval heads, while a total of 101 chemosensory genes (21 OBPs, 9 CSPs, 51 ORs, 18 IRs, and 2 SNMPs) were specifically or preferentially expressed in adult antennae. Our study found differences in chemosensory gene expression between larvae and adults, suggesting their specialized functions at different developmental stages of C. medinalis. These results provide a theoretical basis for screening chemosensory genes as potential molecular targets and developing novel management strategies to control C. medinalis.

Background: Patients who survive initial esophagogastric variceal bleeding (EVB) are at an increased risk of recurrent bleeding and death; however, a reliable predictive model is lacking. We aimed to develop a model for rebleeding prediction in patients with EVB after modified percutaneous transhepatic variceal embolization (PTVE) with cyanoacrylate. Methods: A total of 122 patients with EVB who underwent PTVE from January 2015 to November 2020 were enrolled. Multivariate logistic analyses were conducted to determine independent risk factors for nomogram construction. The discrimination, calibration, and clinical utility of the nomogram were compared with the Model for End-stage Liver Disease score (MELD) and the Child–Pugh model. Risk stratification was performed according to the nomogram. Results: Rebleeding within 3 months of PTVE occurred in 32 patients (26.2%). Independent rebleeding indicators included prior history of endoscopic therapy, Child–Pugh score, partial splenic embolization, and creatinine level. The nomogram incorporating these four predictors achieved excellent calibration and discriminatory abilities, with a concordance index of 0.85, which was confirmed to be 0.83 through bootstrapping validation. The nomogram demonstrated superior discrimination and clinical applicability than the MELD and Child–Pugh models. As shown in the Kaplan–Meier curves, high-risk patients had a high probability of rebleeding (P ​

In this paper, an incremental nonlinear dynamic inversion (INDI) control scheme is proposed for the attitude tracking of a helicopter with model uncertainties, and actuator delay and saturation constraints. A finite integral compensation based on model reduction is used to compensate the actuator delay, and the proposed scheme can guarantee the semi-globally uniformly ultimately bounded tracking. The overall attitude controller is separated into a rate, an attitude, and a collective pitch controller. The rate and collective pitch controllers combine the proposed method and INDI to enhance the robustness to actuator delay and model uncertainties. Considering the dynamic of physical actuators, pseudo-control hedging (PCH) is introduced both in the rate and attitude controller to improve tracking performance. By using the proposed controller, the helicopter shows good dynamics under the multiple restrictions of the actuators.

CO2 injection technology into coal seams to enhance CH4 recovery (CO2-ECBM), therefore presenting the dual benefit of greenhouse gas emission reduction and clean fossil energy development. In order to gaze into the features of CO2 injection’s influence on reservoir pressure and permeability, the Thermal-Hydraulic-Mechanical coupling mechanism of CO2 injection into the coal seam is considered for investigation. The competitive adsorption, diffusion, and seepage flowing of CO2 and CH4 as well as the dynamic evolution of fracture porosity of coal seams are considered. Fluid physical parameters are obtained by the fitting equation using MATLAB to call EOS software Refprop. Based on the Canadian CO2-ECBM project CSEMP, the numerical simulation targeting shallow low-rank coal is carried out, and the finite element method is used in the software COMSOL Multiphysics. Firstly, the direct recovery (CBM) and CO2-ECBM are compared, and it is confirmed that the injection of CO2 has a significant improvement effect on methane production. Secondly, the influence of injection pressure and temperature is discussed. Increasing the injection pressure can increase the pressure difference in the reservoir in a short time, so as to improve the CH4 production and CO2 storage. However, the increase in gas injection pressure will also lead to the rapid attenuation of near-well reservoir permeability, resulting in the weakening of injection capacity. Also, when the injection temperature increases, the CO2 concentration is relatively reduced, and the replacement effect on CH4 is weakened, resulting in a slight decrease in CBM production and CO2 storage.

On the basis of a conceptual model for an Excavation based Enhanced Geothermal System (EGS-E), which proposed to extract heat from Hot Dry Rock at depth through dominantly adopting shaft, roadways, and caved rock failure techniques but not depending on either wellbore drilling or fracturing stimulation, a novel extensive version of heat extraction is proposed in this paper. Considering its mechanical stability issues, the new scheme contains two fields apart away: the ones are near-field by piping flow to touch the tunnel wall; the others are far-field through filling and driving fluid within the voids of collapsed rock. The former is represented as a tunnel unit being installed hollow linear, which can extract and produce heat precisely according to structural design and accurate operative prediction. The latter is represented as interconnective fissures being induced by stope excavation due to gravitational weight and unloading of a deep-buried squeeze. The EGS-E uses a two-stage heat exchange system of “fluid-rock” and “fluid-fluid.” Then, a 3D transient thermal-hydraulic model is established to demonstrate the heat extraction performance. The temperature field and accumulated heat energy are investigated. The modeling work provides a tentative workflow to simulate an EGS-E system and, most probably for the first time, demonstrated that the deep underground Hot Dry Rock heat mining turns out to be preliminarily studied in a quantitative way.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and a leading cause of cancer-related deaths. Due to late diagnosis, early intrahepatic metastasis and nonresponse to systemic treatments, surgical resection and/or biopsy specimens remain the gold standard for disease staging, grading and clinical decision-making. Since only a small amount of tissue was obtained in a needle biopsy, the conventional tissue biopsy is unable to represent tumor heterogeneity in HCC. For this reason, it is imperative to find a new non-invasive and easily available diagnostic tool to detect HCC at an early stage and to monitor HCC recurrence. The past decade has witnessed considerable evolution in the development of liquid biopsy technologies with the emergence of next-generation sequencing. As a liquid biopsy approach, molecular analysis of cell-free DNA (cfDNA), characterized by noninvasiveness and real-time analysis, may accurately represent the tumor burden and comprehensively reflect genetic profile of HCC. Therefore, cfDNA may be used clinically as a predictive biomarker in early diagnosis, outcome assessment, and even molecular typing. In this review, we provide an update on the recent advances made in clinical applications of cfDNA in HCC.

BackgroundChronic cough is a common complaint which affects a large number of patients worldwide. Increased cough sensitivity is a very important cause of chronic persistent cough. However, there are limited clinical diagnosis and treatment for increased cough sensitivity. Transient receptor potential vanilloid-1 (TRPVl) is a member of the transient receptor potential (TRP) family of channels which is very closely associated with respiratory diseases. However, the mechanism through which TRPV1 that influences downstream events is still poorly understood.ResultsCapsaicin induced increase in cough sensitivity by upregulating the protein level of TRPV1, leading to the secretions of Substance P and neurokinin A which stimulated neurogenic inflammation. However, sinomenine, a component of traditional Chinese medicine, significantly attenuated the capsaicin-induced cough by inhibiting the expression of TRPV1 in guinea pigs. In addition, capsaicin increased the expression of SOX5 which mediated the transcriptional upregulation of TRPV1. However, pretreatment with sinomenine reduced the expression of SOX5.ConclusionThese results indicate that capsaicin induced increase in cough sensitivity by activating neurogenic inflammation, while sinomenine attenuated the increase in cough sensitivity by inhibiting the expressions of SOX5 and TRPV1 in guinea pigs. This finding may provide a novel target for the treatment of aggravated cough sensitivity.

Wet-mix shotcrete has been widely used to support roadways during the excavation of underground mining. In practice, the mix proportion of wet-mix shotcrete plays a key role in later successful application. To obtain an optimal mix proportion, a large number of trial physical experiments should be carried out. Therefore, in this paper, a new ANN–PSO model is proposed to obtain the mix proportion of wet-mix shotcrete quickly, precisely and economically. The artificial neural network (ANN) model was used to establish the objective functions for particle swarm optimization (PSO) optimization, while the PSO was adopted to optimize mix proportions of wet-mix shotcrete to achieve optimal objectives. This hybrid model was applied to optimize mix proportions of wet-mix shotcrete in the Jinchuan mine. The results revealed that the ANN model yielded a mean relative error (MRE) of 2.755% and an R2 of 0.980, indicating an excellent prediction to establish the reasonable objective function. Additionally, PSO spent less than 60 s obtaining an optimal mix proportion of wet-mix shotcrete required by the mine. Consequently, this ANN–PSO model can be used as an efficient design guide to facilitate decision making, prior to the construction phase.

Abstract Resistance to cisplatin (DDP) and dose-related toxicity remain two important obstacles in the treatment of prostate cancer (PCa) patients with DDP-based chemotherapy. We have investigated whether the knockdown of hypoxia-inducible factor-1 alpha (HIF-1α) by siRNA could enhance the antitumor activity of DDP, and aimed to determine the underlying mechanisms. Intravenous injection of attenuated Salmonella carrying a HIF-1α siRNA-expressing plasmid was used to knockdown HIF-1α in a PC-3 xenograft model. The in vitro and in vivo effects of HIF-1α siRNA treatment and/or DPP on PCa cell proliferation, apoptosis, glycolysis, and production of reactive oxygen species (ROS) were assessed by examining molecular markers specific to each process. The results demonstrated that the treatment of tumor-bearing mice with attenuated Salmonella carrying the HIF-1α siRNA plasmid greatly enhanced the antitumor effects of low-dose DDP. Further mechanistic studies demonstrated that knockdown of HIF-1α improved the response of PCa cells to DDP by redirecting aerobic glycolysis toward mitochondrial oxidative phosphorylation, leading to cell death through overproduction of ROS. Our findings indicate that DDP-based chemotherapy combined with targeting the HIF-1α-regulated cancer metabolism pathway might be an ideal strategy to treat PCa.

Carthamus tinctorius L., commonly known as safflower, is an important oilseed crop containing oil bodies. Oil bodies are intracellular organelles in plant cells for storing triacylglycerols (TAGs) and sterol esters. Oleosins are the most important surface proteins of the oil bodies. We predicted and retrieved the sequences of eight putative C. tinctorius oleosin (Ctoleosin) genes from the genome database of safflower. The bioinformatics analyses revealed the size of their open reading frames ranging from 414 to 675 bp, encoding 137 to 224 aa polypeptides with predicted molecular weights of 14.812 to 22.155 kDa, all containing the typical “proline knot” motif. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) determined the spatiotemporal expression pattern of Ctoleosin genes, which gradually increased and peaked during flowering and seed ripening, and decreased thereafter. To validate their role in plant development, we transformed and overexpressed these eight putative Ctoleosin genes in Arabidopsis. Overexpressing Ctoleosins did not affect leaf size, although silique length was altered. Arabidopsis transformed with Ctoleosin3, 4, and 5 grew longer siliques than did the wild-type plants, without altering seed quantity. The 100-grain weight of the transgenic Arabidopsis seeds was slightly more than that of the wild-type seeds. The seed germination rates of the plants overexpressing Ctoleosin4 and 6 were slightly lower as compared with that of the wild-type Arabidopsis, whereas that in the other transgenic lines were higher than that in the wild-type plants. The overexpression of Ctoleosin genes elevated the oil content in the seeds of transgenic Arabidopsis. Our findings not only provide an approach for increasing the oil content, but also for elucidating the intricate mechanisms of oil body synthesis.

High expression of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) has been detected in a variety of human tumors. However, the association of positive p-STAT3 expression with clinicopathological parameters and the prognosis of colorectal cancer patients remain controversial. To identify the relationship between p-STAT3 expression and clinicopathological parameters and prognosis in patients with colorectal cancer, a systematic review and meta-analysis were performed.We performed a comprehensive literature search from PubMed, EMBASE, and SinoMed through 27 March, 2016. Hazard ratios (HRs) with 95% confidence intervals (CI) were combined to evaluate the association between p-STAT3 expression and overall survival of colorectal cancer patients. Odds ratios (ORs) with 95% CI were combined to evaluate the association between p-STAT3 expression and clinicopathological parameters in patients with colorectal cancer.Seventeen studies including a total of 2,346 colorectal cancer patients were included in this meta-analysis. The combined HR was 1.43 (95% CI: 1.23-1.67, P < 0.001), which suggested a positive relationship between p-STAT3 overexpression and poorer overall survival of colorectal cancer patients. In addition, the results indicated that positive p-STAT3 expression was significantly associated with the presence of lymph node metastasis (OR: 2.43, 95% CI: 1.18-5.01, P = 0.02) but was not associated with TNM stage, tumor differentiation or gender.The meta-analysis results suggest that p-STAT3 overexpression is unfavorable for the prognosis of colorectal cancer patients, and p-STAT3 overexpression is associated with the presence of lymph node metastasis among colorectal cancer patients.

A readily and rapidly accessible triazine dendrimer was manipulated in four steps with 23% overall yield to give a construct displaying four maleimide groups and DOTA. The maleimide groups of the dendrimer are sensitive to hydrolysis under basic conditions. The addition of up to four molecules of water can be observed via mass spectrometry and HPLC. The evolution in the alkene region of the 1H-NMR—the transformation of the maleimide singlet to the appearance of two doublets—is consistent with imide hydrolysis and not the Michael addition. The hydrolysis events that proceeded over hours are sufficiently slower than the desired thiol addition reactions that occur in minutes. The addition of thiols to maleimides can be accomplished in a variety of solvents. The thiols examined derived from cysteine and include the protected amino acid, a protected dipeptide, and native oligopeptides containing either 9 or 18 amino acids. The addition reactions were monitored with HPLC and mass spectrometry in most cases. Complete substitution was observed for small molecule reactants. The model peptides containing nine or eighteen amino acids provided a mixture of products averaging between 3 and 4 substitutions/dendrimer. The functionalization of the chelate group with gadolinium was also accomplished easily.

Abstract Metal hydrides are crucial intermediates in numerous catalytic reactions. Intensive efforts have been dedicated to constructing molecular metal hydrides, where toxic precursors and delicate mediators are usually involved. Herein, we demonstrate a facile pressure-induced methodology to generate a cost-effective heterogeneous electrocatalytic metal hydride surface for sustainable hydrogen transfer. Taking carbon dioxide (CO2) electroreduction as a model system and zinc (Zn), a well-known carbon monoxide (CO)-selective catalyst, as a model catalyst, we showcase a homogeneous-type hydrogen atom transfer process induced by heterogeneous hydride surfaces, enabling direct hydrogenation pathways traditionally considered “prohibited”. Specifically, the maximal Faradaic efficiency for formate is enhanced by ~fivefold to 83% under ambient conditions. Experimental and theoretical analyses reveal that unlike the distal hydrogenation route for CO2 to CO over pristine Zn, the Zn hydride surface enables direct hydrogenation at the carbon site of CO2 to form formate. This work provides a promising material platform for sustainable synthesis.

An endophytic fungus CWJ01 with good antibacterial activity was isolated from the leaves of Acanthopanax senticosus. In order to improve the antibacterial activity of the fermentation broth of this strain and explore the substance basis of its antibacterial activity, the fermentation conditions of the endophytic fungus CWJ01 were optimized by orthogonal experiment according the antibacterial activity on the basis of single factor experiments. The secondary metabolites contained in the endophytic fungus CWJ01 were separated by column chromatography. The strains of the endophytic fungus CWJ01 were identified by morphology and ITS sequence analysis. The results showed that the optimum fermentation conditions of CWJ01 were as follows: PDB as the base medium, 2% glucose as the carbon source, 1% peptone as the nitrogen source. The initial pH of the medium was 7.0, the liquid content of the medium was 60%, the inoculated strain was 5%, the rotating speed was 140 r/min, the temperature was 28 ℃, and the culture time was 15 days. Under the optimal process conditions, the diameter of inhibition zone of CWJ01 fermentation broth against Staphylococcus aureus was 27.48±0.17 mm. Trans-cinnamic acid and benzoic acid were isolated from the fermentation broth of endogenous fungus CWJ01, and the endophytic fungus CWJ01 was identified as Penicillium polonicum. This study can provide reference for further exploration of antibacterial active substances of endophytes.

Abstract Heterogeneous thermocatalysis of formic acid dehydrogenation by metals in solution is of great importance for chemical storage and production of hydrogen. Insightful understanding of the complicated formic acid dehydrogenation kinetics at the metal-solution interface is challenging and yet essential for the design of efficient heterogeneous formic acid dehydrogenation systems. In this work, formic acid dehydrogenation kinetics is initially studied from a perspective of electrochemistry by decoupling this reaction on Pd catalyst into two short-circuit half reactions, formic acid oxidation reaction and hydrogen evolution reaction and manipulating the electrical double layer impact from the solution side. The pH-dependences of formic acid dehydrogenation kinetics and the associated cation effect are attributed to the induced change of electric double layer structure and potential by means of electrochemical measurements involving kinetic isotope effect, in situ infrared spectroscopy as well as grand canonical quantum mechanics calculations. This work showcases how kinetic puzzles on some important heterogeneous catalytic reactions can be tackled by electrochemical theories and methodologies.

Abstract Background Sleeping late has been a common phenomenon and brought harmful effects to our health. The purpose of this study was to investigate the association between sleep timing and major adverse cardiovascular events (MACEs) in patients with percutaneous coronary intervention (PCI). Methods Sleep onset time which was acquired by the way of sleep factors questionnaire in 426 inpatients was divided into before 22:00, 22:00 to 22:59, 23:00 to 23:59 and 24:00 and after. The median follow-up time was 35 months. The endpoints included angina pectoris (AP), new myocardial infarction (MI) or unplanned repeat revascularization, hospitalization for heart failure, cardiac death, nonfatal stroke, all-cause death and the composite endpoint of all events mentioned above. Cox proportional hazards regression was applied to analyze the relationship between sleep timing and endpoint events. Results A total of 64 composite endpoint events (CEEs) were reported, including 36 AP, 15 new MI or unplanned repeat revascularization, 6 hospitalization for heart failure, 2 nonfatal stroke and 5 all-cause death. Compared with sleeping time at 22:00–22:59, there was a higher incidence of AP in the bedtime ≥ 24:00 group (adjusted HR: 5.089; 95% CI: 1.278–20.260; P = 0.021). In addition, bedtime ≥ 24:00 was also associated with an increased risk of CEEs in univariate Cox regression (unadjusted HR: 2.893; 95% CI: 1.452–5.767; P = 0.003). After multivariable adjustments, bedtime ≥ 24:00 increased the risk of CEEs (adjusted HR: 3.156; 95% CI: 1.164–8.557; P = 0.024). Conclusion Late sleeping increased the risk of MACEs and indicated a poor prognosis. It is imperative to instruct patients with PCI to form early bedtime habits.

Currently, the hierarchical structure is one of the most effective means to enhance the strength and plasticity of metal materials, since the strain localization can be effectively delayed by the coordination of the unique microstructure. In this study, a hierarchical structure of Mg-15Gd-1Zn-0.4Zr (GZ151K) alloys containing grain, twin, and precipitation structural units was prepared by ultrasonic surface rolling process (USRP) and recrystallization annealing (RU). The results showed that the stress gradient generated by USRP formed a twin gradient structure, which will activate the twin-assisted precipitation (TAP) effect and twin-induced recrystallization (TIR) effect during RU. Then, the twin gradient structure transformed into a twin-precipitation gradient structure, and finally into a hierarchical structure with grain-twin-precipitation as the increasement of recrystallization degree. Besides, the dual gradient structure with twin and precipitation structural units had the highest strength and microhardness owing to the precipitation strengthening. However, the hierarchical structure with grain, twin, and precipitation structural units exhibited the most excellent combination of strength and plasticity under grain refinement and precipitation strengthening.

Abstract In conventional superconductors, Bogoliubov quasiparticles and Cooper instability provide a paradigm to describe the superconducting state and the superconducting transition, respectively. However, whether these concepts can be adapted to describe Fe-based superconductors requires rigorous examinations from experiments. Here, we report angle-resolved photoemission studies on single-layer FeSe films grown on SrTiO3 substrate. Due to the improved clarity, our results reveal both particle and hole branches of the energy band with clear quasiparticles. The dispersion and coherence factors are extracted, which unveil the particle-hole mixed Bogoliubov quasiparticles in the superconducting state of the FeSe/STO films. Effective pairing susceptibility is also deduced as a function of temperature, which indicates the persistence of Cooper instability in Fe-based superconductors.

An ultra-high strain rate (104 s−1) dynamic plastic deformation treatment at liquid nitrogen temperature (LNT-DPD) followed by annealing is carried out to obtain dual heterogeneity of grain size and dislocation density in an equiatomic CrCoNi medium entropy alloy (MEA). Such extreme loading conditions resulted in extensive phase transformation in this MEA. Subsequent annealing at 650 °C for 1 h further induced reverse phase transformation and partial recrystallization, forming a complex heterogeneous microstructure characterized by nested trimodal grain sizes and partitioned dislocation density. A superior yield strength of ∼800 MPa and a good ductility of ∼40% were simultaneously achieved in this heterogeneous alloy. In order to reveal the effects of grain size and dislocation density distributions on the mechanical property improvements, the underlying deformation mechanisms were systematically discussed. High density of geometrically necessary dislocations (GNDs) would be induced in complex heterogeneous structures during tensile deformation due to strain gradients or partitioning between different regions, which would lead to additional strengthening and work hardening. These results provide a novel approach to overcome the strength-ductility trade-off dilemma for FCC-structured MEAs.

The ability to control stem cell function is the key to stem cell-based therapy and living tissue regeneration. In natural conditions, histone deacetylases (HDAC) are regarded as the important defining epigenetic reprogramming for stem cell differentiation. To date, human adipose-derived stem cells (hADSCs) have been widely utilised for bone tissue engineering applications. The present study aimed to examine the effect of a novel HDAC2&3-selective inhibitor, MI192, on hADSCs epigenetic reprogramming for regulating its osteogenic potential in vitro. The results confirmed that MI192 treatment reduced the hADSCs viability in a time and dose-dependent manner. The optimal concentration and pre-treatment time of MI192 for hADSCs osteogenic induction was 30 μMand 2 days representatively. A quantitative biochemical assay confirmed that the pre-treatment with MI192 (30 μM) for 2 days significantly enhanced hADSCs alkaline phosphatase (ALP) specific activity (P<0.05) compared with that of the valproic acid (VPA) pre-treatment group. Real-time PCR analysis revealed that MI192 pre-treatment up-regulated hADSCs gene expressions of osteogenic markers (e.g., Runx2, Col1, and OCN) under the osteogenic induction. DNA flow cytometric analysis indicated that two days' pre-treatment with MI192 (30 μM) resulted in G2/M arrest in hADSCs and this G2/M arrest was reversible. Our results suggest that MI192 is capable of epigenetic reprogramming of hADSCs via HDAC inhibition for controlling the cell cycle, resulting in enhancing hADSCs osteogenic differentiation, which indicates the potential of using MI192 for promoting bone tissue regeneration. [ABSTRACT FROM AUTHOR]

Abstract The etiopathogenesis of late-onset Alzheimer’s disease (AD) is increasingly recognized as the result of the combination of the aging process, toxic proteins, brain dysmetabolism, and genetic risks. Although the role of mitochondrial dysfunction in the pathogenesis of AD has been well-appreciated, the interaction between mitochondrial function and genetic variability in promoting dementia is still poorly understood. In this study, by tissue-specific transcriptome-wide association study (TWAS) and further meta-analysis, we examined the genetic association between mitochondrial solute carrier family (SLC25) genes and AD in three independent cohorts and identified three AD-susceptibility genes, including SLC25A10, SLC25A17, and SLC25A22. Integrative analysis using neuroimaging data and hippocampal TWAS-predicted gene expression of the three susceptibility genes showed an inverse correlation of SLC25A22 with hippocampal atrophy rate in AD patients, which outweighed the impacts of sex, age, and apolipoprotein E4 (ApoE4). Furthermore, SLC25A22 downregulation demonstrated an association with AD onset, as compared with the other two transcriptome-wide significant genes. Pathway and network analysis related hippocampal SLC25A22 downregulation to defects in neuronal function and development, echoing the enrichment of SLC25A22 expression in human glutamatergic neurons. The most parsimonious interpretation of the results is that we have identified AD-susceptibility genes in the SLC25 family through the prediction of hippocampal gene expression. Moreover, our findings mechanistically yield insight into the mitochondrial cascade hypothesis of AD and pave the way for the future development of diagnostic tools for the early prevention of AD from a perspective of precision medicine by targeting the mitochondria-related genes.

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

Abstract Mitochondria are important for the activation of endothelial cells and the process of angiogenesis. NDUFS8 (NADH:ubiquinone oxidoreductase core subunit S8) is a protein that plays a critical role in the function of mitochondrial Complex I. We aimed to investigate the potential involvement of NDUFS8 in angiogenesis. In human umbilical vein endothelial cells (HUVECs) and other endothelial cell types, we employed viral shRNA to silence NDUFS8 or employed the CRISPR/Cas9 method to knockout (KO) it, resulting in impaired mitochondrial functions in the endothelial cells, causing reduction in mitochondrial oxygen consumption and Complex I activity, decreased ATP production, mitochondrial depolarization, increased oxidative stress and reactive oxygen species (ROS) production, and enhanced lipid oxidation. Significantly, NDUFS8 silencing or KO hindered cell proliferation, migration, and capillary tube formation in cultured endothelial cells. In addition, there was a moderate increase in apoptosis within NDUFS8-depleted endothelial cells. Conversely, ectopic overexpression of NDUFS8 demonstrated a pro-angiogenic impact, enhancing cell proliferation, migration, and capillary tube formation in HUVECs and other endothelial cells. NDUFS8 is pivotal for Akt-mTOR cascade activation in endothelial cells. Depleting NDUFS8 inhibited Akt-mTOR activation, reversible with exogenous ATP in HUVECs. Conversely, NDUFS8 overexpression boosted Akt-mTOR activation. Furthermore, the inhibitory effects of NDUFS8 knockdown on cell proliferation, migration, and capillary tube formation were rescued by Akt re-activation via a constitutively-active Akt1. In vivo experiments using an endothelial-specific NDUFS8 shRNA adeno-associated virus (AAV), administered via intravitreous injection, revealed that endothelial knockdown of NDUFS8 inhibited retinal angiogenesis. ATP reduction, oxidative stress, and enhanced lipid oxidation were detected in mouse retinal tissues with endothelial knockdown of NDUFS8. Lastly, we observed an increase in NDUFS8 expression in retinal proliferative membrane tissues obtained from human patients with proliferative diabetic retinopathy. Our findings underscore the essential role of the mitochondrial protein NDUFS8 in regulating endothelial cell activation and angiogenesis.

This work aimed to clarify the potential regulating effects of Qufeng Xuanfei formula (QFXF) on airway neurogenic inflammation and its underlying target signal pathway. Guinea pig model of airway hyperergy (AHR) was used. The relative susceptibility of major proteins to airway neurogenic inflammation was assessed using Western blot immunoassay followed by being separated by SDS-PAGE. Compared to the model group, QFXF of all concentrations effectively depressed the capsaicin enhanced cough in guinea pigs and the peak values of airway resistance significantly decreased. The results illustrated that QFXF alleviated cough symptom in guinea pigs and reduced airway neurogenic inflammation when compared to AHR model group. Airway inflammation and damage, as well as the levels of NGF, SP and c-Fos in QFXF decreased the most in the high-dose group. The mechanism of antitussive activity may be associated with reducing airway inflammation. QFXF displayed effect on chronic cough through reducing the levels of neuropeptides, attenuating airway inflammation and promoting recovery from disease to decrease the airway neuro sensitivity, suggesting that the potential mechanism may be related to Ras/ERK/c-Fos pathway. [ABSTRACT FROM AUTHOR]

Global climate change has been widely recognized as important factors that threaten biodiversity. Rhododendron species are not only famous woody ornamental plants worldwide but are also indispensable components in alpine and subalpine vegetation in southwest China. However, the geographical distribution ranges response of this broad taxonomic group to future climate change remains not be fully understood. Herein, we studied the impact of climate change on the distribution of Rhododendron species in China by predicting the changes in their suitable habitats, centroid, and species richness under three climate change scenarios (SSP1-2.6, SSP2-4.5 and SSP5-8.5) in the 2090s. The species richness changes of Rhododendrons along altitude were also evaluated. In addition, we calculated the phylogenetic signals of distribution response to climate change. We found that the distribution responses of Rhododendron to climate change have weak phylogenetic signals. In the 2090s, the suitable habitats of about 87% of Rhododendron species will be reduced, 77% of Rhododendron species are manifested as northward migration. The high species richness of Rhododendrons tends to migrate to transboundary areas with high altitudes in China. Some Rhododendron species with no concern previously should be taken seriously for their high risk of habitat loss under climate change. Thus, the urgent protection of Rhododendron species under climate change need to be paid more attention than previous acknowledged. We recommend carrying out the reintroduction of endangered species in future suitable habitat, strengthening the protection of transboundary areas with high species richness, and focusing on species with few concerns previously. [ABSTRACT FROM AUTHOR]

IntroductionBovine torovirus (BToV), Bovine enterovirus (BEV), Bovine norovirus (BNoV), Bovine coronavirus (BCoV), Bovine rotavirus (BRV), and Bovine viral diarrhea virus (BVDV) are significant pathogens causing diarrhea in calves, characterized by their high prevalence and challenging prevention and control measures.MethodsWe analyzed 295 calf diarrhea samples, amplifying the M gene from BToV-positive samples, the 5’UTR gene from BEV-positive samples, the RdRp gene from BNoV-positive samples, the VP7 gene from BRV-positive samples, the S gene from BCoV-positive samples, and the 5’UTR gene from BVDV-positive samples. Subsequent homology analysis and phylogenetic tree construction were performed.ResultsThe overall viral positive rate in Guangdong Province was 21.36%. Specific detection rates were as follows: Foshan City at 50.00% (18/36), Guangzhou City at 43.90% (36/82), Huizhou City at 21.21% (7/33), Yangjiang City at 2.08% (1/48), Meizhou City at 1.39% (1/72), and Heyuan City at 0.00% (0/24). The detection rates for BToV, BEV, BNoV, BCoV, BRV, and BVDV were 0.34% (1/295), 6.10% (18/295), 0.68% (2/295), 1.36% (4/295), 10.85% (32/295), and 2.03% (6/295), respectively. Notably, the highest overall virus detection rate was observed in the Guangzhou-Foshan region, with BRV and BEV showing the highest detection rates among the six viruses. This study marks the first report of BToV and BNoV in Guangdong Province. Phylogenetic analysis revealed that the BToV strain belonged to type II, sharing genetic similarities with epidemic strains from various provinces in China. The BEV strains were categorized into E and F types, with the F type being the predominant strain in Guangdong Province and exhibiting the closest genetic relationship to strains from Heilongjiang and Guangxi. The BNoV strains, along with Hebei strains, were identified as GIII.2 subgenotype. BCoV strains showed the highest genetic similarity to strains from Sichuan. All BRV strains were classified under the G6 subtype and had the closest genetic relationship with human rotavirus strains. BVDV strains were identified as subtype 1b, closely related to the Beijing strain. In conclusion, this study investigated the prevalence and evolutionary characteristics of diarrhea-associated viruses in calves in specific areas of Guangdong Province, providing a valuable reference for establishing effective prevention and control measures in cattle farms.

Abstract The Bambusoideae subfamily, originating in the late Cretaceous, has evolved to include over 1500 species globally. Notably, China hosts the richest diversity of Bambusoideae, with 728 species documented. After a long period of coevolution, plenty of animals could feed on these plants rich in cellulose and lignin. As an important group of pests and participants in the ecosystem, bamboo‐feeding true bugs (BFTBs, or bamboo‐feeding Heteropteran insects) have attracted the attention of researchers. However, the diversity and distribution of BFTBs still lack systematic and generalized research. In this study, we reviewed the BFTBs in China and simulated the diversity pattern and the driving forces of this pattern. A list of 36 genera with 69 species of BFTBs in China was obtained through paper review and field surveys. And their bamboo‐feeding habit had multiple independent origins. The spatial diversity pattern showed that the biodiversity hotspots of BFTBs are located in and around the tropics of southern China. Environmental driving force analysis showed that the minimum temperature of coldest month and annual precipitation were the dominant environmental factors shaping the spatial diversity of BFTBs. Our work quantified the diversity and distribution of BFTBs in China, providing fundamental data support for pest control and evolutionary research.

IntroductionCancer-associated cachexia (CC) is a progressive syndrome characterized by unintentional weight loss, muscle atrophy, fatigue, and poor outcomes that affects most patients with pancreatic ductal adenocarcinoma (PDAC). The ability to identify and classify CC stage along its continuum early in the disease process is challenging but critical for management.ObjectivesThe main objective of this study was to determine the prevalence of CC stage overall and by sex and race and ethnicity among treatment-naïve PDAC cases using clinical, nutritional, and functional criteria. Secondary objectives included identifying the prevalence and predictors of higher symptom burden, supportive care needs, and quality of life (QoL), and examining their influence on overall survival (OS).Materials and methodsA population-based multi-institutional prospective cohort study of patients with PDAC was conducted between 2018 and 2021 by the Florida Pancreas Collaborative. Leveraging patient-reported data and laboratory values, participants were classified at baseline into four stages [non-cachexia (NCa), pre-cachexia (PCa), cachexia (Ca), and refractory cachexia (RCa)]. Multivariate regression, Kaplan Meier analyses, and Cox regression were conducted to evaluate associations.ResultsCC stage was estimated for 309 PDAC cases (156 females, 153 males). The overall prevalence of NCa, PCa, Ca, and RCa was 12.9%, 24.6%, 54.1%, and 8.4%, respectively. CC prevalence across all CC stages was highest for males and racial and ethnic minorities. Criteria differentiated NCa cases from other groups, but did not distinguish PCa from Ca. The most frequently reported symptoms included weight loss, fatigue, pain, anxiety, and depression, with pain significantly worsening over time. The greatest supportive care needs included emotional and physical domains. Males, Black people, and those with RCa had the worst OS.ConclusionsUsing clinical, nutritional, and functional criteria, nearly one-quarter of the PDAC cases in our diverse, multi-institutional cohort had PCa and 62.5% had Ca or RCa at the time of diagnosis. The PCa estimate is higher than that reported in prior studies. We recommend these criteria be used to aid in CC classification, monitoring, and management of all incident PDAC cases. Findings also highlight the recommendation for continued emotional support, assistance in alleviating pain, and supportive care needs throughout the PDAC treatment journey.

The heterogeneity of pore system of deep shale reservoir determines the occurrence, enrichment and migration behavior of shale gas within shales. In this study, multi-fractal analysis was applied to analyze CO2 and N2 adsorption data for obtaining multi-fractal parameters including Hurst index and multi-fractal spectrum (D5--D5+) of the deep Wufeng-Longmaxi shales collected from the Sichuan Basin, China, in order to study the connectivity and heterogeneity of micropore pores and meso-macropores as well as their influencing factors. The results showed that pore system of the Wufeng-Longmaxi deep shale exhibits distinct multifractal nature. There exists significant differences in the pore volume (PV) of micropores (50 nm) across different shale lithofacies due to their differences in TOC content and mineral composition. The heterogeneity and connectivity of micropores and meso-macropores within deep shales in the Sichuan Basin are controlled by multiple factors including shale lithofacies, burial depth, and pressure coefficients. Notably, siliceous shale (SL) and calcareous/argillaecous siliceous shale (C/ASL), known as sweet spot for current shale gas exploitation, exhibits characteristics such as relative low micropore connectivity, high micropore heterogeneity, high micropore PV and low meso-macropore connectivity. These suggest that isolated pressure-sealing compartment is easier formed within the overpressured SL and C/ASL. Thus, pressure in these shales is less likely to release during the Yanshanian-Xishanian tectonic uplift process, favoring the preservation of organic matter (OM) pores and residual interparticle pores, which is conducive to the accumulation of deep shale gas dominated by free gas.

The gun-track launch system is a new special launch device that connects the track outside the muzzle. Because it is constrained by the track, the characteristics of development of the muzzle jet differ from those of the traditional muzzle jet. Specifically, it changes from freely developing to doing so in a constrained manner, where this results in an asymmetric direction of flow as well as spatio-temporal coupling-induced interference between various shock waves and the formation of vortices. In this background, the authors of this article formulate and consider the development and characteristics of evolution of the muzzle jet as it impacts a constrained moving body. We designed simulations to test the gun-track launch system, and established a numerical model based on the dynamic grid method to explore the development and characteristics of propagation of disturbances when the muzzle jet impacted a constrained moving body. We also considered models without a constrained track for the sake of comparison. The results showed that the muzzle jet assumed a circumferential asymmetric shape, and tended to develop in the area above the muzzle. Because the test platform was close to the ground, the muzzle jet was subjected to reflections from it that enhanced the development and evolution of various forms of shock waves and vortices in the muzzle jet to exacerbate its rate of distortion and asymmetric characteristics. This in turn led to significant differences in the changes in pressure at symmetric points that would otherwise have been identical. The results of a comparative analysis showed that the constrained track could hinder the influence of reflections from the ground on the muzzle jet to some extent, and could reduce the velocity of the shock waves inducing the motion of the muzzle as well as the Mach number of the moving body. The work here provides a theoretical basis and the requisite technical support for applications of the gun-track launch system. It also sheds light on the technical bottlenecks that need to be considered to recover high-value warheads.