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Abstract Background Obesity and overweight, as determined by the body mass index (BMI), are harmful to metabolic health. However, the BMI can not reflect body composition or fat distribution. The fat-free mass index (FFMI) and the fat mass index (FMI) can provide more information on body composition. The aim of the observational research was to determine whether the FMI and the FFMI are significantly associated with the risk of developing diabetes and prediabetes. Methods The investigators included data for 10,085 National Health and Nutrition Examination Survey (2011–2018) participants aged over 20 years who underwent dual-energy X-ray absorptiometry (DXA). The FFMI and the FMI were determined based on total fat mass and lean mass measured by DXA. Diabetes and prediabetes status were determined by medical history and laboratory examination. Logistic regression analyses were performed to explore the correlations between the FMI/FFMI and the risk of developing diabetes/prediabetes. Restricted cubic spline analysis was used to explore underlying nonlinear associations. Results In the present study, 1,135 patients were diagnosed with diabetes, 3,258 had prediabetes, and 5,692 were classified as control participants. The FFMI (odds ratio (OR) = 1.10, 95% confidence interval (CI) = 1.04–1.16) and the FMI (OR = 1.08, 95% CI = 1.04–1.12) were independently related to an increased risk of developing diabetes. Moreover, the FFMI (OR 1.08, 95% CI 1.02–1.16) and the FMI (OR 1.07, 95% CI 1.02–1.13) also independently correlated with a rising risk of developing prediabetes. The restricted cubic spline (RCS) outcomes suggested that the associations are approximately linear. Conclusions Both the FMI and the FFMI significantly correlated with the danger of developing diabetes and prediabetes, and the correlations are approximately linear.

Abstract Objective To explore the mechanism of action of MicroRNAs-34a (miR-34a) and Eurite growth guiding factor 1 (Netrin1) in cisplatin resistance in gastric cancer (GC), providing new clues for overcoming tumor resistance and optimizing anti-tumor therapy for GC. Methods The Cancer Genome Atlas (TCGA), Differentially Expressed MicroRNAs (miRNAs) in human cancers (dbDEMC), and Starbase online databases were used to analyze the correlation between miR-34a and Netrin-1 and prognosis in GC, and to predict and verify the targeted binding of miR-34a to Netrin-1. The experimental methods including Cell transfection, real-time polymerase chain reaction (RT-PCR), Cell-Counting-Kit-8 (CCK8) assay, flow cytometry, wound scratch assay, transwell assay, and western blotting were used to investigate the effects of miR-34a and Netrin1 on chemotherapy resistance and biological characteristics in cisplatin-resistant GC cells (HGC27/DDP), and to analyze the molecular mechanism of cisplatin resistance. Results miR-34a expression was downregulated in gastric cancer clinical samples and cisplatin-resistant cells, while Netrin1 was upregulated, and was related to overall survival (OS). Upregulation of miR-34a can significantly reduce the IC50 value of cisplatin(0.65 vs 1.6 ng/mL) and Multidrug Resistance 1 (MDR-1) protein level, inhibit the proliferation activity, reduce the expression levels of proliferating cell nuclear antigen (PCNA) and ki-67 protein, and induce the increase of apoptosis rate and the enhancement of cycle arrest. Upregulation of miR-34a can also significantly reduce the expression level of Matrix metalloproteinase 9 (MMP9) protein, promote the expression of E-cadherin protein, reduce the wound healing rate and invasion number to inhibit migration and invasion ability in drug-resistant gastric cancer cells. Moreover, overexpression of Netrin1 on the basis of upregulation of miR-34a can weaken the above changes caused by upregulation of miR-34a. In addition, upregulation of miR-34a can significantly inhibit the Mitogen-activated protein kinase kinase (MEK) / Extracellular regulated protein kinases (ERK) pathway, while overexpression of Netrin1 can activate the MEK/ERK pathway, and inhibition of MEK/ERK pathway can effectively counteract the protein expression of Netrin1, and reverse changes in the expression of cisplatin IC50 and MDR-1 proteins caused by co-upregulation of miR-34a/Netrin1 in HGC27/DDP, as well as changes in proliferation, apoptosis, migration and invasion. In addition, upregulation of miR-34a can significantly inhibit the MEK/ERK pathway, while overexpression of Netrin1 can activate the MEK/ERK pathway. If the MEK/ERK pathway was inhibited, it can effectively counteract the protein overexpression of Netrin1, and reverse the changes in the expression of cisplatin IC50 and MDR-1 proteins in HGC27/DDP induced by co-upregulation of miR-34a / Netrin1, as well as changes in proliferation, apoptosis, migration and invasion. Conclusion miR-34a targets and negatively regulates Netrin1 to mediate the proliferation, apoptosis, apoptosis, migration, and invasion of drug-resistant gastric cancer cells via the MEK/ERK pathway, and change the chemosensitivity in GC cells. miR-34a/Netrin1/MEK/ERK axis may serve as a novel therapeutic target for chemoresistance in GC, it is of great significance for overcoming drug resistance and developing new therapeutic strategies for GC.

Abstract This study aims at the controllability of acoustically manipulated non-contact aggregation of bi-particle. Based on the acoustic wave radiation model of the transducer and the acoustic wave interference theory, the mathematical model between the spatial levitation point and the phase of the phased array ultrasonic array unit is established. A double-sided phased array test system was developed and the phase calculation algorithm for independently manipulating bi-particle was optimized. The algorithm is capable of independently distributing the energy applied to each levitation point. Through simulation and experiment, the horizontally aggregation characteristics of two levitated particles are investigated, and a interesting relationship between particles aggregation and standing wave phase difference is revealed, which follows the law of “attraction in the same phase but repulsion in the opposite phase”. By adjusting the tilt angle of the standing wave acoustic trap, the critical distance when particles to accelerate and collision is sharply reduced from 1.5λ to 0.5λ, which provides a new perspective and potential application path for acoustic manipulation technology.

The development of miniaturized electronic devices is highly dependent on precision manufacturing techniques. To achieve device miniaturization, material removal and processing accuracy down to the submicrometer or even nanometer level are required. The precision machining of the mass block, a key component of the silicon micro-gyroscope, is taken as a reference. To achieve the precision positioning function of the micro-gyroscope, the mass at a certain position of the Si-based mass block must be precisely controlled. Therefore, the ultra-fine quantitative removal process of silicon materials is studied. A femtosecond laser processing system is constructed, and the evolution of micro–nanostructure and etching depth on the silicon surface is explored. An ultra-fine quantitative removal process is developed to achieve quantitative removal of different etching depths on the silicon surface. The experimental results show that the minimum removal thickness can be 0.502 µm. The processing index requirement for a silicon surface removal thickness of less than 0.001 mm has been fulfilled. It is critical to resolve the issue of high-quality manufacturing of miniaturized silicon-based devices.

This study aimed to evaluate the effects of mulberry leaf extract (MLE) on the digestive system, liver lipid metabolism, and hypoglycemic capacity of Siniperca chuatsi. The control group (D1) was fed basal diet without MLE, while the treatment groups received MLE supplementation at 2.5 g/kg (D2), 5.0 g/kg (D3), 7.5 g/kg (D4), and 10.0 g/kg (D5). A total of 225 Siniperca chuatsi of initial body weight (47.82 ± 0.19 g) were selected and fed for 8 weeks. The results indicated that weight gain rate (WGR), feed intake (FI), and feed efficiency (FE) initially increased and subsequently decreased with MLE supplementation, peaking in the 7.5 g/kg MLE group (D4) (P < 0.05). The highest activities of digestive enzymes in the stomach, intestine, and pyloric caecum also exhibited in this group (P < 0.05). The intestinal villi height, branching of villi, density of goblet cells significantly increased, and reduced cavity rate in the D4 group (P < 0.05). The diversity of intestinal flora, as assessed by the Chao1, Simpson, and Shannon indices, was significantly greater in this group (P < 0.05). Liver lipid metabolism indices, including CPT-1 and the CPT-1/ACC ratio, were highest in the D4 group, while the crude lipid content displayed inverse trend (P < 0.05). Additionally, the D4 group showed a reduced number of liver lipid droplets and improved antioxidant capacity, with liver cells exhibiting less swelling and vacuolation. Notably, the D4 group demonstrated a significantly better hypoglycemic response after glucose injection compared to the control group (D1). The study concludes that MLE, when incorporated at an optimal level of 6.71–6.75 g/kg, significantly enhances the structure and function of the gastrointestinal tract, pyloric caecum, and liver, stimulates liver lipid metabolism, improves hypoglycemic capacity, and promotes the growth of Siniperca chuatsi.

Gymnocypris eckloni, an economically important cold-water fish widely cultivated in southwest China, is at increased risk of prolonged exposure to heat stress owing to persistent high temperatures in summer, extreme climate changes, and expansion of factory farming. In this study, G. eckloni was subjected to both chronic and acute heat stress, with subsequent analysis focusing on changes in the pathological and physiological characteristics and transcriptomic and metabolic responses of the liver to high temperature. The results revealed heat stress-induced damage to liver tissues, lipid accumulation and mitochondrial abnormalities in hepatocytes, and an increased number of apoptotic cells, with the damage being more severe under acute heat stress conditions. Assessment of biochemical indices showed that the antioxidant enzyme catalase (CAT) was activated in response to oxidative stress and energy demands increased following heat stress. Transcriptomic analysis showed significant enrichment in the protein processing in the endoplasmic reticulum pathway, along with upregulation of key genes associated with protein degradation (hsp40, hsp70, hsp90, ero1l, and pdia4) and activation of the unfolded protein response (UPR), which effectively reduces or clears the accumulation of misfolded proteins to combat stress. Most identified differential metabolites were associated with amino acid and lipid metabolism under heat stress. Notably, integrated transcriptomic and metabolomic analysis suggested that tryptophan metabolism played an important role in the adaptation of G. eckloni to chronic heat stress. These findings improve the understanding of the mechanisms through which G. eckloni adapts to high temperatures, providing a valuable foundation and novel avenues for developing strategies to alleviate the effects of heat stress and improve the outcomes of aquaculture.

Gymnocypris eckloni (G. eckloni), a cold-water economic fish, is widely cultivated in southwestern China. The increase in extreme summer weather conditions owing to global warming can significantly affect their survival and health. The fish intestine and its microbiota are closely associated with fish feeding and growth, nutritional metabolism, and immune defense. However, the mechanisms underlying the changes in the G. eckloni intestine and its microbiota under acute heat stress remain unknown. In this study, we investigated the effects of acute heat stress on the G. eckloni intestine employing histology, plasma biochemical indices, transcriptomics, and 16S rDNA sequencing. Histological analysis showed that acute heat stress induced significant morphological damage to the intestine, with microvilli detachment and mitochondrial abnormalities in the ultrastructure. Biochemical indicators associated with stress (reactive oxygen species and catalase), inflammation (interleukin-1β and tumor necrosis factor-α), and intestinal permeability (diamine oxidase and lipopolysaccharide) were significantly elevated after acute heat stress, indicating an intestinal inflammatory response and disruption of barrier function. Many DEGs were mined by transcriptomic analysis, with tfrc, pfkp, egln1 enriched in the HlF-1 signaling pathway, hsp70, hsp90aa1 and hspa4 enriched in the Antigen processing and presentation pathway, pmm1, pfkfb3 and hk1 enriched in the Fructose and mannose metabolism patyway. The HIF-1 signaling pathway is a crucial regulatory pathway during acute heat stress in the G. eckloni intestine, while significant downregulation of genes associated with adaptive immunity (mica, hla-dpa1, hla-dpb1, and hla-dqb2) suggested impaired immune function. Additionally, the composition of the intestinal microbiota was dominated by Aeromonas, Citrobacter, and Acinetobacter in the control group; but there was a significant decrease in the abundance of Citrobacter and Acinetobacter, and a significantly increased in Shewanella and Hafnia-Obesumbacterium after acute heat stress. Correlation analyses revealed that changes in the abundance of Hafnia-Obesumbacterium, Buttiauxella, and Pseudomonas were closely associated with changes in gene expression associated with stress, inflammation, and immunity. These results comprehensively demonstrate the adaptive mechanisms of the G. eckloni intestine in response to acutely high temperatures and provide a theoretical basis for the future advancement of artificial culture of cold-water fish.

Schizothoracine fishes in saltwater lakes of the Tibetan Plateau are important models for studying the evolution and uplift of the Tibetan Plateau. Examining their adaptation to the high-salt environment is interesting. In this study, we first assembled the RNA-Seq data of each tissue of G. przewalskii, G. selincuoensis, and G. namensis from Qinghai Lake, Selincuo Lake, and Namtso Lake, respectively, obtained by the group previously. After obtaining reliable results, the adaptation of the gills, kidneys, and livers of the three species to the high-salinity environment was assessed by weighted gene co-expression network analysis (WGCNA). Using module eigengenes (ME), 21, 22, and 22 gene modules were identified for G. przewalskii, G. selincuoensis, and G. nemesis, respectively. Functional clustering analysis of genes in the significant association module identified several genes associated with osmolarity-regulated potential KEGG pathways in the gills of three species of Schizothoracine fish. Th17 cell differentiation pathway was up-regulated in the gills of all three species; histocompatibility class 2 II antigen and E alpha (h2-ea) were up-regulated genes in this pathway. Functional clustering analysis of genes in apparently related modules in the kidney unveiled several differential KEGG pathways. The pentose phosphate pathway was up-regulated in the three Schizothoracine fishes, and glucose-6-phosphate dehydrogenase (g6pd) was an up-regulated gene in this pathway. In the livers of the three Schizothorax species, the propanoate metabolism pathway was up-regulated, and succinate-CoA ligase GDP-forming subunit beta (suclg2) was an up-regulated gene in this pathway. The above analyses provide reference data for the adaptation of Schizothorax to high-salt environments and lay the foundation for future studies on the adaptive mechanism of Schizothorax in the plateau. These results partly fill the void in the knowledge gap in the survival adaptations of Schizothoracine fishes to highland saline lakes.

Global warming has heightened the severity and frequency of extreme high-temperature events, presenting challenges to fish survival and negatively affecting the production of fishery. Gymnocypris eckloni, native to the Tibetan Plateau, is widely cultured in southwest China. Its sensitivity to heat makes it a suitable model for studying the impact of high temperatures on fish. The heart is a vital organ for survival, while is relatively understudied concerning the impact of high temperatures on fish hearts. In this study, G. eckloni was subjected to a seven-day exposure to 27 °C followed by a transfer to 18 °C for a seven-day recovery period. Behavioral tests revealed a significant increase in locomotor speed, distance, and respiratory rate of G. eckloni at 27 °C. Serum indices exhibited significantly elevated stress indicators (cortisol) and kinases associated with heart damage (lactate dehydrogenase, lactate dehydrogenase isoenzyme 1, creatine kinase, creatine kinase isoenzyme, and aspartate transaminase) at 27 °C, and histological analyses have confirmed the occurrence of heart damage subjected to high temperatures. After 7 days of recovery, most of these indicators showed a significant decrease compared to the heat stress group, with no significant differences observed compared to the control group. Transcriptomic analyses have revealed the widespread involvement of ferroptosis, P53 signaling pathway, oxidative phosphorylation, myocardial contraction, and DNA repair pathway in the response of G. eckloni to high temperatures. Our study offers a systematic exploration of the effects of heat stress on G. eckloni, providing valuable insights for the cultivation of high-altitude fish.

Abstract The outbreak of the 2022 Russia-Ukraine conflict exacerbated the natural gas supply shortage in European countries. European countries restarted coal-fired power plants to maintain economic and social operations. The uneven distribution of coal resources in the world makes coal international trade inevitable. The intricate trade relations between trading countries have formed a coal trade network. When a country’s coal exports are limited due to geopolitical factors, it will cause coal supply risks. The risk will spread to more countries along the trade network, eventually leading to the collapse of the trade network. This paper builds a crisis propagation model of the coal supply under the Russia-Ukraine conflict using the cascading failure model. The results showed that the Czech Republic, Ireland, Portugal, and Bulgaria become abnormal as the proportion of coal exports β increases. When the Russian Federation reduced its coal exports by 80% and countries maintained only 10% coal exports against crisis, 23 European countries were the worst. Iceland, Ireland, Turkey and other countries were spread by the indirect risk and became abnormal countries. The Czech Republic and Bulgaria were spread by multiple risk and became abnormal countries.

OsNRAMP5 is a pivotal gene involved in the uptake and transport of cadmium and manganese in rice plants. While the knockout of OsNRAMP5 has significantly decreased cadmium accumulation in rice grains, its impact on the adaptability of indica hybrid rice and its paternal parent still needs to be more adequately explored. This study conducted a three-year field experiment with two of the OsNRAMP5 knockout lines (indica hybrid rice LYDG-1 and its paternal parent DG-1) and their wild-type at four distinct locations in the middle reaches of the Yangtze River. Their adaptability was evaluated by cadmium and manganese accumulation, yield traits, and grain quality. The findings reveal that OsNRAMP5 knockout lines, when grown in mildly and moderately Cd-contaminated paddies, exhibit significantly and stably lower cadmium and manganese accumulation compared with the wild-type. However, there were no significant differences in cadmium and manganese content between LYDG-1 and DG-1. Regarding yield traits, OsNRAMP5 knockout lines did not show a significant reduction compared with the wild-type, except for DG-1 in soil with lower manganese content. For grain quality, the quality of the appearance of OsNRAMP5 knockout lines significantly improved compared with the wild-type. However, the milling quality of DG-1 significantly reduced compared with the wild-type, while this negative impact for LYDG-1 was only observed in soils with lower manganese content. Overall, the indica hybrid rice with an OsNRAMP5 knockout exhibits better adaptability than its paternal parent in the middle reaches of the Yangtze River. These findings offer valuable insights into the potential application and promotion of OsNRAMP5 mutant rice varieties in the middle reaches of the Yangtze River.

Nasopharyngeal carcinoma (NPC) is closely linked to Epstein–Barr virus (EBV) infection. Curcumae Rhizoma, a traditional Chinese herb, has shown antitumor effects, primarily through its component curcumol (Cur), which has been shown to reduce NPC cell invasion and migration by targeting nucleolin (NCL) and Epstein–Barr Virus Nuclear Antigen 1 (EBNA1). We constructed an EBV-positive NPC cell model using C666-1 cells and performed transcriptomics studies after treatment with curcumol, which revealed a significant enrichment of ubiquitin-mediated proteolysis, the PI3K-AKT and mTOR signaling pathways, cell cycle and apoptosis involved in tumor invasion and migration. To investigate the importance of NCL and EBNA1 in curcumol-resistant EBV-positive NPC, we performed a multi-omics study using short hairpin NCL (shNCL) and shEBNA1 EBV-positive NPC cells, and the proteomics results showed enrichment in complement and coagulation cascades and ubiquitin-mediated proteolysis signaling pathways. Here, we focused on ubiquitin-conjugating enzyme E2C (UBE2C), which plays an important role in the ubiquitin-mediated proteolysis signaling pathway. In addition, metabolomics revealed that UBE2C is highly associated with 4-Aminobutanoic acid (GABA). In vitro studies further validated the function of the key targets, suggesting that UBE2C plays an important role in NCL and EBNA1-mediated curcumol resistance to nasopharyngeal carcinoma invasion and metastasis.

IntroductionThe type VI secretion system (T6SS) is a crucial virulence factor in the nosocomial pathogen Acinetobacter baumannii. However, its association with drug resistance is less well known. Notably, the roles that different T6SS components play in the process of antimicrobial resistance, as well as in virulence, have not been systematically revealed.MethodsThe importance of three representative T6SS core genes involved in the drug resistance and virulence of A. baumannii, namely, tssB, tssD (hcp), and tssM was elucidated.ResultsA higher ratio of the three core genes was detected in drug-resistant strains than in susceptible strains among our 114 A. baumannii clinical isolates. Upon deletion of tssB in AB795639, increased antimicrobial resistance to cefuroxime and ceftriaxone was observed, alongside reduced resistance to gentamicin. The ΔtssD mutant showed decreased resistance to ciprofloxacin, norfloxacin, ofloxacin, tetracycline, and doxycycline, but increased resistance to tobramycin and streptomycin. The tssM-lacking mutant showed an increased sensitivity to ofloxacin, polymyxin B, and furazolidone. In addition, a significant reduction in biofilm formation was observed only with the ΔtssM mutant. Moreover, the ΔtssM strain, followed by the ΔtssD mutant, showed decreased survival in human serum, with attenuated competition with Escherichia coli and impaired lethality in Galleria mellonella.DiscussionThe above results suggest that T6SS plays an important role, participating in the antibiotic resistance of A. baumannii, especially in terms of intrinsic resistance. Meanwhile, tssM and tssD contribute to bacterial virulence to a greater degree, with tssM being associated with greater importance.

Glyptosternum maculatum, predominantly found in the middle and upper reaches of the Yarlung Zangbo River (YR) and its tributaries, is a fish species accorded second-class national protection. In 2021, it was recognized as one of the top ten excellent aquatic germplasm resources in China. However, its living conditions are far from promising. Therefore, in this study, we used the MaxEnt model to simulate potentially suitable habitat for G. maculatum, and then reconstructed the ecologically suitable habitat for G. maculatum using the kernel density algorithm after taking into account the distribution characteristics of hydropower stations. We predicted changes in area of the ecologically suitable habitat for G. maculatum under future climate change scenarios. The results indicate that the primary ecologically suitable areas for G. maculatum are situated in Ngamring County, Saga County, and Mainling County, covering a total area of 553.15 km2. Flow accumulation, NDVI, and the seasonality of temperature change are the main environmental factors affecting the distribution of G. maculatum. In the future, considering the ongoing impacts of factors such as hydropower stations and climate conditions, the projected suitable habitat area for G. maculatum is expected to span between 433.90 and 516.23 km2, marking a forecasted decrease of approximately 6.68 to 21.56 %. To prevent further reduction of suitable habitat, protective measures should be taken as early as possible.

Abstract Background and aims The effect of body fat deposition on the kidney has received increasing attention. The Chinese visceral adiposity index (CVAI) is an important indicator of recent research. The purpose of this study was to explore the predictive value of CVAI and other organ obesity indicators in predicting CKD in Chinese residents. Methods A retrospective cross-sectional study of 5355 subjects was performed. First, the study utilized locally estimated scatterplot smoothing to describe the dose–response relationship between the estimated glomerular filtration rate (eGFR) and CVAI. The L1-penalized least absolute shrinkage and selection operator (LASSO) regression algorithm was used for covariation screening, and the correlation between CVAI and eGFR was quantified using multiple logistic regression. At the same time, the diagnostic efficiency of CVAI and other obesity indicators was evaluated by ROC curve analysis. Results CVAI and eGFR were negatively correlated. Using group one as the control, an odds ratio (OR) was calculated to quantify CVAI quartiles (ORs of Q2, Q3, and Q4 were 2.21, 2.99, and 4.42, respectively; P for trend

Abstract Natural killer (NK) cells are unique immune effectors able to kill cancer cells by direct recognition of surface ligands, without prior sensitization. Allogeneic NK transfer is a highly valuable treatment option for cancer and has recently emerged with hundreds of clinical trials paving the way to finally achieve market authorization. Advantages of NK cell therapies include the use of allogenic cell sources, off-the-shelf availability, and no risk of graft-versus-host disease (GvHD). Allogeneic NK cell therapies have reached the clinical stage as ex vivo expanded and differentiated non-engineered cells, as chimeric antigen receptor (CAR)-engineered or CD16-engineered products, or as combination therapies with antibodies, priming agents, and other drugs. This review summarizes the recent clinical status of allogeneic NK cell-based therapies for the treatment of hematological and solid tumors, discussing the main characteristics of the different cell sources used for NK product development, their use in cell manufacturing processes, the engineering methods and strategies adopted for genetically modified products, and the chosen approaches for combination therapies. A comparative analysis between NK-based non-engineered, engineered, and combination therapies is presented, examining the choices made by product developers regarding the NK cell source and the targeted tumor indications, for both solid and hematological cancers. Clinical trial outcomes are discussed and, when available, assessed in comparison with preclinical data. Regulatory challenges for product approval are reviewed, highlighting the lack of specificity of requirements and standardization between products. Additionally, the competitive landscape and business field is presented. This review offers a comprehensive overview of the effort driven by biotech and pharmaceutical companies and by academic centers to bring NK cell therapies to pivotal clinical trial stages and to market authorization.

Abstract Background This study aimed to evaluate the efficacy and safety of oral anticoagulants (OACs) in real-world elderly patients with comorbidities of stable coronary artery disease (SCAD) and atrial fibrillation (AF). Methods Elderly patients (aged ≥ 65 years old) diagnosed with SCAD and AF were consecutively recruited and grouped into patients with or without oral anticoagulant (OAC) treatment. Follow-up was performed for 5 years. Major adverse cardiac events (MACEs) were defined as a composite of all-cause death, nonfatal myocardial infarction (MI), nonfatal stroke, and systemic embolism. Major bleeding outcomes were defined as events that were type ≥ 3 based on the Bleeding Academic Research Consortium (BARC) criteria. The net clinical outcomes were defined as the combination of MACEs and bleeding of BARC type ≥ 3. Results A cohort of 832 eligible patients (78 ± 6.70 years) was included. Compared to the patients without OAC treatment (n = 531, 63.82%), the patients treated with OAC (n = 301, 36.18%) were much younger, had higher body mass index (BMI), and had lower prevalence of heart failure, chronic obstructive pulmonary disease (COPD), renal insufficiency, and previous myocardial infarction. During the follow-up of 5 years, compared to the patients without OAC treatment, patients with OAC had a significantly lower risk of MACEs (20.60% vs. 58.95%, adjusted HR: 0.21, 95% CI: 0.15–0.30, p

Abstract Background Despite strong antiplatelet therapy with ticagrelor, serious ischemic events still occur in patients with acute coronary syndrome (ACS). The predictability of platelet reactivity to the residual risk of ischemic events during ticagrelor treatment remains uncertain. Objectives We aimed to investigate the predictability of the thromboelastography (TEG)-measured adenosine disphosphate (ADP)-induced platelet inhibition rate (ADP%) to the ischemic events in ticagrelor-treated patients with ACS. Methods A cohort of ticagrelor-treated patients with ACS were consecutively recruited. ADP% was measured by TEG after 3 days of ticagrelor maintenance treatment. The primary ischemic event was defined as rehospitalization for unstable angina (UA) within 1 year, and the secondary ischemic event was a composite of the primary ischemic event plus all-cause death, nonfatal myocardial infarction (MI), stent thrombosis, stroke, and unplanned revascularization within 1 year. Results A total of 751 eligible patients with ACS were included in the analysis, with 336 patients randomly assigned to the derivation group and 415 to the validation group. The overall rates of primary and secondary ischemic events were 14.51% (n = 109) and 16.91% (n = 127), respectively. Compared to the patients without ischemic events, those with ischemic events had a significantly lower ADP% both in the derivation group (for primary ischemic events: 66.05% vs. 92.80%, p

Information regarding relationships between forage yield and soil enzymes of legume–grass mixtures under nitrogen (N) fertilization can guide the decision-making during sustainable forage production. The objective was to evaluate the responses of forage yield, nutritional quality, soil nutrients, and soil enzyme activities of different cropping systems under various N inputs. Alfalfa (Medicago sativa L.), white clover (Trifolium repens L.), orchardgrass (Dactylis glomerata L.), and tall fescue (Festuca arundinacea Schreb.) were grown in monocultures and mixtures (A1: alfalfa, orchardgrass, and tall fescue; A2: alfalfa, white clover, orchardgrass, and tall fescue) under three N inputs (N1: 150 kg ha−1; N2, 300 kg ha−1; and N3: 450 kg ha−1) in a split plot arrangement. The results highlight that A1 mixture under N2 input had a greater forage yield of 13.88 t ha−1 year−1 than the other N inputs, whereas A2 mixture under N3 input had a greater forage of 14.39 t ha−1 year−1 than N1 input, but it was not substantially greater than N2 input (13.80 t ha−1 year−1). The crude protein (CP) content of grass monocultures and mixtures significantly (P < 0.05) increased with an increase in the rate of N input, and A1 and A2 mixtures under N3 input had a greater CP content of 18.91% and 18.94% dry matter, respectively, than those of grass monocultures under various N inputs. The A1 mixture under N2 and N3 inputs had a substantially greater (P < 0.05) ammonium N content of 16.01 and 16.75 mg kg−1, respectively, whereas A2 mixture under N3 had a greater nitrate N content of 4.20 mg kg−1 than the other cropping systems under various N inputs. The A1 and A2 mixtures under N2 input had a substantial higher (P < 0.05) urease enzyme activity of 0.39 and 0.39 mg g−1 24 h−1 and hydroxylamine oxidoreductase enzyme activity of 0.45 and 0.46 mg g−1 5 h−1, respectively, than the other cropping systems under various N inputs. Taken together, growing legume–grass mixtures under N2 input is cost-effective, sustainable, and eco-friendly, which provide greater forage yield and improved nutritional quality by the better utilization of resources.

Glyptosternum maculatum (G. maculatum) is a species of endemic fish to the aquatic ecosystem of Tibetan Plateau and has been listed as a critically endangered species in the Red List of China’s Vertebrates. The change in water temperature due to global warming may induce plasticity in G. maculatum to adapt to temperature stress. In this study, we performed transcriptome analysis to characterize the genes and pathways involved in temperature stress response in the liver of G. maculatum. Compared with group A (habitat temperature = 12 °C), changes in expression profiles were more significant in C (habitat temperature = 24 °C) group than that in B (habitat temperature = 4 °C) group. These results suggest the possible lack of reponse to cold stress in G. maculatum. A total of 1247 annotated differentially expressed genes (DEGs) were identified between groups A and C. Based on enrichment analysis, 17 candidate genes with potential roles in heat stress were identified. Additionally, eight important heat-stress-reducing pathways were identified and classified into folding, sorting and degradation, endocrine system, signal transduction, translation, infectious diseases (bacterial), glycan biosynthesis and metabolism, and digestive system. This study also showed that heat stress-regulated DEGs are not only related to intracellular biochemical reactions, metabolism, immune response, and protein folding, but also to the response to heat stress in the liver of G. maculatum. In conclusion, our present results revealed the response of G. maculatum to heat stress at the transcriptional level, which is beneficial for further research and conservation of G. maculatum.

Objective: This study aimed to investigate the effect of a two-week machine massage on the physical properties of the erector spinae and serum biochemical indexes of adolescent athletes after training.Methods: Sixteen male adolescent wrestlers were recruited (age: 15 ± 1 year; height: 166 ± 7 cm; weight: 56 ± 7 kg) and randomly assigned to machine massage (MA, 8) and control (CO, 8) groups. Participants in the MA group received machine massage for 20 min after each wrestling training from Monday to Saturday (except on Thursday) for two weeks, while the participants in the CO group recovered naturally. Over the course of two weeks, all the participants underwent similar wrestling training program under the guidance of a professional coach. Before and after the intervention, serum urea and creatine kinase (CK) levels were measured in a fasting state. A Myoton Pro digital muscle evaluation system was used to measure the physical properties of the erector spinae, including the oscillation frequency, logarithmic decrement of a muscle’s natural oscillation, and dynamic stiffness.Results: After two weeks of machine massage treatment, the dynamic stiffness of the erector spinae in the MA group decreased by 12.90% and that in the CO group increased by 2.34%, indicating a significant difference between the two groups (p = 0.04, ƞ2 = 0.286). The decrease in the logarithmic decrement of a muscle’s natural oscillation value in the MA was significantly greater than that in the CO (p = 0.003, ƞ2 = 0.286). Moreover, the serum CK values decreased by 33.84% in the MA group and by 1.49% in the CO group, despite a trend of change between the groups (p = 0.062, ƞ2 = 0.084). No significant difference was found in the improvement in serum urea levels between the two groups after two weeks of treatment.Conclusion: Results of the present study indicated that a two-week machine massage had a positive effect on the improvement of the physical properties of the erector spinae of wrestlers during training.

Oat (Avena sativa L.) is one of the important forage crops in the world. However, oat grown in Southwest China has higher moisture content and their preservation face significant challenges. In addition, existing commercial lactic acid bacteria (LAB) have poor fermentation effects in hot and humid regions. Consequently, the current study investigated the response of oat fermentation quality and microbial community to self-selected LAB inoculation. The treatments were: CK, sterilized water; LP694, Lactobacillus plantarum 694; LR753, Lactobacillus rhamnosus 753; and LPLR, LP694 combined with LR753, followed by 1, 3, 7, 14, and 60 days (d) of fermentation. The results showed that LAB inoculation significantly raised the lactic acid content, and decreased the level of pH value, acetic acid, and ammonia-N in oat silage. The LR753 group had a significantly higher (p < 0.05) lactic acid content (60.95 g kg–1 DM), and lower pH value (3.95) and ammonia-N content (10.1 g kg–1 DM) followed by the LPLR group. The LR753 showed lower NDF (54.60% DM) and ADF (39.73% DM) contents than other groups. The Lactobacillus was a prevalent genus in LAB-treated groups, and its relative abundance reached maximum in LP694 (69%) on day 3, while in the LR753 group (72%) on 60 days. The Lactobacillus rhamnosus, Lactobacillus plantarum, and Lactobacillus fermentum became the dominant species in LAB-treated groups with fermentation time. The Lactobacillus genus was positively correlated with WSC (R = 0.6, p < 0.05), while negatively correlated with pH (R = −0.5, p < 0.05), and BA (R = −0.5, p < 0.01). Overall, the LR753 group had better fermentation quality and preservation of nutritional components providing theoretical support and guidance for future oat silage production in Southwest China.

Since risk preference affects the behavior of decision makers, the study of its characteristics and impact on decision-making contributes to good planning for emergency coordination. The consistency of a member’s risk preferences in the conventional risk field and emergencies of a supply chain was analyzed by applying the prospect theory and adapting the domain-specific risk-taking (DOSPERT) scale. The influence of time pressure on the risk preferences and decision-making behaviors of members was studied in the emergency field and its sub-emergencies of a supply chain. The conclusions were drawn based on the empirical study. First, the risk preference could be measured in terms of conventional risk and emergencies. Second, the members tended to be risk averse with no time pressure, and the degree of risk aversion was weakened with time pressure, which had the greatest effect in the natural disaster event. Third, even though the change in risk preference had a consistency regarding the four types of sub-events of supply chain emergencies, it was inconsistent regarding the conventional risks and emergencies. With the evolution trend of risk preference demonstrated and the relationship between preference and time pressure revealed, this study may provide a decision-making reference for the formulation of a supply chain emergency coordination scheme.

Background Primary aldosteronism (PA) is a common but under‐recognized cause of secondary hypertension. Data directly comparing screening rates across single and overlapping indications are lacking. Methods and Results We conducted a retrospective review of adults with hypertension seen in outpatient clinics at a tertiary referral academic center between January 1, 2017, and June 30, 2020. We included patients with hypertension plus at least one of the following: resistant hypertension; age

Glioma is a common primary malignant tumor that has a poor prognosis and often develops drug resistance. The coumarin derivative osthole has previously been reported to induce cancer cell apoptosis. Recently, we found that it could also trigger glioma cell necroptosis, a type of cell death that is usually accompanied with reactive oxygen species (ROS) production. However, the relationship between ROS production and necroptosis induced by osthole has not been fully elucidated. In this study, we found that osthole could induce necroptosis of glioma cell lines U87 and C6; such cell death was distinct from apoptosis induced by MG‐132. Expression of necroptosis inhibitor caspase‐8 was decreased, and levels of necroptosis proteins receptor‐interacting protein 1 (RIP1), RIP3 and mixed lineage kinase domain‐like protein were increased in U87 and C6 cells after treatment with osthole, whereas levels of apoptosis‐related proteins caspase‐3, caspase‐7, and caspase‐9 were not increased. Lactate dehydrogenase release and flow cytometry assays confirmed that cell death induced by osthole was primarily necrosis. In addition, necroptosis induced by osthole was accompanied by excessive production of ROS, as observed for other necroptosis‐inducing reagents. Pretreatment with the RIP1 inhibitor necrostatin‐1 attenuated both osthole‐induced necroptosis and the production of ROS in U87 cells. Furthermore, the ROS inhibitor N‐acetylcysteine decreased osthole‐induced necroptosis and growth inhibition. Overall, these findings suggest that osthole induces necroptosis of glioma cells via ROS production and thus may have potential for development into a therapeutic drug for glioma therapy.

Graphene has presented promising features for application in lithium ion batteries(LIBs) due to its superior electronic conductivity and high surface area. It has been successfully used for modifying cathode materials to meet the increasing demand for LIBs with longer cycle life. However, the improving effect of graphene on cycling stability is still unclear, which restricts its further application in LIBs. Herein, graphene coated hollow sphere-like structure LiNi0.5Mn1.5O4(LNMO) wasdesigned and the improvement mechanism of graphene coating on LNMO’s cycling stability was investigated. The results show that graphene coating not only contributes to suppress structural deformation from mechanistic reaction and extend solid-solution reaction, but also helps protect electrode from corrosion by the products from electrolyte decomposition and suppress the generation of surface defects, especially at high temperature. Owing to graphene coating, graphene coated LNMO can deliver a discharge capacity of 91 mAh g−1 with high capacity retention of 82.5% after 1000 cycles under 20C and 83.8 mAh g−1 with 94.5% capacity retention after 100 cycles under 2C at 55 °C. This work deeply explores the effect of graphene coating on cycling stability from crystal stability and surface stability, which will help a wider application of graphene in energy storage field.

BackgroundThe efficacy and safety of antithrombotic treatment with oral anticoagulants (OACs) in elderly patients with comorbidities of acute coronary syndrome (ACS) and atrial fibrillation (AF) are unclear.MethodsA cohort of hospitalized elderly patients (≥65 years of age) diagnosed with ACS and AF and treated with oral antithrombotic agents were consecutively recruited. Follow-up was performed for at least 1 year. Major adverse cardiac events (MACEs) were defined as a composite of all-cause death, nonfatal myocardial infarction (MI), nonfatal stroke, and systemic embolism. The safety outcomes of bleeding were defined according to the Bleeding Academic Research Consortium (BARC) criteria.ResultsA cohort of 548 eligible patients (76 ± 6.6 years) was analyzed. Compared to the patients with OAC treatment (n = 184, 33.6%), patients treated without OAC (n = 364, 66.4%) were older, had a lower prevalence of persistent AF and unstable angina (UA), and more often presented with paroxysmal AF, acute myocardial infarction (AMI), stent implantation and dual antiplatelet therapy (DAPT). Compared to the patients without OAC treatment (n = 364, 66.4%), patients treated with OAC (n = 184, 33.6%) had a lower risk of MACEs at both the 1-year (4.3 vs. 15.1%, adjusted HR: 0.34, 95% CI: 0.15–0.80, p = 0.014) and 5-year (17.5 vs. 48.4%, adjusted HR: 0.36, 95% CI: 0.19–0.67, p = 0.001) follow-up. No significant difference was observed for bleeding events of BARC ≥2 between the groups (8.0 vs. 9.0%, adjusted HR: 1.17, 95% CI: 0.58–2.34, p = 0.667). Compared with warfarin-treated patients, the non-vitamin K antagonist oral anticoagulant-treated patients had lower risks of all-cause mortality (2.1 vs. 9.5%, HR: 0.18, 95% CI: 0.03–0.98, p = 0.047) and bleeding events of BARC ≥ 3 (2.1 vs. 4.8%, HR: 0.14, 95% CI: 0.02–1.10, p = 0.062).ConclusionsAntithrombotic therapy with OACs in elderly patients with ACS and AF was associated with a lower risk of ischemic events without an increase in bleeding events. In real-world practice, the clinical awareness of anticoagulation treatments in elderly patients with ACS and AF needs to be strengthened.

BackgroundImmunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulonephritis. Although an important link between intestinal metabolites and immune activity is widely established, the metabolic profile of IgAN is still poorly understood, which severely limits the mechanistic studies and therapy of IgAN.MethodsThe diversity of intestinal flora and relative abundance of metabolites in IgAN patients and healthy subjects were measured by 16s ribosomal RNA gene sequencing combined with liquid chromatography tandem-mass spectrometry. The levels of serum Gd-IgA1, IL-6, IL-10, IL-22, and TNF-a were tested by ELISA. We employed the tryptophan-targeted UHPLC-MRM-MS approach to assess the content of tryptophan metabolites quantitatively.ResultsIntestinal fatty acid levels, mainly unsaturated fatty acids, were observed to be dramatically decreased in IgAN patients. Disorders in linoleic acid and arachidonic acid metabolism, metabolic imbalances of anti-/pro- inflammatory fatty acid metabolites, and intestinal AhR signaling deficiency might reflect the damage of the intestinal mucosal barrier in IgAN patients. In addition, we found that high levels of Gd-IgA1, IL-22, and TNF-α were associated with the activity of the tryptophan-kynurenine metabolic pathway, as well as lower levels of 3-indolepropionic acid. 3-indolepropionic acid, kynurenine, and indoleacrylic acid had synergistic effects on regulating immuno-inflammatory responses in IgAN patients.ConclusionsThe metabolic characteristic of fatty acids and tryptophan in the intestinal system is disturbed in IgAN patients, leading to active immune-inflammatory reactions.

Gelsemium elegans (G. elegans) Benth., recognized as a toxic plant, has been used as traditional Chinese medicine for the treatment of neuropathic pain and cancer for many years. In the present study, we aim to obtain the anti-tumor effects of alkaloids of G. elegans and their active components in hepatocellular carcinoma (HCC) and the potential mechanism was also further investigated. We demonstrated that sempervirine induced HCC cells apoptosis and the apoptosis was associated with cell cycle arrest during the G1 phase, up-regulation of p53 and down-regulation of cyclin D1, cyclin B1 and CDK2. Furthermore, sempervirine inhibited HCC tumor growth and enhances the anti-tumor effect of sorafenib in vivo. In addition, inactivation of Wnt/β-catenin pathway was found to be involved in sempervirine-induced HCC proliferation. The present study demonstrated that alkaloids of G. elegans were a valuable source of active compounds with anti-tumor activity. Our findings justified that the active compound sempervirine inhibited proliferation and induced apoptosis in HCC by regulating Wnt/β-catenin pathway.

ObjectivesThis project aimed to construct an individualized PET/CT prognostic biomarker to accurately quantify the progression risk of patients with stage IIIC-IV epidermal growth factor receptor (EGFR)-mutated Non-small cell lung cancer (NSCLC) after first-line first and second generation EGFR- tyrosine kinase inhibitor (TKI) drug therapy and identify the first and second generation EGFR-TKI treatment-sensitive population.MethodsA total of 250 patients with stage IIIC-IV EGFR-mutated NSCLC underwent first-line first and second generation EGFR-TKI drug therapy were included from two institutions (140 patients in training cohort; 60 patients in internal validation cohort, and 50 patients in external validation cohort). 1037 3D radiomics features were extracted to quantify the phenotypic characteristics of the tumor region in PET and CT images, respectively. A four-step feature selection method was performed to enable derivation of stable and effective signature in the training cohort. According to the median value of radiomics signature score (Rad-score), patients were divided into low- and high-risk groups. The progression-free survival (PFS) behaviors of the two subgroups were compared by Kaplan–Meier survival analysis.ResultsOur results shown that higher Rad-scores were significantly associated with worse PFS in the training (p < 0.0001), internal validation (p = 0.0153), and external validation (p = 0.0006) cohorts. Rad-score can effectively identify patients with a high risk of rapid progression. The Kaplan–Meier survival curves of the three cohorts present significant differences in PFS between the stratified slow and rapid progression subgroups.ConclusionThe PET/CT-derived Rad-score can realize the precise quantitative stratification of progression risk after first-line first and second generation EGFR-TKI drug therapy for NSCLC and identify EGFR-mutated NSCLC populations sensitive to targeted therapy, which might help to provide precise treatment options for NSCLC.

Abstract Background Family caregivers of elderly patients with spinal tumours experience considerable pain and burden during the care process. This study aims to investigate the factors associated with caregiver burden in family caregivers of elderly patients with spinal tumours. Methods A total of 220 elderly patients with spinal tumours (age ≥ 65 years) hospitalized at the spine centre of our hospital from January 2015 to December 2017 and their family caregivers were recruited for this cross-sectional study. All participants completed a sociodemographic questionnaire. Caregiver burden, social support and self-efficacy were assessed by the Chinese version of the Zarit Burden Interview (ZBI), the Social Support Rating Scale (SSRS) and the General Self-Efficacy Scale (GSE), respectively. The factors related to caregiver burden were analysed by multivariate analysis. P

In the mixed reality (MR) environment, the task of target motion perception is usually undertaken by vision. This approach suffers from poor discrimination and high cognitive load when the tasks are complex. This cannot meet the needs of the air traffic control field for rapid capture and precise positioning of the dynamic targets in the air. Based on this problem, we conducted a multimodal optimization study on target motion perception judgment by controlling the hand tactile sensor to achieve the use of tactile sensation to assist vision in MR environment. This allows it to adapt to the requirements of future development-led interactive tasks under the mixed reality holographic aviation tower. Motion perception tasks are usually divided into urgency sensing for multiple targets and precise position tracking for single targets according to the number of targets and task division. Therefore, in this paper, we designed experiments to investigate the correlation between tactile intensity-velocity correspondence and target urgency, and the correlation between the PRS (position, rhythm, sequence) tactile indication scheme and position tracking. We also evaluated it through comprehensive experiment. We obtained the following conclusions: (1) high, higher, medium, lower, and low tactile intensities would bias human visual cognitive induction to fast, faster, medium, slower, and slow motion targets. Additionally, this correspondence can significantly improve the efficiency of the participants’ judgment of target urgency; (2) under the PRS tactile indication scheme, position-based rhythm and sequence cues can improve the judgment effect of human tracking target dynamic position, and the effect of adding rhythm cues is better. However, when adding rhythm and sequence cues at the same time, it can cause clutter; (3) tactile assisted vision has a good improvement effect on the comprehensive perception of dynamic target movement. The above findings are useful for the study of target motion perception in MR environments and provide a theoretical basis for subsequent research on the cognitive mechanism and quantitative of tactile indication in MR environment.

In modern warfare, operators of radar equipment are confronted with a large amount of information in a short period of time that they must process to make decisions. Such conditions often lead to human error, resulting in the loss of the best operational opportunities and putting themselves at a disadvantage. To address this issue, in this paper, we presents three intuitive designs for radar display interface icons, namely image schema, stereotypes, and expert intuition. Based on event-related potential techniques and eye-movement techniques, a modified sample delay matching task experimental paradigm is used to investigate the advantages and mechanisms of three intuitionistic designs with varying time pressures and numbers of tasks. The experimental results showed: (1) When representing the attributes of a target, image schema are most suitable for expressing the motion attributes of the target, such as speed and height, whereas stereotypes are most suitable for expressing fixed attributes, such as target threat. (2) Tasks with high time pressure are more difficult, leading to higher error rates; the reaction time of a single task should be no less than 4000 ms. (3) When multiple attributes of the target need to be observed at the same time, the same type of expression should be used. (4) Rational use of color to represent the target attributes can effectively reduce the cognitive load of people searching for the target.

Forage deficiency is the bottleneck that restricts the development of plateau animal husbandry. Maize (Zea mays L.)–soybean (Glycine max L.) intercropping can improve the forage biomass yield and silage quality. This experiment was conducted in Ganzi Tibetan Autonomous Prefecture to explore the effects of four maize varieties (M1, Rongyu Silage No. 1; M2, Yayu 04889; M3, Demeiya No. 1; M4, Zhenghong 505) on biomass yield, nutritional composition, and silage quality in maize–soybean intercropping. The results showed that M1S had the highest total dry matter yield (18.03 t ha−1), M3S had the highest crude protein (CP) content (8.46% DM), and soybeans had the highest water-soluble carbohydrate (WSC) content (8.55% DM). After silage, the CP content (13.44% DM) of mixed silage in M3S was higher, and the contents of neutral detergent fiber (39.42% DM) and acid detergent fiber (25.42% DM) were lower than those in maize silage alone. The WSC content (4.45% DM) of mixed silage in M3S was higher and the pH value (4.46) and ammonia–nitrogen to total nitrogen (3.97%) were lower than those of soybean silage alone. The results of membership function analysis showed that M3S was the best in fresh feeding and silage utilization, followed by M1S. Therefore, M3S (Demeiya No 1. intercropped with soybeans) is recommended in high-altitude areas.

Nano lanthanum oxide particles (La2O3 NPs) are important nanoparticle materials which are widely used in photoelectric production, but their potential health hazards to the respiratory system are not clear. The purpose of this study was to explore the possible mechanism of lung injury induced by La2O3 NPs. In this study, 40 SPF male SD rats were randomly divided into low-, medium-, and high-dose groups and control groups, with 10 animals in each group. Rats were poisoned by tracheal injection. The low-, medium-, and high-dose groups were given La2O3 NPs suspension of 25, 50, and 100 mg/kg, respectively, and the control group was given an equal volume of high-temperature sterilized ultrapure water. The rats in each group were exposed once a week for 12 consecutive times. The gene transcription and protein expression levels of PINK1 and parkin in rat lung tissue were mainly detected. Compared with the control group, the gene transcription and protein expression levels of PINK1 and Parkin in the exposed group were significantly higher (p < 0.05). La2O3 NPs may activate PINK1/parkin-induced mitochondrial autophagy.

Objective: The technology, network pharmacology and molecular docking technology of the ultra performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) were used to explore the potential molecular mechanism of Platycodon grandiflorum (PG) in the treatment of lung cancer (LC).Methods: UPLC-Q-TOF-MS/MS technology was used to analyze the ingredients of PG and the potential LC targets were obtained from the Traditional Chinese Medicine Systems Pharmacology database, and the Analysis Platform (TCMSP), GeneCards and other databases. The interaction network of the drug-disease targets was constructed with the additional use of STRING 11.0. The pathway enrichment analysis was carried out using Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) in Metascape, and then the “Drug-Ingredients-Targets-Pathways-Disease” (D-I-T-P-D) network was constructed using Cytoscape v3.7.1. Finally, the Discovery Studio 2016 (DS) software was used to evaluate the molecular docking.Results: Forty-seven compounds in PG, including triterpenoid saponins, steroidal saponins and flavonoids, were identified and nine main bioactive components including platycodin D were screened. According to the method of data mining, 545 potential drug targets and 2,664 disease-related targets were collected. The results of topological analysis revealed 20 core targets including caspase 3 (CASP3) and prostaglandin-endoperoxide synthase 2 (PTGS2) suggesting that the potential signaling pathway potentially involved in the treatment of LC included MAPK signaling pathway and P13K-AKT signaling pathway. The results of molecular docking proved that the bound of the ingredients with potential key targets was excellent.Conclusion: The results in this study provided a novel insight in the exploration of the mechanism of action of PG against LC.

Koumine (KM), one of the primary constituents of Gelsemium elegans, has been used for the treatment of inflammatory diseases such as rheumatoid arthritis, but whether KM impacts the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome remains unknown. This study aimed to explore the inhibitory effect of KM on NLRP3 inflammasome activation and the underlying mechanisms both in vitro using macrophages stimulated with LPS plus ATP, nigericin or monosodium urate (MSU) crystals and in vivo using an MSU-induced peritonitis model. We found that KM dose-dependently inhibited IL-1β secretion in macrophages after NLRP3 inflammasome activators stimulation. Furthermore, KM treatment efficiently attenuated the infiltration of neutrophils and suppressed IL-1β production in mice with MSU-induced peritonitis. These results indicated that KM inhibited NLRP3 inflammasome activation, and consistent with this finding, KM effectively inhibited caspase-1 activation, mature IL-1β secretion, NLRP3 formation and pro-IL-1β expression in LPS-primed macrophages treated with ATP, nigericin or MSU. The mechanistic study showed that, KM exerted a potent inhibitory effect on the NLRP3 priming step, which decreased the phosphorylation of IκBα and p65, the nuclear localization of p65, and the secretion of TNF-α and IL-6. Moreover, the assembly of NLRP3 was also interrupted by KM. KM blocked apoptosis-associated speck-like protein containing a CARD (ASC) speck formation and its oligomerization and hampered the NLRP3-ASC interaction. This suppression was attributed to the ability of KM to inhibit the production of reactive oxygen species (ROS). In support of this finding, the inhibitory effect of KM on ROS production was completely counteracted by H2O2, an ROS promoter. Our results provide the first indication that KM exerts an inhibitory effect on NLRP3 inflammasome activation associated with blocking the ROS/NF-κB/NLRP3 signal axis. KM might have potential clinical application in the treatment of NLRP3 inflammasome-related diseases.

Summary: Whole-genome duplications (WGDs) of Schizothoracinae are believed to have played a significant role in speciation and environmental adaptation on the Qinghai-Tibet Plateau (QTP). Here, we present a genome for Schizothorax o'connori, a QTP endemic fish and showed the species as a young tetraploid with a recent WGD later than ∼1.23 mya. We exhibited that massive insertions between duplicated genomes caused by transposon bursts could induce mutagenesis in adjacent sequences and alter the expression of neighboring genes, representing an early re-diploidization process in a polyploid genome after WGD. Meanwhile, we found that many genes involved in DNA repair and folate transport/metabolism experienced natural selection and might contribute to the environmental adaptation of this species. Therefore, the S. o'connori genome could serve as a young tetraploid model for investigations of early re-diploidization in polyploid genomes and offers an invaluable genetic resource for environmental adaptation studies of the endemic fish of the QTP.

Abstract Background Photoperiod-sensitivity is a critical endogenous regulatory mechanism for plant growth and development under specific environmental conditions, while phosphate and sucrose signaling processes play key roles in cell growth and organ initiation. MicroRNA399 is phosphate-responsive, but, whether it has roles in other metabolic processes remains unknown. Results MicroRNA399 was determined to be sucrose-responsive through a microRNA array assay. High levels of sucrose inhibited the accumulation of microRNA399 family under phosphate starvation conditions in Arabidopsis thaliana. Similarly, exogenous sucrose supplementation also reduced microRNA399 expression in maize at developmental transition stages. RNA sequencing of a near-isogenic line(photoperiod-sensitive) line and its recurrent parent Huangzao4, a photoperiod-insensitive line, was conducted at various developmental stages. Members of microRNA399 family were down-regulated under long-day conditions in the photoperiod-sensitive near-isogenic line that accumulated more sucrose in vivo compared with the control line Huangzao4. Conclusion MicroRNA399s may play central roles in the integration of sucrose sensing and photoperiodic responses under long day conditions in maize.

Abstract Background Ovarian cancer is a prominent public health problem which affects people all around the world. Platinum-based chemotherapy is a common treatment for ovarian cancer, however, the effectiveness of chemotherapy varies from patient to patient. The excision repair cross complementation group 1 (ERCC1) protein may mediate chemotherapy resistance. A meta-analysis was conducted to explore whether platinum-based chemotherapy effectiveness could be attributed to the ERCC1 C19007T polymorphisms. Methods Seven major databases (EMBASE, Web of Science, Pubmed, Springer Link, Chinese National Knowledge Infrastructure (CNKI), EBSCO and Science Direct databases) were searched for eligible studies. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the results. Results In this meta-analysis, 1169 subjects (425 non-responders and 744 responders) from 8 studies were included. The overall OR (C vs. T alleles) using random model was 1.07 (95% CI 0.75-1.52, P = 0.7), which was not statistically significant. Moreover, there was no significant difference in the analysis by race. Conclusion There is no association between the ERCC1 C19007T polymorphism and platinum-based chemotherapy effectiveness in ovarian cancer. The polymorphism did not have a significant impact on platinum-based chemotherapy in non-responders and responders.

Objective The type of surgical treatment that should be adopted for thoracic tuberculosis (TB) remains controversial. This study was performed to compare the clinical efficacy of surgery via the single anterior and single posterior approaches for treatment of thoracic spinal TB. Methods Seventy-eight patients with thoracic TB undergoing surgical treatment were divided into two groups on the basis of the surgical methods employed: Group A (single anterior debridement + bone graft fusion and internal fixation) and Group B (single posterior debridement + bone graft fusion and internal fixation). Results of clinical and imaging examinations were analysed and compared between the two groups. Results The surgical duration and mean hospital stay were significantly longer and the perioperative bleeding volume was significantly higher in Group A than B. At the last follow-up, changes in the American Spinal Injury Association grade showed no obvious differences between the two groups. Before and after the surgery and at the last follow-up, no significant differences were detected in the Cobb angle change or correction rate between the two groups. Conclusion Surgery via the single anterior and single posterior approaches achieved good clinical efficacy in the treatment of thoracic spinal TB.

Water matrix certified reference material (MCRM) of volatile organic compounds (VOCs) is used to provide quality assurance and quality control (QA/QC) during the analysis of VOCs in water. In this research, a water MCRM of 28 VOCs was developed using a “reconstitution” approach by adding VOCs spiking, methanol solution into pure water immediately prior to analysis. The VOCs spiking solution was prepared gravimetrically by dividing 28 VOCs into seven groups, then based on ISO Guide 35, using gas chromatography-mass spectrometry (GC-MS) to investigate the homogeneity and long-term stability. The studies of homogeneity and long-term stability indicated that the batch of VOCs spiking solution was homogeneous and stable at room temperature for at least 15 months. Moreover, the water MCRM of 28 VOCs was certified by a network of nine competent laboratories, and the certified values and expanded uncertainties of 28 VOCs ranged from 6.2 to 17 μg/L and 0.5 to 5.3 μg/L, respectively.

In maize (Zea mays), leaf senescence acts as a nutrient recycling process involved in proteins, lipids, and nucleic acids degradation and transport to the developing sink. However, the molecular mechanisms of pre-maturation associated with pollination-prevention remain unclear in maize. To explore global gene expression changes during the onset and progression of senescence in maize, the inbred line 08LF, with severe early senescence caused by pollination prevention, was selected. Phenotypic observation showed that the onset of leaf senescence of 08LF plants occurred approximately 14 days after silking (DAS) by pollination prevention. Transcriptional profiling analysis of the leaf at six developmental stages during induced senescence revealed that a total of 5,432 differentially expressed genes (DEGs) were identified, including 2314 up-regulated genes and 1925 down-regulated genes. Functional annotation showed that the up-regulated genes were mainly enriched in multi-organism process and nitrogen compound transport, whereas down-regulated genes were involved in photosynthesis. Expression patterns and pathway enrichment analyses of early-senescence related genes indicated that these DEGs are involved in complex regulatory networks, especially in the jasmonic acid pathway. In addition, transcription factors from several families were detected, particularly the CO-like, NAC, ERF, GRAS, WRKY and ZF-HD families, suggesting that these transcription factors might play important roles in driving leaf senescence in maize as a result of pollination-prevention.

Schizothorax integrilabiatus is an endangered fish species found in the Buqun Lake of Qinghai-Tibet Plateau. In this study, we determined the complete mitochondrial genome sequence of the S. integrilabiatus. The circular mitochondrial genome was 16,621 bp in length, containing 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, two ribosomal RNA (rRNA) genes and a control region (D-loop). The overall base composition is A 30.1%, C 26.9%, G 17.4%, and T 25.6%, with a high A + T content (55.7%). Further, phylogenetic analysis suggested that S. integrilabiatus is closely related to species of S. plagiostomus, and then clustered into a clade with other Schizothoracinae species. This work provides additional molecular information for studying S. integrilabiatus conservation genetics and evolutionary relationships.

Congestion in a Wireless Sensor Network (WSN) can lead to buffer overflow, resource waste and delay or loss of critical information from the sensors. In this paper, we propose the Priority-based Coverage-aware Congestion Control (PCC) algorithm which is distributed, priority-distinct, and fair. PCC provides higher priority to packets with event information in which the sink is more interested. PCC employs a queue scheduler that can selectively drop any packet in the queue. PCC gives fair chance to all sensors to send packets to the sink, irrespective of their specific locations, and therefore enhances the coverage fidelity of theWSN. Based on a detailed simulation analysis, we show that PCC can efficiently relieve congestion and significantly improve the system performance based on multiple metrics such as event throughput and coverage fidelity. We generalize PCC to address data collection in a WSN in which the sensor nodes have multiple sensing devices and can generate multiple types of information. We propose a Pricing System that can under congestion effectively collect different types of data generated by the sensor nodes according to values that are placed on different information by the sink. Simulation analysis show that our Pricing System can achieve higher event throughput for packets with higher priority and achieve fairness among different categories. Moreover, given a fixed system capacity, our proposed Pricing System can collect more information of the type valued by the sink.

The large scale genome wide association studies (GWAS) have identified approximately 80 single nucleotide polymorphisms (SNPs) conferring susceptibility to type 2 diabetes (T2D). However, most of these loci have not been replicated in diverse populations and much genetic heterogeneity has been observed across ethnic groups. We tested 28 SNPs previously found to be associated with T2D by GWAS in a Mongolian sample of Northern China (497 diagnosed with T2D and 469 controls) for association with T2D and diabetes related quantitative traits. We replicated T2D association of 11 SNPs, namely, rs7578326 (IRS1), rs1531343 (HMGA2), rs8042680 (PRC1), rs7578597 (THADA), rs1333051 (CDKN2), rs6723108 (TMEM163), rs163182 and rs2237897 (KCNQ1), rs1387153 (MTNR1B), rs243021 (BCL11A), and rs10229583 (PAX4) in our sample. Further, we showed that risk allele of the strongest T2D associated SNP in our sample, rs757832 (IRS1), is associated with increased level of TG. We observed substantial difference of T2D risk allele frequency between the Mongolian sample and the 1000G Caucasian sample for a few SNPs, including rs6723108 (TMEM163) whose risk allele reaches near fixation in the Mongolian sample. Further study of genetic architecture of these variants in susceptibility of T2D is needed to understand the role of these variants in heterogeneous populations.

SMN (Survival motor neuron protein) was characterized as a dimethyl-arginine binding protein over ten years ago. TDRD3 (Tudor domain-containing protein 3) and SPF30 (Splicing factor 30 kDa) were found to bind to various methyl-arginine proteins including Sm proteins as well later on. Recently, TDRD3 was shown to be a transcriptional coactivator, and its transcriptional activity is dependent on its ability to bind arginine-methylated histone marks. In this study, we systematically characterized the binding specificity and affinity of the Tudor domains of these three proteins quantitatively. Our results show that TDRD3 preferentially recognizes asymmetrical dimethylated arginine mark, and SMN is a very promiscuous effector molecule, which recognizes different arginine containing sequence motifs and preferentially binds symmetrical dimethylated arginine. SPF30 is the weakest methyl-arginine binder, which only binds the GAR motif sequences in our library. In addition, we also reported high-resolution crystal structures of the Tudor domain of TDRD3 in complex with two small molecules, which occupy the aromatic cage of TDRD3.