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Abstract Background Previous studies have shown that an elevated triglyceride-glucose (TyG) index was associated with all-cause mortality in both general adult individuals and critically ill adult patients. However, the relationship between the TyG index and clinical prognosis in pediatric patients admitted to the intensive care unit (ICU) remains unknown. We aimed to investigate the association of the TyG index with in-hospital all-cause mortality in critically ill pediatric patients. Methods A total of 5706 patients in the Pediatric Intensive Care database were enrolled in this study. The primary outcome was 30-day in-hospital all-cause mortality, and secondary outcome was 30-day in-ICU all-cause mortality. The restricted cubic spline (RCS) curves and two-piecewise multivariate Cox hazard regression models were performed to explore the relationship between the TyG index and outcomes. Results The median age of the study population was 20.5 [interquartile range (IQR): 4.8, 63.0] months, and 3269 (57.3%) of the patients were male. The mean TyG index level was 8.6 ± 0.7. A total of 244 (4.3%) patients died within 30 days of hospitalization during a median follow-up of 11 [7, 18] days, and 236 (4.1%) patients died in ICU within 30 days of hospitalization during a median follow-up of 6 [3, 11] days. The RCS curves indicated a U-shape association between the TyG index and 30-day in-hospital and in-ICU all-cause mortality (both P values for non-linear

Abstract End-stage nasopharyngeal carcinoma (NPC) has unsatisfactory survival. The limited benefit of chemotherapy and the scarcity of targeted drugs are major challenges in NPC. New approaches to treat late-stage NPC are urgently required. In this study, we explored whether the dual PI3K/mTOR inhibitor, PQR309, exerted a favorable antineoplastic effect and sensitized the response to gemcitabine in NPC. We observed that PI3K expression was positive and elevated in 14 NPC cell lines compared with that in normal nasopharygeal cell lines. Patients with NPC with higher PI3K levels displayed poorer prognosis. We subsequently showed that PQR309 alone effectively decreased the viability, invasiveness, and migratory capability of NPC cells and neoplasm development in mice xenograft models, and dose-dependently induced apoptosis. More importantly, PQR309 remarkably strengthened the anti-NPC function of gemcitabine both in vivo and in vitro. Mechanistically, PQR309 sensitized NPC to gemcitabine by increasing caspase pathway-dependent apoptosis, blocking GSK-3β and STAT3/HSP60 signaling, and ablating epithelial-mesenchyme transition. Thus, targeting PI3K/mTOR using PQR309 might represent a treatment option to promote the response to gemcitabine in NPC, and provides a theoretical foundation for the study of targeted drugs combined with chemotherapy for NPC.

Abstract Sequential immunotherapy has shown certain advantages in malignancy. Here, we aim to evaluate the efficacy of sequential anti-CTLA-4 and anti-PD-1 treatment for recurrent or metastatic nasopharyngeal carcinoma patients (R/M NPC). We retrospectively analysis 2 phase I trial of ipilimumab and camrelizumab in Chinese R/M NPC patients. These patients were initially treated with ipilimumab, a CTLA4 blockade, followed by anti-PD-1 treatment. We observed a durable tumor remission in these patients (mPFS: 12.3 months; mDoR: 20.9 months). Multimodal investigations of biopsy samples disclosed remodeling of tumor-immune microenvironment triggered by ipilimumab. In responders, we found increased tumoral PD-L1/PD-L2 expression and T-cell infiltration after ipilimumab treatment, accompanied by reduced stroma and malignant cell components. In contrast, non-responders exhibited increased B-cell infiltration and increased peripheral CD19 + B cells, suggesting a defective transition from memory B cells to plasma cells. This study proposes that sequential therapy can potentially enhance treatment efficacy in chemotherapy-resistant NPC patients and provides insights into how preexisting anti-CTLA4 blockade can influence subsequent anti-PD-1 efficacy by remodeling the TME. Additionally, our results highlight the need for therapeutic strategies targeting naïve/memory B cells.

Abstract Background Combined small-cell lung carcinoma (cSCLC) represents a rare subtype of SCLC, the mechanisms governing the evolution of cancer genomes and their impact on the tumor immune microenvironment (TIME) within distinct components of cSCLC remain elusive. Methods Here, we conducted whole-exome and RNA sequencing on 32 samples from 16 cSCLC cases. Results We found striking similarities between two components of cSCLC-LCC/LCNEC (SCLC combined with large-cell carcinoma/neuroendocrine) in terms of tumor mutation burden (TMB), tumor neoantigen burden (TNB), clonality structure, chromosomal instability (CIN), and low levels of immune cell infiltration. In contrast, the two components of cSCLC-ADC/SCC (SCLC combined with adenocarcinoma/squamous-cell carcinoma) exhibited a high level of tumor heterogeneity. Our investigation revealed that cSCLC originated from a monoclonal source, with two potential transformation modes: from SCLC to SCC (mode 1) and from ADC to SCLC (mode 2). Therefore, cSCLC might represent an intermediate state, potentially evolving into another histological tumor morphology through interactions between tumor and TIME surrounding it. Intriguingly, RB1 inactivation emerged as a factor influencing TIME heterogeneity in cSCLC, possibly through neoantigen depletion. Conclusions Together, these findings delved into the clonal origin and TIME heterogeneity of different components in cSCLC, shedding new light on the evolutionary processes underlying this enigmatic subtype.

Background The sustained effectiveness of anti-programmed cell death protein-1/programmed death-ligand 1 treatment is limited to a subgroup of patients with advanced nasopharyngeal carcinoma (NPC), and the specific biomarker determining the response to immunotherapy in NPC remains uncertain.Methods We assessed the associations between pre-immunotherapy and post-immunotherapy serum lipoproteins and survival in a training cohort (N=160) and corroborated these findings in a validation cohort (N=100). Animal studies were performed to explore the underlying mechanisms. Additionally, the relationship between high-density lipoprotein-cholesterol (HDL-C) levels and M1/M2-like macrophages, as well as activated CD8+T cells in tumor tissues from patients with NPC who received immunotherapy, was investigated.Results The lipoproteins cholesterol, HDL-C, low-density lipoprotein-cholesterol, triglycerides, apolipoprotein A-1 (ApoA1), and apolipoprotein B, were significantly altered after immunotherapy. Patients with higher baseline HDL-C or ApoA1, or those with increased HDL-C or ApoA1 after immunotherapy had longer progression-free survival, a finding verified in the validation cohort (p

Abstract TP53 comutation is related to poor prognosis of non‐small cell lung cancer. However, there is limited study focusing on the structural influence of TP53 mutation on third‐generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) treatment. We retrospectively analyzed the clinical and molecular data of patients treated with third‐generation EGFR‐TKIs in two independent cohorts. A total of 117 patients from the Sun Yat‐sen University Cancer Center (SYSUCC) and 141 patients from the American Association for Cancer Research Project GENIE database were included. In the SYSUCC cohort, TP53 comutations were found in 59 patients (50.4%) and were associated with poor median progress‐free survival (mPFS) and median overall survival (mOS). The additional subtype analysis found that TP53 mutation in the alpha‐helix region had shorter mOS compared with those with TP53 mutations in other regions in the SYSUCC cohort (mOS, 12.2 vs. 21.7 months; p = 0.027). Similar findings were confirmed in the GENIE cohort. Specifically, the presence of TP53 mutation in the alpha‐helix region was an independent negative predictive factor for PFS [hazard ratio (HR) 2.05(1.01–4.18), p = 0.048] and OS [HR 3.62(1.60–8.17), p = 0.002] in the SYSUCC cohort. TP53 mutation in alpha‐helix region was related to inferior clinical outcomes in patients treated with third‐generation EGFR‐TKIs.

To minimize the global pandemic COVID-19 spread, understanding the possible transmission routes of SARS-CoV-2 and discovery of novel antiviral drugs are necessary. We describe here that the virus can infect ocular surface limbal epithelial, but not other regions. Limbal supports wild type and mutant SARS-CoV-2 entry and replication depending on ACE2, TMPRSS2 and possibly other receptors, resulting in slight CPE and arising IL-6 secretion, which symbolizes conjunctivitis in clinical symptoms. With this limbal model, we have screened two natural product libraries and discovered several unreported drugs. Our data reveal important commonalities between COVID-19 and ocular infection with SARS-CoV-2, and establish an ideal cell model for drug screening and mechanism research.

K418 alloy was prepared by selective laser melting (SLM) at different laser powers (160∼240 W) in this paper. The influence of laser power on the densification behavior, microstructure, microhardness, and tensile properties was studied systematically. The results showed that the densities of the material increased rapidly first and then decreased slowly with the increase of laser power. When the laser power increased from 160 W to 240 W, the surface defects of the specimen decreased, the microstructure changed from columnar dendrites to cellular, and the grains grew in the direction preferentially. When the laser power is 200 W, the grain size is the smallest, the content of small-angle grain boundaries is more, the Schmidt factor is less, and then the best mechanical properties are achieved, at which the microhardness reaches 362.89 ± 5.01 HV, the tensile strength reaches 1244.35 ± 70.1 MPa, the yield strength reaches 863.89 ± 23.1 MPa, and the elongation of the material reaches a maximum of 12.53 ± 0.71 %. In addition, the fracture mode of the material is a mixed tough-brittle fracture mechanism.

Polyploid plants often exhibit superior yield, stress resistance, and quality. In this study, homologous tetraploid wucai (Brassica campestris L.) was successfully obtained by spraying seedling growth points with colchicine. The morphological, cytological, and physiological characteristics of diploid and tetraploid wucai were analyzed, and transcriptomic sequencing was performed at three stages of development. Tetraploid seedings grew slowly but exhibited darker leaves, enlarged organs and cells, increased stomatal volume, decreased stomatal density, improved nutritional content, and enhanced photosynthesis. Differentially expressed genes (DEGs) identified in diploid and tetraploid plants at three stages of development were enriched in different pathways. Notably, DEGs identified in the tetraploid plants were specifically enriched in starch and sucrose metabolism, pentose and glucuronate interconversions, and ascorbate and aldarate metabolism. In addition, we found that the light green module was most relevant to ploidy, and DEGs in this module were significantly enriched in the glycolysis/gluconeogenesis and TCA cycle pathways. The differential expression of key glycolysis-associated genes at different developmental stages may be the driver of the observed differences between diploid and tetraploid wucai. This study lays a technical foundation for the development of polyploid wucai germplasm resources as well as the breeding of new varieties with improved quality, yield, and stress resistance. It also provides a good empirical reference for the genetic breeding of closely related Brassica species.

L-theanine (L-Thea), an amino acid that is found in tea, possesses significant nutraceutical properties. This study aimed to investigate the anti-cardiac injury caused by obese mechanism of L-Thea by transcriptome and metabolome. L-Thea enhanced serum biochemical indicators and reduced inflammatory cytokine levels in serum and cardiac tissues, and cardiac injury associated with high-fat diet (HFD)-induced obesity in rats. Transcriptome data revealed that the amelioration of cardiac injury was associated with aldosterone synthesis and secretion. The metabolome indicated that the cardiac disorder induced by an HFD is influenced by the contents of succinic acid and 4-hydroxyphenylacetic acid. The joint analysis of transcriptome and metabolome showed that L-Thea reversed cardiac injury mainly through amino acid metabolism, nucleotide metabolism, energy metabolism, and endocrine system pathways. Collectively, L-Thea has the potential to serve as a dietary supplement for the prevention or management of cardiac injury induced by obesity.

In order to explore the fermentation performance of lactic acid bacteria and yeast with different species relationships in the process of pickle fermentation, a pair of lactic acid bacteria and yeast with mutual promoting relationship from 8 strains of lactic acid bacteria and 5 strains of yeast from different food sources, were screened through the cross-culture of metabolites and co-culture methods, namely Lactobacillus plantarum J05 and Saccharomyces cerevisiae Y21. The co-culture relationship of this group of bacteria was analyzed by culture mode, inoculation sequence and inoculation ratio, then the pH, total acid, reducing sugar content and nitrite content were measured during the fermentation process. The results showed that the addition of the sterile metabolites of Saccharomyces cerevisiae Y21 in standing culture significantly promoted the growth of Lactobacillus plantarum J05 in the growing stage; the growth of both strains was promoted by inoculation of Saccharomyces cerevisiae Y21 followed by Lactobacillus plantarum J05 and the optimal inoculation ratio of two strains was 30:1 and 40:1. When the inoculation ratio of bacteria group was 30:1, at the stable stag of pickle fermentation, compared with natural fermentation group, single bacteria group and mutual inhibition group, the pH of mutual promotion group was 3.4~3.5, which was significantly lower than that of other groups (P

Abstract Aims Mean arterial pressure (MAP) is widely used for evaluating organ perfusion, but its impact on clinical outcomes in patients with heart failure (HF) remains poorly understood. The aim of this study is to investigate the relationship between MAP and all‐cause mortality and readmission in patients with HF. Methods and results We retrospectively analysed data from PhysioNet, involving 2005 patients with HF admitted to Zigong Fourth People's Hospital between 2016 and 2019. The primary outcomes were composite outcomes of all‐cause mortality and readmission at 3 and 6 months. The secondary outcomes were readmission at 3 and 6 months. Multivariate‐adjusted Cox regression models, restricted cubic spline curves (RCS), and propensity score matching (PSM) were used to explore the relationship between MAP and clinical outcomes. Among 2005 patients with HF [≥70 years, 1460 (72.8%); male, 843 (42.0%)], the incidence of primary outcome at 3 months was 33.4% (223/668), 24.4% (163/668), and 22.7% (152/669), and at 6 months, it was 47.5% (317/668), 38.5% (257/668), and 38.0% (254/669) across MAP tertiles [from Tertile 1 (T1) to Tertile 3 (T3)], respectively. The RCS showed an ‘L‐shaped’ relationship between MAP and primary or secondary endpoints. Multivariate‐adjusted Cox models showed that a higher MAP was significantly associated with a lower risk of composite endpoints at 3 months [adjusted hazard ratio (aHR) 0.75, 95% confidence interval (CI) 0.61–0.92, P = 0.006, Tertile 2 (T2); aHR 0.69, 95% CI 0.56–0.86, P = 0.001, T3] and 6 months (aHR 0.79, 95% CI 0.67–0.93, P = 0.005, T2; aHR 0.77, 95% CI 0.64–0.91, P = 0.003, T3) compared with T1. After 1:1 PSM, the effect of maintaining a relatively higher MAP was slightly attenuated. Threshold analyses indicated that per 10 mmHg increase in MAP, there was a 21% and 14% decrease in composite endpoints at 3 and 6 months, respectively (aHR 0.79, 95% CI 0.69–0.91, P = 0.001), and 6 months (aHR 0.86, 95% CI 0.77–0.97, P = 0.013) in patients with MAP ≤ 93 mmHg. The associations were consistent in readmission (secondary outcomes), various subgroups, and sensitivity analysis. Conclusions A higher MAP was associated with a lower risk of a composite of all‐cause mortality and readmission. Maintaining a relatively higher MAP could potentially improve the clinical prognosis for patients with HF.

Enterococcus faecium B13, selected from fermentation chili, has been proven to promote animal growth by previous studies, but it belongs to opportunistic pathogens, so a comprehensive evaluation of its probiotic properties and safety is necessary. In this study, the probiotic properties and safety of B13 were evaluated at the genetic and phenotype levels in vitro and then confirmed in vivo. The genome of B13 contains one chromosome and two plasmids. The average nucleotide identity indicated that B13 was most closely related to the fermentation-plant-derived strain. The strain does not carry the major virulence genes of the clinical E. faecium strains but contains aac(6′)-Ii, ant (6)-Ia, msrC genes. The strain had a higher tolerance to acid at pH 3.0, 4.0, and 0.3% bile salt and a 32.83% free radical DPPH clearance rate. It can adhere to Caco-2 cells and reduce the adhesion of E. coli to Caco-2 cells. The safety assessment revealed that the strain showed no hemolysis and did not exhibit gelatinase, ornithine decarboxylase, lysine decarboxylase, or tryptophanase activity. It was sensitive to twelve antibiotics but was resistant to erythromycin, rifampicin, tetracycline, doxycycline, and minocycline. Experiments in vivo have shown that B13 can be located in the ileum and colon and has no adverse effects on experiment animals. After 28 days of feeding, B13 did not remarkable change the α-diversity of the gut flora or increase the virulence genes. Our study demonstrated that E. faecium B13 may be used as a probiotic candidate.

Abstract Objective The aim of this work was to evaluate the predictive value of FAR combined with CACS for MACCEs. Background The fibrinogen-albumin-ratio (FAR), a novel biomarker of inflammation, is associated with the severity of coronary artery disease (CAD). Coronary calcification score (CACS) is associated with the severity of coronary stenosis and is closely related to the prognosis of CAD patients. What is the prognostic value of FAR in patients with chest pain, which has not been reported. This study aims to evaluate the relationship between CACS and FAR and their impact on prognosis in patients with suspected CAD. Methods We used information from 12,904 individuals who had coronary computed tomography angiography (CTA) for chest pain and tracked down any significant adverse cardiac and cerebrovascular events (MACCEs). The following formula was used to calculate FAR: fibrinogen (g/L)/albumin (g/L). Patients were separated into groups with greater levels of FAR (FAR-H) and lower levels of FAR (FAR-L) in accordance with the ideal cut-off value of FAR for MACCEs prediction. In addition, patients were divided into three groups based on their CACS scores (CACS ≤ 100, 100 400). Results 4946 patients [62(55–71) years, 64.4% male] were ultimately enrolled in the present study. During follow-up, a total of 234 cases (4.7%) of MACCEs were documented. Linear regression analysis results showed that CACS (R2 = 0.004, Standard β = 0.066, P

AbstractBackground Immune checkpoint inhibitors (ICIs) have achieved substantial advancements in clinical care. However, there is no strong evidence for identified biomarkers of ICIs in NPC.Methods In this retrospective study, 284 patients were enrolled into a training or validation cohort. Inflammatory indexes based on peripheral blood parameters were evaluated, including the systemic immune-inflammation index (SII), the neutrophil-lymphocyte ratio (NLR), the platelet-lymphocyte ratio (PLR), the lymphocyte-to-C-reactive protein ratio (LCR), and the lymphocyte-monocyte ratio (LMR). The optimum cut-off value for patient stratification was identified using X-tile. The Kaplan-Meier method and Cox’s proportional regression analyses were used to identify prognostic factors.Results Immunotherapy significantly changed the levels of SII, NLR, PLR, LCR and LMR in NPC patients. Patients with lower SII, NLR, and PLR, as well as those with higher LCR and LMR, before immunotherapy had superior PFS (all p

PurposeCentral obesity may contribute to breast cancer (BC); however, there is no dose–response relationship. This meta-analysis examined the effects of central obesity on BC and their potential dose–response relationship.MethodsIn the present study, PubMed, Medline, Embase, and Web of Science were searched on 1 August 2022 for published articles. We included the prospective cohort and case–control studies that reported the relationship between central obesity and BC. Summary effect size estimates were expressed as risk ratios (RRs) or odds ratios (ORs) with 95% confidence intervals (95% CI) and were evaluated using random-effect models. The inconsistency index (I2) was used to quantify the heterogeneity magnitude derived from the random-effects Mantel–Haenszel model.ResultsThis meta-analysis included 57 studies (26 case–control and 31 prospective cohort) as of August 2022. Case–control studies indicated that waist circumference (WC) (adjusted OR = 1.18; 95% CI: 1.00–1.38; P = 0.051) and waist-to-hip ratio (WHR) (adjusted OR = 1.28; 95% CI: 1.07–1.53; P = 0.008) were significantly positively related to BC. Subgroup analysis showed that central obesity measured by WC increased the premenopausal (adjusted OR = 1.15; 95% CI: 0.99–1.34; P = 0.063) and postmenopausal (adjusted OR = 1.18; 95% CI: 1.03–1.36; P = 0.018) BC risk and the same relationship appeared in WHR between premenopausal (adjusted OR = 1.38; 95% CI: 1.19–1.59; P < 0.001) and postmenopausal (adjusted OR = 1.41; 95% CI: 1.22–1.64; P < 0.001). The same relationship was observed in hormone receptor-positive (HR+) (adjusted ORWC = 1.26; 95% CI: 1.02–1.57; P = 0.035, adjusted ORWHR = 1.41; 95% CI: 1.00–1.98; P = 0.051) and hormone receptor-negative (HR–) (adjusted ORWC = 1.44; 95% CI: 1.13–1.83; P = 0.003, adjusted ORWHR = 1.42; 95% CI: 0.95–2.13; P = 0.087) BCs. Prospective cohort studies indicated that high WC (adjusted RR = 1.12; 95% CI: 1.08–1.16; P < 0.001) and WHR (adjusted RR = 1.05; 95% CI: 1.018–1.09; P = 0.017) may increase BC risk. Subgroup analysis demonstrated a significant correlation during premenopausal (adjusted RR = 1.08; 95% CI: 1.02–1.14; P = 0.007) and postmenopausal (adjusted RR = 1.14; 95% CI: 1.10–1.19; P < 0.001) between BC and central obesity measured by WC, and WHR was significantly positively related to BC both premenopausal (adjusted RRpre = 1.04; 95% CI: 0.98–1.11; P = 0.169) and postmenopausal (adjusted RRpost = 1.04; 95% CI: 1.02–1.07; P = 0.002). Regarding molecular subtype, central obesity was significantly associated with HR+ (adjusted ORWC = 1.13; 95% CI: 1.07–1.19; P < 0.001, adjusted ORWHR = 1.03; 95% CI: 0.98–1.07; P = 0.244) and HR– BCs (adjusted ORWC =1.11; 95% CI: 0.99–1.24; P = 0.086, adjusted ORWHR =1.01; 95% CI: 0.91–1.13; P = 0.808). Our dose–response analysis revealed a J-shaped trend in the relationship between central obesity and BC (measured by WC and WHR) in case–control studies and an inverted J-shaped trend between BMI (during premenopausal) and BC in the prospective cohort.ConclusionCentral obesity is a risk factor for premenopausal and postmenopausal BC, and WC and WHR may predict it. Regarding the BC subtype, central obesity is proven to be a risk of ER+ and ER- BCs. The dose–response analysis revealed that when BMI (during premenopausal) exceeded 23.40 kg/m2, the risk of BC began to decrease, and WC higher than 83.80 cm or WHR exceeded 0.78 could efficiently increase the BC risk.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022365788.

The development and progression of autism spectrum disorder (ASD) is characterized by multiple complex molecular events, highlighting the importance of the prefrontal brain regions in this process. Exosomes are nanovesicles that play a critical role in intercellular communication. Peripheral systems influence brain function under both physiological and pathological conditions. We investigated whether this influence was mediated by the direct sensing of peripheral blood exosomes by brain cells. Administration of serum exosomes from rats with valproic acid-induced ASD resulted in ASD-related phenotypes in mice, whereas exosomes from normal rats did not exhibit such effects. RNA sequencing and bioinformatics analysis suggested that negative regulation of medial prefrontal cortex (mPFC) insulin-like growth factor 1 (IGF-1) by exosome-derived miR-29b-3p may contribute to these ASD-associated effects. Further evidence showed that miR-29b-3p-enriched exosomes crossed the blood–brain barrier to reach the mPFC, subsequently inducing the suppression of IGF-1 expression in neurons. Optogenetic activation of excitatory neurons in the mPFC improved behavioral abnormalities in exosome-treated mice. The addition of exogenous IGF-1 or inhibition of miR-29b-3p expression in the mPFC also rescued the ASD-related phenotypes in mice. Importantly, administration of miR-29b-3p-enriched serum exosomes from human donors with ASD into the mouse medial prefrontal cortex was sufficient to induce hallmark ASD behaviors. Together, our findings indicate that blood–brain cross-talk is crucial for ASD pathophysiology and that the brain may sense peripheral system changes through exosomes, which could serve as the basis for future neurological therapies.

Abstract Background Previous studies showed that the triglyceride-glucose (TyG) index was a better predictor of adverse cardiovascular events than triglycerides or fasting blood glucose alone. However, few studies have focused on new-onset hypertension. We aimed to explore the association of TyG index with new-onset hypertension in Chinese adults. Methods A total of 4,600 participants who underwent at least 2 rounds of visits from 2009 to 2015 in the China Health and Nutrition Survey were enrolled in this study. Our outcome of interest was new-onset hypertension. Multivariate Cox hazard regression models and restricted cubic spline were performed to explore the relationship between TyG index and new-onset hypertension. Results The mean (standard deviation, SD) age of the study population was 48.1 (13.6) years, and 2058 (44.7%) of the participants were men. The mean (SD) TyG index level was 8.6 (0.7). A total of 1,211 (26.3%) participants developed new-onset hypertension during a median (interquartile range) follow-up duration of 6.0 (2.0–6.1) years. The incidences of new-onset hypertension were 18.1%, 25.3%, 28.5%, and 33.4% by quartiles of TyG index [from quartile 1 (Q1) to Q4], respectively. The Cox model showed that high levels of TyG index were significantly associated with increased risk of new-onset hypertension (adjusted hazard ratio [aHR]: 1.29, 95% confidence interval [CI] 1.07–1.55, Q2; aHR, 1.24, 95% CI 1.03–1.49, Q3; aHR, 1.50, 95% CI 1.22–1.84, Q4) compared with Q1. Consistently, as a continuous variable, for every 1.0 increase in TyG index, there was a 17% increase in the risk of new-onset hypertension (aHR, 1.17; 95% CI 1.04–1.31). The associations were consistent in various subgroups and sensitivity analysis. The dose–response curve indicated a positive, linear association between TyG index and the risk of new-onset hypertension. Conclusions High TyG index was significantly associated with an increased risk of new-onset hypertension among Chinese adults. Our findings suggest that maintaining a relatively low level of TyG index might be effective in the primary prevention of hypertension.

In comparison to orthogonal frequency division multiplexing (OFDM), the OFDM linear frequency modulation (OFDM-LFM) signal has similar time-bandwidth product, lower peak-to-average power ratio, and higher sensitivity to Doppler frequency shift, making it a promising candidate waveform for multiple-in multiple-out (MIMO) radar applications. However, the OFDM-LFM signal is unsatisfactory in practical applications due to the challenges in waveform design and its non-stationary property, which significantly degrades the performance of current high-resolution subspace techniques for direction of departure (DoD) and direction of arrival (DoA) angle estimation. In this paper, we first proposed a novel OFDM-LFM waveform design method based on the scale discrete Fresnel transform (SDFnT), which efficiently generates orthogonal LFM signals with unlimited number of subcarriers and can be convieniently implemented using the fast Fourier transform (FFT). Then, for angle estimation in OFDM-LFM MIMO radars, we presented a new scale discrete Fresnel transform multiple signal classification (SDFnT-MUSIC) method. By converting the steering vector into the chirp domain and making it non-time-vary, high resolution angle estimation for OFDM-LFM wideband signals can be achieved. Simulation results shows that the proposed waveform design method requires less computational time than conventional method based based on the fractional Fourier transform (FrFT), whereas the proposed DoA-DoD estimation method outperform the FrFT-MUSIC method in terms of computational complexity and target angle estimate performance.

The Nanling region is located at the intersection of the Yangtze Block and Cathaysia Block and is characterized by complex geological and tectonic processes, as well as distinct W-Sn-REE mineralization. Despite extensive research on the mineralization of W-Sn and REE deposits in the Nanling region, the factors impacting the distribution pattern of eastern tungsten and western tin deposits, as well as the mechanism of REE enrichment in the parent rocks, remain uncertain. Deep structural and tectonic variability plays a crucial role in the formation of mineral deposits in the upper crust. Information on deep structural and tectonic variability is contained in the Moho depth, Curie depth, effective elastic thickness, lithospheric density, and thermal structure derived from the processing and inversion of satellite gravity and magnetic data. In this paper, we comprehensively analyse satellite gravity and magnetic data from the Nanling region, integrating the processing and inversion results with the tectonic evolution of this region and relevant geological information. It is hypothesized that the Chenzhou–Linwu fault serves as a channel for mineral and thermal transfer in the Sn ore aggregation zone, facilitating the material transport from the deep mantle to the surface and ultimately leading to the formation of Sn-enriched granite. The collection area of tungsten ore is more weakly associated with the Chenzhou–Linwu fault, and through deep heat transfer, tungsten components are primarily concentrated in the Earth’s crust to produce W-enriched granite. The primary source of REE enrichment in the parent rocks associated with REE mineralization is predominantly derived from the felsic crust, and the rapid intrusion of deep magma resulting from the subduction and retraction of the Palaeo-Pacific Plate is a contributing factor to the contrasting enrichment of light and heavy rare-earth elements. Mineral crystalline differentiation is relatively high, leading to the formation of ore-forming parent rocks with high heavy rare-earth element contents.

Abstract Background Effective team leadership and good activation criteria can effectively initiate rapid response system (RRS) to reduce hospital mortality and improve quality of life. The first reaction time of nurses plays an important role in the rescue process. To construct a nurse-led (nurse-led RRS) and activation criteria and then to conduct a pragmatic evaluation of the nurse-led RRS. Methods We used literature review and the Delphi method to construct a nurse-led RRS and activation criteria based on the theory of “rapid response system planning.” Then, we conducted a quasi-experimental study to verify the nurse-led RRS. The control group patients were admitted from August to October 2020 and performed traditional rescue procedures. The intervention group patients were admitted from August to October 2021 and implemented nurse-led RRS. The primary outcome was success rate of rescue. Setting Emergency department, Gansu Province, China. Results The nurse-led RRS and activation criteria include 4 level 1 indicators, 14 level 2 indicators, and 88 level 3 indicators. There were 203 patients who met the inclusion criteria to verify the nurse-led RRS. The results showed that success rate of rescue in intervention group (86.55%) was significantly higher than that in control group (66.5%), the rate of cardiac arrest in intervention group (33.61%) was significantly lower than that in control group (72.62%), the effective rescue time of intervention group (46.98 ± 12.01 min) was shorter than that of control group (58.67 ± 13.73 min), and the difference was statistically significant (P 0.05). Conclusions The nurse-led RRS and activation criteria can improve the success rate of rescue, reduce the rate of cardiac arrest, shorten the effective time of rescue, effectively improve the rescue efficiency of patients.

Abstract With the deep integration of wireless communication technology and automobile industry, vehicular communication has become one of the key technologies supporting the development of Internet-of-vehicle. Due to the high-speed mobility of vehicles and the rapid change of the propagation environments, vehicle-to-vehicle (V2V) wireless communication channels are generally non-stationary. Meanwhile, the variability of V2V channel characteristics is obvious in different scattering environments. Focusing on these research points, this paper presents the analysis and comparison of V2V channel characteristics for different scattering scenarios based on a series of 5.9 GHz channel measurements. The measurement data are collected from the iron bridge, the soundproof wall, and the road lamp scenarios. The stationary time and frequency are investigated on the basis of method of local scattering functions. The classical channel characteristics, including power delay profile, Ricean K-factor, root means square (RMS) delay spread and RMS Doppler spread are extracted following the propagation principle. Furthermore, considering the source and birth-death process of multi-path components (MPCs) in different scattering propagation environments, cluster identification and statistical results are presented and compared. The different values of the channel parameters and the different performance of the channel under different scattering environments can help us understand the V2V channel deeply. The research results can be used for the design and optimization of vehicular communication systems in different scattering environments.

Abstract Background Several studies have reported that NFKB1 gene rs28362491 polymorphism was associated with susceptibility to coronary heart disease in populations of different genetic backgrounds. To date, there have been no studies on the association between NFKB1 gene rs28362491 polymorphism and the occurrence of major adverse cardiac and cerebrovascular event (MACCE). The present study was to explore the relationship between NFKB1 gene rs28362491 polymorphism and MACCEs to investigate whether identifying NFKB1 gene polymorphism is beneficial to evaluating MACCE risks and patients’ prognoses. Methods We recruited 257 high-risk of cardiovascular disease patients with chest pain or precordial discomfort. The SNPscan™ were used to analyze the NFKB1 gene rs28362491 polymorphism. All patients were followed up in the clinic or by telephone interview for MACCEs. Results During the followed-up time (mean: 30.1 months) 49 patients had MACCEs (19.1%). Patients with the different genotypes of NFKB1 rs28362491 had different incidence rate of MACCE. The incidence of MACCE in patients carried II, ID and DD genotype was 16.5%, 15.9%, 32.6%, respectively. Log-rank analysis showed that the survival rate in patients with NFKB1 rs28362491 DD genotype was much lower than that in II or ID genotype carriers (P = 0.034). After excluding the influence of traditional risk factors of MACCEs, Cox regression showed that the DD genotype carriers had 2.294-fold relative risk of MACCEs comparing with patients carried II or ID genotype. Conclusion The NFKB1 gene rs28362491 mutant was an independent predictor of worse long-term prognosis for MACCEs. Therefore, identifying NFKB1 gene rs28362491 mutant may be used as a good way for guiding the standardized management of patients with high-risk of cardiovascular diseases.

The Middle and Upper Permian Dalong and Gufeng Formations in South China have recently been considered as potential gas-producing shales. However, their pore structure characteristics remain poorly understood. To investigate the pore structure and fractal characteristics of the pores in these two formations, a suite of shale samples from the Dalong and Gufeng Formations in the western Hubei Province, South China were analyzed by multiple techniques, namely, TOC content, X-ray diffraction (XRD) mineralogy analysis, optical microscopy observations, major elemental analysis, field emission-scanning electron microscopy (FE-SEM), and low-pressure gas adsorption measurements (N2 and CO2). The identified major shale lithofacies include siliceous mudstone, carbonaceous mudstone, argillaceous-siliceous mixed mudstone, and calcareous-siliceous mixed mudstone. SEM images show that the dominant pore types include the pores between brittle minerals, slit-shaped pores between clay sheets, and secondary organic matter (OM) pores within solid bitumen. The pore size distribution is dominated by micropores and mesopores (1, D2) calculated from the nitrogen adsorption data have a range of from 2.489 to 2.772 (D1) and from 2.658 to 2.963 (D2), and are higher in the Gufeng Formation (average TOC = 8.3 wt.%) due to a higher TOC content comparing to the Dalong Formation (average TOC = 6.2 wt.%). The pore development and fractal characteristics are primarily controlled by organic matter (OM), carbonate minerals, and clay minerals for both the Dalong and Gufeng Formations. Shale samples with high TOC content, low carbonate content, and high clay content tend to develop more heterogeneous micropores and mesopores, which is ascribed to the generation of clay-related and OM-hosted pores, along with the destruction of primary pores by pore-filling carbonate cements.

Abstract Sour is an important taste in some foods, beers, and teas; organic acids, in particular, are thought to play a key role in the formation of the sour taste of beer. It has been generally thought that organic acids also contribute to some teas tasting sour. In this study, through sensory evaluation experiments with black tea (BT) and green tea (GT), the difference in the sour taste of BT and GT was quantitatively characterized. Then the organic acids in the two types of tea were identified and quantified via high‐performance liquid chromatography (HPLC) with taste activity value (TAV) analysis. The results showed that both teas had 12 identical common organic acids (including 11 taste‐active components), but the results of the TAV analysis were not consistent with those of the sensory evaluation. Therefore, there is no direct relationship between organic acids and the acidity in BT and GT. It is related to the interaction between organic acids and other substances, pH value, or other sour substances in tea infusions. The mechanism of the disappearance of sourness in tea infusions was also discussed. These results help us to understand the correlation between tastes in teas.

Abstract Background Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) participates in the occurrence and development of cardiovascular and cerebrovascular diseases such as stroke and coronary heart disease by regulating inflammatory reactions, programmed cell death, and other pathological processes. Previous studies revealed that the MALAT1 gene polymorphism was associated with cardiac and cerebrovascular diseases. However, the prognostic role of the MALAT1 polymorphism in major adverse cardiac and cerebrovascular events (MACCEs) remains unknown. Therefore, this study intends to explore the association between the MALAT1 rs3200401 polymorphism and MACCEs. Method We enrolled 617 myocardial infarction (MI) patients and 1125 control participants who attended the First Affiliated Hospital of Xinjiang Medical University from January 2010 to 2018. SNPscan™ typing assays were used to detect the MALAT1 rs3200401 genotype. During the follow-up, MACCEs were recorded. Kaplan–Meier curves and univariate and multivariate Cox survival analyses were used to explore the correlation between MALAT1 gene polymorphisms and the occurrence of MACCEs. Results Among the total participants and MI patients, the frequencies of the T allele (total Participants 19.5% vs. 15.3%, P = 0.047, MI patients 20.7% vs. 14.1%, P = 0.014) and CT + TT genotypes (total Participants 37.4% vs. 28.1%, P = 0.013, MI patients 39.5% vs. 25.8%, P = 0.003) were significantly higher in subjects with MACCEs than in subjects without MACCEs. However, in control participants, the frequencies of the T allele (16.6% vs. 16.0%, P = 0.860) and CT + TT genotypes (31.4% vs. 29.3%, P = 0.760) were not higher in subjects with MACCEs than in subjects without MACCEs. In addition, among the total participants and MI patients, the Kaplan–Meier curve analysis indicated that the subjects with rs3200401 CT + TT genotypes had a higher incidence of MACCEs than CC genotype carriers (P = 0.015, P = 0.001). Nevertheless, similar results were not observed in the control participants (P = 0.790). Multivariate Cox regression indicated that compared with patients with the CC genotype, patients with CT + TT genotypes had a 1.554-fold increase in MACCE risk (hazard ratio: 1.554, 95% confidence interval: 1.060–2.277, P = 0.024). Conclusions The MALAT1 rs3200401 CT + TT genotypes could be a risk factor for MACCEs in MI patients, suggesting that the MALAT1 gene may become a biomarker for poor prognosis in MI patients.

IntroductionPrecise identification of crop insects is a crucial aspect of intelligent plant protection. Recently, with the development of deep learning methods, the efficiency of insect recognition has been significantly improved. However, the recognition rate of existing models for small insect targets is still insufficient for insect early warning or precise variable pesticide application. Small insects occupy less pixel information on the image, making it more difficult for the model to extract feature information.MethodsTo improve the identification accuracy of small insect targets, in this paper, we proposed S-ResNet, a model improved from the ResNet, by varying its convolution kernel. The branch of the residual structure was added and the Feature Multiplexing Module (FMM) was illustrated. Therefore, the feature expression capacity of the model was improved using feature information of different scales. Meanwhile, the Adjacent Elimination Module (AEM) was furtherly employed to eliminate the useless information in the extracted features of the model.ResultsThe training and validation results showed that the improved residual structure improved the feature extraction ability of small insect targets compared to the original model. With compare of 18, 30, or 50 layers, the S-ResNet enhanced the identification accuracy of small insect targets by 7% than that on the ResNet model with same layer depth.

Weed suppression is an important factor affecting crop yields. Precise identification of weed species will contribute to automatic weeding by applying proper herbicides, hoeing position determination, and hoeing depth to specific plants as well as reducing crop injury. However, the lack of datasets of weeds in the field has limited the application of deep learning techniques in weed management. In this paper, it presented a dataset of weeds in fields, Weed25, which contained 14,035 images of 25 different weed species. Both monocot and dicot weed image resources were included in this dataset. Meanwhile, weed images at different growth stages were also recorded. Several common deep learning detection models—YOLOv3, YOLOv5, and Faster R-CNN—were applied for weed identification model training using this dataset. The results showed that the average accuracy of detection under the same training parameters were 91.8%, 92.4%, and 92.15% respectively. It presented that Weed25 could be a potential effective training resource for further development of in-field real-time weed identification models. The dataset is available at https://pan.baidu.com/s/1rnUoDm7IxxmX1n1LmtXNXw; the password is rn5h.

BackgroundPhysical activity (PA) is considered a favorable preventive intervention for postpartum depression (PPD), but evidence defining a corresponding dose-response relationship is lacking. This meta-analysis was conducted to assess the protective effects of PA on PPD and define a potential dose-response relationship between them.MethodsPubMed, Medline, Embase, and Web of Science were searched from 1968 to May 2022. Only randomized control trials (RCTs) and prospective studies were considered, and the PICOS tool was used to identify eligible articles based on the inclusion and exclusion criteria. Effect-size estimates were unified as odds ratio (OR) and 95% confidence interval (CI). We calculated the ORs and their 95% CI for studies that did not report them using the Practical Meta-Analysis Effect Size Calculator.ResultsA total of 23 studies were eligible, including 14 RCTs and 9 prospective cohort studies. The overall analysis showed a statistically significant positive association between PA and PPD prevention (adjusted OR = 0.73; 95% CI: 0.61–0.87; P < 0.001). Subgroup analyses indicated that studies conducted in Europe demonstrated a significant correlation between PA and reduced PPD risk (adjusted OR = 0.85, 95% CI: 0.76–0.95, P = 0.004). Concerning PA type, sports activity was associated with relieving PPD symptoms (adjusted OR = 0.89, 95% CI: 0.78 to 1.00, P < 0.001), while work (adjusted OR = 1.05, 95% CI: 0.37–2.97, P = 0.065) and household activities (adjusted OR = 1.16, 95% CI: 0.89–1.52, P = 0.986) contributed to a greater risk of PPD. Our dose-response analysis revealed a reverse J-shaped trend between ascending PA duration and PPD incidence.ConclusionThis meta-analysis identified PA as a potential intervention to reduce the risk of PPD. The dose-response analysis revealed that at least 90 min of PA per week could efficiently decrease the risk of PPD.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022335731.

Abstract Background Cancer patients often exhibit chemotherapy-associated changes in serum lipid profiles, however, their prognostic value before and after adjuvant chemotherapy on survival among non-small-cell lung cancer (NSCLC) patients is unknown. Methods NSCLC patients undergoing radical resection and subsequent adjuvant chemotherapy from 2013 to 2017 at Sun Yat-sen University Cancer Center were retrospectively reviewed. Fasted serum lipid levels were measured before and after chemotherapy. The optimal lipid cut-off values at baseline and fluctuation were determined using X-tile™. The fluctuations in serum lipid levels and disease-free survival (DFS) were assessed. Results Serum cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglyceride, apolipoprotein (Apo) A-I, and ApoB all significantly increased after adjuvant chemotherapy. X-tile determined 1.52 mmol/L of HDL-C and 0.74 g/L of ApoB as the optimal cut-off values before chemotherapy. Patients with HDL-C ≥ 1.52 mmol/L (median DFS: not reached vs. 26.30 months, P = 0.0005) and a decreased HDL-C level after adjuvant chemotherapy (median DFS: 80.43 vs. 26.12 months, P = 0.0204) had a longer DFS. An HDL-C level that increased by ≥ 0.32 mmol/L after chemotherapy indicated a worse DFS. A high baseline ApoB level were associated with a superior DFS. In the univariate analysis and the multivariate Cox analyses, a high baseline HDL-C level and a HDL-C reduction after adjuvant chemotherapy were independent indicators for superior DFS. High baseline HDL-C was related to N0-1 stage (χ2 = 6.413, P = 0.011), and HDL-C fluctuation was significantly correlated with specific chemotherapy regimens (χ2 = 5.002, P = 0.025). Conclusions Adjuvant chemotherapy increased various lipid levels in resected NSCLC patients. A higher HDL-C level before chemotherapy and a reduced HDL-C level after adjuvant chemotherapy were independent predictors of longer DFS in patients with curable NSCLC.

Abstract Advanced nasopharyngeal carcinoma (NPC) has a poor prognosis, with an unfavorable response to palliative chemotherapy. Unfortunately, there are few effective therapeutic regimens. Therefore, we require novel treatment strategies with enhanced efficacy. The present study aimed to investigate the antitumor efficacy of APG-1252-M1, a dual inhibitor of BCL-2/BCL-XL, as a single agent and combined with gemcitabine. We applied various apoptotic assays and used subcutaneous transplanted NPC model to assess the in vitro and in vivo antitumor activity. Moreover, phospho-tyrosine kinase array was used to investigate the combined therapy’s potential synergistic mechanism. In addition, further validation was performed using immunohistochemistry and western blotting. In vitro, we observed that APG-1252-M1 had moderate antitumor activity toward NPC cells; however, it markedly improved gemcitabine’s ability to promote NPC cell apoptosis and suppress invasion, migration, and proliferation. Specifically, APG-1252 plus gemcitabine exhibited even remarkable antitumor activity in vivo. Mechanistically, the drug combination synergistically suppressed NPC by activating caspase-dependent pathways, blocking the phospho (p)-JAK-2/STAT3/MCL-1 signaling pathway, and inhibiting epithelial-mesenchymal transition. In conclusion, the results indicated that the combination of APG-1252 and gemcitabine has synergistic anticancer activities against NPC, providing a promising treatment modality for patients with NPC.

Abstract Background The bispecific antibody (bsAbs) research around the world has undergone great changes. We analyzed the global trend of bsAbs research and compared the differences in clinical research of bsAbs between China and worldwide. Methods BsAbs research clinical trials information was retrieved through the online open-resource clinical trial registration platform. Research information including organizations, identity numbers, locations, phases, participating centers, conditions, status, enrollment, targets, spectrums of mechanism of action (MOA), and start date was collected. Clinical trials were divided into two categories based on the attributes of pharmaceutical companies (international or China-initiated or involved). Results From 1997 to 2020, 272 clinical trials regarding bsAbs research were retrieved. Twenty-nine percent of the studies were contributed by companies from Chinese institutions, which followed the USA and ranked second. The clinical trials of bsAbs are mainly concentrated on phase I (n = 161), phase I/II (n = 54), and phase II (n = 51), and the number of phase III trials is still rare (n = 4). Tumor species distribution analysis shows that there are significantly higher focuses on gastric cancer (n = 18), esophageal/gastroesophageal junction cancer (n = 16), bladder cancer (n = 10), biliary malignant tumor (n = 8), nasopharyngeal cancer (n = 6), and thymic cancer (n = 2) in China. BsAbs target and spectrums of MOA analysis showed that international companies mainly focus on bsAbs with CD3-based (n = 63) target with MOA of T-cell redirection, while researches in China pay more attention to PD-1 (n = 9)/PD-L1 (n = 7) axises with MOA of double immune checkpoint blocking. Conclusion Global bsAbs research increased rapidly during the 1997 to 2020 period. The developed countries in America and Europe are leading the trend of bsAbs research. Anticancer bsAbs clinical research in China is booming and chasing after the world trend.

Abstract Background Immunotherapy has shown promising efficacy in patients with nasopharyngeal carcinoma (NPC). Lymphocyte activating 3 gene (LAG-3) represents a significant immune target, however, its relationship with NPC remains unclear. This study aimed to evaluate LAG-3 expression in NPC and its association with CD3+ tumor-infiltrating lymphocytes (TILs), Granzyme B (GZMB), programmed death ligand 1 (PD-L1), and programmed death 1 (PD-1) expression. Methods A total of 182 patients with NPC from Sun Yat-sen University Cancer Center, China, were included in this retrospective study. LAG-3 expression in 15 NPC cell lines and LAG-3, CD3+ TILs, GZMB, PD-L1 and PD-1 in clinical samples were estimated using immunohistochemistry. The Chi-square test was used to estimate the association between LAG-3, other biomarkers, and clinical characteristics. Survival analysis was performed using the Kaplan–Meier method and the Cox regression model. Results LAG-3 was negatively expressed in all of the 15 NPC cell lines, whereas, 147 patients with NPC (80.8%) exhibited high LAG-3 expression on TILs from tumor tissues. Male patients and those who were EBV-positive presented higher LAG-3 expression. Correlation analyses showed that LAG-3 expression was related to PD-1 expression on TILs, as well as, PD-L1 expression on tumor cells (TCs) and TILs. Both the univariate and multivariate Cox models indicated that pathological type III (P = 0.036), higher LAG-3 on TILs (P

AimsThe efficacy and safety of sacubitril/valsartan for patients with heart failure with preserved ejection fraction (HFpEF) are controversial. Hence, the primary objective of the study was to evaluate the efficacy and safety of sacubitril/valsartan treatment for patients with HFpEF.Methods and resultsWe used the PubMed, Embase, and Web of Science databases to search for randomized controlled trials of sacubitril–valsartan in patients with HFpEF. Three studies, involving a total of 7,663 patients, were eligible for inclusion. Sacubitril–valsartan reduced the risk of hospitalization for heart failure (HF) [odds ratio (OR): 0.78; 95% CI: 0.70–0.88; p < 0.0001] and the incidence of worsening renal function [risk ratio (RR): 0.79, p = 0.002] among patients with HFpEF in the three trials, but there was no significant reduction in all-cause mortality (0.99, 95% CI: 0.84–1.15; p = 0.86) or cardiovascular mortality (0.95, 95% CI: 0.78–1.15; p = 0.16). Moreover, sacubitril/valsartan was associated with an increased risk of symptomatic hypotension (RR: 1.44; p < 0.00001) and angioedema (RR: 2.66; p < 0.04); there was no difference for decreasing the incidence of hyperkalemia (RR: 0.89; p = 0.11).ConclusionCompared with valsartan or individualized medical therapy (IMT), sacubitril/valsartan significantly decreased the risk of hospitalization for HF and reduced the incidence of renal dysfunction.

BackgroundPlatelet-related parameters and HDL-C have been regarded as reliable and alternative markers of coronary heart disease (CHD) and the independent predictors of cardiovascular outcomes. PDW is a simple platelet index, which increases during platelet activation. Whether the PDW/HDL-C ratio predicts major adverse cardiovascular and cerebrovascular events (MACCEs) in patients who complained of chest pain and confirmed coronary artery calcification remains to be investigated. This study aimed to investigate the prognostic value of the PDW/HDL-C ratio in patients with chest pain symptoms and coronary artery calcification.MethodsA total of 5,647 patients with chest pain who underwent coronary computer tomography angiography (CTA) were enrolled in this study. Patients were divided into two groups according to their PDW/HDL-C ratio or whether the MACCE occurs. The primary outcomes were new-onset MACCEs, defined as the composite of all-cause death, non-fatal MI, non-fatal stroke, revascularization, malignant arrhythmia, and severe heart failure.ResultsAll patients had varying degrees of coronary calcification, with a mean CACS of 97.60 (22.60, 942.75), and the level of CACS in the MACCEs group was significantly higher than that in non-MACCE (P 13.33. The K–M survival curves showed that patients in the high PDW/HDL-C ratio group had significantly lower survival rates than patients in the low PDW/HDL-C ratio group (log-rank test: P < 0.001). Multivariate Cox hazard regression analysis reveals that the PDW/HDL ratio was an independent predictor of MACCEs (HR: 1.604, 95% CI: 1.263–2.035; P < 0.001). Cox regression analysis showed that participants with a lower PDW/HDL-C ratio had a higher risk of MACCEs than those in the higher ratio group. The incidence of MACCEs was also more common in the PDW/HDL-C ratio > 13.33 group among different severities of coronary artery calcification. Furthermore, adding the PDW/HDL-C ratio to the traditional prognostic model for MACCEs improved C-statistic (P < 0.001), the NRI value (11.3% improvement, 95% CI: 0.018–0.196, P = 0.01), and the IDI value (0.7% improvement, 95% CI: 0.003–0.010, P < 0.001).ConclusionThe higher PDW/HDL-C ratio was independently associated with the increasing risk of MACCEs in patients with chest pain symptoms and coronary artery calcification. In patients with moderate calcification, mild coronary artery stenosis, and CAD verified by CTA, the incidence of MACCEs increased significantly in the PDW/HDL-C ratio > 13.33 group. Adding the PDW/HDL-C ratio to the traditional model provided had an incremental prognostic value for MACCEs.

Background: The prognostic value of coronary artery calcium (CAC) combined with risk factor burdens in middle-aged and elderly patients with symptoms is unclear. Methods: A cohort study comprising 7432 middle-aged and elderly symptomatic patients (aged above 55 years) was conducted between December 2013 and September 2020. All patients had undergone coronary computed tomography angiography, and the Agatston score were used to measure CAC scores. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE), which was defined as a composite outcome of nonfatal myocardial infarction, revascularization (percutaneous coronary intervention or coronary artery bypass graft), stroke, and cardiovascular death. Congestive heart failure, cardiogenic shock, malignant arrhythmia, and all-cause mortality were defined as the secondary outcomes. Results: There are 970 (13%) patients with CAC 0–10, 2331 (31%) patients with CAC 11–100, and 4131 (56%) patients with CAC ≥101. The proportion of patients aged 55–65 years, 65–75 years and ≥75 years was 40.7%, 38.1% and 21.2%, respectively. The total number of MACCEs over the 3.4 years follow-up period was 478. The percentage of CAC ≥101 was higher among the 75-year-old group than the 55–65-year-old group, increasing from 46.5% to 68.2%. With the increase in the CAC score, the proportion of patients aged ≥75 years increased from 12.9% to 25.8%, compared to those aged 55–65 years. The number of risk factors gradually increased as the CAC scores increased in the symptomatic patients aged over 55 years and the similar tendencies were observed among the different age subgroups. The proportion of non-obstructive coronary artery disease (CAD) was comparable between the three age groups (53.5% vs 51.9% vs 49.1%), but obstruction CAD increased with age. The incidence of MACCE in the group with CAC ≥101 and ≥4 risk factors was 1.71 times higher (95% confidence interval (CI) 1.01–2.92; p = 0.044) than the rate in the group with CAC ≥101 and 1 risk factor. In the CAC 0–10 group, the incidence of MACCE in patients aged ≥75 years was 12.65 times higher (95% CI: 6.74–23.75; p < 0.0001) than that in patients aged 55–65 years. By taking into account the combination of CAC score, age, and risk factor burden, the predictive power of MACCE can be increased (area under the curve (AUC) = 0.614). Conclusions: In symptomatic patients aged 55 or above, a rise in age, CAC scores, and risk factor burden was linked to a considerable risk of future MACCE. In addition, combining CAC scores, age and risk factors can more accurately predict outcomes for middle-aged and elderly patients with symptoms.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12885-018-4559-3.

The Upper Ordovician Wufeng to Lower Silurian Longmaxi formations are important exploration targets for shale gas in the western Hubei province. The lithology, sedimentary facies, gas-bearing characteristics and preservation conditions of the Wufeng-Longmaxi formations were analyzed with the samples of more than 20 survey wells. The Wufeng Formation is dominated by black carbonaceous siliceous shale of deep-water siliceous argillaceous shelf facies, while the Longmaxi Formation is dominated by gray-black carbonaceous shale of deep-water argillaceous shelf facies. The Wufeng-Longmaxi formations and the lower part of Lower Silurian Xintan Formation consist of two three-level sequences, and the gas content conforms to the characteristics of TST1 > TST2 > HST2 > HST1. The gas content of the Wufeng Formation is slightly higher than that of the Longmaxi Formation. A good gas potential has been found to the north of Tianyangping Fault and the east of Xianfeng Fault. Since most wells were in the deep shelf facies area, sedimentary facies have little effect on the plane distribution of shale gas content. The studies of preservation conditions showed that both the Xintan Formation as the roof and the Ordovician as the floor have good sealing properties. The burial history of Wufeng-Longmaxi formations can be divided into four stages, and shows the characteristics of "early uplift time" and "rapid uplift rate" when compared with the Sichuan Basin. The burial depth and the distance to normal fault have certain influence on the gas content. However, the matching pattern between fault and fold is the most important factor affecting gas content. Two structural patterns are beneficial to shale gas accumulation, one is being far away from normal fault and locating at the syncline wing or core, the other is being far away from normal fault and locating at the footwall of fault and the target stratum is not connected to the fault in the up-dip direction.

A filter and neural network (NN) based fault tolerant control (FTC) strategy is developed for a family of nonlinear systems expressed in strict feedback form in the event of unknown system dynamics and actuator failures. Specifically, adaptive neural network (ANN) is first utilized to facilitate the state observer design such that unmeasurable system states can be obtained. Note that ANN is only used when designing state observer instead of being used when designing controller. In our method, filter technique is introduced to construct virtual control inputs, which can not only reduce the adverse effects caused by ANN approximation errors and state estimation errors, but also deal with the expansion problem of the differential terms. Moreover, the fault tolerant tracking controller is designed by combining backstepping technique with the proposed NN with a novel weight updating law that is different from the above ANN. Theoretical analysis and simulation results demonstrate that the proposed FTC strategy can ensure that the tracking error converges to a small region of zero when there exist actuator faults and unknown system dynamics.

The organic-rich shales found in the Wufeng–Longmaxi Formation are typically deposited in oxygen-deficient reducing environments. One of the primary sources of debate revolves around the question of whether the anoxic bottom water found in these shales is either euxinic or ferruginous, and this matter remains unresolved. Previous studies have mostly focused on the Wufeng–Longmaxi Formation as a whole in order to understand the key factors that control organic matter accumulation (OMA). However, research on OMA for each member, including the Wufeng Formation (WF), the lower Longmaxi Formation (LLM), and the upper Longmaxi Formation (ULM), has been insufficient. This paper aims to investigate the palaeoenvironmental conditions and OMA mechanisms of the Wufeng–Longmaxi shales in western Hubei by integrating data on total organic carbon (TOC) content, mineral compositions, major and trace elements, and iron speciation. The results indicate that the Wufeng–Longmaxi shales were deposited under highly restricted hydrographic conditions, except for relatively open and upwelling conditions in the upper WF. Silica in the upper WF was primarily biogenic origin and not hydrothermal. Ferruginous conditions were the primary redox conditions for organic-rich shales except for minor formations in the lower LLM that were deposited under euxinic conditions. Due to the tectonic uplift caused by the Kwangsian Orogeny in the upper LLM, the palaeoenvironment was characterized by a warmer and wetter climate, high terrigenous influx, oxic conditions, and low productivity as the result of the insufficient nutrients caused by the weak upwelling, leading to the turnover of graptolite biozones from LM5 to LM6. The factors influencing OMA changed vertically. TOC contents have a highly positive correlation with Al content, indicating that terrigenous influx was the main factor affecting OMA in the WF, which significantly differed from patterns found in other regions. This suggests that the sedimentation rate of organic matter was higher than the terrigenous dilution rate during the WF stage. The combination of redox conditions and productivity were the main factors affecting OMA in the LLM, while terrigenous influx was the key factor controlling OMA in the ULM, resulting in the dilution of organic matter. Regions in the eastern Yiling block, which are close to the Qinling Ocean, show better prospects for shale gas exploration. This research will further facilitate the development of shale gas in this area.

Background Platinum resistance is a major challenge in the clinical treatment of advanced ovarian cancer (OC). Accumulating evidence shows that the tumor-promotive M2 macrophage is linked to the limiting chemotherapy efficacy of multiple malignancies including OC. Circular RNAs (circRNAs) are a novel class of non-coding RNAs which function as the critical regulator in biological process of cancer. However, their impact on macrophage polarization and chemoresistance of OC remain unclear.Methods Platinum-resistant circRNAs were screened using circRNA deep sequencing and validated using in situ hybridization in OC tissues with or without platinum resistance. The role of circITGB6 in inducing cisplatin (CDDP) resistance was evaluated by clone formation, immunofluorescence and annexin V assays in vitro, and by intraperitoneal tumor model in vivo. The mechanism underlying circITGB6-mediated tumor-associated macrophage (TAM) polarization into M2 phenotype was investigated using RNA pull-down, luciferase reporter, electrophoretic mobility shift, RNA binding protein immunoprecipitation (RIP), ELISA and immunofluorescence assays.Results We identified that a novel circRNA, circITGB6, robustly elevated in tumor tissues and serums from patients with OC with platinum resistance, was correlated with poor prognosis. circITGB6 overexpression promoted an M2 macrophage-dependent CDDP resistance in both vivo and vitro. Mechanistic research determined that circITGB6 directly interacted with IGF2BP2 and FGF9 mRNA to form a circITGB6/IGF2BP2/FGF9 RNA–protein ternary complex in the cytoplasm, thereby stabilizing FGF9 mRNA and inducing polarization of TAMs toward M2 phenotype. Importantly, blocking M2 macrophage polarization with an antisense oligonucleotide targeting circITGB6 markedly reversed the circITGB6-induced CDDP resistance of OC in vivo.Conclusions This study reveals a novel mechanism for platinum resistance in OC and demonstrates that circITGB6 may serve as a potential prognostic marker and a therapeutic target for patients with OC.

The objective of this paper is to examine the representativeness of charcoal taxa at archeological sites in northern China. We carried out standardized laboratory compression tests on 168 samples representing 21 taxa charred at four different temperatures to characterize the mechanical properties of common taxa in temperate China. The results indicate that significant fragmentation differences occur between taxa. Ring-porous/semi-ring-porous taxa with a moderate density (>0.55 g/cm3) are overrepresented, while those with a very low to low density (

To explore the applicability of the carbon isotope composition (δ13C) of fossil charcoal for the quantitative reconstruction of paleoclimates, we selected five points in Shaanxi province, from north to south, to collect modern Pinus species and Quercus species to sample covering areas with obvious climatic differences. In order to reveal the relationships between δ13C of charcoal and climate variables on the basis of carbonization experiments, we evaluated the fractionation mechanism of δ13C of charcoal, and compared the differences between δ13C of charcoal in wildfire experiments and indoor experiments regarding genera and species. The results showed significant differences in δ13C between genera but no significant differences among species. Additionally, the δ13C of charcoal was significantly negatively correlated with precipitation and positively correlated with evaporation, which could be determined from δ13C values in the study area to reconstruct ancient precipitation and evaporation in the future.

As an emerging charity model, critical illness network crowdfunding provides a source of funds for some critically ill patients in China who have difficulty paying their high treatment costs by themselves. This study aims to investigate the influencing factors of the public’s willingness to donate to critical illness crowdfunding projects on Internet platforms. From a perspective combining the technology acceptance model and the theory of planned behavior, a complex and comprehensive structural equation model is proposed. We randomly selected 1,000 members of the public in China and empirically verified the study framework through structural equation modeling (SEM) based on 710 valid questionnaires. The results show that the public’s donation willingness and the social distance to a critical illness crowdfunding project on an online platform positively affect the public’s donation behavior, and donation attitude positively affect donation willingness; perceived usefulness and empathic concern positively affect the public’s donation attitude, which in turn affects its donation willingness. This study confirms that members of the public are more likely to help people who have similar demographic factors or people who are similar to themselves and have the same values, i.e., people who have a close social distance. It innovatively proposes and verifies the hypothesis that empathic concern can significantly positively affect users’ perceived usefulness and donation attitude. Strong empathic concern triggers donation willingness and behavior.