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BackgroundImmunological-related genes (IRGs) play a critical role in the immune microenvironment of tumors. Our study aimed to develop an IRG-based survival prediction model for hepatocellular carcinoma (HCC) patients and to investigate the impact of IRGs on the immune microenvironment.MethodsDifferentially expressed IRGs were obtained from The Genomic Data Commons Data Portal (TCGA) and the immunology database and analysis portal (ImmPort). The univariate Cox regression was used to identify the IRGs linked to overall survival (OS), and a Lasso-regularized Cox proportional hazard model was constructed. The International Cancer Genome Consortium (ICGC) database was used to verify the prediction model. ESTIMATE and CIBERSORT were used to estimate immune cell infiltration in the tumor immune microenvironment (TIME). RNA sequencing was performed on HCC tissue specimens to confirm mRNA expression.ResultsA total of 401 differentially expressed IRGs were identified, and 63 IRGs were found related to OS on the 237 up-regulated IRGs by univariate Cox regression analyses. Finally, five IRGs were selected by the LASSO Cox model, including SPP1, BIRC5, STC2, GLP1R, and RAET1E. This prognostic model demonstrated satisfactory predictive value in the ICGC dataset. The risk score was an independent predictive predictor for OS in HCC patients. Immune-related analysis showed that the immune infiltration level in the high-risk group was higher, suggesting that the 5-IRG signature may play an important role in mediating immune escape and immune resistance in the TIME of HCC. Finally, we confirmed the 5-IRG signature is highly expressed in 65 HCC patients with good predictive power.ConclusionWe established and verified a new prognosis model for HCC patients based on survival-related IRGs, and the signature could provide new insights into the prognosis of HCC.

Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) have exhibited great promise in the treatment of tumors with homologous recombination (HR) deficiency, however, PARPi resistance, which ultimately recovers DNA repair and cell progress, has become an enormous clinical challenge. Recently, KP372-1 was identified as a novel potential anticancer agent that targeted the redox enzyme, NAD(P)H:quinone oxidoreductase 1 (NQO1), to induce extensive reactive oxygen species (ROS) generation that amplified DNA damage, leading to cancer cell death. To overcome PARPi resistance and expand its therapeutic utility, we investigated whether a combination therapy of a sublethal dose of KP372-1 with a nontoxic dose of PARPi rucaparib would synergize and enhance lethality in NQO1 over-expressing cancers. We reported that the combination treatment of KP372-1 and rucaparib induced a transient and dramatic AKT hyperactivation that inhibited DNA repair by regulating FOXO3a/GADD45α pathway, which enhanced PARPi lethality and overcame PARPi resistance. We further found that PARP inhibition blocked KP372-1-induced PARP1 hyperactivation to reverse NAD+/ATP loss that promoted Ca2+-dependent autophagy and apoptosis. Moreover, pretreatment of cells with BAPTA-AM, a cytosolic Ca2+ chelator, dramatically rescued KP372-1- or combination treatment-induced lethality and significantly suppressed PAR formation and γH2AX activation. Finally, we demonstrated that this combination therapy enhanced accumulation of both agents in mouse tumor tissues and synergistically suppressed tumor growth in orthotopic pancreatic and non-small-cell lung cancer xenograft models. Together, our study provides novel preclinical evidence for new combination therapy in NQO1+ solid tumors that may broaden the clinical utility of PARPi.

BackgroundThe NF-κB signaling pathway plays an important role in associating inflammation with tumor development and progression. However, few studies have reported that roles of genetic variants of the NF-κB signaling pathway genes in survival of patients with HBV-related hepatocellular carcinoma (HBV-HCC), especially with regards to potentially functional SNPs.MethodsWe used multivariate Cox proportional hazards regression to evaluate associations between 2,060 single nucleotide polymorphisms (SNPs) in 20 NF-κB signaling pathway genes and survival of 866 HBV-HCC patients, which were randomly split (1:1) into discovery and validation datasets. Expression quantitative trait loci (eQTL) analysis was conducted to identify associations between survival-associated SNPs and mRNA expression of corresponding genes. Furthermore, online database was used to assess mRNA expression of corresponding genes and survival. Finally, receiver operating characteristic (ROC) curves were used to assess the prediction accuracy of models integrating both clinical and genetic variables on HCC survival.ResultsA total of 6 SNPs in MAP3K14 remained significantly associated with OS of HBV-HCC patients (PA) A allele was associated with higher mRNA expression levels of MAP3K14 (P=0.044) in normal liver tissue, which was associated with worse survival of HBV-HCC patients. In the additive model, after adjusting for age, sex, smoking status, drinking status, AFP level, cirrhosis, embolus and BCLC stage, the combined dataset showed that HBV-HCC patients carrying the rs2074292 AA and GA genotypes (HR=1.71, 95%CI= 1.29-2.27, P=0.000) (HR=1.40, 95%CI=1.10-1.77, P=0.005) have worse OS than GG genotype, respectively. The addition of risk genotypes to the prediction models increased the AUC significantly from 71.15% to 73.11% (P=0.012) and from 72.55% to 74.21% (P=0.010) for 1-year and 3-year OS, respectively.ConclusionOur study indicated that MAP3K14 rs2074292 A allele may be a potential predictor of HBV-HCC survival, likely regulating MAP3K14 mRNA expression.

Objective To compare the clinical outcomes of fresh embryo transfers (ETs) and frozen-thawed embryo transfers (FETs) after a freeze-all cycle in women ≥40 years old with poor ovarian response (POR). Methods We performed a single-center, retrospective, case-control study of patients who underwent in vitro fertilization between January 2014 and June 2019. We included a total of 192 patients aged 40 years or older from whom 3 or fewer oocytes had been retrieved and who were receiving cleavage-stage ET in this study. Of these patients, 101 and 91 patients underwent fresh ET and FET, respectively. The primary outcome was the live birth rate (LBR) after the first ET. Logistic regression analysis was used to compare the IVF outcomes and neonatal characteristics between the fresh ET and FET groups, adjusting for maternal age, body mass index, luteinizing hormone, and the number of good quality embryos transferred. Results The mean maternal ages and number of oocytes retrieved (43.2 years and 2.3 in both groups, P=0.902 and P=0.927, respectively) were similar in the fresh ET and FET groups. No significant difference was observed between the LBRs of the fresh ET and FET groups (adjusted odds ratio, 1.28; 95% confidence interval, 0.29–5.70). The clinical pregnancy and miscarriage rates, and neonatal characteristics (birth weights and premature infant rates) were similar between the 2 groups. Conclusions FET after the freeze-all strategy had no beneficial impact on the clinical outcomes of women ≥40 years with POR.

BackgroundAspartate transaminase/alanine transaminase (De Ritis) ratio is a good predictor of liver function damage, but its prognostic value in patients with hepatocellular carcinoma (HCC) undergoing hepatectomy remains unclear. This study aimed to assess the association of the De Ritis ratio with overall survival (OS) among hepatitis B virus (HBV)-related HCC patients undergoing hepatectomy.MethodsA total of 1,147 HCC patients were recruited. Cox regression analysis was used to identify the independent risk factors. Restricted cubic spline (RCS) was used to evaluate the association between the De Ritis ratio and mortality risk. Nomogram was constructed to determine the predictive power of the De Ritis ratio.ResultsMultivariate Cox regression analysis revealed that the tertile of the De Ritis ratio was an independent risk factor for mortality. After adjustment for confounding factors, the adjusted hazard ratios (HRs) with corresponding 95% CIs of mortality for the 2nd tertile and 3rd tertile were 1.175 (0.889–1.554) and 1.567 (1.199–2.046), respectively. RCS confirmed a non-linear association between the natural logarithm of the De Ritis ratio and the risk of mortality (p for non-linearity = 0.0375). The nomogram showed that the natural logarithm of the De Ritis ratio contributed the most to the prediction of prognosis in HBV-related HCC patients, and Harrell’s C-index was 0.680 with a 95% CI of 0.645–0.715.ConclusionThe De Ritis ratio is an independent predictor for OS in HBV-related HCC patients undergoing hepatectomy, which allows for prognostic stratification of patients, hence, individualized treatment and follow-up.

Abstract Background Triazine coccidiostats are widely used in chickens and turkeys for coccidiosis control. Ethanamizuril is a novel triazine compound that exhibits anticoccidial activity in poultry. This study was designed to evaluate the subchronic toxicity of ethanamizuril in beagle dogs at doses of 12, 60 or 300 mg/kg/day in diet for 90 days. Results Ethanamizuril was well tolerated at low and middle dosages in beagle dogs, and no drug-related toxical effects were observaed in terms of survival, clinical observations, organs weight and damage in these dose groups. However, in high dose administration group, food consumption and histologic changes in kidneys were noticed in both sexes of beagle dog, although the renal lesions were finally resolved at the end of 4 weeks exposure of ethanamizuril. Conclusions No-observed-adverse-effect level (NOAEL) was considered for ethanamizuril at dose of 60 mg/kg/day in Beagle dog. This result added toxicity effects of ethanamizuril to the safety database, which might guide safely using of ethanamizuril as a novel coccidiostat.

Abstract MicroRNAs (miRNAs) play important roles in the regulation of gene expression at the posttranscriptional level and are involved in human carcinogenesis. The aim of the current study was to investigate the associations between miR-182 single nucleotide polymorphisms and HCC risk in a southern Chinese population. In this case-control study of 863 HCC patients and 908 cancer-free controls, we performed genotyping of miR-182 rs4541843 and assessed its association with HCC risk. We found that individuals carrying the AG/AA genotypes of miR-182 rs4541843 were significantly associated with an increased risk of HCC compared with those carrying the GG genotype (adjusted odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.07–2.76, P = 0.026). In the stratified analysis, this increased risk was more pronounced in the subgroups of older individuals (adjusted OR = 1.98, 95% CI = 1.04–3.76, P = 0.037), males (adjusted OR = 1.81, 95% CI = 1.09–2.99, P = 0.021), and never drinkers (adjusted OR = 1.84, 95% CI = 1.03–3.30, P = 0.041). Our results suggested that miR-182 polymorphism rs4541843 may contribute to the susceptibility to HCC. Our findings require validation in further studies with larger sample sizes.

Abstract Objectives Both low vitamin D status and metabolic syndrome (MetS) are worldwide concerns, and low 25-hydroxyvitamin D [25(OH)D] levels are associated with MetS; however, related epidemiological evidence based on elderly Chinese individuals, especially those over 80 years of age, is limited. In the present study, we aimed to evaluate the association between serum 25(OH)D and MetS in elderly Chinese individuals. Method Serum 25(OH)D was measured in a cross-sectional sample of 2493 elderly people aged 65–112 years from eight areas of China in which the density of centenarians is exceptionally high. MetS was diagnosed according to blood pressure, lipid, and blood sugar levels; waist circumference; and body mass index (BMI). Adjusted multivariable logistic regression was used to analyze the associations between vitamin D and MetS based on different diagnostic criterias. Results A total of 890 (35.7%) of the recruited elderly individuals had insufficient levels of vitamin D, and 1029 participants (41.3%) were vitamin D deficient. High serum vitamin D concentrations were associated with a low prevalence of MetS according to the modified Adult Treatment Panel III (ATP III) criteria for adequate versus deficient vitamin D levels (OR: 0.63, 95% CI: 0.45, 0.88) and inadequate versus deficient vitamin D levels (OR: 0.70, 95% CI: 0.52, 0.92). Each 10 ng/ml increase in serum vitamin D was significantly associated with a decreased prevalence of MetS according to the modified ATP III criteria for people with normal waist circumference (WC) (OR: 0.55, 95% CI: 0.43,0.71). However, no significant statistical correlation was found among elderly people with a high WC. Additionally, in the analysis of the individual components, the ORs of adequate versus deficient vitamin D levels were 0.46 (95% CI: 0.30, 0.71) for elevated triglycerides and 0.64 (95% CI: 0.42, 0.97) for reduced high-density lipoprotein cholesterol (HDL-C) after adjustment for other components. Conclusions Vitamin D deficiency is very common among elderly Chinese individuals. Vitamin D deficiency may be a risk factor for MetS; however, the association was only statistically significant among elderly people with noncentral obesity. Further studies are needed to examine the causal direction of the association.

Abstract Background The value of contrast-enhanced ultrasound (CEUS) in differentiating between renal cell carcinoma (RCC) and angiomyolipoma (AML) was analyzed. The purpose of this study was to identify the independent indicators of CEUS for predicting RCC. Methods A total of 172 renal tumors (150 RCCs, 22 AMLs) in 165 patients underwent conventional ultrasound (CUS) and CEUS examinations before radical or partial nephrectomy, and the features on CUS and CEUS were analyzed. Results There were significant differences in echogenicity, blood flow signals in color Doppler flow imaging (CDFI), peak intensity, homogeneity of enhancement, wash in, wash out, and perilesional rim-like enhancement between RCC and AML (P

Abstract Background General self-efficacy is considered one of the most influential parameters affecting the quality of clinical practice and nurses’ perceived professional benefits (NPPB). Perceived organizational support (POS) is regarded as being central in understanding job-related attitudes, and it is important to enhance POS for nurses to maintain their current employment. NPPB can further reduce nurses’ job burnout and turn-over intention. Many studies have explored the relationships among general self-efficacy, POS, nursing practice environment (NPE) and NPPB. However, a moderating effect of NPE has not been fully explored in nurses, especially among paediatric nurses. Methods A descriptive cross-sectional study was conducted from July to October 2018 with 300 paediatric nurses from 3 Class A tertiary hospitals in Jilin Province. The respondents completed the General Self-Efficacy Scale, Perceived Organizational Support Scale, Practice Environment Scale and Nurses’ Perceived Professional Benefits Scale. The data were analyzed using path analysis and SPSS (version 23.0, IBM). Results General self-efficacy and POS were significantly positively associated with NPPB, which showed that the model had a good fit to the data. NPE was found to play a partial mediating role between POS and NPPB and also had a complete mediating role between general self-efficacy and NPPB. Conclusions The results suggest that general self-efficacy indirectly influences NPPB, and POS directly and indirectly influences NPPB by NPE. Effective measures should be taken to improve nurses’ practice environment in hospitals to raise nurses’ enthusiasm and confidence in their work.

Evidence has shown the roles of taVNS and TECS in improving depression but few studies have explored their synergistic effects on MDD. Therefore, the treatment responsivity and neurological effects of TECAS were investigated and compared to escitalopram, a commonly used medication for depression. Fifty patients with mild-to-moderate MDD (29 in the TECAS group and 21 in another) and 49 demographically matched healthy controls were recruited. After an eight-week treatment, the outcomes of TECAS and escitalopram were evaluated by the effective rate and reduction rate based on the Montgomery–Asberg Depression Rating Scale, Hamilton Depression Rating Scale, and Hamilton Anxiety Rating Scale. Altered brain networks were analyzed between pre- and post-treatment using independent component analysis. There was no significant difference in clinical scales between TECAS and escitalopram but these were significantly decreased after each treatment. Both treatments modulated connectivity of the default mode network (DMN), dorsal attention network (DAN), right frontoparietal network (RFPN), and primary visual network (PVN), and the decreased PVN–RFPN connectivity might be the common brain mechanism. However, there was increased DMN–RFPN and DMN–DAN connectivity after TECAS, while it decreased in escitalopram. In conclusion, TECAS could relieve symptoms of depression similarly to escitalopram but induces different changes in brain networks.

Aim Reports on the association of the CGG repeat length in the FMR1 gene with the severity of idiopathic POI are inconclusive. Therefore, a meta analysis was performed to investigate the relationship between the expansion of repeat CGG and idiopathic POI risk.Methods Up to January 2019, 18 case-control or cohort studies involving 3022 idiopathic POI patients and 8461 controls were included for meta analysis.Results Thirteen studies, including 2047 cases and 6912 controls, met our criteria for the assessment of the premutation and intermediate repeat length in patients patients with POI. Compared with controls, FMR1 gene premutation is significantly associated with POI (OR = 8.13; 95% CI: 4.35–15.19; p

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death globally. Currently there is a lack of tumor-selective and efficacious therapies for hepatocellular carcinoma. β-Lapachone (ARQ761 in clinical form) selectively kill NADPH: quinone oxidoreductase 1 (NQO1)-overexpressing cancer cells. However, the effect of β-Lapachone on HCC is virtually unknown. In this study, we found that relatively high NQO1 and low catalase levels were observed in both clinical specimens collected from HCC patients and HCC tumors from the TCGA database. β-Lapachone treatment induced NQO1-selective killing of HCC cells and caused ROS formation and PARP1 hyperactivation, resulting in a significant decrease in NAD+ and ATP levels and a dramatic increase in double-strand break (DSB) lesions over time in vitro. Administration of β-Lapachone significantly inhibited tumor growth and prolonged survival in a mouse xenograft model in vivo. Our data suggest that NQO1 is an ideal potential biomarker, and relatively high NQO1:CAT ratios in HCC tumors but low ratios in normal tissues offer an optimal therapeutic window to use β-Lapachone. This study provides novel preclinical evidence for β-Lapachone as a new promising chemotherapeutic agent for use in NQO1-positive HCC patients.

Background: It remains unsolved that whether blood uric acid (UA) is a neuroprotective or neurotoxic agent. This study aimed to evaluate the longitudinal association of blood UA with mild cognitive impairment (MCI) among older adults in China.Methods: A total of 3,103 older adults (aged 65+ years) free of MCI at baseline were included from the Healthy Aging and Biomarkers Cohort Study (HABCS). Blood UA level was determined by the uricase colorimetry assay and analyzed as both continuous and categorical (by quartile) variables. Global cognition was assessed using the Mini-Mental State Examination four times between 2008 and 2017, with a score below 24 being considered as MCI. Cox proportional hazards models were used to examine the associations.Results: During a 9-year follow-up, 486 (15.7%) participants developed MCI. After adjustment for all covariates, higher UA had a dose-response association with a lower risk of MCI (all Pfor trend < 0.05). Participants in the highest UA quartile group had a reduced risk [hazard ratio (HR), 0.73; 95% (CI): 0.55–0.96] of MCI, compared with those in the lowest quartile group. The associations were still robust even when considering death as a competing risk. Subgroup analyses revealed that these associations were statistically significant in younger older adults (65–79 years) and those without hyperuricemia. Similar significant associations were observed when treating UA as a continuous variable.Conclusions: High blood UA level is associated with reduced risks of MCI among Chinese older adults, highlighting the potential of managing UA in daily life for maintaining late-life cognition.

Eimeria species are intracellular parasites residing inside the intestinal epithelial cell, which cause poultry coccidiosis and result in significant financial losses in the poultry industry. Genome editing of Eimeria is of immense importance for the development of vaccines and drugs. CRISPR/Cas9 has been utilized for manipulating the genome of Eimeria tenella (E. tenella). Ectopic expression of Cas9, i.e., via plasmids, would introduce transgene, which substantially limits its application, especially for vaccine development. In this study, we initially optimized the condition of the transfection protocol. We demonstrated that with the optimized condition, the transfection of FnCas12a (also known as “FnCpf1”) protein and crRNA targeting EtHistone H4 triggered DNA double-strand breaks in vivo. We then used this strategy to knock-in a coding cassette for an enhanced yellow fluorescent protein (EYFP) and dihydrofolate reductase–thymidylate synthase gene (DHFR) as a selection marker to tag endogenous EtActin. The engineered E. tenella parasite possesses EYFP expression in its entire life cycle. Our results demonstrated that FnCas12a could trigger genome editing in E. tenella, which augments the applicability of the dissection of gene function and the development of anticoccidial drugs and vaccines for Eimeria species.

Abstract Background Inflammatory markers, such as high sensitivity C-reactive protein (hs-CRP), and cognitive impairment (CI) are associated with mortality; CRP is related to the deterioration of CI. However, it is still unknown whether these two indices predict mortality independent of each other. Furthermore, their joint effect on all-cause mortality has not been well established, especially in oldest-old adults. Methods Based on data from the 2012 wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS), we included 1447 oldest-old adults (mean age 84.7 years and 58.7% were female, weighted) with information on hs-CRP (stratified by a cutoff value of 3.0 mg/L) and cognition (quantified by Mini-Mental Status Examination (MMSE) scored according to the personal educational level) at baseline. Mortality was assessed in followed 2014 and 2017 waves. Cox proportional hazards regression models were used, with adjustment for hs-CRP and cognition (mutually controlled) and several traditional mortality risk factors. Results During a median follow-up period of 32.8 months (Q1-Q3, 9.7–59.0 months), 826 participants died. Hs-CRP [HR > 3.0 mg/L vs ≤ 3.0 mg/L: 1.64 (95% CI, 1.17, 2.30)] and cognition [HR CI vs normal: 2.30 (95% CI, 1.64, 3.21)] each was independent predictor of all-cause mortality, even after accounting for each other and other covariates. Monotonic and positive associations were observed in combined analyses, in which the highest mortality risk was obtained in elders with both high hs-CRP> 3.0 mg/L and CI [HR: 3.56 (95% CI, 2.35, 5.38)].The combined effects were stronger in male and younger oldest-old (aged 80–89 years). Conclusion High hs-CRP and CI, both individually and jointly, were associated with increased all-cause mortality risks in Chinese oldest-old. Intervention strategies for preventing inflammation and maintaining adequate cognitive function may be more important in male and younger oldest-old for reducing mortality risk.

Objective An experiment was conducted to investigate the effects of feed intake restriction during late pregnancy on the function, anti-oxidation capability and acute phase protein synthesis of ovine liver. Methods Eighteen time-mated ewes with singleton fetuses were allocated to three groups: restricted group 1 (RG1, 0.18 MJ ME/kg W0.75 d, n = 6), restricted group 2 (RG2, 0.33 MJ ME/kg W0.75 d), n = 6) and a control group (CG, ad libitum, 0.67 MJ ME/kg W0.75 d, n = 6). The feed restriction period was from 90 days to 140 days of pregnancy. Results The ewe’s body weight, liver weights, water, and protein content of liver in the restricted groups were reduced compared with the CG group (p0.05). Conclusion The fat accumulation, increased hepatic fibrosis, antioxidant imbalance and modified synthesis of acute phase proteins were induced in ewe’s liver by maternal malnutrition during late pregnancy, which were detrimental for liver function to accommodate pregnancy.

In order to investigate the bearing capacity of composite columns composed of ultra-high performance concrete, (UHPC)-filled high-strength elliptical steel tube with encased high-strength H-shape steel (HUCFESTCs) were subjected to eccentric load. Forty-four HUCFESTCs were designed with varying parameters: yield strength of the steel tube (fy), yield strength of the H-shape steel (fy1), concrete-cube compressive strength (fcu), steel tube thickness (t), eccentricity (e), slenderness ratio (λ), the section area of the H-shape steel (AHS), and long–short axis ratio (ψ). Based on a bilinear elastic–plastic constitutive model of steel that considered stress hardening and a nonlinear constitutive model of UHPC, 44 HUCFESTCs models were established by ABAQUS software. The influence of different parameters on the ultimate bearing capacity of the HUCFESTCs was analyzed. The whole process of HUCFESTCs under eccentric load was studied, and the typical failure modes of HUCFESTCs are described. The results show that the main failure mode of the HUCFESTCs subjected to eccentrical load is bulging outward of the steel tube, the buckling of the H-shape steel, and crushing of the concrete in the middle part of the column and the inner part of the H-shape steel. The stiffness of HUCFESTCs increases gradually with the increase in fy, t, and e. The ultimate eccentrical compression bearing capacity of HUCFESTCs improves gradually with increases in fy, t, fy1, AHS, ψ, and fcu, but it decreases gradually with increases in λ and e. By using statistical regression and introducing the reduction coefficient of eccentricity, the calculation formula for the eccentric bearing capacity of HUCFEST columns is developed, which can provide a basis for the application of HUCFESTCs in practical engineering.

The effects of recycled powder (RP) on hydration, micro-structures, compressive strength and tensile properties of high-ductility cementitious composites (HDCC) were studied. Three mass ratios of RP ranging from 10, 30 to 60% were employed to partially replace the cement. The hydration kinetics of RP-amended matrix was measured to investigate the influence of RP on the cementitious hydration process and the phase development was quantified by the thermal gravimetric analysis. Mechanical properties, including the compressive and tensile properties of HDCCs were obtained at 28 days. The morphology of reinforced polyethylene fiber at the fracture surface was obtained by the environmental scanning electron microscope (SEM) analysis.

Objective: Globally, developed countries such as the United States, Canada, Germany, Korea, have carried out long-term and systematic biomonitoring programs for environmental chemicals in their populations. The China National Human Biomonitoring (CNHBM) was to document the extent of human exposure to a wide array of environmental chemicals, to understand exposure profiles, magnitude and ongoing trends in exposure in the general Chinese population, and to establish a national biorepository. Methods: CNHBM adopted three-stage sampling method to obtain a nationally representative sample of the population. A total of 21,888 participants who were permanent residents in 31 provinces were designed to interviewed in this national biomonitoring (152 monitoring sites × 3 survey units × 2 sexes × 6 age groups × 4 persons = 21,888 persons) in 2017–2018. Unlike the US National Health and Nutrition Examination Survey, the CNHBM will follow the same participants in subsequent cycles allowing for dynamic, longitudinal data sets for epidemiologic follow-up. Each survey cycle of CNHBM will last 2 years and each subsequent cycle will occur 3 years after the prior cycle’s completion. Results: In 2017–2018, the CNHBM created a large cohort of Chinese citizens that included districts/counties questionnaire, community questionnaire collecting information on villages/communities, individual questionnaire, household questionnaire, comprehensive medical examination, and collection of blood and urine samples for measurement of clinical and exposure biomarkers. A total of 21,746 participants were finally included in CNHBM, accounting for 99.4% of the designed sample size; and 152 PSUs questionnaires, 454 community questionnaires, 21,619 family questionnaires, 21,712 cases of medical examinations, 21,700 individual questionnaires, 21,701 blood samples and 21,704 urine samples were collected, respectively. Planned analyses of blood and urine samples were to measure both inorganic and organic chemicals, including 13 heavy metals and metalloids, 18 poly- and per-fluorinated alkyl substances, 12 phthalate metabolites, 9 polycyclic aromatic hydrocarbons metabolites, 4 environmental alkylated phenols, and 2 benzene metabolites. Conclusions: CNHBM established the first nationally representative, prospective cohort in the Chinese population to understand the baseline and trend of internal exposure of environmental chemicals in general population, and to understand environmental toxicity.

The real-time performance of ship detection is an important index in the marine remote sensing detection task. Due to the computing resources on the satellite being limited by the solar array size and the radiation-resistant electronic components, information extraction tasks are usually implemented after the image is transmitted to the ground. However, in recent years, the one-stage based target detector such as the You Only Look Once Version 5 (YOLOv5) deep learning framework shows powerful performance while being lightweight, and it provides an implementation scheme for on-orbit reasoning to shorten the time delay of ship detention. Optimizing the lightweight model has important research significance for SAR image onboard processing. In this paper, we studied the fusion problem of two lightweight models which are the Coordinate Attention (CA) mechanism module and the YOLOv5 detector. We propose a novel lightweight end-to-end object detection framework fused with a CA module in the backbone of a suitable position: YOLO Coordinate Attention SAR Ship (YOLO-CASS), for the SAR ship target detection task. The experimental results on the SSDD synthetic aperture radar (SAR) remote sensing imagery indicate that our method shows significant gains in both efficiency and performance, and it has the potential to be developed into onboard processing in the SAR satellite platform. The techniques we explored provide a solution to improve the performance of the lightweight deep learning-based object detection framework.

It has been reported that extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (HUCMSCs) can promote the proliferative and secretive functions of granulosa cells. In vivo study further demonstrated that EVs derived from HUCMSCs can not only promote the angiogenesis of ovarian tissue but also restore the function of an ovary of chemically induced premature ovarian insufficiency (POI) mice. However, no study investigates the effects of HUCMSCs derived EVs on fertility recovery of POI mice and evaluating their offspring. This study investigates the effects of HUCMSCs derived EVs on fertility recovery and the cognitive function of their offspring. A POI model was established by intraperitoneal injection of cyclophosphamide (CTX) and busulfan (BUS), and randomly divided into EVs-transplantation group (a single injection of 150 µg EVs proteins which suspended in 0.1 ml phosphate buffer saline [PBS] via tail vein), POI group (a single injection of 0.1 ml PBS via tail vein), and normal control group (a single injection of 0.1 ml PBS via tail vein without intraperitoneal injection of CTX and BUS). After EVs treatment, not only the ovarian function of POI mice recovered but also the fertility increased with less time to get pregnant, evaluating by in vitro fertilization and mating test. Cognitive behaviors of the offspring were similar among the three groups through the Y-maze test and novel object recognition task. An anti-apoptotic effect was identified through immunohistochemistry, real-time polymerase chain reaction and western blot. These findings indicate that HUCMSCs derived EVs can improve the fertility of POI mice without adverse effects on the cognitive behavior of their offspring, highlighting the potential value of EVs to be a cell-free therapy for patients suffering from POI.

Concrete-filled tubular flange girders have been used in bridges, and torsional bracings are widely used in them to increase the lateral-torsional buckling strength. This article proposes an analytical solution for the lateral-torsional buckling (LTB) of concrete-filled tubular flange steel girders with torsional bracing under a concentrated load. The modal trial functions of lateral displacement and the torsional angle are expressed by the first six terms of the trigonometric function. By introducing dimensionless parameters, the variational solution of energy for the buckling equation of the LTB of the girders is obtained, and the formula for the dimensionless critical moment of its LTB is derived using 1stOpt based on 32,550 data sets. Compared with the finite element method, the proposed critical formula is highly accurate and can be applied to engineering design. Finally, parametric studies were conducted on the effects of the stiffness of torsional bracing, the span of the girder, and the flange steel ratio.

Tubular flange composite beams are increasingly applied in modern bridge structures. In order to investigate the overall stability behavior of doubly symmetric tubular flange composite beams with lateral bracing under concentrated load, the analysis of elastic lateral-torsional buckling is conducted by the energy variation method. The analytical solution of critical moment of doubly symmetric tubular flange composite beams with lateral bracing is obtained. Meanwhile, the simplified calculation formula of critical moment is fitted by 1stOpt software based on 26,000 groups of data, and the accuracy is verified by the finite element method. It is found that, the critical moment rises obviously with increasing lateral bracing stiffness, and adding lateral bracing to doubly symmetric tubular flange composite beams is beneficial to improve the overall stability in engineering practice. Finally, the influence of several parameters including concrete strength, span, steel ratio of flange and height-thickness ratio of web are studied. The results show that the concrete strength and the web height-thickness ratio have a weak influence on critical moment of elastic lateral-torsional buckling, while the influence of span-depth ratio and flange steel ratio is very significant.

Background: Ferroptosis is a known crucial player in the development of cancers. However, the effect of single nucleotide polymorphisms (SNPs) in ferroptosis-related genes on survival in hepatitis B virus (HBV)-related hepatocellular carcinoma (HBV-HCC) patients remains unknown. Methods: We used two-stage multivariable Cox proportional hazards regression analyses to estimate the associations between 48,774 SNPs in 480 ferroptosisrelated genes and overall survival (OS) of 866 HBV-HCC patients. Results: We identified that two potentially functional SNPs (CREB3 rs10814274 C>T and GALNT14 rs17010547 T>C) were significantly independently associated with the OS of HBV-HCC patients (CT+TT verse CC, hazards ratio (HR)=0.77, 95% confidence interval (CI)=0.67–0.89, p<0.001 for rs10814274 and TC+CC verse TT, HR=0.66, 95% CI=0.53–0.82, p<0.001 for rs17010547, respectively). Additional joint assessment of protective genotypes of these two SNPs showed that patients with 1–2 protective genotypes had a significantly better OS compared with those carrying 0 protective genotypes (HR=0.56, 95% CI=0.45– 0.70, p<0.001). Moreover, the expression quantitative trait loci (eQTL) analysis revealed that the survival-associated SNP rs10814274 T allele was significantly correlated with reduced CREB3 transcript levels in both normal liver tissues and whole blood cells, while the GALNT14 rs17010547 C allele had a significant correlation with increased GALNT14 transcript levels in whole blood cells. Conclusion: These results suggest that genetic variants of CREB3 and GALNT14 may affect the survival of HBV-HCC patients, likely via transcriptional regulation of respective genes. However, further studies are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Molybdenum nickel alloy has been proved to be an efficient noble-metal-free catalyst for hydrogen evolution reaction (HER) in alkaline medium, but its electrocatalytic activity and stability need to be further improved to meet industrial requirements. In this study, carboxymethylated enzymatic hydrolysis lignin (EHL) was used as a biomacromolecule frame to coordinate with transition metal ions and reduced by pyrolysis to obtain the MoNi4--NiO heterojunction (MoNi4--NiO/C). The oblate sphere structure of MoNi4--NiO/C exposed a large catalytic active surface to the electrolyte. As a result, the hydrogen evolution reaction of MoNi4--NiO/C displayed a low overpotentials of 41 mV to achieve 10 mA cm-2 and excellent stability of 100 h at 100 mA cm-2 in 1 mol L-1 KOH, which was superior to that of commercial Pt/C. Lignin assisted the formation of NiO to construct the MoNi4--NiO interface and MoNi4--NiO heterojunction structure, which reduced the energy barrier by forming a more favorable transition states and then promoted the formation of adsorbed hydrogen at the heterojunction interface through water dissociation in alkaline media, leading to the rapid reaction kinetics. This work provided an effective strategy for improving the electrocatalytic performance of noble-metal-free electrocatalysts encapsulated by lignin-derived carbon. [ABSTRACT FROM AUTHOR]

To develop an effective and sustainable cell therapy for sickle cell disease (SCD), we investigated the feasibility of targeted disruption of the BCL11A gene, either within exon 2 or at the GATAA motif in the intronic erythroid-specific enhancer, using zinc finger nucleases in human bone marrow (BM) CD34+ hematopoietic stem and progenitor cells (HSPCs). Both targeting strategies upregulated fetal globin expression in erythroid cells to levels predicted to inhibit hemoglobin S polymerization. However, complete inactivation of BCL11A resulting from bi-allelic frameshift mutations in BCL11A exon 2 adversely affected erythroid enucleation. In contrast, bi-allelic disruption of the GATAA motif in the erythroid enhancer of BCL11A did not negatively impact enucleation. Furthermore, BCL11A exon 2-edited BM-CD34+ cells demonstrated a significantly reduced engraftment potential in immunodeficient mice. Such an adverse effect on HSPC function was not observed upon BCL11A erythroid-enhancer GATAA motif editing, because enhancer-edited CD34+ cells achieved robust long-term engraftment and gave rise to erythroid cells with elevated levels of fetal globin expression when chimeric BM was cultured ex vivo. Altogether, our results support further clinical development of the BCL11A erythroid-specific enhancer editing in BM-CD34+ HSPCs as an autologous stem cell therapy in SCD patients.