The interaction of sea breezes with urban heat island (UHI) in coastal areas has been extensively investigated. Nevertheless, the impact of pure sea breeze (PSB), characterized by a prevailing wind direction perpendicular to the coastline, on UHI remains rarely unexplored. In this study, the PSB events from 2015 to 2022 in Tianjin are identified using 10-m wind observations, and their occurrence frequency is found to show significant seasonality with least frequency in autumn. Besides, we identify the event of all sea breeze (ASB), as well as the days with non-sea breeze (NSB), and the PSB events are found to only account for about one tenth of ASB events. To analyze the potential impact of PSB on UHI, we propose a term of urban-rural temperature difference (URTD) to represent UHI. This is implemented by calculating the difference of 2-m air temperature (T2m) at the city center station of Tianjin minus T2m at other meteorological stations along both directions: the PSB prevailing direction (PSB_H), and the direction perpendicular to PSB_H (PSB_V). Results show that the URTD in the presence of PSB tends to decline gradually from the coastline to the city center along the PSB_H. In contrast, the URTD doesn't change much along the direction of PSB_V. Shifting focus to the direction of PSB_H, the most pronounced alterations in URTD (upstream minus downstream) are found in the presence of PSB (2.14 degrees C), compared with ASB (0.85 degrees C) and NSB (0.57 degrees C). This indicates that the most substantial variation in URTD from coastline to city center occurs under the influence of PSB compared to others. Finally, a case study by comparing PSB against NSB is conducted, which confirms the above-mentioned phenomena. Our findings highlight the importance of classifying sea breeze in elucidating the impact of sea breeze on the UHI.

To evaluate the impact of different momentum control variable (CV) schemes (CV5, the momentum control variable option with ψχ and CV7, the momentum control variable option with UV) on radar data assimilation (DA) in weather research and forecasting model data-assimilation (WRFDA) systems, a heavy snowfall in central and eastern regions of China, which started on 6 February 2022, was taken as a case in this study. The results of the wind-field increments from the single observation tests indicated that the wind-field increments had a larger range of influence when stream function and velocity potential (ψχ) were used as momentum control variables in CV5. Some spurious increments were also generated in the wind-field analysis, since CV5 tended to maintain the integrated value of the wind field. When U-wind and V-wind were used as control variables in CV7, the wind-field increments had a smaller impact range, and there was less dependence among different locations on the wind increments. For the heavy snow case, the CV7 schemes displayed some improvements in simulating the composite reflectivity compared to the other two experiments, since the composite reflectivity in the CV5 and control experiments were overestimated to some level. It was also found that the RMSEs were lower in the CV7 compared to those in the CV5 in the short-term forecasts during the data-assimilation cycles. Results also indicated that the CV7 had a more significant effect on the 6 h accumulated precipitation forecasts. Meanwhile, the experiment Exp_CV7 achieved the best ETS and FSS scores among the three groups of experiments, while Exp_CV5 appeared to be generally superior to the CTRL. In summary, the precipitation of Exp_CV7 yielded the rainfall intensity and location most close to the observation compared to those from both the CTRL and Exp_CV5 experiments.

目的 基于通过 Toll 样受体 4(Toll-like receptor 4,TLR4)/核因子-κB(nuclear factor-κB,NF-κB)/NOD 样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)通路探讨羟基红花黄色素A(hydroxysafflor yellow A,HSYA)抑制血管紧张素 Ⅱ(angiotensin Ⅱ,ANGⅡ)诱导的血管外膜成纤维细胞(vascular adventitial fibroblasts,VAFs)迁移作用.方法 组织贴块法培养大鼠胸主动脉VAFs,免疫荧光实验检测细胞中Vimentin和α-平滑肌肌动蛋白(α-smoothmuscle actin,α-SMA)蛋白表达,鉴定 VAFs.设置对照组、ANGⅡ 组、HSYA 组、脂多糖(lipopolysaccharide,LPS)组和LPS+HSYA组,对照组VAFs给予培养基正常培养,其余各组给予1×10-7mol/LANGⅡ处理24h,然后更换为含100nmol/LLPS或40μmol/LHSYA的培养基,继续培养24h,划痕实验检测VAFs的迁移能力;CCK-8法检测细胞活力;Western blotting检测TLR4、NF-κB和p-NF-κB蛋白表达;免疫荧光实验检测NLRP3炎性小体相关蛋白NLRP3、半胱氨酸天冬氨酸蛋白酶-1(cystein-asparate protease-1,Caspase-1)及凋亡斑点样蛋白(apoptotic spot-like protein,ASC)共表达情况.结果 免疫荧光结果证实VAFs培养成功.划痕实验结果显示,ANGⅡ能够显著增加细胞的迁移率(P＜0.01),LPS刺激进一步提高VAFs的迁移率(P＜0.01),HSYA能够抑制ANG Ⅱ及LPS对VAFs迁移的促进作用(P＜0.01).Western blotting结果显示,ANGⅡ显著提高细胞内TLR4和p-NF-κB的表达(P＜0.05、0.001),并促进NF-κB入核(P＜0.001);HSYA显著抑制ANG Ⅱ诱导的细胞内TLR4和p-NF-κB的表达(P＜0.05、0.01、0.001),并抑制NF-κB入核(P＜0.05、0.01、0.001).免疫荧光实验结果表明,ANGⅡ及LPS促进NLRP3炎症小体相关蛋白NLRP3、Caspase-1及ASC共表达,HSYA可减少ANGⅡ及LPS诱导NLRP3、Caspase-1及ASC蛋白共表达,抑制NLRP3炎症小体的组装.结论 HSYA通过抑制TLR4/NF-κB/NLRP3通路减少ANG Ⅱ诱导的VAFs迁移.

Objectives To explore the association of Children's Dietary Inflammatory Index (C-DII) scores with inflammation and markers of inflammatory factors in children and adolescents. Methods Data on dietary nutrient intake, markers of inflammation (ferritin, alkaline phosphatase, C-reactive protein (CRP), absolute neutrophil cell count and lymphocyte count) and oxidative stress (serum bilirubin, albumin, and iron) were available for participants aged 6–19 years (n = 1281). Each participant's C-DII score was calculated based on a 24-h diet and recall. Generalized linear models were applied to examine associations between C-DII and markers of inflammation and oxidative stress, while adjusting for covariates. Restricted cubic splines were used to explore the dose-response association of C-DII scores with indicators of inflammatory oxidative stress. Akaike's Information Criterionwas applied to compare the performance of linear and non-linear models. Results After adjusting for potential confounders, quantile regression results showed that when comparing C-DII quartile 4 (most pro-inflammatory) and quartile 1 (most anti-inflammatory), lymphocytes, ferritin, CRP were statistically significant differences in serum bilirubin, albumin and serum iron (P < 0.05). The C-DII score showed a non-linear relationship with inflammatory oxidative stress indicators. Overweight/obese children and adolescents who ate a high pro-inflammatory diet were more likely to have higher levels of inflammatory cytokines (P = 0.002). Conclusions The dietary inflammatory index in children is associated with markers of chronic inflammation and oxidative stress. A pro-inflammatory diet resulted in increased serum concentrations of these markers, implying that early dietary interventions have implications for reducing chronic inflammation and oxidative stress in children and adolescents.

Pulmonary hypertension is associated with increased postoperative risk. This study analyzed the relation between the preoperative echocardiographic estimated blood pressure (estimated pulmonary arterial systolic pressure [ePASP]) of noncardiac patients and postoperative cardiac outcome and tried to identify a clinically meaningful threshold for ePASP in postcapillary pulmonary hypertensive patients. This was a single-center retrospective cohort study with propensity score analysis based on patients who underwent elective noncardiac surgery from June 2012 to December 31, 2018. We evaluated the relation between ePASP and the development of postoperative major adverse cardiac events (MACEs). Multivariate logistic regression models and generalized additive models were used, and the minimum p value approach was used to identify the threshold of ePASP that independently indicated the risk of MACEs. Finally, propensity score matching was used for patients with ePASP above or below the threshold, and the exposure effect was evaluated. Of the 16,210 surgeries, 7.0% experienced postoperative MACEs. The threshold for the ePASP was 47 mm Hg. Adjusted odds ratios for MACEs before and after propensity score matching were 2.03 (1.22 to 2.83) and 1.62 (1.01 to 2.23), respectively. In conclusion, the incidence of postoperative MACEs was 7.0% in patients who underwent elective noncardiac surgery. An ePASP ≥47 mm Hg was significantly associated with an increased risk of postoperative MACEs in postcapillary pulmonary hypertensive patients.

The purpose of this study was to evaluate at the link between gastrointestinal illness and urine phthalate metabolite concentrations in children and adolescents in the United States between 2005 and 2016. A total of 4008 National Health and Nutrition Examination Survey (NHANES) participants had urine samples obtained during the survey and self-reported their gastrointestinal functional status over the previous week. High performance liquid chromatography/tandem mass spectrometry (HPLC/MS–MS) was used to identify twelve phthalate metabolites in urine samples. The link between PAE concentrations and gastrointestinal illnesses was investigated using logistic regression, which was controlled for possible confounders. The combined and independent effects of PAEs on gastrointestinal illnesses were investigated using Bayesian Kernel Machine Regression (BKMR) and quantile-based g-computation (qgcomp). In children and adolescents, the prevalence of gastrointestinal infection was 9.0

BACKGROUND:Upregulated Kindlin-2 expression in hepatocellular carcinoma (HCC) correlates with metastasis and poor prognosis. In this study, we investigated the molecular mechanism of Kindlin-2 in HCC.METHODS:Kindlin-2 downstream pathways were explored through microRNA sequencing. The Kindlin-2-miR-1258-TCF4 axis was verified using bisulfite sequencing, a luciferase reporter assay, quantitative real-time PCR, and rescue assays. Binding of TCF4 to the Kindlin-2 promoter was confirmed by promoter activity analysis and chromatin immunoprecipitation.RESULTS:MiRNA sequencing identified miR-1258 as a downstream effector of Kindlin-2. MiR-1258 expression was increased following Kindlin-2 knockdown and decreased after Kindlin-2 overexpression. Next, we identified transcription factor 7 like 2 (TCF7L2 or TCF4) as a target of miR-1258 and found that Kindlin-2 upregulated TCF4 expression by epigenetically suppressing miR-1258 in HCC. Furthermore, our results suggest that TCF4 binds to the Kindlin-2 promotor to enhance its transcription. Therefore, Kindlin-2-miR-1258-TCF4 interaction creates a positive feedback loop. Functional assays and animal experiments demonstrated critical roles of miR-1258 and TCF4 in HCC cell migration in vitro and HCC metastasis in vivo. In HCC tissues, Kindlin-2 expression correlated negatively with miR-1258 expression and positively with TCF4 expression. Meanwhile, miR-1258 expression correlated negatively with TCF4 expression.CONCLUSIONS:This study illustrates a novel integrin-independent signaling pathway, Kindlin-2-miR-1258-TCF4, that regulates HCC invasion and metastasis and identifies Kindlin-2 as a promising therapeutic target in HCC.

To explore the potential active compounds and molecular mechanism of Xuefu Zhuyu decoction (XFZYD) in the treatment of atherosclerosis (AS) based on network pharmacology and molecular docking. The effective components and action targets of XFZYD were screened by using TCMSP database. And then, the action targets of AS were collected by GeneCards database. The intersection targets between the effective components' targets of XFZYD and AS-related action targets were used to construct PPI networks. GO and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed on these intersection targets. Finally, molecular docking software was used to excavate the active compounds of the core targets VEGFA and AKT1. We detected 225 active components of XFZYD, and found that quercetin, kaempferol, luteolin, naringenin, β-sitosterol, isorhamnetin, stigmasterol, baicalein, nobiletin, and β-carotene are the potential active compounds of XFZYD; STAT3, IL6, JUN, VEGFA, MAPK14, and AKT1 are the core target proteins of the active compounds, among which VEGFA and AKT1 are the key target proteins. PPI network results showed that β-carotene, quercetin, kaempferol, luteolin, and naringenin had higher degree values and more corresponding targets than other 5 active compounds and had the stable binding ability to regulatory proteins VEGFA and AKT1. The core components β-carotene, quercetin, kaempferol, and luteolin exerted their therapeutic effects on AS by acting on the key target proteins VEGFA and AKT1 to regulate fluid shear stress and the AGE-RAGE signaling pathway and IL-17 signaling pathway of diabetic complications of AS. The molecular docking results showed that VEGFA and AKT1 had great docking ability with the targeted active compounds, and β-carotene is the best. The active components of XFZYD, including β -carotene, quercetin, kamanol, and luteolin, can act on VEGFA and AKT1. These active ingredients play a role in alleviating and treating AS by regulating fluid shear stress and participating in signaling pathways such AS AGE-RAGE of atherosclerosis and diabetes mellitus complicated with AS. β-carotene is a potential inhibitor of VEGFA and AKT1 and treats AS through antioxidant action.

Background and aims: Although proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to improve cardiovascular outcomes, their effects on brain stroke risk are unclear. The present meta-analysis aimed to evaluate the effects of PCSK9 inhibitors on brain stroke prevention. Methods and results: We searched PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov for research published until December 30, 2020, to find randomized controlled trials (RCTs) of PCSK9 inhibitors for brain stroke prevention. Relative risk (RR) and 95% confidence intervals (CIs) were used to represent the outcomes. Seven RCTs with 57,440 participants, including 29,850 patients treated with PCSK9 inhibitors and 27,590 control participants, were included. PCSK9 inhibitors were associated with significant reductions in total brain stroke risk (RR, 0.77; 95% CI, 0.67-0.88; P < 0.001) and ischemic brain stroke risk (RR, 0.76; 95% CI, 0.66, 0.89; P < 0.001) in comparison with the control group. There was no significant difference in cardiovascular mortality (RR, 0.95; 95% CI, 0.84-1.07; P = 0.382) and the risk of hemorrhagic brain stroke (RR, 1.00; 95% CI, 0.66-1.51; P = 0.999) between patients treated with PCSK9 inhibitors and controls. PCSK9 inhibitors did not significantly increase the incidence of neurocognitive adverse events (RR, 1.02; 95% CI, 0.81-1.29; P = 0.85). Moreover, subgroup analysis showed no difference in cognitive function disorder risks among different PCSK9 inhibitors and treatment times. Conclusions: PCSK9 inhibitors significantly reduced the risk of total brain stroke and ischemic brain stroke without increasing the risk of brain hemorrhage and neurocognitive impairment. (c) 2021 The Author(s). Published by Elsevier B.V. on behalf of The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Objective Perioperative cardiovascular events constitute the majority of complications in noncardiac surgery. Older and female patients have been less investigated. We aimed to evaluate differences in perioperative cardiovascular outcomes by age and sex. Methods We enrolled 1079 patients (57.5 ± 17.0 years, 42.6% women) undergoing intra-abdominal surgery from July 2007 to June 2008 and compared occurrence of perioperative cardiac events by age (≥65 vs. <65 years) and sex. Multivariable logistic regression was used to investigate associations between age, sex, and outcomes. Results Age ≥65 years was associated with perioperative myocardial infarction (MI) (odds ratio [OR] 2.9, 95% confidence interval [CI]: 1.3–6.6) and total cardiovascular events (OR 2.4, 95% CI: 1.3–4.2). Age ≥65 years was associated with higher perioperative MI risks in men (OR 4.7, 95% CI: 1.3–17.6) than in women (OR 3.1, 95% CI: 1.2–8.3). Advanced age was associated with heart failure in women (OR 13.9, 95% CI: 1.7–110.5). Female sex was a risk factor for heart failure in elderly patients (OR 4.2, 95% CI: 1.1–15.7). Conclusions Advanced age appeared to be associated with increased perioperative cardiac risk but differed by sex. Tailored strategies should be considered with respect to the patient’s sex.

Objective(s): Vitexin, a natural flavonoid, is commonly found in many foods and traditional herbal medicines and has clear health benefits. However, the role of vitexin in cholestasis is presently unclear. This study investigated whether vitexin mitigated glycochenodeoxycholate (GCDC)-induced hepatocyte injury and further elucidated the underlying mechanisms. Materials and Methods: A cell counting kit-8 (CCK-8) assay was conducted to evaluate cell viability. The mitochondrial membrane potential (MMP, Δψm), reactive oxygen species (ROS) levels, and apoptosis rate of hepatocytes exposed to GCDC were detected by flow cytometry (FCM). We then measured the cytoprotective effects of vitexin against oxidative stress. The molecular signaling pathway was further investigated by using Western blotting and signaling pathway inhibitors. Results: Here, we showed that vitexin increased cell viability and reduced cell apoptosis, necroptosis, and oxidative stress in a dose-dependent manner in GCDC-treated hepatocytes. In addition, by using selective inhibitors, we further confirmed that inhibition of the JAK2/STAT3 pathway by vitexin was mediated by prolonged activation of Sirtuin 6 (SIRT6). Conclusion: Vitexin attenuated GCDC-induced hepatocyte injury via SIRT6 and the JAK2/STAT3 pathways.

Abstract Background Treatment decisions in patients undergoing non-cardiac surgery are based on clinical assessment. The Revised Cardiac Risk Index (RCRI) is pragmatic and widely used but has only moderate discrimination. We aimed to test the efficacy of the CHA2DS2-VASc score and the combination of CHA2DS2-VASc and RCRI to predict perioperative risks for non-cardiac surgery. Methods This pre-specified analysis was performed in a retrospective cohort undergoing intra-abdominal surgery in our center from July 1st, 2007 to June 30th, 2008. The possible association between the baseline characteristics (as defined by CHA2DS2-VASc and RCRI) and the primary outcome of composite perioperative cardiac complications (myocardial infarction, cardiac ischemia, heart failure, arrhythmia, stroke, and/or death) and secondary outcomes of individual endpoints were explored using multivariate Logistic regression. The area under the receiver operating characteristic curve (C-statistic) was used for RCRI, CHA2DS2-VASc, and the combined models, and the net reclassification improvement (NRI) was calculated to assess the additional discriminative ability. Results Of the 1079 patients (age 57.5 ± 17.0 years), 460 (42.6%) were women. A total of 83 patients (7.7%) reached the primary endpoint. Secondary outcomes included 52 cardiac ischemic events, 40 myocardial infarction, 20 atrial fibrillation, 18 heart failure, four strokes, and 30 deaths. The endpoint events increased with the RCRI and CHA2DS2-VASc grade elevated (P < 0.05 for trend). The RCRI showed a moderate predictive ability with a C-statistics of 0.668 (95%CI 0.610–0.725) for the composite cardiac outcome. The C-statistics for the CHA2DS2-VASc was 0.765 (95% CI 0.709–0.820), indicating better performance than the RCRI (p = 0.011). Adding the CHA2DS2-VASc to the RCRI further increased the C-statistic to 0.774(95%CI 0.719–0.829), improved sensitivity, negative predictive value, and enhanced reclassification in reference to RCRI. Similar performance of the combined scores was demonstrated in the analysis of individual secondary endpoints. The best cut-off of a total of 4 scores was suggested for the combined CHA2DS2-VASc and RCRI in the prediction of the perioperative cardiac outcomes. Conclusions The CHA2DS2-VASc score significantly enhanced risk assessment for the composite perioperative cardiovascular outcome in comparison to traditional RCRI risk stratification. Incorporation of CHA2DS2-VASc scores into clinical-decision making to improve perioperative management in patients undergoing non-cardiac surgery warrants consideration.

Background:Hypertension is associated with increased postoperative risk. However, no consensus was accepted whether elevated blood pressure in the operating room with normal blood pressure at rest related to additional cardiovascular risk.Methods:This was a single-center retrospective cohort study based on patients who underwent elective noncardiac surgery from 1 January 2012, to 31 December 2018. We evaluated the relationship between the delta SBP (the difference between first operating room blood pressure and baseline blood pressure) and the development of postoperative major adverse cardiac events (MACEs) in patients with normal baseline blood pressure. Multivariate logistic regression before and after propensity score weighting was performed to adjust for perioperative variables, and the minimum P value approach was used to identify the possible threshold of delta SBP that independently indicated the risk of MACE.Results:Of the 55 563 surgeries, in 4.1%, postoperative MACE occurred. The threshold for the delta SBP was 49 mmHg. The adjusted odds ratio for MACE before and after propensity score weighting for the delta SBP threshold was 1.35 (95% CI, 1.11--1.59); P less than 0.001 and 1.28 (1.03-1.60); P = 0.028, respectively.Conclusion:Delta SBP contributed to the elevated risk over and beyond the SBP at rest in patients who underwent elective noncardiac surgery. A rise of SBP of more than 49 mmHg from baseline in the operating room was significantly associated with an increased risk of postoperative MACE.

Abstract Aims The real‐world usage of intra‐aortic balloon pump (IABP) in various cardiogenic shocks (CS) and the association with outcomes are lacking. We aimed to investigate IABP adoption in CS in a nationwide registry in China. Methods and results We retrospectively retrieved data of 30 106 CS patients (age 67.1 ± 14.6 years, 37.6% female patients) in the Hospital Quality Monitoring System registry from 2013 to 2016. Ischaemic heart disease was the leading cause of CS (73.9%). Hypertension, cardiomyopathy, myocarditis, valvular, and congenital heart disease were seen in 36.0%, 7.5%, 2.6%, 7.3%, and 2.4% of the population. IABP was employed in 2320 (7.7%) subjects. The association between IABP usage and primary outcome of in‐hospital mortality and secondary outcomes of expenses and lengths of stay were investigated. The patients with IABP support had similar in‐hospital mortality to those without IABP (39.6% vs. 38.3%, P = 0.226), but longer hospital‐stay [8.0 (2.0–16.0) vs. 6.0 (2.0–13.0) days, P < 0.001] and higher expenses [7.1(4.4–11.1) vs. 2.3 (0.8–5.5) 10 000RMB, P < 0.001]. IABP support was not associated with reduced mortality in the overall CS population in multivariate regression analysis [odds ratio (OR) 1.05, 95% confidence interval (CI) 0.95–1.17], except for subgroups with myocarditis (OR 0.61, 95% CI 0.39–0.95, P for interaction = 0.010) and those who did not receive the early percutaneous coronary intervention (PCI) (OR 0.86, 95% CI 0.75–0.97, P for interaction < 0.001). Similar results were further confirmed in the propensity‐score‐matched population. Conclusions In this nationwide registry of CS patients, IABP was not noted with improved survival but increased healthcare consumption. However, IABP appears protective in those with myocarditis or who failed to receive early PCI.

Background: Obesity is a fundamental factor in metabolic disorders such as hyperlipidemia, insulin resistance, fatty liver, and atherosclerosis. However, effective preventive measures are still lacking. This study aimed to investigate different surgical protocols for removing partial adipose tissue before the onset of obesity and determine whether, and by which protocol, preliminary adipose removal could exert potent preventive effects against diet-induced metabolic disorders. Methods: Male low-density lipoprotein receptor (LDL-R) knockout (KO) mice were randomly divided into four groups and subjected to epididymal fat removal (Epi-FR) surgery, subcutaneous fat removal (suQ-FR) surgery, both subcutaneous and epididymal fat removal (Epi + suQ-FR) surgery, or sham-operation. After 1 week of recovery, all mice were given a high-fat diet (HFD) for 10 weeks to induce metabolic disorders. Results: In the Epi-FR group and the sham-operated group, the mean numbers of the residual subcutaneous fat were 28.59 mg/g and 18.56 mg/g, respectively. The expression of relative genes such as Pparg, Cebpa, Dgat2, Fabp4 and Cd36 in the residual subcutaneous fat increased 2.62, 3.90, 3.11, 2.06, 1.78 times in the Epi-FR group compared with that in the sham-operated group. Whereas in the other fat-removal groups, the residual fat depots had no significant change in either size or gene expression, as compared with those of the sham-operated group. Plasma lipid and glucose levels and insulin sensitivity, as detected by the glucose tolerance test, were not significantly alleviated in the three fat removal groups. Liver mass or lipid content was not attenuated in any of the three fat removal groups. The atherosclerosis burdens in the entire inner aorta and aortic root did not decrease in any of the three fat removal groups. Conclusions: Our data suggest that removal of epididymal adipose or subcutaneous adipose alone or in combination before the onset of obesity did not protect against hyperlipidemia, insulin resistance, fatty liver, or atherosclerosis in LDL-R KO mice fed with a HFD. Hence, adipose removal possibly does not represent a potential approach in preventing obesity-related metabolic disorders in the obesity-susceptible population.

Objectives:Vitexin, a natural flavonoid, is commonly found in many foods and traditional herbal medicines and has clear health benefits. However, the role of vitexin in cholestasis is presently unclear. This study investigated whether vitexin mitigated glycochenodeoxycholate (GCDC)-induced hepatocyte injury and further elucidated the underlying mechanisms.Materials and Methods:A cell counting kit-8 (CCK-8) assay was conducted to evaluate cell viability. The mitochondrial membrane potential (MMP, Δψm), reactive oxygen species (ROS) levels, and apoptosis rate of hepatocytes exposed to GCDC were detected by flow cytometry (FCM). We then measured the cytoprotective effects of vitexin against oxidative stress. The molecular signaling pathway was further investigated by using Western blotting and signaling pathway inhibitors.Results:Here, we showed that vitexin increased cell viability and reduced cell apoptosis, necroptosis, and oxidative stress in a dose-dependent manner in GCDC-treated hepatocytes. In addition, by using selective inhibitors, we further confirmed that inhibition of the JAK2/STAT3 pathway by vitexin was mediated by prolonged activation of Sirtuin 6 (SIRT6).Conclusion:Vitexin attenuated GCDC-induced hepatocyte injury via SIRT6 and the JAK2/STAT3 pathways.

The transmission mode of Legionella from its source was analyzed by microscope and fluorescence Quantitative Polymerase Chain Reaction (qPCR). The Legionella removal efficiency by water surface was 94.5%, and Legionella had difficulty in penetrating through the surface of the water membrane. A deflection point at the interface between water and air indicated a cluster of Legionella that was bonded to the contact surface by some unknown emplastic media. The emplastic media could stick firmly on glass and Legionella like glue. Force analysis showed that the surface tension of water is 106 orders of magnitude larger than the net force from the sum of the buoyancy and the weight of Legionella, and revealed that the surface tension of water is so large that a Legionella bacterium cannot break away from the water surface membrane and escape. The qPCR results showed that no Legionella was found in the air from a Legionella incubator or the Legionella laboratory. The results demonstrate that Legionella cannot be transmitted to people through water vapour or aerosol. The experimental results also indicate that water was able to remove most Legionella bacteria.

To assess the genomic profiles of tigecycline (Tgc)-resistantAcinetobacter baumannii, including antibiotic resistance (AR) genes and virulence factors (VF), whole-genome shotgun sequencing was performed on 19 Tgc-resistant (TgcR)A. baumanniistrains collected in a tertiary hospital during the early phase of the clinical introduction of Tgc in China from late 2012 to mid-2014. The major sample types containing TgcR strains were sputum and drain fluid. Data from an average of 624 Mbp of sequence was generated on each bacterial genome, with Q30 quality of 90%, and an average coverage of 96.6%. TCDC-AB0715 was used as a reference genome. The genome sequences were annotated for functional elements including AR genes, VFs, genome islands, and inserted sequences before they were comparatively analyzed. The antibiotic susceptibility phenotypes of the strains were examined by a broth microdilution method to determine the minimal inhibitory concentration (MIC) of strains against major clinical antibiotics. The AR genes (ARGs) were annotated using the Comprehensive Antibiotic Resistance Database (CARD). Thirty-three ARGs were shared by all 19 TgcR strains, and 24 ARGs were distributed differently among strains. A total of 391 VFs were found to be diversely distributed in all TgcR strains. Based on ARG number distribution, the 19 TgcR strains were divided into several groups. Highly differentiated genes includedgpi,mphG,armA,msrE,adec,catB8,aadA,sul1,bla(OXA-)(435),aph3i, andbla(TEM-)(1), which may represent gene markers for TgcRA. baumanniisub-types. In addition, when compared with Tgc-sensitive (TgcS) strains collected during the same period, TgcR strains featured enrichment of ARGs includingaph6id,aph3ib, andteta. Compared with 26 other whole-genome sequences ofA. baumanniideposited in GeneBank, TgcR strains in this study commonly lacked the EF-Tu mutation for elfamycin resistance. Previous investigation of threeA. baumanniistrains isolated from one patient indicated genomic exchange and a homologous recombination event associated with generation of tigecycline resistance. This study further analyzed additional TgcR strains. Phylogenetic analysis revealed a close evolutionary relationship between 19 TgcR strains and to isolates in East and Northeast China. In short, the comprehensive functional and comparative genomic analysis of 19 clinical TgcRA. baumanniistrains isolated in the early stage of Tgc usage in China revealed their close phylogenetic relationship yet variable genetic background involving multiple resistance mechanisms. Using a simple ARG or VF gene number diversity method and marker genes, TgcR strain sub-types can be identified. The distinct characteristics of TgcRA. baumanniistrains with versatile genomic resistance and regulation patterns raise concern regarding prediction and control of Tgc resistance in the clinic.

Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) is the most severe form of human lipodystrophy and is caused by loss-of-function mutations in the BSCL2/seipin gene. Exactly how seipin may regulate adipogenesis remains unclear. A recent study in vitro suggested that seipin may function to inhibit the activity of glycerol-3-phosphate acyltransferases (GPATs), and increased GPAT activity may be responsible for the defective adipogenesis under seipin deficiency. Here we generated Seipin(-/-)Gpat3(-/-) mice, which had mild but significant recovery of white adipose tissue mass over Seipin(-/-) mice. The mass of brown adipose tissue (BAT) of the Seipin(-/-)Gpat3(-/-) mice was almost completely restored to normal level. Importantly, the Seipin(-/-)Gpat3(-/-) mice showed significant improvement in liver steatosis and insulin sensitivity over Seipin(-/-) mice, which is attributable to the increased BAT mass and to the enhanced browning of the subcutaneous fat of the Seipin(-/-)Gpat3(-/-) mice. Together, our results establish a functional link between seipin and GPAT3 in vivo and suggest that GPAT inhibitors may have beneficial effects on BSCL2 patients.

Objective: Angioimmunoblastic T cell lymphoma (AITL) is an aggressive form of non-Hodgkin lymphoma derived from mature T cells. However, the underlying pathogenesis of AITL remains unresolved. We aimed to explore the role of FOXO1-mediated signaling in the tumorigenesis and progression of AITL.Methods: FOXO1 expression was assessed using immunohistochemistry on a total of 46 AITL tissue samples. Retroviruses encoding FOXO1 shRNA were used to knockdown FOXO1 expression in CD4+ T cells. Flow cytometric assays analyzed the proliferation and survival of FOXO1 knockdown CD4+ T cells. Furthermore, we performed adoptive T-cell transfer experiments to identify whether inactivation of FOXO1 induced neoplastic follicular-helper T (Tfh) cell polarization and function. Results: Patients with low FOXO1 protein levels were prone to have an advanced tumor stage (P = 0.049), higher ECOG ps (P =0.024), the presence of bone marrow invasion (P = 0.000), and higher IPI (P = 0.035). Additionally, the survival rates of patients in the FOXO1 high-expression group were significantly better than those in the FOXO1 low-expression group (χ2 = 5.346, P =0.021). We also observed that inactivation of FOXO1 increased CD4+ T cell proliferation and altered the survival and cell-cycle progression of CD4+ T cells. Finally, we confirmed that inactivation of FOXO1 induces Tfh cell programing and function. Conclusions: Inactivation of FOXO1 in AITL plays a key role in the tumorigenesis and progression of AITL. We propose that FOXO1 expression could be a useful prognostic marker in AITL patients to predict poor survival, and to design appropriate therapeutic strategies.