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ContextExogenous insulin antibody syndrome (EIAS) can lead to unexpected and potentially life-threatening recurrent hypoglycemia.ObjectiveWe aimed to better define autoimmune hypoglycemia caused by EIAS in patients with diabetes and shed light on the improvements in the identification and intervention for this rare but possibly life-threatening condition.MethodsWe summarized the clinical characteristics of autoimmune hypoglycemia caused by EIAS in 23 patients with diabetes. Furthermore, we performed human leukocyte antigen (HLA) genotyping of 10 patients.ResultsWe identified a high frequency of autoimmune comorbidities (21.7%), food or drug allergy (48%), insulin allergy (30%), lipodystrophy at the insulin injection sites (22%), and antinuclear antibodies (25%) in the patients. Alternation between hyperglycemia and hypoglycemia was observed in more than 90% of the patients. Most patients showed a high insulin autoantibody titer (>90%) and inappropriately increased insulin concentration (insulin/C-peptide molar ratio >7, >85%). We detected similar frequencies of DRB1*0405-DQB1*0401 and DRB1*0901-DQB1*0303 compared with previously reported frequencies in type 1 diabetes, and a lower frequency of DRB1*0406 compared with insulin autoimmune syndrome. The spontaneous remission rate exceeded 70%.ConclusionPredisposing factors for autoimmune hypoglycemia caused by EIAS include a strong autoimmune background. Susceptible HLA genotypes for type 1 diabetes or insulin autoimmune syndrome might not explain susceptibility to this condition. Additionally, insulin autoantibodies and the insulin/C-peptide molar ratio are reliable screening options. The prognosis for this condition is favorable. Monitoring of insulin and insulin autoantibodies may contribute to treatment effectiveness.

Background：China is rapidly transforming into an aging society and houses the largest elderly population in the world. Diet patterns increase inflammation and oxidative stress, which may provide effective intervention strategies for mitigating the health burden in aging societies. This study sought to develop a Chinese empirical dietary inflammatory index(CEDII) that assesses Chinese diet quality based on its inflammatory potential and examine whether the index was associated with an accelerated aging process. Methods:A cross-sectional study conducted in the community of Beijing recruited 388 participants. Dietary intake was collected based on 24-h dietary recalls. The Chinese Diet Balance Index(DBI) and its derivatives, as well as the empirical dietary inflammatory pattern(EDIP) based on the western diet, were calculated to assess dietary quality in different aspects. Chinese empirical dietary inflammatory index(CEDII) was derived using reduced-rank regression(RRR) according to Chinese diet patterns. The population was categorized into tertiles of the CEDII. Leukocyte telomere length(LTL) and mitochondrial DNA copy number(mtDNAcn) were determined by polymerase chain reaction assay. Tumor necrosis factor α(TNFα) and interleukin-6(IL-6), 8-oxo-2'-deoxyguanosine (8-oxo-dG), superoxide dismutase (SOD) activities, and glutathione reductase (GR) were measured. ResultsA total of 388 subjects were enrolled. High CEDII group was characterized by high intake of carbohydrates. This pattern predicted higher levels of TNFα, IL-6, shorter LTL and lower mtDNAcn. Neither DBI nor EDIP was correlated with biomarkers of inflammation or aging. High CEDII scores were associated with short LTL and decreased mtDNAcn using multivariate linear regression with adjustment for confounding variables. The stratified analysis demonstrated that the high CEDII group had an increased risk of short LTL in subjects with abnormal metabolic status. Conclusions: This study developed a Chinese empirical dietary inflammatory index(CEDII). High CEDII scores were associated with an increased risk of aging. Compared with indexes related to DBI and EDIP, CEDII was much more effective in assessing inflammation and aging potential of diet patterns for Chinese residents.

A heavy snowfall event that struck Beijing during February 12-13, 2022, affected some of the training sessions and events of the Winter Olympic Games. This heavy snowfall event was simulated using the Advanced Research Weather Research and Forecasting Model with both the two-moment bulk scheme (BULK) and the spectral bin microphysics scheme (BIN), and the differences in surface precipitation, radar reflectivity, and cloud microphysics processes were compared and analyzed. It was found that surface precipitation was dominated by solid precipitation particles. The 24-h accumulated precipitation of the BULK simulation was larger than that of the BIN simulation, but both were smaller than that observed. The BIN simulation was closer to the observations in terms of the trends of variation in precipitation rate and radar reflectivity during the period of heavy precipitation. The maximum and minimum vertical velocities of the BIN simulation were notably higher than those of the BULK simulation, and the water vapor content of the BIN scheme at the heights of the −10 to −20°C levels and above the −38°C level was substantially higher than that of the BULK scheme. The contents of cloud water and snow simulated by the BIN scheme were much higher than those simulated by the BULK scheme. The nucleation of ice crystals in the middle and high layers of the BULK scheme was obvious, whereas such a process was not evident in the BIN scheme. The net production rate of ice crystals and snow simulated by the BULK scheme was stronger near the surface than that simulated by the BIN scheme, and a second peak in the conversion rate existed at heights very close to the surface below 1 km, which might account for the greater intensity of precipitation in the BULK scheme. The latent heat simulated by the BULK scheme was larger (smaller) than that simulated by the BIN scheme below (above) the height of 2 km.

BackgroundPARP inhibitors (PARPis) are novel molecular targeted therapeutics for inhibition of DNA repair in tumor cells, which are commonly used in ovarian cancer. Recent case reports have indicated that haemorrhages-related adverse events may be associated with PARPis. However, little is known about the characteristics and signal strength factors of this kind of adverse event.MethodsA pharmacovigilance study from January 2004 to March 2022 based on the FDA adverse event reporting system (FAERS) database was conducted by adopting the proportional imbalance method based on the four algorithms, including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural networks (BCPNN) and multi-item gamma Poisson shrinker (MGPS).Results725 cases of PARPi-haemorrhages-related adverse events were identified with a fatality rate of 4.72% (30/725) and a median age of 67 years. About 88% of the adverse events occurred within 6 months, and the median duration (IQR) was 68 days. Most adverse events (n=477, 75.11%) were related to the treatment of niraparib. Importantly, niraparib exposure was associated with a significant increase in haemorrhages-related adverse events (ROR (95% CI), 1.13(1.03,1.23), PRR (χ2), 1.12(7.32), IC (IC 025), 0.17(0.15). In addition, petechiae, gingival bleeding, bloody urine, as well as rectal haemorrhage should be monitored when using niraparib.ConclusionRecognition and management of PARPi-haemorrhages-related adverse events is of significance to clinical practice. In this study, we provided a safety signal that haemorrhage-related adverse events should be monitored for when using niraparib. However, larger and more robust post-market safety studies are needed to improve the quality of this evidence.

Xiao Zhen Zhang,1,* Mao Jian Chen,2,3,* Ping Ming Fan,4 Wei Jiang,3 Shi Xiong Liang1 1Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, Guangdong, People’s Republic of China; 3Department of Respiratory Oncology, Guangxi Medical University Cancer Hospital, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China; 4Department of Breast-Thoracic Tumor Surgery, The First Affiliated Hospital of Hainan Medical University, Haikou, 570102, Hainan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shi Xiong Liang; Wei Jiang, Email shixliang@vip.sina.com; weicy2016@163.comBackground: B-cell translocation gene 2 (BTG2) has been revealed to be involved in the occurrence and development of multiple cancers. However, the role of BTG2 in lung adenocarcinoma (LUAD) is still ambiguous. Thus, this study aims to investigate the prognostic value of BTG2 and its correlation with immune infiltration in LUAD.Methods: The expression of BTG2 in LUAD was analyzed using the TIMER and UALCAN databases. The correlations between BTG2 expression and clinicopathological factors were investigated using the UALCAN databases. The Kaplan–Meier plotter, GEPIA, and TCGA databases were employed to assess the prognostic value of BTG2. The STRING database and Cytoscape software were used to construct an interaction network and mine co-expression genes. The TISIDB database was examined for a correlation between BTG2 and driver genes in LUAD. Enrichment analysis of co-expressed genes and BTG2 was performed using the LinkedOmics database. Finally, the correlations between BTG2 and immune infiltrates were investigated using the TIMER, GEO, and TISIDB database.Results: BTG2 was significantly downregulated in LUAD. The decreased expression of BTG2 in LUAD was significantly correlated with higher cancer stages and shorter duration of overall survival. The expressions of BTG2-related co-expression genes were associated with the prognosis in LUAD. The expression of BTG2 was closely associated with the mutations of TP53 and ROS1. Enrichment analysis revealed that BTG2 was significantly correlated with immune‐associated signaling pathways and function. In addition, the expression of BTG2 was found to be closely related to immune infiltration, multiple gene markers of immune cells, chemokines, and chemokine receptors.Conclusion: Our findings have effectively demonstrated that BTG2 expression was downregulated in LUAD, indicating poor prognosis. Closely relating to immune cell infiltration, BTG2 may be a promising immune-related biomarker and molecular target for patients with LUAD.Keywords: BTG2, lung adenocarcinoma, prognosis biomarker, gene mutation, immune infiltration

High glucose and its byproducts are important factors causing dysfunction of endothelial cells. Autophagy is critical for endothelial cellular homeostasis. However, the specific molecular mechanism of how autophagy is regulated in endothelial cells under high-glucose condition remains unknown. We aim to explore the role Sirt6 plays in regulating autophagy in AGE-treated endothelial cells and how this function is exerted via KLF4.Our results indicate that autophagy level increased in AGE-treated endothelial cells alongside with higher Sirt6 and KLF4 expression level. What's more, knock-in of Sirt6 by adenovirus led to augmented autophagy level while knockdown of Sirt6 led to the opposite. We also verified that Sirt6 affected KLF4 expression positively but KLF4 didn't influence Sirt6 expression level while knocking out of KLF4 impaired Sirt6-enhanced autophagy. Finally we found that STZ-induced diabetic mice showed more autophagosomes in endothelium and Sirt6 knockdown by adeno-associated virus reduced the number of autophagosomes. Knockdown of Sirt6 also caused impaired endothelium integrity but echocardiography indicated there were no significant functional differences.Our research reveals more about how Sirt6 regulates autophagy in endothelial cells under high-glucose simulated condition and provides further insight into the relationships between Sirt6 and KLF4.

To analyze the clinical characteristics of patients with pancreatic cancer (PC) and diabetes and to explore the impact of diabetes duration, weight loss, and hypoglycemic drugs on the tumor biological behavior of PC.This is a retrospective study on patients with PC and diabetes. Subjects were grouped according to the onset age of PC, distant metastasis, duration of diabetes, degree of weight loss (∆Wt), and type of hypoglycemic drugs. Logistic regression analysis was used to evaluate the association between diabetes duration, weight loss, hypoglycemic drugs, and early-onset PC, distant metastasis.Compared with late-onset PC, patients with early-onset PC had a higher proportion of new-onset DM (35 [79.5%] vs. 217 [46.9%], p 0.001), smoker, drinker, and more obvious weight loss (8.5 [3.8, 15] kg vs. 5 [0, 10] kg, p 0.001). Patients with remote metastasis had an earlier diagnosis age, heavier weight loss, lower body mass index, and were more likely to be smokers but had cancer less likely to be localized in the head of pancreas. Regression analysis showed that new-onset diabetes and weight loss were independently correlated to early-onset PC: odds ratio (OR) = 3.38 (95% CI 1.36-8.4, p = 0.09; OR = 1.56 (95% CI 1.16-2.1), p = 0.003, respectively. In contrast, long-term diabetes, and heavy weight loss were independently associated with remote metastasis: OR = 3.38 (95% CI 1.36-8.4, p = 0.09; OR = 1.56 (95% CI 1.16-2.1), p = 0.003, respectively.New-onset diabetes and weight loss were common presentation and risk factors of early-onset PC, which required more attention. Long-term diabetes and heavy weight loss were risk factors contributing to distant metastases, indicating potential risk factors contributing to the adverse prognosis of patients with PC.目的: 分析胰腺癌(PC)合并糖尿病患者的临床特点, 探讨糖尿病病程、体重减轻及降糖药物对PC肿瘤生物学行为的影响。 方法: 对PC合并糖尿病患者进行回顾性研究。受试者根据PC的发病年龄、远处转移、糖尿病病程、体重减轻程度(∆Wt)和降糖药物的类型进行分组。采用Logistic回归分析评估糖尿病病程、体重减轻、降糖药物与早发性PC、远处转移之间的关系。 结果: 与晚发PC相比, 早发PC患者新发DM比例更高(35[79.5%]vs 217[46.9%], p0.001), 吸烟、饮酒和体重减轻更明显(8.5[3.8, 15]kg vs 5[0, 10]kg, p0.001)。远处转移的患者诊断年龄较早, 体重减轻较大, 体重指数较低, 且更有可能是吸烟者, 但癌症不太可能发生在胰头。回归分析显示, 新发糖尿病和体重减轻与早发PC独立相关:分别为优势比(OR)=3.38(95%置信区间(CI) 1.36~8.4, P=0.09), OR=1.56(95%CI 1.16~2.1), P=0.003。相反, 长期糖尿病和严重的体重减轻与远处转移独立相关:分别为OR=3.38(95%CI 1.36-8.4, p=0.09, OR=1.56(95%CI 1.16-2.1), p=0.003)。 结论: 新发糖尿病和体重减轻是早发性PC的常见表现和危险因素, 应引起更多重视。长期糖尿病和体重减轻是导致远处转移的危险因素, 这表明潜在的危险因素导致了PC患者的不良预后。.

Background Experimental and epidemiological studies have indicated an association between diabetes exposure and an increased risk of liver cancer due to nonalcoholic steatohepatitis (NASH). However, to date, no systematic study has specifically investigated the burden of NASH-related liver cancer due to exposure to high fasting plasma glucose (HFPG) levels worldwide. Methods The number and rate of deaths and disability-adjusted life years (DALYs) from HFPG-induced NASH-related liver cancer were estimated based on the results of the 2019 Global Burden of Disease Study. The estimated annual percentage changes (EAPCs) for age-standardized death or DALYs rates were calculated using a generalized linear model with a Gaussian distribution to quantify the temporal trends in the global burden of NASH-related liver cancer attributable to HFPG. The strength and direction of the association between the sociodemographic index (SDI) and death or DALY rate were measured using Spearman’s rank-order correlation. Results Globally, approximately 7.59% of all DALY and 8.76% of all mortalities of NASH-related liver cancer in 2019 were due to HFPG. The age-standardized death and DALY rates of NASH-related liver cancer attributable to HFPG increased from 1990 to 2019. The corresponding EAPCs were 0.69 (95% UI 0.48–0.89), and 0.30 (95% UI 0.05–0.56), respectively. This increasing pattern was most obvious in the high- and low-SDI regions. The age-standardized mortality and DALYs rate of NASH-related liver cancer attributable to HFPG varies considerably worldwide, with the middle SDI region having the highest death and DALY rates in 2019 (DALY 0.96 [95% UI 0.23–2.18]; death 0.05 [95% UI 0.01–0.11]). Conclusion The burden of NASH-related liver cancer attributable to HFPG has increased over the past three decades, particularly in regions with high and low SDI.

Homocysteine (Hcy) is an intermediate amino acid formed during the conversion from methionine to cysteine. When the fasting plasma Hcy level is higher than 15 μmol/L, it is considered as hyperhomocysteinemia (HHcy). The vascular endothelium is an important barrier to vascular homeostasis, and its impairment is the initiation of atherosclerosis (AS). HHcy is an important risk factor for AS, which can promote the development of AS and the occurrence of cardiovascular events, and Hcy damage to the endothelium is considered to play a very important role. However, the mechanism by which Hcy damages the endothelium is still not fully understood. This review summarizes the mechanism of Hcy-induced endothelial injury and the treatment methods to alleviate the Hcy induced endothelial dysfunction, in order to provide new thoughts for the diagnosis and treatment of Hcy-induced endothelial injury and subsequent AS-related diseases.

This article discusses the fuel economy optimization of a parallel hydraulic hybrid mining truck (HHMT). Considering the influences of various coupled factors, such as the transmission system, energy management strategy, and driving conditions, on the optimization goal, this article proposes the use of a double-layer optimization strategy with a collaborative optimization algorithm that combines particle swarm optimization (PSO) and a dynamic programming algorithm (DP) to eliminate the mutual effects of these coupled factors. A two-layer optimization model is developed, with powertrain parameters and energy management parameters as the optimization variables and the average fuel consumption under various driving conditions as the target. This model combines a variety of driving conditions to perform global optimization of the transmission system parameters while calculating the optimal energy distribution and analyzing the influences of various factors on the optimization goal. To achieve real-time and reliable control of energy management, the optimal energy management strategy rules obtained under various driving conditions are integrated and extracted, and an improved extraction method compared with the traditional extraction method is proposed. Finally, a rule-based energy management strategy is established. The strategy and optimized transmission system parameters are simulated and verified using a MATLAB and AMESIM joint simulation platform, and the effect of the rule strategy is evaluated. The obtained fuel consumption results are close to the results obtained by PSO-DP optimization, and the strategy is robust. The experiment verifies the effectiveness, feasibility and reliability of the optimization scheme, and extraction rule control strategy.

BackgroundPhysical activity (PA) has been associated with decreased incidence of diabetes. However, few studies have evaluated the influence of occupational and domestic PA on the risk of diabetes with a long-term follow-up. We aimed to examine the association between occupational and domestic PA and the risk of diabetes in a long-term prospective cohort of Chinese adults.MethodsA total of 10,343 adults who were followed up in the China Health and Nutrition Survey from 1997 to 2015 were included in our analysis. Occupational and domestical PA were collected with detailed seven-day data and were converted into metabolic equivalents values. Total PA included occupational, domestic, transportation, and leisure time PA. Diabetes cases were identified by self-reported doctor/health professional diagnosis of diabetes, fasting blood glucose ≥7.0 mmol/L, and glycosylated hemoglobin (HbA1c) ≥6.5%. Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI).ResultsDuring up to 18 years of follow-up (median 10 years), there were 575 diabetes cases documented. Occupational PA accounted for the majority of total PA (68%) in Chinese population, followed by domestic PA (25%). With adjustments for possible covariates, the highest quartiles of total PA (HR, 0.728 [95% CI, 0.570–0.929]) and occupational PA (HR, 0.765 [95% CI, 0.596–0.982]) were significantly associated with a lower risk of diabetes compared with lowest quartiles. The association between domestic PA and the risk of diabetes was insignificant (P >0.05).ConclusionHigher levels of occupational PA were associated with a decreased risk of diabetes risk in the Chinese population. Domestic PA was not associated with the incidence of diabetes.

Context The hemoglobin glycation index (HGI) is correlated with metabolic diseases and inflammation. Whether the HGI is associated with the aging process and how inflammation and oxidative stress affect the relationship remain unclear. Objective We aimed to analyze links between the HGI and aging biomarkers, and to explore a potential role of inflammation and oxidative stress in the correlations. Methods A cross-sectional study of 434 subjects with different glucose intolerances in a rural community was enrolled. The HGI was calculated as the difference between the measured and predicted hemoglobin A1c (HbA1c). The population was categorized into tertiles of the HGI. Telomere length (LTL) and mitochondrial DNA copy number (mtDNAcn) determined by polymerase chain reaction assay. Tumor necrosis factor (TNF) α and interleukin (IL) 6, 8-oxo-2′-deoxyguanosine (8-oxo-dG), superoxide dismutase (SOD) activities, and glutathione reductase (GR) were measured. Results Participants in the high HGI group were older and reported a shorter LTL, higher levels of TNFα, SOD activities, and HbA1c. Correlation analyses demonstrated that HGI was correlated with LTL (r = –0.25, P < .001) and TNFα (r = 0.19, P < .001) regardless of HbA1c levels. No relationship was found between HGI and mtDNAcn. HGI (β = –0.238, 95% CI –0.430, –0.046, P = .015) and TNFα (β = –0.02, 95% CI –0.030, –0.014, P < .001) were proved to be correlated with LTL independently, using multiple linear regression analysis. Ordinal logistic regression models showed that compared with subjects the high HGI group, the possibilities of a higher-level LTL was 5.29-fold in the low HGI group (OR 5.29, 95% CI (2.45, 11.41), P < .001), 2.41-fold in the moderate HGI group (OR 2.41, 95% CI 1.35, 4.30, P = .003) after controlling for confounding variables. Mediation analyses indicated that TNFα accounted for 30.39% of the effects of the HGI on LTL. Conclusion HGI was negatively related to telomere attrition, independent of HbA1c. TNFα acted as a mediator of the relationship between HGI and LTL.

IntroductionDipeptidyl peptidase-4 (DPP-4) inhibitors have various cellular effects that are associated with vascular protection. Here, we examined whether vildagliptin protected endothelial function in diabetic rats and explored the involved mechanism.Material and methodsExperimental diabetic rats were obtained by feeding a high-fat diet and administering an intraperitoneal injection of streptozotocin. Rats were randomly divided into four groups: controls (CON), diabetes (DM), diabetes + low dose of vildagliptin (Lvil, 10 mg/kg/day), and diabetes + high dose of vildagliptin (Hvil, 20 mg/kg/day). The metabolic parameters, endothelial function, and whole miRNA expression were measured.ResultsAfter a 12-week treatment, vildagliptin-treated rats showed a significant reduction in blood glucose and blood lipid levels. Moreover, vildagliptin recovered aortic endothelial function in diabetic rats. We identified 31 miRNAs that were differentially expressed in the Hvil group compared with the diabetic group. Importantly, through miRNA target biological function and pathway analysis, we found that vildagliptin activated miR-190-5p to inhibit Ccl2 expression and inhibited miR-134-5p and miR-375-3p to increase Bdnf and Pdk1 expression in the aorta.ConclusionsOur present study indicates that vildagliptin can recover endothelial function in diabetic rats. Anti-inflammatory and anti-apoptosis mechanisms and endothelial moderation may be the intervention targets of vildagliptin to protect the cardiovascular system through miRNA regulation.

The injection of a third harmonic current can improve the electromagnetic torque output of the five-phase permanent magnet synchronous motor. In this paper, constant copper consumption and constant maximum current are used as constraints, and the influence of the ratio between the third harmonic current and the fundamental current on the electromagnetic torque under the two constraints is analyzed. The electromagnetic torque is the largest when the third harmonic current reference value is equal to the fundamental current reference value of ψf3/ψf times under the premise of the constant copper loss. On the premise that the maximum current is constant, the electromagnetic torque is the largest when the third harmonic current reference value is equal to the fundamental current reference value of kw/(6kw-kw3/3) times. On this basis, according to the vector amplitude, phase and action time, the changing trends of maximum voltage utilization rate with Vref3/Vref1 under three different kinds of methods are given. Finally, through the experimental platform, the control effects of the three kinds of SVPWM are compared under two constraint conditions.

AimsGlucokinase–maturity-onset diabetes of the young (GCK-MODY) is the most common monogenic diabetes in China. We have previously reported on the low levels of high-sensitivity C-reactive protein (hsCRP) in patients with GCK-MODY. In this study, we further explored the correlation between the serum lipid profiles and hsCRP levels of patients with different types of diabetes. We also proposed to determine the possible mechanism of macrovascular protection in GCK genetic variants.MethodsThe serum lipid profiles of the GCK-MODY group (n = 50) were compared with those of the hepatocyte nuclear factor-1 alpha (HNF1A)-MODY group (n = 19), the type 1 diabetes (T1D) group (n = 50), and the type 2 diabetes (T2D) group (n = 54). The associations between the lipid compositions and the hsCRP levels in each group were also explored.ResultsElevated levels of high-density lipoprotein cholesterol (HDL-C) were found in the GCK-MODY group (1.5 ± 0.27) compared with the T1D (1.2 ± 0.47, p p p p p p p > 0.05] compared with the patients in the GCK-MODY group, they had higher TG levels [1.01 (0.66–1.76), p p r = 0.352, p = 0.011) and the Ln(TG/HDL) ratio (r = 0.283, p = 0.047) only in individuals with GCK-MODY.ConclusionsIndividuals harboring GCK variants have the characteristics of protective lipid profiles manifested as a higher level of HDL-C and a lower level of LDL-C compared with type 1 and 2 diabetes milletus (T1DM and T2DM, respectively) patients. In addition, lower ratios of TG/HDL were found to be associated with the inhibition of secretion of hsCRP, even when adjusted for the HbA1c levels in patients with GCK-MODY. It is suggested that the protective effect of macrovascular complications in GCK-MODY patients might partly be due to their unique lipid profiles associated with the suppression of inflammation.

BackgroundBody mass index (BMI) is a common indicator in clinical practice, but it is not sufficient to predict insulin resistance (IR). Other anthropometric methods supplement BMI in the assessment of body composition, which can be predicted more accurately. This cross-sectional study aimed to evaluate the association between mid-upper arm circumference (MUAC), triceps skinfold (TSF) thickness, mid-arm muscle circumference (MAMC) and IR in Chinese adults.MethodsThis cross-sectional study analyzed data from the 2009 China Health and Nutrition Survey database. The study population was divided into four groups according to the MUAC quartiles, and the homeostasis mode assessment was used to evaluate the degree of IR. Logistic regression analysis was performed to calculate odds ratios (ORs) with 95% confidence intervals (CIs), with adjustments for multiple covariates. Subgroup analyses stratified by age, sex, BMI, waist circumference (WC), smoking status, and alcohol consumption were performed.ResultsIn total, 8,070 participants were included in the analysis. As MUAC increased, BMI, TSF thickness, MAMC, and the proportion of IR tended to increase. However, we found that there was a significant negative association between MUAC and MAMC and IR in the logistic regression analysis, independent of BMI and WC, the ORs for the highest quartiles compared with the lowest quartiles were 0.662 (95%CI: 0.540-0.811) and 0.723 (95%CI: 0.609-0.860), respectively. There was no significant association was observed between the TSF thickness and IR (OR=1.035 [95%CI: 0.870-1.231]). The inverse associations were more pronounced among participants with lower BMI and WC. No significant age-specific differences were observed (P-heterogeneity > 0.05).ConclusionsAfter adjusting for BMI and WC, MUAC was negatively associated with IR in Chinese adults, and the association between MUAC and IR was derived from arm muscle instead of subcutaneous fat. MUAC could be an additional predictor of IR besides BMI and WC in clinical practice.

Diabetic nephropathy (DN) is a severe diabetic complication of the kidney and is the main cause of end-stage kidney disease worldwide. Cordyceps sinensis (C. sinensis) is not only a traditional Chinese medicine (TCM) but also a healthy food. In China, C. sinensis has been widely used to treat various kidney diseases. Bailing Capsule, which active ingredient is C. sinensis, is approved to treat kidney disease, respiratory disease, and immune disease. However, its underlying mechanism in DN remains unclear. The purpose of the present study was to investigate the underlying mechanism of Bailing Capsule on kidney in diabetic rats. The DN model was established by streptozotocin (STZ) injection. Low and high doses of Bailing Capsule were orally administrated for 12 weeks after diabetes induction. Renal function was evaluated by serum creatinine, blood urea nitrogen, 24-h urinary protein, and urinary albumin. Mesangial matrix expansion and renal fibrosis were measured using histopathology staining. We found that the disorder of renal function and pathology in DN rats was significantly modified by Bailing Capsule treatment. Consistently, Bailing Capsule markedly alleviated DN rat glomerulosclerosis, tubulointerstitial injury and renal fibrosis as shown by pathological staining. Moreover, Bailing Capsule significantly reduced the kidney triglyceride content and renal lipid droplet formation in DN rats. The renal transcriptome revealed that Bailing Capsule-treated kidneys had 498 upregulated genes and 448 downregulated genes. These differentially expressed genes were enriched in the peroxisome proliferator activated receptor (PPAR) pathway and fatty acid metabolism function ontology. mRNA and protein expression analyses revealed substantial enhancement of the lipolysis pathway and inhibition of lipogenesis in Bailing Capsule-treated rat kidneys compared to DN rats. Bailing Capsule activated the expression of PPARα, ACOX1 (acyl-CoA oxidase 1), and SCD (stearoyl-CoA desaturase) in diabetic nephropathy while suppressing the expression of FASN (fatty acid synthase). In conclusion, Bailing Capsule could attenuate renal triglyceride accumulation in diabetic rats by moderating PPARα pathway.

ObjectivesThe aim of this study is to explore the daily insulin dose and the percentage change in preprandial and basal insulin dosage of women with different types of hyperglycemia in pregnancy (HIP) during the whole gestation and postpartum period.MethodsA total of 121 subjects with HIP requiring insulin therapy were enrolled from a prospective cohort consisted of 436 pregnant women with hyperglycemia. The subjects were divided into three groups: Group 1 [type 1 diabetes mellitus (T1DM) and maturity onset diabetes of the young (MODY)], Group 2 [type 1 diabetes mellitus (T2DM)], and Group 3 [gestation diabetes mellitus (GDM)]. The primary study measurements included daily dose and percentage of different types of exogenous insulin requirements across gestation in different groups.ResultsInsulin total daily dosage of Group 1 was highest among the three groups and increased significantly from the first to the second/third trimester. Percentage of preprandial insulin increased from 53.8% (46.7, 60.0) and 54.5% (42.3, 62.9) in the first trimester to 63.6% (54.9, 75.0) and 67.2% (51.8, 73.7) in the second/third trimester in Group 1 and Group 2. All subjects with T1DM and 18.6% of subjects with T2DM still required insulin administration after delivery, with a 26.9% (19.0, 46.0) and 36.7% (26.9, 52.6) decrease in total insulin dose, respectively, whereas subjects with GDM and MODY weaned off insulin completely.ConclusionThe insulin requirements for pregnancy complicated with T1DM and MODY were higher than those for T2DM and GDM. In the subjects with PGDM, the insulin requirement and percentage of preprandial insulin increased gradually from early to mid- and late pregnancy.

Objective This study aimed to systematically evaluate the association between triceps skinfold (TSF) thickness (which indicates subcutaneous fat) mid-arm muscle circumference (MAMC; which reflects muscle mass), mid-upper arm circumference (MUAC), and all-cause mortality. Methods A total of 17,717 adults from the China Health and Nutrition Survey (1993-2015) were included. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality. The joint effect of TSF thickness and MAMC was examined, and planned subgroup analyses were performed. Results The highest quartiles of TSF thickness, MAMC, and MUAC were significantly associated with low all-cause mortality, independent of BMI (TSF thickness: HR = 0.704 [95% CI: 0.575-0.862]; MAMC: HR = 0.729 [95% CI: 0.607-0.876]; MUAC: HR = 0.713 [95% CI: 0.583-0.872]). A 1-SD increase showed comparable risk reductions for TSF thickness and MAMC (14.6% and 14.0%), with 16.1% risk reductions in MUAC. There were positive additive interactions between TSF thickness and MAMC. The inverse association existed in young, middle-aged, and elderly participants (P-heterogeneity > 0.05). Conclusions Mid-arm muscle and subcutaneous fat were inversely associated with all-cause mortality, independent of BMI, beyond the elderly population. Mid-arm muscle and subcutaneous fat made comparable contributions to and had positive joint effects on all-cause mortality.

Microplastics (MPs) in natural environments undergo complex aging processes, changing their interactions with coexisting antibiotics, and posing unpredictable ecological risks. However, the joint toxicity of aged MPs (aMPs) and antibiotics to bacteria, especially at the molecular level, is unclear. In this study, non-thermal plasma technology was used to simultaneously simulate various radical oxidation and physical reactions that occur naturally in the environment, breaking the limitation of simple aging process in laboratory aging technologies. After aging, we investigated the altered properties of aMPs, their interactions with ciprofloxacin (CIP), and the molecular responses of E. coli exposed to pristine MPs (13.5 mg/L), aMPs (13.5 mg/L), and CIP (2 μg/L) individually or simultaneously. aMPs bound far more CIP to their surfaces than pristine MPs, especially in freshwater ecosystems. Notably, the growth of E. coli exposed to aMPs alone was inhibited, whereas pristine MPs exposure didn't affect the growth of E. coli. Moreover, the most differentially expressed genes in E. coli were induced by the coexposure of aMPs and CIP. Although E. coli depended on chemotaxis to improve its flagellar rotation and escaped the stress of pollutants, the coexposure of aMPs and CIP still caused cell membrane damage, oxidative stress, obstruction of DNA replication, and osmotic imbalance in E. coli. This study filled the knowledge gap between the toxicity of aMPs and pristine MPs coexisting with antibiotics at the transcription level, helping in the accurate assessment of the potential risks of MPs to the environment.

PurposeAn end-of-fast insulin level ≥ 3 µIU/ml, C-peptide level ≥ 0.6 ng/ml, and proinsulin level ≥ 5 pmol/l with end-of-fast glucose level ≤ 3.0 mmol/l have been established as the criteria for endogenous hyperinsulinemic hypoglycemia. However, all these criteria have been proposed based on patients in Western populations. This study aimed to determine the optimal criteria using a large series of Chinese patients.MethodsThis retrospective study comprised 144 patients with surgically proven insulinoma and 40 controls who underwent a 72-h fasting test at the Peking Union Medical College Hospital(PUMCH) from 2000 to 2020. Receiver operating characteristic curves were used for analysis.ResultsIn this series of patients, the optimal diagnostic criteria for endogenous hyperinsulinemic hypoglycemia were insulin ≥ 5.5 μIU/ml, C-peptide ≥ 0.7 ng/ml, and proinsulin ≥ 12 pmol/l with end-of-fast glucose ≤ 2.8 mmol/l; the sensitivity and specificity were 99% and 100% for insulin, 100% and 100% for C-peptide, and 93% and 100% for proinsulin, respectively. The diagnostic efficacy of the criteria based on Western populations was then tested. The sensitivity and specificity of end-of-fast insulin ≥ 3 μIU/ml, C-peptide ≥ 0.6 ng/ml, and proinsulin ≥ 5 pmol/l with end-of-fast glucose ≤ 3.0 mmol/l were 100% and 83%, 100% and 80%, and 97% and 78%, respectively.ConclusionsNew and optimized diagnostic criteria for endogenous hyperinsulinemic hypoglycemia in Chinese populations have been proposed, and these criteria yield satisfactory accuracy.

Insulin and liraglutide have been demonstrated to control blood glucose and exert neuroprotective effects. However, the impact of liraglutide or insulin alone or in combination on brain pathology in type 1 diabetes mellitus (T1DM) and their underlying mechanisms are unclear. In the present study, diabetes mellitus (DM) was induced via intraperitoneal injection of streptozotocin in mice and subsequently mice were treated with insulin, liraglutide, a combination of the two drugs or saline. Changes in body weight and blood glucose were assessed weekly. The pathological changes in the brain tissue and the apoptosis of neurons were assessed using HE staining and TUNEL staining. The mRNA and protein expression levels of apoptosis-related proteins were detected using reverse transcription-quantitative PCR (RT-qPCR) and western blotting, respectively. Moreover, Ki67 protein expression was analyzed using immunohistochemistry and the mRNA and protein expression levels of Wnt/β-catenin signaling pathway-related proteins were examined using RT-qPCR and western blotting, respectively. The results of the present study suggested that DM mice developed hyperglycemia and weight loss and also exhibited significantly increased neural cell apoptosis and significantly reduced numbers of Ki67-positive cells. Liraglutide significantly decreased blood glucose levels in DM mice, whereas both insulin and the combination of the two drugs failed to control blood glucose well. Insulin, liraglutide and their combination also failed to control body weight well, but significantly attenuated brain pathological changes and activation of the pro-apoptotic proteins Caspase-3 and Bax, which may have resulted in the significant increase in the expression levels of Wnt/β-catenin signaling pathway-associated molecules such as Wnt3a and S9-pGSK-3β. Liraglutide also promoted the protein expression of the neurogenesis marker of Ki67 and the antiapoptotic factor Bcl-2. These results suggested that insulin and liraglutide may improve brain damage via upregulation of the Wnt/β-catenin signaling pathway and could be of therapeutic relevance for improvement of cognitive impairment in patients with DM.

Industrial enterprises are one of the main causes of air pollution in eastern China. How to monitor them efficiently is directly related to the result of air pollution control in China. However, the monitoring of enterprises now mainly relies on the ground online monitoring technology, and only for some large enterprises, some small and medium-sized enterprises will be missed which also contribute a lot to the air pollution. Based on the satellite remote sensing technology, this paper explores an operational method of monitoring the whole coverage of pollution enterprises from macro to micro, focusing on monitoring the regional pollution status results of the pollution enterprises and identifying the key monitoring objects including the small and medium-sized ones. Based on the air pollutants retrieval results of satellite remote sensing, a remote sensing high-occurrence index model of air pollution is built. By using the pollution focused grid extract method and high-resolution satellite image identification technology, the key monitoring objects of pollution enterprises can be extracted. The result of the application cases in eastern China and the typical districts show that the remote sensing high-occurrence index model can clearly reflect the comprehensive pollution status by the pollution enterprises; validation of the identification rate of the small and middle-sized enterprises can reach over 77%, which has made a great progress compared with the inspection only relying on the supervision personnel in the absence of specific objects. The method proposed in this paper can greatly improve the scientific and accurate supervision level of environmental management.

Aim and Objective: Myocardial infarction, cerebral infarction, and other diseases caused by vascular obstruction have always jeopardized human life and health. Several reports indicate that Rhei Radix et Rhizoma has a good clinical effect in the prevention and treatment of cardiovascular diseases. Owing to the complexity of herbal medicine, the pharmacodynamic mechanism of Rhei Radix et Rhizoma is still unclear. The objectives of this study were to explore the two-way adjustment mechanism of Rhei Radix et Rhizoma and provide a new solution for the prevention and treatment of cardiovascular disease. Materials and Methods: This study used data mining, reverse pharmacophore matching, network construction, GO and KEGG Analysis, and molecular docking to investigate the two-way adjustment mechanism of Rhei Radix et Rhizoma. The methods used were based on systems pharmacology and big data analysis technology. Results: The results suggest that Rhei Radix et Rhizoma uses a two-way adjustment of activating blood circulation, as well as blood coagulation in the prevention and treatment of cardiovascular diseases. The components involved in activating blood circulation are mainly anthraquinone components. The corresponding targets are NOS2, NOS3, CALM1, and the corresponding pathways are calcium signaling pathway, VEGF signaling pathway, platelet activation, and the PI3K-Akt signaling pathway. For blood coagulation, the components are mainly tannin components; the corresponding targets are F2, F10, ELANE, and the corresponding pathways are the neuroactive ligand-receptor interaction, complement and coagulation cascades. Conclusion: This study indicated that Rhei Radix et Rhizoma exerts the two-way adjustment of activating blood circulation and blood coagulation in the prevention and treatment of cardiovascular diseases. It can make up for the side effects of the existing blood circulation drugs for cardiovascular disease, only activating blood circulation, and the uncontrollable large-area bleeding due to the long-term use of the drugs. This study provides a material basis for the development of new blood-activating drugs based on natural medicine.

Macrophages are a double-edged sword with potential cancer-promoting and anticancer effects. Controversy remains regarding the effect of macrophages, especially M1 macrophages, on tumor promotion and suppression. We aimed to investigate the role of M1 macrophages in the occurrence and progression of esophageal squamous cell carcinoma (ESCC). Analyzing the data in Gene Expression Omnibus database by the CIBERSORT algorithm found that M1 macrophages were one of the important components of many immune cells in ESCCs, and the increase in their number was obviously negatively correlated with tumor T staging. This result was verified by our experimental data: the density of CD68/HLA-DR double-stained M1 macrophages in ESCC tumor nest and tumor stroma was significantly higher than that in cancer-adjacent normal (CAN) tissues. The density of M1 macrophages in ESCC tumor nest was negatively correlated with the patient’s lymph node metastasis and clinical stage (P < 0.05), and the negative tendency was more obvious for M1 macrophages in ESCC tumor stroma (P < 0.001). Exposure to M1 macrophage-conditioned medium inhibited ESCC cell migration and invasion ability significantly (P < 0.05). Moreover, the increased M1 macrophage density in ESCC tumor stroma correlated positively with good prognosis of ESCC. M1 macrophages were involved in inhibiting ESCC cell migration and invasion, which could serve as a good prognostic factor in patients with ESCC.

Purpose High-sensitivity C-reactive protein (hs-CRP) has been shown as an important predictor of cardiovascular risk, and sleep duration is an important factor influencing health outcomes. However, the association between hs-CRP and sleep duration among Chinese adults remained unknown and controversial. We aimed to explore the associations between sleep duration and hs-CRP levels among Chinese adults, and the differences in sex and geographical regions. Methods This cross-sectional study was based on nationally representative Chinese samples from the 2009 China Health and Nutrition Survey, which employed multistage, random cluster designs. Habitual sleep duration was self-reported with short and long sleep duration defined as ≤6h and ≥9h per day, respectively. Participants were divided into 4 groups based on the categories of self-reported sleep duration (≤6h, 7h, 8h, ≥9h per day), excluding hs-CRP levels ≥10 mg/L. Subset samples were stratified by sex and geographical regions. Results A total of 8170 Chinese adults with a mean age of 50.0±14.9 years and 4369 (53.5%) men were included. Participants sleeping eight hours had the lowest hs-CRP levels. Long sleep duration (≥9h) was significantly associated with elevated hs-CRP levels after adjusting for multiple covariates in full samples (β=0.0356; 95% CI: 0.0050-0.0663; P=0.0228), but the associations of short sleep duration (≤ 6h) were limited to the unadjusted model. Long sleep duration was associated with elevated hs-CRP levels in women (β= 0.0512; 95% CI: 0.0097-0.0927; P=0.0155) and in the northern region of China (β=0.0699; 95% CI: 0.0210-0.1187; P=0.0051), but not in men or the southern region. Conclusion Long but not short sleep duration was positively associated with elevated hs-CRP levels, independent from traditional risk factors among Chinese adults, and sex and geographical differences were observed. Our findings imply that modifications of long sleep duration might be added to behavioral therapy to reduce cardiovascular risk in Chinese adults.

Protein arginine methyltransferase 5 (PRMT5) is an important type II arginine methyltransferase that can play roles in cancers in a highly tissue-specific manner, but its role in the carcinogenesis and metastasis of head and neck squamous cell carcinoma (HNSCC) remains unclear. Here, we detected PRMT5 expression in HNSCC tissues and performed series of in vivo and in vitro assays to investigate the function and mechanism of PRMT5 in HNSCC. We found that PRMT5 was overexpressed in dysplastic and cancer tissues, and associated with lymph node metastasis and worse patient survival. PRMT5 knockdown repressed the malignant phenotype of HNSCC cells in vitro and in vivo. PRMT5 specific inhibitor blocked the formation of precancerous lesion and HNSCC in 4NQO-induced tongue carcinogenesis model, prevented lymph node metastasis in tongue orthotopic xenograft model and inhibited cancer development in subcutaneous xenograft model and Patient-Derived tumor Xenograft (PDX) model. Mechanistically, PRMT5-catalyzed H3R2me2s promotes the enrichment of H3K4me3 in the Twist1 promoter region by recruiting WDR5, and subsequently activates the transcription of Twist1. The rescue experiments indicated that overexpressed Twist1 abrogated the inhibition of cell invasion induced by PRMT5 inhibitor. In summary, this study elucidates that PRMT5 inhibition could reduce H3K4me3-mediated Twist1 transcription and retard the carcinogenesis and metastasis of HNSCC.

ObjectiveThe adrenal glands of patients with 17-hydroxylase/17,20-lyase deficiency (17OHD) synthesize excessive 11-deoxycorticosterone(DOC) and progesterone, and produce less amount of sex steroid production. Mineralocorticoids and sex hormones play an important role in regulating glucose homeostasis. This study aimed to describe the glucose metabolism in 17OHD patients diagnosed at Peking Union Medical College Hospital (PUMCH).Design/methodsA total of 69 patients diagnosed with 17OHD after adolescence in PUMCH from 1995 to June in 2021. Among them 23 patients underwent a 3-hours oral glucose tolerance test (3hOGTT) after being diagnosed with 17OHD. Insulin response in patients with normal glucose tolerance (NGT) were further compared between the study two groups with different kalemia status. Another 19 patients were followed up to 30 years and older. All clinical data were obtained from the hospital information system of PUMCH.ResultsBaseline: (1) The average body mass index(BMI) of all patients at baseline was 20.3 ± 3.7kg/m2. Twenty-three patients underwent 3hOGTT, of whom three were diagnosed with diabetes mellitus, and one with impaired glucose tolerance (IGT). Positive correlation between the ratio of progesterone to upper limit of normal range (P times) and hyperglycaemia was exist(r=0.707, P=0.005). (2) In 19 NGT patients, the insulin concentrations at 0 minute, results of the homeostasis model assessment for β-cell function and insulin resistance were lower in the hypokalaemia group than in the normal kalemia group(7.0(5.8-13.2) vs 12.4(8.9-14.9) μIU/ml, P=0.017; 115.5(88.2-240.9) vs 253.1(177.2-305.8), P=0.048; 1.54(1.17-2.61) vs 2.47(1.91-2.98), P=0.022, respectively). Follow-up: Four patients had IGT, while seven patients had diabetes mellitus. Of the 19 patients,11 had hyperglycaemia. P times was significantly higher(7.6(5.0-11.0) vs 3.75(2.2-5.3), P=0.008) in hyperglycemia group than in the normal glucose group.ConclusionsAbnormal glucose metabolism was common in 17OHD patients, which was possibly associated with hypokalaemia and high progesterone levels. Routine monitoring on glucose metabolism in 17OHD patient should be conducted.

Although the biological effects of nanoplastics (100 nm in size) in aquatic environments have been increasingly investigated, almost all such studies have been performed at observed-effect concentrations (higher than 1 μg/mL). The use of observed-effect concentrations of nanoplastics can provide essential data for evaluating the potential risks, but how these results apply to the effects of concentrations of nanoplastics observed in the environment remains unclear. Here, we show that exposure to both positively and negatively charged nanoplastics at the observed-effect concentration (ranging from 0 to 50 μg/mL) can result in physiological changes of

Immunotherapy has developed rapidly and has gradually become one of the important methods for treatment of gastric cancer (GC). The research on tumor infiltrating immune cells (TIICs) and immune-related genes in the tumor microenvironment (TME) greatly encourages the development of immunotherapy. The devolution algorithm (CIBERSORT) was applied to infer the proportion of 22 TIICs based on gene expression profiles of GC tissues, which were downloaded from TCGA and GEO. TCGA was utilized to analyze the differential expression of immune-related genes, and explore the potential molecular functions of these genes. We have observed the enrichment of multiple TIICs in microenvironment of GC. Some of these cells were closely related to tumor mutational burden (TMB), microsatellite instability (MSI), Fuhrman grade, and TNM staging. Survival analysis showed that the infiltration level of CD8+T cells, activated CD4+memory T cells and M2 macrophages were significantly related to the prognosis of GC patients. The functional enrichment analysis of immune-related genes revealed that these genes were mainly associated with cytokine activation and response. Four significant modules were screened by PPI network and 20 key genes were screened from the modules. The expression levels of CALCR and PTH1R are strikingly related to the expression of immune checkpoint and the prognosis of GC patients. The type and number of TIICs in microenvironment of GC, as well as immune-related genes are closely related to tumor progression, and can be used as important indicators for patient prognosis assessment.

Antiestrogen therapy of breast cancer has been a “gold standard” of treatment of estrogen receptor (ER)-positive breast cancer for decades. Resistance to antiestrogen therapy may develop, however, a vulnerability in long-term estrogen deprived (LTED) breast cancer cells was discovered. LTED breast cancer cells may undergo estrogen-induced apoptosis within a week of treatment with estrogen in vitro. This phenomenon has been also validated in vivo and in the clinic. The molecular ER-mediated mechanism of action of estrogen-induced apoptosis was deciphered, however, the relationship between the structure of estrogenic ligands and the activity of the ER in LTED breast cancer cells remained a mystery until recently. In this review we provide an overview of the structure-activity relationship of various estrogens with different chemical structures and the modulation of estrogen-induced apoptosis in LTED breast cancer cells resistant to antihormone therapy. We provide analysis of evidence gathered over more than a decade of structure-activity relationship studies by our group on the role of the change in the conformation of the estrogen receptor and the biological activities of different classes of estrogens and the receptor as well in LTED breast cancer.

Background Oral squamous cell carcinoma (OSCC), the most common epithelial malignant neoplasm in the head and neck, characterizes with local infiltration and metastasis of lymph nodes. The five-year survival rate of OSCC remains low despite the advances in clinical methods. Thus, it is necessary to develop a new effective therapeutic scheme for OSCC. Our previous results showed that metformin and 4SC-202 synergistically promoted the intrinsic apoptosis of OSCC in vitro and in vivo, but the effects on invasion and migration remained unclear. Methods Human OSCC cell lines HSC6 and CAL33 were cultured with metformin (16 mM) or/and 4SC-202 (0.4 μM) for 72 h. STAT3 inhibitor S31-201 was applied at concentration of 60 μM for 48 h. Wound-healing assays and transwell assays were used to determine the invasion and migration ability of OSCC. qRT-PCR and Western blot were performed to detect mRNA levels and protein levels. Results Metformin or/and 4SC-202 suppressed the migration and invasion of OSCC cells. Importantly, the expression of TWIST1 was suppressed by metformin and 4SC-202, while the invasion and migration inhibitory effects of metformin and 4SC-202 were countered by the overexpression of TWIST1. In addition, the phosphorylation level of STAT3 decreased after the administration of metformin or/and 4SC-202. Furthermore, inhibition of STAT3 by S31-201 suppressed the expression of TWIST1 and led to a decline in migration and invasion of OSCC, while overexpression of TWIST1 attenuated these effects. Conclusion Metformin and 4SC-202 suppressed the invasion and migration of OSCC through inhibition of STAT3/TWIST1, and this scheme can serve as a novel therapeutic strategy for OSCC.

By analyzing iron status of 14 ADHR patients, we found that iron deficiency was an important trigger of ADHR. Correcting iron deficiency significantly improved patients’ symptoms. Meanwhile, patients’ serum phosphate showed positive correlations with iron metabolism parameters and hemoglobin-related parameters, suggesting the necessity of monitoring and correcting the iron status in ADHR. Autosomal dominant hypophosphatemic rickets (ADHR) is unique for its incomplete penetrance, variety of disease onsets, and waxing and waning phenotypes. Iron deficiency is a trigger of ADHR. This study aimed to clarify the role of iron deficiency in ADHR. Data of clinical manifestations and laboratory examinations were collected from patients among eight kindreds with ADHR. Multiple regression and Pearson’s correlation tests were performed to test the relationships of serum phosphate levels and other laboratory variables during the patients’ follow-ups. Among 23 ADHR patients with fibroblast growth factor 23 (FGF23) mutations, 14 patients presented with obvious symptoms. Ten patients had iron deficiency at the onset of ADHR, coinciding with menarche, menorrhagia, pregnancy, and chronic gastrointestinal bleeding. Two patients who did not have their iron status tested presented with symptoms after abortion and pregnancy in one patient each, which suggested that they also had iron deficiency at onset. Patients were treated with ferrous succinate tablets, vitamin C, and neutral phosphate and calcitriol. With correction of the iron status, the patients’ symptoms showed notable improvement, with increased serum phosphate levels. Two patients’ FGF23 levels also declined to the normal range. There were strong correlations between serum phosphate and serum iron levels (r = 0.7689, p < 0.0001), serum ferritin levels (r = 0.5312, p = 0.002), iron saturation (r = 0.7907, p < 0.0001), and transferrin saturation (r = 0.7875, p < 0.001). We also examined the relationships between serum phosphate levels and hemoglobin-related indices, which were significant (hemoglobin: r = 0.71, p < 0.0001; MCV: r = 0.7589, p < 0.0001; MCH: r = 0.8218, p < 0.0001; and MCHC: r = 0.7751, p < 0.0001). Longitudinal data of six patients’ follow-up also showed synchronous changes in serum phosphate with serum iron levels. Iron deficiency plays an important role in triggering ADHR. Monitoring and correcting the iron status are helpful for diagnosing and treating ADHR. Iron metabolism parameters and hemoglobin-related parameters are positively correlated with serum phosphate levels in patients with ADHR and iron deficiency, and these might serve as good indicators of prognosis of ADHR.

Purpose Evidence about bone microarchitecture in Asian type 1 diabetes (T1D) patients is lacking. We assessed the bone microarchitecture in T1D patients versus controls and compare the differences between juvenile-onset and adult-onset T1D patients. Methods This cross-sectional study recruited 32 Asian males with T1D and 32 age-, sex-, and body mass index (BMI)-matched controls. Dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT) for ultradistal nondominant radius and tibia were performed. The data were analyzed using Student’s t test and analysis of covariance. Results Among the patients, 15 had juvenile-onset T1D, with a median disease duration of 11 years, and 17 had adult-onset T1D, with a median disease duration of 7 years. At the radius, adult-onset and juvenile-onset T1D patients had lower total volumetric bone mineral density (vBMD), trabecular vBMD, trabecular bone volume fraction (BV/TV), and trabecular thickness (Tb.Th) (p p p Conclusions T1D patients were associated with compromised bone microarchitecture, adult-onset and juvenile-onset T1D patients demonstrated some differences in cortical and trabecular microarchitecture.

We present an alternative concept for omnidirectional bending of light and concentration of energy in an index-continuous structure, comprising two gradient-index SiOx (0≤x≤2) layers and a thermochromic VO2 layer. The concept helps to overcome the constraints of conventional optics that are nonadjustable and only functional at designed wavelengths. The advantages of both gradient-index and thermochromic materials are combined in this work to realize temperature-tuned omnidirectional concentration of energy. Using a double-coated ICS component of AIR/SiOx/SUB/SiOx/VO2 for light manipulation and application near the visible spectrum range, this concept was numerically and experimentally demonstrated. The incoming light under oblique incident angles (0°–80°) was bent effectively and concentrated regardless of polarization. Favorable results demonstrated that a notably high energy concentration efficiency Pe (1.93–2.52) was achieved by varying the ambient temperatures (25–75 °C). This concept is general and can be applied in a variety of elements in light energy-efficient devices.

As the strongest typhoon in 2015, the rapid intensification (RI) process of Typhoon Mujigae is simulated at the cloud-resolving scale by utilizing the Weather Research and Forecasting model, coupled with observed sea surface temperature (SST) and reduced SST as the control and sensitivity experiments, respectively. The spatiotemporal distribution characteristics of upper-tropospheric potential vorticity (PV) and its response to SST changes are analyzed simultaneously. The results show a significant upper-tropospheric PV anomaly 6 h before RI, which indicates the approaching RI of Typhoon Mujigae. Deep convection overlies the strong signals of upper-tropospheric PV anomalies. More insight into the PV budget analysis verifies that the diabatic heating effect and vertical advection terms associated with deep convection dominate the upper-tropospheric PV anomaly, inferring that deep convection plays a crucial role in the upper-tropospheric PV anomaly. As SST decreases, diabatic heating and vertical advection effects are weakened due to reduced deep convection; therefore, the PV anomaly in the model run is not stronger than that in the control run, and the RI process of Mujigae disappears. Therefore, from the viewpoint of upper and lower-level interactions, how SST impacts upper-tropospheric PV anomalies and their interactions with RI are clarified. Thus, in addition to SST, the upper-tropospheric PV anomaly might be a significant factor in differentiating between RI and non-RI tropical cyclones.

The interplays of cellular aging and oxidative stress (OS) markers form a complex network, which has been reported to be interrelated with numerous age-related and metabolic diseases, including metabolic syndrome (MS). However, given the multifactorial mechanisms of MS, several important confounders such as dietary factors and the reciprocal effect among these markers have not been considered and adjusted in previous investigations regarding the associations of cellular aging and OS markers with MS and its related metabolic abnormalities. To explicate this, we conducted a cross-sectional study among 533 Chinese adults. All the participants underwent a 75 g oral glucose tolerance test. Dietary data were collected via a 24-hour dietary recall and subsequently analyzed by a registered dietitian using nutrition calculation software. Clinical diagnosis of MS was made according to the revised National Cholesterol Education Program Adult Treatment Panel III criteria (2004) with waist circumference cutoff modified for an Asian population. The leukocyte telomere length, mitochondrial DNA copy number, 8-hydroxy-2-deoxyguanosine, superoxide dismutase (SOD) activity, and glutathione reductase were examined. SOD activity was significantly decreased in MS subjects (62.06±16.89 U/mL vs. 56.25±22.61 U/mL, P=0.001) and exhibited a descending trend across sequential increase of MS component number (P for trend=0.031). SOD activity is modestly correlated with glucose indicators and insulin sensitivity and β-cell function indices and was independently and negatively correlated with the level of triglyceride. An independent association between SOD activity and MS was observed after adjusting for metabolic indicators, dietary factors, cellular aging, and OS markers, as well as insulin sensitivity and β-cell function indices. However, the statistical significance of the association between SOD activity and MS was attenuated after adjusting for the Matsuda insulin sensitivity index (ISIM) and insulin secretion-sensitivity index-2 (ISSI-2), suggesting a possible mediating effect. Therefore, we conducted a mediation model analysis, which showed that decreased ISIM and ISSI-2 partially and synergistically mediated the contribution of decreased SOD activity to MS. In conclusion, decreased SOD activity is an independent predictor for increased risk of MS, and insulin resistance and β-cell dysfunction partially mediate the relationship between decreased SOD activity and MS.

Solanesol has antibacterial, anticancer, anti-inflammatory and antiulcer biological activities, and is a key intermediate in the synthesis of coenzyme Q10, vitamin K2, and the anticancer synergist N-solanesyl-N,N'-bis(3,4-dimethoxy-benzyl)ethylenediamine (SDB) and other ubiquinone drugs. Due to its unique chemical structure, the chemical synthesis of solanesol is difficult, so solanesol is currently mainly isolated from solanaceous plants. Tobacco (Nicotiana tabacum) has the highest content of solanesol compared to other solanaceous plants. Currently, the research on the extraction of solanesol from tobacco focuses on its extraction and purification. This article reviews the extraction methods, saponification, separation and purification methods of solanesol, as well as the research progress on tobacco solanesol, in China and abroad in recent years. Studies show that the organic solvent extraction method is time-consuming and has a low extraction rate. Modern technology- assisted extraction methods, such as ultrasound-assisted extraction, microwave-assisted extraction, and supercritical carbon dioxide (CO2) extraction not only can improve the extraction rate but also can effectively shorten the extraction time. The separation and purification of solanesol from the extracting solution are critical steps to meet the purity requirements of synthetic drugs, and are also key in limiting the large-scale industrial production of high-purity solanesol. Molecular Imprinting Technology (MIT) has the advantages of small investment, simple operation and ease of large scale production compared to chromatographic methods. Solanesol separated by MIT can meet the requirements for synthesizing coenzyme Q10. Nowadays, the synthesis of molecularly-imprinted solanesol polymers with better adsorption efficiency is one of the important directions in the future research of solanesol purification.

Although the fate of nanoplastics (

BACKGROUND Heat-clearing and detoxifying herbs (HDHs) play an important role in the prevention and treatment of coronavirus infection. However, their mechanism of action needs further study. This study aimed to explore the anti-coronavirus basis and mechanism of HDHs. MATERIAL AND METHODS Database mining was performed on 7 HDHs. Core ingredients and targets were screened according to ADME rules combined with Neighborhood, Co-occurrence, Co-expression, and other algorithms. GO enrichment and KEGG pathway analyses were performed using the R language. Finally, high-throughput molecular docking was used for verification. RESULTS HDHs mainly acts on NOS3, EGFR, IL-6, MAPK8, PTGS2, MAPK14, NFKB1, and CASP3 through quercetin, luteolin, wogonin, indirubin alkaloids, ß-sitosterol, and isolariciresinol. These targets are mainly involved in the regulation of biological processes such as inflammation, activation of MAPK activity, and positive regulation of NF-kappaB transcription factor activity. Pathway analysis further revealed that the pathways regulated by these targets mainly include: signaling pathways related to viral and bacterial infections such as tuberculosis, influenza A, Ras signaling pathways; inflammation-related pathways such as the TLR, TNF, MAPK, and HIF-1 signaling pathways; and immune-related pathways such as NOD receptor signaling pathways. These pathways play a synergistic role in inhibiting lung inflammation and regulating immunity and antiviral activity. CONCLUSIONS HDHs play a role in the treatment of coronavirus infection by regulating the body's immunity, fighting inflammation, and antiviral activities, suggesting a molecular basis and new strategies for the treatment of COVID-19 and a foundation for the screening of new antiviral drugs.

Background & Aims: Chronic hepatitis B (CHB) can cause liver fibrosis and lead to cirrhosis even cancer, antiviral therapy can reverse liver fibrosis with limited effect, thus we aimed to evaluate the effect of An-Luo-Hua-Xian pill (ALHX) on fibrosis regression in CHB patients treated with ETV.Methods: Treatment naïve patients with CHB from Oct 1st, 2013 to Dec 31st, 2020 were randomly treated with ETV alone or combined with ALHX (ETV+ALHX). Patients’ demographic, laboratory and liver histology data before and after 78 weeks of treatment were collected. Ishak fibrosis score (F) was used and fibrosis regression means F decreased ≥1 after treatment.Results: In total, 394 patients with a second liver biopsy after treatment were included in per-protocol population: 132 patients in ETV group and 262 patients in ETV+ALHX group. After 78 weeks of treatment, the fibrosis regression rate in the ETV+ALHX group were significantly higher than ETV group in baseline F≥3 patients: 124/211 (58.8%) verse 45/98 (45.9%), p=0.035. The degradation rate of liver stiffness measurement (LSM) is also consistent with it: 154/262 (73.0%) in ETV+ALHX group and 60/132 (61.2%) in ETV group, p=0.037. Logistic regression analysis showed that combined with ALHX was related to fibrosis regression (OR=1.94, p=0.018), and family history of hepatocellular carcinoma was on the contrary (OR=0.41, p=0.031).Conclusions: ETV combined with ALHX can significantly increase liver fibrosis regression in CHB patients.

One-size-fits-all approach is common in climate-sensitive urban design due to neglecting spatial heterogeneities in urban form and urban climate. This study explores a spatially-varied climate-sensitive urban design based on the Guangdong-Hong Kong-Macau Greater Bay Area (GBA). Three thermal indices, the Wet Bulb Globe Temperature (WBGT), the Apparent Temperature (AT), and the Universal Thermal Climate Index (UTCI) are used to assess the outdoor thermal environments. The local climate zone (LCZ) classification system is used to map urban form including built and land-cover types. Moreover, incorporating spatial effects, geographically weighted regression (GWR) models are used to account for spatially-varied thermal variations due to urban form changes. Our findings indicate that the large low-rise type (LCZ 8) needs more attention in built-up planning for thermal mitigation, and urban low plants type (LCZ D) should be a more effective nature-based climate mitigation strategy compared with the water bodies (LCZ G). The GWR results show a stronger consistency between UTCI and LCZ 8 and LCZ D, compared with WBGT and AT. UTCI is thus suggested for application in future urban climate studies. More importantly, the spatially-varied relationship between UTCI and urban form specifies the strategies and appropriate locations for thermal mitigation in climate-sensitive urban design.

Additional file 3: Table S3. Genotype distribution of SNPs significantly related to gastric cancer risk.