Examining the Effects of PrEP Use on Sexual Behaviors and Sexually Transmitted Infections Among Chinese Men who have Sex with Men: A Cross-Sectional Study.

Men who have sex with men (MSM) is a high-risk population for HIV and sexually transmitted infections (STIs). Pre-exposure prophylaxis (PrEP) is effective in HIV prevention. This study aims to examine the differences in sexual behaviors, STI prevalence and HIV/STI testing across subgroups of MSM with various PrEP use. Data were collected via a cross-sectional survey in an MSM community in Xi'an, Shaanxi, from 2022.01 to 2022.09. Participants were categorized as 'PrEP-naïve and unwilling to use', 'PrEP-naïve but willing to use', and 'current or former PrEP users'. Shannon index was used to assess sexual act diversity and multivariate logistic regression analyzed factors associated with PrEP use. Of the 1,131 MSM participants, 23.52% were PrEP-naïve and unwilling, 64.98% were PrEP-naïve but willing, and 11.49% were current or former PrEP users. The PrEP-naïve but willing group had the highest recent STI testing rates at 73.06% and showed greater sexual act diversity (Shannon index 1.61). This group also had the highest syphilis rates (7.49% vs. 6.47% and2.54%, p < 0.01). Younger age (18-30: OR = 0.39 (0.18-0.85); 31-40: OR = 0.43 (0.20-0.96)) and lower education (high school/vocational: OR = 0.15 (0.04-0.58); associate degree: OR = 0.21 (0.06-0.71)) were factors that negatively influenced PrEP use. Current or former PrEP users had the highest oropharyngeal gonorrhea (14.39% vs. 9.68% and 5.80%, p < 0.01) and overall gonorrhea rates (20.86% vs. 17.17% and 8.37%, p < 0.001). 'PrEP-naïve but willing' participants consistently demonstrated high-risk sexual behavior, increased STI testing, and more diverse sexual acts, whereas PrEP users had the highest STI prevalence.

Reflex Hepatitis C Virus Viral Load Testing Following an Initial Positive Hepatitis C Virus Antibody Test: A Global Systematic Review and Meta-analysis.

BACKGROUND: Many people who have a positive hepatitis C virus (HCV) antibody (Ab) test never receive a confirmatory HCV RNA viral load (VL) test. Reflex VL testing may help address this problem. We undertook a systematic review to evaluate the effectiveness of reflex VL testing compared with standard nonreflex approaches on outcomes across the HCV care cascade. METHODS: We searched 4 databases for studies that examined laboratory-based reflex or clinic-based reflex VL testing approaches, with or without a nonreflex comparator, and had data on the uptake of HCV RNA VL test and treatment initiation and turnaround time between Ab and VL testing. Both laboratory- and clinic-based reflex VL testing involve only a single clinic visit. Summary estimates were calculated using random-effects meta-analyses. RESULTS: Fifty-one studies were included (32 laboratory-based and 19 clinic-based reflex VL testing). Laboratory-based reflex VL testing increased HCV VL test uptake versus nonreflex testing (RR: 1.35; 95% CI: 1.16-1.58) and may improve linkage to care among people with a positive HCV RNA test (RR: 1.47; 95% CI: .81-2.67) and HCV treatment initiation (RR: 1.03; 95% CI: .46-2.32). The median time between Ab and VL test was <1 day for all laboratory-based reflex studies and 0-5 days for 13 clinic-based reflex testing. CONCLUSIONS: Laboratory-based and clinic-based HCV reflex VL testing increased uptake and reduced time to HCV VL testing and may increase HCV linkage to care. The World Health Organization now recommends reflex VL testing as an additional strategy to promote access to HCV VL testing and treatment. CLINICAL TRIALS REGISTRATION: PROSPERO CRD42021283822.

A comparison of the chemiluminescence immunoassay and Crithidia luciliae immunofluorescence test in detecting anti-dsDNA antibodies and assessing the activity of systemic lupus erythematosus.

OBJECTIVES: This study aimed to compare the YHLO chemiluminescence immunoassay (CLIA) with the Crithidia luciliae immunofluorescence test (CLIFT) to detect anti-dsDNA antibodies and its correlation with disease activity in systemic lupus erythematosus (SLE). METHOD: In total, 208 patients diagnosed with SLE, 110 other autoimmune patients, 70 infectious disorders patients, and 105 healthy people were enrolled in this study. Serum samples were tested using CLIA in a YHLO chemiluminescence system and CLIFT. RESULTS: The overall agreement between YHLO CLIA and CLIFT was 76.9% (160/208), with a moderate correlation (kappa = 0.530, p < 0.001). The sensitivity of YHLO CLIA and CLIFT were 58.2% and 55.3%, respectively. The specificity of YHLO CLIA and CLIFT were 95.1% and 99.3%, respectively. The sensitivity of YHLO CLIA was increased to 66.8% with a specificity of 93.6% when the cut-off value was set at 24 IU/mL. Spearman's correlation coefficient between the quantitative results of YHLO CLIA and the titers of CLIFT was 0.59 (p < .01). A significant correlation was found between the anti-dsDNA results detected by YHLO CLIA and the SLE Disease Activity Index 2000 (SLEDAI-2K). Spearman's correlation coefficient between YHLO CLIA and SLEDAI-2K (r = 0.66, p < .01) was higher than that of CLIFT (r = 0.60, p < .01). CONCLUSIONS: Good correlation and agreement were found between YHLO CLIA and CLIFT. In addition, there was a significant correlation between YHLO CLIA and the SLE Disease Activity Index, which was superior to that of CLIFT. The YHLO chemiluminescence system is recommended for the assessment of disease activity.

The predictive value of baseline symptom score and the peripheral CD4CD8 double-positive T cells in patients with AECOPD.

BACKGROUND: Accurate prediction of acute exacerbation helps select patients with chronic obstructive pulmonary disease (COPD) for individualized therapy. The potential of lymphocyte subsets to function as clinical predictive factors for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) remains uncertain. METHODS: In this single-center prospective cohort study with a 2-year follow-up, 137 patients aged 51 to 79 with AECOPD were enrolled. We examined the prognostic indicators of AECOPD by analyzing lymphocyte subsets and baseline symptom score. Furthermore, a predictive model was constructed to anticipate the occurrence of respiratory failure in patients experiencing AECOPD. RESULTS: The COPD Assessment Test (CAT) score combined with home oxygen therapy and CD4+CD8+ T cells% to predict respiratory failure in AECOPD patients were the best (the area under the curves [AUC] = 0.77, 95% CI: 0.70-0.86, P < 0.0001, sensitivity: 60.4%, specificity: 86.8%). The nomogram model, the C index, calibration plot, decision curve analysis, and clinical impact curve all indicate the model's good predictive performance. The observed decrease in the proportions of CD4+CD8+ T cells appears to be correlated with more unfavorable outcomes. CONCLUSIONS: The nomogram model, developed to forecast respiratory failure in patients with AECOPD, utilizing variables such as home oxygen therapy, CAT score, and CD4+CD8+ T cells%, demonstrated a high level of practicality in clinical settings. CD4+CD8+ T cells serve as a reliable and readily accessible predictor of AECOPD, exhibiting greater stability compared to other indices. It is less susceptible to subjective influences from patients or physicians. This model facilitated personalized estimations, enabling healthcare professionals to make informed decisions regarding preventive interventions.

ATM participates in fine particulate matter-induced airway inflammation through regulating DNA damage and DNA damage response.

The relationship between fine particulate matter (PM2.5) and chronic airway inflammatory diseases, such as chronic obstructive pulmonary disease and asthma, have garnered public attention, while the detailed mechanisms of PM2.5-induced airway inflammation remain unclear. This study reveals that PM2.5 induces airway inflammation both in vivo and in vitro, and, moreover, identifies DNA damage and DNA damage repair (DDR) as results of this exposure. Ataxia telangiectasia-mutated heterozygous (ATM+/- ) and wild-type C57BL/6 (WT) mice were exposed to PM2.5. The results show that, following exposure to PM2.5, the number of neutrophils in broncho alveolar lavage fluid and the mRNA expression of CXCL-1 in lung tissues of the ATM+/- mice were lower than those of the WT mice. The mRNA expression of FANCD2 and FANCI were also down-regulated. Human bronchial epithelial (HBE) cells were transfected with ATM-siRNA to induce down-regulation of ATM gene expression and were subsequently stimulated with PM2.5. The results show that the mRNA expression of TNF-α decreased in the ATM-siRNA-transfected cells. The mRNA expression of CXCL-1 and CXCL-2 in peritoneal macrophages, derived from ATM-null mice in which experiments showed that the protein expression of FANCD2 and FANCI decreased, were also decreased after PM2.5 exposure in ATM-siRNA-transfected HBE cells. In conclusion, PM2.5-induced airway inflammation is alleviated in ATM+/- mice compared with WT mice. ATM promotes PM2.5-induced airway inflammation, which may be attributed to the regulation of DNA damage and DDR.

Monitoring Inattention in Construction Workers Caused by Physical Fatigue Using Electrocardiograph (ECG) and Galvanic Skin Response (GSR) Sensors.

Physical fatigue is frequent for heavy manual laborers like construction workers, but it causes distraction and may lead to safety incidents. The purpose of this study is to develop predictive models for monitoring construction workers' inattention caused by physical fatigue utilizing electrocardiograph (ECG) and galvanic skin response (GSR) sensors. Thirty participants were invited to complete an attention-demanding task under non-fatigued and physically fatigued conditions. Supervised learning algorithms were utilized to develop models predicting their attentional states, with heart rate variability (HRV) features derived from ECG signals and skin electric activity features derived from GSR signals as data inputs. The results demonstrate that using HRV features alone could obtain a prediction accuracy of 88.33%, and using GSR features alone could achieve an accuracy of 76.67%, both through the KNN algorithm. The accuracy increased to 96.67% through the SVM algorithm when combining HRV and GSR features. The findings indicate that ECG sensors used alone or in combination with GSR sensors can be applied to monitor construction workers' inattention on job sites. The findings would provide an approach for detecting distracted workers at job sites. Additionally, it might reveal the relationships between workers' physiological features and attention.

Regular Exercise in Drosophila Prevents Age-Related Cardiac Dysfunction Caused by High Fat and Heart-Specific Knockdown of skd.

Skuld (skd) is a subunit of the Mediator complex subunit complex. In the heart, skd controls systemic obesity, is involved in systemic energy metabolism, and is closely linked to cardiac function and aging. However, it is unclear whether the effect of cardiac skd on cardiac energy metabolism affects cardiac function. We found that cardiac-specific knockdown of skd showed impaired cardiac function, metabolic impairment, and premature aging. Drosophila was subjected to an exercise and high-fat diet (HFD) intervention to explore the effects of exercise on cardiac skd expression and cardiac function in HFD Drosophila. We found that Hand-Gal4>skd RNAi (KC) Drosophila had impaired cardiac function, metabolic impairment, and premature aging. Regular exercise significantly improved cardiac function and metabolism and delayed aging in HFD KC Drosophila. Thus, our study found that the effect of skd on cardiac energy metabolism in the heart affected cardiac function. Exercise may counteract age-related cardiac dysfunction and metabolic disturbances caused by HFD and heart-specific knockdown of skd. Skd may be a potential therapeutic target for heart disease.

Knockdown of lncRNA SNHG15 Ameliorates Oxygen and Glucose Deprivation (OGD)-Induced Neuronal Injury via Regulating the miR-9-5p/TIPARP Axis.

Stroke is a cerebrovascular disease with impaired nerve function. Long non-coding RNA (lncRNA) is considered to be an important regulator of various diseases. Nevertheless, the role of lncRNA small nucleolar RNA host gene 15 (SNHG15) in cerebral ischemia injury induced by stroke is still unclear. Cell-counting kit 8 assay and flow cytometry were used to detect cell viability and apoptosis, respectively. The caspase3 activity of cells was measured using Caspase3 Activity Assay Kit. Besides, the protein levels of apoptosis markers and TCCD-induced poly (ADP)-ribose polymerase (TIPARP) were determined using western blot analysis. Moreover, quantitative real-time polymerase chain reaction was employed to examine the relative expression of SNHG15 and miR-9-5p. Furthermore, dual-luciferase reporter assay was used to assess the interaction between miR-9-5p and SNHG15 or TIPARP. In addition, biotin-labeled RNA pull-down assay was performed to evaluate the interaction between miR-9-5p and SNHG15 further. Middle cerebral artery occlusion (MCAO) model was constructed to further explore the role of SNHG15 in neuronal injury in vivo. Our data showed that oxygen and glucose deprivation (OGD) could induce N-2a cell injury and enhance SNHG15 expression. Silenced SNHG15 could promote the viability and suppress the apoptosis of OGD-induced N-2a cells. Also, SNHG15 knockdown also could alleviate the neuronal injury of MCAO mice. Mechanistically, SNHG15 could sponge miR-9-5p, and miR-9-5p could target TIPARP. Further experiments revealed that miR-9-5p inhibition or TIPARP overexpression could reverse the suppressive effect of SNHG15 knockdown on OGD-induced N-2a cell injury. Our findings indicated that SNHG15 knockdown inhibited neuronal injury through the miR-9-5p/TIPARP axis, suggesting that SNHG15 might be a potential target for cerebral ischemia injury induced by stroke.

Evaluating the time of HIV infection, diagnosis and treatment delays based on HIV notification data in Northwest China, 2008­19.

BACKGROUND: Timely diagnosis and treatment are crucial for reducing HIV transmission;therefore, estimating the time from HIV infection to antiretroviral therapy (ART) initiation becomes particularly important for people living with HIV. METHODS: We used a well-characterised CD4 depletion model to estimate the time from HIV infection to initiation of ART and the rate of delayed HIV diagnosis (infection to diagnosis >1year) and treatment initiation (diagnosis to treatment >1year), based on HIV notification data for adults (aged ≥18years) in Xi'an city, China, during 2008-19. RESULTS: Overall, 7402 reported HIV diagnoses were included. We estimated more than two-thirds of HIV infections remained undiagnosed (66.1%, 9489/14 345). The estimated proportion of HIV diagnoses that were delayed (>1year) was 80.3% (5941/7402) during 2008-19, and it increased from 72.7% (32/44) in 2008 to 83.5% (908/1088) in 2019. In contrast, the proportion of cases with delayed treatment (>1year) was 13.1% (971/7402) during 2008-19, and it reduced from 75.0% (33/44) in 2008 to 1.5% (16/1088) in 2019. The estimated median time from HIV infection to diagnosis increased from 5.05 (IQR, 0.27-8.15) years to 5.81 (IQR, 2.31-10.28) years, whereas the time from diagnosis to ART initiation reduced from 3.06 (IQR, 1.01-5.20) years in 2008 to 0.07 (IQR, 0.04-0.12) year in 2019. CONCLUSIONS: Early treatment after diagnosis has significantly improved, but timely diagnosis of HIV infections may still require further improvement. The estimated proportion of undiagnosed HIV cases remains high in 2019 in Xi'an city and is likely to impede effective control.

Application of the Risk-Based Early Warning Method in a Fracture-Karst Water Source, North China.

The paper proposes a risk-based early warning considering characteristics of fracture-karst aquifer in North China and applied it in a super-large fracture-karst water source. Groundwater vulnerability, types of land use, water abundance, transmissivity and spatial temporal variation of groundwater quality were chosen as indexes of the method. Weights of factors were obtained by using AHP method based on relative importance of factors, maps of factors were zoned by GIS, early warning map was conducted based on extension theory with the help of GIS, ENVI+IDL. The early warning map fused five factors very well, serious and tremendous warning areas are mainly located in northwest and east with high or relatively high transmissivity and groundwater pollutant loading, and obviously deteriorated or deteriorated trend of petroleum. The early warning map warns people where more attention should be paid, and the paper guides decision making to take appropriate protection actions in different warning levels areas.

Modified timing characteristic of a scintillation detection system with photonic crystal structures.

It is intuitively expected that an enhanced light extraction of a scintillator can be easily achieved by photonic crystal structures. Here, we demonstrate a modified timing characteristic for a detection system induced by enhanced light extraction with photonic crystal structures. Such improvement is due to the enhanced light extraction which can be clearly proven by the independent measurements of the light output and the timing resolution. The present investigation is advantageous to promote the development of a scintillation detection system performance based on the time-of-flight measurement.

The protective effect of a novel antioxidant gene from Mycobacterium avium against nitrosative and oxidative stress in E. coli.

The production of reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI) is an important host defense mechanism in response to infection by Mycobacterium tuberculosis. A variety of genes have been implicated in resistance to ROI and RNI, including noxR1. However, studies in Mycobacterium avium, an important pathogen among nontuberculous mycobacteria, are limited. We aim to investigate the role of a novel gene cloned from M. avium with high similarity to noxR1, noA, in resistance against RNI and ROI in M. tuberculosis. After subcloning noA into vector for expression in E. coli, we performed survival rate analysis in the bacteria transformed with noA (pET-noA) and without noA (pET-his) after exposure to nitrosative stresses by S-nitrosoglutathione (GSNO) and sodium nitrite, and oxidative stresses by H2O2. Compared with pET-his, the survival rate of pET-noA was 1 log10-fold higher after exposure to GSNO and sodium nitrite. We observed 1 log10-fold, 2 log10-fold and 3 log10-fold higher survival rate in pET-noA than pET-his after exposure to H2O2 for 3, 6 and 9 h, respectively. With the combined treatment of H2O2 and GSNO, we found more than 2 log10-fold increase in survival rate in pET-noA comparing with pET-his, suggesting a possible synergistic effect. In summary, noA gene cloned from M. avium has been shown to protect E. coli from both RNI and ROI.

Experimental and numerical investigations on stress concentration factors of concrete filled steel tube X-joints.

An SHS-CFSHS X-joint is fabricated by welding two square hollow section (SHS) braces to a concrete-filled square hollow section (CFSHS) chord. In this paper, the stress concentration factors (SCFs) of SHS-CFSHS X-joints are investigated through experimental tests and finite element analysis (FEA), with the hot spot stress method serving as the analytical approach. Eight specimens are designed and manufactured, with FE models built in software ANSYS. These FE models are validated against the test results. The specimens are tested under brace axial tension to determine the SCFs of the X-joints. It shows that the concrete filled in the chord effectively reduces the SCFs of the X-joints. To further explore various load conditions and the influence of the parameters, FEA is carried out and a total of 64 FE models are built. Based on the FEA results, multiple regression analysis is used to obtain the SCF formulae of SHS-CFSHS X-joints under axial tension load and in-plane bending load in the brace, respectively. Comparison and analysis of the SCF results obtained from experimental tests, the proposed formulae, and FE simulations reveal that the formulae presented in this study are both conservative and suitable for predicting SCFs.

Optimising HIV pre-exposure prophylaxis and testing strategies in men who have sex with men in Australia, Thailand, and China: a modelling study and cost-effectiveness analysis.

BACKGROUND: Men who have sex with men (MSM) in the Asia-Pacific region have a disproportionately high burden of HIV infection compared with the general population. Although pre-exposure prophylaxis (PrEP) for HIV is highly effective at preventing new HIV infections, the cost-effectiveness of PrEP for MSM in different countries in the Asia-Pacific region with varying PrEP coverage and HIV testing frequencies remains unstudied. We aimed to analyse the economic and health benefits of long-acting injectable cabotegravir (CAB-LA) compared with oral PrEP in high-income countries and low-income and middle-income countries within the Asia-Pacific region. METHODS: We developed a decision-analytic Markov model to evaluate the population impact and cost-effectiveness of PrEP scale-up among MSM in Australia, Thailand, and China. We assumed a static cohort of 100 000 MSM aged 18 years or older who were at risk of HIV infection, with a monthly cycle length over a 40-year time period. We evaluated hypothetical scenarios with universal PrEP coverage of 80% among 100 000 suitable MSM in each country. We modelled oral PrEP and CAB-LA for MSM with diverse HIV testing frequency strategies. We adopted the health-care system's perspective with a 3% annual discount rate. We calculated the incremental cost-effectiveness ratio (ICER), measured as additional cost per quality-adjusted life-year (QALY) gained, to compare different strategies with the status quo in each country. All costs were reported in 2021 US$. We also performed one-way, two-way, and probabilistic sensitivity analyses to assess the robustness of our findings. FINDINGS: Compared with the status quo in each country, expanding oral PrEP to 80% of suitable MSM would avert 8·1% of new HIV infections in Australia, 14·5% in Thailand, and 26·4% in China in a 40-year period. Expanding oral PrEP use with 6-monthly HIV testing for both PrEP and non-PrEP users was cost-saving for Australia. Similarly, expanding oral PrEP use remained the most cost-effective strategy in both Thailand and China, but optimal testing frequency varied, with annual testing in Thailand (ICER $4707 per QALY gained) and 3-monthly testing in China (ICER $16 926 per QALY gained) for both PrEP and non-PrEP users. We also found that replacing oral PrEP with CAB-LA for MSM could avert more new HIV infections (12·8% in Australia, 27·6% in Thailand, and 32·8% in China), but implementing CAB-LA was not cost-effective due to its high cost. The cost of CAB-LA would need to be reduced by 50-90% and be used as a complementary strategy to oral PrEP to be cost-effective in these countries. INTERPRETATION: Expanding oral PrEP use for MSM, with country-specific testing frequency, is cost-effective in Australia, Thailand, and China. Due to the high cost, CAB-LA is currently not affordable as a single-use strategy but might be offered as an additional option to oral PrEP. FUNDING: Ministry of Science and Technology of the People's Republic of China, the Australian National Health and Medical Research Council, National Key Research and Development Program of China, and National Natural Science Foundation of China.

Using complete blood count, serum immunoglobulins G/A/M and complement C3/C4 levels to predict the risk of COPD acute exacerbation: 2-year follow-up in a single-center prospective cohort study.

Autoimmunity is present in patients with stable chronic obstructive pulmonary disease (COPD), playing a role in indirect and direct ways. We aimed to explore whether autoimmunity could play a role in COPD exacerbations and construct autoimmunity-related prediction models. This prospective, longitudinal, observational cohort study enrolled 155 patients with acute COPD exacerbations (AECOPD) followed for at least two years. The laboratory parameters, including complete blood count, serum immunoglobulins G/A/M and complement C3/C4 levels, were collected at enrollment. We studied the demographic characteristics, clinical characteristics and laboratory parameters to identify independent risk factors and build predictive models. The results showed that lower lymphocyte count was associated with noninvasive ventilation (NIV) in patients with AECOPD (the odds ratio [OR] 0.25, the 95% confidence interval [CI]: 0.08-0.81, P = 0.02). Lymphocyte count performed well with an area under the curves (AUC) of 0.75 (P < 0.0001, sensitivity: 78.1%, specificity: 62.3%, cutoff value [Cov] ≤ 1.1). The C index, calibration plot, decision curve analysis (DCA) and bootstrap repetitions indicated that this clinical prediction model based on lymphocyte count for NIV in patients with AECOPD performed well. Having prior home oxygen therapy (OR: 2.82, 95% CI: 1.25-6.36, P = 0.013) and higher COPD Assessment Test (CAT) scores (OR: 1.14, 95% CI: 1.03-1.25, P = 0.011) were associated with the increased risk for respiratory failure. For predicting respiratory failure, CAT scores and home oxygen therapy combined had an AUC-ROC of 0.73 (P < 0.0001). This clinical prediction model based on lymphocyte count may help to assist in treatment decisions for NIV in patients with AECOPD. Lower complement C3 seems to be associated with worse outcomes in patients with AECOPD.

Safety of Inactivated SARS-CoV-2 Vaccines Among Adults with Experience of Allergies to Food or Medicines.

The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), commonly known as COVID-19, poses significant risk to human health worldwide. The primary strategy for controlling the disease is through vaccination. However, there is an urgent need to establish confidence in the safety of global vaccination efforts, particularly among populations with allergies, as evidence on the adverse effects of SARS-CoV-2 vaccines in this group remains limited. To address this gap, our study aimed to evaluate the safety of inactivated SARS-CoV-2 vaccines in individuals with food and/or drug allergies. The study enrolled a total of 150 participants, who were subjected to a series of questionnaires to evaluate local and systemic reactions within 7 days after each dose. The results revealed that the most prevalent adverse reactions were pain at the injection site (30%) and fatigue (16%) following the initial vaccination. Notably, the incidence of both local and systemic adverse reactions decreased after the second vaccination, which was unexpected. The food allergy and drug allergy subgroups exhibited a similar phenomenon. Furthermore, the incidence of adverse events observed in this study was consistent with the range reported in Phase III clinical trials of inactivated SARS-CoV-2 vaccines. Our findings suggest that individuals with pre-existing food and/or drug allergies have a favorable safety profile when receiving inactivated SARS-CoV-2 vaccination.

Aerobic exercise reduced the amount of CHRONO bound to BMAL1 and ameliorated glucose metabolic dysfunction in skeletal muscle of high-fat diet-fed mice.

AIMS: The purpose of this study was to investigate the effects of aerobic exercise on the CHRONO-BMAL1 pathway and glucose metabolism in skeletal muscle of high-fat diet (HFD)-fed mice. MAIN METHODS: Male C57BL/6J mice were randomly allocated into four groups: normal chow diet with control (NCD + CON), NCD with exercise (NCD + EXE), HFD with control (HFD + CON) and HFD with exercise (HFD + EXE). The NCD and HFD groups were respectively fed a diet of 10 % and 60 % kilocalories from fat for 12 weeks. During the dietary intervention, EXE groups were subjected to 70 % VO2max intensity of treadmill exercise six times per week for 12 weeks. Body weight, energy intake, fat weight, serum lipid profiles, systemic glucose homeostasis, the amount of CHRONO bound to BMAL1, the enzymatic activity, mRNA and protein expression involved in glucose metabolism of skeletal muscle were measured. KEY FINDINGS: The results showed that the 12-week HFD feeding without exercise induced weight gain, serum dyslipidemia and insulin resistance. Furthermore, HFD increased the amount of CHRONO bound to BMAL1 and repressed the glucose metabolism in skeletal muscle. However, aerobic exercise prevented weight gain, serum dyslipidemia and systemic insulin resistance in the HFD-fed mice. Meanwhile, aerobic exercise also decreased the amount of CHRONO bound to BMAL1 and increased the glucose uptake, glucose oxidation and glycogenesis in skeletal muscle of the HFD-fed mice. SIGNIFICANCE: These data suggested that aerobic exercise could counterbalance CHRONO interacted with BMAL1 and prevent glucose metabolism dysfunction of skeletal muscle, and finally maintain whole-body insulin sensitivity in the HFD-fed mice.

Small airway dysfunction associated with poor short-term outcomes in patients undergoing thoracoscopic surgery for lung cancer.

BACKGROUND: Although small airway dysfunction is a common respiratory dysfunction, its prognosis after lung cancer surgery is often neglected. This study investigated the relationship between small airway dysfunction and outcomes in patients who underwent thoracoscopic surgery for lung cancer. METHODS: A retrospective cohort study of patients who underwent thoracoscopic surgery was conducted between December 2019 and March 2021 at Ningbo First Hospital. We used univariate and multivariate analyses to assess the possible associations between postoperative outcomes and clinical variables, including small airway dysfunction. To balance the potential confounding factors, propensity score matching was performed to establish 1:1 small airway dysfunction and small airway normal function group matching. RESULTS: In this study, 1,012 patients undergoing thoracoscopic surgery for lung cancer were enrolled. Small airway dysfunction was present in 18.7% of patients (189/1,012). The incidence of postoperative pulmonary complications in the small airway dysfunction group was higher than that of the small airway normal function group (16.4% vs 6.2%, P < .001). The most significant postoperative pulmonary complications were pneumonia (7.4% vs 2.4%, P < .001) in the small airway dysfunction and normal function groups, respectively. In addition, a significantly prolonged median hospital length of stay was observed in the small airway dysfunction group compared to the small airway normal function group (median [interquartile range], 9 [7-12] vs 8 [7-9], P < .001). After 1:1 propensity score matching, 298 patients (149 pairs) were included in the comparison between small airway dysfunction and small airway normal function, and this association remained. Postoperative pulmonary complications (13.4% vs 6.0%, P = .032) were still higher, and length of stay (median [interquartile range] 9 [7-11] vs 8 [6-10] days, P = .001) was still longer in the small airway dysfunction group. Multivariate analysis indicated that small airway dysfunction was the independent risk factor associated with both postoperative pulmonary complications (odds ratio = 2.694, 95% confidence interval: 1.640-4.426, P < .001) and prolonged length of stay (beta = 1.045, standard error = 0.159, 95% confidence interval: 0.733-1.357, P < .001). CONCLUSION: Our study showed that small airway dysfunction increased the incidence of postoperative pulmonary complications and prolonged length of stay in patients undergoing thoracoscopic surgery for lung cancer.

Positive Effects of a Perovskite Film on the Radioluminescence Properties of a ZnO:Ga Crystal Scintillator.

To improve the radioluminescence (RL) performance of ZnO:Ga (GZO) crystal scintillators and overcome the challenge of their self-absorption, we proposed a two-layer composite scintillator consisting of a GZO wafer and a 70 nm lead halide perovskite film(CsPbBr3, CH3NH3PbBr3). The effects of the perovskite film on the RL properties were studied. The results showed that the perovskite quantum dot film substantially changed the RL spectrum of GZO and prevented self-absorption. The RL of the samples were enhanced by 66% to 151% through the photoluminescence (PL) of the perovskite film, while the energy-resolving power and spatial-resolving power were maintained at the same level as that of GZO image converters. The present experiments and discussions confirmed that the perovskite film improved the RL, and this study suggests a new wavelength regulation method among scintillators, converters, and back-end optical devices. The applications of perovskites in the field of radiation detection and imaging have been extended.

Skeletal-Muscle-Specific Overexpression of Chrono Leads to Disruption of Glucose Metabolism and Exercise Capacity.

Disruption of circadian rhythms is related to disorders of glucose metabolism, and the molecular clock also exists in skeletal muscle. The ChIP-derived repressor of network oscillator (Chrono) and brain and muscle ARNT-like 1 (Bmal1) are core circadian components. Chrono is considered to be the repressor of Bmal1, and the Chrono-Bmal1 pathway is important in regulating the circadian rhythm; it has been speculated that this pathway could be a new mechanism for regulating glucose metabolism. The purpose of this study was to investigate the effects of Chrono on glucose metabolism in skeletal muscle and exercise capacity by using mice with skeletal-muscle-specific overexpression of Chrono (Chrono TG) and wild-type (WT) mice as the animal models. The results of this cross-sectional study indicated that the Chrono TG mice had an impaired glucose tolerance, lower exercise capacity, and higher levels of nonfasted blood glucose and glycogen content in skeletal muscle compared to WT mice. In addition, the Chrono TG mice also showed a significant increase in the amount of Chrono bound to Bmal1 according to a co-IP analysis; a remarkable decrease in mRNA expression of Tbc1d1, Glut4, Hk2, Pfkm, Pdp1, Gbe1, and Phka1, as well as in activity of Hk and protein expression of Ldhb; but higher mRNA expression of Pdk4 and protein expression of Ldha compared with those of WT mice. These data suggested the skeletal-muscle-specific overexpression of Chrono led to a greater amount of Chrono bound to Bmal1, which then could affect the glucose transporter, glucose oxidation, and glycogen utilization in skeletal muscle, as well as exercise capacity.