Spatiotemporal drivers of urban water pollution: Assessment of 102 cities across the Yangtze River Basin.

Effective management of large basins necessitates pinpointing the spatial and temporal drivers of primary index exceedances and urban risk factors, offering crucial insights for basin administrators. Yet, comprehensive examinations of multiple pollutants within the Yangtze River Basin remain scarce. Here we introduce a pollution inventory for urban clusters surrounding the Yangtze River Basin, analyzing water quality data from 102 cities during 2018-2019. We assessed the exceedance rates for six pivotal indicators: dissolved oxygen (DO), ammonia nitrogen (NH3-N), chemical oxygen demand (COD), biochemical oxygen demand (BOD), total phosphorus (TP), and the permanganate index (CODMn) for each city. Employing random forest regression and SHapley Additive exPlanations (SHAP) analyses, we identified the spatiotemporal factors influencing these key indicators. Our results highlight agricultural activities as the primary contributors to the exceedance of all six indicators, thus pinpointing them as the leading pollution source in the basin. Additionally, forest coverage, livestock farming, chemical and pharmaceutical sectors, along with meteorological elements like precipitation and temperature, significantly impacted various indicators' exceedances. Furthermore, we delineate five core urban risk components through principal component analysis, which are (1) anthropogenic and industrial activities, (2) agricultural practices and forest extent, (3) climatic variables, (4) livestock rearing, and (5) principal polluting sectors. The cities were subsequently evaluated and categorized based on these risk components, incorporating policy interventions and administrative performance within each region. The comprehensive analysis advocates for a customized strategy in addressing the discerned risk factors, especially for cities presenting elevated risk levels.

Machine learning assisted combined systems of wastewater treatment plants with constructed wetlands optimal decision-making.

This study proposed an efficient framework for optimizing the design and operation of combined systems of wastewater treatment plants (WWTP) and constructed wetlands (CW). The framework coupled a WWTP model with a CW model and used a multi-objective evolutionary algorithm to identify trade-offs between energy consumption, effluent quality, and construction cost. Compared to traditional design and management approaches, the framework achieved a 27 % reduction in WWTP energy consumption or a 44 % reduction in CW cost while meeting strict effluent discharge limits for Chinese WWTP. The framework also identified feasible decision variable ranges and demonstrated the impact of different optimization strategies on system performance. Furthermore, the contributions of WWTP and CW in pollutant degradation were analyzed. Overall, the proposed framework offers a highly efficient and cost-effective solution for optimizing the design and operation of a combined WWTP and CW system.

Indole-Fused Benzoxepine Synthesis via Visible-Light-Driven Aerobic Dehydrogenative [5 + 2] Annulation.

A photocatalyzed oxidative dehydrogenative annulation between 2-(1H-indol-2-yl)phenols and alkenylphenols is presented. Various indole-fused benzoxepines can be obtained at room temperature using atom-efficient strategies. This method not only avoids the use of stoichiometric amounts of oxidants but also exhibits excellent atom economy by generating H2O as the only theoretical byproduct.

Reduced myocardial strain of interventricular septum among male amateur marathon runners: a cardiac magnetic resonance study.

OBJECTIVES: To analyze the long-term effect of multiple marathons on cardiac structure and function in amateur marathon runners compared with healthy controls. DESIGN: Cross-sectional study using male amateur marathon runners (n = 32) and age-matched cohort of male healthy controls (n = 12). METHODS: A total of 32 male amateur marathon runners (age 44 ±â€¯7 years) and 12 male healthy controls (age 42 ±â€¯8 years) underwent cardiac magnetic resonance (CMR). The relevant parameters of cardiac structure and function were studied employing feature-tracking strain analysis. RESULTS: Amateur marathon runners showed lower heart rates, body mass index and body surface area. The left ventricular (LV) mass index, LV end-diastolic volume index and right ventricular end-systolic volume index were significantly higher in amateur marathon runners compared with healthy controls. Furthermore, walls of interventricular septum (IVS) in amateur marathon runners were thicker than healthy controls. There was no significant difference between two groups in the global myocardial strain (MS) in LV. However, the segmental radial and circumferential strains of the LV were lower in amateur marathon runners compared to healthy controls, specifically in the 8th and 9th segments. Finally, we also found as the total running intensity increased, so did global longitudinal strain. CONCLUSIONS: We reported higher wall thickness and lower regional radial and circumferential strain in the IVS region in amateur marathon runners, suggesting that prolonged and high-intensity exercise may cause cardiac remodeling. Further studies are needed to investigate whether this is an adaptive or maladaptive change in amateur marathon runners.

Hippocampal Subfield Volumes in Amateur Marathon Runners.

PURPOSE: Numerous studies have implicated the involvement of structure and function of the hippocampus in physical exercise, and the larger hippocampal volume is one of the relevant benefits reported in exercise. It remains to be determined how the different subfields of hippocampus respond to physical exercise. METHODS: A 3D T1-weighted magnetic resonance imaging was acquired in 73 amateur marathon runners (AMR) and 52 healthy controls (HC) matched with age, sex, and education. The Montreal Cognitive Assessment, the Pittsburgh Sleep Quality Index (PSQI), and the Fatigue Severity Scale were assessed in all participants. We obtained hippocampal subfield volumes using FreeSurfer 6.0. We compared the volumes of the hippocampal subfield between the two groups and ascertained correlation between the significant subfield metrics and the significant behavioral measure in AMR group. RESULTS: The AMR had significantly better sleep than HC, manifested as with lower score of PSQI. Sleep duration in AMR and HC was not significantly different from each other. In the AMR group, the left and right hippocampus, cornu ammonis 1 (CA1), CA4, granule cell and molecular layers of the dentate gyrus, molecular layer, left CA2-3, and left hippocampal-amygdaloid transition area volumes were significantly larger compared with those in the HC group. In AMR group, the correlations between the PSQI and the hippocampal subfield volumes were not significant. No correlations were found between hippocampal subfield volumes and sleep duration in AMR group. CONCLUSIONS: We reported larger volumes of specific hippocampal subfields in AMR, which may provide a hippocampal volumetric reserve that protects against age-related hippocampal deterioration. These findings should be further investigated in longitudinal studies.

Synergistic analysis of performance, functional genes, and microbial community assembly in SNDPR process under Zn(II) stress.

One of the most prevalent heavy metals found in rural sewage is Zn(II), while its effect on simultaneous nitrification, denitrification and phosphorus removal (SNDPR) remains unclear. In this work, the responses of SNDPR performance to long-term Zn(II) stress were investigated in a cross-flow honeycomb bionic carrier biofilm system. The results indicated that Zn(II) stress at 1 and 5 mg L-1 could increase nitrogen removal. Maximum ammonia nitrogen, total nitrogen, and phosphorus removal efficiencies of up to 88.54%, 83.19%, and 83.65% were obtained at Zn(II) concentration of 5 mg L-1. The functional genes, such as archaeal amoA, bacterial amoA, NarG, NirS, NapA, and NirK, also reached the highest value at 5 mg L-1 Zn(II), with the absolute abundances of 7.73 × 105, 1.57 × 106, 6.68 × 108, 1.05 × 109, 1.79 × 108, and 2.09 × 108 copies·g-1 dry weight, respectively. The neutral community model demonstrated that deterministic selection was responsible for the system's microbial community assembly. Additionally, response regimes with extracellular polymeric substances and cooperation among microorganisms facilitated the stability of the reactor effluent. Overall, the findings of this paper contribute to improving the efficiency of wastewater treatment.

Recent Advances in N-O Bond Cleavage of Oximes and Hydroxylamines to Construct N-Heterocycle.

Oximes and hydroxylamines are a very important class of skeletons that not only widely exist in natural products and drug molecules, but also a class of synthon, which have been widely used in industrial production. Due to weak N-O σ bonds of oximes and hydroxylamines, they can be easily transformed into other functional groups by N-O bond cleavage. Therefore, the synthesis of N-heterocycle by using oximes and hydroxylamines as nitrogen sources has attracted wide attention. Recent advances for the synthesis of N-heterocycle through transition-metal-catalyzed and radical-mediated cyclization classified by the type of nitrogen sources and rings are summarized. In this paper, the recent advances in the N-O bond cleavage of oximes and hydroxylamines are reviewed. We hope that this review provides a new perspective on this field, and also provides a reference to develop environmentally friendly and sustainable methods.

Gut Microbiome Associating with Carbon and Nitrogen Metabolism during Biodegradation of Polyethene in Tenebrio larvae with Crop Residues as Co-Diets.

Tenebrio molitor and Tenebrio obscurus (Coleoptera: Tenebrionidae) larvae are two commercial insects that eat plant and crop residues as diets and also biodegrade synthetic plastics polyethylene (PE). We examined biodegradation of low-density PE (LDPE) foam (Mn = 28.9 kDa and Mw = 342.0 kDa) with and without respective co-diets, i.e., wheat brain (WB) or corn flour (CF), corn straw (CS), and rice straw (RS) at 4:1 (w/w), and their gut microbiome and genetic metabolic functional groups at 27.0 ± 0.5 °C after 28 days of incubation. The presence of co-diets enhanced LDPE consumption in both larvae and broad-depolymerized the ingested LDPE. The diet type shaped gut microbial diversity, potential pathways, and metabolic functions. The sequence of effectiveness of co-diets was WB or CF > CS > RS for larval development and LDPE degradation. Co-occurrence networks indicated that the larvae co-fed with LDPE displayed more complex correlations of gut microbiome than the larvae fed with single diets. The primary diet of WB or CF and crop residues CS and RS provided energy and nitrogen source to significantly enhance LDPE biodegradation with synergistic activities of the gut microbiota. For the larvae fed LDPE and LDPE plus co-diets, nitrogen fixation function was stimulated compared to normal diets and associated with LDPE biodegradation.

Gorham-Stout syndrome: A chylothorax disease with bony destruction: A case report.

RATIONALE: Gorham-Stout syndrome is a sporadic condition characterized by a tumor-like lesion with extensive osteolysis, severe symptoms, and a poor prognosis. Poor prognostic indicators include osteolytic lesions of the spine and pleura effusion. PATIENT CONCERNS: A 67-year-old Chinese man with five months history of chest tightness presented to our institution with aggravated shortness of breath. Ultrasonography demonstrated hydrothorax on the right side. The patient's imaging studies (computerized tomography [CT] scan, magnetic resonance imaging, and positron emission tomography [PET]/CT) revealed osteolytic lesions (the skull, several spines, several ribs, both shoulder blades, and the pelvis). DIAGNOSES: Gorham-Stout syndrome. (4) Interventions: We advised the patient to follow a low-fat diet. On the patient, we performed a superior vena cava angiography. The injection of zoledronic acid was used to prevent bone loss. OUTCOMES: We found resolution of chylothorax after a low-fat diet, superior vena cava angiography and injection of zoledronic acid. LESSONS: The possibility of Gorham -Stout syndrome should be ruled out in patients with clinical chylothorax. The relief of chylothorax requires comprehensive treatment.

Sorption and distribution performance of organophosphorus compound (Adenosine 5'-monophosphate)on marine sediments.

In this paper, the kinetics and thermodynamics of Adenosine 5'-monophosphate (AMP) sorption on the sediments obtained from the Yangtze River Estuary and adjacent areas were studied, in combination with the effects of the sediments' properties and media conditions. The kinetics curves could be described by a two-compartment first-order equation, and the equilibrium isotherms fitted well with the modified Langmuir and Freundlich models. The analysis of organic phosphorus (OP) fractions changes after sorption indicated that the contents of exchangeable or loosely sorbed PO increased most significantly. Higher organic matter (OM) of the sediments were favorable for the sorption ability. It was also found that the content of OP and OM in the sediments showed an obvious positive correlation, indicating that organic matter rather than Fe/Al oxides played an important role in the migration of OP in the Yangtze River estuary and its adjacent area. Temperature, salinity and pH of the media influenced the sorption of AMP significantly. Increase of temperature was of benefit to the sorption of AMP, which was a spontaneous and exothermic process according to the calculations of the thermodynamic parameters. The sorption capacity was higher at a moderate salinity in the range of our study. With the pH changing from 3 to 10, the sorption capacity exhibited as a "U-trend" curve.

Resveratrol ameliorates sevoflurane-induced cognitive impairment by activating the SIRT1/NF-κB pathway in neonatal mice.

Sevoflurane, the most commonly used inhaled anesthetic in pediatric anesthesia, has been reported to induce cognitive impairment in developing brain in preclinical and clinical settings. However, the mechanism and therapeutic measures of this developmental neurotoxicity need to be further investigated. Resveratrol, a natural polyphenolic agent, has been reported to improve cognitive function in neurological disorders and aging models through anti-inflammatory activity. However, its effect on sevoflurane-induced cognitive impairment in developing mice remains unknown. The present study was designed to investigate the therapeutic potential of resveratrol on sevoflurane-induced cognitive impairment. Six-day-old mice received anesthesia with 3% sevoflurane 2 h daily on postnatal days (P) 6, P7 and P8. About 100 mg/kg resveratrol were intraperitoneally administered for 6 consecutive days to neonatal mice before anesthesia. Sevoflurane exposure significantly suppressed the expression of Sirtuin 1 (SIRT1) and activated microglia in hippocampi. Furthermore, the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were markedly increased after sevoflurane exposure. Strikingly, resveratrol pretreatment ameliorated sevoflurane-induced SIRT1 inhibition and microglial activation. Of note, resveratrol reversed sevoflurane-induced imbalance of M1/M2 microglia ratio revealed by increasing mRNA level of clusters of differentiation 206 (CD206) and decreasing mRNA levels of clusters of differentiation 86 (CD86) and suppressor of cytokine signaling 3 (SOCS3). Consequently, sevoflurane-induced cognitive impairment in developing mice was ameliorated by resveratrol pretreatment. Taken together, repeated sevoflurane exposure to the developing brain resulted in SIRT1 inhibition, NF-κB acetylation, and microglial activation. Resveratrol pretreatment ameliorated cognitive impairment in developing mice received sevoflurane exposure by modulating SIRT1-NF-κB pathway in microglia. In this regard, our findings open novel directions to explore promising therapeutic targets for preventing the developmental neurotoxicity of sevoflurane.

Chemical Comparison of White Ginseng before and after Extrusion by UHPLC-Q-Orbitrap-MS/MS and Multivariate Statistical Analysis.

Ultrahigh-performance liquid chromatography Quadrupole-Orbitrap tandem mass spectrometry (UHPLC-Q-Orbitrap-MS/MS) was used to compare the composition of ginsenosides in white ginseng (WG) and extruded white ginseng (EWG). A total of 45 saponins, including original neutral ginsenosides, malonyl-ginsenosides, and chemical transformation of ginsenosides, were successfully identified in both WG and EWG. Multivariate statistical analyses including supervised orthogonal partial least squared discrimination analysis (OPLS-DA) and hierarchical clustering analysis (HCA) were used to analyze components of white ginseng before and after extrusion. As a result, three ginsenosides (malonyl (M)-Rb1, M-Rb2, and M-Rc) were found to be increased in WG, while three ginsenosides (Rb2, Rc, and Rg1) were elevated in EWG. In the OPLS-DA S-plot, the different compositions of ginsenoside that were distinguished between WG and EWG were screened out. Experimental results indicate that the UHPLC-Q-Orbitrap-MS/MS is a useful tool to characterize variations of ginsenosides in WG and EWG.

Birth month associates with risk of coronary artery disease and its complications: A propensity score matched analysis / El mes de nacimiento se asocia con el riesgo de padecer una arteriopatía coronaria y sus complicaciones: análisis mediante propensity score

Objective: Birth month and climate affect lifetime disease risk, while the underlying mechanisms remain largely elusive. It is vital to investigate the risks of coronary artery disease (CAD) and its complications in patients born in different months. Methods: A total of 12,263 patient medical records were reviewed from the BioBank of First Affiliated Hospital of Xinxiang Medical University, with 4729 records from patients with CAD (CAD group) and 7534 records from control patients without CAD (control group). Two groups of patients were matched by the propensity score matched method. Birth months were compared between two groups of patients. The relationships between birth month and the numbers of CAD and its complications were also investigated. Interestingly, we also explore the relationship between the birth seasons and the numbers of CAD and its complications. Results: Compared to control, CAD group had greater CAD risks for patients born in November (OR 1.390, 95% CI 1.090-1.772), December (OR 1.358, 95% CI 1.067-1.730), and February (OR 1.332, 95% CI 1.043-1.700) compared to those born in May. Compared to patients born in December, patients born in January to March and May to September had greater risk of heart failure (P<0.05). There was no difference in the incidence of myocardial infarction, conduction block, and atrial fibrillation across birth months (P>0.05). In terms of birth season, patients born in winter have greater CAD risk than those born in spring (OR 1.247, 95% CI 1.075-1.447). And there was no difference in the incidence of CAD complications across with birth seasons (P>0.05). Conclusions: There was a correlation between birth month and CAD. People born in November, December, and February had greater CAD risk, and people born in winter had greater CAD risk. Among CAD patients, those born in January to March and May to September had the greater risk of heart failure

Objetivo: El mes de nacimiento y el clima están relacionados con el riesgo de padecer una enfermedad crónica, aunque siguen desconociéndose en gran medida los mecanismos subyacentes. Resulta fundamental investigar los riesgos de padecer una arteriopatía coronaria (AC) y sus complicaciones en pacientes nacidos en distintos meses. Métodos: Se revisaron un total de 12.263 historias clínicas de pacientes extraídas del Biobanco del primer hospital afiliado de la Universidad Médica de Xinxiang, de las cuales 4.729 correspondían a pacientes con una AC (grupo con AC) y 7.534 correspondían a pacientes control sin una AC (grupo comparativo). Se emparejaron a 2 grupos de pacientes siguiendo el método de pareamiento por puntaje de propensión, y se compararon los meses de nacimiento de los pacientes de ambos grupos. También se investigó la relación existente entre el mes de nacimiento y el número de casos de AC y sus complicaciones. Resulta interesante destacar que también exploramos la relación existente entre las estaciones de nacimiento y el número de casos de AC y sus complicaciones. Resultados: En comparación con los pacientes del grupo comparativo, los pacientes del grupo con AC nacidos en noviembre (razón de posibilidades odds ratio [OR]: 1,390; intervalo de confianza [IC] del 95%: 1,090-1,772), diciembre (OR: 1,358; IC 95%: 1,067-1,730) y febrero (OR: 1,332; IC 95%: 1,043-1,700) presentaban un mayor riesgo de padecer una AC en comparación con los nacidos en mayo. En comparación con los pacientes nacidos en diciembre, los pacientes nacidos entre enero y marzo, y entre mayo y septiembre, presentaron un mayor riesgo de padecer una insuficiencia cardíaca (P<0,05). No se observaron diferencias en la incidencia de infarto de miocardio, bloqueo de la conducción y fibrilación auricular entre los distintos meses de nacimiento (P>0,05). En cuanto a la temporada de nacimiento, los pacientes nacidos en invierno presentaron un mayor riesgo de desarrollar una AC que los nacidos en primavera (OR: 1,247; IC 95%: 1,075-1,447). No se observaron diferencias en la incidencia de complicaciones de la AC entre las distintas temporadas de nacimiento (P>0,05). Conclusiones: Se observó una correlación entre el mes de nacimiento y la AC. Tanto las personas nacidas en los meses de noviembre, diciembre y febrero, como las nacidas en la temporada de invierno presentaron un mayor riesgo de padecer una AC. Entre los pacientes con AC, los nacidos entre enero y marzo, y entre mayo y septiembre, presentaron un mayor riesgo de padecer una insuficiencia cardíaca

Low level of Cyclin-D1 correlates with worse prognosis of clear cell renal cell carcinoma patients.

Cyclin-D1 (CCND1) belongs to the highly conserved cyclin family whose members are characterized by abundant expression during the cell cycle. As an oncogene, high level of CCND1 was observed and related to poor prognosis and tumor recurrence in many cancers. In this study, we focused on the role of CCND1 in the clinical outcome of clear cell renal cell carcinoma (ccRCC). Gene Expression Omnibus database, The Cancer Genome Atlas database, and immunohistochemical staining were used. The mRNA and protein levels of CCND1 were significantly enhanced in ccRCC tumor tissues. However, the low level of CCND1, but not high level of CCND1, was related to poor prognosis and tumor recurrence in ccRCC. Further analysis showed that CCND1 mRNA level decreased with increasing ccRCC tumor grades and the rate of recurrence in ccRCC patients. In a nomogram model, the CCND1 mRNA level was shown to help predict ccRCC patient recurrence. CCND1 is a strong determinant for prediction of recurrence. The patients with high CCND1 level appear to have a more favorable prognosis together with more frequent low-grade tumors and low rate of recurrence. This is the first study to investigate the prognostic roles of CCND1 in ccRCC and discovered that CCND1 had an unconventional positive impact on the clinical outcome of ccRCC patients.

Birth month associates with risk of coronary artery disease and its complications: A propensity score matched analysis.

OBJECTIVE: Birth month and climate affect lifetime disease risk, while the underlying mechanisms remain largely elusive. It is vital to investigate the risks of coronary artery disease (CAD) and its complications in patients born in different months. METHODS: A total of 12,263 patient medical records were reviewed from the BioBank of First Affiliated Hospital of Xinxiang Medical University, with 4729 records from patients with CAD (CAD group) and 7534 records from control patients without CAD (control group). Two groups of patients were matched by the propensity score matched method. Birth months were compared between two groups of patients. The relationships between birth month and the numbers of CAD and its complications were also investigated. Interestingly, we also explore the relationship between the birth seasons and the numbers of CAD and its complications. RESULTS: Compared to control, CAD group had greater CAD risks for patients born in November (OR 1.390, 95% CI 1.090-1.772), December (OR 1.358, 95% CI 1.067-1.730), and February (OR 1.332, 95% CI 1.043-1.700) compared to those born in May. Compared to patients born in December, patients born in January to March and May to September had greater risk of heart failure (P<0.05). There was no difference in the incidence of myocardial infarction, conduction block, and atrial fibrillation across birth months (P>0.05). In terms of birth season, patients born in winter have greater CAD risk than those born in spring (OR 1.247, 95% CI 1.075-1.447). And there was no difference in the incidence of CAD complications across with birth seasons (P>0.05). CONCLUSIONS: There was a correlation between birth month and CAD. People born in November, December, and February had greater CAD risk, and people born in winter had greater CAD risk. Among CAD patients, those born in January to March and May to September had the greater risk of heart failure.

AMPK activation attenuates inflammatory pain through inhibiting NF-κB activation and IL-1ß expression.

BACKGROUND: Chronic pain is a major clinical problem with limited treatment options. Previous studies have demonstrated that activation of adenosine monophosphate-activated protein kinase (AMPK) can attenuate neuropathic pain. Inflammation/immune response at the site of complete Freund's adjuvant (CFA) injection is known to be a critical trigger of the pathological changes that produce inflammatory pain. However, whether activation of AMPK produces an analgesic effect through inhibiting the proinflammatory cytokines, including interleukin-1ß (IL-1ß), in inflammatory pain remains unknown. METHODS: Inflammatory pain was induced in mice injected with CFA. The effects of AICAR (5-aminoimidazole-4-carboxyamide ribonucleoside, an AMPK activator), Compound C (an AMPK inhibitor), and IL-1ra (an IL-1 receptor antagonist) were tested at day 4 after CFA injection. Inflammatory pain was assessed with von Frey filaments and hot plate. Immunoblotting, hematoxylin and eosin (H&E) staining, and immunofluorescence were used to assess inflammation-induced biochemical changes. RESULTS: The AMPK activator AICAR produced an analgesic effect and inhibited the level of proinflammatory cytokine IL-1ß in the inflamed skin in mice. Moreover, activation of AMPK suppressed CFA-induced NF-κB p65 translocation from the cytosol to the nucleus in activated macrophages (CD68+ and CX3CR1+) of inflamed skin tissues. Subcutaneous injection of IL-1ra attenuated CFA-induced inflammatory pain. The AMPK inhibitor Compound C and AMPKα shRNA reversed the analgesic effect of AICAR and the effects of AICAR on IL-1ß and NF-κB activation in inflamed skin tissues. CONCLUSIONS: Our study provides new information that AMPK activation produces the analgesic effect by inhibiting NF-κB activation and reducing the expression of IL-1ß in inflammatory pain.

[Correlation between the genotypes and clinical symptoms of human papilloma virus in male outpatients at STD clinics].

OBJECTIVE: To investigate the distribution of the human papilloma virus (HPV) and its genotypes in the male outpatients at the clinics of sexually transmitted diseases (STD) in Changshu and analyze its association with the primary clinical symptoms so as to provide some evidence for the prevention and treatment of HPV infection in men. METHODS: We collected exfoliated cell samples from the external genitals of 602 male outpatients at the STD clinics in Changshu from February 2016 to February 2018, extracted and amplified nucleic acids from the samples, and detected the HPV genotypes using the gene chip technique. We performed statistical analyses on the types of symptoms in clinical diagnosis and their correlation with the genotypes of HPV using the chi-square test. RESULTS: The HPV positive rate in the male STD clinics was 48.2%, of which 47.2 % fell into the low-risk type, 30.0% with multiple infections. The main genotypes included HPV types 6, 11, 39, and 52, and the main HPV-related clinical symptoms were verruca (43.1%) and erythra (41.0%). Low-risk types 6 and 11 accounted for a significantly higher percentage than the high-risk types in the verruca patients (60.0% vs 15.0%, , P < 0.05), but showed no statistically significant difference from the latter in the erythra patients (38.7% vs 38.7%, P > 0.05). The incidence of low-risk infection was remarkably higher than that of high-risk infection in the acrobystitis and balanitis patients (P < 0.05), while the high-risk types constituted a markedly higher percentage than the low-risk and high- and low-risk mixed types in the asymptomatic men at physical examination (84.6% vs 0.0% and 15.4%, P < 0.05). CONCLUSIONS: The HPV positive rate was as high as 48.2% in the males at the STD clinics in Changshu, and the main infection type was low-risk genotype single infection. The clinical symptoms of low-risk infection were mainly verruca and prepuce balanitis, and the high-risk type was mostly asymptomatic at physical examination.

Secretoneurin suppresses cardiac hypertrophy through suppression of oxidant stress.

The neuropeptide secretoneurin (SN) plays protective roles in myocardial ischemia. In the present study, the effect of SN in cardiac hypertrophy was investigated. We observed that, in isoproterenol (ISO) treatment induced cardiac or cardiomyocytes hypertrophy, a marked increase in the expression of endogenous SN in mouse plasma, myocardium and primary-cultured cardiomyocytes occurs. In hypertrophic mice, the heart size, heart weight/body weight (HW/BW) ratio, cardiomyocyte size, and atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) expression were significantly higher than those in controls but were effectively suppressed by SN gene therapy. Similarly, the protective effects of SN were also observed in cultured cardiomyocytes following ISO treatment. SN significantly increased the activity of catalase and superoxide dismutase (SOD) in parallel with the decrease in reactive oxygen species levels in cardiomyocytes. We observed that SN evoked the activation of all of the AMPK, P38/MAPK and ERK/MAPK pathways in cardiomyocytes, but pretreatment with only AMPK inhibitor (compound C) and ERK1/2/MAPK inhibitor (PD98059) counteracted the protective effects of SN against cardiomyocyte hypertrophy and the suppressive effects of SN on oxidant stress in cardiomyocytes. These results indicated that endogenous SN is induced in hypertrophic cardiomyocytes, and may play a protective role in the pathogenesis of cardiac hypertrophy. These results suggest that exogenous SN supplementation protects the cardiac hypertrophy induced by ISO treatment through the activation of AMPK and ERK/MAPK pathways, thus upregulating antioxidants and suppressing oxidative stress.

iNOS-derived peroxynitrite mediates high glucose-induced inflammatory gene expression in vascular smooth muscle cells through promoting KLF5 expression and nitration.

Inducible NO synthase (iNOS) expression and peroxynitrite formation are significantly increased in diabetic vascular tissues. Transcription factor KLF5 activates iNOS gene transcription and is involved in vascular inflammatory injury and remodeling. However, mutual regulation between KLF5, iNOS and peroxynitrite in diabetic vascular inflammation, as well as the underlying mechanisms, remain largely unknown. In this study, we found a marked increase in KLF5 and iNOS expression in vascular smooth muscle cells (VSMC) of diabetic patients. High glucose-induced expression of KLF5 and iNOS was also observed in cultured mouse VSMCs. Further investigation showed that high glucose induced KLF5 nitration by iNOS-mediated peroxynitrite generation, and nitrated KLF5 increased its interaction with NF-κB p50 and thus cooperatively activated the expression of inflammatory cytokines TNF-α and IL-1ß. Furthermore, we showed that the VSMC-specific knockout of KLF5 dramatically reduced inflammatory cytokine expression in the vascular tissues of diabetic mice. Moreover, 17ß-estradiol (E2) inhibited high glucose-mediated effects in VSMCs, and in the response to E2, estrogen receptor (ER) α competed with KLF5 for binding to NF-κB p50, which in turn leads to the suppression of inflammatory gene expression in VSMCs. Together, the present findings were the first to show that KLF5 expression and nitration by iNOS-mediated peroxynitrite are necessary for the induction of TNF-α and IL-1ß expression in VSMCs of diabetic vascular tissues.

Identification of mTOR as a primary resistance factor of the IAP antagonist AT406 in hepatocellular carcinoma cells.

Dysregulation of inhibitor of apoptosis (IAP) proteins (IAPs) in hepatocellular carcinoma (HCC) is often associated with poor prognosis. Here we showed that AT406, an IAP antagonist, was cytotoxic and pro-apoptotic to both established (HepG2, SMMC-7721 lines) and primary HCC cells. Activation of mTOR could be a key resistance factor of AT406 in HCC cells. mTOR inhibition (by OSI-027), kinase-dead mutation or knockdown remarkably enhanced AT406-induced lethality in HCC cells. Reversely, forced-activation of mTOR by adding SC79 or exogenous expressing a constitutively active S6K1 (T389E) attenuated AT406-induced cytotoxicity against HCC cells. We showed that AT406 induced degradation of IAPs (cIAP-1 and XIAP), but didn't affect another anti-apoptosis protein Mcl-1. Co-treatment of OSI-027 caused simultaneous Mcl-1 downregulation to overcome AT406's resistance. Significantly, shRNA knockdown of Mcl-1 remarkably facilitated AT406-induced apoptosis in HCC cells. In vivo, AT406 oral administration suppressed HepG2 tumor growth in nude mice. Its activity was potentiated with co-administration of OSI-027. We conclude that mTOR could be a key resistance factor of AT406 in HCC cells.