p38-mediated FOXN3 phosphorylation modulates lung inflammation and injury through the NF-κB signaling pathway.

NF-κB activates the primary inflammatory response pathway responsible for methicillin-resistant Staphylococcus aureus (MRSA)-induced lung inflammation and injury. Here, we report that the Forkhead box transcription factor FOXN3 ameliorates MRSA-induced pulmonary inflammatory injury by inactivating NF-κB signaling. FOXN3 competes with IκBα for binding to heterogeneous ribonucleoprotein-U (hnRNPU), thereby blocking ß-TrCP-mediated IκBα degradation and leading to NF-κB inactivation. FOXN3 is directly phosphorylated by p38 at S83 and S85 residues, which induces its dissociation from hnRNPU, thus promoting NF-κB activation. After dissociation, the phosphorylated FOXN3 becomes unstable and undergoes proteasomal degradation. Additionally, hnRNPU is essential for p38-mediated FOXN3 phosphorylation and subsequent phosphorylation-dependent degradation. Functionally, genetic ablation of FOXN3 phosphorylation results in strong resistance to MRSA-induced pulmonary inflammatory injury. Importantly, FOXN3 phosphorylation is clinically positively correlated with pulmonary inflammatory disorders. This study uncovers a previously unknown regulatory mechanism underpinning the indispensable role of FOXN3 phosphorylation in the inflammatory response to pulmonary infection.

Flexible aqueous Cr-ion hybrid supercapacitors with remarkable electrochemical properties in all climates.

The integration of hostless battery-like metal anodes for hybrid supercapacitors is a realistic design method for energy storage devices with promising future applications. With significant Cr element deposits on Earth, exceptionally high theoretical capacity (1546 mAh g-1), and accessible redox potential (-0.74 V vs. reversible hydrogen electrode) of Cr metals, the design of Cr anodes has rightly come into our focus. This work presents a breakthrough design of a flexible Cr-ion hybrid supercapacitor (CHSC) based on a porous graphitized carbon fabric (PGCF) substrate prepared by K2FeO4 activation. In the CHSC device, PGCF acts as both a current collector and cathode material due to its high specific surface area and superior conductivity. The use of a highly concentrated LiCl-CrCl3 electrolyte with high Cr plating/stripping efficiency and excellent antifreeze properties enables the entire PGCF-based CHSC to achieve well-balanced performance in terms of energy density (up to 1.47 mWh cm-2), power characteristics (reaching 9.95 mW cm-2) and durability (95.4% capacity retention after 30,000 cycles), while realizing it to work well under harsh conditions of -40 °C. This work introduces a new concept for low-temperature energy storage technology and confirms the potential application of Cr anodes in hybrid supercapacitors.

Association of metabolically healthy obesity in young adulthood with myocardial structure and function.

BACKGROUND: Obesity is major cause of cardiovascular diseases. Metabolically healthy obesity (MHO) may increase heart failure risk early in life, and may be reflected in impaired cardiac structure and function. Therefore, we aimed to examine the relationship between MHO in young adulthood and cardiac structure and function. METHODS: A total of 3066 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study were included, who completed echocardiography in young adulthood and middle age. The participants were grouped by obesity status (body mass index ≥30 kg/m2) and poor metabolic health (≥2 criteria for metabolic syndrome) into four metabolic phenotypes as follows: metabolically healthy non-obesity (MHN), MHO, metabolically unhealthy non-obesity (MUN), metabolically unhealthy obesity (MUO). The associations of the metabolic phenotypes (MHN serving as the reference) with left ventricular (LV) structure and function were evaluated using multiple linear regression models. RESULTS: At baseline, mean age was 25 years, 56.4% were women, and 44.7% were black. After a follow-up 25 years, MUN in young adulthood was associated with worse LV diastolic function (E/é ratio, ß [95% CI], 0.73 [0.18, 1.28]), worse systolic function (global longitudinal strain [GLS], 0.60 [0.08, 1.12]) in comparison with MHN. MHO and MUO were associated with LV hypertrophy (LV mass index, 7.49 g/m2 [4.63, 10.35]; 18.23 g/m2 [12.47, 23.99], respectively), worse diastolic function (E/é ratio, 0.67 [0.31, 1.02]; 1.47 [0.79, 2.14], respectively), and worse systolic function (GLS, 0.72 [0.38, 1.06]; 1.35 [0.64, 2.05], respectively) in comparison with MHN. These results were consistent in several sensitivity analyses. CONCLUSIONS: In this community-based cohort using data from the CARDIA study, obesity in young adulthood was significantly associated with LV hypertrophy, worse systolic and diastolic function regardless of metabolic status. Relationship of Baseline Metabolic Phenotypes with Young Adulthood and Midlife Cardiac Structure and Function. Adjusted for year 0 covariates: age, sex, race, educational level, smoking status, drinking status, and physical activity; metabolically healthy non-obesity was used as a reference category for comparison. † Criteria for metabolic syndrome are listed in Supplementary Table S6. MUN metabolically unhealthy non-obesity, MHO metabolically healthy obesity, LVMi left ventricular mass index, LVEF left ventricular ejection fraction, E/A early to late peak diastolic mitral flow velocity ratio, E/é mitral inflow velocity to early diastolic mitral annular velocity, CI confidence interval.

CircPSMC3 Suppresses Migration and Invasion of Non-Small Cell Lung Cancer Cells via miR-182-5p/NME2 Axis.

BACKGROUND CircPSMC3 has been reported to play important roles in the occurrence and development of cancer. However, the role of circPSMC3 in NSCLC (non-small cell lung cancer) and the underlying mechanisms remain unclear. MATERIAL AND METHODS The expression of circPSMC3 in NSCLC tissues was measured through qRT-PCR (quantitative real-time polymerase chain reaction). The effect of circPSMC3 on the invasion and migration of NSCLC cell line H1299 was determined through transwell invasion assay and wound healing assay. Dual-luciferase reporter assay was performed for exploring the regulatory interaction between circPSMC3, miR-182-5p, and NME2. RESULTS Compared with adjacent normal tissues, the expression of circPSMC3 in NSCLC tissues was decreased. Lower circPSMC3 expression was closely associated with lymph node metastasis and higher TNM stage in NSCLC patients. Biological function analysis suggested that circPSMC3 inhibits the invasion and migration of H1299 cells through upregulating the expression of NME2. Mechanistically, circPSMC3 sponges miR-182-5p to suppress the invasion and migration of NSCLC cells via upregulating NME2 expression. CONCLUSIONS CircPSMC3 inhibits the invasion and migration of NSCLC cells through the miR-182-5p/NME2 signaling pathway.

PVT1 Promotes Angiogenesis by Regulating miR-29c/Vascular Endothelial Growth Factor (VEGF) Signaling Pathway in Non-Small-Cell Lung Cancer (NSCLC).

BACKGROUND Lung cancer is a common tumor. Non-small-cell lung cancer (NSCLC) accounts for over 85% of lung cancer and has a high degree of malignancy. Angiogenesis plays an important role in NSCLC progression. Some studies have found that PVT1 can promote angiogenesis in tumor tissues, but the role of PVT1 in angiogenesis in NSCLC, as well as the underlying mechanism, is unclear. MATERIAL AND METHODS To explore the role of PVT1 in NSCLC, qRT-PCR, Western blot, luciferase reporter assay, and ELISA were carried out for detecting the relationship among PVT1, miR-29c, and VEGF. Tube formation assay was used to assess the role of PVT1 in angiogenesis in NSCLC. RESULTS Our results showed that higher PVT1 was expressed in NSCLC and the elevated PVT1 was closely related to angiogenesis and poor prognosis in NSCLC. Further functional analysis showed that higher PVT1 expression could promote angiogenesis by regulating VEGF in NSCLC. Mechanistically, the luciferase reporter assay confirmed that VEGF was the targeted gene of miR-29c. In addition, we found that miR-29c is an inhibitory target of PVT1. CONCLUSIONS We found that PVT1 promotes angiogenesis through targeting the miR-29c/VEGF signaling pathway in NSCLC.

[Progress in regulatory T cells and hepatocellular carcinoma].

As a functionally unique subset of T cells, regulatory T cells (Treg) suppress tumor immune responses effectively through a variety of mechanisms and play an important role in tumorigenesis and tumor progression. There is growing evidence to suggest that Treg participates in the formation and development of hepatic tumor, especially the HCC. Elucidation of the mechanisms for involvement of Treg in HCC progression may provide new ideas for liver cancer therapy through a point of view regarding immunology.

Resource Utilization of Waste Cooking Oil Catalyzed by Na2CO3/ZSM-5.

A catalyst with a simple synthetic process and good catalytic performance was prepared using Na2CO3 as the active component and ZSM-5 as the carrier for the resource utilization of waste cooking oil. The structure of Na2CO3/ZSM-5 was characterized by Fourier transform infrared spectroscopy, X-ray diffraction, and scanning electron microscopy, and the effects of parameters such as Na2CO3 loading, catalyst percentage, and reaction time on the yield of fatty acid methyl esters were investigated. The results showed that the conversion of waste cooking oil to fatty acid methyl esters yielded up to 96.89% when the Na2CO3 loading was 35%, the reaction temperature was 65 °C, the reaction time was 2 h, and the catalyst percentage was 1 wt %. The Na2CO3/ZSM-5 catalyst could be used to replace H2SO4 or NaOCH3 in the industrial treatment of waste cooking oil for its resource utilization.

Urchin-like (NH4)2V10O25·8H2O hierarchical arrays with significantly expanded interlayer spacing for superior aqueous zinc-ion batteries.

The practical application of zinc ion batteries (ZIBs) can be facilitated by designing cathode materials with unique structures that can overcome the critical problems of slow reaction kinetics and large volume expansion associated with the intercalation reaction of divalent zinc ions. In this study, a novel urchin-like (NH4)2V10O25·8H2O assembled from nanorods was synthesized by a simple hydrothermal method, noted as U-NVO. The interlayer organic pillar of cetyltrimethylammonium cation (CTAB) has been intercalated between layers to regulate the interlayer microstructure and expand the interlayer spacing to 1.32 nm, which effectively increased the contact between the electrode and electrolyte interface and shortened the diffusion path of electrolyte ions. The interlayer pillars of structural H2O and NH4+ provide a flexible framework structure and enhance the cohesion of the layered structure, which helps to maintain structural stability during the charging and discharging process, resulting in long-term durability. These unique properties result in the U-NVO cathodes demonstrating high specific capacity (401.7 mA h g-1 at 0.1 A g-1), excellent rate capability (99.6 % retention from 0.1 to 5 A g-1 and back to 0.1 A g-1), and long-term cycling performance (∼87.5 % capacity retention after 2600 cycles). These results offer valuable insights into the design of high-performance vanadium oxide cathode materials.

Effect of Intensive Lifestyle Intervention on Cardiovascular Risk Factors: Analysis From the Perspective of Long-Term Variability.

BACKGROUND: An association between variability of cardiovascular risk factors and cardiovascular events has been reported. We examined whether intensive lifestyle intervention (ILI) for weight loss decreased variability of cardiovascular risk factors with a view to additional cardiometabolic benefits. METHODS AND RESULTS: This study was a post hoc secondary analysis of the Look AHEAD (Action for Health in Diabetes) study. Cardiovascular risk factors were measured at 1-year intervals for 4 years in 4249 adults with overweight or obesity and type 2 diabetes who were randomly assigned to ILI or diabetes support and education. Long-term variability was defined as the SD of cardiovascular risk factors during 4-year follow-up. At multiple linear regression analysis, compared with the diabetes support and education group, the ILI group was associated with reduced variability of fasting blood glucose (ß=-1.49 [95% CI, -2.39 to -0.59]), total cholesterol (ß=-1.12 [95% CI, -1.75 to -0.48]), and low-density lipoprotein cholesterol (ß=-1.04 [95% CI, -1.59 to -0.49]), as well as increased variability of systolic blood pressure (ß=0.27 [95% CI, 0.00-0.54]). No significant effect of ILI was found on the variability of diastolic blood pressure (ß=-0.08 [95% CI, -0.22 to 0.05]). CONCLUSIONS: Among adults with overweight or obesity and type 2 diabetes, ILI may reduce long-term variability of fasting blood glucose, total cholesterol, and low-density lipoprotein cholesterol. Our results support that ILI should be recommended to individuals with diabetes as part of management of long-term glycemic and blood lipid control.

Serum Klotho Modifies the Associations of 25-Hydroxy Vitamin D With All-Cause and Cardiovascular Mortality.

BACKGROUND: The association between 25-hydroxyvitamin D and mortality remains controversial. Klotho, a biomarker of vitamin D activation and metabolism, may play a key role in this association. However, it is unclear whether the association between vitamin D deficiency and mortality risk is modified by klotho levels. Therefore, this study investigated the joint association of serum 25-hydroxyvitamin D [25(OH)D] and klotho with mortality risk in American community-dwelling adults. METHODS: A total of 9870 adults from the National Health and Nutrition Examination Survey (2007-2016) were included in our study. Mortality data were ascertained by linking participants to National Death Index records. Cox proportional hazards models were used to assess the association among serum 25(OH)D, serum klotho, and all-cause and cardiovascular disease (CVD) mortality. RESULTS: We found a significant interaction between klotho and serum 25(OH)D in all-cause mortality (P = .028). With klotho > 848.4 pg/mL (risk threshold on mortality), no significant all-cause and CVD mortality risk was observed at any level of serum 25(OH)D. However, with klotho < 848.4 pg/mL, a significant all-cause and CVD mortality risk was observed with serum 25(OH)D < 50 nmol/L [hazards ratio (HR), 1.36; 95% confidence interval (CI), 1.10-1.69; HR, 1.78; 95% CI, 1.16-3.45) and serum 25(OH)D of continuous variable (HR, 0.98; 95% CI, .97-.99; HR, 0.98; 95% CI, .98-.99). In addition, vitamin D metabolism disruption accessed by the combination of decreasing serum 25(OH)D (<50 nmol/L) and klotho (<848.4 pg/mL) was associated with significant all-cause mortality (HR, 1.48; 95% CI, 1.11-1.96) and CVD mortality (HR, 2.36; 95% CI, 1.48-3.75). CONCLUSIONS: Vitamin D-associated mortality risk is observed only with concurrently decreasing klotho, indicating that vitamin D metabolism dysfunction increases the risk of mortality. Klotho levels could help predict long-term mortality outcomes and thus may be useful concurrently for guiding vitamin D supplementation therapy decision-making in populations with vitamin D deficiency.

Cardiovascular effects of weight loss in old adults with overweight/obesity according to change in skeletal muscle mass.

BACKGROUND: Patients with overweight/obesity and type 2 diabetes are encouraged to lose weight, but not all losing weight gain better cardiovascular health, especially old adults. The change in skeletal muscle mass (SMM) could be the key that explains the heterogenous cardiovascular effects of weight loss. This study aims to assess whether the cardiovascular effects of weight loss vary for those gaining skeletal muscle along with weight loss. METHODS: The old adults with overweight/obesity and type 2 diabetes in the Look AHEAD study having muscle measurement from dual-energy X-ray absorptiometry were included. Based on the weight change (WC) and SMM change (SMMC) between baseline and the 4-year follow-up, participants were allocated into three groups-weight gain (WG) group, weight loss with muscle loss (WL-ML) group and weight loss with muscle gain (WL-MG) group. Cox proportional hazards regression was performed to evaluate the cardiovascular risk of those gaining or losing SMM with weight loss compared with those gaining weight. Among the participants with weight loss, the ratio of SMMC/WC was calculated, and the association of SMMC/WC with primary cardiovascular outcome was assessed. RESULTS: A total of 491 participants were included in the study with an average age of 64.56 ± 3.81 years old. A total of 47.0% were male and 49.9% were from the intensive lifestyle intervention arm. Based on their WC and SMMC, 43 were assigned to the WG group, 373 to the WL-ML group and 75 to the WL-MG group. Over a follow-up of almost 10 years, 97 participants encountered the primary endpoint. The WG group had the highest incidence of 25.59%, the WL-MG group had the lowest incidence of 9.33% and the WL-ML group had 21.18% (P = 0.040). In the fourth adjusted Cox model, the WL-MG group achieved significantly decreased odds of the primary endpoint compared with the WG group (hazard ratio [HR] 0.33, 95% confidence interval [CI] [0.12, 0.87], P = 0.026), whilst the WL-ML group did not (HR 0.91, 95% CI [0.47, 1.78], P = 0.670). Among the participants with weight loss, when SMMC/WC reached around 50%, this HR soared to approximately two-fold. CONCLUSIONS: The participants gaining SMM along with weight loss achieved the lowest odds of adverse cardiovascular events, whilst those who lost SMM along with weight loss had comparable cardiovascular risk with those gaining weight. The more muscle lost during weight loss, the greater the harm. The cardiovascular effects of weight loss were modulated by whether the participants gained SMM meanwhile losing weight.

A low-cost and efficient route for large-scale synthesis of NiCoSx nanosheets with abundant sulfur vacancies towards quasi-industrial electrocatalytic oxygen evolution.

Transition-metal sulfides (TMS) have piqued a great deal of interest due to their unprecious nature and high intrinsic catalytic activity for water splitting. In this work, a low-cost and efficient route was developed, which included electrodeposition to prepare Ni-Co layered double hydroxide (NiCo-LDH) followed by ion exchange to form nickel cobalt sulfide (NiCoSx). Electrochemical reduction was used to modulate sulfur vacancies in order to produce sulfur vacancies-rich NiCoSx with nanosheet arrays on -three-dimensional nickel foam (NiCoSx-0.4/NF) with a large area of more than 250 cm2. Combining data from experiments and density functional theoretical (DFT) calculations reveals that engineered sulfur vacancies change the electronic structure, electron transfer property, and surface electron density of NiCoSx, significantly improving the free energy of water adsorption and boosting electrocatalytic activity. The developed NiCoSx-0.4/NF has long-term stability of more than 300 h at 500 mA cm-2 in 1 M KOH at ambient temperature and only needs a 289 mV overpotential at 100 mA cm-2. Remarkably, the synthesized electrocatalyst rich in sulfur vacancies, exhibits exceptional performance with a high current density of up to 1.9 A cm-2 and 1 A cm-2 in 6 M KOH and leads to overpotentials of 286 mV at 80 °C and 358 mV at 60 °C, respectively. The catalyst's practicability under quasi-industrial conditions (60 °C, 6 M KOH) is further demonstrated by its long-term stability for 220 h with only a 3.9 % potential increase at 500 mA cm-2.

MoSe2 hollow nanospheres with expanded selenide interlayers for high-performance aqueous zinc-ion batteries.

Transition metal dichalcogenides (TMDs) as materials for aqueous zinc-ion batteries (ZIBs) have received a lot of interest because of their large theoretical capacity and unique layered structure. However, the sluggish kinetics and inferior cyclic stability limit the usefulness of ZIBs. In the present investigation, the interlayer spacing enlarged MoSe2 hollow nanospheres comprised of nanosheets with ultrathin shells have been successfully synthesized through a combined strategy of template assistance and anion-exchange reaction. The hierarchical ultrathin nanosheets and hollow structure effectively suppress the agglomeration of pure nanosheets and ameliorate volume fluctuations induced by ion migration during (dis)charging/charging. The interlayer expansion provides good channels for the transport of Zn2+ ions and speeds up the insertion/extraction of Zn2+. In addition, in-situ carbon modification can significantly improve electronic conductivity. Therefore, the electrode prepared from MoSe2 hollow nanospheres with enlarged interlayer spacing not only exhibits outstanding cycle stability (capacity retention of 94.5% after 1600 cycles) but also exhibits high-rate capability (266.1 mA h g-1 at 0.1 A g-1 and 203.6 mA h g-1 at 3 A g-1). This work could provide new insights into the design of cathode using TMDs of hollow structure for Zn2+ storage.

Effect of intensive lifestyle intervention on the association between weight variability and major adverse cardiovascular events in overweight or obese adults with type 2 diabetes mellitus.

AIMS/INTRODUCTION: Weight variability is associated with cardiovascular outcomes in diabetic patients. However, whether the guideline-recommended intensive lifestyle intervention (ILI) will affect this association in overweight or obese adults with diabetes is not well established. MATERIALS AND METHODS: In 3,859 participants from the Action for Health in Diabetes (Look AHEAD) trial, the associations of 4 year weight variability measured by variability independent of the mean (VIM) with major adverse cardiovascular event (MACE) and secondary outcomes in ILI and diabetes support & education (DSE) arm were evaluated. RESULTS: During a median follow-up of 9.6 years, 255 (12.9%) participants in the ILI arm and 247 (13.2%) participants in the DSE arm developed MACE. Participants with the highest quartile of weight variability (VIM Q4) experienced a 2.23-fold higher risk of MACE compared with the lowest quartile (VIM Q1) in the DSE arm (hazard ratio [HR] 2.23; 95% CI 1.51-3.30). Compared with the lowest weight variability (VIM Q1), participants with the highest weight variability (VIM Q4) were associated with higher risks of secondary cardiovascular composite outcome (HR 1.88; 95% CI 1.20-2.95), all-cause mortality (HR 3.19; 95% CI 1.75-5.82), and myocardial infarction (HR 1.95; 95% CI 1.12-3.37) in the DSE arm. CONCLUSIONS: Among the overweight or obese individuals with type 2 diabetes mellitus, rising weight variability was independently associated with increased MACE risks in the DSE arm. Therefore, a guideline-recommended ILI strategy for weight loss should be adopted to improve cardiovascular outcomes without worrying about the effect of weight fluctuations.

A systematic pan-cancer analysis identifies RIOK3 as an immunological and prognostic biomarker.

OBJECTIVES: Despite recent research highlighting the critical function of RIO kinase 3 (RIOK3) in a variety of malignancies, a comprehensive evaluation of RIOK3 in human tumors is absent. Our study helps to clarify the molecular mechanism of RIOK3 in carcinogenesis from multiple perspectives. METHODS: Our research looked into the potential oncogenic role of RIOK3 in 33 cancers using TCGA (The Cancer Genome Atlas), GTEx (Genotype-Tissue Expression Project), GEO (Gene Expression Omnibus) datasets, and several bioinformatics tools. RESULTS: RIOK3 expression in tumors is disordered compared to normal tissue, and it is highly linked with the level of MMR (Mismatch repair) gene mutations and DNA methyltransferase expression. According to univariate survival analysis, it could be used as an independent prognostic factor. Further investigation demonstrated that RIOK3 expression was correlated with cancer-associated fibroblast, neutrophil, and endothelial infiltration levels in kidney cancer and was positively correlated with the expression of immune checkpoint markers in different cancers. The functional pathways of RIOK3 also included cell-cell adhesion, protein phosphorylation, and innate immune-related functions. CONCLUSIONS: These findings suggest that RIOK3 could be used as an immunological and prognostic biomarker in various malignant tumors.

Research on Residual Stress of a BS700 Butt-Welded Box Section and Its Influence on the Stability of Axial Compression Members.

BS700 high-strength steel is widely used in engineering. Welding residual stress during the manufacturing process has a significant influence on the structural safety and service life of steel structures. In this study, the residual stress of a BS700 butt-welded box section axial compression member was studied by the blind-hole method, its distribution law was summarized, and a residual stress distribution model was established. By establishing a finite element model considering initial geometric imperfection and residual stress, the influence of residual stress on the stability of axial compression members was analyzed. The results illustrated that the residual tensile stress near the weld in the welded box section axial compression members was the largest: the average residual tensile stress reached 76.6% of the measured steel yield strength, the residual tensile stress at the roof and web were almost the same, and the residual tensile stress at the corner was approximately 11.6% of the measured yield strength. The residual stress had a different influence on the stability factor of the axial compression members with different width-thickness ratios, and the influence decreased with the increase in the width-thickness ratio. In addition, when the slenderness ratio of members ranged between 20 and 70, the residual stress had a significant influence on the stability of members, while outside that interval, the influence was relatively small.

Ginsenoside Rh2 activates α-catenin phosphorylation to inhibit lung cancer cell proliferation and invasion.

The efficacy of ginsenoside Rh2 (Rh2) in cancer therapy has been reported; however, its function in lung cancer remains unknown. To analyze the role of Rh2 in the inhibition of lung cancer cell proliferation in the present study, protein expression levels of E-cadherin, vimentin, ß-catenin, Smo, Gli1, and α-catenin were assessed by western blotting, whilst mRNA expression levels of TCF7 FZD8, Smo, Gli1, Gli2, and Gli3 were determined by reverse transcription-quantitative PCR in the A549 cell line. Phosphorylation sites were detected by proteomic methods and cell proliferation was analyzed by MTT assay. The present study revealed that Rh2 treatment significantly inhibited cell proliferation. Western blotting indicated that the expression levels of E-cadherin were increased and vimentin was downregulated in Rh2-treated cells compared with control cells. Treatment of A549 cells with Rh2 suppressed phosphorylation of five distinct proteins and increased phosphorylation of nine proteins. Among them, the phosphorylation of α-catenin at S641 was significantly induced. Rh2 treatment suppressed the expression levels of key genes involved in Wnt (Wnt3, transcription factor 7 and frizzled class receptor 8) and hedgehog [smoothened, frizzled class receptor (Smo), GLI family zinc finger (Gli)1, Gli2, and Gli3] signaling. Immunoblotting results indicated that ß-catenin, Smo and Gli1 protein expression levels were also suppressed by treatment with Rh2 compared with control treatment. Expression of α-catenin S641D, a phosphomimetic form of α-catenin, inhibited the accumulation of ß-catenin and Gli1 and inhibited cell proliferation and invasion. Furthermore, knockdown of ß-catenin (CTNNB1) or Gli1 with specific small interfering RNAs inhibited cell proliferation, whereas overexpression of these genes had an opposite effect. Additionally, overexpression of ß-catenin or Gli1 activated cell proliferation, even in the presence of Rh2, suggesting that Rh2 affects A549 cell proliferation through inhibition of Wnt and hedgehog signaling by phosphorylation of α-catenin at S641. Together, these data suggested that Rh2 treatment may inhibit the proliferation of A549 lung cancer cells. Further exploration of the underlying mechanism by which Rh2 inhibits cell proliferation is warranted.

Clinical application and analysis of hepatitis C virus NS3 antigen detection by ELISA in human serum.

BACKGROUND: Hepatitis C virus (HCV) core antigen assays have been produced to exclude infectious donations collected during the preseroconversion window phase (PWP). For the same purpose, we evaluated the specificity and sensitivity of a novel hepatitis C virus NS3 antigen detection immunoassay and the application of this assay in clinical diagnosis. METHODS: Samples from 77 healthy subjects, 173 anti-HCV positive patients and 3708 hepatitis patients other than HCV positive were tested with the HCV NS3 antigen assay. Some HCV NS3 antigen positive samples were further validated with HCV-RNA, neutralization and immunodot assays. Twenty-five sequential samples from 11 HCV NS3 antigen positive patients were subjected to kinetic study. RESULTS: Only 48 (1.3%) of 3708 anti-HCV negative samples were positive for HCV NS3 antigen. Among them, 44 of 3030 samples from patients only infected with HBV were HCV NS3 antigen positive, 4 of the 445 samples from patients infected with other type hepatitis were HCV NS3 antigen positive. In addition, 42 (24.3%) of 173 anti-HCV positive samples were HCV NS3 antigen positive and all 77 samples from healthy subjects were negative to HCV NS3 antigen assay. Of the 15 HCV NS3 antigen positive samples, 9 (60%) were HCV-RNA positive. The neutralization and positive percentage of immunodot assay for 23 HCV NS3 antigen positive sera were 87.0% (20/23) and 69.6% (16/23) respectively. Of the 25 sequential samples from 11 HCV NS3 antigen positive patients, there was a negative correlation between the OD values and the duration of test (r = -0.989, P < 0.05), and there were correlations among their HCV NS3 antigen, HCV-RNA and anti-HCV titres. The anti-HCV antibodies of two sera were detected while their OD values of HCV NS3 antigen decreased gradually. CONCLUSIONS: The HCV NS3 antigen detection assay showed perfect specificity and high sensitivity. Thus, it would be useful and economical as a routine test in laboratories for early diagnosis of HCV infection and prevention.

Combined human growth hormone and lactulose for prevention and treatment of multiple organ dysfunction in patients with severe chronic hepatitis B.

AIM: To evaluate the efficiency and safety of combined recombinant human growth hormone (rhGH) and lactulose for treatment and/or prevention of multiple organ dysfunction in patients with chronic severe hepatitis B. METHODS: Forty-eight inpatients with chronic severe hepatitis B were randomly divided into rhGH group (n=28) and control group (n=20). In rhGH group, 4-4.5 IU of rhGH was injected intramuscularly once daily for 2-4 wk, and 100 mL of enema containing 30 mL of lactulose, 2 g of metronidazole and 0.9% saline was administered every 2 d for 2-4 wk. Their symptoms and complications were noted. Liver and kidney functions were analyzed by an Olympus analyzer. Serum GH, IGF-1, IGFBP1 and IGFBP3 were measured by ELISA. RESULTS: Clinical symptoms of 90% of these patients in rhGH group were obviously improved. The total effectiveness in rhGH group was better than that in control group (75% vs 40%, P<0.05). After 2- and 4-wk treatment of rhGH respectively, serum albumin (26.1+/-4.1 vs 30.2+/-5.3, 31.9+/-5.1 g/L), prealbumin (79.6+/-28.0 vs 106.6+/-54.4, 108.4+/-55.0 g/L), cholesterol (76.3+/-16.7 vs 85.6+/-32.3, 96.1+/-38.7 mg/dL), and IGFBP1 (56.8+/-47.2 vs 89.7+/-50.3 ng/mL after 2 wk) were significantly increased compared to control group (P<0.05). However, serum GH was decreased. The increase of serum IGF1 and IGFBP3 after rhGH treatment was also observed. CONCLUSION: rhGH in combination with lactulose may be beneficial to the prevention and treatment of multiple organ dysfunction in patients with chronic severe hepatitis.

RANTES gene single nucleotide polymorphisms and expression in patients with chronic hepatitis B virus infection.

BACKGROUND: Regulated on activation, normal T-cell expressed and secreted (RANTES) plays a critical role in T-lymphocyte activation and proliferation. The process is involved in both acute and chronic phases of inflammation. The present study was to ascertain the possible correlations between chronic hepatitis B virus (HBV) infection and the RANTES gene polymorphisms and their expression. METHODS: The study included 130 HBV negative healthy donors and 152 patients with chronic hepatitis B (CHB) virus infection. The polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RFLPs) were used to detect RANTES gene single nucleotide polymorphisms (SNPs). RANTES levels in the platelet depleted plasma were detected by enzyme linked immunosorbent assay (ELISA). RESULTS: RANTES alleles -403G, -28C and In1.1T were the predominant alleles in the subjects studied. No significant correlation was found between CHB infection and the RANTES alleles, while a significant correlation was found between CHB infection and increased RANTES expression in platelet depleted plasma (P < 0.05). CONCLUSIONS: SNPs in RANTES gene do not affect chronic HBV infection or the outcome of interferon-alpha treatment in patients positive for HBV "e" antigen (HBeAg+). However, patients with CHB infection express the higher levels of plasma RANTES, which is thus associated with CHB infection.