Macrod1 suppresses diabetic cardiomyopathy via regulating PARP1-NAD+-SIRT3 pathway.

Diabetic cardiomyopathy (DCM), one of the most serious long-term consequences of diabetes, is closely associated with oxidative stress, inflammation and apoptosis in the heart. MACRO domain containing 1 (Macrod1) is an ADP-ribosylhydrolase 1 that is highly enriched in mitochondria, participating in the pathogenesis of cardiovascular diseases. In this study, we investigated the role of Macrod1 in DCM. A mice model was established by feeding a high-fat diet (HFD) and intraperitoneal injection of streptozotocin (STZ). We showed that Macrod1 expression levels were significantly downregulated in cardiac tissue of DCM mice. Reduced expression of Macrod1 was also observed in neonatal rat cardiomyocytes (NRCMs) treated with palmitic acid (PA, 400 µM) in vitro. Knockout of Macrod1 in DCM mice not only worsened glycemic control, but also aggravated cardiac remodeling, mitochondrial dysfunction, NAD+ consumption and oxidative stress, whereas cardiac-specific overexpression of Macrod1 partially reversed these pathological processes. In PA-treated NRCMs, overexpression of Macrod1 significantly inhibited PARP1 expression and restored NAD+ levels, activating SIRT3 to resist oxidative stress. Supplementation with the NAD+ precursor Niacin (50 µM) alleviated oxidative stress in PA-stimulated cardiomyocytes. We revealed that Macrod1 reduced NAD+ consumption by inhibiting PARP1 expression, thereby activating SIRT3 and anti-oxidative stress signaling. This study identifies Macrod1 as a novel target for DCM treatment. Targeting the PARP1-NAD+-SIRT3 axis may open a novel avenue to development of new intervention strategies in DCM. Schematic illustration of macrod1 ameliorating diabetic cardiomyopathy oxidative stress via PARP1-NAD+-SIRT3 axis.

Reductive Aza-Pauson-Khand Reaction of Nitriles.

γ-Lactams are valuable heterocycles in synthetic chemistry and drug development. Here, we report a reductive aza-Pauson-Khand reaction (aza-PKR) of an alkyne, a nitrile, and Co2(CO)8. A wide array of bicyclic α,ß-unsaturated γ-lactams containing two adjacent stereocenters, including an all-carbon quaternary center, from alkyne-tethered malononitriles are efficiently accessed in high diastereoselectivity. Preliminary mechanistic investigations by experiments and DFT calculations reveal that the reaction undergoes an aza-PKR process followed by a in situ reduction. The reducing reagent generated in situ from water also provides a practical tool for deuterium incorporation into the γ-position of lactams using D2O as the deuterium source. This study represents a new mode for [2 + 2 + 1] cycloaddition that enables the direct use of nitrile in aza-heterocycle synthesis.

Expediting Toluene Combustion by Harmonizing the Ce-O Strength over Co-Doped CeZr Oxide Catalysts.

Low-temperature catalytic degradation of volatile organic compounds (VOCs) by enhancing the activity of non-precious metal catalysts has always been the focus of attention. The mineralization of aromatic VOCs requires the participation of a large number of oxygen atoms, so the activation of oxygen species is crucial in the degradation reaction. Herein, we originally adjust the Ce-O bond strength in CeZr oxide catalysts by cobalt doping to promote the activation of oxygen species, thus improving the toluene degradation performance while maintaining high stability. Subsequent characterizations and theoretical calculations demonstrate that the weakening of the Ce-O bond strength increases the oxygen vacancy content, promotes the activation of oxygen species, and enhances the redox ability of the catalysts. This strategy also promotes the activation of toluene and accelerates the depletion of intermediate species. This study will contribute a strategy to enhance the activation ability of oxygen species in non-noble metal oxide catalysts, thereby enhancing the degradation performance of VOCs.

Population attributable fractions of fatty liver disease for type 2 diabetes Mellitus.

PURPOSE: To determine the population attributable fraction (PAF) of fatty liver disease (FLD) for type 2 diabetes mellitus (T2DM) and compare it to the PAFs of other metabolic abnormalities. METHODS: We conducted a 10-year retrospective cohort study of 33,346 individuals in Karamay Central Hospital of Xinjiang. Individuals were followed up for T2DM occurrence based on FBS. The PAFs of FLD were calculated generally and respectively in different sex and age groups. A comparison of the PAF of FLD and that of other metabolic abnormalities, as well as the PAFs of FLD in different groups classified based on age and sex, was performed using Cox regression. RESULTS: During an average follow-up period of 3.71 years, 1486 T2DM were diagnosed. The incidence density of T2DM was 1.2/100 person-years, and cumulative incidence rate was 4456.31/100,000 person-years. Partial PAF (PAFp) of FLD in the entire population was 23.11%. In the male population, PAFp was higher at 30-40 years old. In the female population, it was higher when age ≥ 60 years old. In multivariable Cox regression model, FLD, male sex, age ≥ 45 years old, overweight, hypertriglyceridaemia, and systolic hypertension were independent risk factors for T2DM, with corresponding PAFp of 25.00%, 24.99%, 36.47%, 24.96%, 5.71%, and 6.76%, respectively. Age ≥ 45 years old showed the highest PAFp and adjusted hazard ratio, followed by FLD. CONCLUSIONS: FLD contributes more to T2DM incidence than other metabolic disorders. Particular attention should be given to male populations of 30-40 and female populations above 60 for FLD prevention and treatment.

Lipid profiles in patients with juvenile idiopathic arthritis: a systematic literature review and meta-analysis.

OBJECTIVE: The purpose of this study was to comprehensively evaluate the lipid profiles in patients with juvenile idiopathic arthritis (JIA). METHODS: The literature and relevant reviews were searched for published clinical studies on the relationship between JIA and blood lipid levels. The Newcastle-Ottawa scale (NOS) was applied to evaluate the risk and methodological value of the included case‒control and cohort studies. Standardized mean differences (SMDs) and 95% confidence intervals were derived for all variables with adequate unprocessed data. This meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. RESULTS: In total, 16 studies were incorporated through screening. The analysis findings revealed that the levels of very low-density lipoprotein cholesterol [SMD=-0.411, 95% CI (-0.774~-0.048), P = 0.026], high-density lipoprotein cholesterol [SMD=-0.528, 95% CI (-0.976~-0.079), P = 0.021], and apolipoprotein A1 [SMD=-1.050, 95% CI (-1.452~-0.647), P = 0.000] in JIA patients were statistically lower than those observed in healthy controls. The level of low-density lipoprotein cholesterol [SMD = 0.202, 95% CI (0.003 ~ 0.400), P = 0.046] was significantly higher in JIA patients than in healthy controls. In JIA patients, body mass index [SMD=-0.189, 95% CI (-0.690 ~ 0.311), P = 0.459], high-density lipoprotein [SMD =-1.235, 95% CI (-2.845 ~ 0.374), P = 0.133), low-density lipoprotein [SMD = 0.616, 95% CI (-0.813 ~ 2.046), P = 0.398), triglycerides (SMD = 0.278, 95% CI (-0.182 ~ 0.738), P = 0.236], total cholesterol [SMD=-0.073, 95% CI (-0.438 ~ 0.293), P = 0.696] and apolipoprotein B levels [SMD = 0.226, 95% CI (-0.133 ~ 0.585), P = 0.217] were not significantly different from those in healthy controls. CONCLUSIONS: The outcomes of this meta-analysis suggest that dyslipidemia is common in JIA patients compared to healthy controls. Patients with JIA have a significantly increased risk of atherosclerosis and cardiovascular disease later in life.

Photoprotective Effects of Dendrobium nobile Lindl. Polysaccharides against UVB-Induced Oxidative Stress and Apoptosis in HaCaT Cells.

Acute ultraviolet (UV)-B radiation is the major external factor causing photodamage. In this study, we aimed to determine the effects of Dendrobium nobile Lindl. polysaccharides (DNPs) on photodamage in HaCaT keratinocytes after UVB irradiation and the underlying mechanisms. We found that DNPs significantly attenuated the decline in the viability and proliferation of HaCaT cells after UVB irradiation. Moreover, DNPs scavenged reactive oxygen species (ROS), improved the activities of endogenous antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase, and reduced the levels of malondialdehyde, while partially attenuating cell cycle arrest, suggesting their antioxidant and anti-apoptotic properties. The mitogen-activated protein kinase (MAPK) pathway was found to be important for the attenuation of UVB-induced photodamage in the HaCaT cells. Furthermore, DNPs exerted cytoprotective effects by downregulating UVB-induced ROS-mediated phosphorylation of MAPKs, including p38, c-Jun N-terminal kinase, and extracellular signal-regulated kinase, and by inhibiting p53 expression as well as the apoptotic cascade response. Therefore, DNPs ameliorated UVB-induced oxidative damage and apoptosis in HaCaT cells via the regulation of MAPKs. Our findings thus highlight the Dendrobium nobile Lindl polysaccharides as promising therapeutic candidates for UVB-induced photodamage.

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At the end of 2022, the World Health Organization reported an increase in group A Streptococcus (GAS) infections, such as scarlet fever, in multiple countries. The outbreak primarily affected children under 10 years old, and the number of deaths was higher than anticipated, causing international concern. This paper reviews the current state of the GAS disease outbreak, its causes, and response measures. The authors aim to draw attention from clinical workers in China and increase their awareness and vigilance regarding this epidemic. Healthcare workers should be aware of the potential epidemiological changes in infectious diseases that may arise after the optimization of control measures for coronavirus disease 2019 to ensure children's health.

Sodium Ferulate Inhibits Rat Cardiomyocyte Hypertrophy Induced by Angiotensin II Through Enhancement of Endothelial Nitric Oxide Synthase/Nitric Oxide/Cyclic Guanosine Monophosphate Signaling Pathway.

ABSTRACT: Sodium ferulate (SF) is the sodium salt of ferulic acid, which is one of the effective components of Angelica sinensis and Lignsticum chuanxiong , and plays an important role in protecting the cardiovascular system. In this study, myocardial hypertrophy was induced by angiotensin II 0.1 µmol/L in neonatal Sprague-Dawley rat ventricular myocytes. Nine groups were designed, that is, normal, normal administration, model, L-arginine (L-arg 1000 µmol/L), SF (50, 100, 200 µmol/L) group, and N G -nitro-L-arg-methyl ester 1500 µmol/L combined with SF 200 µmol/L or L-arg 1000 µmol/L group, respectively. Cardiomyocyte hypertrophy was confirmed by observing histological changes and measurements of cell diameter, protein content and atrial natriuretic factor, and ß-myosin heavy chain levels of the cells. Notably, SF could inhibit significantly myocardial hypertrophy of neonatal rat cardiomyocytes in a concentration-dependent manner without producing cytotoxicity, and the levels of nitric oxide, NO synthase (NOS), endothelial NOS, and cyclic guanosine monophosphate were increased, but the level of cyclic adenosine monophosphate was decreased in cardiomyocytes. Simultaneously, levels of protein kinase C beta, Raf-1, and extracellular regulated protein kinase 1/2 (ERK1/2) were downregulated, whereas levels of mitogen-activated protein kinase phosphatase-1 were significantly upregulated. All the beneficial effects of SF were blunted by N G -nitro-L-arg-methyl ester. Overall, these findings reveal that SF can inhibit angiotensin II-induced myocardial hypertrophy of neonatal rat cardiomyocytes, which is closely related to activation of endothelial NOS/NO/cyclic guanosine monophosphate, and inhibition of protein kinase C and mitogen-activated protein kinase signaling pathways.

Elevated fasting glucose level increases the risk of fatty liver disease: a 10-year study of 31,154 individuals.

OBJECTIVES: Dysglycemia promotes the occurrence of fatty liver disease (FLD). However, the process is unclear. This study aimed to analyze the median time-to-onset, cumulative prevalence and influencing factors for the occurrence of FLD in people undergoing routine screening and evaluation. METHODS: Data from Karamay Central Hospital (September 2008-April 2017) were analyzed. Survival analysis was performed to calculate the median time and cumulative prevalence of FLD associated with normal and elevated fasting blood glucose (FBG) levels. Cox proportional hazards model was used to determine risk factors. RESULTS: A total of 31,154 participants were included in the two cohorts of this study, including 15,763 men. The mean age was 41.1 ± 12.2 years. There were 2230 patients (1725 male) in the elevated FBG group, the median age was 53 years (range 21-85 years), the median time-to-onset of FLD was 5.2 years. The incidence of FLD was 121/1000 person-years, and the 1-, 3-, 5-, and 7-year prevalence rates were 4%, 30%, 49%, and 64%, respectively. The normal FBG group included 28,924 participants (14,038 male), the median age was 40 years (range 17-87 years), and the corresponding values were as follows: 8.3 years, 66/1000 person-years, and 3%, 16%, 28%, and 41%, respectively. The Cox proportional hazards analysis revealed that age, blood pressure, FBG, body mass index and triglycerides were independent influencing factors for FLD in individuals (P < 0.05). CONCLUSIONS: Elevated FBG levels increase the risk of FLD and should be treated promptly.

Low-Temperature Combustion of Toluene over Cu-Doped SmMn2O5 Mullite Catalysts via Creating Highly Active Cu2+-O-Mn4+ Sites.

Catalytic combustion of volatile organic compounds (VOCs) at low temperatures is still an urgent issue to be solved. Herein, low-temperature combustion of toluene over Cu-doped SmMn2O5 mullite catalysts via creating highly active Cu2+-O-Mn4+ sites has been originally demonstrated. Cu-doped SmMn2O5 mullite catalysts exhibited 90% conversion of toluene at 206 °C and displayed robust stability even in the presence of water. It has been demonstrated that Cu doping created Cu2+-O-Mn4+ active composite sites that were more exposed after removing surface Sm species via acid-etching. Benefiting from this, the redox and oxygen activation ability of catalysts was significantly enhanced. The consumption of benzaldehyde and benzoic acid as intermediate species and the CO2 generation ability were apparently promoted, which were the direct reasons for the enhanced low-temperature combustion of toluene. This work provides novel ideas for the development of high-performance catalysts for low-temperature VOC combustion, which has great industrial application prospects.

SO2-Tolerant Catalytic Reduction of NOx via Tailoring Electron Transfer between Surface Iron Sulfate and Subsurface Ceria.

Currently, SO2-induced catalyst deactivation from the sulfation of active sites turns to be an intractable issue for selective catalytic reduction (SCR) of NOx with NH3 at low temperatures. Herein, SO2-tolerant NOx reduction has been originally demonstrated via tailoring the electron transfer between surface iron sulfate and subsurface ceria. Engineered from the atomic layer deposition followed by the pre-sulfation method, the structure of surface iron sulfate and subsurface ceria was successfully constructed on CeO2/TiO2 catalysts, which delivered improved SO2 resistance for NOx reduction at 250 °C. It was demonstrated that the surface iron sulfate inhibited the sulfation of subsurface Ce species, while the electron transfer from the surface Fe species to the subsurface Ce species was well retained. Such an innovative structure of surface iron sulfate and subsurface ceria notably improved the reactivity of NHx species, thus endowing the catalysts with a high NOx reaction efficiency in the presence of SO2. This work unraveled the specific structure effect of surface iron sulfate and subsurface ceria on SO2-toleant NOx reduction and supplied a new point to design SO2-tolerant catalysts by modulating the unique electron transfer between surface sulfate species and subsurface oxides.

SO2-Induced Alkali Resistance of FeVO4/TiO2 Catalysts for NOx Reduction.

Selective catalytic reduction of nitrogen oxides with ammonia (NH3-SCR) is an efficient NOx abatement strategy, but deNOx catalysts suffer from serious deactivation due to the coexistence of multiple poisoning substances such as K, SO2, etc. in the flue gas. It is essential to understand the interaction among various poisons and their effects on NOx abatement. Here, we unexpectedly identified the K migration behavior induced by SO2 over K-poisoned FeVO4/TiO2 catalysts, which led to alkali-poisoning buffering and activity recovery. It has been demonstrated that the K would occupy both redox and acidic sites, which severely reduced the reactivity of FeVO4/TiO2 catalysts. After the sulfuration of the K-poisoned catalyst, SO2 preferred to be combined with the surface K2O, lengthened the K-OFe and K-OV, and thus released the active sites poisoned by K2O, thereby preserving an increase in the activity. As a result, for the K-poisoned catalyst, the conversion of NOx increased from 21 to 97% at 270 °C after the sulfuration process. This work contributes to the understanding of the specific interaction between alkali metals and SO2 on deNOx catalysts and provides a novel strategy for the adaptive use of one poisoning substance to counter another for practical NOx reduction.

Efficient NOx Abatement over Alkali-Resistant Catalysts via Constructing Durable Dimeric VOx Species.

The presence of alkali metals in flue gas is still an obstacle to the practical application of catalysts for selective catalytic reduction (SCR) of NOx by NH3. Polymeric vanadyl species play an essential role in ensuring the effective NOx abatement for NH3-SCR. However, polymeric vanadyl would be conventionally deactivated by the poison of alkali metals such as potassium, and it still remains a great challenge to construct robust and stable vanadyl species. Here, it was demonstrated that a more durable dimeric VOx active site could be constructed with the assistance of triethylamine, thereby achieving alkali-resistant NOx abatement. Due to the rational construction of polymerization structures, the obtained TiO2-supported cerium vanadate catalyst featured more stable dimeric VOx species and the active sites could survive even after the poisoning of alkali metal. Moreover, the depolymerization of VOx was suppressed endowing the catalysts with more Brønsted and Lewis acid sites after the poisoning of alkali metal, which ensured the efficient NOx reduction. This work unraveled the effects of alkali metal on the polymerization state of active species and opens up a way to develop low-temperature alkali-resistant catalysts for NOx abatement.

Boosting SO2-Resistant NOx Reduction by Modulating Electronic Interaction of Short-Range Fe-O Coordination over Fe2O3/TiO2 Catalysts.

SO2-resistant selective catalytic reduction (SCR) of NOx remains a grand challenge for eliminating NOx generated from stationary combustion processes. Herein, SO2-resistant NOx reduction has been boosted by modulating electronic interaction of short-range Fe-O coordination over Fe2O3/TiO2 catalysts. We report a remarkable SO2-tolerant Fe2O3/TiO2 catalyst using sulfur-doped TiO2 as the support. Via an array of spectroscopic and microscopic characterizations and DFT theoretical calculations, the active form of the dopant is demonstrated as SO42- residing at subsurface TiO6 locations. Sulfur doping exerts strong electronic perturbation to TiO2, causing a net charge transfer from Fe2O3 to TiO2 via increased short-range Fe-O coordination. This electronic effect simultaneously weakens charge transfer from Fe2O3 to SO2 and enhances that from NO/NH3 to Fe2O3, resulting in a remarkable "killing two birds with one stone" scenario, that is, improving NO/NH3 adsorption that benefits SCR reaction and inhibiting SO2 poisoning that benefits catalyst long-term stability.

Synergistic Catalytic Elimination of NOx and Chlorinated Organics: Cooperation of Acid Sites.

The synergistic catalytic removal of NOx and chlorinated volatile organic compounds under low temperatures is still a big challenge. Generally, degradation of chlorinated organics demands sufficient redox ability, which leads to low N2 selectivity in the selective catalytic reduction of NOx by NH3 (NH3-SCR). Herein, mediating acid sites via introducing the CePO4 component into MnO2/TiO2 NH3-SCR catalysts was found to be an effective approach for promoting chlorobenzene degradation. The observation of in situ diffuse reflectance infrared Fourier transform (in situ DRIFT) and Raman spectra reflected that the Lewis acid sites over CePO4 promoted the nucleophilic substitution process of chlorobenzene over MnO2 by weakening the bond between Cl and benzene ring. Meanwhile, MnO2 provided adequate Brønsted acid sites and redox sites. Under the cooperation of Lewis and Brønsted acid sites, relying on the rational redox ability, chlorobenzene degradation was promoted with synergistically improved NH3-SCR activity and selectivity. This work offers a distinct pathway for promoting the combination of chlorobenzene catalytic oxidation and NH3-SCR, and is expected to provide a novel strategy for synergistic catalytic elimination of NOx and chlorinated volatile organic compounds.

Obesity interacts with hyperuricemia on the severity of non-alcoholic fatty liver disease.

BACKGROUND: A series of evidence revealed that body mass index was an important confounding factor in the research of uric acid and ischemic heart disease/hypertension. The objective of this study was to investigate whether obesity status can modify the association between serum uric acid and the severity of liver damage in NAFLD, and the possible interactive effect of hyperuricemia and obesity. METHODS: We conducted a cross-sectional study in a total of 557 ultrasound diagnosed-NAFLD. The hepatic steatosis and liver fibrosis were quantitatively evaluated by transient elastography. Hyperuricemia was defined as serum uric acid > 420 µmol/L in men, > 360 µmol/L in women and obesity was defined as body mass index ≥ 25 kg/m2. The adjusted OR values of hyperuricemia and obesity were analyzed by multivariate logistic regression analysis, and the additive model was used to investigate the possible interactive effect. RESULTS: Multivariate regression analysis showed that hyperuricemia was associated with serious hepatic steatosis (1.74[1.09-2.79]) and elevated ALT (2.17[1.38-3.41]), but not with advanced fibrosis (1.61[0.91-2.85]). The association was further investigated in different BMI group. Hyperuricemia was associated with higher odds of serious hepatic steatosis (2.02[1.14-3.57]) and elevated ALT (2.27[1.37-3.76]) only in obese NAFLD, not in non-obese subjects. Similarly, patients with hyperuricemia had higher odds of advanced fibrosis in obese subjects (2.17[1.13-4.18]), not in non-obese subjects (0.60[0.14-2.70]). Furthermore, there was an additive interaction between hyperuricemia and obesity on the odds of serious hepatic steatosis (AP: 0.39[0.01-0.77]) and advanced fibrosis. (AP: 0.60[0.26-0.95]). CONCLUSIONS: Hyperuricemia and obesity had a significantly synergistic effect on the hepatic steatosis and fibrosis. Thus, management of uric acid may need to be targeted in obese NAFLD.

Bone-targeted erythrocyte-cancer hybrid membrane-camouflaged nanoparticles for enhancing photothermal and hypoxia-activated chemotherapy of bone invasion by OSCC.

BACKGROUND: Jaw bones are the most common organs to be invaded by oral malignancies, such as oral squamous cell carcinoma (OSCC), because of their special anatomical relationship. Various serious complications, such as pathological fractures and bone pain can significantly decrease the quality of life or even survival outcomes for a patient. Although chemotherapy is a promising strategy for bone invasion treatment, its clinical applications are limited by the lack of tumor-specific targeting and poor permeability in bone tissue. Therefore, it is necessary to develop a smart bone and cancer dual targeting drug delivery platform. RESULTS: We designed a dual targeting nano-biomimetic drug delivery vehicle Asp8[H40-TPZ/IR780@(RBC-H)] that has excellent bone and cancer targeting as well as immune escape abilities to treat malignancies in jaw bones. These nanoparticles were camouflaged with a head and neck squamous cell carcinoma WSU-HN6 cell (H) and red blood cell (RBC) hybrid membrane, which were modified by an oligopeptide of eight aspartate acid (Asp8). The spherical morphology and typical core-shell structure of biomimetic nanoparticles were observed by transmission electron microscopy. These nanoparticles exhibited the same surface proteins as those of WSU-HN6 and RBC. Flow cytometry and confocal microscopy showed a greater uptake of the biomimetic nanoparticles when compared to bare H40-PEG nanoparticles. Biodistribution of the nanoparticles in vivo revealed that they were mainly localized in the area of bone invasion by WSU-HN6 cells. Moreover, the Asp8[H40-TPZ/IR780@(RBC-H)] nanoparticles exhibited effective cancer growth inhibition properties when compared to other TPZ or IR780 formulations. CONCLUSIONS: Asp8[H40-TPZ/IR780@(RBC-H)] has bone targeting, tumor-homing and immune escape abilities, therefore, it is an efficient multi-targeting drug delivery platform for achieving precise anti-cancer therapy during bone invasion.

Aconitine disrupts serotonin neurotransmission via 5-hydroxytryptamine receptor in zebrafish embryo.

Medicinal plants of the genus Aconitum are one of the most commonly used herbs in traditional medicine in East Asia to treat conditions related to the heart, pain, or inflammation. However, these herbs are also dangerous as accidental poisoning due to misuse is a recurring issue. These plants contain a number of diester-diterpenoid alkaloid compounds and aconitine is the most abundant and active one. This study investigated neurotoxicity of aconitine to zebrafish embryos in early development in relation to serotonin regulation. Experimental results showed that aconitine exposure (1, 10, and 100 µM) increased frequency of coiling behavior in zebrafish embryos in a dose-dependent manner and this effect can be triggered by either exposure to 5-hydroxytryptamine 1A (5-HT1A) receptor agonist (±)-8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT) or overexpression of serotonin receptor 5-htr1ab. At the same time, coiling behavior caused by aconitine exposure could be rescued by co-exposure to 5-HT1A receptor antagonist WAY-100635 Maleate (WAY100635) and knockdown of 5-htr1ab using morpholino. Exposure to aconitine also significantly increased serotonin receptor 5-htr1ab and 5-htr1bd gene expression at 24 h post fertilization (hpf), but decreased their expression and protein expression of the serotonin receptor at 96 hpf with the high dose. These results suggest that neurotoxicity caused by aconitine is mediated through the 5-HT receptor.

Scavenger receptor class B type I is more conducive for genotype 1b hepatitis C virus internalization than low-density lipoprotein receptor.

The current limited understanding of HCV entry mechanisms hinders the development of specific antiviral drug screening techniques and vaccine assessment. HCV subtypes and cellular surface proteins both can affect virus tropism. Human factors such as low-density lipoprotein receptor (hLDLR), CD81 (hCD81), scavenger receptor class B type I (hSR-BI), claudin 1 (hCLDN1), and occludin (hOCLN) assist HCV entry into hepatocytes. Here, we studied the importance of five human proteins in the process of cell culture-derived (HCVcc) and serum-derived (HCV-sd) HCV entry using constructed humanized mouse hepatocytes and mouse models. We determined that unlike hLDLR, hSR-BI was an indispensable factor for 1b genotype HCV adsorption. Furthermore, this attachment can be completely prevented by treatment with a monoclonal antibody targeting hSR-BI. Our data support the idea that SR-BI is an essential factor in HCV infection, particularly during the initial HCV particle-binding step. This novel finding will facilitate the development of antiviral drugs and vaccines. Keywords: hepatitis C virus; virus internalization; model construction; hSR-BI.

Pyruvate Protects Against Intestinal Injury by Inhibiting the JAK/STAT Signaling Pathway in Rats With Hemorrhagic Shock.

BACKGROUND: This study aimed to investigate the role of Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway in protection by peritoneal resuscitation (PR) using pyruvate-peritoneal dialysis solution (PY-PDS) against intestinal injury from hemorrhagic shock (HS) in rats. MATERIALS AND METHODS: Sixty-four rats were assigned to eight groups: group SHAM; group intravenous resuscitation (VR); groups NS, LA, and PY in which the rats were subjected to HS and PR with normal saline (NS), lactate-peritoneal dialysis solution (LA-PDS), and PY-PDS, respectively, combined with VR; and groups DMSO, RPM, and AG490 in which the rats were subjected to HS and VR with pretreatment of dimethyl sulfoxide (DMSO), rapamycin (RPM), and tyrphostin B42 (AG490). RESULTS: At 2 h after HS and resuscitation, the levels of diamine oxidase, 15-F2t-isoprostane, thromboxane B2, and endothelin-1, in the blood and the intestinal mucosal apoptotic index and caspase-3 were lower in groups PY, RPM, and AG490 than in groups VR, NS, LA, and DMSO. Group PY showed lower levels of malondialdehyde and myeloperoxidase and a higher level of superoxide dismutase than groups VR, NS, and LA. Phosphorylated JAK2 and phosphorylated STAT3 levels were lower in groups PY, RPM, AG490, and LA than in groups VR, NS, and DMSO. CONCLUSIONS: The protection mechanism of PR with PY-PDS combined with VR was related to the inhibition of the JAK/STAT signaling pathway during HS and resuscitation. The process might include suppression of oxidative stress, reduction of neutrophil infiltration, regulation of microcirculation, and inhibition of apoptosis.