Iron-doping and facet engineering of NiSe octahedron for synergistically enhanced triiodide reduction activity in photovoltaics.

Reasonable design of cost-effective counter electrode (CE) catalysts for triiodide (I3-) reduction reaction (IRR) by simultaneously combining heteroatom doping and facet engineering is highly desired in iodine-based dye-sensitized solar cells (DSSCs), but really challenging. Herein, the density function theory (DFT) calculations were first conducted to demonstrate that the Fe-doped NiSe (111) showed an appropriate adsorption energy for I3-, increased number of metal active sites, reinforced charge-transfer ability, and strong interaction between 3d states of metal sites and 5p state of I1 atoms in I3-, compared to NiSe (111). Based on this finding, the well-defined Fe-NiSe octahedron with exposed (111) plane (marked as Fe-NiSe (111)) and NiSe octahedron with the same exposed plane (named as NiSe (111)) are controllably synthesized. When the as-prepared Fe-NiSe (111) and NiSe (111) worked as CE catalysts, Fe-NiSe (111) exhibits improved electrochemical performance with higher power conversion efficiency (PCE) than NiSe (111), providing new opportunity to replace precious Pt for DSSCs.

Enhancing medical students' science communication skills: from the perspective of new media.

With the development of science over the years, people have increasingly realized the importance of science communication. Unfortunately, very little research has focused on helping medical students develop the capabilities of science communication. To improve medical students' science communication and evaluate the effectiveness of New Media through mobile clients in health science communication, a competition was held among medical undergraduates. Outstanding works were selected for publication on our official health science communication WeChat account. Furthermore, the participants volunteered to complete a questionnaire survey to help us assess students' awareness of science communication. Our analysis revealed that students had a strong willingness to serve society and to participate in science communication work. Students generally agreed that science communication work had excellent effects on professional knowledge and related skills. In addition, the correlation results showed that the greater students' willingness to participate in health science communication was, the greater their sense of gain. New Media effectively expand the influence of students' popular science works. Our findings suggest that competition in science communication has a positive impact on enhancing students' awareness and capabilities in science communication. In addition, New Media are an effective way to improve students' scientific communication efficiency. However, we also noted that students' participation rate and enthusiasm for scientific communication were not high. Further research is needed to determine the reasons for this situation and potential strategies to further improve students' science communication.NEW & NOTEWORTHY The science communication competition had a positive impact on helping medical students develop awareness and capabilities for science communication. In addition, New Media are an effective way to improve students' scientific communication efficiency.

Effects of acetazolamide combined with remote ischemic preconditioning on risk of acute mountain sickness: a randomized clinical trial.

BACKGROUND: We aimed to determine whether and how the combination of acetazolamide and remote ischemic preconditioning (RIPC) reduced the incidence and severity of acute mountain sickness (AMS). METHODS: This is a prospective, randomized, open-label, blinded endpoint (PROBE) study involving 250 healthy volunteers. Participants were randomized (1:1:1:1:1) to following five groups: Ripc (RIPC twice daily, 6 days), Rapid-Ripc (RIPC four times daily, 3 days), Acetazolamide (twice daily, 2 days), Combined (Acetazolamide plus Rapid-Ripc), and Control group. After interventions, participants entered a normobaric hypoxic chamber (equivalent to 4000 m) and stayed for 6 h. The primary outcomes included the incidence and severity of AMS, and SpO2 after hypoxic exposure. Secondary outcomes included systolic and diastolic blood pressure, and heart rate after hypoxic exposure. The mechanisms of the combined regime were investigated through exploratory outcomes, including analysis of venous blood gas, complete blood count, human cytokine antibody array, ELISA validation for PDGF-AB, and detection of PDGF gene polymorphisms. RESULTS: The combination of acetazolamide and RIPC exhibited powerful efficacy in preventing AMS, reducing the incidence of AMS from 26.0 to 6.0% (Combined vs Control: RR 0.23, 95% CI 0.07-0.70, P = 0.006), without significantly increasing the incidence of adverse reactions. Combined group also showed the lowest AMS score (0.92 ± 1.10). Mechanistically, acetazolamide induced a mild metabolic acidosis (pH 7.30 ~ 7.31; HCO3- 18.1 ~ 20.8 mmol/L) and improved SpO2 (89 ~ 91%) following hypoxic exposure. Additionally, thirty differentially expressed proteins (DEPs) related to immune-inflammatory process were identified after hypoxia, among which PDGF-AB was involved. Further validation of PDGF-AB in all individuals showed that both acetazolamide and RIPC downregulated PDGF-AB before hypoxic exposure, suggesting a possible protective mechanism. Furthermore, genetic analyses demonstrated that individuals carrying the PDGFA rs2070958 C allele, rs9690350 G allele, or rs1800814 G allele did not display a decrease in PDGF-AB levels after interventions, and were associated with a higher risk of AMS. CONCLUSIONS: The combination of acetazolamide and RIPC exerts a powerful anti-hypoxic effect and represents an innovative and promising strategy for rapid ascent to high altitudes. Acetazolamide improves oxygen saturation. RIPC further aids acetazolamide, which synergistically regulates PDGF-AB, potentially involved in the pathogenesis of AMS. TRIAL REGISTRATION: ClinicalTrials.gov NCT05023941.

Helpful to Live Healthier? Intermittent Hypoxic/Ischemic Training Benefits Vascular Homeostasis and Lipid Metabolism with Activating SIRT1 Pathways in Overweight/Obese Individuals.

INTRODUCTION: The present study aimed to investigate whether and how normobaric intermittent hypoxic training (IHT) or remote ischemic preconditioning (RIPC) plus normoxic training (RNT) has a synergistic protective effect on lipid metabolism and vascular function compared with normoxic training (NT) in overweight or obese adults. METHODS: A total of 37 overweight or obese adults (36.03 ± 10.48 years) were randomly assigned to 3 groups: NT group (exercise intervention in normoxia), IHT group (exercise intervention in normobaric hypoxic chamber), and RNT group (exercise intervention in normoxia + RIPC twice daily). All participants carried out the same 1-h exercise intervention for a total of 4 weeks, 5 days per week. Physical fitness parameters were evaluated at pre- and postexercise intervention. RESULTS: After training, all three groups had a significantly decreased body mass index (p < 0.05). The IHT group had reduced body fat percentage, visceral fat mass (p < 0.05), blood pressure (p < 0.01), left ankle-brachial index (ABI), maximal heart rate (HRmax) (p < 0.05), expression of peroxisome proliferator-activated receptor-γ (PPARγ) (p < 0.01) and increased expression of SIRT1 (p < 0.05), VEGF (p < 0.01). The RNT group had lowered waist-to-hip ratio, visceral fat mass, blood pressure (p < 0.05), and HRmax (p < 0.01). CONCLUSION: IHT could effectively reduce visceral fat mass and improve vascular elasticity in overweight or obese individuals than pure NT with the activation of SIRT1-related pathways. And RNT also produced similar benefits on body composition and vascular function, which were weaker than those of IHT but stronger than NT. Given the convenience and economy of RNT, both intermittent hypoxic and ischemic training have the potential to be successful health promotion strategies for the overweight/obese population.

Vitamin D Improves Cognitive Impairment and Alleviates Ferroptosis via the Nrf2 Signaling Pathway in Aging Mice.

Ferroptosis is an iron-dependent mode of cell death associated with the occurrence and development of age-related neurodegenerative diseases. Currently, there are no effective drugs available to prevent or treat these aging-related neurodegenerative diseases. Vitamin D (VD) is an antioxidant and immunomodulator, but its relationship with ferroptosis in aging-related neurodegenerative diseases has not been extensively studied. In this study, we aimed to investigate the role of VD in learning and memory in aging mice. To examine whether VD protects aging hippocampal neurons, we used physiologically active 1,25(OH)2D3. We established aging models in vivo (C57BL/6 mice) and in vitro (HT22 cells) using D-galactose (D-gal). The results demonstrated that VD could improve learning and memory in mice aged via the use of D-gal, and it reduced damage to hippocampal neurons. VD could regulate ferroptosis-related proteins (increasing GPX4 expression and decreasing ACSL4 and ALOX15 protein expression levels), increasing GSH levels, reducing MDA and intracellular and mitochondrial ROS levels, as well as total iron and Fe2+ levels, and improving mitochondrial morphology, thereby alleviating ferroptosis in aging hippocampal neurons. Additionally, VD activated the VDR/Nrf2/HO-1 signaling pathway, thereby inhibiting ferroptosis. Notably, when the VDR was knocked down, VD lost its ability to activate Nrf2. Consequently, inhibiting Nrf2 decreased the protective effect of VD against ferroptosis in aged hippocampal neurons. In summary, VD activates the Nrf2/HO-1 signaling pathway through the VDR, effectively preventing ferroptosis induced by aging in hippocampal neurons.

Polydopamine-coated mesoporous silica nanoparticles co-loaded with Ziyuglycoside I and Oseltamivir for synergistic treatment of viral pneumonia.

Viral pneumonia (VP) is a serious health risk to humans, however, there is still a lack of specific treatments for VP. The spread of the virus in the body induces an excessive inflammatory response that can cause chronic or irreversible damage to lungs. Hence, VP treatment requires rapid clearance of the virus and sustained inflammation control. In this study, an innovative mesoporous silica medication delivery system co-loaded with Ziyuglycoside I(ZgI) and Oseltamivirv(OST) in fast and slow monomeric forms ZgI@MSNs-OST@ Polydopamine (PDA) was prepared for targeted treatment of VP. The prepared ZgI@MSNs-OST@PDA nanoparticles had a homogeneous and membrane-encapsulated spherical structure, with an average particle size of approximately 760 nm. in vitro release and in vivo pharmacokinetic studies demonstrated that ZgI@MSNs-OST@PDA achieved immediate release of OST and sustained release of ZgI, which was readily taken up by the cells. In vitro anti-H1N1 virus experiments showed that nanoparticles rapidly killed the virus in host cells, and the anti-inflammatory effect was sustained and long-lasting, providing excellent protection to host cells. In vivo antiviral pneumonia experiments confirmed the rapid clearance of influenza viruses from mouse lungs and the effective control of overactivated immune responses by ZgI@MSNs-OST@PDA nanoparticles. Through a mechanistic study, we found that the treatment of viral pneumonia with nanoparticles was associated with inhibition of the NLRP3 inflammasome pathway. In conclusion, the constructed nanoparticles achieved synergistic therapeutic effects of ZgI and OST on VP, that is, rapid killing of influenza viruses by OST and effective control of the virus-induced hyperinflammatory response by ZgI.

Colloid synthesis of Ni12P5/N, S-doped graphene as efficient bifunctional catalyst for alkaline hydrogen evolution and triiodide reduction reaction.

Designing high-efficient bifunction catalysts with excellent catalytic activity and enhanced charge-transfer capability in both alkaline hydrogen evolution reaction (HER) and triiodide reduction reaction (IRR) is of utmost significance to advance the development of green hydrogen production and photovoltaics, respectively, yet remains a crucial challenge. Here, highly dispersed and small-sized Ni12P5 nanocrystals with narrow size distribution was well attached on the surface of N, S co-doped graphene (Ni12P5/NSG) by the facile hot-injection method. As expected, the optimized Ni12P5/NSG requires a relatively low overpotential of 132.94 ± 0.08 mV to deliver a current density of 10 mA cm-2 in alkaline condition, accompanied with remarkable long-time durability with negligible attenuation over 50 h. Density functional theory (DFT) calculations revealed that the positively synergic effect between Ni12P5 and NSG are in favor of modulating the rate determining step of the dissociation of H2O to *(OH-H), thereby upgrading its HER activity. When used as the counter electrode catalyst for IRR in DSSCs, the resultant Ni12P5/NSG exhibits extraordinary Pt-like catalytic activity and well electrochemical stability in iodide-based electrolyte, delivering a high photoelectric conversion performance (PCE) comparable to Pt. The improved PCE can be attributed to the accelerated interfacial charge-transfer capability around active sites for facilitating the reaction kinetics of IRR, as demonstrated by DFT calculations. This work provides an effective strategy for synthesizing cost-effective composites with multi-active sites and offering valuable insight into the structure-performance relationship, which is conducive to guide the synthesis of promising catalysts in the energy conversion field.

Exploring The Synergistic Effect Of CoSeP/CoP Interface Catalyst For Efficient Urea Electrolysis.

Electrocatalytic oxidation of urea (UOR) is a potential energy-saving hydrogen production technology that can replace oxygen evolution reaction (OER). Therefore, CoSeP/CoP interface catalyst is synthesized on nickel foam using hydrothermal, solvothermal, and in situ template methods. The strong interaction of tailored CoSeP/CoP interface promotes the hydrogen production performance of electrolytic urea. During the hydrogen evolution reaction (HER), the overpotential can reach 33.7 mV at 10 mA cm-2 . The cell voltage can reach 1.36 V at 10 mA cm-2 in the overall urea electrolytic process. Notably, the overall urine electrolysis performance of the catalyst in the human urine medium can reach 1.40 V at 10 mA cm-2 and can exhibit durable cycle stability at 100 mA cm-2 . Density functional theory (DFT) proves that the CoSeP/CoP interface catalyst can better adsorb and stabilize reaction intermediates CO* and NH* on its surface through a strong synergistic effect, thus enhancing the catalytic activity.

Defect-rich Mo2S3 loaded wood-derived carbon acts as a spacer in lithium-sulfur batteries: forming a polysulfide capture net and promoting fast lithium flux.

Due to the sluggish kinetics of sulfur conversion and the large volume change of the lithium anode, along with the formation of lithium dendrites, lithium-sulfur batteries (LSBs) usually exhibit severe capacity decay and poor cycle life. It is necessary to consider the factors associated with cathodes, separators and anodes in an integrated manner to solve the problems existing in LSBs. In this paper, a vertically aligned porous carbon decorated with transition metal sulfides was introduced between a cathode and an anode to comprehensively solve the problems of LSBs. Widely existing natural wood was used as the framework structure, and Mo2S3 with abundant sulfur vacancies was deposited into its channels. Theoretical calculations and experimental results have confirmed a low energy barrier for sulfur conversion and the presence of a strong electric field around the spacer, which benefits fast ion transportation. As a result, on employing the multifunctional spacer, LSB full cells delivered a high initial capacity and a long cycle life. This study provides a reference for reducing development cost, simplifying optimization steps and promoting the commercial application of LSBs.

The concordance and discordance of diabetic kidney disease and retinopathy in patients with type 2 diabetes mellitus: A cross-sectional study of 26,809 patients from 5 primary hospitals in China.

Introduction: Diabetic kidney disease (DKD) and diabetic retinopathy (DR) share similar pathophysiological mechanisms. However, signs of DKD may be present at diagnosis of diabetes without retinopathy. Risk factors for the development of DKD and DR may not be identical. Methods: This study aimed to evaluate the concordance and discordance between DKD and DR by investigating the distribution of DKD and DR in patients with type 2 diabetes mellitus from 5 Chinese cities. A total of 26,809 patients were involved in this study. The clinical characteristics were compared among patients based on the presence of DKD and DR. Logistic regression models were used to analyze the independent risk factors of DKD and DR. Results: The prevalence of DKD and DR was 32.3% and 34.6%, respectively. Among eligible patients, 1,752 patients without DR had an increased urinary albumin-to-creatinine ratio (ACR) or reduced estimated glomerular filtration rate (eGFR), and 1,483 patients with DR had no DKD. The positive predictive value of DR for DKD was 47.4% and negative predictive value was 67.1%. Elder age, male gender, a longer duration of disease, higher values of waist circumference and HbA1c were associated with both DR and DKD. A lower educational level was associated with DR. Higher BP and TG would predict increased prevalence of DKD. Conclusions: DKD and DR shared many risk factors, but a significant discordance was present in patients with type 2 diabetes mellitus. DKD was more strongly associated with blood pressure and triglycerides than DR.

The role of poly (ADP-ribose) glycohydrolase in phosphatase and tensin homolog deficiency endometrial cancer.

AIM: To explore the relationship between poly(ADP-ribose) glycohydrolase (PARG) and the occurrence, development, and prognosis of endometrial carcinoma (EC), and investigate whether the PARG inhibitor PDD0017273 could increase the sensitivity of EC cells to cisplatin. METHODS: The expression of PARG, phosphatase and tensin homolog (PTEN), and p53 in normal endometrial tissues (NE), endometrial hyperplasia without atypia (EH), atypical endometrial hyperplasia (AH), and EC was detected by immunohistochemistry. AN3CA EC cells with PTEN deficiency were treated with different cisplatin and PDD0017273, alone or in combination. Cell proliferation was detected by MTT method, apoptosis was detected by flow cytometry, and the expression of PARG in EC cells after treatment with different drugs was detected by western blot and immunohistochemistry. RESULTS: Expression of PARG in NE, EH, AH, and EC increased gradually. In addition, compared with low PARG expression in PTEN-positive EC, patients who had high PARG expression in PTEN-negative EC had more advanced clinical stages (r = -0.399, p = 0.032) and shorter overall survival time (p = 0.037). A dose of 40 µM PDD0017273 effectively inhibited PARG expression, increased the sensitivity of AN3CA cells to cisplatin. CONCLUSIONS: The findings suggest that PARG overexpression is a promising immunohistochemical marker to predict the occurrence and prognosis of EC. Moreover, PARG inhibition produced antitumor effects and increased the sensitivity of EC cells with PTEN deficiency to cisplatin.

Hyponatremia after neuroendoscopic skull base tumor surgery: Clinical characteristics and nursing management.

Purpose: The current study was conducted to explore the clinical characteristics of hyponatremia after neuroendoscopic skull base tumor resection, and to summarize the nursing experience and provide insight for nursing management. Methods: In total, we enrolled 181 patients who underwent neuroendoscopic resection of skull base tumors in the Department of Neurosurgery of our hospital from 2016 to 2021. The patients' general data and parameters, including blood sodium level, polyuria, and other symptoms in different periods after surgery, were retrospectively reviewed. Results: Forty-four patients developed hyponatremia after Surgery. The total incidence of hyponatremia was 24.30%, including 38 cases of mild hyponatremia and 6 cases of moderate and severe hyponatremia. Most cases of moderate and severe hyponatremia occurred 6 days after surgery. The incidence of hyponatremia varied in different pathological types and periods in patients undergoing skull base tumors. After standardized sodium supplementation, water restriction, and urine volume control, hyponatremia was corrected in all patients, and no osmotic demyelination syndrome (ODS) and nursing-related events occurred. Conclusion: Secondary hyponatremia after neuroendoscopic resection of skull base tumors can occur in various time periods after surgery. Early monitoring of manifestations and standardized intervention are thus necessary for clinical nursing practice to timely correct hyponatremia and avoid demyelination.

Research Note: Serological investigation of Ornithobacterium rhinotracheale infection in China.

Ornithobacterium rhinotracheale (ORT) has been associated with avian respiratory disease. On coinfection with other pathogens, ORT can cause serious health problems in avian species, leading to financial losses. To monitor the serologic prevalence of ORT in chicken flocks in China, 1,280 sera were collected to determine ORT antibodies among 64 flocks from 15 provinces of China using a commercial ELISA kit. The overall seroprevalence of ORT among the birds tested was 44.06%. In younger chickens, the serum positive rate was lower than that in older chickens, and with increased age, the serum positive rates increased. Older chickens had not only higher positive rates but also higher antibody levels. These data indicated that ORT infections were common in China. Because an ORT vaccine is currently not available, good disease management and biosecurity measures are required for effective disease control.

lncRNA SNHG1 Knockdown Alleviates Amyloid-ß-Induced Neuronal Injury by Regulating ZNF217 via Sponging miR-361-3p in Alzheimer's Disease.

BACKGROUND: Long noncoding RNAs have been proven to play an important role in the progression of Alzheimer's disease (AD). However, the function of small nucleolar RNA host gene 1 (SNHG1) in AD progression remains to be studied. OBJECTIVE: To explore the role of SNHG1 in AD progression and clarify its potential mechanism. METHODS: Amyloid ß-protein (Aß) was used to construct an AD cell model in vitro. The expression levels of SNHG1 and miR-361-3p were determined by quantitative real-time polymerase chain reaction. Cell viability and apoptosis were measured by cell counting kit 8 assay and flow cytometry. The levels of apoptosis-related proteins and zinc finger gene 217 (ZNF217) protein were evaluated by western blot analysis. Additionally, the contents of inflammatory cytokines and oxidative stress markers were tested by enzyme-linked immunosorbent assay. Furthermore, dual-luciferase reporter and RNA immunoprecipitation assays were used to verify the interaction between miR-361-3p and SNHG1 or ZNF217. RESULTS: Aß could induce cell injury, while resveratrol could reverse this effect. SNHG1 expression was positively regulated by Aß and negatively regulated by resveratrol. SNHG1 knockdown could reverse the promotion effect of Aß on cell injury. Moreover, SNHG1 sponged miR-361-3p, and miR-361-3p targeted ZNF217. Additionally, miR-361-3p overexpression reversed the promotion effect of SNHG1 overexpression on cell injury, and ZNF217 silencing also reversed the promotion effect of miR-361-3p inhibitor on cell injury. CONCLUSION: SNHG1 promoted cell injury by regulating the miR-361-3p/ZNF217 axis, which might provide a theoretical basis for molecular therapy of AD.

Genotype-Guided Dosing of Warfarin in Chinese Adults: A Multicenter Randomized Clinical Trial.

BACKGROUND: Warfarin is an effective treatment for thromboembolic disease but has a narrow therapeutic index; optimal anticoagulation dosage can differ tremendously among individuals. We aimed to evaluate whether genotype-guided warfarin dosing is superior to routine clinical dosing for the outcomes of interest in Chinese patients. METHODS: We conducted a multicenter, randomized, single-blind, parallel-controlled trial from September 2014 to April 2017 in 15 hospitals in China. Eligible patients were ≥18 years of age, with atrial fibrillation or deep vein thrombosis without previous treatment of warfarin or a bleeding disorder. Nine follow-up visits were performed during the 12-week study period. The primary outcome measure was the percentage of time in the therapeutic range of the international normalized ratio during the first 12 weeks after starting warfarin therapy. RESULTS: A total of 660 participants were enrolled and randomly assigned to a genotype-guided dosing group or a control group under standard dosing. The genotype-guided dosing group had a significantly higher percentage of time in the therapeutic range than the control group (58.8% versus 53.2% [95% CI of group difference, 1.1-10.2]; P=0.01). The genotype-guided dosing group also achieved the target international normalized ratio sooner than the control group. In subgroup analyses, warfarin normal sensitivity group had an even higher percentage of time in the therapeutic range during the first 12 weeks compared with the control group (60.8% versus 48.9% [95% CI, 1.1-24.4]). The incidence of adverse events was low in both groups. CONCLUSIONS: The outcomes of genotype-guided warfarin dosing were superior to those of clinical standard dosing. These findings raise the prospect of precision warfarin treatment in China. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02211326.

Immunization With a Secreted Esterase Protects Mice Against Multiple Serotypes (M1, M3, and M28) of Group A Streptococcus.

Streptococcal secreted esterase (Sse) is a platelet-activating factor acetylhydrolase that is critical for Group A Streptococcus (GAS) skin invasion and innate immune evasion. There are two Sse variant complexes that share >98% identity within each complex but display about 37% variation between the complexes in amino acid sequences. Sse immunization protects mice against lethal infection and skin invasion in subcutaneous infection with the hypervirulent CovRS mutant strain, MGAS5005. However, it is not known whether Sse immunization provides significant protection against infection of GAS with functional CovRS and whether immunization with Sse of one variant complex provides protection against infection of GAS that produces Sse of another variant complex. This study was designed to address these questions. Mice were immunized with recombinant Sse of M1 GAS (SseM1) and challenged with MGAS5005 (serotype M1, CovS mutant, and Sse of variant complex I), MGAS315 (M3, CovS mutant, and Sse of variant complex I), MGAS2221 (M1, wild-type CovRS, and Sse of variant complex I), and MGAS6180 (M28, wild-type CovRS, and Sse of variant complex II). SseM1 immunization significantly increased survival rates of mice in subcutaneous MGAS5005 and intraperitoneal MGAS6180 challenges and showed consistently higher or longer survival in the other challenges. Immunized mice had smaller skin lesion and higher neutrophil responses in subcutaneous infections and lower GAS burdens in spleen, liver, and kidney in most of the challenge experiments than control mice. SseM1 immunization enhanced proinflammatory responses. These data suggest that Sse immunization has a broad benefit against GAS infections that can vary in extent from strain to strain and that the benefit may be due to the immunization-enhanced proinflammatory responses. In particular, immunization with SseM1 can provide protection against M28 GAS infection even though its Sse and SseM1 have significant variations.

Active and passive immunizations with HtsA, a streptococcal heme transporter protein, protect mice from subcutaneous group A Streptococcus infection.

BACKGROUND/PURPOSE: HtsA (Streptococcus heme transporter A) is the lipoprotein component of the streptococcal heme ABC transporter (HtsABC). The aim of this study is to investigate whether the HtsA protein has immunoprotective effect against group A Streptococcus (GAS) infection in mice. METHODS: The HtsA protein was purified by sequential chromatography on Ni-sepharose, DEAE-sepharose and Phenyl-sepharose, CD-1 mice were actively immunized with ALUM (control) or HtsA/ALUM, and passively immunized with control or anti-HtsA serum. Mice were challenged with GAS after immunization, and the survival rate, skin lesion size and systemic GAS dissemination were determined. RESULTS: The HtsA gene was cloned, and the recombinant protein HtsA was successfully purified. HtsA has a strong antigenicity, and active immunization with the HtsA protein significantly protected mice against lethal subcutaneous GAS infection, inhibited invasion of the skin by GAS, and reduced GAS systemic dissemination in blood and organs. In addition, passive immunization with anti-HtsA serum also significantly protected mice against subcutaneous GAS infection, and inhibited invasion of the skin by GAS. CONCLUSION: The results showed that both active and passive immunization with the HtsA protein protected mice against subcutaneous GAS infection, suggesting that HtsA may be a candidate of GAS vaccine to protect against GAS infection.

miR-16-5p and miR-19b-3p prevent amyloid ß-induced injury by targeting BACE1 in SH-SY5Y cells.

PURPOSE: Alzheimer's disease is the most common neurodegenerative disease, characterized by accumulation of amyloid ß peptides. MicroRNAs have been identified as significant regulators and therapeutic targets of Alzheimer's disease. However, the roles of miR-16-5p and miR-19b-3p and their mechanisms in Alzheimer's disease progression remain largely unknown. MATERIALS AND METHODS: Amyloid ß-treated SH-SY5Y cells were used to study Alzheimer's disease progression in vitro. Transfection was conducted into SH-SY5Y cells using Lipofectamine 2000. The expression levels of miR-16-5p, miR-19b-3p and beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) were measured by quantitative real-time PCR or western blot, respectively. Cell viability and apoptosis were detected in amyloid ß-treated SH-SY5Y cells by MTT or flow cytometry, respectively. The interaction between BACE1 and miR-16-5p or miR-19b-3p was explored by luciferase reporter and RNA immunoprecipitation analyses. RESULTS: The expression levels of miR-16-5p and miR-19b-3p were reduced but BACE1 protein expression was enhanced in SH-SY5Y cells after treatment of amyloid ß. Overexpression of miR-16-5p or miR-19b-3p attenuated amyloid ß-induced viability inhibition and apoptosis promotion in SH-SY5Y cells, while their knockdown exacerbated amyloid ß-induced injury. BACE1 was confirmed as a target of miR-16-5p and miR-19b-3p and its overexpression aggravated amyloid ß-induced loss of viability and production of apoptosis, while its depletion caused an opposite effect. Moreover, upregulation of BACE1 alleviated the regulatory effects of miR-16-5p and miR-19b-3p on amyloid ß-induced injury. CONCLUSION: MiR-16-5p and miR-19b-3p relieved amyloid ß-induced injury by targeting BACE1 in SH-SY5Y cells, indicating miR-16-5p and miR-19b-3p as protective agents for treatment of Alzheimer's disease.

Therapeutic Potential of Oxytocin in Atherosclerotic Cardiovascular Disease: Mechanisms and Signaling Pathways.

Coronary artery disease (CAD) is a major cardiovascular disease responsible for high morbidity and mortality worldwide. The major pathophysiological basis of CAD is atherosclerosis in association with varieties of immunometabolic disorders that can suppress oxytocin (OT) receptor (OTR) signaling in the cardiovascular system (CVS). By contrast, OT not only maintains cardiovascular integrity but also has the potential to suppress and even reverse atherosclerotic alterations and CAD. These protective effects of OT are associated with its protection of the heart and blood vessels from immunometabolic injuries and the resultant inflammation and apoptosis through both peripheral and central approaches. As a result, OT can decelerate the progression of atherosclerosis and facilitate the recovery of CVS from these injuries. At the cellular level, the protective effect of OT on CVS involves a broad array of OTR signaling events. These signals mainly belong to the reperfusion injury salvage kinase pathway that is composed of phosphatidylinositol 3-kinase-Akt-endothelial nitric oxide synthase cascades and extracellular signal-regulated protein kinase 1/2. Additionally, AMP-activated protein kinase, Ca2+/calmodulin-dependent protein kinase signaling and many others are also implicated in OTR signaling in the CVS protection. These signaling events interact coordinately at many levels to suppress the production of inflammatory cytokines and the activation of apoptotic pathways. A particular target of these signaling events is endoplasmic reticulum (ER) stress and mitochondrial oxidative stress that interact through mitochondria-associated ER membrane. In contrast to these protective effects and machineries, rare but serious cardiovascular disturbances were also reported in labor induction and animal studies including hypotension, reflexive tachycardia, coronary spasm or thrombosis and allergy. Here, we review our current understanding of the protective effect of OT against varieties of atherosclerotic etiologies as well as the approaches and underlying mechanisms of these effects. Moreover, potential cardiovascular disturbances following OT application are also discussed to avoid unwanted effects in clinical trials of OT usages.

Enhanced wound healing activity of PEG/PCL copolymer combined with bioactive nanoparticles in wound care after anorectal surgery: Via bio-inspired methodology.

Over the past decade, the implementation of the novel nanomaterials in the field of nanotechnology for the biomedical applications is essential for the comfort factors such as non-toxicity and biocompatibility in the human biological systems. In this context, a novel synthesis was worked out through bacterial species (citrobacter braakii) in the biofabrication of bioactive gold nanoparticles (Au NPs) for the wound healing management. The biosynthesized Au NPs were further modified and improved its compatibility with polyethylene glycol (PEG) and polycaprolactone (PCL) for formed as Au-PEG/PCL nanocomposites to extent the activity in wound healing application. The combination of bioactive nanoparticles with biocompatible polymeric substances has been upsurges the activity of nanoparticles due to the strong interaction of polymers. The biofabricated Au NPs and its nanocomposites were characterized using UV-Vis, FT-IR, XRD, DLS and TEM studies. Further, the prepared materials were tested in a wound healing model of rat with the wound of 22 mm size. The found results are demonstrated that the improved materials are highly active in growth of keratinocytes proliferation and simultaneously reduce scar formation. After 15 days observations, the wound were almost completely healed by the developed Au- PEG/PCL nanocomposites material which was confirmed by Masson's Trichrome staining histological images and antibacterial efficacy was displayed by the CLSM images. Notably, polymeric Au-PEG/PCL nanocomposites showed no inflammation on the wounded portion and internal implantation on rats thus evidencing it as a safe and biologically very active wound healing agent.