Direct Current Pulse Atmospheric Pressure Plasma Jet Treatment on Electrochemically Deposited NiFe/Carbon Paper and Its Potential Application in an Anion-Exchange Membrane Water Electrolyzer.

An atmospheric pressure plasma jet (APPJ) is used to process electrochemically deposited NiFe on carbon paper (NiFe/CP). The reactive oxygen and nitrogen species (RONs) of the APPJ modify the surface properties, chemical bonding types, and oxidation states of the material at the self-sustained temperature of the APPJ. The APPJ treatment further enhances the hydrophilicity and creates a higher disorder level in the carbon material. Moreover, the metal carbide bonds of NiFe/CP formed in the electrochemical deposition (ED) process are converted to metal oxide bonds after APPJ processing. The potential application of APPJ treatment on NiFe/CP in alkaline water electrolysis is demonstrated. With more oxygen-containing species and better hydrophilicity after APPJ treatment, APPJ-treated NiFe/CP is applied as the electrocatalyst for the oxygen evolution reaction (OER) in alkaline water electrolysis. APPJ-treated NiFe/CP is also used in a custom-made anion-exchange membrane water electrolyzer (AEMWE); this should contribute toward realizing the practical large-scale application of AEM for hydrogen production.

Tailoring Silver Nanowire Nanocomposite Interfaces to Achieve Superior Stretchability, Durability, and Stability in Transparent Conductors.

Silver nanowires (AgNWs) have been considered as a promising candidate for transparent stretchable conductors (TSCs). However, the strong interface mismatch of stiff AgNWs and elastic substrates leads to the stress concentration at their interface and ultimately the low stretchability and poor durability of TSCs. Here, to address the interfacial mismatch of AgNWs-based TSCs we put forward a universal interface tailoring strategy that introduces the mercapto compound as the intermediate cross-linked layer. The mercapto compound strongly interacts with the AgNWs, forming a dense protective layer on their surface to improve their corrosion resistance, and reacts with the polymer substrate, forming a buffer layer to release the concentrated stress. As a result, the optimized TSCs showed superior stretchability (160%), exceptional durability (230 000 cycles), competent optoelectrical performance (18.0 ohm·sq-1 with a transmittance of 86.5%), and prominent stability. This work provides clear guidance and a strong impetus for the development of transparent stretchable electronics.

Recent Advances and Synergistic Effects of Non-Precious Carbon-Based Nanomaterials as ORR Electrocatalysts: A Review.

The use of platinum-free (Pt) cathode electrocatalysts for oxygen reduction reactions (ORRs) has been significantly studied over the past decade, improving slow reaction mechanisms. For many significant energy conversion and storage technologies, including fuel cells and metal-air batteries, the ORR is a crucial process. These have motivated the development of highly active and long-lasting platinum-free electrocatalysts, which cost less than proton exchange membrane fuel cells (PEMFCs). Researchers have identified a novel, non-precious carbon-based electrocatalyst material as the most effective substitute for platinum (Pt) electrocatalysts. Rich sources, outstanding electrical conductivity, adaptable molecular structures, and environmental compatibility are just a few of its benefits. Additionally, the increased surface area and the simplicity of regulating its structure can significantly improve the electrocatalyst's reactive sites and mass transport. Other benefits include the use of heteroatoms and single or multiple metal atoms, which are capable of acting as extremely effective ORR electrocatalysts. The rapid innovations in non-precious carbon-based nanomaterials in the ORR electrocatalyst field are the main topics of this review. As a result, this review provides an overview of the basic ORR reaction and the mechanism of the active sites in non-precious carbon-based electrocatalysts. Further analysis of the development, performance, and evaluation of these systems is provided in more detail. Furthermore, the significance of doping is highlighted and discussed, which shows how researchers can enhance the properties of electrocatalysts. Finally, this review discusses the existing challenges and expectations for the development of highly efficient and inexpensive electrocatalysts that are linked to crucial technologies in this expanding field.

A signature of immune-related gene pairs predicts oncologic outcomes and response to immunotherapy in lung adenocarcinoma.

In this study, we established the predictive model for lung adenocarcinoma (LUAD) depending on immune-related gene pairs (IRGPs) signature, which could not consider the technical bias of different platforms. Furthermore, we explored the predictive model with regard to the immune microenvironment and response to immunotherapy and identified specific drugs targeting the IRGPs model. Twenty-three IRGPs were identified and comprised the predictive model. When compared with the high-risk group, the low-risk group displayed a distinctly favorable prognosis and was characterized by increased immune score and decreased tumor purity. In addition, the low-risk group exhibited higher expression of immune checkpoint molecules, lower tumor stemness index, and was much more sensitive to immunotherapy. Lastly, candidate drugs that aimed at LUAD subtype differentiation were identified. The derived IRGPs model is an adverse independent biomarker for estimating oncologic outcomes in LUAD patients, and may be helpful to formulate personalized immunotherapy strategy.

Effectiveness and safety of human amnion/chorion membrane therapy for diabetic foot ulcers: An updated meta-analysis of randomized clinical trials.

Human amnion/chorion membrane therapy has shown advantages in the management of diabetic foot ulcers and its effectiveness has been evaluated in the systematic reviews and meta-analyses. However, the number of patients included in the previous literatures was small and the safety profile of human amnion/chorion membrane therapy was not concerned. Therefore, we conducted an updated meta-analysis to better understand the effectiveness and safety of human amnion/chorion membrane therapy for diabetic foot ulcers. The PubMed, Embase, Cochrane Library, and ClinicalTrial.gov databases were searched for any randomized clinical trials comparing human amnion/chorion membrane therapy and standard therapy in the treatment of diabetic foot ulcers. Ulcer healing rate was considered as the primary outcome and the secondary outcomes mainly included mean time to ulcer healing and adverse events. Nine RCTs with 541 patients were included. Compared with merely standard therapy, human amnion/chorion membrane therapy plus standard therapy improved the ulcer healing rates at 6 weeks (RR = 3.50, 95% CI: 2.35-5.21), 12 weeks (RR = 2.09, 95% CI: 1.53-2.85) and 16 weeks (RR = 1.70, 95% CI: 1.25-2.30), and also shortened the healing time (MD = -4.58, 95% CI: -5.70 to -3.46). Meanwhile, no significant difference was observed in the number of patients with adverse events (RR = 0.56, 95% CI: 0.31-1.03) between two groups. This meta-analysis suggests that human amnion/chorion membrane therapy as an adjuvant treatment could promote the healing of diabetic foot ulcers and has a safety profile. More evidence from large high-quality randomized clinical trials with long follow-up duration are in urgent need to further confirm our findings.

Role of Lin28A/let-7a/c-Myc Pathway in Growth and Malignant Behavior of Papillary Thyroid Carcinoma.

BACKGROUND Lin28 is a gene involved in many biological processes, including development, glucose metabolism, and tumorigenesis. Let-7 miRNA is a tumor-suppressor gene that is frequently inactivated in cancer cells. The role of c-Myc (a target gene of let-7) and the Lin28-let-7-c-Myc pathway in the growth and malignancy of thyroid cancer is unclear. The purpose of the present study was to evaluate the expression of Lin28A, let-7a, and c-Myc in human papillary thyroid carcinoma (PTC) and to investigate their potential mechanisms in the progression of PTC. MATERIAL AND METHODS Lin28A and c-Myc expression were assessed in PTC tissues and PTC cell lines using immunohistochemistry, Western blotting, and real-time PCR. CCK-8 and Transwell assays were performed to evaluate PTC cell proliferation, migration, and invasion in cells in which the expression of Lin28A was downregulated by RNA interference or in which let-7a was overexpressed after transfection with let-7a mimics. RESULTS The expression of Lin28A and c-Myc was upregulated in PTC tissues and cell lines, whereas the expression of let-7a was downregulated in PTC cell lines. Clinically, Lin28A was linked to a higher tumor/node/metastasis stage and the presence of lymph node metastases. Moreover, knockdown of Lin28A activated let-7a processing and inhibited the expression of the downstream gene c-Myc, suppressing cell proliferation, migration, and invasion. Similar results were obtained after let-7a overexpression. CONCLUSIONS The Lin28A/let-7a/c-Myc pathway is involved in cancer growth and malignant behavior in PTC and is a potential target for therapeutic intervention in this disease.

The overexpression of hypomethylated miR-663 induces chemotherapy resistance in human breast cancer cells by targeting heparin sulfate proteoglycan 2 (HSPG2).

MicroRNAs are involved in regulating the biology of cancer cells, but their involvement in chemoresistance is not fully understood. We found that miR-663 was up-regulated in our induced multidrug-resistant MDA-MB-231/ADM cell line and that this up-regulation was closely related to chemosensitivity. In the present study, we aimed to clarify the role of miR-663 in regulating the chemoresistance of breast cancer. MicroRNA microarray and quantitative RT-PCR assays were used to identify differentially expressed microRNAs. Cell apoptosis was evaluated by annexin V/propidium iodide staining, TUNEL, and reactive oxygen species generation analysis. The expression of miR-663 and HSPG2 in breast cancer tissues was detected by in situ hybridization and immunohistochemistry. The potential targets of miR-663 were defined by a luciferase reporter assay. Bisulfite sequencing PCR was used to analyze the methylation status. We found that miR-663 was significantly elevated in MDA-MB-231/ADM cells, and the down-regulation of miR-663 sensitized MDA-MB-231/ADM cells to both cyclophosphamide and docetaxel. The overexpression of miR-663 in breast tumor tissues was associated with chemoresistance; in MDA-MB-231 cells, this chemoresistance was accompanied by the down-regulation of HSPG2, which was identified as a target of miR-663. MDA-MB-231/ADM contained fewer methylated CpG sites than its parental cell line, and miR-663 expression in MDA-MB-231 cells was reactivated by 5-aza-29-deoxycytidine treatment, indicating that DNA methylation may play a functional role in the expression of miR-663. Our findings suggest that the overexpression of hypomethylated miR-663 induced chemoresistance in breast cancer cells by down-regulating HSPG2, thus providing a potential target for the development of an microRNA-based approach for breast cancer therapy.

Reduced risk of dyslipidaemia with oolong tea consumption: a population-based study in southern China.

Experimental studies have suggested that tea consumption could lower the risk of dyslipidaemia. However, epidemiological evidence is limited, especially in southern China, where oolong tea is the most widely consumed beverage. We conducted a population-based case-control study to evaluate the association between consumption of tea, especially oolong tea, and risk of dyslipidaemia in Shantou, southern China, from 2010 to 2011. Information on tea consumption, lifestyle characteristics and food consumption frequency of 1651 patients with newly diagnosed dyslipidaemia and 1390 controls was obtained using a semi-quantitative questionnaire. Anthropometric variables and serum biochemical indices were determined. Drinking more than 600 ml (2 paos) of green, oolong or black tea daily was found to be associated with the lowest odds of dyslipidaemia risk (P< 0.001) when compared with non-consumption, but only oolong tea consumption was found to be associated with low HDL-cholesterol levels. A dose-response relationship between duration of tea consumption and risk of dyslipidaemia (OR 0.10, 95% CI 0.06, 0.16), as well as that between amount of dried tea leaves brewed and risk of dyslipidaemia (OR 0.34, 95% CI 0.24, 0.48), was found. Moreover, consumption of oolong tea for the longest duration was found to be associated with 3.22, 11.99 and 6.69% lower blood total cholesterol, TAG and LDL-cholesterol levels, respectively. In conclusion, the present study indicates that long-term oolong tea consumption may be associated with a lower risk of dyslipidaemia in the population of Shantou in southern China.

Decreased activated protein C levels are inversely associated with the urinary albumin excretion rate in patients with type 2 diabetes.

BACKGROUND: Activated protein C (APC) plays a vital renoprotective role against diabetic nephropathy in STZ-induced diabetic mice by inhibiting endothelial cell and podocyte apoptosis. This study aimed to examine the relationship between the degree of albuminuria and APC levels in patients with type 2 diabetes. METHODS: Ninety-four patients with type 2 diabetes and 38 healthy subjects were recruited into this study. The urinary albumin concentrations of urine collected over 24 hours were measured by ELISA to evaluate the mean urinary albumin excretion rate (UAER). The HbA1c levels were determined using an HPLC assay. RESULTS: There was no significant difference in the APC levels between diabetic patients with normoalbuminuria and controls, although APC levels were significantly lower in diabetic patients with microalbuminuria (23.06 +/- 19.82 vs. 54.58 +/- 53.63 pg/mL, p < 0.05) or macroalbuminuria (8.06 +/- 10.09 vs. 54.58 +/- 53.63 pg/mL, p < 0.05) as compared to control subjects. In addition, in comparison to diabetic patients with normoalbuminuria, APC levels were lower in diabetic patients with microalbuminuria (23.06 +/- 19.82 vs. 55.69 +/- 31.98 pg/mL, p < 0.05) and they were the lowest in diabetic patients with macroalbuminuria (8.06 +/- 10.09 vs. 55.69 +/- 31.98 pg/mL, p < 0.05). Multivariate regression and ROC analysis found that the levels of APC and HbA1c were independent risk factors for UAER levels (R2(ad) = 0.61, f = 25.69, p < 0.01) and the value of APC < or = 41.588 pg/mL indicated elevated albuminuria in patients with type 2 diabetes. CONCLUSIONS: Decreased APC levels in patients with type 2 diabetes may serve as a biomarker to indicate the early development of diabetic nephropathy.

Apelin-13 decreases lipid storage in hypertrophic adipocytes in vitro through the upregulation of AQP7 expression by the PI3K signaling pathway.

BACKGROUND: Adipocyte-secreted apelin contributes to decreased adiposity and to improved insulin resistance, but the mechanisms remain unknown. The present study aimed to assess if apelin-13 is an upstream signal regulation factor of aquaporin 7 (AQP7), a water-glycerol transporter present in the plasma membrane of adipocytes that plays a key role in the regulation of lipid accumulation. MATERIAL/METHODS: 3T3-L1 pre-adipocytes were induced to fully differentiated adipocytes; hypertrophic adipocytes were then induced using palmitate. The effects of apelin-13 on AQP7 expression in hypertrophic adipocytes were investigated before and after treatment with LY249002, a PI3K inhibitor. Accumulation of cytoplasmic triglycerides (TG) in hypertrophic adipocytes was also determined. RESULTS: We found that 0.1 mM of palmitate induced a model of hypertrophic adipocytes with a lower AQP7 expression (0.26±0.07 vs. 0.46±0.04, P<0.05). Apelin-13 100 nM or 1000 nM upregulated AQP7 mRNA expression (100 nM: 0.54±0.06 and 1000 nM: 0.58±0.09 vs. control: 0.33±0.04, both P<0.05), and decreased accumulation of cytoplasmic triglycerides in hypertrophic adipocytes. Pretreatment using 10 µM LY294002 prevented the increase in AQP7 expression observed when using apelin-13 alone (apelin-13 + LY49002: 0.38±0.03 vs. apelin-13: 0.54±0.06, P<0.05), as well as the decreased cytoplasmic TG accumulation (apelin-13 + LY294002: 3.79±0.04 µM per µg/ml vs. apelin-13: 3.32±0.08 µM per µg/ml, P<0.05). CONCLUSIONS: Apelin-13 decreases lipid storage in hypertrophic adipocytes in vitro, possibly through the upregulation of AQP7 expression by the PI3K signaling pathway. Treatment using apelin-13 and AQP modulators might represent novel treatment strategies against obesity and its related complications.

Binder-Free CNT-Modified Excellent Electrodes for All-Vanadium Redox Flow Batteries.

Electrodes are one of the key components that influence the performance of all-vanadium redox flow batteries (VRFBs). A porous graphite felt with modified fiber surfaces that can provide a high specific activation surface is preferred as the electrode of a VRFB. In this study, a simple binder-free approach is developed for preparing stable carbon nanotube modified graphite felt electrodes (CNT-GFs). Heat-treated graphite felt electrodes (H-GFs) are dip-coated using CNT homogeneous solution. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) results conclude that CNT-GFs have less resistance, better reaction currents, and reversibility as compared to H-GF. Cell performances showed that CNT-GFs significantly improve the performance of a VRFB, especially for the CNT-GF served in the positive side of the VRFB. CNT presence increases the electrochemical properties of the graphite electrode; as a result, reaction kinetics for both VO2+/VO2+ and V3+/V2+ are improved. Positive CNT-GF (P-CNT-GF) configured VRFB exhibits voltage efficiency, coulombic efficiency, and energy efficiency of 85%, 97%, and 82%, respectively, at the operating current density of 100 mA cm-2. At high current density of 200 mA cm-2, the VRFB with P-CNT-GF shows 73%, 98%, and 72% of the voltage, coulombic, and energy efficiencies, respectively. The energy efficiency of the CNT-GF is 6% higher when compared with that of B-H-GF. The VRFB with CNT-GF can provide stable performance for 300 cycles at 200 mA cm-2.

Physiochemical and Electrochemical Properties of a Heat-Treated Electrode for All-Iron Redox Flow Batteries.

Iron redox flow batteries (IRFBs) are cost-efficient RFBs that have the potential to develop low-cost grid energy storage. Electrode kinetics are pivotal in defining the cycle life and energy efficiency of the battery. In this study, graphite felt (GF) is heat-treated at 400, 500 and 600 °C, and its physicochemical and electrochemical properties are studied using XPS, FESEM, Raman and cyclic voltammetry. Surface morphology and structural changes suggest that GF heat-treated at 500 °C for 6 h exhibits acceptable thermal stability while accessing the benefits of heat treatment. Specific capacitance was calculated for assessing the wettability and electrochemical properties of pristine and treated electrodes. The 600 °C GF has the highest specific capacitance of 34.8 Fg-1 at 100 mV s-1, but the 500 °C GF showed the best battery performance. The good battery performance of the 500 °C GF is attributed to the presence of oxygen functionalities and the absence of thermal degradation during heat treatment. The battery consisting of 500 °C GF electrodes offered the highest voltage efficiency of ~74%, Coulombic efficiency of ~94%, and energy efficiency of ~70% at 20 mA cm-2. Energy efficiency increased by 7% in a battery consisting of heat-treated GF in comparison to pristine GF. The battery is capable of operating for 100 charge-discharge cycles with an average energy efficiency of ~ 67% for over 100 cycles.

CVD Grown CNTs-Modified Electrodes for Vanadium Redox Flow Batteries.

Vanadium redox flow batteries (VRFBs) are of considerable importance in large-scale energy storage systems due to their high efficiency, long cycle life and easy scalability. In this work, chemical vapor deposition (CVD) grown carbon nanotubes (CNTs)-modified electrodes and Nafion 117 membrane are utilised for formulating a vanadium redox flow battery (VRFB). In a CVD chamber, the growth of CNTs is carried out on an acid-treated graphite felt surface. Cyclic voltammetry of CNT-modified electrode and acid-treated electrode revealed that CNTs presence improve the reaction kinetics of V3+/V2+ and VO2+/VO2+ redox pairs. Battery performance is recorded for analysing, the effect of modified electrodes, varying electrolyte flow rates, varying current densities and effect of removing the current collector plates. CNTs presence enhance the battery performance and offered 96.30% of Coulombic efficiency, 79.33% of voltage efficiency and 76.39% of energy efficiency. In comparison with pristine electrodes, a battery consisting CNTs grown electrodes shows a 14% and 15% increase in voltage efficiency and energy efficiency, respectively. Battery configured without current collector plates performs better as compared to with current collector plates which is possibly due to decrease in battery resistance.

Measuring treatment burden in people with Type 2 Diabetes Mellitus (T2DM): a mixed-methods systematic review.

BACKGROUND: Measuring treatment burden is important for the effective management of Type 2 Diabetes Mellitus (T2DM) care. The purpose of this systematic review was to identify the most robust approach for measuring treatment burden in people with T2DM based on existing evidence. METHODS: Articles from seven databases were retrieved. Qualitative, quantitative, and mixed-methods studies examining treatment burden in adults with T2DM and/or reporting relevant experiences were included. A convergent segregated approach with a mixed-methods design of systematic review was employed, creating a measurement framework in a narrative review for consistent critical appraisal. The quality of included studies was assessed using the Joanna Briggs Institute tool. The measurement properties of the instruments were evaluated using the Consensus based Standards for selection of Health Measurement Instruments (COSMIN) checklist. RESULTS: A total of 21,584 records were screened, and 26 articles were included, comprising 11 quantitative, 11 qualitative, and 4 mixed-methods studies. A thematic analysis of qualitative data extracted from the included articles summarised a measurement framework encompassing seven core and six associated measurements. The core measurements, including financial, medication, administrative, lifestyle, healthcare, time/travel, and medical information burdens, directly reflect the constructs pertinent to the treatment burden of T2DM. In contrast, the associated measurement themes do not directly reflect the burdens or are less substantiated by current evidence. The results of the COSMIN checklist evaluation demonstrated that the Patient Experience with Treatment and Self-management (PETS), Treatment Burden Questionnaire (TBQ), and Multimorbidity Treatment Burden Questionnaire (MTBQ) have robust instrument development processes. These three instruments, with the highest total counts combining the number of themes covered and "positive" ratings in COSMIN evaluation, were in the top tertile stratification, demonstrating superior applicability for measuring T2DM treatment burden. CONCLUSIONS: This systematic review provides evidence for the currently superior option of measuring treatment burden in people with T2DM. It also revealed that most current research was conducted in well-resourced institutions, potentially overlooking variability in under-resourced settings.

Exploring treatment burden in people with type 2 diabetes mellitus: a thematic analysis in china's primary care settings.

BACKGROUND: Understanding treatment burden is a critical element to the effective management of Type 2 Diabetes Mellitus (T2DM). The current study aims to address the knowledge gap surrounding treatment burden of T2DM from the patient's perspective in China's primary care settings. METHODS: A narrative review informed the creation of an a priori coding structure to identify aspects of T2DM treatment burden. Focus groups were conducted, employing a maximum variation sampling strategy to select participants from diverse sociodemographic backgrounds across urban, suburban, rural, and remote areas in China. Participants included adults with T2DM care in primary care settings for over a year and a Treatment Burden Questionnaire score of 25 or higher. Deductive thematic analysis, guided by the coding structure, facilitated a comprehensive exploration and further development of the conceptual framework of T2DM treatment burden. RESULTS: Four focus groups, each comprising five participants from diverse areas, were conducted. Utilising the Cumulative Complexity Model and Normalisation Process Theory as theoretical underpinnings, the thematic analysis refined the conceptual framework based on the coding structure from the narrative review. Five key themes were refined, encompassing medical information, medication, administration, healthcare system, and lifestyle. Additionally, the financial and time/travel themes merged into a new theme termed "personal resources", illustrating their overlapping within the framework. Participants in these focus groups highlighted challenges in managing medical information, an aspect often underrepresented in prior treatment burden research. The thematic analysis culminated in a finalised conceptual framework, offering a comprehensive understanding of the treatment burden experiences of people with T2DM in China's primary care settings. This framework includes six key constructs, delineating T2DM treatment burden and associated factors, such as antecedents and consequences. CONCLUSIONS: This study provides insights into the treatment burden of T2DM. A conceptual framework was finalised to deepen the understanding of the multifaceted constructs and the nature of treatment burden in people with T2DM. Furthermore, it emphasises the need to tailor T2DM treatment to individual capacities, considering their personal resource allocation and treatment utilisation.

Lactobacillus rhamnosus GG ameliorates hyperuricemia in a novel model.

Hyperuricemia (HUA) is a metabolic syndrome caused by abnormal purine metabolism. Although recent studies have noted a relationship between the gut microbiota and gout, whether the microbiota could ameliorate HUA-associated systemic purine metabolism remains unclear. In this study, we constructed a novel model of HUA in geese and investigated the mechanism by which Lactobacillus rhamnosus GG (LGG) could have beneficial effects on HUA. The administration of antibiotics and fecal microbiota transplantation (FMT) experiments were used in this HUA goose model. The effects of LGG and its metabolites on HUA were evaluated in vivo and in vitro. Heterogeneous expression and gene knockout of LGG revealed the mechanism of LGG. Multi-omics analysis revealed that the Lactobacillus genus is associated with changes in purine metabolism in HUA. This study showed that LGG and its metabolites could alleviate HUA through the gut-liver-kidney axis. Whole-genome analysis, heterogeneous expression, and gene knockout of LGG enzymes ABC-type multidrug transport system (ABCT), inosine-uridine nucleoside N-ribohydrolase (iunH), and xanthine permease (pbuX) demonstrated the function of nucleoside degradation in LGG. Multi-omics and a correlation analysis in HUA patients and this goose model revealed that a serum proline deficiency, as well as changes in Collinsella and Lactobacillus, may be associated with the occurrence of HUA. Our findings demonstrated the potential of a goose model of diet-induced HUA, and LGG and proline could be promising therapies for HUA.

S1PR2 is Important for Cigarette Smoke-induced Pyroptosis in Human Bronchial Epithelial Cells.

BACKGROUND: Chronic obstructive pulmonary disease and other respiratory inflammatory diseases are often associated with cigarette smoke exposure. However, the underlying molecular mechanism remains unclear. AIM OF THE STUDY: This study aimed to investigate the role of sphingosine-1-phosphate receptor 2 (S1PR2) in cigarette smoke extract (CSE)-induced inflammation and pyroptosis in human bronchial epithelial (HBE) cells. METHODS: CSE was administered to HBE cells and inflammation and pyroptosis were assessed. The mRNA levels of S1PR2, NLRP3, IL-1ß, and IL-18 in HBE cells were detected by quantitative RT-PCR. Secreted protein levels of IL-1ß and IL-18 in the culture supernatants were detected using enzyme-linked immunosorbent assay. Western blotting was used to measure the levels of S1PR2 and pyroptosis-related proteins (NLRP3, ASC, caspase-1, GSDMD, IL-1ß, and IL-18). RESULTS: Our study revealed an upregulated expression of S1PR2, NLRP3, ASC, caspase-1, GSDMD, IL-1ß, and regulated IL-18 in HBE cells after CSE exposure. Genetic blockage of S1PR2 could reverse the increased expression of these proteins related to CSE-induced pyroptosis. Conversely, S1PR2 overexpression increased CSE-induced pyroptosis by upregulating the expression of NLRP3, ASC, caspase-1, GSDMD, IL-1ß, and IL-18 in HBE cells. CONCLUSIONS: Our results revealed that a novel S1PR2 signaling pathway may be involved in the pathogenesis of CSE-induced inflammation and pyroptosis in HBE cells. Thus, S1PR2 inhibitors could be an effective treatment for cigarette smoke-induced airway inflammation and injury.

Caffeine ameliorates the metabolic syndrome in diet-induced obese mice through regulating the gut microbiota and serum metabolism.

OBJECTIVE: Obesity is associated with gut microbiota disorders, which has been related to developing metabolic syndromes. The research aims to investigate the effects of caffeine treatment on insulin resistance, intestinal microbiota composition and serum metabolomic changes in high-fat diet (HFD)-induced obesity mice. METHODS: Eight-week-old male C57BL/6 J mice were fed a normal chow diet (NCD) or HFD with or without different concentrations of caffeine. After 12 weeks of treatment, body weight, insulin resistance, serum lipid profiles, gut microbiota and serum metabolomic profiles were assessed. RESULTS: Caffeine intervention improved the metabolic syndrome in HFD-fed mice, such as serum lipid disorders and insulin resistance. 16S rRNA Sequencing analysis revealed that caffeine increased the relative abundance of Dubosiella, Bifidobacterium and Desulfovibrio and decreased that of Bacteroides, Lactobacillus and Lactococcus to reverse HFD-fed obesity in mice. Additionally, Caffeine Supplementation also altered serum metabolomics, mainly focusing on lipid metabolism, bile acid metabolism and energy metabolism. Caffeine increased its metabolite 1,7-Dimethylxanthine, which was positively correlated with Dubosiella. CONCLUSIONS: Caffeine exerts a beneficial effect on insulin resistance in HFD-mice, and the underlying mechanism may be partly related to altered gut microbiota and bile acid metabolism.

NiFe2O4 Material on Carbon Paper as an Electrocatalyst for Alkaline Water Electrolysis Module.

NiFe2O4 material is grown on carbon paper (CP) with the hydrothermal method for use as electrocatalysts in an alkaline electrolyzer. NiFe2O4 material is used as the anode and cathode catalysts (named NiFe(+)/NiFe(-) hereafter). The results are compared with those obtained using CP/NiFe as the anode and CP/Ru as the cathode (named NiFe)(+)/Ru(-) hereafter). During cell operation with NiFe(+)/Ru(-), the current density reaches 500 mA/cm2 at a cell voltage of 1.79 V, with a specific energy consumption of 4.9 kWh/m3 and an energy efficiency of 66.2%. In comparison, for NiFe(+)/NiFe(-), the current density reaches 500 mA/cm2 at a cell voltage of 2.23 V, with a specific energy consumption of 5.7 kWh/m3 and an energy efficiency of 56.6%. The Faradaic efficiency is 96-99%. With the current density fixed at 400 mA/cm2, after performing a test for 150 h, the cell voltage with NiFe(+)/Ru(-) increases by 0.167 V, whereas that with NiFe(+)/NiFe(-) decreases by only 0.010 V. Good, long-term stability is demonstrated.

Discovery of Dual Lysine Methyltransferase G9a and EZH2 Inhibitors with In Vivo Efficacy against Malignant Rhabdoid Tumor.

In recent years, it has been proposed that G9a/EZH2 dual inhibition is a promising cancer treatment strategy. Herein, we present the discovery of G9a/EZH2 dual inhibitors that merge the pharmacophores of G9a and EZH2 inhibitors. Among them, the most promising compound 15h displayed potent inhibitory activities against G9a (IC50 = 2.90 ± 0.05 nM) and EZH2 (IC50 = 4.35 ± 0.02 nM), superior antiproliferative profiles against RD (CC50 = 19.63 ± 0.18 µM) and SW982 (CC50 = 19.91 ± 0.50 µM) cell lines. In vivo, 15h achieved significant antitumor efficacy in a xenograft mouse model of human rhabdoid tumor with a tumor growth inhibitory rate of 86.6% without causing observable toxic effects. The on-target activity assays illustrated that compound 15h can inhibit tumor growth by specifically inhibiting EZH2 and G9a. Therefore, 15h is a potential anticancer drug candidate for the treatment of malignant rhabdoid tumor.