Enhanced Visible-Light-Driven Photocatalytic Overall Splitting of Pure Water in a Porous Microreactor.

Photocatalytic overall splitting of pure water (H2O) without sacrificial reagent to hydrogen (H2) and oxygen (O2) holds a great potential for achieving carbon neutrality. Herein, by anchoring cobalt sulfide (Co9S8) as cocatalyst and cadmium sulfide (CdS) as light absorber to channel wall of a porous polymer microreactor (PP12), continuous violent H2 and O2 bubbling productions from photocatalytic overall splitting of pure H2O without sacrificial reagent is achieved, with H2 and O2 production rates as high as 4.41 and 2.20 mmol h-1 gcat.-1 respectively. These are significantly enhanced than those in the widely used stirred tank-type reactor in which no O2 is produced and H2 production rate is only 0.004 mmol h-1 gcat.-1. Besides improved charge separation and interaction of H2O with photocatalyst in PP12, bonding interaction of Co9S8 with PP12 creates abundant catalytic active sites for simultaneous productions of H2 and O2, thus leading to the significantly enhanced H2 and O2 bubbling productions in PP12. This offers a new strategy to enhance photocatalytic overall splitting of pure H2O without sacrificial reagent.

Bacteroides uniformis Ameliorates Carbohydrate and Lipid Metabolism Disorders in Diabetic Mice by Regulating Bile Acid Metabolism via the Gut-Liver Axis.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a metabolic syndrome characterized by chronic inflammation, insulin resistance, and islet cell damage. The prevention of T2DM and its associated complications is an urgent public health issue that affects hundreds of millions of people globally. Numerous studies suggest that disturbances in gut metabolites are important driving forces for the pathogenesis of diabetes. However, the functions and mechanisms of action of most commensal bacteria in T2DM remain largely unknown. METHODS: The quantification of bile acids (BAs) in fecal samples was performed using ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS). The anti-diabetic effects of Bacteroides uniformis (B. uniformis) and its metabolites cholic acid (CA) and chenodeoxycholic acid (CDCA) were assessed in T2DM mice induced by streptozocin (STZ) plus high-fat diet (HFD). RESULTS: We found that the abundance of B. uniformis in the feces and the contents of CA and CDCA were significantly downregulated in T2DM mice. B. uniformis was diminished in diabetic individuals and this bacterium was sufficient to promote the production of BAs. Colonization of B. uniformis and intragastric gavage of CA and CDCA effectively improved the disorder of glucose and lipid metabolism in T2DM mice by inhibiting gluconeogenesis and lipolysis in the liver. CA and CDCA improved hepatic glucose and lipid metabolism by acting on the Takeda G protein-coupled receptor 5 (TGR5)/adenosine monophosphate-activated protein kinase (AMPK) signaling pathway since knockdown of TGR5 minimized the benefit of CA and CDCA. Furthermore, we screened a natural product-vaccarin (VAC)-that exhibited anti-diabetic effects by promoting the growth of B. uniformis in vitro and in vivo. Gut microbiota pre-depletion abolished the favorable effects of VAC in diabetic mice. CONCLUSIONS: These data suggest that supplementation of B. uniformis may be a promising avenue to ameliorate T2DM by linking the gut and liver.

Discovery of Orally Bioavailable and Potent CDK9 Inhibitors for Targeting Transcription Regulation in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) represents a highly aggressive and heterogeneous malignancy. Currently, effective therapies for TNBC are very limited and remain a significant unmet clinical need. Targeting the transcription-regulating cyclin-dependent kinase 9 (CDK9) has emerged as a promising avenue for therapeutic treatment of TNBC. Herein, we report the design, synthesis, optimization, and evaluation of a new series of aminopyrazolotriazine compounds as orally bioavailable, potent, and CDK9/2 selectivity-improved inhibitors, enabling efficacious inhibition of TNBC cell growth, as well as notable antitumor effect in TNBC models. The compound C35 demonstrated low-nanomolar potency with substantially improved CDK9/2 selectivity, downregulated the CDK9-downstream targets (e.g., MCL-1), and induced apoptosis in TNBC cell lines. Moreover, with the desired oral bioavailability, oral administration of C35 could significantly suppress the tumor progression in two TNBC mouse models. This study demonstrates that target transcriptional regulation is an effective strategy and holds promising potential as a targeted therapy for the treatment of TNBC.

Vaccarin alleviates septic cardiomyopathy by potentiating NLRP3 palmitoylation and inactivation.

BACKGROUND: Sepsis often leads to significant morbidity and mortality due to severe myocardial injury. As is known, the activation of NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome crucially contributes to septic cardiomyopathy (SCM) by facilitating the secretion of interleukin (IL)-1ß and IL-18. The removal of palmitoyl groups from NLRP3 is a crucial step in the activation of the NLRP3 inflammasome. Thus, the potential inhibitors that regulate the palmitoylation and inactivation of NLRP3 may significantly diminish sepsis-induced cardiac dysfunction. PURPOSE: The present study sought to explore the effects of the prospective flavonoid compounds targeting NLRP3 on SCM and to elucidate the associated underlying mechanisms. STUDY DESIGN: The palmitoylation and activation of NLRP3 were detected in H9c2 cells and C57BL/6 J mice. METHODS/RESULTS: Echocardiography, histological staining, western blotting, co-immunoprecipitation, qPCR, ELISA and network pharmacology were used to assess the impact of vaccarin (VAC) on SCM in mice subjected to lipopolysaccharide (LPS) injection. From the collection of 74 compounds, we identified that VAC had the strongest capability to suppress NLRP3 luciferase report gene activity in cardiomyocytes, and the anti-inflammatory characteristics of VAC were further ascertained by the network pharmacology. Exposure of LPS triggered apoptosis, inflammation, oxidative stress, mitochondrial disorder in cardiomyocytes. The detrimental alterations were significantly reversed upon VAC treatment in both septic mice and H9c2 cells exposed to LPS. In vivo experiments demonstrated that VAC treatment alleviated septic myocardial injury, indicated by enhanced cardiac function parameters, preserved cardiac structure, and reduced inflammation/oxidative response. Mechanistically, VAC induced NLRP3 palmitoylation to inactivate NLRP3 inflammasome by acting on zDHHC12. In support, the NLRP3 agonist ATP and the acylation inhibitor 2-bromopalmitate (2-BP) prevented the effects of VAC. CONCLUSION: Our findings suggest that VAC holds promise in protecting against SCM by mitigating cardiac oxidative stress and inflammation via priming NLRP3 palmitoylation and inactivation. These results lay the solid basis for further assessment of the therapeutic potential of VAC against SCM.

Boosted Sacrificial-Agent-Free Selective Photoreduction of CO2 to CH3OH by Rhenium Atomically Dispersed on Indium Oxide.

Solar-energy-driven photoreduction of CO2 is promising in alleviating environment burden, but suffers from low efficiency and over-reliance on sacrificial agents. Herein, rhenium (Re) is atomically dispersed in In2O3 to fabricate a 2Re-In2O3 photocatalyst. In sacrificial-agent-free photoreduction of CO2 with H2O, 2Re-In2O3 shows a long-term stable efficiency which is enhanced by 3.5 times than that of pure In2O3 and is also higher than those on Au-In2O3, Ag-In2O3, Cu-In2O3, Ir-In2O3, Ru-In2O3, Rh-In2O3 and Pt-In2O3 photocatalysts. Moreover, carbon-based product of the photoreduction overturns from CO on pure In2O3 to CH3OH on 2Re-In2O3. Re promotes charge separation, H2O dissociation and CO2 activation, thus enhancing photoreduction efficiency of CO2 on 2Re-In2O3. During the photoreduction, CO is a key intermediate. CO prefers to desorption rather than hydrogenation on pure In2O3, as CO binds to pure In2O3 very weakly. Re strengthens the interaction of CO with 2Re-In2O3 by 5.0 times, thus limiting CO desorption but enhancing CO hydrogenation to CH3OH. This could be the origin for photoreduction product overturn from CO on pure In2O3 to CH3OH on 2Re-In2O3. The present work opens a new way to boost sacrificial-agent-free photoreduction of CO2.

Electronic Interactions on Platinum/(Metal-Oxide)-Based Photocatalysts Boost Selective Photoreduction of CO2 to CH4.

By supporting platinum (Pt) and cadmium sulfide (CdS) nanoparticles on indium oxide (In2 O3 ), we fabricated a CdS/Pt/In2 O3 photocatalyst. Selective photoreduction of carbon dioxide (CO2 ) to methane (CH4 ) was achieved on CdS/Pt/In2 O3 with electronic Pt-In2 O3 interactions, with CH4 selectivity reaching to 100 %, which is higher than that on CdS/Pt/In2 O3 without electronic Pt-In2 O3 interactions (71.7 %). Moreover, the enhancement effect of electronic Pt-(metal-oxide) interactions on selective photoreduction of CO2 to CH4 also occurs by using other common metal oxides, such as photocatalyst supports, including titanium oxide, gallium oxide, zinc oxide, and tungsten oxide. The electronic Pt-(metal-oxide) interactions separate photogenerated electron-hole pairs and convert CO2 into CO2 δ- , which can be easily hydrogenated into CH4 via a CO2 δ- →HCOO*→HCO*→CH*→CH4 path, thus boosting selective photoreduction of CO2 to CH4 . This offers a new way to achieve selective photoreduction of CO2 .

Long-Term Stable Hydrogen Production from Water and Lactic Acid via Visible-Light-Driven Photocatalysis in a Porous Microreactor.

Photocatalytic hydrogen (H2 ) production is significant to overcome challenges like fossil fuel depletion and carbon dioxide emission, but its efficiency is still far below that which is needed for commercialization. Herein, we achieve long-term stable H2 bubbling production from water (H2 O) and lactic acid via visible-light-driven photocatalysis in a porous microreactor (PP12); the catalytic system benefits from photocatalyst dispersion, charge separation, mass transfer, and dissociation of O-H bonds associated with H2 O. With the widely used platinum/cadmium-sulfide (Pt/CdS) photocatalyst, PP12 leads to a H2 bubbling production rate of 602.5 mmol h-1 m-2 , which is 1000 times higher than that in a traditional reactor. Even when amplifying PP12 into a flat-plate reactor with an area as large as 1 m2 and extending the reaction time to 100 h, the H2 bubbling production rate still remains at around 600.0 mmol h-1 m-2 , offering great potential for commercialization.

[Supply-demand bundles and ecological function management of urban ecosystem services: Taking central urban area of Qiqihar as an example]. / 城市生态系统服务供需簇与生态功能管控­­ä»¥é½é½å“ˆå°”市中心城区为例.

The comprehensive management of multiple ecosystem services is the focus of current research in the field of ecosystem service. The ecological space in the central urban area is scarce, but ecological needs are diverse. How to scientifically use urban land while considering various ecological functions has gradually become an academic hotspot. Taking the central urban area of Qiqihar as an example, we applied the ecosystem service bundle theory to analyze the supply and demand relationship of five ecosystem services in the study area, including flood regulation, air purification, carbon storage and sequestration, biodiversity conservation, and cultural recreation. Based on the supply-demand ratio, we identified the supply-demand bundles of ecosystem services in the study area, completed the division of ecological functional areas, and proposed corresponding spatial control strategies. The results showed that the supply of those five services presented a spatial pattern of low in the city center and south side, while high in the northwest and southeast side, and that the demand for those five services presented a spatial pattern of high in the city center and low around the city. Air purification, biodiversity conservation, and cultural recreation ser-vices were in short supply, with a supply-demand ratio of -0.160, -0.071, and -0.008, respectively. The supply to demand ratios of flood regulation and carbon storage and sequestration services were in excess, with a supply to demand ratio of 0.089 and 0.008, respectively. The spatial imbalance between supply and demand of various services was significant. The research area could be divided into six types of ecosystem service bundles. After comprehensive analysis, the research area would be further divided into four types of zones: urban ecological restoration zone, urban ecological strengthening zone, urban development transition zone, and urban ecological conservation zone. We proposed targeted functional optimization strategies based on the spatial relationship, ecological background characteristics, and supply and demand ratios of various services within the zone.

Study on the correlation between extracellular matrix protein-1 and the growth, metastasis and angiogenesis of laryngeal carcinoma.

OBJECTIVE: To investigate the correlation between extracellular matrix protein-1 (ECM1) and the growth, metastasis and angiogenesis of laryngeal carcinoma. MATERIALS AND METHODS: Forty-five samples with laryngeal benign and malignant tumors confirmed by pathology in Laiwu City People's Hospital from March 2006 to March 2011 were collected, in which there were 29 cases with laryngeal carcinoma and 16 with benign tumors. The expression of ECM1 and factor VIII-related antigens in patients with laryngeal carcinoma and those with benign tumors was respectively detected using immunohistochemical method, and the correlation between ECM1 staining grade and microvessel density (MVD) was analyzed. RESULTS: In laryngeal carcinoma tissue, ECM1 was mainly expressed in cytoplasm, less in cytomembrane or intercellular substance. With abundant expression in the tissue of laryngeal benign tumors (benign mesenchymoma and hemangioma), ECM1 was primarily expressed in the connective tissue, which was different from the expression in laryngeal carcinoma tissue. The proportion of positive ECM1 staining (++) in patients with laryngeal carcinoma was dramatically higher than those with benign tumors (p<0.05), and that of strongly-positive ECM1 staining (+++) slightly higher. The results of Spearman nonparametric correlation analysis revealed that ECM1 staining grade in laryngeal carcinoma tissue had a significantly-positive correlation with MVD (r=0.866, p=0.000). CONCLUSIONS: ECM1 expression in laryngeal carcinoma is closely associated with tumor cell growth, metastasis and angiogenesis, which can be considered as an effective predictor in the occurrence and postoperative recurrence of laryngeal carcinoma.

Cordyceps militaris polysaccharides can enhance the immunity and antioxidation activity in immunosuppressed mice.

To evaluate the immune activation and reactive oxygen species scavenging activity of Cordyceps militaris polysaccharides (CMP) in vivo, 90 male BALB/c mice were randomly divided into six groups. The mice in the three experimental groups were given cyclophosphamide at 80 mg/kg/d via intraperitoneal injection and 17.5, 35, or 70 mg/kg body weight CMP via gavage. The lymphocyte proliferation, phagocytic index, and biochemical parameters were measured. The results show that the administration of CMP was able to overcome the CY-induced immunosuppression, significantly increased the spleen and thymus indices, and enhanced the spleen lymphocyte activity and macrophage function. CMP can also improve the antioxidation activity in immunosuppressed mice, significantly increase the superoxidase dismutase, catalase, and glutathione peroxidase levels and the total antioxidant capacity, and decrease the malondialdehyde levels in vivo.