Bioinspired Polyoxo-titanium Cluster for Greatly Enhanced Solar-Driven CO2 Reduction.

Developing artificial enzymes with excellent catalytic activities and uncovering the structural and chemical determinants remain a grand challenge. Discrete titanium-oxo clusters with well-defined coordination environments at the atomic level can mimic the pivotal catalytic center of natural enzymes and optimize the charge-transfer kinetics. Herein, we report the precise structural tailoring of a self-assembled tetrahedral Ti4Mn3-cluster for photocatalytic CO2 reduction and realize the selective evolution of CO over specific sites. Experiments and theoretical simulation demonstrate that the high catalytic performance of the Ti4Mn3-cluster should be related to the synergy between active Mn sites and the surrounding functional microenvironment. The reduced energy barrier of the CO2 photoreduction reaction and moderate adsorption strength of CO* are beneficial for the high selective evolution of CO. This work provides a molecular scale accurate structural model to give insight into artificial enzyme for CO2 photoreduction.

Dietary betaine and/or TMAO affect hepatic lipid accumulation and glycometabolism of Megalobrama amblycephala exposed to a high-carbohydrate diet.

A 12-week experiment was conducted to explore the effects of betaine and/or TMAO on growth, hepatic health, gut microbiota, and serum metabolites in Megalobrama amblycephala fed with high-carbohydrate diets. The diets were as follows: CD group (control diet, 28.5% carbohydrate), HCD group (high-carbohydrate diet, 38.2% carbohydrate), HBD group (betaine-added diet, 38.3% carbohydrate + 1.2% betaine), HTD group (TMAO-added diet, 38.2% carbohydrate + 0.2% TMAO), and HBT group (diet added with both betaine and TMAO, 38.2% carbohydrate + 1.2% betaine + 0.2% TMAO). The results showed that the hepatosomatic index (HSI); whole-body crude fat; hepatic lipid accumulation; messenger RNA expression levels of gk, fpbase, g6pase, ahas, and bcat; serum branched-chain amino acids (BCAAs); ratio of Firmicutes-to-Bacteroidetes; and abundance of the genus Aeromonas were all significantly increased, while the abundance levels of the genus Lactobacillus and phyla Tenericutes and Bacteroidetes were drastically decreased in the HCD group. Compared with the HCD group, the HSI; whole-body crude fat; hepatic lipid accumulation; expression levels of fbpase, g6pase, pepck, ahas, and bcat; circulating BCAA; ratio of Firmicutes-to-Bacteroidetes; and abundance levels of the genus Aeromonas and phyla Tenericutes and Bacteroidetes were significantly downregulated in the HBD, HTD, and HBT groups. Meanwhile, the expression levels of pk were drastically upregulated in the HBD, HTD, and HBT groups as well as the abundance of Lactobacillus in the HBT group. These results indicated that the supplementation of betaine and/or TMAO in high-carbohydrate diets could affect the hepatic lipid accumulation and glycometabolism of M. amblycephala by promoting glycolysis, inhibiting gluconeogenesis and biosynthesis of BCAA, and mitigating the negative alteration of gut microbiota. Among them, the combination of betaine and TMAO had the best effect.

Macrocyclic Inorganic Tin-Containing Oxo Clusters: Heterometallic Strategy for Configuration and Catalytic Activity Modulation.

In this work, the first examples of inorganic macrocyclic tin-oxo clusters which are stabilized by sulfate ligands are reported. As determined by X-ray diffraction and photoelectron spectroscopy analyses, the prepared inorganic Sn10 -oxo cluster displays interesting mixed valence behaviors, with 8 Sn4+ located at the cyclic skeleton and two Sn2+ encapsulated in the center. When further introducing Ti4+ and In3+ ions to the synthetic systems, heterometallic Sn2 Ti6 and SnIn5 Ti6 complexes with Ti6 (SO4 )9 and SnIn5 (SO4 )12 macrocyclic skeletons were prepared whose configuration and packing models were affected by the ionic radius of incorporated metals. Moreover, comparative CO2 reduction experiments confirm that such heterometallic composition can significantly improve the catalytic activities of these inorganic macrocyclic oxo clusters. This work represents a milestone in constructing inorganic tin complexes and also macrocyclic metal oxo clusters with tunable configurations and properties.

Ti4(embonate)6 Cage-Ligand Strategy on the Construction of Metal-Organic Frameworks with High Stability and Gas Sorption Properties.

Herein we report an efficient strategy to construct cage-based metal-organic frameworks (MOFs) via the assembly of Ti4L6 (L = embonate) cages and N-contained ligands with Mn2+ and Zn2+ ions, respectively, and two Ti4L6-cage-based MOFs (PTC-219 and PTC-220) with high stability and gas sorption properties have been generated through two-step reactions, respectively.

Embonic Acid Functionalized Niobium Complexes with Selective Dye Sorption Properties.

Presented here are binuclear Nb2, tetranuclear Ti2Nb2, and dodecanuclear Nb12 complexes decorated by embonic acid ligands. These structures feature a unique Ti-O-Nb or Nb-O-Nb subunit. Besides, the unprecedented dodecanuclear Nb12 cluster further displays a porous three-dimensional packing framework and stability in water, affording an interesting selective uptake for methylene blue molecules over rhodamine B.

Water-Soluble and Ultrastable Ti4L6 Tetrahedron with Coordination Assembly Function.

We have successfully constructed a tetrahedral Ti4L6 cage with calixarene-like coordination-active vertices. It further features high solubility and stability in H2O and DMF/H2O solution, affording an interesting stepwise assembly function with other metal ions. Through trapping of different amounts of Co or Ln ions, the Ti4L6 tetrahedra can be organized into various dimensional architectures, including a Ti4L6-Co3 cage, a Ti4L6-Ln2 cage, a Ti4L6-Ln2 chain, and a three-dimensional Ti4L6-Ln framework. An unusual mixed-valence phenomenon was observed in the Ti4L6 cage, whose Ti3+/4+ compositions were adequately identified by electron spin resonance and X-ray photoelectron spectroscopy analyses. More remarkably, the calixarene-like oxygen vertices of the Ti4L6 cage can also be used for the recognition of C3-symmetric dye molecules through N-H···O hydrogen bonding. Accordingly, driven by visible light, selective and efficient homogeneous photodecomposition of acid blue 93 and alkali blue 4B were successfully achieved. Therefore, this work not only represents a milestone in constructing symmetric Ti-based cages with interesting coordination assembly function but also provides a new method for preparing technologically important soluble photoactive cages.

[Advance in studies on effective components in wheat bran and their pharmacological activities].

Wheat bran, as the testa of wheat, has a long history of medication. Modern studies have discovered that wheat bran contains dietary fiber, phenolic compounds, proteins, vitamins, minerals and many other compounds, and boasts wide pharmacological activities such as blood glucose reduction, hypertension reduction, lipid reduction, anti-oxidation, anti-bacteria, anti-inflammatory, antivirus, prevention of colon cancer and mutations, immunomodulation and adsorption of heavy metals. With great development and utilization values, wheat bran has long attracted wide attention from Chinese and foreign scholars. The paper summarizes the latest advance in domestic and foreign studies on effective components in wheat bran and their pharmacological effect, and gives a brief introduction of the limiting factors in the comprehensive development and utilization of wheat bran, in order to provide new preference for the development and utilization of abundant wheat bran resources in China.

Synthesis and biological evaluation of novel N-acyl substituted quinolin-2(1H)-one derivatives as potential antimicrobial agents.

A series of novel N-acyl substituted quinolin-2(1H)-one derivatives were synthesized and screened in vitro for their antibacterial and antifungal activities by disc diffusion method. All the compounds exhibited moderate to good antimicrobial activities, some of these compounds displayed comparable or better antibacterial or antifungal activities against some tested strains compared to the reference drugs Streptomycin and Fluconazole.

Whole-genome resequencing reveals molecular imprints of anthropogenic and natural selection in wild and domesticated sheep.

The abundance of domesticated sheep varieties and phenotypes is largely the result of long-term natural and artificial selection. However, there is limited information regarding the genetic mechanisms underlying phenotypic variation induced by the domestication and improvement of sheep. In this study, to explore genomic diversity and selective regions at the genome level, we sequenced the genomes of 100 sheep across 10 breeds and combined these results with publicly available genomic data from 225 individuals, including improved breeds, Chinese indigenous breeds, African indigenous breeds, and their Asian mouflon ancestor. Based on population structure, the domesticated sheep formed a monophyletic group, while the Chinese indigenous sheep showed a clear geographical distribution trend. Comparative genomic analysis of domestication identified several selective signatures, including IFI44 and IFI44L genes and PANK2 and RNF24 genes, associated with immune response and visual function. Population genomic analysis of improvement demonstrated that candidate genes of selected regions were mainly associated with pigmentation, energy metabolism, and growth development. Furthermore, the IFI44 and IFI44L genes showed a common selection signature in the genomes of 30 domesticated sheep breeds. The IFI44 c. 54413058 C>G mutation was selected for genotyping and population genetic validation. Results showed that the IFI44 polymorphism was significantly associated with partial immune traits. Our findings identified the population genetic basis of domesticated sheep at the whole-genome level, providing theoretical insights into the molecular mechanism underlying breed characteristics and phenotypic changes during sheep domestication and improvement.

N546 in beta18-beta19 loop is important for binding and toxicity of the Bacillus thuringiensis Cry1Ac toxin.

Our previous mutagenic analysis showed that the unique residue N546 in the apex of beta18-beta19 loop of Bacillus thuringiensis Cry1Ac toxin is important for its toxicity. In this study, trypsin digestion susceptibility, binding to BBMV and oligomer formation activity was therefore analyzed to determine the mechanism of toxicity change of these mutant toxins. The results showed that residue N546 was not involved in toxin oligomerisation and maintaining the stability of toxin, the enhanced toxicity of mutant N546A was just because of increased binding to BBMV, and reduction in toxicity of other mutants were caused by reduction in initial or irreversible binding to BBMV. This is the first report that revealed N546 in Cry1Ac domain III played an essential role in its insecticidal activity and binding to insect BBMV.

Bioactive halogenated dihydroisocoumarins produced by the endophytic fungus Lachnum palmae isolated from Przewalskia tangutica.

Guided by the UPLC-ESIMS profile, seven previously undescribed halogenated dihydroisocoumarins, palmaerones A-G, along with eleven known dihydroisocoumarins, were isolated from Lachnum palmae, an endophytic fungus from Przewalskia tangutica by exposure to a histone deacetylase inhibitor SAHA. Structures of the isolates were elucidated by analysis of their NMR, MS and optical rotation values. The antimicrobial, anti-inflammatory and cytotoxic activities of palmaerones A-G were evaluated. Palmaerones A-G showed antimicrobial activities against the strains (C. neoformans, Penicillium sp., C. albicans, B. subtilis and S. aureus), and palmaerone E exhibited potential antimicrobial activities against all the test strains with the MIC value in the range of 10-55 µg/mL. Palmaerones A and E exhibited moderate inhibitory effects on NO production in LPS-induced RAW 264.7 cells, with the IC50 values of 26.3 and 38.7 µM, respectively and no obvious toxicities were observed at 50 µM. Palmaerone E showed weak cytotoxicity against HepG2 with the IC50 value of 42.8 µM. This work provides an effective strategy for expanding natural product resource.

Polycatenation tuned microporosity of two metal-tris(4'-carboxybiphenyl)amine frameworks with multilayer structures.

By employing a nanosized tris(4'-carboxybiphenyl)amine ligand to assemble with Zn2+ ions, a novel trilayer network (FIR-37) and an unprecedented 2D → 3D microporous polycatenation framework (FIR-38) based on unusual tetralayers have been synthesized and structurally characterized. FIR-38 shows permanent porosity with a Langmuir surface area of 1408.4 m2 g-1.

New advances in nervous system of lipoprotein lipase / 中国临床药理学与治疗学

Lipoprotein lipase (LPL) is a key enzyme in lipid and lipoprotein metabolism. LPL mainly hydrolyzes triglyceride-rich lipoproteins and provides free fatty acid (FFAs) for metabolic tissues. LPL acts as a molecular bridge between lipoproteins and cell surface lipoprotein receptors, facilitating lipoprotein uptake. Recent studies have shown that LPL is widely expressed in tissues. LPL has a variety of physiological functions, Lipoprotein lipase (LPL) is a key enzyme in lipid and lipoprotein metabolism. LPL mainly hydrolyzes triglyceride-rich lipoproteins and provides free fatty acid (FFAs) for metabolic tissues. LPL acts as a molecular bridge between lipoproteins and cell surface lipoprotein receptors, facilitating lipoprotein uptake. Recent studies have shown that LPL is widely expressed in tissues. LPL has a variety of physiological functions, which regulates lipid metabolism and energy balance in the brain. Besides, it is closely related to Alzheimer's disease. This paper mainly reviews the latest research progress of LPL in the nervous system and provides new targets for the treatment and prevention.

[A comparison of knowledge awareness rates and influencing factors of clonorchiasis among residents in 4 counties (cities) of Hunan Province].

OBJECTIVE: To understand the status of knowledge awareness rates and influencing factors of clonorchiasis among the residents in 4 counties (cities) of Hunan Province, so as to provide the references for formulating the prevention and control strategy of clonorchiasis in the province. METHODS: A total of 1 224 subjects were selected by the multi-stage cluster sampling method and investigated with questionnaires and face-to-face interviews. RESULTS: The clonorchiasis knowledge awareness rates of the residents were 15.67% in Yongzhou City, 9.94% in Yueyang City, 13.25% in Wangcheng County, and 21.96% in Tongdao County, respectively. In the whole province, the clonorchiasis knowledge awareness rates of the residents were 44.67%, 56.43%, 60.95%, and 42.46% in the etiology, clinical manifestations, epidemiological characteristics and daily prevention, respectively. The logistic regression showed that the influencing factors of clonorchiasis knowledge awareness rates were the daily dining place, whether or not having the medical personnel in the family, the degree of attention to the relevant news reports, and the history of parasitic diseases. CONCLUSIONS: The level of clonorchiasis than that in other areas, but the overall level of clonorchiasis knowledge awareness of the residents in Hunan Province is not high. Therefore, the relevant authority should strengthen the health education in clonorchiasis prevention knowledge including personal daily food hygienic knowledge. knowledge awareness rate of the residents in the west-southern areas of Hunan Province is higher.

Diagnostic value of circulating tumor cells in cerebrospinal fluid.

OBJECTIVE: To assess circulating tumor cells in cerebrospinal fluid as a diagnostic approach to identify meningeal metastasis in patients with non-small cell lung cancer by using tumor marker immunostaining-fluorescence in situ hybridization (TM-iFISH). METHODS: In 5 non-small cell lung cancer patients who were confirmed to have developed meningeal metastasis by cerebrospinal fluid cytology, 20 ml of cerebrospinal fluid was obtained through lumbar puncture, from which 7.5 ml was utilized for TM-iFISH to identify and quantitate circulating tumor cells, 10ml for cerebrospinal fluid cytology, and 2.5ml for detection of cerebrospinal fluid tumor markers. RESULTS: TM-iFISH examination identified 18 to 1,823 circulating tumor cells per 7.5ml cerebrospinal fluid. In contrast, cytology assessment revealed tumor cells in only 2 cases. The expression levels of cerebrospinal fluid tumor markers were all increased in all 5 patients when compared with their respective serum levels. Contrast-enhanced MRI scans demonstrated presence of meningeal metastasis in all 5 cases. CONCLUSION: TM-iFISH may become a novel cerebrospinal fluid-based diagnostic strategy to identify circulating tumor cells and meningeal metastasis as compared to traditional diagnostic approaches, although its superior sensitivity and specificity needs to be confirmed through additional studies with a larger sample size.

Detected EGFR mutation in cerebrospinal fluid of lung adenocarcinoma patients with meningeal metastasis.

OBJECTIVE: To discuss the application of ARMS method to detect EGFR gene mutation in cerebrospinal fluid of lung adenocarcinoma patients with meningeal metastasis. METHODS: 5 cases of lung adenocarcinoma were identified with meningeal metastasis that were cleared EGFR gene mutation by gene sequencing method. From each patient 5ml cerebrospinal fluid was obtained by lumbar puncture. ARMS method was used to detect EGFR mutations in cerebrospinal fluid. RESULTS: 5 samples of cerebrospinal fluid were successfully detected by ARMS method, 3 samples found that EGFR gene mutations, the mutations in line with direct sequencing method. CONCLUSION: ARMS method can be used to detect EGFR gene mutations of cerebrospinal fluid samples in lung adenocarcinoma with meningeal metastasis. But cerebrospinal fluid specimens from histological specimens, blood samples need to be confirmed by further comparative study whether there is advantage.

Study on sesquiterpenoids from Aquilaria sinensis / 中草药

Objective: To investigate the sesquiterpenoid constituents from Aquilaria sinensis. Methods: The chemical constituents were isolated and purified by various separation techniques such as silica gel, ODS, Sephadex LH-20, and preparative high- performance liquid chromatography, and their structures were determined according to their physicochemical properties, MS, 1D, and 2D NMR. The antibacterial activity of the obtained compounds against methicillin-resistant Staphylococcus aureus was tested by 96-well plate microdilution method. Results: Seven sesquiterpenoids were obtained from 95% ethanol aqueous extract of Aquilaria sinensis and their structures were identified as (+)-4a,5-dimethyl-3-(prop-1-en-2yl)-octahydronaphthalene-2β,8a-diol (1), baimuxinic acid (2), baimuxinol (3), vetaspira-2(11),6-dien-14-al (4), baimuxinal (5), (-)-10-epi-γ-eudesmol (6), and 9β-hydroxyl-α-agarofuran (7). The minimum inhibitory concentration (MIC) of compound 1 against methicillin-resistant Staphylococcus aureus was 210 μmol/L. Conclusion: Compound 1 is a new compound named as 2β,8aα-dihydroxy-11-en-eremophilane, which has a good inhibitory effect against methicillin-resistant Staphylococcus aureus.

Antihypertensive effect of radix paeoniae alba in spontaneously hypertensive rats and excessive alcohol intake and high fat diet induced hypertensive rats.

Radix Paeoniae Alba (Baishao, RPA) has long been used in traditional Chinese medicine formulation to treat hypertension by repression the hyperfunction of liver. However, whether the RPA itself has the antihypertensive effect or not is seldom studied. This study was to evaluate the protective effect of RPA on hypertensive rats. Alcohol in conjunction with a high fat diet- (ACHFD-) induced hypertensive rats and spontaneously hypertensive rats (SHR) was constantly received either RPA extract (25 or 75 mg/kg) or captopril (15 mg/kg) all along the experiments. As a result, RPA extract (75 mg/kg) could significantly reduce systolic blood pressure of both ACHFD-induced hypertensive rats and SHR after 9-week or 4-week treatment. In ACHFD-induced hypertensive rats, the blood pressure was significantly increased and the lipid profiles in serum including triglyceride, total cholesterol, LDL-cholesterol, and HDL-cholesterol were significantly deteriorated. Also, hepatic damage was manifested by a significant increase in alanine transaminase (ALT) and aspartate transaminase (AST) in serum. The RPA extract significantly reversed these parameters, which revealed that it could alleviate the liver damage of rats. In SHR, our result suggested that the antihypertensive active of RPA extract may be related to its effect on regulating serum nitric oxide (NO) and endothelin (ET) levels.

DL-3-n-butylphthalide protects the blood-brain barrier against ischemia/hypoxia injury via upregulation of tight junction proteins / 中华医学杂志(英文版)

Background@#The increased permeability of the blood-brain barrier (BBB) induced by ischemia/hypoxia is generally correlated with alteration of tight junctions (TJs). DL-3-n-butylphthalide (NBP) has been shown to exert neuroprotective effects after ischemic injury. However, few studies have assessed the correlation between NBP and TJs. This study aimed to investigate the potential effect of NBP on the TJ proteins claudin-5, zonula occludens-1 (ZO-1), and occludin during brain ischemia.@*Methods@#A chronic cerebral hypoperfusion (CCH) Sprague-Dawley rat model was established, and NBP (20, 40, or 80 mg/kg, gavage, once a day) treatment was performed for 14 days. NBP (0.1 or 1.0 μmol/L) pre-treatment was applied to an in vitro hypoxia microvascular endothelial cell model (1% O2, 24 h). BBB permeability was assessed by performing the Evans blue assay. The expressions and localization of claudin-5, ZO-1, occludin, phosphorylated/total protein kinase B (p-Akt/Akt), phosphorylated/total glycogen synthase kinase 3β (GSK-3β)/GSK-3β, and β-catenin/β-actin were evaluated by Western blotting or immunofluorescence. Reactive oxygen species (ROS) generation was measured by flow cytometry analysis. TJ ultrastructure was observed by transmission electron microscopy.@*Results@#In CCH rats, treatment with 40 and 80 mg/kg NBP decreased the Evans blue content in brain tissue (9.0 ± 0.9 μg/g vs. 12.3 ± 1.9 μg/g, P = 0.005; 6.7 ± 0.6 μg/g vs. 12.3 ± 1.9 μg/g, P < 0.01), increased the expression of claudin-5 (0.79 ± 0.08 vs. 0.41 ± 0.06, P < 0.01; 0.97 ± 0.07 vs. 0.41 ± 0.06, P < 0.01), and elevated the ZO-1 protein level (P < 0.05) in brain microvascular segments in a dose-dependent manner in comparison with the corresponding values in the model group. There was no significant difference in occludin expression (P > 0.05). In the hypoxia cell model, NBP pre-treatment improved TJ ultrastructure, decreased intracellular ROS level, and increased the expression of claudin-5 (P < 0.01) and ZO-1 (P < 0.01) in comparison with the corresponding values in the hypoxia group. NBP treatment also elevated the relative expression levels of p-Akt/Akt, p-GSK-3β/GSK-3β, and β-catenin/β-actin in comparison with the corresponding values in the hypoxia group (all P < 0.05).@*Conclusion@#NBP improves the barrier function of BBB against ischemic injury by upregulating the expression of TJ proteins, possibly by reducing oxidative stress and activating the Akt/GSK-3β/β-catenin signaling pathway.

DL-3-n-butylphthalide protects the blood-brain barrier against ischemia/hypoxia injury via upregulation of tight junction proteins / 中华医学杂志(英文版)

BACKGROUND@#The increased permeability of the blood-brain barrier (BBB) induced by ischemia/hypoxia is generally correlated with alteration of tight junctions (TJs). DL-3-n-butylphthalide (NBP) has been shown to exert neuroprotective effects after ischemic injury. However, few studies have assessed the correlation between NBP and TJs. This study aimed to investigate the potential effect of NBP on the TJ proteins claudin-5, zonula occludens-1 (ZO-1), and occludin during brain ischemia.@*METHODS@#A chronic cerebral hypoperfusion (CCH) Sprague-Dawley rat model was established, and NBP (20, 40, or 80 mg/kg, gavage, once a day) treatment was performed for 14 days. NBP (0.1 or 1.0 μmol/L) pre-treatment was applied to an in vitro hypoxia microvascular endothelial cell model (1% O2, 24 h). BBB permeability was assessed by performing the Evans blue assay. The expressions and localization of claudin-5, ZO-1, occludin, phosphorylated/total protein kinase B (p-Akt/Akt), phosphorylated/total glycogen synthase kinase 3β (GSK-3β)/GSK-3β, and β-catenin/β-actin were evaluated by Western blotting or immunofluorescence. Reactive oxygen species (ROS) generation was measured by flow cytometry analysis. TJ ultrastructure was observed by transmission electron microscopy.@*RESULTS@#In CCH rats, treatment with 40 and 80 mg/kg NBP decreased the Evans blue content in brain tissue (9.0 ± 0.9 μg/g vs. 12.3 ± 1.9 μg/g, P = 0.005; 6.7 ± 0.6 μg/g vs. 12.3 ± 1.9 μg/g, P  0.05). In the hypoxia cell model, NBP pre-treatment improved TJ ultrastructure, decreased intracellular ROS level, and increased the expression of claudin-5 (P < 0.01) and ZO-1 (P < 0.01) in comparison with the corresponding values in the hypoxia group. NBP treatment also elevated the relative expression levels of p-Akt/Akt, p-GSK-3β/GSK-3β, and β-catenin/β-actin in comparison with the corresponding values in the hypoxia group (all P < 0.05).@*CONCLUSION@#NBP improves the barrier function of BBB against ischemic injury by upregulating the expression of TJ proteins, possibly by reducing oxidative stress and activating the Akt/GSK-3β/β-catenin signaling pathway.