Pore Structure Characteristics and Their Controlling Factors of Deep Shale: A Case Study of the Lower Silurian Longmaxi Formation in the Luzhou Area, Southern Sichuan Basin.

Recently, deep shale reservoirs are emerging as time requires and commence occupying a significant position in the further development of shale gas. However, the understanding of pore characteristics in deep shale remains poor, prohibiting accurate estimation of the hydrocarbon content and insights into fluid mobility. This study focuses on the Longmaxi Formation from the Luzhou (LZ) region, southern Sichuan. Scanning electron microscopy (SEM), low-temperature N2/CO2 adsorption, X-ray diffraction, and geochemical analysis were performed to investigate the micro-nanopore size distribution, main controlling factors, and unique pore features distinct from other regions. Results showed that the pores can be classified into four categories, organic matter (OM) pores, intergranular pores, intragranular pores, and microfractures, according to SEM images. The total pore volume is overwhelmingly dominated by mesopores and contributed by pores in the range of 0.5-0.6, 2-4, and 10-30 nm. The specific surface area is primarily contributed by micropores and mesopores in the range of 0.5-0.7 and 2-4 nm. By analyzing the influencing factors extensively, it is concluded that the buried depth, geochemical factors, and mineral composition can impact the pore structure in the overmature deep shales. Specifically, the total organic carbon content plays a more effective and positive role in the development of micropores, mesopores, total pores, and the porosity when compared with vitreous reflectance (Ro). The micropores are inferred to be OM-related. On the contrary, clay mineral is detrimental to the development of micropores and mesopores and the petrophysical properties (porosity and permeability), which may be attributed to the occurrence of chlorite and kaolinite instead of illite. The plagioclase conforms to the same law as clay due to their coexistence. Quartz, carbonate minerals, and pyrite can barely contribute to the pores. Eventually, the compared results suggest that the Longmaxi Formation of the LZ region are qualified with a superior pore size distribution, complicated structure, and diverse morphology, implying a potential to generate and store hydrocarbons. Overall, this study improves the understanding of complex pore structures in deep shale and provides significant insights into the development and exploration of unconventional resources in the future.

Transcatheter hepatic arterial chemoembolization combined with Kangai injection for hepatitis B virus-related hepatocellular carcinoma: A protocol for a PRISMA-compliant meta-analysis.

BACKGROUND: Kangai injection, a well-known insect-derived traditional Chinese medicine preparation, has been widely applied as a promising adjunctive drug for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). However, its exact clinical efficacy and safety is still not well investigated. In this study, we aimed to summarize the efficacy and safety of Kangai injection for patients with HBV-related HCC through the meta-analysis. METHODS: All available randomized controlled trials (RCTs) and high-quality prospective cohort studies that investigated the efficacy and safety of Kangai injection for patients with HBV-related HCC were searched from ten electronic databases including Google Scholar, PubMed, Excerpt Medica Database (Embase), Cochrane Library, Medline, Web of Science (WOS), China National Knowledge Infrastructure (CNKI), China Scientific Journal Database (CSJ) Chinese, Biomedical Literature Database (CBM) and Wanfang Database. Papers in Chinese or English published from January 2000 to September 2020 will be included without any restrictions.Study selection and data extraction will be performed independently by 2 researchers. The clinical outcomes including overall response rate (ORR), disease control rate (DCR), quality of life (QoL), clinical symptoms, virological indicators, immune function and adverse events, were systematically evaluated. Review Manager 5.3 and Stata 14.0 were used for data analysis, and the quality of the literatures was also evaluated. RESULTS: The results of this study will be published in a peer-reviewed journal, and provide a helpful evidence for clinicians to formulate the best postoperative adjuvant treatment strategy for HBV-related HCC patients. CONCLUSION: Our study will draw an objective conclusion of the efficacy of Kangai injection on curative effect (ORR and DCR), clinical symptoms, virological indicators, QoL, and immune function in patients with HBV-related HCC. INPLASY REGISTRATION NUMBER: INPLASY202090014.

Chinese patent medicine (Jinlong Capsule) for gastric cancer: Protocol for a systematic review and meta-analysis.

BACKGROUND: JLC has been widely applied as a promising adjunctive drug for GC. However, the exact effects and safety of JLC have yet to be systematically investigated. We aimed to summarize the efficacy and safety of JLC for the treatment of advanced GC through the meta-analysis, in order to provide scientific reference for the design of future clinical trials. METHODS: The protocol followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. Relevant randomized controlled trials were searched from Cochrane Library, PubMed, Web of Science (WOS), Excerpt Medica Database (Embase), Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), China Scientific Journal Database (VIP), and Wanfang Database. Papers in English or Chinese published from their inception to January 2020 will be included without any restrictions.Study selection and data extraction will be performed independently by 2 investigators. The clinical outcomes including overall response rate, complete response rate, overall survival, Disease-free survival, quality of life (QoL), immune function, and adverse events, were systematically evaluated. Review Manager 5.3 and Stata 14.0 were used for data analysis, and the quality of the studies was also evaluated. RESULTS AND CONCLUSION: The findings of this research will be published in a peer-reviewed journal, and provide more evidence-based guidance in clinical practice. INTERNATIONAL PLATFORM OF REGISTERED SYSTEMATIC REVIEW AND META-ANALYSIS PROTOCOLS (INPLASY) REGISTRATION NUMBER:: INPLASY202040105. URL: https://inplasy.com/inplasy-2020-4-0105/.

Xiaoaiping injection as adjunct therapy for patients with advanced esophageal carcinoma: A protocol for a systematic review and meta-analysis.

BACKGROUND: Esophageal carcinoma (EC) is one of the worst malignant digestive neoplasms with a strong tendency of invasion and metastasis. Despite the improvement of diagnostic and therapeutic methods in the past decades, the prognosis of EC remains unsatisfactory. Xiaoaiping injection (XAPI), a famous traditional Chinese herbal medicine, has been widely applied as a promising adjunctive drug for EC. However, the exact effects and safety of XAPI have yet to be systematically investigated. We aimed to summarize the efficacy and safety of XAPI for the treatment of advanced EC through the meta-analysis, in order to provide scientific reference for the design of future clinical trials. METHODS: Relevant randomized controlled trials (RCTs) were searched from Cochrane Library, PubMed, Google Scholar, Web of Science, Excerpt Medica Database, Medline, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, China Scientific Journal Database and Wanfang Database. Papers in English or Chinese published from January 2000 to May 2020 will be included without any restrictions.Study selection and data extraction will be performed independently by 2 investigators. The clinical outcomes including overall response rate, complete response rate, overall survival, Disease-free survival, quality of life, immune function and adverse events, were systematically evaluated. Review Manager 5.3 and Stata 14.0 were used for data analysis, and the quality of the studies was also evaluated. RESULTS: The results of this study will be published in a peer-reviewed journal, and provide more evidence-based guidance in clinical practice. CONCLUSION: Our study will draw an objective conclusion of the effects of XAPI combined with conventional treatment for advanced EC and provide a helpful evidence for clinicians to formulate the best postoperative adjuvant treatment strategy for EC patients. INPLASY REGISTRATION NUMBER: INPLASY202050094.

Study on the Correlation between Gene Expression and Enzyme Activity of Seven Key Enzymes and Ginsenoside Content in Ginseng in Over Time in Ji'an, China.

Panax ginseng is a traditional medicine. Fresh ginseng is one of the most important industries related to ginseng development, and fresh ginseng of varying ages has different medicinal properties. Previous research has not systematically reported the correlation between changes in key enzyme activity with changes in ginsenoside content in fresh ginseng over time. In this study, for the first time, we use ginseng samples of varying ages in Ji'an and systematically reported the changes in the activity of seven key enzymes (HMGR, FPS, SS, SE, DS, CYP450, and GT). We investigated the content of ginsenoside and gene expression of these key enzymes. Ginsenoside content was measured using HPLC. HPLC, GC-MS, and LC-MS were combined to measure the enzyme activity of the key enzymes. Quantitative PCR was used in the investigation of gene expression. By analyzing the correlation between the enzyme activity and the transcription level of the key enzymes with ginsenoside content, we found that DS and GT enzyme activities are significantly correlated with the ginsenoside content in different ages of ginseng. Our findings might provide a new strategy to discriminate between ginseng of different years. Meanwhile, this research provides important information for the in-depth study of ginsenoside biosynthesis.

2,3,5,4'-Tetrahydroxystilbene-2-O-ß-D-Glucoside Attenuates Ischemia/Reperfusion-Induced Brain Injury in Rats by Promoting Angiogenesis.

Cerebral ischemia can cause brain infarcts, which are difficult to recover due to poor angiogenesis. 2,3,5,4'-Tetrahydroxystilbene-2-O-ß-D-glucoside is a natural polyphenol, has antioxidant and anti-inflammatory activity, and can protect from ischemic neuronal injury. However, little is known about the effect of 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside on brain microcirculation after stroke. This study aimed at investigating the influence of 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside on brain lesions and angiogenesis after stroke. Sprague-Dawley rats were subjected to right middle cerebral artery occlusion and treated with vehicle, nimodipine, or different doses of 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside daily beginning at 6 h post-middle cerebral artery occlusion for 14 days. The volume of cerebral infarcts, degree of neurological dysfunction, and level of microvessel density were determined longitudinally. The levels of vascular endothelial growth factor, angiopoietin 1, and angiopoietin receptor-2 expression in the brain lesions were characterized by immunohistochemistry and Western blot assays at 14 days post-middle cerebral artery occlusion. We found that 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside significantly promoted postoperative recovery in rats by minimizing the volume of cerebral infarcts and improving neurological dysfunction in a dose- and time-dependent manner. Additionally, 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside significantly increased the microvessel density in the brain and upregulated CD31 expression in ischemic penumbra, relative to that in the control. Finally, treatment with 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside significantly upregulated the relative levels of vascular endothelial growth factor, angiopoietin 1, and angiopoietin receptor-2 expression in the brain lesions of rats. Therefore, these data indicated that 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside treatment promoted angiogenesis and recovery from ischemia/reperfusion-induced brain injury in rats.

A high ratio of dietary n-3/n-6 polyunsaturated fatty acids improves obesity-linked inflammation and insulin resistance through suppressing activation of TLR4 in SD rats.

Dietary ratios of n-3/n-6 polyunsaturated fatty acids (PUFAs) have been implicated in controlling markers of metabolic disorders, including obesity, insulin resistance (IR), inflammation, and lipid profiles, which are also presumed to be partly related to type 2 diabetes mellitus (T2DM). However, molecular mechanisms of the different PUFAs related to metabolic disorders have not been systematically addressed. The present study aimed to investigate the impact of dietary n-3/n-6 PUFA ratios on obesity and IR and, further, to determine the underlying mechanisms. For 16 weeks, 32 SD male rats, randomly divided into four groups (n = 8 per group), received one of the following diets: normal chow, high saturated fatty acid (SFA), high n-3/n-6 PUFA ratio (1∶1, PUFA¹:¹), or low n-3/n-6 PUFA ratio (1∶4, PUFA¹:4). Following the experimental diet period, metabolic parameters related to obesity and IR were measured. Compared to SFA diet-fed rats, PUFA¹:¹ diet-fed rats exhibited decreased body and visceral fat weight, lowered blood lipids, and improved glucose tolerance and insulin sensitivity. Interestingly, these changes were accompanied with decreased expression levels of circulating pro-inflammatory cytokines, including tumor necrosis factor α, interleukin-6, and C-reactive protein. Moreover, the TLR4 protein and mRNA levels were markedly down-regulated by PUFA¹:¹ compared with SFA; however, PUFA¹:4 diet-fed rats failed to exhibit these changes. Cumulatively, our data highlight a role for a PUFA¹:¹ diet in the prevention of obesity and related metabolic disorders by suppressing the activation of TLR4, a critical modulator of pro-inflammatory cytokines.

[Advances in biodiesel research].

Biodiesel is renewable and environmentally friendly; however, there are still many challenges for its commercial production as an alternative of petroleum-based transportation fuels, particularly in China with very limited resources for its biofuels development. In this article, the update progress of biodiesel R & D and production is reviewed, with a focus on its feedstock supply, manufacturing processes, quality control and byproduct utilization. It is concluded that the strategy of biorefinery to ultimately explore feedstock potentials will make biodiesel production more economically competitive.

A DNA sensor based on surface plasmon resonance for apoptosis-associated genes detection.

A practical and simple DNA sensor based on surface plasmon resonance (SPR) had been developed to determine apoptosis-associated genes, bcl-2 and bax. This SPR sensor was designed on the basis of simultaneous multi-wavelength detection. The complementary sequences of bcl-2 or bax oligonucleotide labeled with biotin were used as the probes. Biotin-avidin system was used to immobilize the bio-DNA on the sensor surface. The assembling processes and conditions for the DNA sensor were examined. The SPR sensor could be used to monitor the process of the immobility of the bio-DNA and DNA hybridization in real-time. The determination range of bcl-2 and bax oligonucleotide (20 bases) were 50-400 ng/mL. The determination range of polymerase chain reaction (PCR) product of bcl-2 (405 bases) was 5-60 ng/mL and PCR product of bax (538 bases) was 5-40 ng/mL. The stability, reversibility and specificity of the DNA sensor were also investigated. It was found from the experiment that the sensor could be applied for a quite long time (about 90 times). The relative standard deviation (R.S.D.) for determination oligonucleotides and PCR products of bcl-2 were 1.2 and 1.3%, respectively. The interference of noncomplementary DNA sequence with the determination of DNA was examined and it was found that noncomplementary 20-mer and 21-mer DNA (p53 and p21) do not affect the determination of bcl-2 or bax. This device could be used to study apoptosis and signal transduction routine genes. The sensor was shown to be of simplicity, sensitivity, selectivity, rapid response and cost effectiveness.

A novel dicyclodextrinyl diselenide compound with glutathione peroxidase activity.

A 6A,6A'-dicyclohexylamine-6B,6B'-diselenide-bis-beta-cyclodextrin (6-CySeCD) was designed and synthesized to imitate the antioxidant enzyme glutathione peroxidase (GPX). In this novel GPX model, beta-cyclodextrin provided a hydrophobic environment for substrate binding within its cavity, and a cyclohexylamine group was incorporated into cyclodextrin in proximity to the catalytic selenium in order to increase the stability of the nucleophilic intermediate selenolate. 6-CySeCD exhibits better GPX activity than 6,6'-diselenide-bis-cyclodextrin (6-SeCD) and 2-phenyl-1,2-benzoisoselenazol-3(2H)-one (Ebselen) in the reduction of H(2)O(2), tert-butyl hydroperoxide and cumenyl hydroperoxide by glutathione, respectively. A ping-pong mechanism was observed in steady-state kinetic studies on 6-CySeCD-catalyzed reactions. The enzymatic properties showed that there are two major factors for improving the catalytic efficiency of GPX mimics. First, the substrate-binding site should match the size and shape of the substrate and second, incorporation of an imido-group increases the stability of selenolate in the catalytic cycle. More efficient antioxidant ability compared with 6-SeCD and Ebselen was also seen in the ferrous sulfate/ascorbate-induced mitochondria damage system, and this implies its prospective therapeutic application.

Traditional Chinese medicines Wu Wei Zi (Schisandra chinensis Baill) and Gan Cao (Glycyrrhiza uralensis Fisch) activate pregnane X receptor and increase warfarin clearance in rats.

The traditional Chinese medicines (TCMs) are essential components of alternative medicines. Many TCMs are known to alter the expression of hepatic drug-metabolizing enzymes and transporters. The molecular mechanism by which TCMs and/or their constituents regulate enzyme and transporter expression, however, has remained largely unknown. In this report, we show that two TCMs, Wu Wei Zi (Schisandra chinensis Baill) and Gan Cao (Glycyrrhiza uralensis Fisch), and their selected constituents activate the xenobiotic orphan nuclear receptor pregnane X receptor (PXR). Treatment with TCM extracts and the Schisandrol and Schisandrin constituents of Wu Wei Zi induced the expression of drug-metabolizing enzymes and transporters in reporter gene assays and in primary hepatocyte cultures. The affected enzymes and transporters include CYP3A and 2C isozymes and the multidrug resistance-associated protein 2. In transient transfection and reporter gene assays, the Schisandrin constituents of Wu Wei Zi had an estimated EC50 of 2 and 1.25 microM on hPXR and mPXR, respectively. Interestingly, mutations that were intended to alter the pore of the ligand-binding cavity of PXR had species-specific effects on the activities of the individual Schisandrols and Schisandrins. In rats, the administration of Wu Wei Zi and Gan Cao increased the metabolism of the coadministered warfarin, reinforcing concerns involving the safe use of herbal medicines and other nutraceuticals to avoid PXR-mediated drug-drug interactions. Meanwhile, the activation of PXR and induction of detoxifying enzymes provide a molecular mechanism for the hepatoprotective effects of certain TCMs.

Selenium-containing 15-mer peptides with high glutathione peroxidase-like activity.

Glutathione peroxidase (GPX) is one of the most crucial antioxidant enzymes in a variety of organisms. Here we described a new strategy for generating a novel GPX mimic by combination of a phage-displayed random 15-mer peptide library followed by computer-aided rational design and chemical mutation. The novel GPX mimic is a homodimer consisting of a 15-mer selenopeptide with an appropriate catalytic center, a specific binding site for substrates, and high catalytic efficiency. Its steady state kinetics was also studied, and the values of k(cat)/K(m)(GSH) and k(cat)/ K(mH(2)O(2)) were found to be similar to that of native GPX and the highest among the existing GPX mimics. Moreover, the novel GPX mimic was confirmed to have a strong antioxidant ability to inhibit lipid peroxidation by measuring the content of malondialdehyde, cell viability, and lactate dehydrogenase activity. Importantly, the novel GPX mimic can penetrate into the cell membrane because of its small molecular size. These characteristics endue the novel mimic with potential perspective for pharmaceutical applications.

Protection of epidermal cells against UVB injury by the antioxidant selenium-containing single-chain Fv catalytic antibody.

The antioxidant effect of selenium-containing single-chain Fv catalytic antibody (Se-scFv2F3), a new mimic of glutathione peroxidase, was confirmed using a model system in which cultured rat skin epidermal cells were injured by ultraviolet B (UVB). The cell damage was characterized in terms of lipid peroxidation of the cells, cell viability, and cell membrane integrity. The injury effects of UVB and protection effects of Se-scFv2F3 on the cells were studied using the model system. UVB can damage the cells severely. Upon precultivation of the cells with 0.4U/ml Se-scFv2F3, however, the damage was significantly reduced as shown by the increase in cell viability, the decrease in the malondialdehyde and hydrogen peroxide levels, and the normalization of lactate dehydrogenase activity. In addition, a novel finding that Se-scFv2F3 can stimulate cultured epidermal cells to proliferate under certain conditions was observed.

[Studies on the optimal expression condition, purification and its characterization of ScFv-2F3].

The expression vectors of the gene encoding ScFv-2F3 were transformed into E. coli BL21(DE3). Clones of higher expression were first selected, then were grown in the presence of IPTG at 37 degrees C to induce its expression. The culture conditions were carefully optimized. It was found that optimal conditions were as follows: the induction was started as OD590 reached to 1.0-1.8; the concentration of IPTG was 0.3-0.5 mmol/L and induction time is 7 h. The yield of ScFv-2F3 expressed in the selected clones is about 20% of the total proteins. The optimal culture conditions were successfully applied to fermenter of 50 L. The conditions of washing the inclusion bodies were also optimized. A two-step method was used to renature the inclusion body. The expression product of interest and its biological activities were characterized with Western blotting and ELISA. A novel selenium-containing single-chain abzyme with GPX activity was prepared.