Effects of Probiotics on Gut Microbiota in Type 2 Diabetes Patients

Objective: To study the effect of probiotics on gut microbiota in Type 2 diabetes patients and its clinical application value. Methods: Select Type 2 diabetes patients to take orally probiotics for 24 weeks, collect stool samples of subjects at the baseline and end of the trial, identify and analyze gut microbiota of each sample by 16srRNA high-throughput sequencing, and compare the changes of blood glucose, blood lipid and insulin resistance before and after the intervention. Results: A total of 75 patients completed clinical observations. 16srRNA high-throughput sequencing showed that the proportion of the subjects with increased Actinobacteria and Tenericutes at the end of the trial has increased (37.8% and 75.7% respectively). The genus level analysis showed that the number of subjects with increased intestinal probiotics and with decreased conditioned pathogens all increased. Cluster analysis before and after intervention showed that the gut microbiota of samples in the same group had a higher similarity. Compared with the subjects at the baseline status, at the end of the trial after the intervention, fasting blood glucose (FBG) of the subjects significantly decreased (P<0.05), the proportion of the subjects with triglyceride (TG) and cholesterol up to standard increased, and HOMA-IR was significantly improved (P<0.05). Conclusions: Probiotics can regulate the gut microbiota of Type 2 diabetes patients, promote fasting blood glucose (FBG) to reach the standard and improve insulin resistance, and help improve lipid metabolism

Performance of Combined Process of Air Flotation- Sedimentation - Biological Contact Oxidation - Membrane Biological Reactor Treating Heavy Oil Wastewater

A study of the treatment of heavy oil wastewater was carried out using the combined process of dissolved air flotation-sedimentation- biological contact oxidation - ultra-filtration membrane. When hydraulic retention times (HRT) was 18h, removal rates of COD, oil and suspended substance (SS) approached at 73~75%, 98%~99% and 100%, respectively. The diversity of bacterias was increased after air flotation, the betaproteobacteria dominated after enriched bacterias of BW-1， BW-2， BW-3，WSW-4,1-2-1 and 3-2-1 were added to contact oxidation tank. The combined process provided a suitable process in dealing with the complex heavy oil wastewater

Marmoset Viral Hepatic Inflammation Induced by Hepatitis C Virus Core Protein via IL-32.

Common marmosets infected with GB virus-B (GBV-B) chimeras containing hepatitis C virus (HCV) core and envelope proteins (CE1E2p7) developed more severe hepatitis than those infected with HCV envelope proteins (E1E2p7), suggesting that HCV core protein might be involved in the pathogenesis of viral hepatitis. The potential role of HCV core in hepatic inflammation was investigated. Six individual cDNA libraries of liver tissues from HCV CE1E2p7 or E1E2p7 chimera-infected marmosets (three animals per group) were constructed and sequenced. By differential expression gene analysis, 30 of 632 mRNA transcripts were correlated with the immune system process, which might be associated with hepatitis. A protein-protein interaction network was constituted by STRING database based on these 30 differentially expressed genes (DEGs), showing that IL-32 might play a central regulatory role in HCV core-related hepatitis. To investigate the effect of HCV core protein on IL-32 production, HCV core expressing and mock constructs were transfected into Huh7 cells. IL-32 mRNA and secretion protein were detected at significantly higher levels in cells expressing HCV core protein than in those without HCV core expression (P < 0.01 and P < 0.001, respectively). By KEGG enrichment analysis and using the specific signaling pathway inhibitor LY294002 for inhibition of PI3K, IL-32 expression was significantly reduced (P < 0.001). In conclusion, HCV core protein induces an increase of IL-32 expression via the PI3K pathway in hepatic cells, which played a major role in development of HCV-related severe hepatitis

A high infectious simian adenovirus type 23 vector based vaccine efficiently protects common marmosets against Zika virus infection.

Zika virus (ZIKV) has spread in many countries or territories causing severe neurologic complications with potential fatal outcomes. The small primate common marmosets are susceptible to ZIKV, mimicking key features of human infection. Here, a novel simian adenovirus type 23 vector-based vaccine expressing ZIKV pre-membrane-envelope proteins (Sad23L-prM-E) was produced in high infectious titer. Due to determination of immunogenicity in mice, a single-dose of 3×108 PFU Sad23L-prM-E vaccine was intramuscularly inoculated to marmosets. This vaccine raised antibody titers of 104.07 E-specific and 103.13 neutralizing antibody (NAb), as well as robust specific IFN-γ secreting T-cell response (1,219 SFCs/106 cells) to E peptides. The vaccinated marmosets, upon challenge with a high dose of ZIKV (105 PFU) six weeks post prime immunization, reduced viremia by more than 100 folds, and the low level of detectable viral RNA (103.66) and T-cell response (>726 SFCs/106 PBMCs) were acquired 1-2 weeks post exposure to ZIKV, while non-vaccinated control marmosets developed long-term high titer of ZIKV (105.73 copies/ml) (P<0.05). No significant pathological lesions were observed in marmoset tissues. Sad23L-prM-E vaccine was detectable in spleen, liver and PBMCs at least 4 months post challenge. In conclusion, a prime immunization with Sad23L-prM-E vaccine was able to protect marmosets against ZIKV infection when exposed to a high dose of ZIKV. This Sad23L-prM-E vaccine is a promising vaccine candidate for prevention of ZIKV infection in humans

Prime-boost vaccination of mice and rhesus macaques with two novel adenovirus vectored COVID-19 vaccine candidates.

ABSTRACTCOVID-19 vaccines are being developed urgently worldwide. Here, we constructed two adenovirus vectored COVID-19 vaccine candidates of Sad23L-nCoV-S and Ad49L-nCoV-S carrying the full-length gene of SARS-CoV-2 spike protein. The immunogenicity of two vaccines was individually evaluated in mice. Specific immune responses were observed by priming in a dose-dependent manner, and stronger responses were obtained by boosting. Furthermore, five rhesus macaques were primed with 5 × 109 PFU Sad23L-nCoV-S, followed by boosting with 5 × 109 PFU Ad49L-nCoV-S at 4-week interval. Both mice and macaques well tolerated the vaccine inoculations without detectable clinical or pathologic changes. In macaques, prime-boost regimen induced high titers of 103.16 anti-S, 102.75 anti-RBD binding antibody and 102.38 pseudovirus neutralizing antibody (pNAb) at 2 months, while pNAb decreased gradually to 101.45 at 7 months post-priming. Robust T-cell response of IFN-γ (712.6 SFCs/106 cells), IL-2 (334 SFCs/106 cells) and intracellular IFN-γ in CD4+/CD8+ T cell (0.39%/0.55%) to S peptides were detected in vaccinated macaques. It was concluded that prime-boost immunization with Sad23L-nCoV-S and Ad49L-nCoV-S can safely elicit strong immunity in animals in preparation of clinical phase 1/2 trials

HPRT Mutations in Lymphocytes from 1,3-Butadiene-Exposed Workers in China

BACKGROUND: 1,3-Butadiene (BD) is an important industrial chemical and an environmental and occupational pollutant. The carcinogenicity of BD in rodents has been proved, but its carcinogenic and mutagenic molecular mechanism(s) are not fully elucidated in humans. OBJECTIVES: In the present study, we compared the mutation frequencies and exon deletions of BD-exposed workers with that of control subjects in China to identify the characteristic mutations associated with BD exposure in the human HPRT (hypoxanthine–guanine–phosphoribosyltransferase) gene. METHODS: Seventy-four workers exposed to BD via inhalation and 157 matched controls were evaluated in Nanjing, China. Molecular analysis of HPRT mutant T lymphocytes from BDexposed workers and nonexposed control subjects was conducted to identify changes in the structure of the HPRT gene. A total of 783 HPRT mutants were analyzed by multiplex polymerase chain reaction, in which 368 HPRT mutants were isolated from BD-exposed workers and 415 mutants from control subjects. RESULTS: The BD-exposed workers showed a higher mutation frequency (18.2 ± 9.4 × 10 –6) than the control subjects (12.7 ± 7.3 × 10 –6), but the difference was not significant (p&gt; 0.05). The frequency of exon deletions in BD-exposed workers (27.4%) was significantly higher than that in control subjects (12.5%) (p &lt; 0.05), which mainly included multiplex exon deletions (2–8 exons). CONCLUSIONS: The results of the present study suggest that BD should increase the frequency of large deletions of HPRT gene in human lymphocytes This change confirms and supports the previous findings in BD-exposed workers. KEY WORDS: 1,3-butadiene, BD, exon deletion, HPRT gene, lymphocyte, occupational exposure. Environ Health Perspect 116:203–208 (2008). doi:10.1289/ehp.10353 available vi

A Novel 5-Enolpyruvylshikimate-3-Phosphate Synthase Shows High Glyphosate Tolerance in Escherichia coli and Tobacco Plants

A key enzyme in the shikimate pathway, 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) is the primary target of the broad-spectrum herbicide glyphosate. Identification of new aroA genes coding for EPSPS with a high level of glyphosate tolerance is essential for the development of glyphosate-tolerant crops. In the present study, the glyphosate tolerance of five bacterial aroA genes was evaluated in the E. coli aroA-defective strain ER2799 and in transgenic tobacco plants. All five aroA genes could complement the aroA-defective strain ER2799, and AM79 aroA showed the highest glyphosate tolerance. Although glyphosate treatment inhibited the growth of both WT and transgenic tobacco plants, transgenic plants expressing AM79 aroA tolerated higher concentration of glyphosate and had a higher fresh weight and survival rate than plants expressing other aroA genes. When treated with high concentration of glyphosate, lower shikimate content was detected in the leaves of transgenic plants expressing AM79 aroA than transgenic plants expressing other aroA genes. These results suggest that AM79 aroA could be a good candidate for the development of transgenic glyphosate-tolerant crops

Co-Expression of <i>ZmVPP1</i> with <i>ZmNAC111</i> Confers Robust Drought Resistance in Maize

Drought is a primary environmental factor limiting maize production globally. Although transferring a single gene to maize can enhance drought resistance, maize response to water deficit requires further improvement to accommodate the steadily intensifying drought events worldwide. Here, we generated dual transgene lines simultaneously overexpressing two drought-resistant genes, ZmVPP1 (encoding a vacuolar-type H+ pyrophosphatase) and ZmNAC111 (encoding a NAM, ATAF, and CUC (NAC)-type transcription factor). Following drought stress, survival rates of the pyramided transgenic seedlings reached 62–66%, while wild-type and single transgene seedling survival rates were 23% and 37–42%, respectively. Maize seedlings co-expressing ZmVPP1 and ZmNAC111 exhibited higher photosynthesis rates, antioxidant enzyme activities, and root-shoot ratios than the wild type, and anthesis-silking intervals were shorter while grain yields were higher under water deficit conditions in field trials. Additionally, RNA-sequencing analysis confirmed that photosynthesis and stress-related metabolic processes were stimulated in the dual transgene plants under drought conditions. The findings in this work illustrate how high co-expression of different drought-related genes can reinforce drought resistance over that of individual transgene lines, providing a path for developing arid climate-adapted elite maize varieties

Batch foaming of ultra-high molecular weight polyethylene with supercritical carbon dioxide: Influence of temperature and pressure

This work is aimed at studying the foaming behavior of pure ultra-high molecular weight polyethylene (UHMWPE) with supercritical carbon dioxide (scCO2). The effects of foaming temperature and saturation pressure on the final foam structure were investigated by using two different one-step batch foaming processes. An in-situ high-pressure observing system was used to record the crystal change of UHMWPE film during heating and cooling stages with/without pressurized CO2. The results showed that the cell size and the cell density were affected by the combined effects of crystal, temperature, and pressure. Experimental results with different foaming temperatures showed that higher foaming temperatures led to larger cells and lower cell densities. In the processes of foaming during the heating stage (Proc1) and cooling stage (Proc2), the expansion ratio increased first and then decreased with the increase of temperature. Before obtaining the maximum expansion ratio, compare with Proc2, the cell size and expansion ratio of foams were smaller, and the cell density was higher in Proc1. Experimental results with different saturation pressures showed that higher pressure led to lower cell density and larger average cell diameter in Proc1 due to the reduction of crystals and melt strength. While in Proc2, higher saturation pressure led to higher cell density due to the increase of solubility of CO2, and the cell density decreased as the pressure further increased due to cell coalescence

Numerical Simulation on Air-Liquid Transient Flow and Regression Model on Air-Liquid Ratio of Air Induction Nozzle

Air induction nozzle (AIN) has a special Venturi structure that has been widely used in the field of reducing the probability of drift of pesticide droplets and realizing precise application. The present research mainly adopts the method of comparative test and analyzes the difference between AIN and standard fan nozzle. However, the research on internal flow characteristics and air–liquid ratio (ALR) of AIN is very limited. In order to detect the air-liquid transient flow distribution and the influence of the geometric parameter structure of Venturi on the air–liquid ratio in the air induction nozzle, numerical simulation and air-liquid ratio prediction model of AIN combined with TD (Turbo Drop series) type Venturi tubes and ST110 (standard nozzle series) type fan nozzles are used. Based on the VOF (volume of fluid) model and Realizable k-ε turbulence control method, the TD-ST combined AIN is simulated numerically using open input and exit boundary conditions. The results show that the transient flow characteristic of the combined AIN is determined by the geometric structure of the Venturi tube, and the internal velocity and pressure change significantly at the Venturi angle. Under the same ST110 fan nozzle, the size of the larger TD Venturi tube will decrease the air phase content in the air–liquid flow. TD03-ST06 combined AIN has a maximum volume flow of 0.0092 (L/min) under 0.6 MPa. The air–liquid ratio regression model is established by designing the intake volume measurement system. According to this model, the influence law of tube size and spray parameters on the air–liquid ratio can be clarified. After variance analysis, it is proved that this model is suitable for air–liquid ratio prediction of TD-ST combined AIN. This study clarifies the air–liquid coupling law inside AIN and provides some reference for the quantitative analysis of the relationship between the geometric parameters, spray parameters, and the air–liquid ratio