Publications by authors named "Yaping Wang"

602 Publications

Molecular characterization and functional analysis of peroxiredoxin 4 in grass carp (Ctenopharyngodon idella).

Dev Comp Immunol 2021 Jul 26;125:104213. Epub 2021 Jul 26.

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China; Innovative Academy of Seed Design, Chinese Academy of Sciences, Beijing, 100101, China. Electronic address:

Peroxiredoxins (Prxs) are a group of evolutionarily conserved selenium-independent thiol-specific antioxidant proteins. In this study, the peroxiredoxin-4 (CiPrx4) gene from grass carp was identified and characterized. The full-length of CiPrx4 is 1339 bp, encoding 260 amino acids that contain two peroxiredoxin signature motifs and two GVL motifs. CiPrx4 belongs to the typical 2-Cys subfamily and shows the highest homology with Prx4 from Cyprinus carpio (95.4%). CiPrx4 mRNA was constitutively expressed in all tested tissues and was upregulated by grass carp reovirus and pathogen-associated molecular pattern (PAMP) stimulation. CiPrx4 was localized in the cytoplasm and co-localized with the endoplasmic reticulum. The purified CiPrx4 protein protected DNA from degradation in a dose-dependent manner. Moreover, the overexpression of CiPrx4 in Escherichia coli and fish cells showed apparent antioxidant and antiviral activities. Collectively, the results of the present study provide new insights for further understanding the functions of Prx4 in teleost fish.
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http://dx.doi.org/10.1016/j.dci.2021.104213DOI Listing
July 2021

Application of traditional Chinese and Western medicine combined with chronic disease management in pulmonary rehabilitation and evaluation of efficacy.

Am J Transl Res 2021 15;13(6):6372-6381. Epub 2021 Jun 15.

Department of Pain, Shanghai Quyang Hospital Hongkou, Shanghai 200092, China.

Objective: This study evaluated the efficacy of traditional Chinese and western medicine combined with chronic disease management on rehabilitation of chronic obstructive pulmonary disease (COPD) patients.

Methods: A total of 199 COPD patients in Shanghai Construction Group (SCG) Hospital were recruited as research objects. The control group (CG) consisted of 100 patients treated with conventional western chronic disease management, and the research group (RG) consisted of 99 patients treated with chronic disease management with combined traditional Chinese and western medicine. The efficacy, pulmonary rehabilitation performance, compliance score, 6-minute walk test (6MWT), modified Medical Research Council dyspnoea scale (MMRC), COPD assessment test (CAT), pulmonary function (PaO, PaCO, FEV1, PEF), self-rating anxiety scale (SAS), self-rating depression scale (SDS) and patient satisfaction between the two groups were compared.

Results: Pulmonary rehabilitation performance, 6MWT results, and patient satisfaction in the RG were significantly better than those in the CG. The total effective rate, compliance score, PaO, FEV1 and PEF of the RG were significantly higher than those of the CG. After treatment, the COPD symptom score, CAT score, PaCO, SAS score and SDS score in the RG were significantly lower than those in the CG.

Conclusion: Chronic disease management with combined traditional Chinese and western medicine has great application value and high efficacy in pulmonary rehabilitation.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290697PMC
June 2021

Blockade of GITRL/GITR signaling pathway attenuates house dust mite-induced allergic asthma in mice through inhibition of MAPKs and NF-κB signaling.

Mol Immunol 2021 Jul 20;137:238-246. Epub 2021 Jul 20.

Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, Chongqing, PR China; National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, PR China. Electronic address:

GITRL/GITR signaling pathway plays an important role in allergy, inflammation, transplantation and autoimmunity. However, its role in asthma remains unclear. Thus, the present study aimed to investigate changes in this pathway and observe the therapeutic effect of its blocking on asthma. By using house dust mite-induced asthma model, changes of GITRL/GITR and its downstream molecules MAPKs (e.g., p38 MAPK, JNK and Erk) and NF-κB were observed. After that, GITRL in lung of mice was knocked down by recombinant adeno-associated virus to observe the impact on its downstream molecules and assess the therapeutic effect on asthma. These results showed that GITRL/GITR and its downstream molecules MAPKs/NF-κB were activated in asthmatic mice. This activation was suppressed after GITRL knockdown, and allergic airway inflammation and airway hyperresponsiveness were alleviated. These results demonstrate that GITRL/GITR-MAPKs/NF-κB signaling pathway participates in the pathogenesis of asthma. Blockade of GITRL/GITR signaling pathway exhibits protective effects in a mouse model of house dust mite-induced allergic asthma.
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http://dx.doi.org/10.1016/j.molimm.2021.07.005DOI Listing
July 2021

Laparoscopic radical hysterectomy for cervical cancer by pulling the round ligament without a uterine manipulator.

Eur J Obstet Gynecol Reprod Biol 2021 Jul 1;264:31-35. Epub 2021 Jul 1.

Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address:

Objective: To demonstrate the experience of laparoscopic radical hysterectomy for cervical cancer without the use of a uterine manipulator and investigate the feasibility and treatment effectiveness of this surgical approach.

Materials And Methods: The laparoscopic radical hysterectomy for cervical cancer by pulling the round ligament without a uterine manipulator prevented the oppression of the uterine manipulator on the tumour. Vaginal ligation was performed below the lesion of cervical cancer, and the vagina was cut off below the ligation line. Consequently, the exposure of cancer tissues in the abdominal cavity was prevented, enabling a tumour-free operation. We reviewed the medical records of the 22 patients with stage IB1-IIA2 cervical squamous cell carcinoma who were treated at our hospital between May 2019 and February 2020. All the patients underwent the laparoscopic radical hysterectomy for cervical cancer by pulling the round ligament. All the patients were informed about the different therapeutic schemes and surgical approaches as well as their advantages and disadvantages. Information about operative time, intraoperative blood loss, hospitalisation duration, postoperative complications, postoperative adjuvant therapy, prognosis and other data were recorded.

Results: All the surgical procedures were successfully completed without perioperative complications, such as vascular injury, pelvic injury and abdominal organ injury. The mean operative duration was 204 min, and the mean operative blood loss was 102 mL. The mean duration of postoperative hospital stay was 13 days. Nineteen patients received postoperative chemotherapy once before hospital discharge. Urinary retention was the major postoperative complication. All the patients were followed up for 14-23 months. The median follow-up time was 18 months. 21 of the 22 patients survived. No recurrence was detected in the patients during follow-up. One patient who had a pelvic lymph node metastasis but refused complete chemoradiotherapy died before the last follow-up.

Conclusions: This surgical approach appears to be safe and feasible for patients with cervical cancer. A larger sample size and longer follow-up period are required to confirm whether this surgical approach can actually and effectively improve the prognosis.
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http://dx.doi.org/10.1016/j.ejogrb.2021.06.045DOI Listing
July 2021

Characterization of SR-B2a and SR-B2b genes and their ability to promote GCRV infection in grass carp (Ctenopharyngodon idellus).

Dev Comp Immunol 2021 Jul 8;124:104202. Epub 2021 Jul 8.

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China.

Scavenger receptor class B type 2 (SR-B2) is a pattern recognition receptor involved in innate immunity in mammals; however, the immunological function of SR-Bs in fish remains unclear. In this study, the full-length cDNA sequences of SR-B2a and SR-B2b from grass carp (Ctenopharyngodon idellus) were cloned and designated as CiSR-B2a and CiSR-B2b. Multiple alignments and phylogenetic analyses deduced that CiSR-B2a and CiSR-B2b had the highest evolutionary conservation and were closely related to the zebrafish (Danio rerio) homologs, DrSR-B2a and DrSR-B2b, respectively. Both CiSR-B2a and CiSR-B2b were expressed in all the tested tissues, with the highest expression levels found in the hepatopancreas. In Ctenopharyngodon idellus kidney cells (CIK), CiSR-B2a and CiSR-B2b were mainly located in the cytoplasm, and a small amount located on the plasma membrane. After challenge with Grass Carp Reovirus (GCRV), the expression of CiSR-B2a and CiSR-B2b were significantly upregulated in the spleen (about 10.27 and 27.19 times higher than that at 0 day, p < 0.01). With CiSR-B2a or CiSR-B2b overexpressed in CIK, the relative copy number of GCRV in the cells was both significantly increased compared to that in the control group, indicating that CiSR-B2a and CiSR-B2b may be important proteins during the infection processes of GCRV.
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http://dx.doi.org/10.1016/j.dci.2021.104202DOI Listing
July 2021

Pseudomonas aeruginosa outer membrane vesicles ameliorates lung ischemia-reperfusion injury by regulating the balance of regulatory T cells and Th17 cells through Tim-3 and TLR4/NF-κB pathway.

Inflamm Res 2021 Aug 5;70(8):891-902. Epub 2021 Jul 5.

Department of Cardiothoracic Surgery, Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical Research Center for Child Health and Disorders; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, No. 136, Zhongshan 2nd Road, Yuzhong Dis, Chongqing, 400014, People's Republic of China.

Objective: Regulatory T cells (Tregs) and T helper (Th) 17 cells are two subsets of CD4 + T cells with opposite effects which play a crucial role in the pathogenesis of lung injury. In this study, we aim to investigate the protective effect of Pseudomonas aeruginosa outer membrane vesicles (OMVs) preconditioning on lung ischemia-reperfusion (I/R) injury and potential mechanisms.

Methods: Pathogen-free C57BL/6 mice were randomly divided into four groups: control, Control + OMVs, I/R and I/R + OMVs groups. Bronchoalveolar lavage fluid (BALF), serum, and lung tissues were collected and analyzed for pathophysiology and immune mechanism.

Results: OMVs not only attenuated tissue injury and respiratory physiologic function but also mediated the downregulation of lung wet-to-dry weight ratio and the reduction of total protein concentration. The numbers of total cells, macrophages, neutrophils, and lymphocytes were markedly decreased in the I/R mice following OMVs preconditioning. OMVs also decreased inflammatory cytokines associated with CD4 + T cells in both BALF and serum. In addition, the level of Tregs and its transcription factor forkhead box P3 (Foxp3) were significantly increased, while the level of Th17 cells and its transcription factor retinoid-related orphan receptor γ (RORγt) were significantly decreased following OMVs preconditioning. In the process of exploring the underlying protection mechanisms of OMVs, we found that OMVs preconditioning significantly reduced protein expression of Toll-like receptor 4 (TLR4), which in turn not only inactivated myeloid differentiation factor 88 (MyD88) and Phosphorylated nuclear factor kappa B (p-NF-κB), but also simultaneously increased the levels of T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3).

Conclusions: These results suggest that OMVs preconditioning may ameliorate lung I/R injury by regulating the balance of Tregs and Th17 cells through Tim-3 and TLR4/NF-κB pathway.
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http://dx.doi.org/10.1007/s00011-021-01483-wDOI Listing
August 2021

Multi-Omics Sequencing Provides Insights Into Age-Dependent Susceptibility of Grass Carp () to Reovirus.

Front Immunol 2021 17;12:694965. Epub 2021 Jun 17.

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.

Grass carp () is an important aquaculture species in China that is affected by serious diseases, especially hemorrhagic disease caused by grass carp reovirus (GCRV). Grass carp have previously shown age-dependent susceptibility to GCRV, however, the mechanism by which this occurs remains poorly understood. Therefore, we performed transcriptome and metabolome sequencing on five-month-old (FMO) and three-year-old (TYO) grass carp to identify the potential mechanism. Viral challenge experiments showed that FMO fish were susceptible, whereas TYO fish were resistant to GCRV. RNA-seq showed that the genes involved in immune response, antigen presentation, and phagocytosis were significantly upregulated in TYO fish before the GCRV infection and at the early stage of infection. Metabolome sequencing showed that most metabolites were upregulated in TYO fish and downregulated in FMO fish after virus infection. Intragroup analysis showed that arachidonic acid metabolism was the most significantly upregulated pathway in TYO fish, whereas choline metabolism in cancer and glycerophospholispid metabolism were significantly downregulated in FMO fish after virus infection. Intergroup comparison revealed that metabolites from carbohydrate, amino acid, glycerophospholipid, and nucleotide metabolism were upregulated in TYO fish when compared with FMO fish. Moreover, the significantly differentially expressed metabolites showed antiviral effects both and . Based on these results, we concluded that the immune system and host biosynthesis and metabolism, can explain the age-dependent viral susceptibility in grass carp.
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http://dx.doi.org/10.3389/fimmu.2021.694965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247658PMC
June 2021

Characterization of fungal microbial diversity in healthy and diarrheal Tibetan piglets.

BMC Microbiol 2021 Jul 3;21(1):204. Epub 2021 Jul 3.

College of Veterinary Medicine, Huazhong Agricultural University, 430070, Wuhan, People's Republic of China.

Background: Diarrhea is an important ailment limiting the production of the Tibetan pig industry. Dynamic balance of the intestinal microbiota is important for the physiology of the animal. The objective of this work was to study fungal diversity in the feces of early weaning Tibetan piglets in different health conditions.

Results: In the present study, we performed high-throughput sequencing to characterize the fungal microbial diversity in healthy, diarrheal and treated Tibetan piglets at the Tibet Autonomous Region of the People's Republic of China. The four alpha diversity indices (Chao1, ACE, Shannon and Simpson) revealed no significant differences in the richness across the different groups (P > 0.05). In all samples, the predominant fungal phyla were Ascomycota, Basidiomycota and Rozellomycota. Moreover, the healthy piglets showed a higher abundance of Ascomycota than the treated ones with a decreased level of Basidiomycota. One phylum (Rozellomycota) showed higher abundance in the diarrheal piglets than in the treated. At genus level, compared with that to the healthy group, the proportion of Derxomyces and Lecanicillium decreased, whereas that of Cortinarius and Kazachstania increased in the diarrheal group. The relative abundances of Derxomyces, Phyllozyma and Hydnum were higher in treated piglets than in the diarrheal ones.

Conclusions: A decreased relative abundance of beneficial fungi (e.g. Derxomyces and Lecanicillium) may cause diarrhea in the early-weaned Tibetan piglets. Addition of probiotics into the feed may prevent diarrhea at this stage. This study presented the fungal diversity in healthy, diarrheal and treated early-weaned Tibetan piglets.
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http://dx.doi.org/10.1186/s12866-021-02242-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254304PMC
July 2021

Anti-Fibrotic Effects of Low Toxic Microcystin-RR on Bleomycin-Induced Pulmonary Fibrosis: A Comparison with Microcystin-LR.

Front Pharmacol 2021 8;12:675907. Epub 2021 Jun 8.

Department of Medical Genetics, Nanjing University School of Medicine, Nanjing, China.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial pulmonary disease characterized with radiographically evident pulmonary infiltrates and extracellular matrix deposition with limited treatment options. We previously described that microcystin-LR (MC-LR) reduces transforming growth factor (TGF)-β1/Smad signaling and ameliorates pulmonary fibrosis in bleomycin (BLM)-induced rat models. In the present study, we further demonstrate that microcystin-RR (MC-RR), an MC congener with lower toxicity than MC-LR, exerted an anti-fibrotic effect on BLM-induced pulmonary fibrosis rodent models and compared it with MC-LR. Our data show that MC-RR treatment attenuated BLM-associated pulmonary inflammation and collagen deposition in both therapeutic and preventive models. MC-RR reduced the expression of fibrotic markers, including vimentin, α-smooth muscle actin, collagen 1α1, and fibronectin, in rat pulmonary tissues. Furthermore, the core features of BLM-induced pulmonary fibrotic lesions were better alleviated by MC-RR than by MC-LR. MC-RR treatment substantially decreased the number of pulmonary M2 macrophages. , MC-RR attenuated the epithelial-mesenchymal transition and fibroblast-myofibroblast transition triggered by M2 macrophages. Therefore, we highlight MC-RR as a promising molecule for developing therapeutic and prophylactic strategies against IPF, a refractory lung disease.
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http://dx.doi.org/10.3389/fphar.2021.675907DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217630PMC
June 2021

Low expression of developing brain homeobox 2 (Dbx2) may serve as a biomarker to predict poor prognosis in endometrial cancer.

Am J Transl Res 2021 15;13(5):4738-4748. Epub 2021 May 15.

Gynecologic Oncology, The Third Affiliated Hospital of Zhengzhou University Zhengzhou 450000, Henan, P. R. China.

Objective: For investigating Dbx2's expression in endometrial cancer (EC) and its effect on prognosis of patients with EC.

Methods: A comparison was performed in the Cancer Genome Atlas (TCGA) database in terms of the expression profiling of EC and the survival data. To obtain differential expression genes (DEGs), Volcano plot and Venn analysis were adopted. DEGs function was performed by carrying out the GO annotation analysis (GO) and gene set enrichment analysis (GSEA). In clinical EC samples, PCR was applied to the verification of Dbx2's expression.

Results: Dbx2 was a downregulated expression in tumor tissues. Dbx2 can have a poor prognosis role in EC by regulating the apoptotic signaling pathway and the immune pathway. Lower expression of Dbx2 was related to lymph node metastasis and FIGO stage.

Conclusion: Dbx2 is downregulated in endometrial cancer, which serves as a biomarker to predict poor prognosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205784PMC
May 2021

Efficacy and safety of ciprofol for the sedation/anesthesia in patients undergoing colonoscopy: Phase IIa and IIb multi-center clinical trials.

Eur J Pharm Sci 2021 Sep 8;164:105904. Epub 2021 Jun 8.

Department of Anesthesiology, West China Hospital, Sichuan University & The Research Units of West China (2018RU012), Chinese Academy of Medical Sciences, Chengdu, China. Electronic address:

Objective: Ciprofol is a new intravenous anesthetic agent similar to propofol that has the pharmacodynamic characteristics of a rapid rate of onset and recovery in pre-clinical experiments. The aims of the present clinical trials were to compare the efficacy and safety of ciprofol emulsion for sedation or general anesthesia during colonoscopy and to define optimal doses for a subsequent phase III clinical trial.

Methods: A phase IIa multi-center, open-label, non-randomized, positive control, dose-escalating study was performed to determine a recommended phase IIb dose (RP2D) of ciprofol to induce sedation or anesthesia in patients undergoing colonoscopy. Phase IIb was also a multi-center clinical trial, but the patients were randomized into 3 groups at a ratio of 1:1:1. It was a double-blinded, propofol controlled study that administered ciprofol 0.4 mg/kg (n = 31) and 0.5 mg/kg (n = 32) or propofol at 2.0 mg/kg (n = 31), with the aim of establishing the optimal dose of ciprofol. The primary endpoint was the colonoscopy success rate. Secondary endpoints were the duration of colonoscope insertion, recovery time, number of top-up doses needed, and the total dose of ciprofol or propofol required to maintain adequate sedation or anesthesia. In addition, we evaluated the satisfaction of sedation/anesthesia from the endoscopists, anesthetists and patients' points of view. Safety was assessed according to the incidence of AEs including serious AEs and drug related AEs and the assessment of vital signs, a 12-lead ECG and laboratory tests.

Results: In the phase IIa trial, the colonoscopy success rates in the 0.2-0.5 mg/kg ciprofol and propofol 2.0 mg/kg groups were 100% and all doses were safe and well tolerated. Ciprofol doses of 0.4 mg/kg and 0.5 mg/kg are recommended for subsequent IIb phases. In the phase IIb trial, a 100% success rate was reconfirmed in all the dosage groups. The mean time of colonoscope insertion in the ciprofol 0.4 mg/kg, ciprofol 0.5 mg/kg and propofol 2.0 mg/kg groups were 1.9, 1.5 and 1.5 min, the mean recovery times from colonoscope withdrawal were 6.1, 5.1, and 4.3 min, and the times to discharge were 11.8, 11.2 and 10.6 min, respectively. The satisfaction ratings of anesthetists in the ciprofol 0.5 mg/kg group (9.5 ± 0.8) were higher than in the ciprofol 0.4 mg/kg (9.2 ± 1.0) and propofol 2.0 mg/kg (9.2 ± 0.9) groups. The incidence of sedation and anesthesia-related AEs was highest in the propofol 2.0 mg/kg group (25.8%), followed by the ciprofol 0.5 mg/kg group (21.9%), and was least in the ciprofol 0.4 mg/kg group (16.1%) (P = 0.750).

Conclusions: Ciprofol was safe and well tolerated at doses ranging from 0.1 mg/kg to 0.5 mg/kg. Ciprofol 0.4-0.5 mg/kg induced equivalent sedation/anesthesia and had a similar safety profile to propofol 2.0 mg/kg during colonoscopy without producing serious AEs.
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http://dx.doi.org/10.1016/j.ejps.2021.105904DOI Listing
September 2021

Efficacy observation and analysis of metoprolol combined with dopamine in patients with severe pneumonia complicated with heart failure.

Panminerva Med 2021 Jun 11. Epub 2021 Jun 11.

Department of Critical Care Medicine, Weihai Central Hospital, Weihai, China.

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http://dx.doi.org/10.23736/S0031-0808.21.04376-7DOI Listing
June 2021

Roles of tolC on tolerance to bile salts and biofilm formation in Cronobacter malonaticus.

J Dairy Sci 2021 Jun 4. Epub 2021 Jun 4.

School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, China. Electronic address:

Bile salts is one of essential components of bile secreted into the intestine to confer antibacterial protection. Cronobacter species are associated with necrotizing enterocolitis in newborns and show a strong tolerance to bile salts. However, little attempt has been made to focus on the molecular basis of the tolerance to bile salts. In this study, we investigated the roles of tolC on growth, cell morphology, motility, and biofilm formation ability in Cronobacter malonaticus under bile salt stress. The results indicated that the absence of tolC significantly affected the colony morphology and outer membrane structure in a normal situation, compared with those of the wild type strain. The deletion of tolC caused the decline in resistance to bile salt stress, inhibition of growth, and observable reduction in relative growth rate and motility. Moreover, the bacterial stress response promoted the biofilm formation ability of the mutant strain. The expression of the AcrAB-TolC system (acrA, acrB, and tolC) was effectively upregulated compared with the control sample when exposed to different bile salt concentrations. The findings provide valuable information for deeply understanding molecular mechanisms about the roles of tolC under bile salt stress and the prevention and control of C. malonaticus.
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http://dx.doi.org/10.3168/jds.2021-20128DOI Listing
June 2021

Association between meteorological factors and daily new cases of COVID-19 in 188 countries: A time series analysis.

Sci Total Environ 2021 Aug 23;780:146538. Epub 2021 Mar 23.

Department of Epidemiology and Biostatics, School of Public Health, Peking University, No. 38, Xueyuan Road, Haidian District, Beijing 100191, China. Electronic address:

By 31 December 2020, Coronavirus disease 2019 (COVID-19) had been prevalent worldwide for one year, and most countries had experienced a complete seasonal cycle. The role of the climate and environment are essential factors to consider in transmission. We explored the association between global meteorological conditions (including mean temperature, wind speed, relative humidity and diurnal temperature range) and new cases of COVID-19 in the whole past year. We assessed the relative risk of meteorological factors to the onset of COVID-19 by using generalized additive models (GAM) and further analyzed the hysteresis effects of meteorological factors using the Distributed Lag Nonlinear Model (DLNM). Our findings revealed that the mean temperature, wind speed and relative humidity were negatively correlated with daily new cases of COVID-19, and the diurnal temperature range was positively correlated with daily new cases of COVID-19. These relationships were more apparent when the temperature and relative humidity were lower than their average value (21.07°Cand 66.83%). The wind speed and diurnal temperature range were higher than the average value(3.07 m/s and 9.53 °C). The maximum RR of mean temperature was 1.30 under -23°C at lag ten days, the minimum RR of wind speed was 0.29 under 12m/s at lag 24 days, the maximum RR of range of temperature was 2.21 under 28 °C at lag 24 days, the maximum RR of relative humidity was 1.35 under 4% at lag 0 days. After a subgroup analysis of the countries included in the study, the results were still robust. As the Northern Hemisphere enters winter, the risk of global covid-19 remains high. Some countries have ushered in a new round of COVID-19 epidemic. Thus, active measures must be taken to control the source of infection, block transmission and prevent further spread of COVID-19 in winter.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986348PMC
August 2021

An Iridium Complex as an AIE-active Photosensitizer for Image-guided Photodynamic Therapy.

Chem Asian J 2021 Jul 26;16(13):1780-1785. Epub 2021 May 26.

Hunan Provincial Key Laboratory of Micro & Nano Materials Interface Science, College of Chemistry and Chemical Engineering, Central South University, Changsha, 410083, P. R. China.

Image-guided photodynamic therapy (PDT) has received growing attention due to its non-invasiveness and precise controllability. However, the PDT efficiency of most photosensitizers are decreased in living system due to the aggregation-caused singlet oxygen ( O ) generation decreasing. Herein, we present an Iridium (III) pyridylpyrrole complex (Ir-1) featuring of aggregation-induced emission (AIE) and O generation characteristics for image-guided PDT of cancer. Ir-1 aqueous solution exhibits bright red phosphorescence peaked at 630 nm, large Stokes shift of 227 nm, and good O generation ability. The O generating rate of Ir-1 in EtOH/water mixture solution is 2.3 times higher than that of Rose Bengal. In vitro experimental results revealed that Ir-1 has better biocompatibility and higher phototoxicity compared with clinically used photosensitizers (Rose Bengal and Ce6), suggesting that Ir-1 can serve as a photosensitizer for image-guided PDT of cancer.
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http://dx.doi.org/10.1002/asia.202100291DOI Listing
July 2021

Emerging role of interleukin-13 in cardiovascular diseases: A ray of hope.

J Cell Mol Med 2021 Jun 4;25(12):5351-5357. Epub 2021 May 4.

Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Despite the great progress made in the treatment for cardiovascular diseases (CVDs), the morbidity and mortality of CVDs remains high due to the lack of effective treatment strategy. Inflammation is a central pathophysiological feature of the heart in response to both acute and chronic injury, while the molecular basis and underlying mechanisms remains obscure. Interleukin (IL)-13, a pro-inflammatory cytokine, has been known as a critical mediator in allergy and asthma. Recent studies appraise the role of IL-13 in CVDs, revealing that IL-13 is not only involved in more obvious cardiac inflammatory diseases such as myocarditis but also relevant to acute or chronic CVDs of other origins, such as myocardial infarction and heart failure. The goal of this review is to summarize the advancement in our knowledge of the regulations and functions of IL-13 in CVDs and to discuss the possible mechanisms of IL-13 involved in CVDs. We highlight that IL-13 may be a promising target for immunotherapy in CVDs.
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http://dx.doi.org/10.1111/jcmm.16566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184673PMC
June 2021

Enhancement of oral bioavailability and anti-hyperuricemic activity of aloe emodin via novel Soluplus®-glycyrrhizic acid mixed micelle system.

Drug Deliv Transl Res 2021 Apr 15. Epub 2021 Apr 15.

Department of Pharmaceutics, School of Pharmacy, Centre for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, Zhenjiang, 212013, People's Republic of China.

The objective of this study was to fabricate a novel drug delivery system using Soluplus® (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer) and glycyrrhizic acid to improve solubility, bioavailability, and anti-hyperuricemic activity of aloe emodin (AE). The AE-loaded mixed micelles (AE-M) were prepared by thin-film hydration method. The optimal AE-M contained small-sized (30.13 ± 1.34 nm) particles with high encapsulation efficiency (m/m, %) of 90.3 ± 1.08%. The release rate of AE increased in the micellar formulation than that of free AE in the four media (DDW, pH 7.0; phosphate buffer solution, pH 7.4; phosphate buffer solution, pH 6.8; and hydrochloric acid aqueous solution, pH 1.2). In comparison to free AE, the pharmacokinetic study of AE-M showed that its relative oral bioavailability increased by 3.09 times, indicating that mixed micelles may promote gastrointestinal absorption. More importantly, AE-M effectively reduced uric acid level by inhibiting xanthine oxidase (XOD) activity in model rats. The degree of ankle swelling, serum levels of interleukin (IL)-1, and IL-6-related inflammatory factors levels all decreased in the gouty arthritis model established via monosodium urate (MSU) crystals. Taken together, the AE-M demonstrated the potential to improve the bioavailability, anti-hyperuricemic activity, and anti-inflammation of AE.
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http://dx.doi.org/10.1007/s13346-021-00969-8DOI Listing
April 2021

Inactivation of cysteine 674 in the sarcoplasmic/endoplasmic reticulum calcium ATPase 2 causes retinopathy in the mouse.

Exp Eye Res 2021 Jun 15;207:108559. Epub 2021 Apr 15.

Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331, China. Electronic address:

Diabetic retinopathy is a multifactorial microvascular complication, and its pathogenesis hasn't been fully elucidated. The irreversible oxidation of cysteine 674 (C674) in the sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) was increased in the type 1 diabetic retinal vasculature. SERCA2 C674S knock-in (SKI) mouse line that half of C674 was replaced by serine 674 (S674) was used to study the effect of C674 inactivation on retinopathy. Compared with wild type (WT) mice, SKI mice had increased number of acellular capillaries and pericyte loss similar to those in type 1 diabetic WT mice. In the retina of SKI mice, pro-apoptotic proteins and intracellular Ca-dependent signaling pathways increased, while anti-apoptotic proteins and vessel density decreased. In endothelial cells, C674 inactivation increased the expression of pro-apoptotic proteins, damaged mitochondria, and induced cell apoptosis. These results suggest that a possible mechanism of retinopathy induced by type 1 diabetes is the interruption of calcium homeostasis in the retina by oxidation of C674. C674 is a key to maintain retinal health. Its inactivation can cause retinopathy similar to type 1 diabetes by promoting apoptosis. SERCA2 might be a potential target for the prevention and treatment of diabetic retinopathy.
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http://dx.doi.org/10.1016/j.exer.2021.108559DOI Listing
June 2021

Personality differences in brain network mechanisms for placebo analgesia and nocebo hyperalgesia in experimental pain: a functional magnetic resonance imaging study.

Ann Transl Med 2021 Mar;9(5):371

Department of Rehabilitation, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

Background: Placebo and nocebo responses have been increasingly gaining the attention of clinical and scientific researchers. Inconsistent conclusions from current studies indicate that different factors potentially affect both placebo and nocebo responses. Increasing evidence suggests that personality differences may affect the mechanisms of both two responses. In the present work, we explored the characteristics of neural signals of placebo and nocebo responses based on functional connectivity (FC) analysis and Granger causality analysis (GCA).

Methods: A total of 34 healthy participants received conditional induction training to establish placebo and nocebo responses. Every participant completed the following experimental workflow, including scanning of baseline, experimental low back pain model establishment, scanning of acute pain status, and scanning of placebo response or nocebo response. We collect visual analogue scale (VAS) data after each scanning. Functional magnetic resonance imaging (fMRI) data from different personality groups were subjected to FC analysis and multivariate GCA (mGCA).

Results: Pain scores for placebo and nocebo responses were statistically different across different personality. There are also statistically differences in the neural signals of two responses across different personality.

Conclusions: The findings of the present study indicated that extroverted and introverted participants are likely to experience placebo analgesic effects and nocebo hyperalgesia effects, respectively. Both extroverted and introverted participants showed significant changes in brain networks under placebo response. Variation in emotional control and ventromedial prefrontal cortex inactivity may constitute the bulk of the personality differences in placebo analgesia. Differences in the regulation of the sensory conduction system (SCS) and release of the emotional circuit could be important factors affecting personality differences in nocebo hyperalgesia.
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http://dx.doi.org/10.21037/atm-20-5123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033354PMC
March 2021

Efficacy and Safety of Sacubitril/Valsartan Therapy for Acute Decompensated Heart Failure with Reduced Ejection Fraction during the Vulnerable Phase: A Multicenter, Assessor-Blinded, Prospective, Observational, Cohort Study.

Cardiology 2021;146(3):335-344. Epub 2021 Mar 29.

Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.

Background: The 3-month period after hospitalization for acute cardiac failure is a vulnerable phase with the highest risk of mortality and rehospitalization. Safety and efficacy of early initiation of sacubitril/valsartan during the index hospitalization for acute decompensated heart failure (ADHF) is unclear. Therefore, we tested whether sacubitril/valsartan could result in a lower rate of a composite outcome of first hospitalization for heart failure and death from cardiovascular causes compared to inhibition of the renin-angiotensin system alone.

Methods: We enrolled patients hospitalized for ADHF and reduced ejection fraction at 4 sites; patients were divided into a sacubitril/valsartan group or an angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) group. All patients were followed up for 3 months after discharge. The primary endpoint was outcomes as a composite of death from cardiovascular causes and rehospitalization for heart failure.

Results: In total, 251 patients who received sacubitril/valsartan and 251 patients who received ACEIs/ARBs had similar propensity scores and were included and compared. The primary endpoint was reached in 40 patients (15.9%) treated with sacubitril/valsartan and in 59 patients (23.5%) managed by ACEI/ARB (HR, 0.650; 95% CI: 0.435-0.971; p = 0.035). The NYHA class improved in 72.1% of patients in the sacubitril/valsartan group and in 59.8% of patients in the ACEI/ARB group (HR, 1.303; 95% CI: 1.097-1.548, p = 0.004). The key safety outcomes endpoints did not significantly differ.

Conclusions: Among patients hospitalized with ADHF and reduced left ventricular ejection fraction, we observed that sacubitril/valsartan therapy led to reduction in death from cardiovascular causes and rehospitalizations for heart failure when compared to ACEI/ARB therapy alone during the vulnerable phase. Our results support that sacubitril/valsartan may be administered early in the vulnerable phase after ADHF and improves NYHA class.
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http://dx.doi.org/10.1159/000512418DOI Listing
March 2021

Analysis of the molecular basis of Saccharomyces cerevisiae mutant with high nucleic acid content by comparative transcriptomics.

Food Res Int 2021 04 6;142:110188. Epub 2021 Feb 6.

Key Laboratory of Industrial Fermentation Microbiology of Ministry of Education, Tianjin Industrial Microbiology Key Lab, College of Biotechnology of Tianjin University of Science and Technology, Tianjin 300547, China; Tianjin Food Safety & Low Carbon Manufacturing Collaborative Innovation Center, 300457 Tianjin, China; Tianjin Engineering Research Center of Microbial Metabolism and Fermentation Process Control, 300457 Tianjin, China.

Ribonucleic acid (RNA) and its degradation products are important functional components widely used in the food industry. Transcription analysis was used to explore the genetic mechanism underlying nucleic acid synthesis in the chemical mutant Saccharomyces cerevisiae strain BY23-195 with high nucleic acid content. Results showed that ribosome biogenesis, meiosis, RNA transport, mitogen-activated protein kinase (MAPK) signaling pathway, tryptophan metabolism, carbon metabolism, and longevity regulating pathway are closely related to the high nucleic acid metabolism of S. cerevisiae. Fourteen most promising genes were selected to evaluate the effect of single-gene deletion or overexpression on the RNA synthesis of S. cerevisiae. Compared with the RNA content of the parent strain BY23, that of mutant strains BY23-HXT1, BY23-ΔGSP2 and BY23-ΔCTT1 increased by 8.19%, 11.60% and 14.00%, respectively. The possible reason why HXT1, GSP2, and CTT1 affect RNA content is by regulating cell fitness. This work was the first to report that regulating the transcription of HXT1, GSP2, and CTT1 could increase the RNA content of S. cerevisiae. This work also provides valuable knowledge on the genetic mechanism of high nucleic acid synthesis in S. cerevisiae and new strategies for increasing its RNA content.
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http://dx.doi.org/10.1016/j.foodres.2021.110188DOI Listing
April 2021

Ultrafine molybdenum oxycarbide nanodots encapsulated in N,P co-doped carbon nanofibers as an advanced anode material for lithium-ion batteries.

Nanotechnology 2021 Apr 30;32(29). Epub 2021 Apr 30.

Automotive Engineering Research Institute, Jiangsu University, 301 Xuefu Road, Zhenjiang 212013, People's Republic of China.

Molybdenum oxycarbide (MoOC) is a single-phase compound, which can serve as a potential anode for Li-ion batteries (LIBs) that integrates the merits of the high specific capacity of MoOand high conductivity of MoC. Herein, a novel architecture with N,P co-doped C nanofibers and MoOC nanodots is constructed from a one-step phosphorization of MoO/aniline organic-inorganic hybrid. Ultrafine MoOC nanodots are well confined by N,P co-doped C nanofibers, which ensures fast Li/electron transfer and good stability of the structure under repeated charge/discharge processes. When this unique hybrid is employed as an anode material for LIBs, promising Listorage properties are gained in terms of high specific capacity, superb rate and long-term cycling performance. The remarkable capacitive contribution facilitates the fast Liuptake/release. This work may shed light on the development of well-defined Mo-based anodes for advanced LIBs.
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http://dx.doi.org/10.1088/1361-6528/abf26eDOI Listing
April 2021

Diagnosis and management of secondary malposition of PICC into the azygos vein.

J Vasc Access 2021 Mar 9:1129729821999484. Epub 2021 Mar 9.

Department of IV team, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Background: Peripherally inserted central catheter (PICC) has been widely used. The catheter-related complications might occur and the reports of secondary malposition into azygos veins were rare.

Methods: This retrospective review summarized the experience in diagnosis and management of secondary malposition of PICC into azygos veins in 25 cases.

Results: When the catheter dysfunction occurred in the PICC on the left limb, it was necessary to consider whether there would be malposition into azygos veins after other reasons were excluded. The malposition could be diagnosed by chest lateral radiograph or chest computed tomography. The secondary malposition into azygos veins was resolved by repositioning or withdrawing the PICC. After re-inserting the catheter, it should be closely monitored whether the malposition occurred again. Intracavitary electrocardiogram positioning technology was used to confirm the catheter tip position before using corrosive drug. After the catheters withdrawn from the azygos veins, close attention should be paid to the property and concentration of the infusion drug strictly and the complications such as blockage and re-malposition. No serious complications such as infection, thrombosis and extravasation occurred in this group of patients after treatment.

Conclusions: The results of our study suggested that the right limb is recommended for PICC catheterization in order to avoid secondary malposition into azygos veins and the malposition into azygos veins should be dealt with in time.
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http://dx.doi.org/10.1177/1129729821999484DOI Listing
March 2021

Experimental study for the establishment of a chemotherapy-induced ovarian insufficiency model in rats by using cyclophosphamide combined with busulfan.

Regul Toxicol Pharmacol 2021 Jun 9;122:104915. Epub 2021 Mar 9.

Department of Gynecology and Obstetics, The Second Affiliated Hospital, Chongqing MedicalUniversity, Chongqing, 400010, People's Republic of China. Electronic address:

With an improvement in the survival rate of cancer patients, chemotherapy-induced premature ovarian insufficiency (POI) is increasingly affecting the quality of life of female patients. Currently, there are many relevant studies using mice as an animal model. However, a large coefficient of variation for weight in mice is not appropriate for endocrine-related studies, compared with rats; therefore, it is necessary to identify an appropriate experimental model in rats. In this study, cyclophosphamide combined with busulfan was used to establish an animal model. We compared several common modeling methods using chemotherapeutic drugs, cisplatin, cyclophosphamide, and 4-vinylcyclohexene diepoxide (VCD), and we found that the combination of cyclophosphamide and busulfan was more effective in establishing a POI model in rats with few side effects by analyzing general physical conditions, pathological tissue sections of heart, liver, lung, spleen, kidney, uterus, and ovary, serum hormone levels, and follicle counts; thus, providing a more reliable model basis for subsequent studies.
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http://dx.doi.org/10.1016/j.yrtph.2021.104915DOI Listing
June 2021

25-Hydroxycholesterol 3-sulfate is an endogenous ligand of DNA methyltransferases in hepatocytes.

J Lipid Res 2021 Mar 8;62:100063. Epub 2021 Mar 8.

Department of Internal Medicine, Virginia Commonwealth University/McGuire VA Medical Centre, Richmond, VA, USA. Electronic address:

The oxysterol sulfate, 25-hydroxycholesterol 3-sulfate (25HC3S), has been shown to play an important role in lipid metabolism, inflammatory response, and cell survival. However, the mechanism(s) of its function in global regulation is unknown. The current study investigates the molecular mechanism by which 25HC3S functions as an endogenous epigenetic regulator. To study the effects of oxysterols/sterol sulfates on epigenetic modulators, 12 recombinant epigenetic enzymes were used to determine whether 25HC3S acts as their endogenous ligand. The enzyme kinetic study demonstrated that 25HC3S specifically inhibited DNA methyltransferases (DNMTs), DNMT1, DNMT3a, and DNMT3b with IC of 4.04, 3.03, and 9.05 × 10 M, respectively. In human hepatocytes, high glucose induces lipid accumulation by increasing promoter CpG methylation of key genes involved in development of nonalcoholic fatty liver diseases. Using this model, whole genome bisulfate sequencing analysis demonstrated that 25HC3S converts the CpG to CpG in the promoter regions of 1,074 genes. In addition, we observed increased expression of the demethylated genes, which are involved in the master signaling pathways, including MAPK-ERK, calcium-AMP-activated protein kinase, and type II diabetes mellitus pathways. mRNA array analysis showed that the upregulated genes encoded for key elements of cell survival; conversely, downregulated genes encoded for key enzymes that decrease lipid biosynthesis. Taken together, our results indicate that the expression of these key elements and enzymes are regulated by the demethylated signaling pathways. We summarized that 25HC3S DNA demethylation of CpG in promoter regions is a potent regulatory mechanism.
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http://dx.doi.org/10.1016/j.jlr.2021.100063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058565PMC
March 2021

Corrigendum to article "A programmable omnipotent Argonaute nuclease from mesophilic bacteria Kurthia massiliensis''.

Nucleic Acids Res 2021 04;49(6):3600

State Key Laboratory of Biocatalysis and Enzyme Engineering, Hubei Collaborative Innovation Center for Green Transformation of Bio-resources, Hubei Key Laboratory of Industrial Biotechnology, School of Life Sciences, Hubei University, Wuhan, Hubei 430062, China.

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http://dx.doi.org/10.1093/nar/gkab192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034638PMC
April 2021

Genome-wide identification, evolution of Krüppel-like factors (klfs) and their expressions during GCRV challenge in grass carp (Ctenopharyngodonidella).

Dev Comp Immunol 2021 Jul 2;120:104062. Epub 2021 Mar 2.

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, China.

The Krüppel-like factors (KLFs) are a family of transcription factors containing three highly conserved tandem zinc finger structures, and each member participates in multiple physiological and pathological processes. The publication of genome sequences and the application of bioinformatics tools have led to the discovery of numerous gene families in fishes. Here, 24 klf genes were re-annotated in grass carp. Subsequently, the number of klf family members were investigated in some representative vertebrate species. Then, a series of bioinformatics analysis showed that grass carp klfs in the same subfamily had similar genome structure patterns and conserved distribution patterns of motifs, which supported their molecular evolutionary relationships. Furthermore, the mRNA expression profiles showed that 24 grass carp klfs were ubiquitously expressed in 11 different tissues, and some of them displayed tissue-enriched expression patterns. Finally, the expressions of the evolutionarily expanded klf members (klf2a, 2b, 2l, 5a, 5b, 5l, 6a, 6b, 7a, 7b, 11a, 11b, 12a, 12b, 15 and 15l) during GCRV infection were also analyzed. The results suggested that grass carp klf genes with common evolutionary sources may share functional diversity and conservation. In conclusion, this study provides preliminary clues for further researches on grass carp klf members and their underlying transcriptional regulatory mechanisms during GCRV infection.
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http://dx.doi.org/10.1016/j.dci.2021.104062DOI Listing
July 2021

High-level extracellular production and immobilisation of methyl parathion hydrolase from Plesiomonas sp. M6 expressed in Pichia pastoris.

Protein Expr Purif 2021 Jul 27;183:105859. Epub 2021 Feb 27.

National Biopesticide Engineering Technology Research Center, Hubei Biopesticide Engineering Research Center, Hubei Academy of Agricultural Sciences, Biopesticide Branch of Hubei Innovation Centre of Agricultural Science and Technology, Wuhan, People's Republic of China. Electronic address:

Methyl parathion hydrolase (MPH) hydrolyses methyl parathion efficiently and specifically. Herein, we produced MPH from Plesiomonas sp. M6 using a Pichia pastoris multi-copy expression system. The original signal peptide sequence of the target gene was removed, and a modified coding sequence was synthesised. Multi-copy expression plasmids containing MPH were constructed using pHBM905BDM, and used to generate recombinant strains containing 1, 2, 3 or 4 copies of the MPH gene. The results showed that a higher target gene copy number increased the production of recombinant MPH (MPH-R), as anticipated. The expression level of the recombinant strain containing four copies of the MPH gene was increased to 1.9 U/ml using 500 ml shake flasks, and the specific activity was 15.8 U/mg. High-density fermentation further increased the target protein yield to 18.4 U/ml. Several metal ions were tested as additives, and Ni, Co and Mg at a concentration of 1 mM enhanced MPH-R activity by 196%, 201% and 154%, respectively. Enzyme immobilisation was then applied to overcome the difficulties in recovery, recycling and long-term stability associated with the free enzyme. Immobilised MPH-R exhibited significantly enhanced thermal and long-term stability, as well as broad pH adaptability. In the presence of inhibitors and chelating agents such as sodium dodecyl sulphate (SDS), immobilised MPH-R displayed 2-fold higher activity than free MPH-R, demonstrating its potential for industrial application.
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http://dx.doi.org/10.1016/j.pep.2021.105859DOI Listing
July 2021

[Higher alcohols metabolism by Saccharomyces cerevisiae: a mini review].

Sheng Wu Gong Cheng Xue Bao 2021 Feb;37(2):429-447

College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.

Higher alcohols are one of the main by-products of Saccharomyces cerevisiae in brewing. High concentration of higher alcohols in alcoholic beverages easily causes headache, thirst and other symptoms after drinking. It is also the main reason for chronic drunkenness and difficulty in sobering up after intoxication. The main objective of this review is to present an overview of the flavor characteristics and metabolic pathways of higher alcohols as well as the application of mutagenesis breeding techniques in the regulation of higher alcohol metabolism in S. cerevisiae. In particular, we review the application of metabolic engineering technology in genetic modification of amino transferase, α-keto acid metabolism, acetate metabolism and carbon-nitrogen metabolism. Moreover, key challenges and future perspectives of realizing optimization of higher alcohols metabolism are discussed. This review is intended to provide a comprehensive understanding of metabolic regulation system of higher alcohols in S. cerevisiae and to provide insights into the rational development of the excellent industrial S. cerevisiae strains producing higher alcohols.
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http://dx.doi.org/10.13345/j.cjb.200302DOI Listing
February 2021
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