Publications by authors named "Xiao-Juan Zhang"

156 Publications

Divergent Antiviral Mechanisms of Two Homeologs in a Recurrent Polyploid Fish.

Front Immunol 2021 31;12:702971. Epub 2021 Aug 31.

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

Polyploidy and subsequent diploidization provide genomic opportunities for evolutionary innovations and adaptation. The researches on duplicated gene evolutionary fates in recurrent polyploids have seriously lagged behind that in paleopolyploids with diploidized genomes. Moreover, the antiviral mechanisms of Viperin remain largely unclear in fish. Here, we elaborate the distinct antiviral mechanisms of two homeologs ( and ) in auto-allo-hexaploid gibel carp (). First, and showed differential and biased expression patterns in gibel carp adult tissues. Subsequently, using co-immunoprecipitation (Co-IP) screening analysis, both Viperin-A and Viperin-B were found to interact with crucian carp () herpesvirus (HV) open reading frame 46 right (ORF46R) protein, a negative herpesvirus regulator of host interferon (IFN) production, and to promote the proteasomal degradation of ORF46R decreasing K63-linked ubiquitination. Additionally, Viperin-B also mediated ORF46R degradation through autophagosome pathway, which was absent in Viperin-A. Moreover, we found that the N-terminal α-helix domain was necessary for the localization of Viperin-A and Viperin-B at the endoplasmic reticulum (ER), and the C-terminal domain of Viperin-A and Viperin-B was indispensable for the interaction with degradation of ORF46R. Therefore, the current findings clarify the divergent antiviral mechanisms of the duplicated homeologs in a recurrent polyploid fish, which will shed light on the evolution of teleost duplicated genes.
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http://dx.doi.org/10.3389/fimmu.2021.702971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438203PMC
August 2021

gen. nov., sp. nov., isolated from an anaerobic fermentation cellar of Chinese strong-flavour .

Int J Syst Evol Microbiol 2021 Sep;71(9)

Key Laboratory of Industrial Biotechnology of Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, PR China.

A Gram-stain-negative, coccus-shaped, obligately anaerobic, non-motile and non-spore-forming bacterium, designated strain JN500902, was isolated from the mud in a fermentation cellar used continuously over 30 years for Chinese strong-flavour production. Colonies were white, circular, convex and smooth-edged. Growth was observed at 20-40 °C (optimum, 37 °C), at pH 5.0-10 (optimum, pH 7.5), with 0-2 % (w/v) NaCl and with 0-4 % (v/v) ethanol. The Biolog assay demonstrated positive reactions of strain JN500902 in the metabolism of l-fucose and pyruvate. The predominant cellular fatty acids (>10 %) consisted of C and C. The major end metabolites of strain JN500902 were acetic acid and ethanol when incubated anaerobically in liquid reinforced clostridial medium. Acetate was the major organic acid end product. The complete genome size of strain JN500902 was 3 420 321 bp with 3327 identified genes. The G+C content was 43.5 mol%. Phylogenetic analysis based on 16S rRNA gene sequences affiliated strain JN500902 with the family , having low sequence similarity (92.8 %) to the nearest type strain, DSM 3224 and forming a clearly distinct branch. Core genome phylogenetic analysis of the isolate and 134 strains belonging to the family also revealed that strain JN500902 was well-separated from other genera of this family as a monophyletic clade. The average nucleotide identity and amino acid identity values between strain JN500902 and 134 strains were less than 74 and 65 %, respectively. Considering its polyphasic characteristics, strain JN500902 represents a novel genus and species within the family , for which the name gen. nov., sp. nov. is proposed. The type strain is JN500902 (=CICC 24502=JCM 33939).
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http://dx.doi.org/10.1099/ijsem.0.004991DOI Listing
September 2021

Genomic anatomy of male-specific microchromosomes in a gynogenetic fish.

PLoS Genet 2021 Sep 7;17(9):e1009760. Epub 2021 Sep 7.

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, The Innovative Academy of Seed Design, Hubei Hongshan Laboratory, Chinese Academy of Sciences, Wuhan, China.

Unisexual taxa are commonly considered short-lived as the absence of meiotic recombination is supposed to accumulate deleterious mutations and hinder the creation of genetic diversity. However, the gynogenetic gibel carp (Carassius gibelio) with high genetic diversity and wide ecological distribution has outlived its predicted extinction time of a strict unisexual reproduction population. Unlike other unisexual vertebrates, males associated with supernumerary microchromosomes have been observed in gibel carp, which provides a unique system to explore the rationales underlying male occurrence in unisexual lineage and evolution of unisexual reproduction. Here, we identified a massively expanded satellite DNA cluster on microchromosomes of hexaploid gibel carp via comparing with the ancestral tetraploid crucian carp (Carassius auratus). Based on the satellite cluster, we developed a method for single chromosomal fluorescence microdissection and isolated three male-specific microchromosomes in a male metaphase cell. Genomic anatomy revealed that these male-specific microchromosomes contained homologous sequences of autosomes and abundant repetitive elements. Significantly, several potential male-specific genes with transcriptional activity were identified, among which four and five genes displayed male-specific and male-biased expression in gonads, respectively, during the developmental period of sex determination. Therefore, the male-specific microchromosomes resembling common features of sex chromosomes may be the main driving force for male occurrence in gynogenetic gibel carp, which sheds new light on the evolution of unisexual reproduction.
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http://dx.doi.org/10.1371/journal.pgen.1009760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448357PMC
September 2021

Cooperation within the microbial consortia of fermented grains and pit mud drives organic acid synthesis in strong-flavor Baijiu production.

Food Res Int 2021 09 3;147:110449. Epub 2021 Jun 3.

Key Laboratory of Industrial Biotechnology of Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, PR China; National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, PR China; National Engineering Research Center of Solid-State Brewing, Luzhou 646000, PR China. Electronic address:

Mud cellars have long been used as anaerobic bioreactors for the fermentation of Chinese strong-flavor Baijiu, where starchy raw materials (mainly sorghum) are metabolized to ethanol and various flavor compounds by multi-species microorganisms. Jiupei (fermented grains) and pit mud are two spatially linked microbial habitats in the mud cellar, yet their metabolic division of labor remains unclear. Here, we investigated the changes in environmental variables (e.g., temperature, oxygen, pH), key metabolites (e.g., ethanol, organic acids) and microbial communities in jiupei and pit mud during fermentation. Jiupei (low pH, high ethanol) and pit mud (neutral pH) provided two habitats with distinctly different environmental conditions for microbial growth. Lactic acid accumulated in jiupei, while butyric and hexanoic acids were mainly produced by microbes inhabiting the pit mud. Biomass analysis using quantitative real-time PCR showed that bacteria dominated the microbial consortia during fermentation, moreover cluster and principal coordinate analysis (PCoA) analysis showed that the bacterial communities of jiupei and pit mud were significantly divergent. The bacterial community diversity of jiupei decreased significantly during the fermentation process, and was relatively stable in pit mud. Lactobacillus dominated the jiupei bacterial community, and its relative abundance reached 98.0% at the end of fermentation. Clostridia (relative abundance: 42.9-85.5%) was the most abundant bacteria in pit mud, mainly distributed in the genus Hydrogenispora (5.3-68.4%). Fungal communities of jiupei and pit mud showed a similar succession pattern, and Kazachstania, Aspergillus and Thermoascus were the predominant genera. PICRUSt analysis demonstrated that enzymes participating in the biosynthesis of acetic and lactic acid were mainly enriched in jiupei samples, while the bacterial community in the pit mud displayed greater potential for butyric and hexanoic acid synthesis. Assays from an in vitro simulated fermentation further validated the roles of jiupei microbiota in acetic and lactic acid production, and these acids were subsequently metabolized to butyric and hexanoic acid by the pit mud microbiota. This work has demonstrated the synergistic cooperation between the microbial communities of jiupei and pit mud for the representative flavor formation of strong-flavor Baijiu.
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http://dx.doi.org/10.1016/j.foodres.2021.110449DOI Listing
September 2021

Usefulness of metagenomic next-generation sequencing in adenovirus 7-induced acute respiratory distress syndrome: A case report.

World J Clin Cases 2021 Jul;9(21):6067-6072

Department of Infectious Disease, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China.

Background: Direct metagenomic next-generation sequencing (mNGS) of clinical samples is an effective method for the molecular diagnosis of infection. However, its role in the diagnosis of patients with acute respiratory distress syndrome (ARDS) of an unknown infectious etiology remains unclear.

Case Summary: A 33-year-old man was admitted to our center for a cough and febrile sensation. Shortly after admission, the patient was diagnosed with ARDS and treated in the intensive care unit. Subsequently, chest computed tomography features suggested an infection. mNGS was performed and the results were indicative of an infection caused by adenovirus type 7. The patient recovered after receiving appropriate treatment.

Conclusion: mNGS is a promising tool for the diagnosis of ARDS caused by infectious agents. However, further studies are required to develop strategies for incorporating mNGS into the current diagnostic process for the disease.
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http://dx.doi.org/10.12998/wjcc.v9.i21.6067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316940PMC
July 2021

Mining the Factors Driving the Evolution of the Pit Mud Microbiome under the Impact of Long-Term Production of Strong-Flavor Baijiu.

Appl Environ Microbiol 2021 08 11;87(17):e0088521. Epub 2021 Aug 11.

Key Laboratory of Industrial Biotechnology of Ministry of Education, School of Biotechnology, Jiangnan Universitygrid.258151.a, Wuxi, People's Republic of China.

The mud cellar creates a unique microenvironment for the fermentation of strong-flavor baijiu (SFB). Recent research and long-term practice have highlighted the key roles of microbes inhabiting pit mud in the formation of SFB's characteristic flavor. A positive correlation between the quality of SFB and cellar age was extracted from practice; however, the evolutionary patterns of pit mud microbiome and driving factors remain unclear. Here, based on the variation regularity analysis of microbial community structure and metabolites of samples from cellars of different ages (∼30/100/300 years), we further investigated the effects of lactate and acetate (main microbial metabolites in fermented grains) on modulating the pit mud microbiome. Esters (50.3% to 64.5%) dominated the volatile compounds identified in pit mud, and contents of the four typical acids (lactate, hexanoate, acetate, and butyrate) increased with cellar age. Bacteria (9.5 to 10.4 log [lg] copies/g) and archaea (8.3 to 9.1 lg copies/g) mainly constituted pit mud microbiota, respectively dominated by (39.7% to 81.2%) and (32.8% to 92.9%). An upward trend with cellar age characterized the relative and absolute abundance of the most predominant bacterial and archaeal genera, and . Correlation analysis revealed significantly ( < 0.05) positive relationships between the two genera and major metabolites. Anaerobic fermentation with acetate and lactate as carbon sources enhanced the enrichment of , and furthermore, the relative abundance of (40.9%) significantly increased after 15-day fed-batch fermentation with lactate compared with the initial pit mud (0.22%). This work presents a directional evolutionary pattern of pit mud microbial consortia and provides an alternative way to accelerate the enrichment of functional microbes. The solid-state anaerobic fermentation in a mud cellar is the most typical feature of strong-flavor baijiu (SFB). Metabolites produced by microbes inhabiting pit mud are crucial to create the unique flavor of SFB. Accordingly, craftspeople have always highlighted the importance of the pit mud microbiome and concluded by centuries of practice that the production rate of high-quality baijiu increases with cellar age. To deepen the understanding of the pit mud microbiome, we determined the microbial community and metabolites of different-aged pit mud, inferred the main functional groups, and explored the forces driving the microbial community evolution through metagenomic, metabolomic, and multivariate statistical analyses. The results showed that the microbial consortia of pit mud presented a regular and directional evolutionary pattern under the impact of continuous batch-to-batch brewing activities. This work provides insight into the key roles of the pit mud microbiome in SFB production and supports the production optimization of high-quality pit mud.
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http://dx.doi.org/10.1128/AEM.00885-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357292PMC
August 2021

Sphingosine-1-phosphate induces myocyte autophagy after myocardial infarction through mTOR inhibition.

Eur J Pharmacol 2021 Sep 16;907:174260. Epub 2021 Jun 16.

The Second Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, PR China; Shanxi Medical University, Taiyuan, 030001, Shanxi, PR China.

Sphingosine-1-phosphate (S1P)/S1P receptor 1 signaling exerts cardioprotective effects including inhibition of myocyte apoptosis. However, little is known about the effect of S1P treatment on myocyte autophagy after myocardial infarction (MI). In the present study, we tested the hypothesis that S1P induces myocyte autophagy through inhibition of the mammalian target of rapamycin (mTOR), leading to improvement of left ventricular (LV) function after MI. Sprague-Dawley rats underwent MI or sham operation. The animals were randomized to receive S1P (50 μg/kg/day, i.p.) or placebo for one week. H9C2 cardiomyocytes cultured in serum- and glucose-deficient medium were treated with or without S1P for 3 h. MI rats exhibited an increase in LV end-diastolic dimension (EDD) and decreases in LV fractional shortening (FS) and the maximal rate of LV pressure rise (+dP/dt). S1P treatment attenuated the increase in LV EDD and decreases in LV FS and +dP/dt. In the MI placebo group, the LC3 II/I ratio, a marker of autophagy, was increased, and increased further by S1P treatment. S1P also enhanced the autophagy-related proteins Atg4b and Atg5 after MI. Similarly, in cultured cardiomyocytes, autophagy was increased under glucose and serum deprivation, and increased further by S1P treatment. The effect of S1P on myocyte autophagy was associated with mTOR inhibition after MI or in cultured cardiomyocytes under glucose and serum deprivation. S1P treatment prevents LV remodeling, enhances myocyte autophagy and inhibits mTOR activity after MI. These findings suggest that S1P treatment induces myocyte autophagy through mTOR inhibition, leading to the attenuation of LV dysfunction after MI.
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http://dx.doi.org/10.1016/j.ejphar.2021.174260DOI Listing
September 2021

Efficacy and safety of low-dose corticosteroids for acute respiratory distress syndrome: A systematic review and meta-analysis.

World J Emerg Med 2021 ;12(3):207-213

General ICU, the First Affiliated Hospital of Zhengzhou University, Henan Key Laboratory of Critical Care Medicine, Zhengzhou Key Laboratory of Sepsis, Henan Engineering Research Center for Critical Care Medicine, Zhengzhou 450052, China.

Background: There are conflicting results regarding whether corticosteroids have better efficacy than placebo in acute respiratory distress syndrome (ARDS) patients. Therefore, we aim to further evaluate the efficacy and safety of corticosteroids in adult ARDS patients.

Methods: The databases, including Medline, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, were searched from their inception to May 2, 2020. Randomized controlled trials (RCTs) and observational cohort studies were selected to assess the use of corticosteroids in adult ARDS patients. The quality of the results was judged by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The inverse-variance method with random or fixed effects modeling was used to compute pooled odds ratio (), standardized mean difference (), and their 95% confidence interval ().

Results: Eight eligible RCTs and six cohort studies were included. The use of corticosteroids was associated with reduced mortality ( 0.57, 95% 0.43-0.76, 2=35.1%, =0.148) in ARDS patients, and the result was confirmed in the included cohort studies ( 0.51, 95% 0.27-0.95, 2=66.7%, =0.010). The subgroup analysis stratified by the initiation time and duration of corticosteroid use showed that early ARDS and prolonged corticosteroid use had significant survival benefits in the RCTs. The low-dose corticosteroid use was also associated with significantly more ventilator-free days and a reduced rate of new infections in ARDS patients.

Conclusions: The low-dose corticosteroid therapy may be safe and reduce mortality, especially in patients with prolonged treatment and early ARDS.
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http://dx.doi.org/10.5847/wjem.j.1920-8642.2021.03.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188282PMC
January 2021

Genotypic Males Play an Important Role in the Creation of Genetic Diversity in Gynogenetic Gibel Carp.

Front Genet 2021 28;12:691923. Epub 2021 May 28.

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, The Innovative Academy of Seed Design, Hubei Hongshan Laboratory, Chinese Academy of Sciences, Wuhan, China.

Unisexual lineages are commonly considered to be short-lived in the evolutionary process as accumulation of deleterious mutations stated by Muller's ratchet. However, the gynogenetic hexaploid gibel carp () with existence over 0.5 million years has wider ecological distribution and higher genetic diversity than its sexual progenitors, which provides an ideal model to investigate the underlying mechanisms on countering Muller's ratchet in unisexual taxa. Unlike other unisexual lineages, the wild populations of gibel carp contain rare and variable proportions of males (1-26%), which are determined via two strategies including genotypic sex determination and temperature-dependent sex determination. Here, we used a maternal gibel carp from strain F to be mated with a genotypic male from strain A, a temperature-dependent male from strain A, and a male from another species common carp (), respectively. When the maternal individual was mated with the genotypic male, a variant of gynogenesis was initiated, along with male occurrence, accumulation of microchromosomes, and creation of genetic diversity in the offspring. When the maternal individual was mated with the temperature-dependent male and common carp, typical gynogenesis was initiated that all the offspring showed the same genetic information as the maternal individual. Subsequently, we found out that the genotypic male nucleus swelled and contacted with the female nucleus after fertilization although it was extruded from the female nucleus eventually, which might be associated with the genetic variation in the offspring. These results reveal that genotypic males play an important role in the creation of genetic diversity in gynogenetic gibel carp, which provides insights into the evolution of unisexual reproduction.
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http://dx.doi.org/10.3389/fgene.2021.691923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194356PMC
May 2021

Atlas of Human Skeleton Hardness Obtained Using the Micro-indentation Technique.

Orthop Surg 2021 Jun 11;13(4):1417-1422. Epub 2021 May 11.

The Third Hospital of Hebei Medical University, Shijiazhuang, China.

Objectives: Measure and systematically evaluate the distribution of microhardness in the human skeleton.

Methods: Three fresh corpses were obtained, aged 62 (male), 45 (female), and 58 years (male). Soft tissues were removed, and all axial and unilateral appendicular bones were freshly harvested. All three skeletons were examined by X-ray and computed tomography (CT) to exclude skeletal pathology. Only bones from donors with no known skeletal pathology were included in the study. Axial and unilateral appendicular skeleton bones from each of the three donors were obtained, except for ear ossicles, hyoid bone, tailbone, and 14 phalanges of the foot, for which samples were difficult to obtain. Precision bone specimens with a thickness of 3 mm, which were cut with a Buehler IsoMet 11-1280-250 low-speed diamond saw (Buehler, USA), were obtained from all important anatomic sites in a direction perpendicular to the mechanical axis of each bone. Micro-indentation (the Vickers hardness test) was performed on the surface of each specimen using a microhardness tester with a diamond indenter. Hardness value (HV) was computed for each indentation. Each bone specimen was divided into several regions of interest. Indentations were carefully made and computed. Then we analyzed the data to identify hardness distribution rules at different anatomic sites.

Results: In total, 5360 indentations were made in 1072 regions of interest in each donor. Hardness of the axial and appendicular bones were all inhomogeneous depending on the anatomic sites, but the distribution of microhardness followed certain rules. The mean hardness value ranged from 24.46 HV (HV = hardness value, kgf/mm ) for the sacrum to 53.20 HV for the shaft of the tibia. The diaphysis was harder than the metaphysis, and the proximal and distal epiphysis had lower values (8.85%- 40.39%) than the diaphysis. Among the long bone diaphyses, the tibia cortical bone (51.20 HV) was the hardest, harder than the humerus (47.25 HV), the ulna (43.26 HV), the radius (42.54 HV), and the femur (47.53 HV). However, in some anatomic sites such as the lumbar vertebra (cortical bone 32.86 HV, cancellous bone 31.25 HV), the cortical shells were sometimes not harder than the internal cancellous bones. The lumbar vertebra (32.86 HV) was harder than the cervical vertebra (28.51 HV) and the thoracic vertebra (29.01 HV).

Conclusions: The distribution of microhardness in the human skeleton follows certain rules. These distribution rules could be used to predict the mechanical properties of bone and progress in this field could provide data for the basis of a new three-dimensional printing technique, which may lead to new perspectives for custom-made implants.
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http://dx.doi.org/10.1111/os.12841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274143PMC
June 2021

Comparative transcriptomic analysis reveals an association of gibel carp fatty liver with ferroptosis pathway.

BMC Genomics 2021 May 5;22(1):328. Epub 2021 May 5.

College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, China.

Background: Fatty liver has become a main problem that causes huge economic losses in many aquaculture modes. It is a common physiological or pathological phenomenon in aquaculture, but the causes and occurring mechanism are remaining enigmatic.

Methods: Each three liver samples from the control group of allogynogenetic gibel carp with normal liver and the overfeeding group with fatty liver were collected randomly for the detailed comparison of histological structure, lipid accumulation, transcriptomic profile, latent pathway identification analysis (LPIA), marker gene expression, and hepatocyte mitochondria analyses.

Results: Compared to normal liver, larger hepatocytes and more lipid accumulation were observed in fatty liver. Transcriptomic analysis between fatty liver and normal liver showed a totally different transcriptional trajectory. GO terms and KEGG pathways analyses revealed several enriched pathways in fatty liver, such as lipid biosynthesis, degradation accumulation, peroxidation, or metabolism and redox balance activities. LPIA identified an activated ferroptosis pathway in the fatty liver. qPCR analysis confirmed that gpx4, a negative regulator of ferroptosis, was significantly downregulated while the other three positively regulated marker genes, such as acsl4, tfr1 and gcl, were upregulated in fatty liver. Moreover, the hepatocytes of fatty liver had more condensed mitochondria and some of their outer membranes were almost ruptured.

Conclusions: We reveal an association between ferroptosis and fish fatty liver for the first time, suggesting that ferroptosis might be activated in liver fatty. Therefore, the current study provides a clue for future studies on fish fatty liver problems.
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http://dx.doi.org/10.1186/s12864-021-07621-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101161PMC
May 2021

Daqu microbiota exhibits species-specific and periodic succession features in Chinese baijiu fermentation process.

Food Microbiol 2021 Sep 12;98:103766. Epub 2021 Feb 12.

Key Laboratory of Industrial Biotechnology of Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, 214122, PR China; National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi, 214122, PR China; National Engineering Research Center of Solid-State Brewing, Luzhou, 646000, PR China. Electronic address:

Daqu, a brick-shaped product spontaneously fermented under an open environment, has been regarded as the starter of fermentation, raw enzyme preparation and raw materials for baijiu production. However, its contribution in baijiu fermentation has not been fully elaborated yet. Here, the effects of daqu microbiota on baijiu fermentation were investigated under both field-scale and lab-scale conditions. In field-scale baijiu fermentation, the dominant daqu microbes (average relative abundance>10.0%), including unclassified_Leuconostocaceae, Thermoascus, and Thermomyces, tended to dominate the early stage (0-7 d). However, the rare daqu microbes (average relative abundance <0.1%, e.g., Kazachstania) tended to dominate the middle and late stages (11-40 d). In addition, some genera showed differences in species diversity between daqu and fermented grains. The average relative abundance of Lactobacillus was over 75% during baijiu fermentation, and most of them were affiliated with Lactobacillus acetotolerans, while Lactobacillus crustorum dominated the Lactobacillus OTUs in daqu. The similar patterns were also observed during lab-scale baijiu fermentation. The results of function prediction showed the enriched metabolic pathways were associated with glycolysis and long-chain fatty acid esters in baijiu fermentation. These results improved the understanding of daqu microbiota function during baijiu fermentation and provided a basic theory to support the regulation of baijiu production.
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http://dx.doi.org/10.1016/j.fm.2021.103766DOI Listing
September 2021

Apocynin prevents reduced myocardial nerve growth factor, contributing to amelioration of myocardial apoptosis and failure.

Clin Exp Pharmacol Physiol 2021 05 1;48(5):704-716. Epub 2021 Mar 1.

Schepens Eye Research Institute, Massachusetts Eye and Ear, Harvard Medical School Affiliate, Boston, MA, USA.

Reduced nerve growth factor (NGF) is associated with cardiac sympathetic nerve denervation in heart failure (HF) which is characterized by increased oxidative stress. Apocynin is considered an antioxidant agent which inhibits NADPH oxidase activity and improves reactive oxygen species scavenging. However, it is unclear whether apocynin prevents reduced myocardial NGF, leading to improvement of cardiac function in HF. In this study, we tested the hypothesis that apocynin prevents reduced myocardial NGF, contributing to amelioration of myocardial apoptosis and failure. Rabbits with myocardial infarction (MI) or sham operation were randomly assigned to receive apocynin or placebo for 4 weeks. MI rabbits exhibited left ventricular (LV) dysfunction, and elevation in oxidative stress, as evidenced by a decreased reduced-to-oxidized glutathione ratio and an increased 4-hydroxynonenal expression, and reduction in NGF and NGF receptor tyrosine kinase A (TrKA) expression in the remote non-infarcted myocardium. Apocynin treatment ameliorated LV dysfunction, reduced oxidative stress, prevented decreases in NGF and TrKA expression and reduced cardiomyocyte apoptosis after MI. In cultured H9C2 cardiomyocytes, hypoxia or hydrogen peroxide decreased NGF expression, and apocynin normalized hypoxia-induced reduction of NGF. Recombinant NGF attenuated hypoxia-induced apoptosis. Apocynin prevented hypoxia-induced apoptosis, and the suppressive effect of apocynin on apoptosis was abolished by NGF receptor TrKA inhibitor K252a. We concluded that apocynin prevented reduced myocardial NGF, leading to attenuation of cardiomyocyte apoptosis and LV remodelling and dysfunction in HF after MI. These findings suggest that strategies to prevent NGF reduction by inhibition of oxidative stress may be of value in amelioration of LV dysfunction in HF.
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http://dx.doi.org/10.1111/1440-1681.13465DOI Listing
May 2021

Metagenomics unveils microbial roles involved in metabolic network of flavor development in medium-temperature daqu starter.

Food Res Int 2021 02 24;140:110037. Epub 2020 Dec 24.

School of Biotechnology, Jiangnan University, Wuxi 214122, China; National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, China; National Engineering Research Center of Solid-State Brewing, Luzhou 646000, China. Electronic address:

As a widely used Asian starter culture, the quality of daqu can significantly affect the organoleptic characteristics of the final products, yet the microbial metabolic network involved in flavor development remains unclear. This study aims to investigate that network based on the dynamics of physicochemical properties, microbial community, and volatile compounds in medium-temperature daqu (MT-daqu) during spontaneous fermentation. Analyses using the metagenomic data set facilitated the gene repertoire overview of this ecosystem, indicating that Lactobacillales (mainly Weissella, Lactobacillus, and Pediococcus), Mucorales (mainly Lichtheimia), and Eurotiales (mainly Aspergillus, Rasamsonia and Byssochlamys) were the potential predominant populations successively responsible for the production of lytic enzymes and flavor precursors/compounds in MT-daqu. Flavor-relevant pathways were found to exist in multiple species, but only bacteria showed the potential to participate in butane-2,3-diol (e.g. Weissella, Lactobacillus, and Staphylococcus) and butanoate (Thermoactinomyces) metabolism, and only fungi were potentially involved in biosynthesis of guaiacol (Byssochlamys) and 4-vinylguaiacol (Aspergillus). Furthermore, a combined analysis revealed that the acidic thermal environment present in early phases was mainly due to the catabolic activities of Lactobacillales and Lichtheimia, which could contribute to the effective self-domestication of microbiota. The study helps elucidate the different metabolic roles of microorganisms and disclose the formation mechanism of daqu's partial functions, namely providing various aromatic substances/precursors and enzymes.
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http://dx.doi.org/10.1016/j.foodres.2020.110037DOI Listing
February 2021

Comparative mitogenome analyses uncover mitogenome features and phylogenetic implications of the subfamily Cobitinae.

BMC Genomics 2021 Jan 14;22(1):50. Epub 2021 Jan 14.

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

Background: Loaches of Cobitinae, widely distributed in Eurasian continent, have high economic, ornamental and scientific value. However, the phylogeny of Cobitinae fishes within genera or family level remains complex and controversial. Up to now, about 60 Cobitinae mitogenomes had been deposited in GenBank, but their integrated characteristics were not elaborated.

Results: In this study, we sequenced and analyzed the complete mitogenomes of a female Cobits macrostigma. Then we conducted a comparative mitogenome analysis and revealed the conserved and unique characteristics of 58 Cobitinae mitogenomes, including C. macrostigma. Cobitinae mitogenomes display highly conserved tRNA secondary structure, overlaps and non-coding intergenic spacers. In addition, distinct base compositions were observed among different genus and significantly negative linear correlation between AT% and AT-skew were found among Cobitinae, genus Cobitis and Pangio mitogenomes, respectively. A specific 3 bp insertion (GCA) in the atp8-atp6 overlap was identified as a unique feature of loaches, compared to other Cypriniformes fish. Additionally, all protein coding genes underwent a strong purifying selection. Phylogenetic analysis strongly supported the paraphyly of Cobitis and polyphyly of Misgurnus. The strict molecular clock predicted that Cobitinae might have split into northern and southern lineages in the late Eocene (42.11 Ma), furthermore, mtDNA introgression might occur (14.40 Ma) between ancestral species of Cobitis and ancestral species of Misgurnus.

Conclusions: The current study represents the first comparative mitogenomic and phylogenetic analyses within Cobitinae and provides new insights into the mitogenome features and evolution of fishes belonging to the cobitinae family.
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http://dx.doi.org/10.1186/s12864-020-07360-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809818PMC
January 2021

Functional Divergence of Multiple Duplicated Foxl2 Homeologs and Alleles in a Recurrent Polyploid Fish.

Mol Biol Evol 2021 05;38(5):1995-2013

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

Evolutionary fates of duplicated genes have been widely investigated in many polyploid plants and animals, but research is scarce in recurrent polyploids. In this study, we focused on foxl2, a central player in ovary, and elaborated the functional divergence in gibel carp (Carassius gibelio), a recurrent auto-allo-hexaploid fish. First, we identified three divergent foxl2 homeologs (Cgfoxl2a-B, Cgfoxl2b-A, and Cgfoxl2b-B), each of them possessing three highly conserved alleles and revealed their biased retention/loss. Then, their abundant sexual dimorphism and biased expression were uncovered in hypothalamic-pituitary-gonadal axis. Significantly, granulosa cells and three subpopulations of thecal cells were distinguished by cellular localization of CgFoxl2a and CgFoxl2b, and the functional roles and the involved process were traced in folliculogenesis. Finally, we successfully edited multiple foxl2 homeologs and/or alleles by using CRISPR/Cas9. Cgfoxl2a-B deficiency led to ovary development arrest or complete sex reversal, whereas complete disruption of Cgfoxl2b-A and Cgfoxl2b-B resulted in the depletion of germ cells. Taken together, the detailed cellular localization and functional differences indicate that Cgfoxl2a and Cgfoxl2b have subfunctionalized and cooperated to regulate folliculogenesis and gonad differentiation, and Cgfoxl2b has evolved a new function in oogenesis. Therefore, the current study provides a typical case of homeolog/allele diversification, retention/loss, biased expression, and sub-/neofunctionalization in the evolution of duplicated genes driven by polyploidy and subsequent diploidization from the recurrent polyploid fish.
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http://dx.doi.org/10.1093/molbev/msab002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097289PMC
May 2021

Upregulation of the PPAR signaling pathway and accumulation of lipids are related to the morphological and structural transformation of the dragon-eye goldfish eye.

Sci China Life Sci 2021 Jul 5;64(7):1031-1049. Epub 2021 Jan 5.

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

Goldfish comprise around 300 different strains with drastically altered and aesthetical morphologies making them suitable models for evolutionary developmental biology. The dragon-eye strain is characterized by protruding eyes (analogous to those of Chinese dragons). Although the strain has been selected for about 400 years, the mechanism of its eye development remains unclear. In this study, a stable dragon-eye goldfish strain with a clear genetic background was rapidly established and studied. We found that upregulation of the PPAR signaling pathway accompanied by an increase in lipid accumulation might trigger the morphological and structural transformation of the eye in dragon-eye goldfish. At the developmental stage of proptosis (eye protrusion), downregulation of the phototransduction pathway was consistent with the structural defects and myopia of the dragon-eye strain. With the impairment of retinal development, cytokine-induced inflammation was activated, especially after proptosis, similar to the pathologic symptoms of many human ocular diseases. In addition, differentially expressed transcription factors were significantly enriched in the PAX and homeobox families, two well-known transcription factor families involved in eye development. Therefore, our findings reveal the dynamic changes in key pathways during eye development in dragon-eye goldfish, and provide insights into the molecular mechanisms underlying drastically altered eyes in goldfish and human ocular disease.
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http://dx.doi.org/10.1007/s11427-020-1814-1DOI Listing
July 2021

Azospirillum oleiclasticum sp. nov, a nitrogen-fixing and heavy oil degrading bacterium isolated from an oil production mixture of Yumen Oilfield.

Syst Appl Microbiol 2021 Jan 28;44(1):126171. Epub 2020 Nov 28.

China General Microbiological Culture Collection Center, State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China. Electronic address:

Two nitrogen-fixing and heavy oil degrading strains, designated RWY-5-1-1 and ROY-1-1-2, were isolated from an oil production mixture from Yumen Oilfield in China. The 16S rRNA gene sequence showed they belong to Azospirillum and have less than 96.1 % pairwise similarity with each species in this genus. The average nucleotide identity and digital DNA-DNA hybridization values between them and other type strains of Azospirillum species were less than 75.69 % and 22.0 %, respectively, both below the species delineation threshold. Pan-genomic analysis showed that the novel isolate RWY-5-1-1 shared 2145 core gene families with other type strains in Azospirillum, and the number of strain-specific gene families was 1623, almost two times more than the number known from other species. Furthermore, genes related to nitrogenase, hydrocarbon degradation and biosurfactant production were found in the isolates' genomes. Also, this strain was capable of reducing acetylene to ethylene at a rate of 22nmol ethylene h (10 cells) and degrading heavy oil at a rate of 36.2 %. The major fatty acids and polar lipids were summed feature 8 (Cω7c/Cω6c), and phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylcholine. Furthermore, a combination of phenotypic, chemotaxonomic, phylogenetic and genotypic data clearly indicated that strains RWY-5-1-1 and ROY-1-1-2 represent a novel species, for which the name Azospirillum oleiclasticum sp. nov. is proposed. The type strain is RWY-5-1-1 (=CGMCC 1.13426 =KCTC 72259 ). Azospirillum novel strains with the ability of heavy oil degradation associated with the promotion of plant growth has never been reported to date.
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http://dx.doi.org/10.1016/j.syapm.2020.126171DOI Listing
January 2021

Qualitative analysis on chemical constituents from different polarity extracted fractions of the pulp and peel of ginger rhizomes by ultra-high-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry.

Rapid Commun Mass Spectrom 2021 Apr;35(8):e9029

School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, Henan, China.

Rationale: Ginger pulp is the dried rhizome scraped off the skin which originates from Zingiber officinale Rosc., a Zingiberaceae plant. Ginger peel is the dried rhizome skin of Zingiber officinale Rosc. (Zingiberaceae). The present work aims to investigate the different chemical constituents that are related to the medicinal properties of the ginger pulp and ginger peel.

Methods: A rapid ultra-high-performance liquid chromatography/electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC/ESI-QTOF/MS) method was developed for qualitative analysis of the constituents in different polarity extracted fractions of the pulp and peel of ginger rhizomes.

Results: A total of 83 compounds were identified from the pulp and peel of ginger rhizomes, including 36 diarylheptanoids, 25 gingerols and 22 other compounds. Nine of these were new compounds. In total, 46, 27, 65 and 51 compounds were identified from the crude extract, petroleum ether, ethyl acetate, and n-butanol fractions of the ginger pulp, respectively, and 60, 30, 70 and 62 compounds were identified from the crude extract, petroleum ether, ethyl acetate, n-butanol fractions of the ginger peel, respectively. Each identified compound is marked on the corresponding chromatogram.

Conclusions: The integrated method is sensitive and reliable for searching the different chemical constituents from different polarity extracted fractions of the ginger pulp and ginger peel. This work may provide a significant contribution to research into the medicinal properties of the ginger pulp and ginger peel.
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http://dx.doi.org/10.1002/rcm.9029DOI Listing
April 2021

Modulating microbiota metabolism via bioaugmentation with Lactobacillus casei and Acetobacter pasteurianus to enhance acetoin accumulation during cereal vinegar fermentation.

Food Res Int 2020 12 22;138(Pt A):109737. Epub 2020 Sep 22.

Key Laboratory of Industrial Biotechnology of Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, PR China; National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi 214122, PR China; National Engineering Research Center of Solid-State Brewing, Luzhou 646000, PR China. Electronic address:

Acetoin, giving a creamy yogurt aroma and buttery taste, exists in cereal vinegar as an important flavor substance and is mainly produced by the metabolism of Lactobacillus and Acetobacter during multispecies solid-state acetic acid fermentation. However, the impacts of Lactobacillus-Acetobacter interactions on acetoin accumulation and the microbial metabolism during acetic acid fermentation are not completely clear. Here, six strains isolated from vinegar fermentation culture and associated with acetoin metabolism, namely, Lactobacillus reuteri L-0, L. buchneri F2-6, L. brevis 4-20, L. fermentum M10-7, L. casei M1-6 and Acetobacter pasteurianus G3-2, were selected for microbial growth and metabolism analysis in monoculture and coculture fermentations. Lactobacillus sp. and A. pasteurianus G3-2 respectively utilized glucose and ethanol preferentially. In monocultures, L. casei M1-6 (183.7 mg/L) and A. pasteurianus G3-2 (121.0 mg/L) showed better acetoin-producing capacity than the others. In the bicultures with Lactobacillus sp. and A. pasteurianus G3-2, biomass analysis in the stationary phase demonstrated that significant growth depressions of Lactobacillus sp. occurred compared with monocultures, possibly due to intolerance to acetic acid produced by A. pasteurianus G3-2. Synergistic effect between Lactobacillus sp. and A. pasteurianus G3-2 on enhanced acetoin accumulation was identified, however, cocultures of two Lactobacillus strains could not apparently facilitate acetoin accumulation. Coculture of L. casei M1-6 and A. pasteurianus G3-2 showed the best performance in acetoin production amongst all mono-, bi- and triculture combinations, and the yield of acetoin increased from 1827.7 to 7529.8 mg/L following optimization of culture conditions. Moreover, the interactions of L. casei M1-6 and A. pasteurianus G3-2 regulated the global metabolism of vinegar microbiota during fermentation through performing in situ bioaugmentation, which could accelerate the production of acetic acid, lactic acid, acetoin, ethyl acetate, ethyl lactate, ligustrazine and other important flavoring substances. This work provides a promising strategy for the production of acetoin-rich vinegar through Lactobacillus sp.-A. pasteurianus joint bioaugmentation.
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http://dx.doi.org/10.1016/j.foodres.2020.109737DOI Listing
December 2020

EGCG targeting Notch to attenuate renal fibrosis inhibition of TGFβ/Smad3 signaling pathway activation in streptozotocin-induced diabetic mice.

Food Funct 2020 Nov;11(11):9686-9695

Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming, 650201, China.

Renal fibrosis is a characteristic of diabetic nephropathy, which is a serious complication of diabetes. It has been reported that (-)-epigallocatechin gallate (EGCG) attenuates renal fibrosis. However, the molecular mechanism of regulation by EGCG in this process remains unclear. Previous studies showed that abnormal activation of Notch signaling contributes to the development of renal fibrosis. Previous studies have demonstrated that EGCG attenuates Notch1 expression. In this study, we found that the levels of fibronectin and Notch1 expression were decreased in human embryonic kidney cells after treatment with EGCG. We also observed that the type II transforming growth factor beta receptor (TGFβRII) and Smad3 pathway were inhibited in kidney cells by treatment with EGCG. In the diabetic kidney, we found that the activation of Notch signaling was attenuated by administration of EGCG. Moreover, TGFβRII and Smad3 phosphorylation could be inhibited by treatment with EGCG in the kidney. These results indicated that EGCG may improve renal fibrosis by targeting Notch via inhibition of the TGFβ/Smad3 pathway in diabetic mice. Our findings provide insight into the therapeutic strategy for diabetes-induced renal fibrosis, and suggest EGCG to be a novel potential medicine for the treatment of chronic kidney disease in patients with diabetes.
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http://dx.doi.org/10.1039/d0fo01542cDOI Listing
November 2020

Dynamic and Differential Expression of Duplicated Cxcr4/Cxcl12 Genes Facilitates Antiviral Response in Hexaploid Gibel Carp.

Front Immunol 2020 11;11:2176. Epub 2020 Sep 11.

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, The Innovation Academy of Seed Design, Chinese Academy of Sciences, Graduate University of the Chinese Academy of Sciences, Wuhan, China.

Chemokine receptor and its ligand have evolved two paralogs in the teleost lineage. In this study, we have identified four duplicated and genes from hexaploid gibel carp, , respectively. s and s were dynamically and differentially expressed in immune-related tissues, and significantly up-regulated in head kidney and spleen after crucian carp herpesvirus (HV) infection. Blocking Cxcr4/Cxcl12 axis by injecting AMD3100 brought more severe bleeding symptom and lower survival rate in HV-infected fish. AMD3100 treatment also suppressed the up-regulation of key antiviral genes in head kidney and spleen, and resulted in more acute replication of HV in . Consistently, the similar suppression of up-regulated expression of key antiviral genes were also observed in CAB cells treated by AMD3100 after poly(I:C) stimulation. Finally, MAPK3 and JAK/STAT were identified as the possible pathways that Cxcr4s and Cxcl12s participate in to promote the antiviral response in .
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http://dx.doi.org/10.3389/fimmu.2020.02176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7516010PMC
April 2021

Two new dammarane-type triterpenoids from the green walnut husks of Maxim.

Nat Prod Res 2020 Sep 21:1-8. Epub 2020 Sep 21.

College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, China.

Two new dammarane-type triterpenoids, dammar-3,12(),20()-triol-12,32();20,32-diepoxy-25-methy-25-en-tridecacyclic ether () and (23)-12,20(),25(),26-tetrahydroxydammar-23-en-3-one () were isolated from the green walnut husks of Maxim together with six known compounds. Their structures were elucidated through extensive spectroscopic analyses and by comparison with the literature, and the cytotoxic activities of these compounds were evaluated.
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http://dx.doi.org/10.1080/14786419.2020.1818233DOI Listing
September 2020

Deciphering the d-/l-lactate-producing microbiota and manipulating their accumulation during solid-state fermentation of cereal vinegar.

Food Microbiol 2020 Dec 12;92:103559. Epub 2020 Jun 12.

Key Laboratory of Industrial Biotechnology of Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, 214122, PR China; National Engineering Laboratory for Cereal Fermentation Technology, Jiangnan University, Wuxi, 214122, PR China; National Engineering Research Center of Solid-State Brewing, Luzhou, 646000, PR China. Electronic address:

Symphony orchestra of multi-microorganisms characterizes the solid-state acetic acid fermentation process of Chinese cereal vinegars. Lactate is the predominant non-volatile acid and plays indispensable roles in flavor formation. This study investigated the microbial consortia driving the metabolism of D-/l-lactate during fermentation. Sequencing analysis based on D-/l-lactate dehydrogenase genes demonstrated that Lactobacillus (relative abundance: > 95%) dominated the production of both d-lactate and l-lactate, showing species-specific features between the two types. Lactobacillus helveticus (>65%) and L. reuteri (~80%) respectively dominated l- and d-lactate-producing communities. D-/l-lactate production and utilization capabilities of eight predominant Lactobacillus strains were determined by culture-dependent approach. Subsequently, D-/l-lactate producer L. plantarum M10-1 (d:l ≈ 1:1), l-lactate producer L. casei 21M3-1 (D:L ≈ 0.2:9.8) and D-/l-lactate utilizer Acetobacter pasteurianus G3-2 were selected to modulate the metabolic flux of D-/l-lactate of microbial consortia. The production ratio of D-/l-lactate was correspondingly shifted coupling with microbial consortia changes. Bioaugmentation with L.casei 21M3-1 merely enhanced l-lactate production, displaying ~4-fold elevation at the end of fermentation. Addition of L.plantarum M10-1 twice increased both D- and l-lactate production, while A. pasteurianus G3-2 decreased the content of D-/l-isomer. Our results provided an alternative strategy to specifically manipulate the metabolic flux within microbial consortia of certain ecological niches.
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http://dx.doi.org/10.1016/j.fm.2020.103559DOI Listing
December 2020

Clinical Indications of Recombinant Human Erythropoietin in a Single Center: A 10-Year Retrospective Study.

Front Pharmacol 2020 24;11:1110. Epub 2020 Jul 24.

Department of Transfusion, The First Medical Center of Chinese PLA General Hospital, Beijing, China.

In the 1980s, recombinant human erythropoietin (rhEPO) began to be used in clinical practice. In this study, the clinical application of rhEPO from single-center in recent ten years was reviewed, and the scope of indications and clinical efficacy were evaluated. The medical records of 35829 in-patients who were treated with rhEPO in the first Medical Center of the Chinese PLA General Hospital from 2009 to 2018 were collected. According to the scope of indications approved by CFDA (China Food and Drug Administration), curative effect and off-label of rhEPO were analyzed. Of the 35829 patients, 19013 (53.1%) were male and 16816 (46.9%) were female, with an average age of (52.1 ± 18.6) years. The usage of rhEPO is increasing year by year. The overall effective rate was 53.1%. The number of patients who met the indications accounted for 67.2%, and the effective rate patients with indications and Off-label were 48.8% and 50.7%. Among the patients with irregular use of rhEPO perioperative imperfect laboratory examination patients accounted for the highest proportion (7.1%). The volume of RBC(s) (red blood cell(s)) transfusion in patients with rhEPO was significantly less than that in patients without rhEPO (p<0.05). The use of rhEPO Off-label is very common and has a certain curative effect. It can be used as evidence support for the update of the scope of indications. In addition, There are still irregular use of rhEPO and transfusion in clinic. The unreasonable use of rhEPO and transfusion should be further standardized to ensure the safety and effectiveness.
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http://dx.doi.org/10.3389/fphar.2020.01110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7397815PMC
July 2020

Fasudil inhibits the activation of microglia and astrocytes of transgenic Alzheimer's disease mice via the downregulation of TLR4/Myd88/NF-κB pathway.

J Neuroimmunol 2020 Jun 23;346:577284. Epub 2020 Jun 23.

Institute of Brain Science, Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases, Shanxi Datong University, Datong 037009, China; Research Center of Neurobiology, The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Shanxi University of Chinese Medicine, Jinzhong 030619, China; Dept. of Neurology, First Affiliated Hospital, Shanxi Medical University, Taiyuan 030001, China. Electronic address:

Emerging evidence suggests an association of Alzheimer's Disease (AD) with microglial and astrocytic dysregulation. Recent studies have proposed that activated microglia can transform astrocytes to a neurotoxic A1 phenotype, which has been shown to be involved in the promotion of neuronal damage in several neurodegenerative diseases, including AD. In the present study, we observed an obvious microglial activation and A1-specific astrocyte response in the brain tissue of APP/PS1 Tg mice. Fasudil treatment improved the cognitive deficits of APP/PS1 Tg mice, inhibited microglial activation and promoted their transformation to an anti-inflammatory phenotype, and further shifted astrocytes from an A1 to an A2 phenotype. Our experiments suggest Fasudil exerted these functions by inhibing the expression of TLR4, MyD88, and NF-κB, which are key mediators of inflammation. Using in vitro experiments, we further validated in vivo findings. Our cell experiments indicated that Fasudil induces a shift of inflammatory microglia towards an anti-inflammatory phenotype. LPS-induced microglia-conditioned medium promotes A1 astrocytic polarization, but Fasudil treatment resulted in a direct transformation of A1 astrocytes to A2. To summarize, our results show that Fasudil inhibits the neurotoxic activation of microglia and shifts astrocytes towards a neuroprotective A2 phenotype, representing a promising candidate for AD treatment.
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http://dx.doi.org/10.1016/j.jneuroim.2020.577284DOI Listing
June 2020

Regain of sex determination system and sexual reproduction ability in a synthetic octoploid male fish.

Sci China Life Sci 2021 Jan 10;64(1):77-87. Epub 2020 Jun 10.

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

Polyploids in vertebrates are generally associated with unisexual reproduction, but the direct consequences of polyploidy on sex determination system and reproduction mode remain unknown. Here, we synthesized a group of artificial octoploids between unisexual gynogenetic hexaploid Carassius gibelio and sexual tetraploid Carassius auratus. The synthetic octoploids were revealed to have more than 200 chromosomes, in which 50 chromosomes including the X/Y sex determination system were identified to transfer from sexual tetraploid C. auratus into the unisexual gynogenetic hexaploid C. gibelio. Significantly, a few synthetic octoploid males were found to be fertile, and one octoploid male was confirmed to regain sexual reproduction ability, which exhibits characteristics that are the same to sexual reproduction tetraploid males, such as 1:1 sex ratio occurrence, meiosis completion and euploid sperm formation in spermatogenesis, as well as normal embryo development and gene expression pattern during embryogenesis. Therefore, the current finding provides a unique case to explore the effect of sex determination system incorporation on reproduction mode transition from unisexual gynogenesis to sexual reproduction along with genome synthesis of recurrent polyploidy in vertebrates.
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http://dx.doi.org/10.1007/s11427-020-1694-7DOI Listing
January 2021

Efficacy of mesenchymal stem cell therapy for sepsis: a meta-analysis of preclinical studies.

Stem Cell Res Ther 2020 06 3;11(1):214. Epub 2020 Jun 3.

General ICU, Henan Key Laboratory of Critical Care Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou Key Laboratory of Sepsis, Zhengzhou, 450052, China.

Background: Multiple studies have reported that mesenchymal stem cell (MSC) therapy has beneficial effects in experimental models of sepsis. However, this finding remains inconclusive. This study was performed to systematically determine the connection between MSC therapy and mortality in sepsis animal models by pooling and analyzing data from newly published studies.

Methods: A detailed search of related studies from 2009 to 2019 was conducted in four databases, including MEDLINE, EMBASE, Cochrane Library, and Web of Science. After browsing and filtering out articles that met the inclusion criteria for statistical analysis, the inverse variance method of the fixed effects model was used to calculate the pooled odds ratios (ORs) and their 95% confidence intervals (CIs).

Results: Twenty-nine animal studies, including 1266 animals, were identified. None of the studies was judged to have a low risk of bias. The meta-analysis demonstrated that MSC therapy was related to a significantly lower mortality rate (OR 0.29, 95% CI 0.22-0.38, P < 0.001). Subgroup analyses performed based on the MSC injection dose (< 1.0 × 10 cells, OR = 0.33, 95% CI 0.20-0.56, P < 0.001; 1.0 × 10 cells, OR = 0.24, 95% CI 0.16-0.35, P < 0.001) and injection time (< 1 h, OR = 0.24, 95% CI 0.13-0.45, P < 0.001; 1 h, OR = 0.28, 95% CI 0.17-0.46, P < 0.001) demonstrated that treatment with MSCs significantly reduced the mortality rate of animals with sepsis.

Conclusion: This up-to-date meta-analysis showed a connection between MSC therapy and lower mortality in sepsis animal models, supporting the potential therapeutic effect of MSC treatment in future clinical trials. The results in this study contradict a previous meta-analysis with regards to the ideal dose of MSC therapy. Thus, further research is required to support these findings.
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http://dx.doi.org/10.1186/s13287-020-01730-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268531PMC
June 2020

microRNA-146b promotes neuroblastoma cell growth through targeting NUMB.

Exp Ther Med 2020 Jun 23;19(6):3531-3536. Epub 2020 Mar 23.

Department of Pathology, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China.

Accumulating evidence has demonstrated that the abnormal expression of microRNA (miRNA/miR) serves a crucial role in the development of numerous types of human cancer, including neuroblastoma (NB). The present study aimed to investigate the expression levels and biological roles of miR-146b in NB. miR-146b expression levels in NB cell lines and human umbilical vein endothelial cells (HUVECs) were analyzed using reverse transcription-quantitative PCR, and the regulatory effects of miR-146b on NB cell proliferation, invasion and apoptosis were investigated using CCK-8 assay, transwell invasion assay and flow cytometry. In addition, bioinformatics analysis, western blotting and dual-luciferase reporter assays were used to determine whether NUMB was a target gene of miR-146b. miR-146b expression levels were increased in NB cell lines compared with HUVECs. The knockdown of miR-146b using a miR-146b inhibitor significantly inhibited NB cell proliferation and invasion, but promoted cell apoptosis . Furthermore, it was revealed that miR-146b promoted NB cell proliferation through targeting NUMB. In conclusion, miR-146b was suggested to serve as an oncogene, at least in part, through directly targeting NUMB, which indicated that miR-146b may be a potential therapeutic target for NB treatment.
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http://dx.doi.org/10.3892/etm.2020.8623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7185190PMC
June 2020

Pseudomonas Saliphila sp. nov., a Bacterium Isolated from Oil-Well Production Water in Qinghai Oilfield of China.

Curr Microbiol 2020 Aug 18;77(8):1924-1931. Epub 2020 Apr 18.

Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education & Talent Base of Microbiology and Human Health of Guizhou Province, School of Basic Medical Sciences, Guizhou Medical University, Guiyang, Guizhou, 550025, People's Republic of China.

Strain 16W4-4-3 was isolated from the oil-well production water in Qinghai Oilfield, China. Cells were Gram-stain-negative, rod-shaped, catalase- and oxidase-positive, facultatively anaerobic and motile by single polar flagellum. The 16S rRNA gene sequences of strain 16W4-4-3 showed the highest similarities with Pseudomonas profundi M5 (98.8%), P. pelagia CL-AP6 (98.0%), P. salina XCD-X85 (97.7%), and P. sabulinigri J64 (97.5%). The phylogenetic trees based on multilocus sequence analyses with concatenating 16S rRNA, gyrB, rpoD and rpoB genes suggested that this strain should be affiliated to the genus Pseudomonas but remotely related from other species. In addition, whole genome analyses revealed that the digital DNA-DNA hybridization values and average nucleotide identities of strain 16W4-4-3 against its close relatives were all below 28.8% and 86.5%, respectively. Furthermore, the isolate had totally different whole cell protein profile as compared to those of other species. Major fatty acids were summed feature 8 (Cω7c and/or Cω6c), C, summed feature 3 (Cω7c and/or Cω6c) and Ccyclo. Major isoprenoid quinone was ubiquinone (Q-9), and major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylethanolamine. The DNA G + C content was 58.5 mol%. Therefore, phenotypic, phylogenetic, genomic, chemotaxonomic, and proteomic traits showed that the isolate represented a novel species of the genus Pseudomonas, the name Pseudomonas saliphila sp. nov. is proposed. Type strain is 16W4-4-3 (= CGMCC 1.13350 = KCTC 72619).
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http://dx.doi.org/10.1007/s00284-020-01986-5DOI Listing
August 2020
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