The banana Fusarium wilt (BFW) caused by Fusarium oxysporum f. sp. cubense tropical race4 (FocTR4) is difficult to control worldwide, which causes a huge economic losse to banana industry. The purpose of this study was to screen Trichoderma strains with antagonistic activity against FocTR4, to isolate and purify the active compound from the fermentation broth, so as to provide important biocontrol strains and active compound resources. In this work, Trichoderma strains were isolated and screened from the rhizosphere soil of crops, and the strains capable of efficiently inhibiting FocTR4 were screened by plate confrontation, and further confirmed by testing inhibition for the conidial germination and mycelial growth of FocTR4. The phylogenetic tree clarified the taxonomic status of the biocontrol strains. Moreover, the active components in the fermentation broth of the strains were separated and purified by column chromatography, the structure of the most active component was analyzed by nuclear magnetic resonance spectroscopy (NMR), the BFW control effect was tested by pot experiments. We obtained a strain JSHA-CD-1003 with antagonistic activity against FocTR4, and the inhibition rate from plate confrontation was 60.6%. The fermentation broth of JSHA-CD-1003 completely inhibited the germination of FocTR4 conidia within 24 hours. The inhibition rate of FocTR4 hyphae growth was 52.6% within 7 d. A phylogenetic tree was constructed based on the ITS and tef1-α gene tandem sequences, and JSHA-CD-1003 was identified as Trichoderma brevicompactum. Purification and NMR identification showed that the single active compound was trichodermin, and the minimum inhibitory concentration (MIC) was 25 μg/mL. Pot experiments showed that the fermentation broth of strain JSHA-CD-1003 was effective against BFW. The control rate of leaf yellowing was 47.4%, and the rate of bulb browning was 52.0%. Therefore, JSHA-CD-1003 effectively inhibited FocTR4 conidial germination and mycelium growth through producing trichodermin, and showed biocontrol effect on banana wilt caused by FocTR4, thus is a potential biocontrol strain.
Fusarium ; Musa ; Phylogeny ; Trichodermin ; Hypocreales

Isolated vertigo due to vascular mechanisms manifests as vertigo, dizziness or imbalance only. Due to the lack of focal neurological symptoms or signs, it is often misdiagnosed as peripheral vestibular disease, resulting in serious adverse consequences. This article reviews the lesion location, cerebrovascular basis, clinical evaluation, and imaging examination of isolated vertigo caused by vascular mechanisms.

Objective:To evaluate the status of T, B and NK lymphocytes in peripheral blood of patients with chronic hepatitis B virus(HBV) infection and low-level viremia after nucleos(t)ide analogue (NA) treatment and to provide ideas for solving low-level viremia.Methods:This retrospective study involved 344 patients with chronic HBV infection who had been treated with NAs. They were divided into two groups: low-level viremia group (LLV group) and complete virological response group (CVR group). Clinical data including basic information, biochemistry and coagulation test results, HBV DNA, peripheral blood lymphocyte counts, PD1 and CD28 expression by T lymphocytes, and perforin and granzyme B expression by NK lymphocytes were collected and compared between the two groups. Propensity matching analysis was performed to verify the accuracy of the results.Results:Among the 344 cases, 162 were in the LLV group and 182 in the CVR group. There were no significant differences in disease diagnosis, alanine aminotransferase (ALT), aspartate aminotransferase (AST) or albumin (ALB) level between the two groups ( P>0.05), but the differences in gender and age were statistically significant ( P<0.05). The differences in the counts and percentages of peripheral blood CD3 +, CD4 + and CD8 + T lymphocyte and CD4 + /CD8 + ratios between the two groups were not statistically significant ( P>0.05), but the expression of PD1 and CD28 by peripheral blood CD3 +, CD4 + and CD8 + T lymphocytes was higher in the LLV group than in the CVR group ( P<0.05). The count of peripheral blood CD19 + B lymphocytes in the LLV group was higher than that in the CVR group ( P>0.05), and the percentage of peripheral blood CD19 + B lymphocytes was also higher in the LLV group ( P<0.05). The count of peripheral blood CD16 + CD56 + NK lymphocytes and the expression of perforin in the LLV group were lower than those in the CVR group ( P>0.05). The percentage of peripheral blood CD16 + CD56 + NK lymphocytes and the expression of granzyme B in the LLV group were lower than those in the CVR group ( P<0.05). After propensity score matching, 108 cases in the LLV group and 108 cases in the CVR group showed no significant differences in basic information ( P>0.05); the percentage of CD4 + T lymphocytes and CD4 + /CD8 + ratio in peripheral blood T lymphocyte subsets were higher in the LLV group than in the CVR group, while the percentage of CD8 + lymphocytes was lower in the LLV group ( P<0.05); the expression of PD1 and CD28 by CD3 +, CD4 + and CD8 + T lymphocytes remained higher in the LLV group ( P<0.05); the differences in the counts and percentages of peripheral blood CD19 + B lymphocytes as well as CD16 + CD56 + NK lymphocytes between the two groups were not statistically significant ( P>0.05); no significant difference in the expression of perforin by CD16 + CD56 + NK lymphocytes was found between the two groups ( P>0.05), and the expression of granzyme B remained lower in the LLV group ( P<0.05). Conclusions:Abnormal number and function of T lymphocytes and decreased function of NK lymphocytes might be related to the development of LLV in patients with chronic HBV infection after treatment. Therefore, in addition to adjusting NAs, targeting of T and NK lymphocytes might also be a feasible measure for future LLV treatment.

Objective:To explore potential role and mechanism of N6-methyladenine(m6A)RNA methylation regulators in prognosis and tumor immune microenvironment of cervical cancer.Methods:Clinical and survival data as well as RNA sequencing data were acquired from TCGA and GEO database.Expressions and correlation among m6A RNA methylation regulators were analyzed by bioinformatics analysis and tissue validation experiments.LASSO Cox regression analysis was used to generate a prognostic risk sig-nature based on m6A regulators.Two m6A-modification patterns were identified based on m6A regulators and their abundance of im-mune cell inflitration were analyzed by ssGSEA.Results:Compared with normal tissues,RBM15,IGF2BP2,IGF2BP3,FMR1,YTHDF1,METTL3 and YTHDF2 expressions were significantly up-regulated in cervical cancer tissues,while ZC3H13,METTL4,YTHDC1,FTO and ALKBH3 expressions were significantly down-regulated.Five m6A regulators HNRNPC,LRPPRC,METTL3,ELAVL1 and FMR1 were selected to establish prognostic risk signature,whose expressions in cervical cancer were verified by HPA database and qRT-PCR with good predictive value,and could be used as independent poor prognostic factor(AUC=0.734).Based on expressions of 25 m6A regulators,two m6A modification patterns m6Acluster A and m6Acluster B were determined.There were differ-ences between two groups in biological functions,signal pathways and immune cells infiltration levels in tumor microenvironment.Conclusion:m6A RNA methylation regulators are closely related to prognosis and immune infiltration of cervical cancer,which provides guidance for immunotherapy strategy.

Acetaminophen (APAP) overdose is a major cause of liver injury. Neural precursor cell expressed developmentally downregulated 4-1 (NEDD4-1) is an E3 ubiquitin ligase that has been implicated in the pathogenesis of numerous liver diseases; however, its role in APAP-induced liver injury (AILI) is unclear. Thus, this study aimed to investigate the role of NEDD4-1 in the pathogenesis of AILI. We found that NEDD4-1 was dramatically downregulated in response to APAP treatment in mouse livers and isolated mouse hepatocytes. Hepatocyte-specific NEDD4-1 knockout exacerbated APAP-induced mitochondrial damage and the resultant hepatocyte necrosis and liver injury, while hepatocyte-specific NEDD4-1 overexpression mitigated these pathological events both in vivo and in vitro. Additionally, hepatocyte NEDD4-1 deficiency led to marked accumulation of voltage-dependent anion channel 1 (VDAC1) and increased VDAC1 oligomerization. Furthermore, VDAC1 knockdown alleviated AILI and weakened the exacerbation of AILI caused by hepatocyte NEDD4-1 deficiency. Mechanistically, NEDD4-1 was found to interact with the PPTY motif of VDAC1 through its WW domain and regulate K48-linked ubiquitination and degradation of VDAC1. Our present study indicates that NEDD4-1 is a suppressor of AILI and functions by regulating the degradation of VDAC1.

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis and insulin resistance and there are currently no approved drugs for its treatment. Hyperactivation of mTOR complex 1 (mTORC1) and subsequent impairment of the transcription factor EB (TFEB)-mediated autophagy-lysosomal pathway (ALP) are implicated in the development of NAFLD. Accordingly, agents that augment hepatic TFEB transcriptional activity may have therapeutic potential against NAFLD. The objective of this study was to investigate the effects of nuciferine, a major active component from lotus leaf, on NAFLD and its underlying mechanism of action. Here we show that nuciferine activated ALP and alleviated steatosis, insulin resistance in the livers of NAFLD mice and palmitic acid-challenged hepatocytes in a TFEB-dependent manner. Mechanistic investigation revealed that nuciferine interacts with the Ragulator subunit hepatitis B X-interacting protein and impairs the interaction of the Ragulator complex with Rag GTPases, thereby suppressing lysosomal localization and activity of mTORC1, which activates TFEB-mediated ALP and further ameliorates hepatic steatosis and insulin resistance. Our present results indicate that nuciferine may be a potential agent for treating NAFLD and that regulation of the mTORC1-TFEB-ALP axis could represent a novel pharmacological strategy to combat NAFLD.

Objective:To evaluate and compare the early and long-term outcomes of rheumatic patients who underwent left-side heart valve replacement with concomitant tricuspid valve replacement, and analyze the difference of early mortality and long-term survival rate between mild pulmonary artery systolic pressure (PASP) and moderate to severe PASP patients.Methods:From January 2009 to December 2018, 79 cases of patients were reviewed and summarized. The mean age before operation was (45.7±7.8) years old. These patients were divided into mild PASP group(<50 mmHg, 38 cases) (1 mmHg=0.133 kPa) and moderate-severe PASP group (>50 mmHg, 41 cases) . Kaplan- Meier method was used to estimate the overall long-term survival rate and the incidence of complications, and to compare the long-term survival rate of patients with mild and moderate -severe PASP elevation. Results:The mortality rate of early postoperative patients was 8.9% (7/79). The causes of death included: low cardiac output syndrome in 3 cases, multiple organ failure caused by pulmonary infection in 2 cases, acute renal insufficiency in 1 case, sudden cardiac arrest in 1 case. Although the mortality rate of early moderate-severe PASP group (12.2% vs. 5.3%) was higher than that of mild PASP group, there was no significant difference ( P>0.05). The mean follow-up time was (51.8±31.7) months (3-115 months). Kaplan- Meier method was used to estimate the 10-year survival rate, the rate of avoiding thrombosis, the rate of avoiding serious bleeding event and the rate of avoiding reoperation, which were (67.2±10.6)%, (85.7±6.2)%, (83.4± 6.9)% and (93.7 ± 3.7)%, respectively. Although the long-term survival rate of mild PASP (78.0±10.6) % was higher than that of moderate-severe PASP (62.8 ± 13.4) %, there was no significant difference ( P>0.05). Conclusion:The early mortality rate of rheumatic patients who underwent left-side heart valve replacement with concomitant tricuspid valve replacement is still relatively high. The recurrent heart failure is the major causes of long-term death.

Single-cell RNA sequencing (scRNA-seq) is generally used for profiling transcriptome of individual cells.The droplet-based 10X Genomics Chromium (10X) approach and the plate-based Smart-seq2 full-length method are two frequently used scRNA-seq platforms,yet there are only a few thorough and systematic comparisons of their advantages and limitations.Here,by directly comparing the scRNA-seq data generated by these two platforms from the same samples of CD45-cells,we systematically evaluated their features using a wide spectrum of analyses.Smart-seq2 detected more genes in a cell,especially low abundance transcripts as well as alterna-tively spliced transcripts,but captured higher proportion of mitochondrial genes.The composite of Smart-seq2 data also resembled bulk RNA-seq data more.For 10X-based data,we observed higher noise for mRNAs with low expression levels.Approximately 10％-30％ of all detected tran-scripts by both platforms were from non-coding genes,with long non-coding RNAs (lncRNAs)accounting for a higher proportion in 10X.10X-based data displayed more severe dropout prob-lem,especially for genes with lower expression levels.However,10X-data can detect rare cell types given its ability to cover a large number of cells.In addition,each platform detected distinct groups of differentially expressed genes between cell clusters,indicating the different characteristics of these technologies.Our study promotes better understanding of these two platforms and offers the basis for an informed choice of these widely used technologies.

Chinese medicine-probiotics compound microecological preparation for livestock and poultry is a new type of animal microecological preparations that combine probiotics with traditional Chinese medicine by modern fermentation technology. It could exert synergistic effects of both probiotics and traditional Chinese medicine, with the purpose of improving immune function of livestock and poultry and protect their health. By investigating the literature on probiotics and Chinese medicine microecological preparations in recent years, we summarized the background and strain characteristics of Chinese medicine-probiotics compound microecological preparations (CPCMP) for livestock and poultry in this paper. Furthermore, we elaborated the mechanisms of CPCMP for livestock and poultry and introduced the application of CPCMP in livestock and poultry breeding. Finally, we pointed out the existing problems and proposed the suggestions on the development of CPCMP. This review is expected to provide reference and basis for further research on CPCMP for livestock and poultry.
Animals ; Fermentation ; Livestock ; Medicine, Chinese Traditional ; Poultry ; Probiotics

Objective To investigate the characteristics of adenovirus infection in hospitalized children with respiratory tract infection in Shenzhen.Methods Nasopharyngeal swabs obtained from 25 602 children hospitalized with respiratory tract infections in Shenzhen Children's Hospital during 2014 to 2016,were tested for adenovirus with direct immunofluorescence assay.The detection rate of adenovirus and diagnosis in hospitalized children with respiratory tract infection were analyzed.Results The total adenovirus detection rate was 2.97 ％ in 25 602 samples,with a male to female ratio of 2.04:1,no significantly difference in detection rate in male (3.12％) and female (2.70％).Accounted for 724 (95.14％) of the total adenovirus positive detection children below six years old,and 409(53.75％) children were detected below two years old.There was a distinct seasonality;the detection rate was higher in summer and winter (x2 =36.631,P＜0.01).In 761 hospitalized patients of ADV positive,431 were pneumonia,109 were bronchitis,74 were tonsillitis,14 were conjunctivitis pharynx and 133 were acute upper respiratory infection.Conclusion Our study demonstrates that respiratory adenovirus infection is an important cause of hospitalization in children below the age of 6 years in Shenzhen,China.The detection rate was higher in summer and winter than spring and autumn.Most adenovirus positive children were diagnosed by pneumonia,bronchitis and acute upper respiratory tract infection.