Publications by authors named "Yong Zhang"

5,480 Publications

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Correction to: Norovirus P particle-based tau vaccine-generated phosphorylated tau antibodies markedly ameliorate tau pathology and improve behavioral deficits in mouse model of Alzheimer's disease.

Signal Transduct Target Ther 2021 Jun 14;6(1):237. Epub 2021 Jun 14.

National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130012, China.

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http://dx.doi.org/10.1038/s41392-021-00657-6DOI Listing
June 2021

Correlation between white blood cell count at admission and mortality in COVID-19 patients: a retrospective study.

BMC Infect Dis 2021 Jun 14;21(1):574. Epub 2021 Jun 14.

Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China.

Background: Coronavirus disease-19 (COVID-19) has become a world health threaten. Its risk factors with death were still not known. White blood cells (WBC) count as a reflection of inflammation has played a vital role in COVID-19, however its level with death is not yet investigated.

Methods: In this retrospective, single-center study, all confirmed patients with COVID-19 at West Branch of Union Hospital from Jan 29 to Feb 28, 2020 were collected and analyzed. Demographic and clinical data including laboratory examinations were analyzed and compared between recovery and death patients.

Results: A total of 163 patients including 33 death cases were included in this study. Significant association was found between WBC count and death (HR = 1.14, 95%CI: 1.09-1.20, p < 0.001). The regression analysis results showed there was a significant association between WBC count and death (HR = 5.72, 95%CI: 2.21-14.82, p < 0.001) when use the second quartile as a cutoff value (> 6.16 × 10^9/L). The difference was still exist after adjusting for confounding factors (HR = 6.26, 95%CI: 1.72-22.77, p = 0.005). In addition, Kaplan-meier survival analysis showed that there was a significant decline of the cumulative survival rate (p < 0.001) in those with WBC count ≥6.16 × 10^9/L.

Conclusion: WBC count at admission is significantly corelated with death in COVID-19 patients. Higher level of WBC count should be given more attention in the treatment of COVID-19.
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http://dx.doi.org/10.1186/s12879-021-06277-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202964PMC
June 2021

OsLSD1.1 is involved in the photosystem II reaction and affects nitrogen allocation in rice.

Plant Physiol Biochem 2021 Jun 7;166:246-257. Epub 2021 Jun 7.

State Key Laboratory of Crop Genetics and Germplasm Enhancement, College of Resources and Environmental Sciences, Nanjing Agricultural University, Nanjing, 210095, China; Key Laboratory of Plant Nutrition and Fertilization in Lower-Middle Reaches of the Yangtze River, Ministry of Agriculture, Nanjing Agricultural University, Nanjing, 210095, China. Electronic address:

Nitrogen (N) is an essential nutrient element for plants; however, high N accumulation often leads to a decrease in photosynthetic nitrogen use efficiency (PNUE). In rice (Oryza sativa L.), well-developed aerenchyma is formed to promote oxygen transport from the shoot to the root tips as an adaptation to submerged and oxygen-deficient environment. Total N concentrations were increased in the rice root by changes in O levels in the rhizosphere. However, few reports have focused on how aerenchyma formation-related genes participate in photosynthesis and affect nitrogen allocation in rice. In this study, we found that OsLSD1.1, located in the chloroplast, cell membrane, and nucleus, may be involved in the photosystem II reaction and affect chloroplast development. OsLSD1.1 knockout was found to significantly reduce the quantum efficiency of the PSII reaction center (ΦPSII). Furthermore, we observed that the nitrogen accumulation decreased in the grain of OsLSD1.1 mutants. RNA-Seq transcriptome analysis revealed that OsPEPC3, OsPsbR1, OsNRG2, OsNRT1.5A, OsNRT1.7, and OsAMT3;2 were downregulated in m12 compared with N-WT (wild-type Nipponbare), which may be a reason that photosynthesis and nitrogen transport were inhibited. Taken together, our findings demonstrated that OsLSD1.1 may be key in plant growth, photosynthesis, and nitrogen allocation in rice. Our results may provide theoretical support for the discovery of key genes for nitrogen physiological use efficiency.
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http://dx.doi.org/10.1016/j.plaphy.2021.06.004DOI Listing
June 2021

The Efficacy of Intra-Arterial Plus Intravesical Chemotherapy Intravesical Chemotherapy Alone After Bladder-Sparing Surgery in High-Risk Bladder Cancer: A Systematic Review and Meta-Analysis of Comparative Study.

Front Oncol 2021 27;11:651657. Epub 2021 May 27.

Department of Urology, Beijing TianTan Hospital, Capital Medical University, Beijing, China.

Background: Due to the poor prognosis, the treatment of high-risk bladder cancer (HRBC) remains controversial. This meta-analysis aims to access the efficacy of intra-arterial chemotherapy (IAC) combined with intravesical chemotherapy (IC) IC alone after bladder-sparing surgery in HRBC.

Methods: A systematic search of PubMed, Cochrane Library databases, EMBASE (until June 2020) was conducted. PRISMA checklist was followed. The data were analyzed by RevMan v5.3.0.

Results: A total of five articles including 843 patients were studied. The analysis demonstrated that the IAC + IC group had a greater improvement of overall survival (P = 0.02) and significant reduction in terms of tumor recurrence rate (P = 0.0006) and tumor progression rate (P = 0.008) compared with the IC group. The recurrence-free survival in the IAC + IC group was significantly higher than that in the IC group (P = 0.004), but there was no significant difference in progression-free survival between the two groups (P = 0.32). In addition, the combination of IAC and IC significantly extended tumor recurrence interval (P = 0.0001) and reduced tumor-specific death rate (P = 0.01) for patients with HRBC compared with IC alone. For side effects related with IAC, although about half of the patients experienced some toxicities, most of them were mild and reversible (grades 1-2, 22.3% . grade 3-4, 2.7%), mainly including nausea/vomiting (P = 0.0001), neutropenia (P = 0.002), and alanine aminotransferase (P = 0.0001).

Conclusion: Patients with HRBC treated with IAC + IC after bladder-sparing surgery had a marked improvement in the overall survival, recurrence-free survival, time interval to first recurrence, tumor recurrence rate, tumor progression rate, and tumor-specific death rate than patients treated with IC alone. However, progression-free survival was not significantly correlated with treatment strategy. In addition, patients seemed to tolerate well the toxicities related with IAC.

Systematic Review Registration: PROSPERO, identifier CRD42021232679.
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http://dx.doi.org/10.3389/fonc.2021.651657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190377PMC
May 2021

Therapeutic effects of the TST36 stapler on rectocele combined with internal rectal prolapse.

World J Gastrointest Surg 2021 May;13(5):443-451

Department of Anorectal Disease, Shenyang Coloproctology Hospital, Shenyang 110000, Liaoning Province, China.

Background: The most common causes of outlet obstructive constipation (OOC) are rectocele and internal rectal prolapse. The surgical methods for OOC are diverse and difficult, and the postoperative complications and recurrence rate are high, which results in both physical and mental pain in patients. With the continuous deepening of the surgeon's concept of minimally invasive surgery and continuous in-depth research on the mechanism of OOC, the treatment concepts and surgical methods are continuously improved.

Aim: To determine the efficacy of the TST36 stapler in the treatment of rectocele combined with internal rectal prolapse.

Methods: From January 2017 to July 2019, 49 female patients with rectocele and internal rectal prolapse who met the inclusion criteria were selected for treatment using the TST36 stapler.

Results: Forty-five patients were cured, 4 patients improved, and the cure rate was 92%. The postoperative obstructed defecation syndrome score, the defecation frequency score, time/straining intensity, and sensation of incomplete evacuation were significantly decreased compared with these parameters before treatment, and the differences were statistically significant ( < 0.05). The postoperative anal canal resting pressure and maximum squeeze pressure in patients decreased compared with before treatment, and the differences were statistically significant ( < 0.05). The initial and maximum defecation thresholds after surgery were significantly lower than those before treatment, and the differences were statistically significant ( < 0.05). The postoperative ratings of rectocele, resting phase, and defecation phase in these patients were significantly decreased compared with those before treatment, and the differences were statistically significant ( < 0.05).

Conclusion: The TST36 stapler is safe and effective in treating rectocele combined with internal rectal prolapse and is worth promoting in clinical work.
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http://dx.doi.org/10.4240/wjgs.v13.i5.443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167842PMC
May 2021

Using vaginal discharge score (VDS) grading system to evaluate the effect of clinical endometritis on reproductive performance of dairy cows in China.

Anim Reprod 2021 May 14;18(1):e20200228. Epub 2021 May 14.

College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China.

Clinical endometritis (CE) is a major cause in affecting the reproductive performance of dairy cows. The objectives of this study were to ascertain the prevalence of CE and to evaluate the effect of CE on reproductive performance in dairy cows using vaginal discharge score (VDS) grading system. 803 dairy cows were examined by vaginoscope with 4-point VDS at 26 ± 3 days in milk (DIM) and classified into six groups: non-endometritis with VDS 0 (control; CON), endometritis with VDS 1 (MEM), non-treated endometritis with VDS 2 (NTME), treated endometritis with VDS 2 (TME), non-treated endometritis with VDS 3 (NTPE), and treated endometritis with VDS 3 (TPE). Cows in TME and TPE groups were treated with 200 mL of 50% dextrose solution by intrauterine infusion. The prevalence of CE was 33% at 26 ± 3 DIM. Binary logistic regression analysis revealed cows in MEM, NTME and NTPE groups had a less likelihood of first artificial insemination (AI) pregnancy than those in CON group ( < 0.05). Kaplan-Meier survival curves for days open were statistically different ( = 0.004). In Cox regression model, cows in NTME and NTPE groups had a reduced pregnancy rate than those in CON group ( < 0.05). The hazard of pregnancy in NTME group was lower than that in TME group ( = 0.044). Similarly, it was lower for the hazard of pregnancy in NTPE group than in TPE group ( = 0.048). Cows in MEM, NTME, and NTPE groups required more services per pregnancy than those in CON group ( < 0.05). In conclusion, CE examined by the VDS grading system impaired reproductive performance, and mild endometritis with VDS 1 should be treated in the early postpartum period to ameliorate fertility in dairy herds.
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http://dx.doi.org/10.1590/1984-3143-AR2020-0228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189348PMC
May 2021

NUCOME: A comprehensive database of nucleosome organization referenced landscapes in mammalian genomes.

BMC Bioinformatics 2021 Jun 13;22(1):321. Epub 2021 Jun 13.

Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Science and Technology, Tongji University, 1239 Siping Road, Shanghai, 200092, China.

Background: Nucleosome organization is involved in many regulatory activities in various organisms. However, studies integrating nucleosome organization in mammalian genomes are very limited mainly due to the lack of comprehensive data quality control (QC) assessment and uneven data quality of public data sets.

Results: The NUCOME is a database focused on filtering qualified nucleosome organization referenced landscapes covering various cell types in human and mouse based on QC metrics. The filtering strategy guarantees the quality of nucleosome organization referenced landscapes and exempts users from redundant data set selection and processing. The NUCOME database provides standardized, qualified data source and informative nucleosome organization features at a whole-genome scale and on the level of individual loci.

Conclusions: The NUCOME provides valuable data resources for integrative analyses focus on nucleosome organization. The NUCOME is freely available at http://compbio-zhanglab.org/NUCOME .
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http://dx.doi.org/10.1186/s12859-021-04239-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201709PMC
June 2021

Discovery of chiral N-2'-aryletheryl-1'-alkoxy-ethyl substituted arylisoquinolones with anti-inflammatory activity from the nucleophilic addition reactions of the thiophenols and oxazolinium.

Eur J Med Chem 2021 Jun 1;222:113583. Epub 2021 Jun 1.

CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, 201203, China; Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, 201203, China; School of Pharmacy, University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing, 100049, China. Electronic address:

Herein we disclosed the novel nucleophilic addition reactions of the thiophenols and oxazolinium (DCZ0358) to produce N-2'-aryletheryl-1'-alkoxy-ethyl substituted arylisoquinolones. After evaluating the anti-inflammatory activity in vitro, 2d was found having significant anti-TNFα activity. Through the amplified synthesis of 2d, four monomers (3a-b and 4a-d) were obtained by chiral separation of the product. The reaction mechanism was proposed and explored by the control experiments. However, only the R-stereoisomers 3b and 4b have significant anti-TNFα activity in vitro (IC = 56 and 14 nM, respectively). Moreover, 4b exerts potent therapeutic effects on ulcerative colitis in vivo (30 mg/kg bw, qd, i. g.). The subsequent bio-target exploration of compound 4bvia molecular docking and the experimental validation disclosed that 4b has 3-fold selectivity of binding activity on estrogen receptor (ER) beta (β) (Ki = 760.86 nM) vs. alpha (α) (Ki = 2320.58 nM). Thus, it provides a novel type of non-steroidal leads for developing anti-inflammatory drugs.
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http://dx.doi.org/10.1016/j.ejmech.2021.113583DOI Listing
June 2021

Calcaneal fractures: 3D-printing model to assist spatial weaving of percutaneous screws versus conventional open fixation-a retrospective cohort study.

Int Orthop 2021 Jun 11. Epub 2021 Jun 11.

Department of Foot and Ankle Surgery, Shanghai Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, China.

Purpose: This study compared the clinical effectiveness and wound complications of a three-dimensional model-assisted spatial weaving screw fixation (3D-SWSF) versus open reduction and internal fixation (ORIF) via an L-shaped extensile lateral approach for calcaneal fractures.

Methods: This single-centre retrospective cohort study was conducted with two cohort groups in which patients with Sanders II and III calcaneal fractures underwent 3D-SWSF or conventional ORIF. The clinical outcome measures included operation duration, time to operation, wound complications, blood loss volume, hospital stays, American Orthopedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot score, and visual analog scale (VAS) score. The pre-operative, post-operative, and one-year follow-up Gissane's angle (GA), Böhler's angle (BA), height, and width and length of the calcaneal fractures were also compared between the two groups.

Results: From Oct 2015 to Oct 2019, 31 patients received 3D-SWSF and 41 received conventional ORIF. A total of 11 (26.8%) patients in ORIF group had wound complications, compared with only two (6.5%) in 3D-SWSF group (p = 0.032). Operative time, blood loss, and hospital stay in 3D-SWSF group were lesser than those in ORIF group. The patients treated with 3D-SWSF had better AOFAS and VAS scores than those treated with ORIF at the last follow-up. The post-operative and one-year follow-up radiographic indexes as well as the GA, BA, length, width, and height of the calcaneal fractures were relatively comparable between the two groups.

Conclusion: Our study revealed that 3D-SWSF could effectively decrease the risk of wound complications, shorten operation time, reduce length of hospitalization, and improve post-operative rehabilitation.
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http://dx.doi.org/10.1007/s00264-021-05094-2DOI Listing
June 2021

Different clinical parameters inform epicardial fat thickness in pre- and post-menopausal women with obstructive sleep apnea.

BMC Womens Health 2021 06 11;21(1):239. Epub 2021 Jun 11.

Medical Imaging College, Shanxi Medical University, Taiyuan, 030001, Shanxi, China.

Background: Obstructive sleep apnea (OSA) is a sleep-related disorder with breathing difficulties. Previous studies revealed that epicardial fat thickness (EFT) correlates with OSA severity. Interestingly, female patients display a stronger EFT-OSA correlation than males. The purpose of this study is to investigate the relationship between EFT and different clinical characteristics in pre- and post-menopausal women diagnosed with OSA.

Methods: Patients diagnosed with OSA were divided into pre/early peri-menopausal (Group 1) and post/late peri-menopausal (Group 2) according to the menopause status. EFT was obtained from parasternal long-axis echocardiographic images. We also collected general clinical characteristics of patients involved in this study, and performed spearman correlation analysis to explore the correlations between EFT and the general clinical characteristics. We further applied Multiple stepwise linear regression analysis to explore the predictors for EFT in both groups.

Results: A total number of 23 and 59 patients were enrolled in Group 1 and Group 2 respectively. EFT in Group 2 was significantly higher than that of Group 1. In both groups, EFT was positively correlated with apnea-hypopnea index (AHI), percentage of total sleep time when blood oxygen saturation was less than 90% (T90), oxygen desaturation index (ODI) and glucose; while EFT was negatively correlated with mean and lowest SaO (oxygen saturation) levels. However, EFT was positively correlated with total cholesterol (TC) only in Group 1 and body mass index (BMI) only in Group2, respectively. Multiple stepwise linear regression analysis showed that AHI was independently associated with EFT in Group 1. However, both AHI and BMI were independent predictors of EFT in Group 2.

Conclusion: EFT was notably correlated with menopausal status in women with OSA. AHI was the independent predictor of EFT in women with OSA. BMI was the independent predictor of EFT in post/late peri-menopausal women with OSA.
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http://dx.doi.org/10.1186/s12905-021-01384-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193883PMC
June 2021

Integrating miRNA and mRNA Profiling to Assess the Potential miRNA-mRNA Modules Linked With Testicular Immune Homeostasis in Sheep.

Front Vet Sci 2021 25;8:647153. Epub 2021 May 25.

College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, China.

Beyond its well-known role in spermatogenesis and androgen production, mammalian testes are increasingly recognized as an immune-privileged organ for protecting autoantigenic germ cells, especially meiotic and postmeiotic germ cells, from systemic immune responses. Despite its importance, the molecular mechanisms underlying this regulation in mammals, including sheep, are far from known. In this study, we searched for the genes associated with testicular immune privilege and assessed their possible modulating mechanisms by analyzing systematic profiling of mRNAs and miRNAs on testicular tissues derived from prepubertal and postpubertal Tibetan sheep acquired by RNA sequencing. We identified 1,118 differentially expressed (DE) mRNAs associated with immunity (245 increased mRNAs and 873 decreased mRNAs) and 715 DE miRNAs (561 increased miRNAs and 154 decreased miRNAs) in postpubertal testes compared with prepuberty. qPCR validations for 20 DE mRNAs and 16 miRNAs showed that the RNA-seq results are reliable. By using Western blot, the postpubertal testes exhibited decreased protein abundance of CD19 and TGFBR2 (two proteins encoded by DE mRNAs) when compared with prepuberty, consistent with mRNA levels. The subsequent immunofluorescent staining showed that the positive signals for the CD19 protein were observed mainly in Sertoli cells and the basement membrane of pre- and postpubertal testes, as well as the prepubertal testicular vascular endothelium. The TGFBR2 protein was found mostly in interstitial cells and germ cells of pre- and postpubertal testes. Functional enrichment analysis indicated that DE mRNAs were mainly enriched in biological processes or pathways strongly associated with the blood-testis barrier (BTB) function. Many decreased mRNAs with low expression abundance were significantly enriched in pathways related to immune response. Also, multiple key miRNA-target negative correlation regulatory networks were subsequently established. Furthermore, we verified the target associations between either oar-miR-29b or oar-miR-1185-3p and ITGB1 by dual-luciferase reporter assay. Finally, a putative schematic model of the miRNA-mRNA-pathway network mediated by immune homeostasis-related genes was proposed to show their potential regulatory roles in sheep testicular privilege. Taken together, we conclude that many immune-related genes identified in this study are negatively regulated by potential miRNAs to participate in the homeostatic regulation of testicular immune privilege of sheep by sustaining BTB function and inhibiting immune responses under normal physiological conditions. This work offers the first global view of the expression profiles of miRNAs/mRNAs involved in sheep testicular immune privilege and how the genes potentially contribute to immune-homeostatic maintenance.
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http://dx.doi.org/10.3389/fvets.2021.647153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185144PMC
May 2021

Case Report: Abomasum Impaction in Beef Cattle Due to High Intake of Distillers' Grain and Treatment Options in Southwest China.

Front Vet Sci 2021 24;8:615871. Epub 2021 May 24.

The Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.

In Southern China, distillers' grain is the main feed ingredient for small beef cattle farms. High intake of distillers' grain may lead to abomasum impaction, a disorder caused by the accumulation of solid content within the organ. For treatment, there are non-surgical and surgical options. In this study, we aimed to describe the clinical presentation, diagnosis, and treatment of beef cattle with abomasum impaction due to high intake of distillers' grain. Forty-nine Simmental beef cattle from 13 farms in Chongqing, China, were diagnosed with abomasum impaction. Animals were male, aged ≤2 years, and weighed between 200 and 350 kg. In this retrospective study, information on distillers' grain intake and clinical data were collected for 49 beef cattle diagnosed with abomasum impaction. The animals were treated between 2011 and 2019 with either non-surgical therapy or surgery. Animals diagnosed with mild abomasum impaction ( = 14) fully recovered after non-surgical treatment. Among moderate cases ( = 19), 12 cattle recovered after non-surgical treatment (63%), while the remaining seven did not respond well and underwent surgery. Three of those animals were subsequently cured (3/7). Among the severe cases ( = 16), four cattle were cured after non-surgical treatment (25%) (4/16). Of the remaining 12 cattle, six were slaughtered, and six died after surgery. Non-surgical treatment is efficient for mild abomasum impaction caused by a high intake of distillers' grain and may be considered for both moderate and severe cases. However, the treatment success rate for more severe cases decreases as the disease severity worsens.
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http://dx.doi.org/10.3389/fvets.2021.615871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180562PMC
May 2021

Early combined rehabilitation intervention to improve the short-term prognosis of premature infants.

BMC Pediatr 2021 Jun 9;21(1):269. Epub 2021 Jun 9.

Department of Neonatology, Sichuan Provincial Maternity and Child Health Care Hospital, No. 290 West Second Street, Shayan Road, Chengdu, 610031, Sichuan, China.

Background: To explore the clinical effect of early combined rehabilitation intervention on premature infants in the neonatal intensive care unit (NICU).

Methods: Premature infants with gestational ages less than 32 weeks or birth weights less than 1500 g were included in the present study.The participants were divided into the intervention group and control group. All infants received the current routine treatment based on the clinical guidelines, and the intervention group was additionally treated by visual and auditory stimulation, oral motor function, respiratory function and neurodevelopmental training. The following clinical outcomes were compared: durations of oxygen supplementation and indwelling gastric tube use; incidences of retinopathy of prematurity (ROP) and neonatal necrotizing enterocolitis (NEC); Sliverman scores; incidences of bronchopulmonary dysplasia (BPD) and intraventricular haemorrhage; days of hospitalization; and neurodevelopmental outcomes. Datas were analysed using the following statistical tests: the chi-square test, the independent samples or paired t test, repeated measures ANOVA, and the Wilcoxon rank sum test.

Results: Compared with those in the control group, premature infants in the intervention group had shorter durations of oxygen supplementation and indwelling gastric tube use, fewer hospitalization days and lower incidences of ROP, BPD, and NEC.The intervention group had lower Sliverman scores and higher Ballard neuromuscular scores than the control group.

Conclusion: Early combined rehabilitation intervention can improve the short-term clinical outcomes of premature infants.
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http://dx.doi.org/10.1186/s12887-021-02727-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188692PMC
June 2021

MET amplification attenuates lung tumor response to immunotherapy by inhibiting STING.

Cancer Discov 2021 Jun 7. Epub 2021 Jun 7.

Hubei Cancer Hospital.

Immune checkpoint blockade (ICB) has revolutionized cancer therapy. However, the response of patients to ICB is difficult to predict. Here, we examined 81 lung cancer patients under ICB treatment and found that patients with MET amplification were resistant to ICB and had a poor progress-free survival. Tumors with MET amplifications had significantly decreased STING levels and antitumor T cell infiltration. Furthermore, we performed deep single-cell RNA sequencing on more than 20000 single immune cells and identified an immunosuppressive signature with increased subsets of XIST- and CD96-positive exhausted NK cells and decreased CD8+ T cell and NK cell populations in patients with MET-amplification. Mechanistically, we found that oncogenic MET signaling induces phosphorylation of UPF1 and downregulates tumor cell STING expression via modulation of the 3'-UTR length of STING by UPF1. Decreased efficiency of ICB by MET amplification can be overcome by inhibiting MET.
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http://dx.doi.org/10.1158/2159-8290.CD-20-1500DOI Listing
June 2021

Venlafaxine Caffeic Acid Salt: Synthesis, Structural Characterization, and Hypoglycemic Effect Analysis.

ACS Omega 2021 Jun 17;6(21):13895-13903. Epub 2021 May 17.

Beijing City Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. Beijing 100050, China.

Depression is a recurrent and chronic mental disorder requiring long-term treatment. Major depressive disorder is present in 15-20% of patients with type 1 or type 2 diabetes. Large-scale evidence revealed that depression and depressive symptoms are independent risk factors for the development of type 2 diabetes, and they may contribute to hyperglycemia and even accelerate the premature onset of diabetes complications. Venlafaxine is a clinical first-line antidepressant used for more than 30 years. Recently, clinical reports showed that venlafaxine overdose might cause hypoglycemia. Venlafaxine is insoluble and salt formation technology is the most appropriate method to improve the physicochemical properties and the pharmacokinetic profile of the drug. In the present work, the use of the solvent evaporation method, slurry, and the liquid-assisted grinding method resulted in the crystalline salt venlafaxine-caffeic acid (1:1). The compounds were characterized using a series of solid-state techniques, viz., powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, Fourier transform infrared spectroscopy, and solid-state nuclear magnetic resonance, and the crystal structure was determined by single-crystal X-ray diffraction. Besides, a comparative study of solubility, dissolution, and hypoglycemic activity of the parent drug and the new salt has been carried out. The tested venlafaxine-caffeic acid salt showed about 16-fold higher solubility than the pure drug. Moreover, the glucose consumption assay results showed that the novel salt possesses potent hypoglycemic activity , suggesting that it is a promising candidate effective for major depressive disorder patients with type 2 diabetes.
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http://dx.doi.org/10.1021/acsomega.1c01581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173613PMC
June 2021

Temporal phylogeny and molecular characterization of echovirus 30 associated with aseptic meningitis outbreaks in China.

Virol J 2021 Jun 6;18(1):118. Epub 2021 Jun 6.

WHO WPRO Regional Polio Reference Laboratory, National Health Commission Key Laboratory of biosafety, National Health Commission Key Laboratory of Medical Virology, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, People's Republic of China.

Background: An outbreak of aseptic meningitis occurred from June to August 2016, in Inner Mongolia Autonomous Region, China.

Methods: To determine its epidemiological characteristics, etiologic agent, and possible origin, specimens were collected for virus isolation and identification, followed by molecular epidemiological analysis.

Results: A total of 363 patients were clinically diagnosed from June 1st to August 31st 2016, and most cases (63.1%, n = 229) were identified between June 22nd and July 17th, with children aged 6 to 12 years constituting the highest percentage (68.9%, n = 250). All viral isolates from this study belonged to genotype C of echovirus 30 (E30), which dominated transmission in China. To date, two E30 transmission lineages have been identified in China, of which Lineage 2 was predominant. We observed fluctuant progress of E30 genetic diversity, with Lineage 2 contributing to increased genetic diversity after 2002, whereas Lineage 1 was significant for the genetic diversity of E30 before 2002.

Conclusions: We identified the epidemiological and etiological causes of an aseptic meningitis outbreak in Inner Mongolia in 2016, and found that Lineage 2 played an important role in recent outbreaks. Moreover, we found that Gansu province could play an important role in E30 spread and might be a possible origin site. Furthermore, Fujian, Shandong, Taiwan, and Zhejiang provinces also demonstrated significant involvement in E30 evolution and persistence over time in China.
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http://dx.doi.org/10.1186/s12985-021-01590-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182919PMC
June 2021

PknG manipulates host autophagy flux to promote pathogen intracellular survival.

Autophagy 2021 Jun 7. Epub 2021 Jun 7.

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Beijing, China.

The eukaryotic-type protein kinase G (PknG), one of the eleven eukaryotic type serine-threonine protein kinase (STPK) in (Mtb), is involved in mycobacterial survival within macrophages, presumably by suppressing phagosome and autophagosome maturation, which makes PknG an attractive drug target. However, the exact mechanism by which PknG inhibits pathogen clearance during mycobacterial infection remains largely unknown. Here, we show that PknG promotes macroautophagy/autophagy induction but inhibits autophagosome maturation, causing an overall effect of blocked autophagy flux and enhanced pathogen intracellular survival. PknG prevents the activation of AKT (AKT serine/threonine kinase) via competitively binding to its pleckstrin homology (PH) domain, leading to autophagy induction. Remarkably, PknG could also inhibit autophagosome maturation to block autophagy flux via targeting host small GTPase RAB14. Specifically, PknG directly interacts with RAB14 to block RAB14-GTP hydrolysis. Furthermore, PknG phosphorylates TBC1D4/AS160 (TBC1 domain family member 4) to suppress its GTPase-activating protein (GAP) activity towards RAB14. In macrophages and , PknG promotes Mtb intracellular survival through blocking autophagy flux, which is dependent on RAB14. Taken together, our data unveil a dual-functional bacterial effector that tightly regulates host autophagy flux to benefit pathogen intracellular survival.
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http://dx.doi.org/10.1080/15548627.2021.1938912DOI Listing
June 2021

AQP3-mediated H O uptake inhibits LUAD autophagy by inactivating PTEN.

Cancer Sci 2021 Jun 6. Epub 2021 Jun 6.

Department of Thoracic Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, 110042, China.

It is widely accepted that redox reprogramming participates in malignant transformation of lung adenocarcinoma (LUAD). However, the source of excessive reactive oxygen species (ROS) and the downstream signaling regulatory mechanism are complicated and unintelligible. In current study, we newly identified the aquaporin 3 (AQP3) as a LUAD oncogenic factor with capacity to transport exogenous hydrogen peroxide (H O ) and increase intracellular ROS levels. Subsequently, we demonstrated that AQP3 was necessary for the facilitated diffusion of exogenous H O in LUAD cells and that the AQP3-dependent transport of H O accelerated cell growth and inhibited rapamycin-induced autophagy. Mechanistically, AQP3-mediated H O uptake increased intracellular ROS levels to inactivate PTEN and activate the AKT/mTOR pathway subsequently inhibit autophagy and 1promote proliferation in LUAD cells. Finally, we suggested that AQP3 depletion retarded subcutaneous tumorigenesis in vivo and simultaneously decreased ROS levels and promoted autophagy. These findings underscore the importance of AQP3-induced oxidative stress in malignant transformation and suggest a therapeutic target for LUAD.
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http://dx.doi.org/10.1111/cas.15008DOI Listing
June 2021

Coxsackievirus B4: an underestimated pathogen associated with a hand, foot, and mouth disease outbreak.

Arch Virol 2021 Jun 6. Epub 2021 Jun 6.

Shandong Center for Disease Control and Prevention, Jinan, Shandong, People's Republic of China.

In order to discover the causes of a coxsackievirus B4 (CV-B4)-associated hand, foot, and mouth disease (HFMD) outbreak and to study the evolutionary characteristics of the virus, we sequenced isolates obtained during an outbreak for comparative analysis with previously sequenced strains. Phylogenetic and evolutionary dynamics analysis was performed to examine the genetic characteristics of CV-B4 in China and worldwide. Phylogenetic analysis showed that CV-B4 originated from a common ancestor in Shandong. CV-B4 strains isolated worldwide could be classified into genotypes A-E based on the sequence of the VP1 region. All CV-B4 strains in China belonged to genotype E. The global population diversity of CV-B4 fluctuated substantially over time, and CV-B4 isolated in China accounted for a significant increase in the diversity of CV-B4. The average nucleotide substitution rate in VP1 of Chinese CV-B4 (5.20 × 10 substitutions/site/year) was slightly higher than that of global CV-B4 (4.82 × 10 substitutions/site/year). This study is the first to investigate the evolutionary dynamics of CV-B4 and its association with an HFMD outbreak. These findings explain both the 2011 outbreak and the global increase in CV-B4 diversity. In addition to improving our understanding of a major outbreak, these findings provide a basis for the development of surveillance strategies.
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http://dx.doi.org/10.1007/s00705-021-05128-5DOI Listing
June 2021

More than just statics: Temporal dynamic changes of intrinsic brain activity in cigarette smoking.

Addict Biol 2021 Jun 3:e13050. Epub 2021 Jun 3.

Department of Magnetic Resonance Imaging, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Smoking is companied with altered intrinsic activity of the brain measured by amplitude of low-frequency fluctuation. Evidence has revealed that human brain activity is a highly dynamic and rapidly changing system. How exactly cigarette smoking affect temporal dynamic intrinsic brain activity is not fully understood nor is it clear how smoking severity influences spontaneous brain activity. Dynamic amplitude of low-frequency fluctuation (dALFF) was used to examine the dynamic temporal variability in 93 participants (63 smokers, 30 nonsmokers). We further divided smokers into light and heavy smokers. The temporal variability in intrinsic brain activity among these groups was compared. Correlation analyses were performed between dALFF in areas showing group differences and smoking behaviour (e.g., the Fagerström Test for Nicotine Dependence [FTND] scores and pack-years). Smokers showed significantly increased dALFF in the left inferior/middle frontal gyrus, right orbitofrontal gyrus, right insula, left superior/medial frontal gyrus and right middle frontal gyrus than nonsmokers. Light smokers showed increased dALFF variability in the left prefrontal cortex. Heavy smokers showed increased dynamics in specific brain regions, including the right postcentral gyrus, right insula and left precentral gyrus. Furthermore, the temporal variability in dALFF in the left superior/medial frontal gyrus, left superior/middle frontal gyrus, right middle frontal gyrus and right insula was positively correlated with pack-years or FTND. Combined, these results suggest that smokers increase stable and persistent spontaneous brain activity in prefrontal cortex, involved impaired gold-directed action and value-based decision-making. In addition, individuals with heavier smoking severity show increased perturbance on spontaneous brain activity of perception and sensorimotor, related to increased reliance.
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http://dx.doi.org/10.1111/adb.13050DOI Listing
June 2021

A case report of infantile parkinsonism-dystonia-2 caused by homozygous mutation in the gene.

Int J Neurosci 2021 Jun 2:1-4. Epub 2021 Jun 2.

Rehabilitation and Treatment Centre for Cerebral Palsy, Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.

A 6-month-old male infant who presented with developmental delay and suspected cerebral palsy was diagnosed with infantile parkinsonism-dystonia-2 (MIM: 618049). The whole-exome sequencing identified a homozygous c.710C > T (p.Pro237His) transition in the monoamine transporter gene , which was due to paternal uniparental disomy (UPD) of chromosome 10p15.3q26.3, resulting in brain dopamine-serotonin vesicular transport disease. Sanger sequencing confirmed that his unaffected father carried the same mutation in the heterozygous state, while his mother did not carry the same mutation. Autosomal recessive gene mutations in has been identified in three families in different countries. The infant was treated with pramipexole, a dopamine agonist, and the static tremor was better compared with that before treatment, but the movement disorder was not significantly improved. This case confirmed the causal mutation of gene and brain dopamine-serotonin vesicular transport disease, which suggested the mechanism of UPD homozygous formation, and confirmed that dopamine agonist treatment could improve some symptoms in affected individuals.
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http://dx.doi.org/10.1080/00207454.2021.1938036DOI Listing
June 2021

Extraction of the Structural Properties of Skin Tissue via Diffuse Reflectance Spectroscopy: An Inverse Methodology.

Sensors (Basel) 2021 May 28;21(11). Epub 2021 May 28.

State Key Laboratory of Multiphase Flow in Power Engineering, Xi'an Jiaotong University, Xi'an 710049, China.

For the laser treatment of vascular dermatosis, the blood vessel morphology and depth in skin tissue is essential to achieve personalized intelligent therapy. The morphology can be obtained from the laser speckle imaging, and vessel depth was extracted by an inverse methodology based on diffuse reflectance spectrum. With optimized spot size of 0.5 mm and known optical properties, the proposed method was experimentally validated via the spectral measurement of microcapillary with known size and depth embedded in an epoxy resin-based skin phantom. Results prove that vessel depth can be extracted with an average relative error of 5%, thereby providing the foundation for a personalized, precise, and intelligent laser treatment of vascular dermatosis.
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http://dx.doi.org/10.3390/s21113745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8199232PMC
May 2021

Large-Size Suspended Mono-Layer Graphene Film Transfer Based on the Inverted Floating Method.

Micromachines (Basel) 2021 May 6;12(5). Epub 2021 May 6.

College of Intelligence Science and Technology, National University of Defense Technology, Changsha 410073, China.

Suspended graphene can perfectly present the excellent material properties of graphene, which has a good application prospect in graphene sensors. The existing suspended graphene pressure sensor has several problems that need to be solved, one of which is the fabrication of a suspended sample. It is still very difficult to obtain large-size suspended graphene films with a high integrity that are defect-free. Based on the simulation and analysis of the kinetic process of the traditional suspended graphene release process, a novel setup for large-size suspended graphene release was designed based on the inverted floating method (IFM). The success rate of the single-layer suspended graphene with a diameter of 200 μm transferred on a stainless-steel substrate was close to 50%, which is greatly improved compared with the traditional impregnation method. The effects of the defects and burrs around the substrate cavity on the stress concentration of graphene transfer explain why the transfer success rate of large-size suspended graphene is not high. This research lays the foundation for providing large-size suspended graphene films in the area of graphene high-precision sensors.
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http://dx.doi.org/10.3390/mi12050525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148557PMC
May 2021

A Microtester for Measuring the Reliability of Microdevices in Controlled Environmental Conditions.

Micromachines (Basel) 2021 May 20;12(5). Epub 2021 May 20.

Key Laboratory of Micro/Nano Systems for Aerospace, Ministry of Education, Northwestern Polytechnical University, Xi'an 710072, China.

A miniaturized reliability test system for microdevices with controlled environmental parameters is presented. The system is capable of measuring key electrical parameters of the microdevices while controlling the environmental conditions around the microdevices. The test system is compact and thus can be integrated with standard test equipment for microdevices. By using a feed-forward decoupling algorithm, the presented test system is capable of generating a temperature range of 0-120 °C and a humidity range of 20-90% RH (0-55 °C), within a small footprint and weight. The accuracy for temperature and humidity control is ±0.1 °C and ±1% RH (30 °C), respectively. The functionality of the proposed test system is verified by integrating it with a piezo shaker to test the environmental reliability of an electromagnetic vibration energy harvester. The proposed system can be used as a proof-of-technology platform for characterizing the performance of microdevices with controlled environmental parameters.
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http://dx.doi.org/10.3390/mi12050585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161092PMC
May 2021

Structures of wild-type and H451N mutant human lymphocyte potassium channel K1.3.

Cell Discov 2021 Jun 1;7(1):39. Epub 2021 Jun 1.

Hefei National Laboratory of Physical Sciences at Microscale, Anhui Laboratory of Advanced Photonic Science and Technology, and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China.

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http://dx.doi.org/10.1038/s41421-021-00269-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167131PMC
June 2021

GLEANER: a web server for GermLine cycle Expression ANalysis and Epigenetic Roadmap visualization.

BMC Bioinformatics 2021 May 31;22(1):289. Epub 2021 May 31.

Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Science and Technology, Tongji University, Shanghai, 200092, China.

Background: Germline cells are important carriers of genetic and epigenetic information transmitted across generations in mammals. During the mammalian germline cell development cycle (i.e., the germline cycle), cell potency changes cyclically, accompanied by dynamic transcriptional changes and epigenetic reprogramming. Recently, to understand these dynamic and regulatory mechanisms, multiomic analyses, including transcriptomic and epigenomic analyses of DNA methylation, chromatin accessibility and histone modifications of germline cells, have been performed for different stages in human and mouse germline cycles. However, the long time span of the germline cycle and material scarcity of germline cells have largely limited the understanding of these dynamic characteristic changes. A tool that integrates the existing multiomics data and visualizes the overall continuous dynamic trends in the germline cycle can partially overcome such limitations.

Results: Here, we present GLEANER, a web server for GermLine cycle Expression ANalysis and Epigenetics Roadmap visualization. GLEANER provides a comprehensive collection of the transcriptome, DNA methylome, chromatin accessibility, and H3K4me3, H3K27me3, and H3K9me3 histone modification characteristics in human and mouse germline cycles. For each input gene, GLEANER shows the integrative analysis results of its transcriptional and epigenetic features, the genes with correlated transcriptional changes, and the overall continuous dynamic trends in the germline cycle. We further used two case studies to demonstrate the detailed functionality of GLEANER and highlighted that it can provide valuable clues to the epigenetic regulation mechanisms in the genetic and epigenetic information transmitted during the germline cycle.

Conclusions: To the best of our knowledge, GLEANER is the first web server dedicated to the analysis and visualization of multiomics data related to the mammalian germline cycle. GLEANER is freely available at http://compbio-zhanglab.org/GLEANER .
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http://dx.doi.org/10.1186/s12859-021-04217-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165803PMC
May 2021

Abnormal neuronal damage and inflammation in the hippocampus of kainic acid-induced epilepsy mice.

Cell Biochem Funct 2021 May 30. Epub 2021 May 30.

Stem Cells & Biotherapy Engineering Research Center of Henan, College of Life Science and Technology, Xinxiang Medical University, Xinxiang, China.

In this study, we established a mouse model of epilepsy and analysed abnormal neuronal damage and inflammation in the hippocampus of mice with kainic acid (KA)-induced epilepsy to provide the basis for the pathogenesis of epilepsy. C57 mice, aged 4 weeks, were injected intraperitoneally in the KA group with 20 mg/kg of KA and in the sham experimental group with normal saline. The whole brain and hippocampus of mice in the sham experimental group and KA epilepsy model group were collected on days 7, 14, 21 and 28 after injection. The difference in the protein expression in the hippocampus was detected using fluorescence immunohistochemistry. The hippocampal tissue was also collected and frozen to detect protein expression by western blot. The results of the haematoxylin and eosin (HE) and Nissl staining showed that the mouse model of temporal lobe epilepsy could be established by intraperitoneal injection of KA, and the success rate of the model was 53.8%. The expression of DCX-, β-catenin-, GFAP- and Iba-1-labelled glial cells in the KA-induced epilepsy model group were higher than those in the sham group. The results of western blotting showed that the expression of DCX and β-catenin in the KA-induced epilepsy model group was higher than that in the sham experimental group, while the expression of N-cadherin and Iba-1 on days 14 and 28 was significantly (P < .05) higher than that in the sham experimental group. In KA-induced epilepsy model group, the expression of Bcl-2 was decreased, while the expression of Bad and PUMA was increased.
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http://dx.doi.org/10.1002/cbf.3651DOI Listing
May 2021

A novel phosphoramide compound, DCZ0805, shows potent anti-myeloma activity via the NF-κB pathway.

Cancer Cell Int 2021 May 30;21(1):285. Epub 2021 May 30.

CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, 201203, China.

Background: Multiple myeloma (MM) is a highly aggressive and incurable clonal plasma cell disease with a high rate of recurrence. Thus, the development of new therapies is urgently needed. DCZ0805, a novel compound synthesized from osalmide and pterostilbene, has few observed side effects. In the current study, we intend to investigate the therapeutic effects of DCZ0805 in MM cells and elucidate the molecular mechanism underlying its anti-myeloma activity.

Methods: We used the Cell Counting Kit-8 assay, immunofluorescence staining, cell cycle assessment, apoptosis assay, western blot analysis, dual-luciferase reporter assay and a tumor xenograft mouse model to investigate the effect of DCZ0805 treatment both in vivo and in vitro.

Results: The results showed that DCZ0805 treatment arrested the cell at the G0/G1 phase and suppressed MM cells survival by inducing apoptosis via extrinsic and intrinsic pathways. DCZ0805 suppressed the NF-κB signaling pathway activation, which may have contributed to the inhibition of cell proliferation. DCZ0805 treatment remarkably reduced the tumor burden in the immunocompromised xenograft mouse model, with no obvious toxicity observed.

Conclusion: The findings of this study indicate that DCZ0805 can serve as a novel therapeutic agent for the treatment of MM.
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http://dx.doi.org/10.1186/s12935-021-01973-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165811PMC
May 2021

The intestinal microbiota contributes to the growth and physiological state of muscle tissue in piglets.

Sci Rep 2021 May 27;11(1):11237. Epub 2021 May 27.

Chongqing Academy of Animal Science, Rongchang, Chongqing, 402460, China.

Although the importance of the intestinal microbiota in host growth and health is well known, the relationship between microbiota colonization and muscle development is unclear. In this study, the direct causal effects of the colonization of gut microorganisms on the muscle tissue of piglets were investigated. The body weight and lean mass of germ-free (GF) piglets were approximately 40% lower than those of normal piglets. The deletion of the intestinal microbiota led to weakened muscle function and a reduction in myogenic regulatory proteins, such as MyoG and MyoD, in GF piglets. In addition, the blinded IGF1/AKT/mTOR pathway in GF piglets caused muscle atrophy and autophagy, which were characterized by the high expression of Murf-1 and KLF15. Gut microbiota introduced to GF piglets via fecal microbiota transplantation not only colonized the gut but also partially restored muscle growth and development. Furthermore, the proportion of slow-twitch muscle fibers was lower in the muscle of GF piglets, which was caused by the reduced short-chain fatty acid content in the circulation and impaired mitochondrial function in muscle. Collectively, these findings suggest that the growth, development and function of skeletal muscle in animals are mediated by the intestinal microbiota.
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http://dx.doi.org/10.1038/s41598-021-90881-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160342PMC
May 2021

A new nairo-like virus associated with human febrile illness in China.

Emerg Microbes Infect 2021 Dec;10(1):1200-1208

Department of Emerging Infectious Diseases, The First Hospital of Jilin University, Changchun, People's Republic of China.

Several nairo-like viruses have been discovered in ticks in recent years, but their relevance to public health remains unknown. Here, we found a patient who had a history of tick bite and suffered from a febrile illness was infected with a previously discovered RNA virus, Beiji nairovirus (BJNV), in the nairo-like virus group of the order . We isolated the virus by cell culture assay. BJNV could induce cytopathic effects in the baby hamster kidney and human hepatocellular carcinoma cells. Negative-stain electron microscopy revealed enveloped and spherical viral particles, morphologically similar to those of nairoviruses. We identified 67 patients as BJNV infection in 2017-2018. The median age of patients was 48 years (interquartile range 41-53 years); the median incubation period was 7 days (interquartile range 3-12 days). Most patients were men (70%), and a few (10%) had underlying diseases. Common symptoms of infected patients included fever (100%), headache (99%), depression (63%), coma (63%), and fatigue (54%), myalgia or arthralgia (45%); two (3%) patients became critically ill and one died. BJNV could cause growth retardation, viremia and histopathological changes in infected suckling mice. BJNV was also detected in sheep, cattle, and multiple tick species. These findings demonstrated that the newly discovered nairo-like virus may be associated with a febrile illness, with the potential vectors of ticks and reservoirs of sheep and cattle, highlighting its public health significance and necessity of further investigation in the tick-endemic areas worldwide.
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http://dx.doi.org/10.1080/22221751.2021.1936197DOI Listing
December 2021