Economic burden of pertussis in children: A single-center analysis in Hangzhou, China.

The "reemergence of pertussis" has elicited international concerns, occurring paradoxically amidst the expansion of immunization programs. This study was aimed to evaluate quantitatively the economic burden and identify the determinants that influence the cost associated with treating pertussis in Chinese children. We evaluated the economic burden by Chinese children diagnosed with pertussis at the Children's Hospital, Zhejiang University School of Medicine in 2022. Direct medical expenses and the utilization of medical resources attributed to pertussis were calculated. A generalized linear regression model was applied to analyze the determinants that were associated with the direct medical expenses among patients. Among the 1110 pertussis patients included in the study, 1060 were outpatients and 50 were inpatients. The average direct medical cost was ¥1878.70(i.e. $279.33). Living in urban areas (OR:1.27, p = .04), complications (OR:1.40, p < .001), hospitalization (OR:10.04, p < .001), and ≥ 3 medical visits (OR:3.71, p < .001) were associated with increased direct medical expenses. Having received four doses of the pertussis vaccine was associated with reduced direct medical expenses (OR:0.81, p = .04). This study underscores a substantial economic burden of pertussis in Hangzhou, with pronounced implications for patients residing in urban areas, experiencing complications, requiring hospitalization, having multiple medical consultations, or lacking comprehensive pertussis vaccination.

Study of decreased serum levels of C1q/TNF-related protein 4 (CTRP4) in major depressive disorder.

BACKGROUND: The adipokines secreted by adipocytes might play an important role through crossing the blood brain barrier to the brain, which could mediate the common physiological pathway between depression and obesity. CTRP4, a member of the CTRP family, is highly expressed in human adipose tissue and brain tissue. OBJECTIVE: this study aimed to measure serum C1q/TNF-related protein 4 (CTRP4) levels in depressive patients to explore the association between CTRP4 levels and depression. METHODS: depressive patients (n = 138), healthy controls (n = 100) were enrolled from September 2020 to December 2021. The level of serum CTRP4 was measured by enzymes linked to immunosorbent assay (ELISA). Other biochemical indicators were measured by Advia 2400 automatic biochemistry analyzer. Depressive symptoms of patients were assessed using the Hamilton Depression Scale-24 item (HAMD-24). RESULTS: this study found that serum CTRP4 levels in the MDD group were lower than that of the health control (P < 0.001). Serum CTRP4 levels were negatively correlated with HAMD-24 scores (r = -0.368; P = 0.001). The serum CTRP4 levels were negatively correlated with Total Cholesterol (TC), Triglyceride (TG) and Low-Density Lipoprotein Cholesterol (LDL-C), but were positively associated with high density lipid-cholesterol (HDL-C) (r = -0.267, r = -0.255, r = -0.312 and r = 0.280; P = 0.017, P = 0.023, P = 0.005 and P = 0.012). The ROC curve of CTRP4 showed that the Area Under Curve (AUC) was 0.856, P < 0.001. CONCLUSION: the serum CTRP4 levels in MDD patients were lower than that in health control, which might mediate the physiological progress of MDD patients.

Acceptance of influenza vaccination and associated factors among teachers in China: A cross-sectional study based on health belief model.

Teachers played an important role on the transmission of influenza in schools and communities. The study aims to investigate the influenza vaccination coverage and the factors determining flu vaccination acceptance among teachers in Hangzhou, China. A total of 1039 junior high school teachers in Hangzhou were recruited. The self-made questionnaire was used to investigate the influenza vaccine coverage among teachers and the influencing factors of influenza vaccination acceptance. Univariate analysis using the chi-square test and multivariable analysis using binary logistic regression were conducted to determine the relative predictors. The Influenza vaccine coverage among teachers was 5.9% (62/1039). 52.9% of teachers had the intention to receive influenza vaccine, 25.3% (247/977)/21.8% (213/977) of participants was hesitant/did not have the intention to get influenza vaccine. The top three sources for teachers to gain knowledge about influenza were website (72%), TV/radio (66.1%) and social media (58%). Whether get influenza vaccination before, knowledge about influenza and influenza vaccine, the beliefs for the likelihood of catching flu, the severity of getting flu, the effectiveness of influenza vaccine, the possibility of side effects after vaccination, and the troublesome of vaccination, doctors' recommendation, as well as the situation of vaccination among other teachers were the associated factors of influenza vaccination acceptance. The influenza vaccination coverage was low but the intentions were relatively high among junior high school teachers. Future research should focus on the relationship between vaccination acceptance and behavior to increase influenza vaccination rates.

Do adolescents need a rubella vaccination campaign? Rubella serosurvey among healthy children in Hangzhou, China.

The aim of this study was to evaluate the seroprevalence of rubella antibodies and factors associated with antibody seropositivity after vaccination among healthy children aged 14 and below. A multi-stage stratified random sampling method was employed to recruit participants for the rubella serological test. An enzyme-linked immunosorbent assay method was used to detect human IgG antibodies with avidity for rubella virus in the sera of participants. Univariate and multivariate analyses were used to analyze associations between variables. A total of 778 subjects were included in the subsequent analysis. The overall positive rate of rubella antibody was 83.0% (95%CI: 80.2-85.5%), and the overall geometric mean concentration (GMC) was 58.05 IU/ml. In multivariate analysis, gender, residence, birth year group, and time since the last rubella-containing vaccines (RCV) vaccination were significantly associated with the seroprevalence of rubella antibodies. Our study showed a decreasing trend in rubella antibody positivity and GMC in the population aged five to 14 years. Therefore, we recommend a catch-up dose of RCV for adolescents and young people aged over 14 years not yet vaccinated.

Analysis of 13-valent pneumococcal polysaccharide conjugate vaccine among children born in Hangzhou from 2017 to 2021.

Background: 13-valent pneumococcal polysaccharide conjugate vaccine (PCV13) has been introduced in Hangzhou since 2017, whereas its current immunization state in children is not clear. Therefore, this study aims to describe the PCV13 vaccination distribution among children born in Hangzhou from 2017 to 2021 to provide data for reducing vaccination differences among different populations. Methods: Descriptive epidemiology was used for data analysis and PCV13 vaccination related information of children was collected from children vaccination management system of Zhejiang Province (ZJCVMS). Results: Among the 649,949 children born in Hangzhou from 2017 to 2021, 169,230 were vaccinated with an average full course vaccination rate of 26.0%. The full course vaccination rates in 5 years were different (P = 0.000) with an increasing trend (P fortrend < 0.01). The first dose vaccination rates were different in 5 years (P = 0.000) with an increasing trend (P fortrend < 0.01). The distribution of age when first dose PCV13 was administered varied, most people at 2 months and least people at 5 months. The full course vaccination rate varied by areas, highest in central urban areas and lowest in remote areas respectively (all P-value < 0.05). Overall, the full course vaccination rate of PCV13 was higher in the registered residence population than the non-registered residence population, which was 136,693 (31.4%) and 32,537 (15.1%) respectively (P = 0.000). The full course vaccination rates were the same between men and women (P = 0.502), which was 87,844 for men (26.0%) and 81,386 for women (26.1%). Conclusion: Although the number of people who received PCV13 full course vaccination and received the first dose vaccination showed yearly increasing trends in Hangzhou, the full course vaccination rate for the whole population was relatively low. In addition, the PCV13 vaccination rates also differed by geography and household registration status. Measures such as expanding vaccination publicity or including national immunization should be taken to increase vaccination rates and reduce the differences in vaccination among groups with different characteristics.

Real-world vaccination status of children with hematologic tumors before and after chemotherapy.

BACKGROUND: There is a high incidence and mortality rate in children with hematologic tumors (CHT), who are more prone to various infectious diseases. This study aims to clarify the real-world National Immunization Program (NIP) vaccination status of CHT before and after chemotherapy. METHODS: Medical records, NIP vaccination data, and the Adverse Event Following Immunization (AEFI) of CHT who were admitted to the Children's Hospital, Zhejiang University School of Medicine, from 1 January 2011 to 1 December 2021 were completely collected. RESULTS: A total of 2,874 CHT were included, and 1975 (68.7%) had vaccination records. Among the enrolled patients, the vaccination rate of all NIP vaccines was lower than 90% before diagnosis. Only 24.29% of CHT (410/1688) resumed vaccination after chemotherapy, and 69.02% (283/410) resumed vaccination more than 12 months after chemotherapy. No uncommon or serious side effects were reported. CONCLUSION: The vaccination rate of CHT after chemotherapy was lower than that before the disease was diagnosed. It is necessary to provide more evidence-based support and formulate specific regimens to perfect the vaccination procedure after chemotherapy so as to improve the quality of life of CHT.

Awake Fiberoptic Nasotracheal Intubation and Anesthetic Management of a Patient With a Compressed and Deviated Airway From a Massive Thyroid Goiter: A Case Report.

Difficult airway management is a challenge for anesthesiologists, requiring proper assessment, planning, and sometimes a multidisciplinary approach to establish a secure airway. Here we present a case where the patient had a large thyroid goiter with significant tracheal compression. Due to the large size of the thyroid mass and the location of tracheal narrowing, fiberoptic intubation appeared to be challenging, and a surgical airway was not a viable option to obtain a secure airway for a total thyroidectomy. This case report discusses awake fiberoptic intubation and intraoperative anesthetic management of a patient with known airway compression and explores the alternative method for obtaining a definitive airway through venovenous extracorporeal membrane oxygenation.

Associated factors of burnout among Chinese vaccination staff during COVID-19 epidemic: A cross-sectional study.

Objective: During the COVID-19 epidemic, vaccination staff had three main aspects of work: routine vaccination for children and adults, COVID-19 vaccination and COVID-19 prevention and control. All these works significantly increased the workload of vaccination staff. This study aimed to investigate the prevalence and influencing factors of burnout among vaccination staff in Hangzhou, China. Methods: A total of 501 vaccination staff from 201 community/township healthcare centers in Hangzhou were recruited using a cross-sectional survey through WeChat social platform. The Maslach Burnout Inventory-General Scale (MBI-GS) was used to assess the level of burnout. Descriptive statistics were made on the characteristics of participants. Univariate analysis using the chi-square test and multivariable analysis using binary logistic regression were conducted to determine the relative predictors of burnout. Univariate analysis and multiple linear regression were used to determine the relative predictors of exhaustive emotion, cynicism, and personal accomplishment. Results: During the COVID-19 pandemic, 20.8% of the vaccination staff experienced burnout. Educational level above undergraduate education level, medium professional title, and more working time in COVID-19 vaccination work reported a higher degree of job burnout. The vaccination staff was experiencing a high degree of exhaustive emotion, cynicism, and low personal accomplishment. Professional title, working place, and working time for COVID-19 vaccination were associated with exhaustive emotion and cynicism. Professional title and participation time for COVID-19 prevention and control were associated with personal accomplishment. Conclusions: Our findings suggest that the prevalence rate of burnout is high among vaccination staff during the COVID-19 pandemic, especially with a low level of personal accomplishment. Psychological intervention for vaccination staff is urgently needed.

Current vaccination status and safety of children with peripheral neuroblastoma in the real-world.

Background: peripheral neuroblastic tumors (pNT) have high incidence and mortality, and infants are prone to various infectious diseases. The purpose of this study is to understand the immunization status of children with pNT in the real-world and the incidence of adverse reactions after vaccination, and to evaluate the feasibility of vaccination and the influencing factors of vaccination. Methods: Children with pNT treated in the Children's Hospital Affiliated to Zhejiang University from January 1, 2011 to December 1, 2021 were included. By referring to medical records, the vaccination history of the national immunization program (NIP) vaccines and the occurrence of adverse events following immunization(AEFI), current status and safety of immunization in children with pNT in the real-world were analyzed. Results: Among 784 children with pNT, 394 were able to obtain the history of vaccination. The overall vaccination rate of NIP vaccines was 71.49% before chemotherapy and 37.67% after chemotherapy, and the recovery time of vaccination after treatment was 16.00 (6.00,24.00) months. Age, time of tumor diagnosis and disease classification were significantly correlated with vaccination. AEFI reported an incidence of 0.23‰. Conclusion: The vaccination rate of children with pNT is generally low, especially the vaccination rate after chemotherapy. The vaccination safety is good, children should be encouraged to immunize.

Cost-effectiveness of various immunization schedules with inactivated Sabin strain polio vaccine in Hangzhou, China.

Background: It is necessary to select suitable inactivated poliovirus vaccine(IPV) and live, attenuated oral poliovirus vaccine (OPV) sequential immunization programs and configure the corresponding health resources. An economic evaluation was conducted on the sequential procedures of Sabin strain-based IPV (sIPV) and bivalent OPV (bOPV) with different doses to verify whether a cost-effectiveness target can be achieved. This study aimed to evaluate the cost-effectiveness of different sIPV immunization schedules, which would provide convincing evidence to further change the poliovirus vaccine (PV) immunization strategies in China. Methods: Five strategies were included in this analysis. Based on Strategy 0(S0), the incremental cost (IC), incremental effect (IE), and incremental cost-effectiveness ratio (ICER) of the four different strategies (S1/S2/S3/S4) were calculated based on the perspective of the society. Seven cost items were included in this study. Results of field investigations and expert consultations were used to calculate these costs. Results: The ICs of S1/S2/S3/S4 was Chinese Yuan (CNY) 30.77, 68.58, 103.82, and 219.82 million, respectively. The IE of vaccine-associated paralytic poliomyelitis (IEVAPP) cases of S1/S2/S3/S4 were 0.22, 0.22, 0.22, and 0.11, respectively, while the IE of disability-adjusted life-years (IEDALY) of S1/S2/S3/S4 were 8.98, 8.98, 8.98, and 4.49, respectively. The ICERVAPP of S1/S2/S3/S4 gradually increased to CNY 13.99, 31.17, 47.19, and 199.83 million/VAPP, respectively. The ICERDALY of S1/S2/S3/S4 also gradually increased to CNY 0.34, 0.76, 1.16, and 4.90 million/DALY, respectively. Conclusion: ICERVAPP and ICERDALY were substantially higher for S3 (four-sIPV) and S4 (replacement of self-funded sIPV based on one-sIPV-three-bOPV). Two-sIPV-two-bOPV had a cost-effectiveness advantage, whereas S2/S3/S4 had no cost-effectiveness advantage.

TRIM56 impairs HBV infection and replication by inhibiting HBV core promoter activity.

Members of the tripartite motif (TRIM) protein family strongly induced by interferons (IFNs) are parts of the innate immune system with antiviral activity. However, it is still unclear which TRIMs could play important roles in hepatitis B virus (HBV) inhibition. Here, we identified that TRIM56 expression responded in IFN-treated HepG2-NTCP cells and HBV-infected liver tissues, which was a potent IFN-inducible inhibitor of HBV replication. Mechanistically, TRIM56 suppressed HBV replication via its Ring and C-terminal domain. C-terminal domain was essential for TRIM56 translocating from cytoplasm to nucleus during HBV infection. Further analysis revealed that TRIM56's Ring domain targeted IκBα for ubiquitination. This modification induced phosphorylation of p65, which subsequently inhibited HBV core promoter activity, resulting in the inhibition of HBV replication. The p65 was found to be necessary for NF-κB signal pathway to inhibit HBV replication. We verified our findings using HepG2-NTCP and primary human hepatocytes. Our findings reveal that TRIM56 is a critical antiviral immune effector and exerts an anti-HBV activity via NF-κB signal pathway, which is essential for inhibiting transcription of HBV covalently closed circular DNA.

Influence of Bacillus subtilis strain Z-14 on microbial communities of wheat rhizospheric soil infested with Gaeumannomyces graminis var. tritici.

Wheat take-all disease caused by Gaeumannomyces graminis var. tritici (Ggt) spreads rapidly and is highly destructive, causing severe reductions in wheat yield. Bacillus subtilis strain Z-14 that significantly controlled wheat take-all disease effectively colonized the roots of wheat seedlings. Z-14 increased the metabolic activity and carbon source utilization of rhizospheric microorganisms, thus elevating average well-color development (AWCD) values and functional diversity indexes of soil microbial communities. Z-14 increased the abundance of Bacillus in the rhizosphere, which was positively correlated with AWCD and functional diversity indexes. The Z-14-treated samples acquired more linkages and relative connections between bacterial communities according to co-occurrence network analyses. After the application of Ggt, the number of linkages between fungal communities increased but later decreased, whereas Z-14 increased such interactions. Whole-genome sequencing uncovered 113 functional genes related to Z-14's colonization ability and 10 secondary metabolite gene clusters in the strain, of which nine substances have antimicrobial activity. This study clarifies how bacterial agents like Z-14 act against phytopathogenic fungi and lays a foundation for the effective application of biocontrol agents.

Epidemiological characteristic of rubella by age group during 12 years after the national introduction of rubella vaccine in Hangzhou, China.

This study aimed to evaluate the implementation and impact of rubella-containing vaccine (RCV) by describing the rubella epidemiology and seroepidemiology in Hangzhou. We collected rubella cases of Hangzhou in the Information System for Disease Control and Prevention in China between 2009 and 2020, and performed a descriptive analysis. We applied a multi-stage stratified random sampling method to recruit participants for serological tests of rubella. Enzyme Linked Immunosorbent Assay (ELISA) was used to detect Immunoglobulin G (IgG) antibodies against rubella in serum samples. Univariate and multivariate analyses are used to detect the association between the level of rubella IgG and related factors. The incidence of rubella cases per million population decreased from 15.8 in 2009 to .1 in 2020. The proportion of rubella cases in women of childbearing age was higher than in men. A total of 4,362 subjects were tested serologically for rubella. The percentage of people whose rubella IgG antibody titers were above the minimum protective level (20 IU/ml) was 80.60% (95% CI: 79.4%-81.8%) and the geometric mean concentration (GMC) for rubella IgG was 58.34 IU/ml. The data indicated that Hangzhou had made good progress toward the elimination of rubella, whereas women of childbearing age still had a higher proportion of rubella cases, which might lead to increased risk of subsequent CRS. The positive rate and GMC of rubella IgG were significantly influenced by age and immunization history of RCV. Therefore, we should stress the importance of pushing forward the campaign for supplementary vaccination of rubella in adults.

The enhancement role of Matrigel on HBV infection in HepG2-NTCP cells.

The hepatoma cell lines stably expressing sodium taurocholate cotransporting polypeptide (NTCP), the receptor of hepatitis B virus (HBV) infection, serve as important infection models for studying viral biology and drug discovery. However, the efficiency of infection greatly varies. In this study, we studied the effects and potential mechanisms of Matrigel® hESC-qualified (M-hq), a biological basement membrane matrix commonly used in cell culture, on promotion HBV in vitro infection in HepG2-NTCP cells. For the first time, our findings demonstrate that M-hq could enhance the infection efficiency of cell culture-derived HBV with no impact on the cell viability, the HBV transcription and response to antiviral treatments. The infection enhancement is reproducible and is suggested to occur at HBV attachment step. Our study suggests that this novel system is applicable for studying HBV biology and new drugs.

Analysis on the intention and influencing factors of free influenza vaccination among the elderly people aged 70 and above in Hangzhou in 2022.

Background: Although influenza vaccination is recommended for people aged 70 and above in Hangzhou, and the vaccine is provided free of charge, the elderly influenza vaccination rate is still low. The purpose of this study was to understand the barriers and motivations of older people in deciding to receive free influenza vaccine through questionnaires. Methods: The method of stratified random sampling was adopted to take samples. A questionnaire survey was conducted among the elderly aged 70 years and above by face-to-face interview or telephone interview. Results: A total of 11,663 elderly people aged 70-100 years were successfully and effectively interviewed. 85.98% of the respondent were willing to get the influenza shot, 8.91% were unwilling to get the influenza shot, and 5.11% were on vaccine hesitancy. The people of age of 70-79 years old (hesitancy: OR 70~79 = 0.668, 95%CI: 0.571 0.782, Unwilling: OR 70 - 79 = 0.755, 95%CI: 0.622 0.916), primary school degree or below (hesitancy: OR Secondary school degree or above = 1.467, 95%CI: 1.249 1.724, Unwilling: OR Secondary school degree or above = 1.255, 95%CI: 1.028 1.535), remote areas (hesitancy: OR near central urban area = 2.111, 95%CI: 1.604 2.778, OR central urban area = 2.957, 95%CI: 2.255 3.877, Unwilling: OR near central urban area = 1.687, 95%CI: 1.230 2.313. OR centralurbanarea = 2.218, 95%CI: 1.626 3.027), and convenient for movement (hesitancy: OR yes = 0.494, 95%CI: 0.420 0.580, Unwilling: OR yes = 0.585, 95%CI: 0.480 0.713), understanding of the free vaccine policy (hesitancy: OR understand = 0.204, 95%CI: 0.171 0.245, Unwilling: OR understand = 0.164, 95%CI: 0.128 0.210), influenza knowledge level≥ 13 points (hesitancy: OR ≥13points = 0.628, 95%CI: 0.533 0.739, Unwilling: OR ≥13points = 0.538, 95%CI: 0.437 0.662), influenza vaccine knowledge level≥ 12 points (hesitancy: OR ≥12points = 0.422, 95%CI: 0.350 0.508, Unwilling: OR ≥12points = 0.370, 95%CI: 0.290 0.472), and social trust level ≥ 12 points (hesitancy: OR ≥12points = 0.134, 95%CI: 0.112 0.160, Unwilling: OR ≥12points = 0.220, 95%CI: 0.180 0.269) are more willing to receive free influenza vaccine. Conclusion: The proportion of elderly people aged 70 and above who are willing to receive free influenza vaccine is high in Hangzhou. But the level of knowledge about influenza, vaccine and trust in society is low. The government should continue to improve the elderly's awareness and trust in society through medical staff, family members, television and radio media, and guide the elderly to actively vaccinate against influenza. Effective publicity should be carried out through the above channels to guide the elderly to actively vaccinate against influenza.

Uncovering a conserved vulnerability site in SARS-CoV-2 by a human antibody.

An essential step for SARS-CoV-2 infection is the attachment to the host cell receptor by its Spike receptor-binding domain (RBD). Most of the existing RBD-targeting neutralizing antibodies block the receptor-binding motif (RBM), a mutable region with the potential to generate neutralization escape mutants. Here, we isolated and structurally characterized a non-RBM-targeting monoclonal antibody (FD20) from convalescent patients. FD20 engages the RBD at an epitope distal to the RBM with a KD of 5.6 nM, neutralizes SARS-CoV-2 including the current Variants of Concern such as B.1.1.7, B.1.351, P.1, and B.1.617.2 (Delta), displays modest cross-reactivity against SARS-CoV, and reduces viral replication in hamsters. The epitope coincides with a predicted "ideal" vulnerability site with high functional and structural constraints. Mutation of the residues of the conserved epitope variably affects FD20-binding but confers little or no resistance to neutralization. Finally, in vitro mode-of-action characterization and negative-stain electron microscopy suggest a neutralization mechanism by which FD20 destructs the Spike. Our results reveal a conserved vulnerability site in the SARS-CoV-2 Spike for the development of potential antiviral drugs.

Hepatitis B virus infection seromarkers among college freshmen and their immune responses to different vaccination policies of hepatitis B vaccine.

BACKGROUND: College students are one of the susceptible population of Hepatitis B virus (HBV) infection. We aim to delineate HBV infection seromarkers among college freshmen and to evaluate immunological response of vaccination immunization for hepatitis B vaccine (HepB). METHODS: A simple random sampling method was adopted to select subjects and who met the "inclusion and exclusion criteria" and who with history of vaccination were selected as the observation objects. HBsAg and anti-HBs levels were detected before revaccination. Subjects with negative anti-HBs before immunization were inoculated with 20 ug HepB according to the 0-1-6 procedure and those with weak positive anti-HBs before immunization were inoculated with 1-dose 20 ug HepB. Anti-HBs levels were detected after HepB booster. Combined with the results of anti-HBs, their immune response to HepB and influencing factors in freshmen were investigated. Anti-HBs before immunization was negative and ≥10 m IU/ml after immunization was considered positive conversion; anti-HBs before immunization was weak positive and anti-HBs≥100 m IU/ml after immunization was also considered positive conversion. RESULTS: A total of 10645 freshmen were included. The total rate of HBsAg carriers was 0.6% (63/10645), and the strong positive rate of anti-HBs was 16.1% (1706/10645), the weak positive rate was 14.4% (1526/10645).1286 freshmen were vaccinated with HepB and completed the questionnaire survey. About 79.0% (154/195) of freshmen's anti-HBs turned strong positive after receiving 1-dose HepB and 100.0% (1091/1091) turned positive after receiving 3-doses HepB. The Geometrical Mean Titer (GMT) of anti-HBs was significantly influenced by gender, registration and the immunization doses of HepB. CONCLUSION: The HBsAg carrying rate and anti-HBs positive rate of college freshmen were low, and the HepB has a good effect on the immunity of college freshmen. Increasing the immunization rate of HepB is very important for the prevention and control of hepatitis B.

Activity of Fengycin and Iturin A Isolated From Bacillus subtilis Z-14 on Gaeumannomyces graminis Var. tritici and Soil Microbial Diversity.

Bacillus subtilis Z-14 can inhibit phytopathogenic fungi, and is used as a biocontrol agent for wheat take-all disease. The present study used the soil-borne fungus Gaeumannomyces graminis var. tritici (Ggt), which causes wheat take-all disease, and the soil microbial community as indicators, and investigated the antifungal effects of fengycin and iturin A purified from strain Z-14 using high performance liquid chromatography and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, respectively. The results showed that fengycin destroyed the internal structure of Ggt cells by digesting the cytoplasm and organelles, forming vacuoles, and inducing hyphal shrinkage and distortion. Iturin A induced cell wall disappearance, membrane degeneration, intracellular material shrinkage, and hyphal fragmentation. A biocontrol test demonstrated a 100% control effect on wheat take-all when wheat seedlings were treated with fengycin at 100 µg/ml or iturin A at 500 µg/ml. Iturin A and fengycin both reduced the relative abundance of Aspergillus and Gibberella. At the genus level, iturin A reduced the relative abundance of Mortierella and Myrothecium, while fengycin reduced that of Fusarium. Only fengycin treatment for 7 days had a significant effect on soil bacterial diversity.

The Genotype (A to H) Dependent N-terminal Sequence of HBV Large Surface Protein Affects Viral Replication, Secretion and Infectivity.

Genetic variability has significant impacts on biological characteristics and pathogenicity of hepatitis B virus (HBV), in which the N-terminal sequence of the presurface 1 (preS1) region of HBV large surface protein (LHBs) displays genotype (GT) dependent genetic heterogeneity. However, the influence of this heterogeneity on its biological roles is largely unknown. By analyzing 6560 full-length genome sequences of GTA-GTH downloaded from HBVdb database, the preS1 N-terminal sequences were divided into four representative types, namely C-type (representative of GTA, GTB, and GTC), H-type (GTF and GTH), E-type (GTE and GTG), and D-type (GTD), respectively. We artificially substituted the preS1 N-termini of GTC and GTD plasmids or viral strains with each sequence of the four representative types. The roles of preS1 N-terminus on HBV replication, secretion and infectivity were investigated using HepG2 or HepG2-NTCP cells. In the transfection experiments, the results showed that the extracellular HBsAg levels and HBsAg secretion coefficients in D- and E-type strains were significantly higher than those in C- and H-type strains. D-type strain produced more extracellular HBV DNA than C-type strain. We further observed that D-, H-, and E-type strains increased the levels of intracellular replicative HBV DNAs, comparing with C-type strain. In the infection experiments, the levels of extracellular HBeAg, intracellular HBV total RNA and pgRNA/preC mRNA in D- and E-type strains were markedly higher than C and H-type ones. Our data suggest that the preS1 N-termini affect HBV replication, secretion and infectivity in a genotype dependent manner. The C- and H-type strains prefer to attenuate HBsAg secretion, while the strains of D- and E-type promoted infectivity. The existence and function of the intergenotypic shift of preS1 in naturally occurring recombination requires further investigation, as the data we acquired are mostly related to recombinant preS1 region between N-terminus of preS1 from genotypes A-H and the remaining preS1 portion of GTC or GTD.

Genetic diversity and evolutionary patterns of Taraxacum kok-saghyz Rodin.

Taraxacum kok-saghyz Rodin (TKS) is an important potential alternative source of natural inulin and rubber production, which has great significance for the production of industrial products. In this study, we sequenced 58 wild TKS individuals collected from four different geography regions worldwide to elucidate the population structure, genetic diversity, and the patterns of evolution. Also, the first flowering time, crown diameter, morphological characteristics of leaf, and scape of all TKS individuals were measured and evaluated statistically. Phylogenetic analysis based on SNPs and cluster analysis based on agronomic traits showed that all 58 TKS individuals could be roughly divided into three distinct groups: (a) Zhaosu County in Xinjiang (population AB, including a few individuals from population C and D); (b) Tekes County in Xinjiang (population C); and (c) Tuzkol lake in Kazakhstan (population D). Population D exhibited a closer genetic relationship with population C compared with population AB. Genetic diversity analysis further revealed that population expansion from C and D to AB occurred, as well as gene flow between them. Additionally, some natural selection regions were identified in AB population. Function annotation of candidate genes identified in these regions revealed that they mainly participated in biological regulation processes, such as transporter activity, structural molecule activity, and molecular function regulator. We speculated that the genes identified in selective sweep regions may contribute to TKS adaptation to the Yili River Valley of Xinjiang. In general, this study provides new insights in clarifying population structure and genetic diversity analysis of TKS using SNP molecular markers and agronomic traits.