Spatial analysis and influencing factors of pulmonary tuberculosis among students in Nanning, during 2012-2018.

BACKGROUND: Economically underdeveloped areas in western China are hotspots of tuberculosis, especially among students. However, the related spatial and temporal patterns and influencing factors are still unclear and there are few studies to analyze the causes of pulmonary tuberculosis in students from the perspective of space. METHODS: We collected data regarding the reported incidence of pulmonary tuberculosis (PTB) among students at township level in Nanning, from 2012 to 2018. The reported incidence of pulmonary tuberculosis among students in Nanning was analyzed using spatial autocorrelation and spatial scan statistical analysis to depict hotspots of PTB incidence and spatial and temporal clustering. Spatial panel data of the reported incidence rates and influencing factors at district and county levels in Nanning were collected from 2015 to 2018. Then, we analyzed the spatial effects of incidence and influencing factors using the spatial Durbin model to explore the mechanism of each influencing factor in areas with high disease prevalence under spatial effects. RESULTS: From 2012 to 2018, 1609 cases of PTB were reported among students in Nanning, with an average annual reported incidence rate of 14.84/100,000. Through the Joinpoint regression model, We observed a steady trend in the percentage of cases reported each year (P>0.05). There was spatial autocorrelation between the annual reported incidence and the seven-years average reported incidence from 2012 to 2018. The high-incidence area was distributed in the junction of six urban areas and spread to the periphery, with the junction at the center. The population of college students, per capita financial expenditure on health, per capita gross domestic product, and the number of health technicians per 1,000 population were all influencing factors in the reported incidence of PTB among students. CONCLUSION: We identified spatial clustering of the reported incidence of PTB among students in Nanning, mainly located in the urban center and its surrounding areas. The clustering gradually decreased from the urban center to the surrounding areas. Spatial effects influenced the reported incidence of PTB. The population density of college students, per capita health financial expenditure, gross domestic product (GDP) per capita, and the number of health technicians per 1,000 were all influencing factors in the reported incidence of PTB among students.

Anti-SARS-CoV-2 activities in vitro of Shuanghuanglian preparations and bioactive ingredients.

Human infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and there is no cure currently. The 3CL protease (3CLpro) is a highly conserved protease which is indispensable for CoVs replication, and is a promising target for development of broad-spectrum antiviral drugs. In this study we investigated the anti-SARS-CoV-2 potential of Shuanghuanglian preparation, a Chinese traditional patent medicine with a long history for treating respiratory tract infection in China. We showed that either the oral liquid of Shuanghuanglian, the lyophilized powder of Shuanghuanglian for injection or their bioactive components dose-dependently inhibited SARS-CoV-2 3CLpro as well as the replication of SARS-CoV-2 in Vero E6 cells. Baicalin and baicalein, two ingredients of Shuanghuanglian, were characterized as the first noncovalent, nonpeptidomimetic inhibitors of SARS-CoV-2 3CLpro and exhibited potent antiviral activities in a cell-based system. Remarkably, the binding mode of baicalein with SARS-CoV-2 3CLpro determined by X-ray protein crystallography was distinctly different from those of known 3CLpro inhibitors. Baicalein was productively ensconced in the core of the substrate-binding pocket by interacting with two catalytic residues, the crucial S1/S2 subsites and the oxyanion loop, acting as a "shield" in front of the catalytic dyad to effectively prevent substrate access to the catalytic dyad within the active site. Overall, this study provides an example for exploring the in vitro potency of Chinese traditional patent medicines and effectively identifying bioactive ingredients toward a specific target, and gains evidence supporting the in vivo studies of Shuanghuanglian oral liquid as well as two natural products for COVID-19 treatment.

Exogenous FABP4 interferes with differentiation, promotes lipolysis and inflammation in adipocytes.

PURPOSE: Fatty acid binding protein 4 (FABP4) has been demonstrated to be secreted from adipocytes in an unconventional pathway associated with lipolysis. Circulating FABP4 is elevated in metabolic disorders and has been shown to affect various peripheral cells such as pancreatic ß-cells, hepatocytes and macrophages, but its effects on adipocytes remains unclear. The aim of this study was to investigate the effects of exogenous FABP4 (eFABP4) on adipocyte differentiation and function. METHODS: 3T3-L1 pre-adipocytes or mature adipocytes were treated with recombinant FABP4 in the absence or presence of FABP4 inhibitor I-9/p38 MAPK inhibitor SB203580; Meanwhile male C57BL/6J mice were subcutaneously injected twice a day with recombinant FABP4 (0.35 mg/kg) with or without I-9 (50 mg/kg) for 2 weeks. The effects of eFABP4 on differentiation, lipolysis and inflammation were determined by triglyceride measurement or lipolysis assay, western blotting, or RT-qPCR analysis. RESULTS: eFABP4 treatment significantly reduced intracellular triglyceride content and decreased expression of adipogenic markers peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer binding protein alpha (C/EBPα), intracellular FABP4, and adiponectin in 3T3-L1 cells. Besides, eFABP4 promoted lipolysis and inflammation in differentiated 3T3-L1 adipocytes as well as in adipose tissue of eFABP4-treated C57BL/6J mice, with elevated gene expression of monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF)-α, and elevated protein expression of adipose triglyceride lipase (ATGL), phosphorylation of hormone-sensitive lipase (HSL) (Ser-660), p38, and nuclear factor-kappa B (NF-κB). The pro-inflammatory and pro-lipolytic effects of eFABP4 could be reversed by SB203580/I-9. CONCLUSIONS: These findings indicate that eFABP4 interferes with adipocyte differentiation, induces p38/HSL mediated lipolysis and p38/NF-κB mediated inflammation in adipocytes in vitro and in vivo.

From hit to lead: Structure-based discovery of naphthalene-1-sulfonamide derivatives as potent and selective inhibitors of fatty acid binding protein 4.

Fatty acid binding protein 4 (FABP4) plays a critical role in metabolism and inflammatory processes and therefore is a potential therapeutic target for immunometabolic diseases such as diabetes and atherosclerosis. Herein, we reported the identification of naphthalene-1-sulfonamide derivatives as novel, potent and selective FABP4 inhibitors by applying a structure-based design strategy. The binding affinities of compounds 16dk, 16do and 16du to FABP4, at the molecular level, are equivalent to or even better than that of BMS309403. The X-ray crystallography complemented by the isothermal titration calorimetry studies revealed the binding mode of this series of inhibitors and the pivotal network of ordered water molecules in the binding pocket of FABP4. Moreover, compounds 16dk and 16do showed good metabolic stabilities in liver microsomes. Further extensive in vivo study demonstrated that 16dk and 16do exhibited a dramatic improvement in glucose and lipid metabolism, by decreasing fasting blood glucose and serum lipid levels, enhancing insulin sensitivity, and ameliorating hepatic steatosis in obese diabetic (db/db) mice.

[Discussion of scattering in THz time domain spectrum tests].

Using THz-TDS to extract the absorption spectrum of a sample is an important branch of various THz applications. Basically, we believe that the THz radiation scatters from sample particles, leading to an obvious baseline increasing with frequencies in its absorption spectrum. The baseline will affect the measurement accuracy due to ambiguous height and pattern of the spectrum. The authors should try to remove the baseline, and eliminate the effects of scattering. In the present paper, we investigated the causes of baselines, reviewed some of scatter mitigating methods and summarized some of research aspects in the future. In order to validate the correctness of these methods, we designed a series of experiments to compare the computational accuracy of molar concentration. The result indicated that the computational accuracy of molar concentration can be improved, which can be the basis of quantitative analysis in further researches. Finally, with comprehensive experimental results, we presented further research directions on THz absorption spectrum that is needed for the removal of scattering effects.

Epidemiology of Hepatitis B Virus Infection in China: Current Status and Challenges.

The prevalence of hepatitis B is high in China. Based on the National Disease Supervision Information Management System of China, the mean reported incidence of hepatitis B was 84.3 per 100,000 in China between 2005 and 2010. There are differences in population distribution based on region and ethnic group. Here, risk factors, virological characteristics, and prophylaxis of hepatitis B in China are reviewed. Although the prevalence of HBV infection is gradually declining, there are many challenges in HBV infection control, including higher prevalence in floating population, poor compliance of antiviral therapy, and high disease burden.

[Intrinsic section and its interception model for temporal pulse of THz-TDS].

Using THz-TDS to detect the THz temporal pulse and calculate the absorption spectrum of the sample is the main access to qualitative and quantitative analysis. The shape and the amplitude of the THz absorption spectra are not only related to the sample, but also closely related to the length of the chosen THz pulse in the calculation, which was discovered in our experiments. It is the main cause of this problem that the flaky sample reflects the THz wave many times, which will give rise to the Fabry-Perot effect. So the sample-probing temporal signal is divided into the intrinsic section with the sample's information directly, low SNR noise section, and unwanted Fabry-Perot reflections section with the overlapped information. Based on THz pulse generation mechanism and the relationship between the pulse amplitude and the attenuate process, a model of intercepting the intrinsic section in terahertz time-domain pulse was proposed and was proved reliable and stable by the results from experiments performed with amino acids: glutamine(Gln), histidine(His), and cystine(Cys).

[The Lambert-Beer's law characterization of formal analysis in Terahertz spectrum quantitative testing].

The present paper discusses the Lambert-Beer' s law application in the terahertz spectrum, studies the single amino acid tablet sample (glutamine) and two kinds of amino acids mixture tablet (threonine and cystine) under the condition of different concentrations. Absorbance and absorption coefficient was analyzed in the description of the terahertz optical properties of matter. By comparing absorption coefficient and absorbance value of the single component in the vicinity of 1. 72 THz, we verified the material under two kinds of absorption characterization of quantity of THz wave absorption along with the change in the concentration. Using the index of goodness of fit R , it studied the stand or fall of linear relationship between the terahertz absorption quantity of material and concentration under two kinds of representation. This paper analyzes the two components mixture under two kinds of absorption characterization of quantity of terahertz absorption in 0. 3-2. 6 THz. Using the similarity co- efficient and the estimate concentration error as evaluation index, it has been clear that the absorbance of additivity instead of the absorption coefficient should be used during the terahertz spectrum quantitative test, and the Lambert-Beer's law application in the terahertz wave band was further clarified.

[Extracting THz absorption coefficient spectrum based on accurate determination of sample thickness].

Extracting absorption spectrum in THz band is one of the important aspects in THz applications. Sample's absorption coefficient has a complex nonlinear relationship with its thickness. However, as it is not convenient to measure the thickness directly, absorption spectrum is usually determined incorrectly. Based on the method proposed by Duvillaret which was used to precisely determine the thickness of LiNbO3, the approach to measuring the absorption coefficient spectra of glutamine and histidine in frequency range from 0.3 to 2.6 THz(1 THz = 10(12) Hz) was improved in this paper. In order to validate the correctness of this absorption spectrum, we designed a series of experiments to compare the linearity of absorption coefficient belonging to one kind amino acid in different concentrations. The results indicate that as agreed by Lambert-Beer's Law, absorption coefficient spectrum of amino acid from the improved algorithm performs better linearity with its concentration than that from the common algorithm, which can be the basis of quantitative analysis in further researches.

High conservation of hepatitis B virus surface genes during maternal vertical transmission despite active and passive vaccination.

OBJECTIVE: Our purpose was to explore the relationship between hepatitis B virus (HBV) gene heterogeneity and maternal vertical transmission. METHODS: HBsAg-positive mothers and their neonates were selected and classified into a vertical infection neonate group (group N), a vertical infection mother group (group M) and a control group (group C). Serum HBsAg and HBeAg were examined. HBV gene fragments, including the pre-S1, and pre-S2 and S coding regions, were amplified and sequenced, and the genotype and serotype of the sequences were identified. Mutation sites and frequency of mutations were then compared between group N and group C. RESULTS: A total of 104 HBV clone sequences were obtained. All obtained sequences belonged to genotype C and serotype adr. Upon comparing sequences between group N and group C, 4 nonsynonymous mutations were found with significant difference in mutation frequency (p < 0.05). When the mothers were both HBsAg and HBeAg positive, 10 nonsynonymous mutations were found. The frequencies of these mutations were significantly lower in group N than in group C (p < 0.05). CONCLUSION: The 10 HBV mutations were negatively associated with vertical transmission when maternal HBeAg was positive. Furthermore, the species that were vertically transmitted to the fetus were mainly wild-type.

[A follow-up study on the efficacy of hepatitis B immunoglobulin combining hepatitis B vaccine in infants born to HBsAg positive mothers].

OBJECTIVE: To study the efficacy of hepatitis B immunoglobulin (HBIG) combining hepatitis B vaccine in high risk infants born to HBsAg positive mothers through a follow-up study program. METHODS: 184 infants (4 twin pairs) born to HBsAg carrier mothers who were consecutively recruited from December 2002 to August 2004 were followed. Major HBV serologic markers in all infants were detected by enzyme-linked immunosorbent assay (ELISA) when they were at birth, at 7th, at 24th and at 36th months. RESULTS: 7 of the 184 infants were HBsAg positive at birth, making the transplacental intrauterine infection rate of HBV as 3.80% (7/184). 125 infants were followed up at 7th months and 108 infants were followed up at 24th and 36th months. Only 2 of the 7 infants born to HBsAg-positive and HBeAg-positive mothers were persistently sera positive for HBsAg, making the chronic infection rate of HBV as 28.57%. The other 140 infants were HBsAg negative during t he follow-up period. The rate o f detectable anti-HBs i ninfants was 7.02% at birth. After infants were immunized by HBIG combining hepatitis B vaccine, the anti-HBs-positive rate reached 92% at 7th months, and gradually descended thereafter. 72.04% of the infants at 24th and 60% at 36th months showed detectable levels of anti-HBs. There was significant correlation between the produce of anti-HBs in infants and HBsAg-positive at birth while HBsAg-positive and HBeAg-positive in mothers did not relate to the produce of anti-HBs in their infants. Of 39 infants born to HBsAg-positive and HBeAg-positive mothers, 25 showed detectable levels of HBeAg. During the follow-up peirod, HBeAg was still detectable in 2 infants who were also HBsAg positive and the others all became HBeAg-negative but no infant became HBeAg-positive. CONCLUSION: The efficacy of HBIG combining hepatitis B vaccine in high risk infants was fine.

Screening cellular proteins binding to the core region of hepatitis C virus RNA genome with digoxin-labeled nucleic acids.

OBJECTIVE: To screen and identify cellular proteins binding to the core region of hepatitis C virus (HCV) RNA genome. METHODS: The plasmid pHCV core was constructed to generate in vitro transcripts of the core region of HCV RNA genome. Ultraviolet (UV) cross-linking experiment and competition analysis were performed to screen HepG2 cellular proteins, which interact with digoxin-labeled transcripts of the core region of HCV RNA genome. RNA-binding proteins were separated by immunoprecipitation, analyzed by electrophoresis on SDS-PAGE and detected by immunoblotting with anti-digoxingenin-AP. After being excised from SDS-PAGE, the proteins bands were analyzed by MALDI-TOF-MS. RESULTS: Several cellular proteins of hepG2 cell specifically bound to the core region of HCV RNA genome. The binding of cellular proteins to digoxin-labeled HCV core RNA was competed out in proportion to the increasing amount of unlabeled RNA. One of the HCV RNA-binding proteins was the B (brain) isozyme of human phosphoglycerate mutase (PGAM-B) identified by MALDI-TOF-MS. CONCLUSION: PGAM-B could specifically bind to the core region of HCV RNA genome in vitro.

[Screening of cellular proteins binding to the core region of hepatitis C virus RNA by ultraviolet cross-linking assay].

OBJECTIVE: To screen cellular proteins binding to the core region of hepatitis C virus (HCV) from human hepatoma cells. METHODS: Unlabeled and labeled RNA transcripts were prepared by in vitro transcription. Cytoplasmic extracts were prepared from human hepatoma cells HepG2. Ultraviolet (UV) cross-linking was used to screen the cellular proteins that would bind to the core region of HCV. Competition experiment was performed to confirm the specificity of the binding in which excess unlabeled RNA of HCV core region and plasmid RNA were used as competitors. RESULTS: Two cellular proteins of 6.6 x 10(4) and 5.5 x 10(4) were found binding to the core region of HCV RNA by UV cross-linking assay. The unlabeled core region of HCV RNA could compete out this binding whereas the unlabeled plasmid RNA could not. CONCLUSION: The cellular proteins from HepG2 cells could bind to the core region of HCV RNA.

Heterogeneity analysis of the hepatitis B virus genome in intrauterine infection.

There are many factors leading to intrauterine infection with hepatitis B virus (HBV). These factors include viral structure, HBV mutations, HBV DNA level, placenta barrier, immune status of the mother, and susceptibility of the fetus. The purpose of this study was to investigate the possible relationship between intrauterine infection with and HBV mutations of the genome of the virus. In this study, HBsAg-positive mothers were divided into two groups: intrauterine infection group and non-infection group according to whether the newborn infants were infected or not. The intrauterine infection group included four pairs of mother and their newborn infants infected in utero, and non-infection group included five HBsAg-positive mothers. HBV sequences from the two groups were analyzed and compared. The predominant strains in the mothers and infants from the intrauterine infection group were not completely consistent. This suggested that both HBV predominant strains and minority strains in the mothers could infect their infants through intrauterine transmission. Some HBV mutations probably related to intrauterine infection were examined and it was found that the frequencies of mutations were low in isolates of the virus of infants from the intrauterine infection group and high in the non-infection group. These results suggest that some strains of HBV from the mother may be transmitted selectively to the fetus in utero because of viral heterogeneity. The strains without screened mutations such as P21L in the pre-S1 region may infect the fetus more readily.