Biology subjects

Hu, F.

Publications and source records attributed to Hu, F..

82 records · Page 5Linked to original sources

bioRxiv2019

Study on the Health Communication Behavior of Chinese Doctors on Network Media----Based on the Empirical Investigation of 119 Chinese Doctors

IntroductionIn order to reduce the perceived risk of medical decision-making, Chinese patients tend to spend time and energy to understand relevant medical knowledge. After comparing online reviews and news reports of Chinese doctors, they carefully choose doctors. It is precisely because of the patients treatment habits that many doctors have spread health information through their own microblogs, WeChat public numbers, websites, videos and other means. Therefore, doctors speeches in cyberspace often play a dominant role in the development of health communication and guide the risk communication. This paper studies the influencing factors of Chinese doctors healthy communication behavior in online media. This has positive reference value for improving the health literacy of the whole people and the crisis management and guidance of public events.\n\nMethodsIn order to maximize the representativeness of the sample, the universality of the problems reflected in the survey data, and the adaptability of the purpose and method of the research questions, this paper adopts a multi-stage sampling method. In each region, a medical institution is selected according to a simple random sampling method in three types of hospitals: public hospitals, social hospitals, and primary medical institutions. A total of 10-11 medical institutions were selected in each region, and a total of 32 hospitals were selected from the three regions. According to the PPS sampling method, a corresponding number of working doctors are drawn in each hospital. Statistical analysis of the data was performed using SPSS 21.0 statistical software.\n\nAnalysisThe study found that doctors transmission of health-related content on online media is still at a lower level of involvement, and the frequency of transmission is significantly lower than the general level. There are also significant differences in the health transmission of doctors from different backgrounds on the Internet. In the context of control hospital background, continue to examine the impact of Media usage and occupational psychology on doctors dissemination of health-related content. The results show that the influence of Media usage on the health communication behavior of doctors on the Internet media, to a certain extent, verifies that the rise of online media plays a significant role in putting doctors into health science. This also shows that the media has fostered the doctors communication behavior. In addition, the higher the self-efficacy of doctors in the workplace, the more cautious they are about their words and deeds, the more they care about the impact of their speech on interpersonal communication.

scientific communication and education↗

bioRxiv2019

Live-cell Imaging Analysis of Antimycin-Type Depsipeptides via Bioorthogonal Stimulated Raman Scattering Microscopy

Small-molecule natural products have been an essential source of pharmaceuticals to treat human diseases, but very little is known about their behavior inside dynamic, living human cells. Here, we demonstrate the first structure-activity-distribution study of complex natural products, the anti-cancer antimycin-type depsipeptides, using the emerging bioorthogonal Stimulated Raman Scattering (SRS) Microscopy. Our results show that the intracellular enrichment and distribution of these compounds are driven by their potency and specific protein targets, as well as the lipophilic nature of compounds.

bioengineering↗

bioRxiv2019

Progranulin deficiency leads to reduced glucocerebrosidase activity

Mutation in the GRN gene, encoding the progranulin (PGRN) protein, shows a dose-dependent disease correlation, wherein haploinsufficiency results in frontotemporal lobar degeneration (FTLD) and complete loss results in neuronal ceroid lipofuscinosis (NCL). Although the exact function of PGRN is unknown, it has been increasingly implicated in lysosomal physiology. Here we report that PGRN interacts with the lysosomal enzyme, glucocerebrosidase (GBA), and is essential for proper GBA activity. GBA activity is significantly reduced in tissue lysates from PGRN-deficient mice. This is further evidence that reduced lysosomal hydrolase activity may be a pathological mechanism in cases of GRN-related FTLD and NCL.

neuroscience↗

bioRxiv2018

Chemogenetic ligands for translational neurotheranostics

Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are a popular chemogenetic technology for manipulation of neuronal activity in uninstrumented awake animals with potential for precision medicine-based clinical theranostics. DREADD ligands developed to date are not appropriate for such translational applications. The prototypical DREADD agonist clozapine N-oxide (CNO) lacks brain entry and converts to clozapine. The second-generation DREADD agonist, Compound 21 (C21), was developed to overcome these limitations. We found that C21 has low brain penetrance, weak affinity, and low in vivo DREADD occupancy. To address these drawbacks, we developed two new DREADD agonists, JHU37152 and JHU37160, and the first dedicated positron emission tomography (PET) DREADD radiotracer, [18F]JHU37107. JHU37152 and JHU37160 exhibit high in vivo DREADD potency. [18F]JHU37107 combined with PET allows for DREADD detection in locally-targeted neurons and at their long-range projections, enabling for the first time, noninvasive and longitudinal neuronal projection mapping and potential for neurotheranostic applications.

neuroscience↗

bioRxiv2018

SMCR8 negatively regulates AKT and MTORC1 signaling to modulate lysosome biogenesis and tissue homeostasis

The intronic hexanucleotide expansion in the C9orf72 gene is one of the leading causes of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS), 2 devastating neurodegenerative diseases. C9orf72 forms a heterodimer with SMCR8 (Smith-Magenis syndrome chromosome region, candidate 8) protein. However, the physiological function of SMCR8 remains to be characterized. Here we report that ablation of SMCR8 in mice results in splenomegaly with autoimmune phenotypes similar to that of C9orf72 deficiency. Furthermore, SMCR8 loss leads to a drastic decrease of C9orf72 protein levels. Many proteins involved in the macroautophagy-lysosome pathways are downregulated upon SMCR8 loss due to elevated activation of MTORC1 and AKT, which also leads to increased spine density in the Smcr8 knockout neurons. In summary, our studies demonstrate a key role of SMCR8 in regulating MTORC1 and AKT signaling and tissue homeostasis.

cell biology↗

bioRxiv2018

Sequencing of the MHC region defines HLA-DQA1 as the major independent risk for anti-citrullinated protein antibodies (ACPA)-positive rheumatoid arthritis in Han population

The strong genetic contribution of the major histocompatibility complex (MHC) to rheumatoid arthritis (RA) susceptibility has been generally attributed to HLA-DRB1. However, due to the high linkage disequilibrium in the MHC region, it is difficult to define the real or/and additional independent genetic risks using the conventional HLA genotyping or chip-based microarray technology. By the capture sequencing of entire MHC region for discovery and HLA-typing for validation in 2,773 subjects of Han ancestry, we identified HLA-DQ1:160D as the strongest independent genetic risk for anti-citrullinated protein antibodies (ACPA)-positive RA in Han population (P = 6.16 x 10-36, OR=2.29). Further stepwise conditional analysis revealed that DR{beta}1:37N has an independent protective effect on ACPA-positive RA (P = 5.81 x 10-16, OR=0.49). The DQ1:160 coding allele DQA1*0303 displayed high impact on joint radiographic severity, especially in patients with early disease and smoking (P = 3.02 x 10-5). Interaction analysis by comparative molecular modeling revealed that the negative charge of DQ1:160D stabilizes the dimer of dimers, leading to an increased T cell activation. The electrostatic potential surface analysis indicated that the negative charged DR{beta}1:37N encoding alleles could bind with epitope P9 arginine, thus may result in a decreased RA susceptibility.\n\nIn this study, we provide the first evidence that HLA-DQA1, instead of HLA-DRB1, is the strongest and independent genetic risk for ACPA-positive RA in Chinese Han population. Our study also illustrates the value of MHC deep sequencing for fine mapping disease risk variants in the MHC region.

genetics↗

bioRxiv2018

Inhibition of Hsp70 suppresses neuronal hyperexcitability and attenuates seizures by enhancing A-type potassium currents

The heat shock protein 70 (Hsp70) is upregulated in response to stress and has been implicated as a stress marker in temporal lobe epilepsy (TLE). However, whether Hsp70 plays a pathologic or protective role in TLE remains unclear. Here we report that Hsp70 exerts an unexpected deleterious role in kainic acid (KA)-induced seizures, and inhibition of Hsp70 suppresses neuronal hyperexcitability and attenuates both acute and chronic seizures via enhancing A-type potassium currents primarily formed by Kv4 -subunits and auxiliary KChIPs. Proteosomal degradation of Kv4-KChIP4a channel complexes is enhanced by Hsp70, which can be reversed by the Hsp70 inhibitors, 2-phenylethynesulfonamide (PES) and VER-155008 (VER). In cultured hippocampal neurons, either PES or VER can increase A-type Kv4 current to suppress neuronal hyperexcitability. Mechanistically, Hsp70-CHIP complexes directly bind to the N-terminus of auxiliary KChIP4a and target Kv4-KChIP4a complexes to the proteasome. Our findings reveal a previously unrecognized role of Hsp70 in mediating degradation of Kv4-KChIP4a complexes and regulating neuronal excitability, thus highlighting a therapeutic potential for hyperexcitability-related neurological disorders through Hsp70 inhibition.

neuroscience↗

bioRxiv2016

Chimeras Link to Tandem Repeats and Transposable Elements in Tetraploid Hybrid Fish

The formation of the allotetraploid hybrid lineage (4nAT) encompasses both distant hybridization and polyploidization processes. The allotetraploid offspring have two sets of sub-genomes inherited from both parental species and therefore it is important to explore its genetic structure. Herein, we construct a bacterial artificial chromosome library of allotetraploids, and then sequence and analyze the full-length sequences of 19 bacterial artificial chromosomes. Sixty-eight DNA chimeras are identified, which are divided into four models according to the distribution of the genomic DNA derived from the parents. Among the 68 genetic chimeras, 44 (64.71%) are linked to tandem repeats (TRs) and 23 (33.82%) are linked to transposable elements (TEs). The chimeras linked to TRs are related to slipped-strand mispairing and double-strand break repair while the chimeras linked to TEs are benefit from the intervention of recombinases. In addition, TRs and TEs are linked not only with the recombinations, but also with the insertions/deletions of DNA segments. We conclude that DNA chimeras accompanied by TRs and TEs coordinate a balance between the sub-genomes derived from the parents which reduces the genomic shock effects and favors the evolutionary and adaptive capacity of the allotetraploidization. It is the first report on the relationship between formation of the DNA chimeras and TRs and TEs in the polyploid animals.

genetics↗

bioRxiv2016

A comprehensive survey of genetic variation in 20,691 subjects from four large cohorts

The Nurses Health Study (NHS), Nurses Health Study II (NHSII), Health Professionals Follow Up Study (HPFS) and the Physicians Health Study (PHS) have collected detailed longitudinal data on multiple exposures and traits for approximately 310,000 study participants over the last 35 years. Over 160,000 study participants across the cohorts have donated a DNA sample and to date, 20,691 subjects have been genotyped as part of genome-wide association studies (GWAS) of twelve primary outcomes. However, these studies utilized six different GWAS arrays making it difficult to conduct analyses of secondary phenotypes or share controls across studies. To allow for secondary analyses of these data, we have created three new datasets merged by platform family and performed imputation using a common reference panel, the 1,000 Genomes Phase I release. Here, we describe the methodology behind the data merging and imputation and present imputation quality statistics and association results from two GWAS of secondary phenotypes (body mass index (BMI) and venous thromboembolism (VTE)).\n\nWe observed the strongest BMI association for the FTO SNP rs55872725 ({beta}=0.45, p=3.48x10-22), and using a significance level of p=0.05, we replicated 19 out of 32 known BMI SNPs. For VTE, we observed the strongest association for the rs2040445 SNP (OR=2.17, 95% CI: 1.79-2.63, p=2.70x10-15), located downstream of F5 and also observed significant associations for the known ABO and F11 regions. This pooled resource can be used to maximize power in GWAS of phenotypes collected across the cohorts and for studying gene-environment interactions as well as rare phenotypes and genotypes.

epidemiology↗

bioRxiv2016

Chimeric Genes Revealed in the Polyploidy Fish Hybrids of Carassius cuvieri (Female) x Megalobrama amblycephala (Male)

The genomes of newly formed natural or artificial polyploids may experience rapid gene loss and genome restructuring. In this study, we obtained tetraploid hybrids (4n=148, 4nJB) and triploid hybrids (3n=124, 3nJB) derived from the hybridization of two different subfamily species Carassius cuvieri ([female], 2n = 100, JCC) and Megalobrama amblycephala ([male], 2n = 48, BSB). Some significant morphological and physiological differences were detected in the polyploidy hybrids compared with their parents. To reveal the molecular traits of the polyploids, we compared the liver transcriptomes of 4nJB, 3nJB and their parents. The results indicated high proportion chimeric genes (31 > %) and mutated orthologous genes (17 > %) both in 4nJB and 3nJB. We classified 10 gene patterns within three categories in 4nJB and 3nJB orthologous gene, and characterized 30 randomly chosen genes using genomic DNA to confirm the chimera or mutant. Moreover, we mapped chimeric genes involved pathways and discussed that the phenotypic novelty of the hybrids may relate to some chimeric genes. For example, we found there is an intragenic insertion in the K+ channel kcnk5b, which may be related to the novel presence of the barbels in 4nJB. Our results indicated that the genomes of newly formed polyploids experienced rapid restructuring post-polyploidization, which may results in the phenotypic and phenotypic changes among the polyploidy hybrid offspring. The formation of the 4nJB and 3nJB provided new insights into the genotypic and phenotypic diversity of hybrid fish resulting from distant hybridization between subfamilies.

developmental biology↗