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1.
Front Cell Dev Biol ; 9: 714320, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34900982

RESUMO

Precise regulation of cell cycle is essential for tissue homeostasis and development, while cell cycle dysregulation is associated with many human diseases including renal fibrosis, a common process of various chronic kidney diseases progressing to end-stage renal disease. Under normal physiological conditions, most of the renal cells are post-mitotic quiescent cells arrested in the G0 phase of cell cycle and renal cells turnover is very low. Injuries induced by toxins, hypoxia, and metabolic disorders can stimulate renal cells to enter the cell cycle, which is essential for kidney regeneration and renal function restoration. However, more severe or repeated injuries will lead to maladaptive repair, manifesting as cell cycle arrest or overproliferation of renal cells, both of which are closely related to renal fibrosis. Thus, cell cycle dysregulation of renal cells is a potential therapeutic target for the treatment of renal fibrosis. In this review, we focus on cell cycle regulation of renal cells in healthy and diseased kidney, discussing the role of cell cycle dysregulation of renal cells in renal fibrosis. Better understanding of the function of cell cycle dysregulation in renal fibrosis is essential for the development of therapeutics to halt renal fibrosis progression or promote regression.

2.
Nutrients ; 13(12)2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34959962

RESUMO

Age-related macular degeneration (AMD) is one of the major causes of blindness in elderly populations. However, the dry form of AMD has lack of effective treatments. The fruits of Aronia melanocarpa are rich in anthocyanins. In this study, the protective effects of aronia fruit extract on rat retina were investigated using a NaIO3-induced dry AMD model. Full-field electroretinograms (ERGs) showed that b-wave amplitudes were significantly decreased and the retina structures were disordered in the model. The extract treatment alleviated the injuries. The b-wave amplitudes increased 61.5% in Scotopic 0.01ERG, 122.0% in Photopic 3.0ERG, and 106.8% in Photopic 3.0 flicker; the retina structure disorder was improved with the thickness of outer nuclear layer increasing by 44.1%; and the malonaldehyde level was significantly reduced in extract-treated rat retinas compared to the model. The proteomics analysis showed the expressions of five crystallin proteins, α-crystallin A chain, ß-crystallin B2, ß-crystallin A3, α-crystallin B chain, and γ-crystallin S, which protect retina ganglion cells, were increased by 7.38-, 7.74-, 15.30-, 4.86-, and 9.14-fold, respectively, in the extract treatment compared to the control, which was also confirmed by immunoblotting. The results suggest that aronia fruit extract, probably due to its anthocyanins, could protect the rat retina by alleviating oxidative damages and by upregulating the crystallin proteins to protect its nerve system.

3.
R Soc Open Sci ; 8(11): 210023, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34804560

RESUMO

Due to the complex permittivity, it is difficult to directly clarify the transient mechanism between electromagnetic waves and Debye media. To overcome the above problem, the temporal relationship between the electromagnetic waves and permittivity is explicitly derived by applying the Fourier inversion and introducing the remnant displacement. With the help of the Poynting theorem and energy conservation equation, the transient power loss density is derived to describe the transient dissipation of electromagnetic field and the mechanism on phase displacement has been explicitly revealed. Besides, the unique solution can be obtained by applying the time-domain analysis method rather than involving the frequency-domain characteristics. The effectiveness of transient analysis is demonstrated by giving a comparison simulation on one-dimensional example.

4.
Sci Rep ; 11(1): 22244, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34782661

RESUMO

Cutaneous melanoma could be treated by immunotherapy, which only has limited efficacy on uveal melanoma (UM). UM immunotyping for predicting immunotherapeutic responses and guiding immunotherapy should be better understood. This study identified molecular subtypes and key genetic markers associated with immunotherapy through immunosignature analysis. We screened a 6-immune cell signature simultaneously correlated with UM prognosis. Three immune subtypes (IS) were determined based on the 6-immune cell signature. Overall survival (OS) of IS3 was the longest. Significant differences of linear discriminant analysis (LDA) score were detected among the three IS types. IS3 with the highest LDA score showed a low immunosuppression. IS1 with the lowest LDA score was more immunosuppressive. LDA score was significantly negatively correlated with most immune checkpoint-related genes, and could reflect UM patients' response to anti-PD1 immunotherapy. Weighted correlation network analysis (WGCNA) identified that salmon, purple, yellow modules were related to IS and screened 6 prognostic genes. Patients with high-expressed NME1 and TMEM255A developed poor prognosis, while those with high-expressed BEX5 and ROPN1 had better prognosis. There was no notable difference in OS between patients with high-expressed LRRN1 and ST13 and those with low-expressed LRRN1 and ST13. NME1, TMEM255A, Bex5 and ROPN1 showed potential prognostic significance in UM.

5.
Front Cell Dev Biol ; 9: 766142, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722550

RESUMO

As an evolutionarily conserved cellular process, autophagy plays an essential role in the cellular metabolism of eukaryotes as well as in viral infection and pathogenesis. Under physiological conditions, autophagy is able to meet cellular energy needs and maintain cellular homeostasis through degrading long-lived cellular proteins and recycling damaged organelles. Upon viral infection, host autophagy could degrade invading viruses and initial innate immune response and facilitate viral antigen presentation, all of which contribute to preventing viral infection and pathogenesis. However, viruses have evolved a variety of strategies during a long evolutionary process, by which they can hijack and subvert host autophagy for their own benefits. In this review, we highlight the function of host autophagy in the key regulatory steps during viral infections and pathogenesis and discuss how the viruses hijack the host autophagy for their life cycle and pathogenesis. Further understanding the function of host autophagy in viral infection and pathogenesis contributes to the development of more specific therapeutic strategies to fight various infectious diseases, such as the coronavirus disease 2019 epidemic.

6.
J Immunol Res ; 2021: 4973589, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722779

RESUMO

Method: This study included 74 Chinese male patients with HCC. They were divided into early (n = 19), intermediate (n = 37), and terminal (n = 18) groups, referred to as Barcelona Clinic Liver Cancer stage 0+A, B, and C+D, respectively. Paired fecal and plasma samples were collected. Microbial composition and profiles were analyzed by 16S rRNA gene sequencing. The levels of gut damage marker (regenerating islet-derived protein 3α (REG3α)) and microbial translocation markers (soluble CD14 (sCD14), lipopolysaccharide-binding protein (LBP), peptidoglycan recognition proteins (PGRPs)) were determined in plasma samples of patients by ELISA. Twenty plasma cytokine and chemokines were determined by Luminex. Results: In early, intermediate, and terminal groups, the abundance of the Bifidobacteriaceae family decreased significantly (3.52%, 1.55%, and 0.56%, respectively, P = 0.003), while the abundance of the Enterococcaceae family increased significantly (1.6%, 2.9%, and 13.4%, respectively, P = 0.022). Levels of REG3α and sCD14 were markedly elevated only in the terminal group compared with the early (P = 0.025 and P = 0.048) and intermediate groups (P = 0.023 and P = 0.046). The level of LBP significantly increased in the intermediate (P = 0.035) and terminal (P = 0.025) groups compared with the early group. The PGRP levels were elevated only in the terminal group compared with the early group (P = 0.018). The ratio of Enterococcaceae to Bifidobacteriaceae was significantly associated with the levels of REG3α, LBP, sCD14, and PGRPs. With HCC progression, increased levels of inflammatory cytokines accompanied by a T cell-immunosuppressive response and microbial translocation were observed. Conclusion: Gut microbiota compositional and functional shift, together with elevated gut damage and microbial translocation, may promote HCC development by stimulating inflammatory response and suppressing T cell response.

7.
JCI Insight ; 6(23)2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34699383

RESUMO

Understanding viral rebound in pediatric HIV-1 infection may inform the development of alternatives to lifelong antiretroviral therapy (ART) to achieve viral remission. We thus investigated viral rebound after analytical treatment interruption (ATI) in 10 infant macaques orally infected with SHIV.C.CH505 and treated with long-term ART. Rebound viremia was detected within 7 to 35 days of ATI in 9 of 10 animals, with posttreatment control of viremia seen in 5 of 5 Mamu-A*01+ macaques. Single-genome sequencing revealed that initial rebound virus was similar to viral DNA present in CD4+ T cells from blood, rectum, and lymph nodes before ATI. We assessed the earliest sites of viral reactivation immediately following ATI using ImmunoPET imaging. The largest increase in signal that preceded detectable viral RNA in plasma was found in the gastrointestinal (GI) tract, a site with relatively high SHIV RNA/DNA ratios in CD4+ T cells before ATI. Thus, the GI tract may be an initial source of rebound virus, but as ATI progresses, viral reactivation in other tissues likely contributes to the composition of plasma virus. Our study provides potentially novel insight into the features of viral rebound in pediatric infection and highlights the application of a noninvasive technique to monitor areas of HIV-1 expression in children.

8.
Ecotoxicology ; 30(10): 1997-2010, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34529203

RESUMO

Microplastics (MPs) are common environmental contaminants that present a growing health concern due to their increasing presence in aquatic and human systems. However, the mechanisms behind MP effects on organisms are unclear. In this study, zebrafish (Danio rerio) were used as an in vivo model to investigate the potential risks and molecular mechanisms of the toxic effects of polyethylene MPs (45-53 µm). In the zebrafish intestine, 6, 5, and 186 genes showed differential expression after MP treatment for 1, 5, and 10 days, respectively. In the gills, 318, 92, and 484 genes showed differential expression after MP treatment for 1, 5, and 10 days, respectively. In both the intestine and the gills, Gene Ontology (GO) annotation showed that the main enriched terms were biological regulation, cellular process, metabolic process, cellular anatomical entity, and binding. KEGG enrichment analysis on DEGs revealed that the dominant pathways were carbohydrate metabolism and lipid metabolism, which were strongly influenced by MPs in the intestine. The dominant pathways in the gills were immune and lipid metabolism. The respiratory rate of gills, the activity of SOD and GSH in the intestine significantly increased after exposure to MPs compared with the control (p < 0.05), while the activity of SOD did not change in the gills. GSH activity was only significantly increased after MP exposure for 5 days. Also, the MDA content was not changed in the intestine but was significantly decreased in the gills after MP exposure. The activity of AChE significantly decreased only after MPs exposure for 5 days. Overall, these results indicated that MPs pollution significantly induced oxidative stress and neurotoxicity, increased respiratory rate, disturbed energy metabolism and stimulated immune function in fish, displaying an environmental risk of MPs to aquatic ecosystems.


Assuntos
Microplásticos , Poluentes Químicos da Água , Animais , Ecossistema , Brânquias , Humanos , Intestinos/química , Plásticos/toxicidade , Polietileno/toxicidade , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade , Peixe-Zebra
9.
Arch Gynecol Obstet ; 2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34390385

RESUMO

PURPOSE: To ascertain if assisted hatching (AH) increases the risk of placenta-associated diseases and perinatal outcomes after frozen-thawed cleavage-stage embryo transfer. METHODS: We retrospectively evaluated 924 women who conceived with frozen-thawed cleavage-stage embryos transfer with (n = 390) or without (n = 534) laser-AH between 2013 and 2015. Data were obtained from the database on in vitro fertilization (IVF) patients in Shanghai First Maternity and Infant Hospital. We assessed neonatal (preterm birth, low birthweight, fetal macrosomia, stillbirth) and obstetric (miscarriage, ectopic pregnancy, post-term pregnancy, gestational diabetes (GDM), preeclampsia, intrahepatic cholestasis (ICP), placenta previa, placental abruption, premature rupture of membranes) outcomes. RESULTS: In twins, the median birthweight was lower in the AH group than that in the control group, and the prevalence of low birthweight (< 2500 g) was significantly higher in the AH group; after adjusting for maternal age, body mass index, mode of fertilization, and parity, no significant difference was found. In twins, no significant difference was detected in the prevalence of stillbirth or preterm pregnancy. In singleton births, there was no significant difference in the prevalence of low birthweight, macrosomia, preterm pregnancy or post-term pregnancy between the two groups. In singletons and twins, there were no significant differences in the prevalence of miscarriage, ectopic pregnancy, preeclampsia, GDM, ICP, or placenta abruption between the two groups. CONCLUSIONS: AH is a relatively safe method and our study provides important information for using this method in carefully selected patients.

10.
Exp Ther Med ; 22(2): 873, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34194551

RESUMO

MicroRNAs (miRNAs/miRs) serve an important role in the pathogenesis of chronic heart failure (CHF). A number of reports have illustrated the regulatory effect of serum exosomal miRNA on myocardial fibrosis. The present study aimed to investigate the expression of miR-320a in serum exosomes, as well as the effect of miR-320a on myocardial fibroblast proliferation. Serum exosome samples from 10 patients with CHF and 5 healthy volunteers were obtained and characterized. mRNA and protein expression levels were measured via reverse transcription-quantitative PCR and western blotting, respectively. The content of soluble growth stimulation expressed gene 2 (sST2) was determined via ELISA. HEH2 cell viability and apoptosis were detected by performing MTT assays and flow cytometry, respectively. The results demonstrated that serum miR-320a expression levels and sST2 content were significantly increased in patients with CHF compared with healthy controls, and the expression of serum miR-320a was significantly correlated with clinical CHF indexes. miR-320a expression levels were significantly increased in exosomes isolated from patients with CHF compared with those isolated from healthy controls. Phosphoinositide-3-kinase catalytic α polypeptide gene (PIK3CA) expression levels and sST2 content were increased in HEH2 cells following transfection with miR-320a mimics compared with NC-mimic, whereas miR-320a inhibitor displayed contrasting effects by reduced the cell viability and apoptosis in myocardial fibroblasts compared with the NC-inhibitor group. The protein expression levels of collagen I, collagen III, α-smooth muscle actin, phosphorylated (p)-mTOR (ser 2448)/mTOR, p-Akt (ser 473)/Akt, p-Akt (thr 308)/Akt and PIK3CA were significantly increased in miR-320a mimic-transfected HEH2 cells compared with the NC-mimics groups. By contrast, miR-320a inhibitor notably downregulated the expression levels of these proteins compared with the NC-inhibitor group. Collectively, the results of the present study demonstrated that miR-320a promoted myocardial fibroblast proliferation via regulating the PIK3CA/Akt/mTOR signaling pathway in HEH2 cells, suggesting that serum exosomal miR-320a may serve as a potential biomarker for the diagnosis of CHF.

11.
Genomics ; 113(4): 2605-2613, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34116169

RESUMO

Blood is an important non-reproductive tissue, but little is known about the sex-specific gene expressions in the blood. Therefore, we investigated sex-specific gene expression differences in the blood tissues of four primates, rhesus macaques (Macaca mulatta), Tibetan macaques (M. thibetana), yellow baboons (Papio cynocephalus), and humans. We identified seven sex-specific differentially expressed genes (SDEGs) in each non-human primate and 31 SDEGs in humans. The four primates had only one common SDEG, MAP7D2. In humans, immune-related SDEGs were identified as up-regulated, but also down-regulated in females. We also found that most of the X-Y gene pairs had similar expression levels between species, except pair EIF1AY/EIF1AX. The expression level of X-Y gene pairs of rhesus and Tibetan macaques showed no significant differential expression levels, while humans had six significant XY-biased and three XX-biased X-Y gene pairs. Our observed sex differences in blood should increase understanding of sex differences in primate blood tissue.

12.
Pharmaceutics ; 13(6)2021 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-34070708

RESUMO

It is necessary to prepare porous lactose in order to improve the dissolution behavior of insoluble active ingredient. In this study, polyvinylpyrrolidone K30 (PVP K30) was firstly utilized as a templating agent with different use levels in preparing porous lactose. Then, the physical properties were profoundly characterized. Finally, the porous lactose was also employed as a health functional food/drug carrier to explore the effect on the dissolution behavior of curcumin. The results confirmed that (i) porous lactose was successfully prepared using PVP K30 as templating agent; (ii) PVP K30 significantly improved the yield of lactose in the spray drying; (iii) the improved powder properties of porous lactose were more conducive to the downstream operating process for the preparation of health functional food or drug; and (iv) the porous lactose significantly improved the dissolution behavior of curcumin. Therefore, the results obtained are beneficial to boosting the development of porous materials.

13.
ACS Appl Mater Interfaces ; 13(18): 21680-21692, 2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33934598

RESUMO

Herein, a Au-Au/IrO2 nanocomposite with tandem enzyme-mimicking activity was innovatively synthesized, which can show outstanding glucose oxidase (GOx)-like activity and peroxidase-like activity simultaneously under neutral conditions. Moreover, a Au-Au/IrO2@Cu(PABA) reactor was prepared via encapsulation of the Au-Au/IrO2 nanocomposite in a Cu(PABA) metal organic framework. The reactor not only exhibits excellent organic solvent stability, acid resistance, and reusability but also displays better cascade reaction catalytic efficiency (kcat/Km = 148.86 min-1 mM-1) than the natural free enzyme system (GOx/HRP) (kcat/Km = 98.20 min-1 mM-1) and Au-Au/IrO2 nanocomposite (kcat/Km = 135.24 min-1 mM-1). In addition, it is found that the reactor can catalyze glucose or dissolved oxygen to produce active oxygen species (ROS) including HO, 1O2, and O2-· through its enzyme-mimicking activity. Finally, the novel reactor was successfully used in organic dye degradation and antibacterial application. The results show that it can effectively degrade methyl orange, methylene blue, and rhodamine B, which all can reach a degradation rate of nearly 100% after interacting with Au-Au/IrO2@Cu (PABA) for 3.5 h. Furthermore, the reactor also exhibits excellent antibacterial activity, so as to achieve a complete bactericidal effect to Staphylococcus aureus and Escherichia coli at a concentration of 12.5 µg mL-1.


Assuntos
Antibacterianos/farmacologia , Corantes/química , Complexos de Coordenação/química , Enzimas/química , Estruturas Metalorgânicas/química , Metais/química , Catálise , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Staphylococcus aureus/efeitos dos fármacos
14.
Vet Microbiol ; 257: 109083, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33894663

RESUMO

MicroRNAs (miRNAs) are known to play important regulatory roles in host-virus interactions. Avian-origin H3N2 canine influenza virus (CIV) has emerged as the most prevalent subtype among dogs in Asia since 2007. To evaluate the roles of host miRNAs in H3N2 CIV infection, here, miRNA profiles obtained from primary canine bronchiolar epithelial cells (CBECs) and canine alveolar macrophages (CAMCs) were compared between infected and mock-infected cells with the H3N2 CIV JS/10. It was found that the expressions of cfa-miR-125b and cfa-miR-151, which have been reported to be associated with innate immunity and inflammatory response, were significantly decreased in CIV-infected canine primary cells. Bioinformatics prediction indicated that 5' seed regions of the two miRNAs are partially complementary to the mRNAs of nucleoprotein (NP) and non-structural protein 1 (NS1) of JS/10. As determined by virus titration, quantitative real-time PCR (qRT-PCR) and western blotting, overexpression of the two miRNAs inhibited CIV replication in cell culture, while their inhibition facilitated this replication, suggesting that the two miRNAs could act as negative regulators of CIV replication. Our findings support the notion that some cellular miRNAs can influence the outcome of virus infection, which helps to elucidate the resistance of host cells to viral infection and to clarify the pathogenesis of H3N2 CIV.


Assuntos
Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Vírus da Influenza A Subtipo H3N2/fisiologia , Macrófagos Alveolares/virologia , MicroRNAs/genética , Replicação Viral/genética , Animais , Brônquios/citologia , Células Cultivadas , Doenças do Cão/virologia , Cães , Células Epiteliais/virologia , Vírus da Influenza A Subtipo H3N2/genética , Células Madin Darby de Rim Canino , Masculino
15.
Neural Netw ; 141: 225-237, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33930564

RESUMO

The traditional generalized sidelobe canceller (GSC) is a common speech enhancement front end to improve the noise robustness of automatic speech recognition (ASR) systems in the far-field cases. However, the traditional GSC is optimized based on the signal level criteria, causing it not to guarantee the optimal ASR performance. To address this issue, we propose a novel dual-channel deep neural network (DNN)-based GSC structure, called nnGSC, which is optimized by using the objective of maximizing the ASR performance. Our key idea is to make each module of the traditional GSC fully learnable and use the acoustic model to perform joint optimization with GSC. We use the coefficients of the traditional GSC to initialize nnGSC, so that both traditional signal processing knowledge and large amounts of data can be used to guide the network learning. In addition, nnGSC can automatically track the target direction-of-arrival (DOA) frame-by-frame without the need for additional localization algorithms. In the experiments, nnGSC achieves a relative character error rate (CER) improvement of 23.7% compared to the microphone observation, 13.5% compared to the oracle direction-based super-directive beamformer, 12.2% compared to the oracle direction-based traditional GSC and 5.9% compared to the oracle mask-based minimum variance distortionless response (MVDR) beamformer. Moreover, we can improve the robustness of nnGSC against array geometry mismatches by training with multi-geometry data.


Assuntos
Aprendizado Profundo , Interface para o Reconhecimento da Fala , Fala , Humanos , Ruído
16.
IEEE Trans Image Process ; 30: 3922-3933, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33755566

RESUMO

Robust text reading is a very challenging problem, due to the distribution of text images changing significantly in real-world scenarios. One effective solution is to align the distribution between different domains by domain adaptation methods. However, we found that these methods might struggle when dealing sequence-like text images. An important reason is that conventional domain adaptation methods strive to align images as a whole, while text images consist of variable-length fine-grained character information. To address this issue, we propose a novel Adversarial Sequence-to-Sequence Domain Adaptation (ASSDA) method to learn "where to adapt" and "how to align" the sequential image. Our key idea is to mine the local regions that contain characters, and focus on aligning them across domains in an adversarial manner. Extensive text recognition experiments show the ASSDA could efficiently transfer sequence knowledge and validate the promising power towards the various domain shift in the real world applications.

17.
Medicine (Baltimore) ; 100(4): e24467, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33530257

RESUMO

ABSTRACT: Although recent gathered evidence indicates that obtaining the diagnostic value of serum carbohydrate-deficient transferrin might be more useful for identifying alcohol abuse than other widely available biochemical tests; however, its precise value as an indicator of chronic alcoholism is unclear. The main objective is to investigate the diagnostic significance of carbohydrate-deficient transferrin in chronic alcoholism in the Chinese population.In this study, we enrolled (1) 52 physically healthy subjects, (2) 20 patients with nonalcoholic liver disease, and (3) 70 alcoholics. Patients with liver injuries and a history of liver surgery were excluded. Serum gamma-glutamyltransferase, aspartate aminotransferase, alanine aminotransferase, and mean corpuscular volume were determined by standard biochemical assays, and serum carbohydrate-deficient transferrin was estimated in each group using capillary electrophoresis. Subsequently, the diagnostic value of carbohydrate-deficient transferrin (CDT) in chronic alcoholism was determined based on differences between each indicator among the three groups.The CDT level in the alcoholic group was significantly higher than that of the non-alcoholic liver disease and healthy control groups (P < .05). The area under the curve for alcoholism diagnosis was the highest for CDT, at 0.922, whereas those for gamma-glutamyltransferase, aspartate aminotransferase, alanine aminotransferase, and mean corpuscular volume were 0.860, 0.744, 0.615, and 0.754, respectively. When the cutoff value of CDT was set at 1.25%, the sensitivity and specificity were 85.5% and 89.6%, respectively. However, the correlation between CDT and daily alcohol consumption was weak (r = 0.175; P = .16).Compared with the other parameters evaluated, CDT was a better indicator of alcoholism. It should, therefore, be actively promoted in clinical practice. However, the correlation between CDT and daily alcohol consumption needs further evaluation.


Assuntos
Alcoolismo/sangue , Transferrina/análogos & derivados , Adulto , Alcoolismo/diagnóstico , Biomarcadores/sangue , Estudos de Casos e Controles , China , Eletroforese Capilar , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Transferrina/análise
18.
Sci China Life Sci ; 64(6): 942-956, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33521857

RESUMO

Bats are a potential natural reservoir for SARS-CoV-2 virus and other viruses detrimental to humans. Accumulated evidence has shown that, in their adaptation to a flight-based lifestyle, remodeling of the gut microbiota in bats may have contributed to immune tolerance to viruses. This evidence from bats provides profound insights into the potential influence of gut microbiota in COVID-19 disease in humans. Here, we highlight recent advances in our understanding of the mechanisms by which the gut microbiota helps bats tolerate deadly viruses, and summarize the current clinical evidence on the influence of gut microbiota on the susceptibility to SARS-CoV-2 infection and risk of COVID-19 leading to a fatal outcome. In addition, we discuss the implications of gut microbiota-targeted approaches for preventing infection and reducing disease severity in COVID-19 patients.


Assuntos
COVID-19/microbiologia , Quirópteros/microbiologia , Reservatórios de Doenças/microbiologia , Microbioma Gastrointestinal/imunologia , Animais , COVID-19/imunologia , COVID-19/patologia , Quirópteros/imunologia , Quirópteros/virologia , Reservatórios de Doenças/virologia , Suscetibilidade a Doenças/imunologia , Suscetibilidade a Doenças/microbiologia , Suscetibilidade a Doenças/patologia , Voo Animal , Microbioma Gastrointestinal/genética , Humanos , Imunidade , SARS-CoV-2
19.
J Virol ; 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568515

RESUMO

Inducing latency reversal to reveal infected cells to the host immune system represents a potential strategy to cure HIV infection. In separate studies, we have previously shown that CD8+ T cells may contribute to the maintenance of viral latency and identified a novel SMAC mimetic/IAP inhibitor (AZD5582) capable of reversing HIV/SIV latency in vivo by activating the non-canonical (nc) NF-κB pathway. Here, we use AZD5582 in combination with antibody-mediated depletion of CD8α+ cells to further evaluate the role of CD8+ T cells in viral latency maintenance. Six rhesus macaques (RM) were infected with SIVmac239 and treated with ART starting at week 8 post-infection. After 84-85 weeks of ART, all animals received a single dose of the anti-CD8α depleting antibody (Ab), MT807R1 (50mg/kg, s.c.), followed by 5 weekly doses of AZD5582 (0.1 mg/kg, i.v.). Following CD8α depletion + AZD5582 combined treatment, 100% of RMs experienced on-ART viremia above 60 copies per ml of plasma. In comparator groups of ART-suppressed SIV-infected RMs treated with AZD5582 only or CD8α depletion only, on-ART viremia was experienced by 56% and 57% of the animals respectively. Furthermore, the frequency of increased viremic episodes during the treatment period was greater in the CD8α depletion + AZD5582 group as compared to other groups. Mathematical modeling of virus reactivation suggested that, in addition to viral dynamics during acute infection, CD8α depletion influenced the response to AZD5582. This work suggests that the latency reversal induced by activation of the ncNF-κB signaling pathway with AZD5582 can be enhanced by CD8α+ cell depletion.

20.
Chin Med ; 16(1): 2, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407711

RESUMO

BACKGROUND: Insomnia as one of the dominant diseases of traditional Chinese medicine (TCM) has been extensively studied in recent years. To explore the novel approaches of research on TCM diagnosis and treatment, this paper presents a strategy for the research of insomnia based on machine learning. METHODS: First of all, 654 insomnia cases have been collected from an experienced doctor of TCM as sample data. Secondly, in the light of the characteristics of TCM diagnosis and treatment, the contents of research samples have been divided into four parts: the basic information, the four diagnostic methods, the treatment based on syndrome differentiation and the main prescription. And then, these four parts have been analyzed by three analysis methods, including frequency analysis, association rules and hierarchical cluster analysis. Finally, a comprehensive study of the whole four parts has been conducted by random forest. RESULTS: Researches of the above four parts revealed some essential connections. Simultaneously, based on the algorithm model established by the random forest, the accuracy of predicting the main prescription by the combinations of the four diagnostic methods and the treatment based on syndrome differentiation was 0.85. Furthermore, having been extracted features through applying the random forest, the syndrome differentiation of five zang-organs was proven to be the most significant parameter of the TCM diagnosis and treatment. CONCLUSIONS: The results indicate that the machine learning methods are worthy of being adopted to study the dominant diseases of TCM for exploring the crucial rules of the diagnosis and treatment.

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