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The explosive growth of China's express delivery industry has greatly increased plastic waste, with low-value plastics not effectively utilized, such as PE packaging bags, which are often not recycled and end up in landfills or incinerators, causing significant resource waste and severe plastic pollution. A gate -to- grave life cycle assessment was adopted to assess the impacts of express delivery plastic waste (EDPW) management models (S1, landfill; S2, incineration; S3, mechanical pelletization), with Suzhou, China as a case. Results showed that mechanical pelletization, was the most environmentally advantageous, exhibiting a comprehensive environmental impact potential of -215.54 Pt, significantly lower than that of landfill (S1, 78.45 Pt) and incineration (S2, -121.77 Pt). The analysis identified that the end-of-life disposal and sorting stages were the principal contributors to environmental impacts in all three models, with transportation and transfer stages of residual waste having minimal effects. In terms of all environmental impact categories, human carcinogenic toxicity (HTc) emerged as the most significant contributor in all three scenarios. Specifically, S1 exhibited the most detrimental effect on human health, while S2 and S3 showed positive environmental impacts. Based on these findings, it is recommended that the application and innovation in mechanical recycling technologies be enhanced, the promotion of the eco-friendly transformation of packaging materials be pursued, and a sustainable express delivery packaging recycling management system be established. These strategies are essential for achieving more eco-friendly management of EDPW, reducing its environmental pollution, and moving towards more sustainable express delivery management practices.
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Incineração , Plásticos , Reciclagem , Instalações de Eliminação de Resíduos , Gerenciamento de Resíduos , China , Gerenciamento de Resíduos/métodos , Eliminação de Resíduos/métodos , HumanosRESUMO
BACKGROUND: Pradefovir is a liver-targeted prodrug of adefovir, a nucleoside/nucleotide analogue with antiviral activity against hepatitis B virus (HBV) DNA polymerase. This phase 2 study compared the efficacy and safety of oral pradefovir (30, 45, 60, or 75 mg) versus tenofovir disoproxil fumarate (TDF; 300 mg) and aimed to identify the most appropriate dose of pradefovir for the forthcoming phase 3 study. METHODS: Treatment-naive and experienced (not on treatment >6 months) patients with chronic hepatitis B were eligible. RESULTS: A total of 240 participants were randomized and treated in the study (48 per group). Approximately 80% were hepatitis B e antigen (HBeAg) positive, and 10% had liver cirrhosis. The reductions from baseline in HBV DNA levels achieved at week 24 were 5.40, 5.34, 5.33, and 5.40 log10 IU/mL, with pradefovir doses of 30-, 45-, 60-, and 75-mg, respectively, compared with 5.12 log10 IU/mL with TDF. However, HBeAg loss was attained by more participants who received 45-, 60-, or 75-mg pradefovir than by those receiving TDF (12%, 6%, and 9% vs 3%). The TDF group exhibited a more significant increase in serum creatinine than the pradefovir 30- and 45-mg groups, and serum phosphate levels were comparable among all groups. Most adverse events (AEs) were mild (grade 1). No treatment-related severe AEs were reported. Overall, AEs and laboratory abnormalities were comparable to those in the TDF group. CONCLUSIONS: Pradefovir and TDF exhibited comparable reductions in HBV DNA levels. All treatments were safe and well tolerated. CLINICAL TRIALS REGISTRATION: NCT00230503 and China Drug Trials CTR2018042.
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Hepatite B Crônica , Pró-Fármacos , Adenina/análogos & derivados , Antivirais/efeitos adversos , DNA Viral , Antígenos E da Hepatite B , Vírus da Hepatite B/genética , Humanos , Compostos Organofosforados , Pró-Fármacos/efeitos adversos , Tenofovir/efeitos adversos , Resultado do Tratamento , Carga ViralRESUMO
BACKGROUND: Concerns regarding potential toxicity and drug-drug interactions during long-term treatment with three-drug active antiretroviral therapy (ART) regimens have been attracting increasing attention. We aimed to evaluate the efficacy and safety of dolutegravir (DTG) plus lamivudine (3TC) in ART-naive adults in China. METHODS: This prospective observational cohort study enrolled HIV-naive inpatients treated with DTG + 3TC (2DR arm) or efavirenz (EFV) plus tenofovir disoproxil fumarate (TDF) and 3TC (3DR arm). There were no limits on baseline viral load. Inflammatory biomarkers were also investigated in the 2DR arm. RESULTS: Between September 2019 and January 2020, 27 patients treated with DTG + 3TC and 28 patients treated with EFV + TDF + 3TC were enrolled in the study. At week 12, the proportion of patients with viral loads < 50 copies/mL in the 2DR arm was 81.5% (22/27) compared with 53.6% (15/28) in the 3DR arm (p < 0.01). At week 24, the proportion of patients with viral loads < 50 copies/mL in the 2DR arm was 100% (26/26) compared with 83.3% (20/24) in the 3DR arm (p < 0.05). Mean changes in CD4 cell counts from baseline at week 12 were 125.46 cells/µL in the 2DR arm and 41.20 cells/µL in the 3DR arm (p < 0.05). Mean changes in CD4 cell counts from baseline at week 24 were 209.68 cells/µL in the 2DR arm and 73.28 cells/µL in the 3DR arm (p < 0.05). CONCLUSIONS: DTG + 3TC achieved virologic suppression more rapidly than EFV + TDF + 3TC after 12 and 24 weeks. DTG + 3TC could represent an optimal regimen for advanced patients. Clinical Trial Registration ChiCTR1900027640 (22/November/2019).
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Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Alcinos , Fármacos Anti-HIV/efeitos adversos , Benzoxazinas/efeitos adversos , Ciclopropanos , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis , Humanos , Lamivudina/uso terapêutico , Oxazinas , Piperazinas , Estudos Prospectivos , Piridonas , Tenofovir/uso terapêuticoRESUMO
Coronavirus disease 2019 (COVID-19) have become a pandemic in the world. This study is aim to explore risk factors for COVID-19 severity in the early stage and the correlation between the viral shedding and COVID-19 severity. We included inpatient with laboratory confirmed COVID-19 who had been discharged by 9 March 2020. The medical record data and dynamic change of biochemical indicators in-hospital were compared between common and severe patients. Eighty patients were included in this study. Multivariable regression demonstrated increasing odds of severity associated with the duration of fever (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.10-1.82, per day increase; P = .007), C-reactive protein (CRP) (OR, 1.26; 95% CI, 1.04-1.52; P = .02), and PO2 < 80 mm Hg (28.07, 95% CI, 1.50-524.12; P = .026) on admission. We found severe acute respiratory syndrome coronavirus 2 viral RNA could be long-term presence in respiratory tract and fecal sample, up to 43 and 46 days, respectively. However, the duration of viral shedding have no correlation with the COVID-19 severity. The duration of fever, elevated CRP and PO2 < 80 mm Hg on admission were associated with the COVID-19 severity in the early stage and there is no correlation between the viral shedding and COVID-19 severity.
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COVID-19/fisiopatologia , COVID-19/virologia , SARS-CoV-2/patogenicidade , Eliminação de Partículas Virais , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , Fezes/virologia , Feminino , Febre/virologia , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Razão de Chances , Sistema Respiratório/virologia , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/fisiologia , Índice de Gravidade de Doença , Adulto JovemRESUMO
Aeromonas dhakensis is an important ubiquitous Gram-negative and freshwater bacterium detected in different reservoirs. It can cause invasive diseases in humans. Herein, we report the first case in Mainland China of a fulminant death of a 29-year-old man as a result of a new, unexpected association between septicemic A. dhakensis and hepatitis B viral infection (HBV). Herein, the patient died from multiple organ failure 5 d postadmission after the ingestion of Snakehead Fish meal. The isolated bacterium was initially misidentified as Aeromonas hydrophila using VITEK-2, while whole-genome sequencing (WGS) revealed that the isolate is A. dhakensis. WGS revealed the occurrence of three antimicrobial genes of resistance: imiH, cphA2, and blaOXA-12; besides, major virulence factors were detected. In silico, multilocus sequence typing (MLST) showed that our A. dhakensis 17FW001 belonged to a novel sequence type (ST557). A comparative genomic analysis of our isolate with nine selected Aeromonas species was done, which elucidated the pathogenicity of our A. dhakensis. In conclusion, we reported for the first time the association between A. dhakensis and HBV in Mainland China. We revealed that septicemic A. dhakensis could result in severe adverse clinical outcomes that end up with unexpected fulminant death especially when it is accompanied with HBV and sheds light on the virulence of A. dhakensis and the high rate of its misdiagnosis that requires to urgently consider screening of all cases of A. dhakensis for HBV in the future. Besides, caution should be taken while dealing with snakeheads which act as a vector for A. dhakensis.
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Aeromonas/isolamento & purificação , Infecções por Bactérias Gram-Negativas/mortalidade , Hepatite B/complicações , Sepse/microbiologia , Adulto , Aeromonas/classificação , Animais , Técnicas de Tipagem Bacteriana , China , Farmacorresistência Bacteriana/genética , Evolução Fatal , Peixes , Contaminação de Alimentos , Microbiologia de Alimentos , Genes Bacterianos , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Masculino , Tipagem de Sequências Multilocus , Sepse/mortalidade , Fatores de Virulência/genéticaRESUMO
The hepatitis B core antigen (HBcAg) is an important target for antiviral response in chronic hepatitis B (CHB) patients. However, the correlation between HBcAg in the hepatocyte nucleus and nucleos(t)ide analogue (NA) therapeutic response is unclear. We sought to evaluate the role of HBcAg by analysing liver biopsies for viral response in NA-naïve hepatitis B e antigen (HBeAg) positive (+) CHB patients via immunohistochemistry (IHC). A total of 48 HBcAg-negative (-) patients and 48 HBcAg (+) patients with matching baseline characteristics were retrospectively analysed for up to 288 weeks. Virological response (VR) rates of patients in the HBcAg (-) group were significantly higher at week 48 and 96 than the HBcAg (+) group (77.1% versus 45.8% at week 48, respectively, P = 0.002 and 95.3% versus 83.3% at week 96, respectively, P = 0.045). The serological negative conversion rate of HBeAg was significantly higher in the HBcAg (-) than in the HBcAg (+) group from week 96 to 288 (35.4 % versus 14.6% at week 96, respectively, P = 0.018; 60.4% versus 14.6%, respectively, P < 0.001 at week 144; 72.9% versus 35.4%, respectively, P < 0.001 at week 288). The cumulative frequencies of VR and lack of HBeAg were higher in the HBcAg (-) group (both P < 0.05). Binary logistic regression analysis showed that HBcAg (-) was the predictor for the lack of HBeAg (OR 4.482, 95% CI: 1.58-12.68). In summary, the absence of HBcAg in the hepatocyte nucleus could be an independent predictor for HBeAg seroconversion rates during NA-naïve treatment in HBeAg (+) CHB patients.
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Antivirais/uso terapêutico , Antígenos do Núcleo do Vírus da Hepatite B/biossíntese , Hepatite B Crônica/tratamento farmacológico , Fígado/efeitos dos fármacos , Adulto , Biópsia , Feminino , Antígenos E da Hepatite B/biossíntese , Hepatite B Crônica/patologia , Hepatite B Crônica/virologia , Humanos , Imuno-Histoquímica , Fígado/patologia , Fígado/virologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: MOV10 protein has ATP-dependent 5'-3' RNA helicase activity and belongs to the UPF1p superfamily. It can inhibit human immunodeficiency virus type 1 (HIV-1) replication at multiple stages and interact with apolipoprotein-B-mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G or A3G), a member of the cytidine deaminase family that exerts potent inhibitory effects against HIV-1 infection. However, HIV-1-encoded virion infectivity factor (Vif) protein specifically mediates the degradation of A3G via the ubiquitin-proteasome system (UPS). RESULTS: We demonstrate that MOV10 counteracts Vif-mediated degradation of A3G by inhibiting the assembly of the Vif-CBF-ß-Cullin 5-ElonginB-ElonginC complex. Through interference with UPS, MOV10 enhances the level of A3G in HIV-1-infected cells and virions, and synergistically inhibits the replication and infectivity of HIV-1. In addition, the DEAG-box of MOV10 is required for inhibition of Vif-mediated A3G degradation as the DEAG-box mutant significantly loses this ability. CONCLUSIONS: Our results demonstrate a novel mechanism involved in the anti-HIV-1 function of MOV10. Given that both MOV10 and A3G belong to the interferon antiviral system, their synergistic inhibition of HIV-1 suggests that these proteins may play complicated roles in antiviral functions.
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Desaminase APOBEC-3G/metabolismo , Infecções por HIV/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , RNA Helicases/metabolismo , Produtos do Gene vif do Vírus da Imunodeficiência Humana/metabolismo , Antivirais/metabolismo , Linhagem Celular Transformada , Células HEK293 , Infecções por HIV/enzimologia , Infecções por HIV/virologia , Interações Hospedeiro-Patógeno/fisiologia , Humanos , Mutação , RNA Helicases/genética , Transdução de Sinais , Ubiquitina/metabolismo , Replicação ViralRESUMO
BACKGROUND The antiviral effect of HBV in different nucleos (t) ide analogues is still not well known. This study was conducted to compare the effectiveness of lamivudine (LMV), adefovir dipivoxil (ADV), telbivudine (LdT), and entecavir (ETV) monotherapy in chronic HBeAg-negative hepatitis B patients with medium load of HBV DNA. MATERIAL AND METHODS The effective data of 207 patients treated by LMV (n=43), ADV (n=57), LdT (n=54) or ETV (n=53) were collected and analyzed during 144-week follow-up by retrospective analysis. RESULTS Serum HBV DNA levels were significantly lower in the ETV group 1.91±0.45 log10 IU/ml) than in the LdT group (2.09±0.62 log10 IU/ml), ADV group (2.26±0.73 log10 IU/ml), and LMV group (2.08±0.75 log10 IU/ml) at 12 weeks (P=0.0464). HBV DNA levels were maintained at lower levels in the ETV group compared to other 3 groups during follow-up (48 weeks, P<0.001; 96 weeks, P<0.001). Multivariate Cox regression analysis showed that LMV (P=0.001), ADV, (P<0.001), and LdT (P<0.001) were all negative predictors of HBV DNA-negative time, but ETV was not. Viral breakthrough occurred in 34.8% (15/43) of patients in the LMV group; 5.26% (3/57) in the ADV group, 7.4.0% (4/54) in the LdT group, and 0% (0/53) in the ETV group at the end of follow-up. No significant differences were found in mean ALT levels (all P>0.05) or in cumulative normalization rates (P=0.473). CONCLUSIONS ETV was more potent and faster for viral response and lower viral breakthrough in medium load of HBV DNA when compared to LMV, ADV, or LdT monotherapy in HBeAg-negative CHB.
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Adenina/análogos & derivados , DNA Viral/sangue , Guanina/análogos & derivados , Antígenos E da Hepatite B/sangue , Hepatite B/sangue , Hepatite B/tratamento farmacológico , Lamivudina/uso terapêutico , Nucleosídeos/química , Organofosfonatos/uso terapêutico , Timidina/análogos & derivados , Adenina/efeitos adversos , Adenina/uso terapêutico , Adulto , Alanina Transaminase/sangue , Feminino , Seguimentos , Guanina/efeitos adversos , Guanina/uso terapêutico , Hepatite B/virologia , Humanos , Lamivudina/efeitos adversos , Masculino , Análise Multivariada , Organofosfonatos/efeitos adversos , Modelos de Riscos Proporcionais , Telbivudina , Timidina/efeitos adversos , Timidina/uso terapêuticoRESUMO
AIMS: This study aimed to investigate miR-106a expression in peripheral blood mononuclear cells (PBMCs) of chronic hepatitis B (CHB) patients and to analyze the function of miR-106a. MATERIALS AND METHODS: miR-106a expression levels in PBMCs from 40 healthy controls and 56 CHB patients were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The luciferase activity assays were used to determine whether miR-106a binds to 3'UTR of IL-8. miR-106a mimics and inhibitors were transfected into healthy PBMCs. IL-8 mRNA and protein levels were detected and determined by qRT-PCR and ELISA, respectively. RESULTS: The qRT-PCR results suggested that the PBMC miR-106a levels were decreased in CHB patients. IL-8 was augmented in CHB patients and was inversely correlated with miR-106a levels. The luciferase activity assays indicated that IL-8 is a target of miR-106a. Exogenous expression of miR-106a could significantly repress IL-8 expression at both mRNA and protein levels in PBMCs, whereas miR-106a inhibitor had the opposite effects. CONCLUSIONS: This study suggested that miR-106a is downregulated in PBMCs of CHB patients and that miR-106a may play an important role in CHB by targeting IL-8.
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Hepatite B Crônica/sangue , Hepatite B Crônica/metabolismo , Interleucina-8/sangue , Interleucina-8/metabolismo , Leucócitos Mononucleares/metabolismo , MicroRNAs/sangue , MicroRNAs/metabolismo , Adulto , Feminino , Humanos , Interleucina-8/genética , MasculinoRESUMO
OBJECTIVE: To investigate the efficacy of anti-hepatitis B virus (HBV) drugs for preventing vertical transmission of HBV and the safety of these drugs when given as treatment during pregnancy (to women) or insemination (to men). METHODS: Cases of women and men who had taken anti-HBV drug therapy during pregnancy or insemination, respectively, were retrospectively selected for study from among 18 hospitals and 33 specialists in the Guangdong Province. Demographic, HBV infection and treatment data was collected for puerperal men or women and their newborns from the medical records. RESULTS: A total of 122 cases with detailed follow-up data were included in the study and including 74 women who were administered lamivudine (LAM) more than telbivudine (LdT) more than adefovir (ADV)more than entecavir (ETV) (hierarchy ranking by number of cases) and 48 men who were administered LAM more than ADV more than LdT more than ETV.None of the 122 newborns related to these cases showed HBV infection at 7 months of follow-up.None of the 74 puerperal women showed complications related to reproduction.There was one ease of a newborn being underweight at birth (2.1 kg), for which the mother had taken LdT during pregnancy. There was also one case of a newborn with a harelip and one case of a newborn with an inguinal hernia, for which both of the fathers had taken ADV during the time of insemination. CONCLUSION: This retrospective investigation carried out in Guangdong Province indicated that not only are anti-HBV drugs efficacious for blocking vertical transmission of HBV but also are safe for both mothers and infants when taken by fathers or mothers during the reproduction phases of insemination and pregnancy.
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Antivirais/uso terapêutico , Hepatite B/tratamento farmacológico , Adenina/análogos & derivados , Antivirais/efeitos adversos , Feminino , Guanina/análogos & derivados , Vírus da Hepatite B , Humanos , Lactente , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Lamivudina , Masculino , Mães , Organofosfonatos , Gravidez , Estudos Retrospectivos , Telbivudina , Timidina/análogos & derivados , Fatores de TempoRESUMO
The association between air pollutants and hepatobiliary pancreatic diseases remains inconclusive. This study analyzed up to 247,091 participants of White European ancestry (aged 37 to 73 years at recruitment) from the UK Biobank, a large-scale prospective cohort with open access. An air pollution score was utilized to assess the combined effect of PM2.5, PM2.5-10, PM10, NO2, and NOX on total hepatobiliary pancreatic diseases, liver diseases, cholecyst diseases, and pancreatic diseases. Cox proportional hazard models were employed to evaluate the relationships between air pollutants and the incidence of these diseases. Restricted cubic spline regressions were used to examine the dose-response association between air pollutants and the risk of hepatobiliary pancreatic diseases. We identified 4865 cases of total hepatobiliary pancreatic diseases, over a median follow-up of 10.86 years. The air pollution scores were moderately associated with increased liver disease risk (HR = 1.009, 95 % CI: 1.004, 1.014), but not with cholecyst and pancreatic diseases. Among the individual air pollutants, PM2.5 (HR = 1.069, 95 % CI: 1.025, 1.115) and PM10 (HR = 1.036, 95 % CI: 1.011, 1.061) significantly increased liver disease risk. Males showed a higher risk of liver diseases with PM2.5 (HR = 1.075, 95 % CI: 1.015, 1.139). Additionally, individuals with overweight (HR = 1.125, 95 % CI: 1.052, 1.203), age ≥ 60 and ≤73 (HR = 1.098, 95 % CI: 1.028, 1.172), and alcohol intake ≥ 14 unit/week (HR = 1.078, 95 % CI: 1.006, 1.155) had a higher risk of developing liver diseases at high expose to PM2.5. This study suggests that prolonged exposure to ambient air pollutants may elevate the risk of liver diseases.
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Weil's disease, an icterohemorrhagic infection, is the most severe and fatal form of leptospirosis and is characterized by jaundice, renal dysfunction, and hemorrhagic predisposition. Weil's disease with HIV infection has rarely been reported. A 68-year-old male with HIV infection presented to our hospital with fever and dyspnea that progressed to severe hemoptysis and systemic multiple organ failure, necessitating a tracheal intubation ventilator. A diagnosis of Weil's disease was made after Leptospira interrogans was identified via metagenomic next-generation sequencing (mNGS) in bronchoalveolar lavage fluid (BALF). After immediately receiving supportive therapy and targeted antimicrobial agents, the patient achieved complete recovery upon discharge. The co-infection of HIV infection and leptospirosis resulting in systemic multi-organ failure is rare, but awareness should be raised of the differential diagnosis. mNGS can help identify pathogens and facilitate the use of targeted and efficacious antimicrobial therapy in unusual clinical environments.
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PURPOSE: The purpose of this study was to assess the role of leukocyte immunoglobulin-like receptor A5 (LILRA5) in regulating bacterial infection and corneal inflammation. METHODS: The human corneal tissue microarray data set GSE58291 from Gene Expression Omnibus was downloaded. Then, the differentially expressed genes, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Gene Set Enrichment Analysis, and the immune infiltration analysis were conducted. We constructed the Pseudomonas aeruginosa ( P. aeruginosa ) keratitis mice model using wild-type and LILRA5-deficient mice. The results of the bioinformatics analysis were verified by the cell in vitro and animal in vivo experiments. RESULTS: This study revealed that LILRA5 is substantially expressed in human keratitis and regulates the immune response negatively. Neutrophils were identified as the core fraction of immune cells in keratitis. After P. aeruginosa infection, neutrophils lacking LILRA5 induced elevated levels of proinflammatory cytokines and toll-like receptor 4. LILRA5 deficiency exacerbated the severity of the infection and the production of proinflammatory cytokines in mice. CONCLUSIONS: LILRA5 was discovered as an immunosuppressive regulator in P. aeruginosa keratitis, highlighting its significance in activated immune responses.
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Ceratite , Infecções por Pseudomonas , Receptores Imunológicos , Animais , Humanos , Camundongos , Córnea/patologia , Citocinas/metabolismo , Imunoglobulinas/metabolismo , Ceratite/microbiologia , Camundongos Endogâmicos C57BL , Neutrófilos , Pseudomonas aeruginosa , Infecções por Pseudomonas/microbiologia , Receptores Imunológicos/genéticaRESUMO
Objective: To evaluate the diagnostic value of metagenomic next-generation sequencing (mNGS) in Vibrio vulnificus (V. vulnificus) infection. Methods: A retrospective analysis of patients with V. vulnificus infection at the Fifth Affiliated Hospital of Sun Yat-Sen University from January 1, 2020 to April 23, 2023 was conducted. 14 enrolled patients were diagnosed by culture or mNGS. The corresponding medical records were reviewed, and the clinical data analyzed included demographics, epidemiology laboratory findings, physical examination, symptoms at presentation, antibiotic and surgical treatment, and outcome. Results: In this study, 78.6% (11/14) patients had a history of marine trauma (including fish stab, shrimp stab, crab splints and fish hook wounds), 7.1% (1/14) had eaten seafood, and the remaining 14.3% (2/14) had no definite cause. Isolation of V. vulnificus from clinical samples including blood, tissue, fester and secreta. 9 cases were positive for culture, 5 cases were detected synchronously by mNGS and got positive for V. vulnificus. 85.7% (12/14) cases accepted surgical treatment, with 1 patient suffering finger amputated. 14 enrolled patients received appropriate antibiotic therapy, and all of them had recovered and discharged. 9 strains V. vulnificus isolated in this study were sensitive to most beta-lactam antibiotics, aminoglycosides, quinolones, etc. Conclusion: Vibrio vulnificus infection is a common water-exposed disease in Zhuhai, which requires identification of a number of pathogens. Of severe infections with unknown pathogen, mNGS can be used simultaneously, and the potential to detect multiple pathogens is of great help in guiding treatment.
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Vibrioses , Vibrio vulnificus , Animais , Humanos , Estudos Retrospectivos , Vibrioses/diagnóstico , Vibrioses/epidemiologia , Vibrio vulnificus/genética , Antibacterianos/uso terapêutico , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
BACKGROUND: Wogonin, a flavone isolated from Scutellaria baicalensis Georgi, is a commonly used phytochemical with anti-inflammatory and antitumor properties. However, the antiviral activity of wogonin against human immunodeficiency virus type 1 (HIV-1) has not been reported. PURPOSE: The current study aimed to explore whether wogonin can suppress latent HIV-1 reactivation and the mechanism of wogonin in inhibiting proviral HIV-1 transcription. METHODS: We assessed the effects of wogonin on HIV-1 reactivation using flow cytometry, cytotoxicity assay, quantitative PCR (qPCR), viral quality assurance (VQA), and western blot analysis. RESULTS: Wogonin, a flavone isolated from S. baicalensis, significantly inhibited the reactivation of latent HIV-1 in cellular models and in primary CD4+ T cells from antiretroviral therapy (ART)-suppressed individuals ex vivo. Wogonin exhibited low cytotoxicity and long-lasting inhibition of HIV-1 transcription. Triptolide is a latency-promoting agent (LPA) that inhibits HIV-1 transcription and replication; wogonin had a stronger ability to inhibit HIV-1 latent reactivation than triptolide. Mechanistically, wogonin inhibited the reactivation of latent HIV-1 by inhibiting the expression of p300, a histone acetyltransferase, and decreasing the crotonylation of histone H3/H4 in the HIV-1 promoter region. CONCLUSION: Our study found that wogonin is a novel LPA that can inhibit HIV-1 transcription by HIV-1 epigenetic silencing, which could bear promising significance for future applications of HIV-1 functional cure.
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Infecções por HIV , HIV-1 , Humanos , Histonas/metabolismo , HIV-1/fisiologia , Latência Viral/fisiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/metabolismo , Linfócitos T CD4-PositivosRESUMO
At a global scale, organisms are under threat due to various kinds of environmental changes, such as artificial light at night (ALAN), noise, climatic change and vegetation destruction. Usually, these changes co-vary in time and space and may take effect simultaneously. Although impacts of ALAN on biological processes have been well documented, our knowledge on the combined effects of ALAN and other environmental changes on animals remains limited. In this study, we conducted field experiments in semi-natural enclosures to explore the combined effects of ALAN and vegetation height on foraging behavior, vigilance, activity patterns and body weight in dwarf striped hamsters (Cricetulus barabensis), a nocturnal rodent widely distributed in East Asia. We find that ALAN and vegetation height affected different aspects of behavior. ALAN negatively affected search speed and positively affected handling speed, while vegetation height negatively affected giving-up density and positively affected body weight. ALAN and vegetation height also additively shaped total time spent in a food patch. No significant interactive effect of ALAN and vegetation height was detected. C. barabensis exposed to ALAN and short vegetation suffered a significant loss in body weight, and possessed a much narrower temporal niche (i.e. initiated activity later but became inactive earlier) than those under other combinations of treatments. The observed behavioral responses to ALAN and changes in vegetation height may bring fitness consequences, as well as further changes in structure and functioning of local ecosystems.
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Ecossistema , Roedores , Animais , Poluição Luminosa , Fotoperíodo , Peso CorporalRESUMO
Whether hypervariable region 1 (HVR1)-targeting antibodies elicited during natural hepatitis C virus (HCV) infection contribute to virus clearance and what is the mechanism underlying remain unclear. Here, we demonstrated that treatment of HCV-infected hepatoma Huh7.5 cells with the IgGs purified from 2 of 28 (7.1%) chronic hepatitis C (CHC) patients efficiently controlled the infection, for which genotype 1b HVR1 (1bHVR1)-binding antibody was critical. Moreover, we found that 1bHVR1 peptide was superior to 2aHVR1 in rabbit immunization to elicit antibodies neutralizing genotypes 1a, 2a, 3a, and 4a. The neutralization effect of 1bHVR1 IgG could be augmented by HH-1, an antibody constructed from CHC memory B cells but without binding to HVR1 peptide. Mechanistic studies showed that 1bHVR1 antisera and IgGs disrupted the interaction of E2-SR-B1 receptor. This study highlights the neutralizing activity of HVR1 antibody elicited by CHC patients and generated by HVR1-immunization against the established infections of multiple HCV genotypes.
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Objective: The incidence of inappropriate and excessive empirical antibiotic therapy is unclear. The aim of this study was to determine the prevalence of different empirical antibiotic therapy prescriptions, related factors, and outcomes in hospitalized patients with bacterial infection. Methods: A retrospective cohort study was performed and patients with bacterial infection who were admitted between October 1, 2019, and September 30, 2020, were included. Multivariable analysis was performed by the logistic regression model. Results: A total of 536 (42.6%) of the 1257 included patients received inappropriate empirical antibiotic therapy (IEAT), and 368 (29.3%) patients received appropriate but unnecessarily broad-spectrum empirical antibiotic therapy (AUEAT). MDRO (adjusted OR 2.932 [95% CI 2.201~3.905]; p < 0.001) and fever on admission (adjusted OR 0.592 [95% CI 0.415~0.844]; p = 0.004) were correlates of IEAT; sepsis (adjusted OR 2.342 [95% CI 1.371~3.999]; p = 0.002), age (adjusted OR 1.019 [95% CI 1.008~1.030]; p < 0.001), MDRO (adjusted OR 0.664 [95% CI 0.469~0.941]; p = 0.021), and urinary tract infection (adjusted OR 0.352 [95% CI 0.203~0.611]; p < 0.001) were correlates of AUEAT. Patients who received AUEAT were more likely to have a poor prognosis (63 [17.8%] vs 101 [27.4%]; p = 0.002). Both IEAT (median [IQR], 24,971 [13,135-70,155] vs 31,489 [14,894-101,082] CNY; p = 0.007) and AUEAT (median [IQR], 24,971 [13,135-70,155] vs 30,960 [16,475-90,881] CNY; p = 0.002) increased hospital costs. 45.3% (570/1257) of patients were infected with MDRO and 62.9% of them received IEAT. Conclusion: Inappropriate and excessive empirical antibiotic use was widely prevalent among hospitalized patients. Either inappropriate or excessive use of antibiotics may increase the burden of healthcare costs, the latter of which may be associated with poor prognosis. Clinicians need to be more judicious in choosing antibiotic(s). The MDRO epidemic was severe, especially in patients who received IEAT. It is imperative to take effective measures to improve the current situation of antibiotic abuse and antimicrobial resistance.
RESUMO
Emerging infectious diseases have brought a huge impact on human society in recent years. The outbreak of Zika virus (ZIKV) in the Americas resulted in a large number of babies born with microcephaly. More seriously, the Coronavirus Disease 2019 (COVID-19) was globally spread and caused immeasurable damages. Thus, the monitoring of highly pathogenic viruses is important to prevent and control emerging infectious diseases. Herein, a dendritic polymer probe-amplified ECL-scan imaging system was constructed to realize trace analysis of viral emerging infectious diseases. A dendritic polymer probe was employed as the efficient signal emitter component that could generate an amplified ECL signal on the integrated chip, and the signal was detected by a single-photon level charge coupled device-based ECL-scan imaging system. With this strategy, the ZIKV in a complex system of blood, urine, and saliva was detected. The results indicated that a high sensitivity of 50 copies and superior specificity were achieved. Furthermore, this strategy realized highly sensitive detection (10 copies) of the S and N protein gene sequence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov2) and spiked pseudovirus samples. Thus, the dendritic polymer probe-amplified ECL-scan imaging system suitably met the strict clinical requirements for trace analysis of an emerging virus, and thus has the potential to serve as a paradigm for monitoring emerging infectious diseases.