Intermittent fasting and health outcomes: an umbrella review of systematic reviews and meta-analyses of randomised controlled trials.

Background: Benefits of Intermittent fasting (IF) on health-related outcomes have been found in a range of randomised controlled trials (RCTs). Our umbrella review aimed to systematically analyze and synthesize the available causal evidence on IF and its impact on specific health-related outcomes while evaluating its evidence quality. Methods: We comprehensively searched the PubMed, Embase, Web of Science, and Cochrane databases (from inception up to 8 January 2024) to identify related systematic reviews and meta-analyses of RCTs investigating the association between IF and human health outcomes. We recalculated the effect sizes for each meta-analysis as mean difference (MD) or standardized mean difference (SMD) with corresponding 95% confidence intervals (CIs). Subgroup analyses were performed for populations based on three specific status: diabetes, overweight or obesity, and metabolic syndrome. The quality of systematic reviews was evaluated using A Measurement Tool to Assess Systematic Reviews (AMSTAR), and the certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system. This study is registered with PROSPERO (CRD42023382004). Findings: A total of 351 associations from 23 meta-analyses with 34 health outcomes were included in the study. A wide range of outcomes were investigated, including anthropometric measures (n = 155), lipid profiles (n = 83), glycemic profiles (n = 57), circulatory system index (n = 41), appetite (n = 9), and others (n = 6). Twenty-one (91%) meta-analyses with 346 associations were rated as high confidence according to the AMSTAR criteria. The summary effects estimates were significant at p < 0.05 in 103 associations, of which 10 (10%) were supported by high certainty of evidence according to GRADE. Specifically, compared with non-intervention diet in adults with overweight or obesity, IF reduced waist circumference (WC) (MD = -1.02 cm; 95% CI: -1.99 to -0.06; p = 0.038), fat mass (MD = -0.72 kg; 95% CI: -1.32 to -0.12; p = 0.019), fasting insulin (SMD = -0.21; 95% CI: -0.40 to -0.02; p = 0.030), low-density lipoprotein cholesterol (LDL-C) (SMD = -0.20; 95% CI: -0.38 to -0.02; p = 0.027), total cholesterol (TC) (SMD = -0.29; 95% CI: -0.48 to -0.10; p = 0.003), and triacylglycerols (TG) (SMD = -0.23; 95% CI: -0.39 to -0.06; p = 0.007), but increased fat free mass (FFM) (MD = 0.98 kg; 95% CI: 0.18-1.78; p = 0.016). Of note, compared with the non-intervention diet, modified alternate-day fasting (MADF) reduced fat mass (MD = -0.70 kg; 95% CI: -1.38 to -0.02; p = 0.044). In people with overweight or obesity, and type 2 diabetes, IF increases high-density lipoprotein cholesterol (HDL-C) levels compared to continuous energy restriction (CER) (MD = 0.03 mmol/L; 95% CI: 0.01-0.05; p = 0.010). However, IF was less effective at reducing systolic blood pressure (SBP) than a CER diet in adults with overweight or obesity (SMD = 0.21; 95% CI: 0.05-0.36; p = 0.008). Interpretation: Our findings suggest that IF may have beneficial effects on a range of health outcomes for adults with overweight or obesity, compared to CER or non-intervention diet. Specifically, IF may decreased WC, fat mass, LDL-C, TG, TC, fasting insulin, and SBP, while increasing HDL-C and FFM. Notably, it is worth noting that the SBP lowering effect of IF appears to be weaker than that of CER. Funding: This work was supported by the National Key Research and Development Program of China (Q-JW), the Natural Science Foundation of China (Q-JW and T-TG), Outstanding Scientific Fund of Shengjing Hospital of China Medical University (Q-JW), and 345 Talent Project of Shengjing Hospital of China Medical University (T-TG).

Functional assessments of SARS-CoV-2 single-round infectious particles with variant-specific spike proteins on infectivity, drug sensitivity, and antibody neutralization.

Working with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is restricted to biosafety level III (BSL-3) laboratory. The study used a trans-complementation system consisting of virus-like particles (VLPs) and DNA-launched replicons to generate SARS-CoV-2 single-round infectious particles (SRIPs) with variant-specific spike (S) proteins. S gene of Wuhan-Hu-1 strain (SWH1) or Omicron BA.1 variant (SBA.1), along with the envelope (E) and membrane (M) genes, were cloned into a tricistronic vector, co-expressed in the cells to produce variant-specific S-VLPs. Additionally, the replicon of the WH1-like strain without S, E, M and accessory genes, was engineered under the control by a CMV promoter to produce self-replicating RNAs within VLP-producing cells, led to create SWH1- and SBA.1-based SARS-CoV-2 SRIPs. The SBA.1-based SRIP showed lower virus yield, replication, N protein expression, fusogenicity, and infectivity compared to SWH1-based SRIPs. SBA.1-based SRIP also exhibited intermediate resistance to neutralizing antibodies produced by SWH1-based vaccines, but were effective at infecting cells with low ACE2 expression. Importantly, both S-based SRIPs responded similarly to remdesivir and GC376, with EC50 values ranging from 0.17 to 1.46 µM, respectively. The study demonstrated that this trans-complementation system is a reliable and efficient tool for generating SARS-CoV-2 SRIPs with variant-specific S proteins. SARS-CoV-2 SRIPs, mimicking authentic live viruses, facilitate comprehensive analysis of variant-specific virological characteristics, including antibody neutralization, and drug sensitivity in non-BSL-3 laboratories.

The relationship of superoxide dismutase and malondialdehyde levels with left ventricular geometry and function in patients with primary hypertension.

INTRODUCTION: To investigate the relationship of superoxide dismutase (SOD) and malondialdehyde (MDA) levels with left ventricular geometry (LVG) and function in patients with primary hypertension (PH). METHODS: A total of 222 PH patients and 25 healthy control (HC)s were enrolled in this study. All subjects underwent echocardiography and blood biochemical examination. PH patients were divided into four groups based on Ganau classification: normal geometry (NG) group, concentric remodeling (CR) group, eccentric hypertrophy (EH) group, and concentric hypertrophy (CH) group. Pearson correlation analysis and logistic regression analysis were used to analyze the relationship between SOD and MDA with left ventricular structure and function. RESULTS: Compared to the HC, NG and CR groups, MDA level was higher while SOD level was lower in the EH and CH groups (all P < 0.001). SOD level was negatively correlated with IVSd, LVDd, LVPW, and global longitudinal strain (GLS), but positively correlated with LVEF. MDA level was positively correlated with IVSd, LVPW, and GLS, while negatively correlated with e'/a' and LVEF. SOD and MDA were independently associated with CR (OR = 0.970, P = 0.003; OR = 1.204, P = 0.043), EH (OR = 0.879, P < 0.001; OR = 2.197, P = 0.001) and CH (OR = 0.796, P < 0.001; OR = 3.669, P < 0.001). CONCLUSION: The SOD and MDA levels were correlated with LVG and function in PH patients. SOD and MDA may be important influencing factors of LVG change.

Development of Fluorescence-Tagged SARS-CoV-2 Virus-like Particles by a Tri-Cistronic Vector Expression System for Investigating the Cellular Entry of SARS-CoV-2.

Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has caused the pandemic that began late December 2019. The co-expression of SARS-CoV-2 structural proteins in cells could assemble into several types of virus-like particles (VLPs) without a viral RNA genome. VLPs containing S proteins with the structural and functional properties of authentic virions are safe materials to exploit for virus-cell entry and vaccine development. In this study, to generate SARS-CoV-2 VLPs (SCoV2-SEM VLPs) composed of three structural proteins including spike (S), envelop (E) protein and membrane (M) protein, a tri-cistronic vector expression system was established in a cell line co-expressing SARS-CoV-2 S, E and M proteins. The SCoV2-SEM VLPs were harvested from the cultured medium, and three structure proteins were confirmed by Western blot assay. A negative-stain TEM assay demonstrated the size of the SCoV2-SEM VLPs with a diameter of about 90 nm. To further characterize the infectious properties of SCoV2-SEM VLPs, the VLPs (atto647N-SCoV2-SEM VLPs) were fluorescence-labeled by conjugation with atto-647N and visualized under confocal microscopy at a single-particle resolution. The results of the infection assay revealed that atto647N-SCoV2-SEM VLPs attached to the surface of the HEK293T cells at the pre-binding phase in a ACE2-dependent manner. At the post-infection phase, atto647N-SCoV2-SEM VLPs either fused with the cellular membrane or internalized into the cytoplasm with mCherry-rab5-positive early endosomes. Moreover, fusion with the cellular membrane and the internalization with early endosomes could be inhibited by the treatment of camostat (a pharmacological inhibitor of TMPRSS2) and chlorpromazine (an endocytosis inhibitor), respectively. These results elucidated that SCoV2-SEM VLPs behave similarly to the authentic live SARS-CoV-2 virus, suggesting that the development of SCoV2-SEM VLPs provide a realistic and safe experimental model for studying the infectious mechanism of SARS-CoV-2.

Inflammatory cytokines and their correlations with different left ventricular geometries and functions in PHT patients.

OBJECTIVES: To investigate relationships between hypersensitive C-reactive protein (hs-CRP), tumor necrosis factor -α (TNF-α), interleukin-17A (IL-17A), and interferon -γ (IFN-γ), with left ventricular geometry (LVG) and function in patients with primary hypertension (PHT). METHODS: A total of 396 PHT patients were assigned into four groups: Normal Geometry (NG), Concentric Remodeling (CR), Eccentric Hypertrophy (EH), and Concentric Hypertrophy (CH). The correlation between hs-CRP, TNF-α, IL-17A, IFN-γ, and clinical, biochemical parameters were analyzed by Pearson correlation analysis and Logistic regression. Receiver Operating Characteristic (ROC) curve was used to analyze the clinical values of hs-CRP, TNF-α, IL-17A, and IFN-γ for abnormal LVG prediction. RESULTS: NG, CR, EH, and CH group all presented increasingly higher levels of Hs-CRP, TNF-α, IL-17A, and IFN-γ, and the increase was the most prominent in the CH group. Pearson correlation analysis showed that hs-CRP, IL-17A, and IFN-γ were all positively correlated with LASct. Hs-CRP, TNF-α, and IL-17A were all negatively correlated with GLS, LASr, and LAScd. However, IFN-γ was only negatively correlated with GLS and LAScd. Logistic regression analysis showed that hs-CRP and IL-17A were independently correlated with CR; hs-CRP, TNF-α, IFN-γ, and IL-17A were independently correlated with EH and CH. ROC curve analysis showed that the area under the curve (AUC) of hs-CRP was 0.816. When the optimal diagnostic threshold of hs-CRP was 3.04 mg/L, the sensitivity and specificity of the abnormal LVG were 72.1% and 81.5%, respectively. CONCLUSION: In PHT patients, hs-CRP, TNF-α, IL-17A, and IFN-γ were correlated with abnormal LVG and left ventricular function, suggesting that inflammatory cytokines may be involved in the process of PHT-induced abnormal left ventricular structure and function. In addition, hs-CRP can be used as a health screening index for patients at high risk of abnormal LVG.

The relationship of interleukin-6 and C-reactive protein with left ventricular geometry and function in patients with obstructive sleep apnea syndrome and pre-hypertension.

OBJECTIVE: To assess the relationship of interleukin-6 (IL-6) and C-reactive protein (CRP) levels with left ventricular geometry (LVG) and function in patients with obstructive sleep apnea syndrome (OSAS) and pre-hypertension. METHODS: A total of 458 patients were assigned into four groups: normal geometry (NG), concentric remodeling (CR), eccentric hypertrophy (EH), and concentric hypertrophy (CH). Pearson correlation and multivariate logistic regression analyses were used to determine the correlation between IL-6, CRP, and clinical, polysomnographic, and biochemical parameters with LVG and function. RESULTS: IL-6 and CRP levels were higher in the EH and CH groups than those in the NG and CR groups. The results of the Pearson correlation analysis showed that IL-6 level was positively correlated with the E/e' ratio and peak systolic pulmonary venous reverse velocity (PVa) duration time (PVaD), while negatively correlated with the E/A ratio, s', and left ventricular ejection fraction (LVEF). CRP level was positively correlated with A-wave duration time (AD), peak systolic pulmonary venous flow velocity (PVs), PVa and PVaD, while negatively correlated with the E/A ratio. The results of the multivariate logistic regression analysis revealed that IL-6 and CRP levels were correlated with EH (ß = 1.213, odds ratio [OR] = 3.363, p < 0.001; ß = 1.258, OR = 3.518, p < 0.001) and CH (ß = .938, OR = 2.555, p = 0.008; ß = 1.239, OR = 3.454, p < 0.001). CONCLUSION: IL-6 and CRP levels are associated with LVG and function, suggesting that IL-6 and CRP levels are involved in OSAS and pre-hypertension, leading to abnormal left ventricular structure and function.

Associação da hipertensão com a gravidade e a mortalidade de pacientes hospitalizados com COVID-19 em Wuhan, China: Estudo unicêntrico e retrospectivo / Association of hypertension with severity and mortality in hospitalized patients with COVID-19 in wuhan, China: A single-centered, retrospective study

Resumo Fundamento A doença Coronavírus 2019 (COVID-19), causada pela síndrome respiratória aguda grave Coronavírus 2 (SARS-CoV-2), espalhou-se pelo mundo. Objetivo Investigar a associação entre a hipertensão e a gravidade/mortalidade de pacientes hospitalizados com COVID-19 em Wuhan, China. Métodos Um total de 337 pacientes diagnosticados com COVID-19 no Sétimo Hospital da cidade de Wuhan, de 20 de janeiro a 25 de fevereiro de 2020, foram inseridos e analisados em um estudo de caso unicêntrico e retrospectivo. O nível de significância adotado para a análise estatística foi 0,05. Resultados Dos 337 pacientes com diagnóstico confirmado de COVID-19, 297 (87.8%) tiveram alta do hospital e 40 pacientes (22,9%) morreram. A idade média foi de 58 anos (variando de 18 a 91 anos). Havia 112 (33,2%) pacientes diagnosticados com hipertensão no momento da internação (idade média, 65,0 anos [variação, 38-91 anos]; sendo 67 homens [59,8%, IC95%: 50,6%-69,0%], p=0,0209). Pacientes com hipertensão apresentaram uma porção significativamente maior de casos graves (69 [61,6%, IC95%: 52,5%-70,8%] vs. 117 [52,0%, IC95%: 45,4%-58,6%] em pacientes graves e 23 [19,3%, IC95%: 12,9%-28,1%] vs. 27 [12,0%, IC95%: 7,7%-16,3%] em pacientes críticos, p=0,0014) e maiores taxas de mortalidade (20 [17,9%, IC95%: 10,7%-25,1%] vs. 20 [8,9%, IC95%: 5,1%-12,6%, p=0,0202). Além disso, pacientes hipertensos apresentaram níveis anormais de vários indicadores, como linfopenia e inflamação, e nas funções cardíacas, hepáticas, renais e pulmonares no momento da internação. O grupo de pacientes com hipertensão também demonstrou níveis maiores de TNT e creatinina próximo da alta. Conclusão A hipertensão está altamente associada à gravidade ou mortalidade da COVID-19. Um tratamento agressivo deve ser considerado para pacientes hipertensos com COVID-19, principalmente com relação a lesões cardíacas e dos rins.

Abstract Background Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide. Objective To investigate the association between hypertension and severity/mortality in hospitalized patients with COVID-19 in Wuhan, China. Methods A total of 337 patients diagnosed with COVID-19 at the Seventh Hospital of Wuhan City, from January 20 to February 25, 2020, were enrolled and analyzed in a retrospective, single-center case study. The significance level adopted in the statistical analysis was 0.05. Results Of the 337 patients with confirmed diagnosis of COVID-19, 297 (87.8%) were discharged from the hospital and 40 patients (22.9%) died. The median age was 58 years (range, 18-91 years). There were 112 (33.2%) patients diagnosed with hypertension at admission (median age, 65.0 years [range, 38-91 years]; 67 [59.8%, 95%CI: 50.6%-69.0%] men, p=0.0209). Patients with hypertension presented a significantly higher portion of severe cases (69 [61.6%, 95%CI:52.5%-70.8%] vs. 117 [52.0%, 95%CI: 45.4%-58.6%] in severe patients and 23 [19.3%, 95%CI:12.9%-28.1%] vs. 27 [12.0%, 95%CI: 7.7%-16.3%] in critical patients, p=0.0014) and higher mortality rates (20 [17.9%, 95%CI: 10.7%-25.1%] vs. 20 [8.9%, 95%CI: 5.1%-12.6%, p=0.0202). Moreover, hypertensive patients presented abnormal levels of multiple indicators, such as lymphopenia, inflammation, heart, liver, kidney, and lung function at admission. The hypertension group still displayed higher levels of TnT and creatinine at approaching discharge. Conclusion Hypertension is strongly associated with severity or mortality of COVID-19. Aggressive treatment may be considered for COVID-19 patients with hypertension, especially regarding cardiac and kidney injury.

Association of Hypertension with Severity and Mortality in Hospitalized Patients with COVID-19 in Wuhan, China: A Single-centered, Retrospective Study. / Associação da Hipertensão com a Gravidade e a Mortalidade de Pacientes Hospitalizados com COVID-19 em Wuhan, China: Estudo Unicêntrico e Retrospectivo.

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide. OBJECTIVE: To investigate the association between hypertension and severity/mortality in hospitalized patients with COVID-19 in Wuhan, China. METHODS: A total of 337 patients diagnosed with COVID-19 at the Seventh Hospital of Wuhan City, from January 20 to February 25, 2020, were enrolled and analyzed in a retrospective, single-center case study. The significance level adopted in the statistical analysis was 0.05. RESULTS: Of the 337 patients with confirmed diagnosis of COVID-19, 297 (87.8%) were discharged from the hospital and 40 patients (22.9%) died. The median age was 58 years (range, 18-91 years). There were 112 (33.2%) patients diagnosed with hypertension at admission (median age, 65.0 years [range, 38-91 years]; 67 [59.8%, 95%CI: 50.6%-69.0%] men, p=0.0209). Patients with hypertension presented a significantly higher portion of severe cases (69 [61.6%, 95%CI:52.5%-70.8%] vs. 117 [52.0%, 95%CI: 45.4%-58.6%] in severe patients and 23 [19.3%, 95%CI:12.9%-28.1%] vs. 27 [12.0%, 95%CI: 7.7%-16.3%] in critical patients, p=0.0014) and higher mortality rates (20 [17.9%, 95%CI: 10.7%-25.1%] vs. 20 [8.9%, 95%CI: 5.1%-12.6%, p=0.0202). Moreover, hypertensive patients presented abnormal levels of multiple indicators, such as lymphopenia, inflammation, heart, liver, kidney, and lung function at admission. The hypertension group still displayed higher levels of TnT and creatinine at approaching discharge. CONCLUSION: Hypertension is strongly associated with severity or mortality of COVID-19. Aggressive treatment may be considered for COVID-19 patients with hypertension, especially regarding cardiac and kidney injury.

FUNDAMENTO: A doença Coronavírus 2019 (COVID-19), causada pela síndrome respiratória aguda grave Coronavírus 2 (SARS-CoV-2), espalhou-se pelo mundo. OBJETIVO: Investigar a associação entre a hipertensão e a gravidade/mortalidade de pacientes hospitalizados com COVID-19 em Wuhan, China. MÉTODOS: Um total de 337 pacientes diagnosticados com COVID-19 no Sétimo Hospital da cidade de Wuhan, de 20 de janeiro a 25 de fevereiro de 2020, foram inseridos e analisados em um estudo de caso unicêntrico e retrospectivo. O nível de significância adotado para a análise estatística foi 0,05. RESULTADOS: Dos 337 pacientes com diagnóstico confirmado de COVID-19, 297 (87.8%) tiveram alta do hospital e 40 pacientes (22,9%) morreram. A idade média foi de 58 anos (variando de 18 a 91 anos). Havia 112 (33,2%) pacientes diagnosticados com hipertensão no momento da internação (idade média, 65,0 anos [variação, 38-91 anos]; sendo 67 homens [59,8%, IC95%: 50,6%-69,0%], p=0,0209). Pacientes com hipertensão apresentaram uma porção significativamente maior de casos graves (69 [61,6%, IC95%: 52,5%-70,8%] vs. 117 [52,0%, IC95%: 45,4%-58,6%] em pacientes graves e 23 [19,3%, IC95%: 12,9%-28,1%] vs. 27 [12,0%, IC95%: 7,7%-16,3%] em pacientes críticos, p=0,0014) e maiores taxas de mortalidade (20 [17,9%, IC95%: 10,7%-25,1%] vs. 20 [8,9%, IC95%: 5,1%-12,6%, p=0,0202). Além disso, pacientes hipertensos apresentaram níveis anormais de vários indicadores, como linfopenia e inflamação, e nas funções cardíacas, hepáticas, renais e pulmonares no momento da internação. O grupo de pacientes com hipertensão também demonstrou níveis maiores de TNT e creatinina próximo da alta. CONCLUSÃO: A hipertensão está altamente associada à gravidade ou mortalidade da COVID-19. Um tratamento agressivo deve ser considerado para pacientes hipertensos com COVID-19, principalmente com relação a lesões cardíacas e dos rins.

Association of diabetes with severity and mortality in hospitalized patients with COVID-19 in Wuhan, China: a single-centered, retrospective study.

OBJECTIVE: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide. The aim this study was to investigate the association of diabetes with severity and mortality among hospitalized patients with COVID-19 in Wuhan, China. METHODS: This retrospective, single-center case study enrolled a total of 564 patients diagnosed with COVID-19 at the Seventh Hospital of Wuhan City, between January 20 and March 15, 2020. RESULTS: Among the 564 patients with confirmed COVID-19, 509 (85.1%) were discharged and 55 (9.8%) died. The median age was 59 years (range, 10-93 years). A total of 85 (15.1%) patients were diagnosed with diabetes on admission (median age, 65.0 [range, 34-91] years). Patients with diabetes had significantly higher proportions of critical cases (24 [28.2%] vs. 66 [13.8%]) and in-hospital mortality (17 [20%] vs. 38 [7.9%]). Moreover, patients with diabetes presented abnormal levels of multiple indicators concerning lymphopenia, inflammation, heart, liver, kidney, and lung function on admission, while diabetic patient group still display higher troponin T (TnT) levels when approaching discharge. The Kaplan-Meier survival curve indicated a trend toward poorer survival in diabetic patients compared to non-diabetic patients, also evidenced by abnormal laboratory biomarker changes regarding multiple system impairments among COVID-19 patients with diabetes with in-hospital death. CONCLUSION: The detailed clinical investigation of 564 hospitalized patients with COVID-19 indicated a considerable association between diabetes and COVID-19 severity or mortality. Thus, more intensive treatment may be considered for COVID-19 patients with diabetes, especially regarding to cardiac injury.

Association of diabetes with severity and mortality in hospitalized patients with COVID-19 in Wuhan, China: a single-centered, retrospective study

ABSTRACT Objective: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide. The aim this study was to investigate the association of diabetes with severity and mortality among hospitalized patients with COVID-19 in Wuhan, China. Subjects and methods: This retrospective, single-center case study enrolled a total of 564 patients diagnosed with COVID-19 at the Seventh Hospital of Wuhan City, between January 20 and March 15, 2020. Results: Among the 564 patients with confirmed COVID-19, 509 (85.1%) were discharged and 55 (9.8%) died. The median age was 59 years (range, 10-93 years). A total of 85 (15.1%) patients were diagnosed with diabetes on admission (median age, 65.0 [range, 34-91] years). Patients with diabetes had significantly higher proportions of critical cases (24 [28.2%] vs. 66 [13.8%]) and in-hospital mortality (17 [20%] vs. 38 [7.9%]). Moreover, patients with diabetes presented abnormal levels of multiple indicators concerning lymphopenia, inflammation, heart, liver, kidney, and lung function on admission, while diabetic patient group still display higher troponin T (TnT) levels when approaching discharge. The Kaplan-Meier survival curve indicated a trend toward poorer survival in diabetic patients compared to non-diabetic patients, also evidenced by abnormal laboratory biomarker changes regarding multiple system impairments among COVID-19 patients with diabetes with in-hospital death. Conclusion: The detailed clinical investigation of 564 hospitalized patients with COVID-19 indicated a considerable association between diabetes and COVID-19 severity or mortality. Thus, more intensive treatment may be considered for COVID-19 patients with diabetes, especially regarding to cardiac injury.

Exosomal miR-145-5p derived from orthohantavirus-infected endothelial cells inhibits HTNV infection.

Human infection of orthohantavirus can cause potentially fatal diseases, such as hemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus (HTNV) in Eurasia. Exosomes are new carriers for information exchange between cells. Cumulative findings suggest that exosomes released from parental infected cells can block or promote viral infection in recipient cells, but the role of exosomes in hantavirus infection is poorly understood. In our study, we identified the exosomes derived from HTNV-infected human vascular endothelial cells (HUVECs) (Exo-HV) and found the antiviral properties of Exo-HV in the uninfected recipient cells. High-throughput sequencing revealed the distinctly expressed miRNAs transcriptomes in Exo-HV. MiR-145-5p, one of the abundant miRNAs packaged into Exo-HV, was found to be able to transferred to recipient cells and functioned by directly targeting M RNA of HTNV 76-118 and inducing type I interferon (IFN-I) response, thus, blocking the viral replication. Concluding, this study indicated that exosomes released by HTNV-infected HUVECs were able to transfer active molecules, miR-145-5p as a proving sample, to mediate novel anti-HTNV activity in the neighboring uninfected cells, which will help us to explore new strategies for the treatment of infectious disease utilizing exosomes with miRNA.

HTNV Sensitizes Host Toward TRAIL-Mediated Apoptosis-A Pivotal Anti-hantaviral Role of TRAIL.

Hantaviruses can cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia and have led to public health threat in China. The pathogenesis of HFRS is complex and involves capillary leakage due to the infection of vascular endothelial cells. Accumulating evidence has demonstrated that hantavirus can induce apoptosis in many cells, but the mechanism remains unclear. Our studies showed that Hantaan virus (HTNV) infection could induce TNF-related apoptosis-inducing ligand (TRAIL) expression in primary human umbilical vein endothelial cells (HUVECs) and sensitize host cells toward TRAIL-mediated apoptosis. Furthermore, TRAIL interference could inhibit apoptosis and enhance the production of HTNV as well as reduce IFN-ß production, while exogenous TRAIL treatment showed reverse outcome: enhanced apoptosis and IFN-ß production as well as a lower level of viral replication. We also observed that nucleocapsid protein (NP) and glycoprotein (GP) of HTNV could promote the transcriptions of TRAIL and its receptors. Thus, TRAIL was upregulated by HTNV infection and then exhibited significant antiviral activities in vitro, and it was further confirmed in the HTNV-infected suckling mice model that TRAIL treatment significantly reduced viral load, alleviated virus-induced tissue lesions, increased apoptotic cells, and decreased the mortality. In conclusion, these results demonstrate that TRAIL-dependent apoptosis and IFN-ß production could suppress HTNV replication and TRAIL treatment might be a novel therapeutic target for HTNV infection.

[Effects of stand structure regulation on soil labile organic carbon in Pinus elliottii plantation].

Taking 21-year-old Pinus elliottii pure plantation as the control, effects of enrichment planting with broadleaf trees (Liquidambar fornosana) after thinning the conifer trees (P. elliottii) on soil labile organic carbon of different plantations, including 3-year-old, 6-year-old, 9-year-old P. elliottii and 21-year-old P. elliottii-L. fornosana mixed plantations, were investigated. The results showed that the contents of soil dissolved organic carbon (DOC), readily oxidizable organic carbon (ROC), and microbial biomass carbon (MBC) significantly increased in the 6-year-old and 9-year-old plantations compared with those in the 21-year-old P. elliottii pure plantation. Soil labile organic carbon contents in the 21-year-old P. elliottii-L. fornosana mixed plantation increased significantly than those in 3-year-old, 6-year-old, 9-year-old stands, and the DOC, ROC and MBC contents increased by 113.1%, 53.3% and 54.6%, respectively, compared with those in the 21-year-old P. elliottii pure plantation. The results suggested that replanting with broadleaf trees are an effective measure to improve the soil ecological function in pure P. elliottii plantation.