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1.
J Infect Dis ; 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32227123

RESUMO

BACKGROUND: Since December 2019, novel coronavirus (SARS-CoV-2)-infected pneumonia (COVID-19) occurred in Wuhan, and rapidly spread throughout China. We aimed to clarify the characteristics and clinical significance of peripheral lymphocyte subset alteration in COVID-19. METHODS: The levels of peripheral lymphocyte subsets were measured by flow cytometry in 60 hospitalized COVID-19 patients before and after treatment, and their association with clinical characteristics and treatment efficacy was analyzed. RESULTS: Total lymphocytes, CD4+ T cells, CD8+ T cells, B cells and natural killer (NK) cells decreased in COVID-19 patients, and severe cases had a lower level than mild cases. The subsets showed a significant association with the inflammatory status in COVID-19, especially CD8+ T cells and CD4+/CD8+ ratio. After treatment, 37 patients (67%) reached clinical response, with an increase of CD8+ T cells and B cells. No significant change of any subset was detected in non-response cases. In multivariate analysis, post-treatment decrease of CD8+ T cells and B cells and increase of CD4+/CD8+ ratio were indicated as independent predictors for poor efficacy. CONCLUSIONS: Peripheral lymphocyte subset alteration was associated with the clinical characteristics and treatment efficacy of COVID-19. CD8+ T cells tended to be an independent predictor for COVID-19 severity and treatment efficacy.

2.
Immunopharmacol Immunotoxicol ; 42(2): 147-155, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32116077

RESUMO

Objective: Sinomenine (SIN), an alkaloid isolated from sinomenium acutum plant, possesses many pharmacological properties, such as anti-inflammation, anti-hyperalgesia, anti-allergy, anti-apoptosis, and anti-angiogenesis. In this study, we aimed to investigate the detailed molecular mechanisms associated with the anti-inflammatory activity of SIN in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages.Methods: RAW264.7 cells were treated with LPS and/or indicated concentrations of SIN. Inflammatory cytokine production, such as TNF-α, IL-1ß, and IL-6, was detected by ELISA. Expression of microRNA-155 (miR-155), SOCS1 and NF-κB was assessed by qRT-PCR and Western blot, separately. Simultaneously, miR-155 inhibitor and SOCS1 SiRNA were transfected to observe the regulative effects of SIN on the expression of miR-155, SOCS1, and NF-κB.Results: Our result showed that SIN treatment significantly reduced LPS-induced inflammatory cytokine release, suppressed the expression of miR-155, enhanced SOCS1 expression at mRNA and protein levels, and prevented NF-ĸB transcription. Furthermore, transfection of miR-155 inhibitor and SOCS1 SiRNA emphasized that the regulation of miR-155, SOCS1, and NF-ĸB was associated with the anti-inflammatory activation of SIN in LPS-treated macrophages.Conclusions: This study indicated that SIN alleviated LPS-induced inflammatory responses in RAW264.7 macrophages by downregulating miR-155 and upregulating SOCS1, at least partly, leading to the suppression of NF-ĸB transcription. These findings suggest that SIN might be developed as an alternative and promising drug for the treatment of inflammatory diseases.

3.
Front Med ; 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32166600

RESUMO

The COVID-19 caused by a novel strain of Coronavirus has been spreading rapidly since its onset in Wuhan, the capital city of central China's Hubei Province, in December 2019. It is highly communicable through human-to-human transmission. China has been making unprecedented efforts in treating the confirmed cases, identifying and isolating their close contacts and suspected cases to control the source of infection and cut the route of transmission. China's devotion in handling this epidemic has effectively and efficiently curbed communication domestically and across the border. Representative measures adopted by Wenzhou, the worst hit city out of Hubei Province, are examined to elucidate those massive undertakings with the aim of enhancing international understanding and building global rapport in fighting this evolving epidemic situation.

4.
Clin Infect Dis ; 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32173725

RESUMO

BACKGROUND: Since December 2019, novel coronavirus (SARS-CoV-2)-infected pneumonia (COVID-19) occurred in Wuhan, and rapidly spread throughout China. This study aimed to clarify the characteristics of patients with refractory COVID-19. METHODS: In this retrospective single-center study, we included 155 consecutive patients with confirmed COVID-19 in Zhongnan Hospital of Wuhan University from January 1st to February 5th. The cases were divided into general and refractory COVID-19 groups according to the clinical efficacy after hospitalization, and the difference between groups were compared. RESULTS: Compared with general COVID-19 patients (45.2%), refractory patients had an older age, male sex, more underlying comorbidities, lower incidence of fever, higher levels of maximum temperature among fever cases, higher incidence of breath shortness and anorexia, severer disease assessment on admission, high levels of neutrophil, aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and C-reactive protein, lower levels of platelets and albumin, and higher incidence of bilateral pneumonia and pleural effusion (P<0.05). Refractory COVID-19 patients were more likely to receive oxygen, mechanical ventilation, expectorant, and adjunctive treatment including corticosteroid, antiviral drugs and immune enhancer (P<0.05). After adjustment, those with refractory COVID-19 were also more likely to have a male sex and manifestations of anorexia and fever on admission, and receive oxygen, expectorant and adjunctive agents (P<0.05) when considering the factors of disease severity on admission, mechanical ventilation, and ICU transfer. CONCLUSION: Nearly 50% COVID-19 patients could not reach obvious clinical and radiological remission within 10 days after hospitalization. The patients with male sex, anorexia and no fever on admission predicted poor efficacy.

5.
Aging (Albany NY) ; 12(3): 2952-2973, 2020 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-32039831

RESUMO

We conducted a cross-sectional study investigating community-dwelling older population to determine association between immunoscenescence marker, inflammatory cytokines and frailty. Frailty status was classified with 33-item modified frailty index and latent class analysis was applied to explore the latent classes (subtypes) of frailty. In multivariable analysis, higher Tfh2 cells were associated with a higher risk of frailty [1.13(1.03-1.25)] in females, but a lower risk of cognitive and functional frail [0.92(0.86-0.99)] and physiological frail [0.92(0.87-0.98)]. Additionally, a greater risk of multi-frail and physiological frail correlated with low Tfh1 [0.77(0.60-0.99); 0.87(0.79-0.96)] and Tfh17 cells [0.79(0.65-0.96); 0.86(0.78-0.94)], respectively. Higher B cells were associated with decreased frailty/pre-frailty both in females [0.89(0.81-0.98)] and males [0.82(0.71-0.96)], but did not correlate with frailty subtypes. Regarding inflammatory markers, participants in the TGF-ß 2nd quartile showed a decreased risk of pre-frailty/frailty in females [0.39(0.17-0.89)] and psychological frail [0.37(0.16-0.88)], compared with those in the top tertile. Moreover, we found participants in the 2nd tertile for IL-12 levels showed a decreased risk of physiological frail [0.40 (0.17-0.97)]. Our study highlights the importance of Tfh cell subsets and inflammatory markers in frailty in a sex-specific manner, particularly in terms of frailty subtype.

6.
JAMA ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32031570

RESUMO

Importance: In December 2019, novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited. Objective: To describe the epidemiological and clinical characteristics of NCIP. Design, Setting, and Participants: Retrospective, single-center case series of the 138 consecutive hospitalized patients with confirmed NCIP at Zhongnan Hospital of Wuhan University in Wuhan, China, from January 1 to January 28, 2020; final date of follow-up was February 3, 2020. Exposures: Documented NCIP. Main Outcomes and Measures: Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Outcomes of critically ill patients and noncritically ill patients were compared. Presumed hospital-related transmission was suspected if a cluster of health professionals or hospitalized patients in the same wards became infected and a possible source of infection could be tracked. Results: Of 138 hospitalized patients with NCIP, the median age was 56 years (interquartile range, 42-68; range, 22-92 years) and 75 (54.3%) were men. Hospital-associated transmission was suspected as the presumed mechanism of infection for affected health professionals (40 [29%]) and hospitalized patients (17 [12.3%]). Common symptoms included fever (136 [98.6%]), fatigue (96 [69.6%]), and dry cough (82 [59.4%]). Lymphopenia (lymphocyte count, 0.8 × 109/L [interquartile range {IQR}, 0.6-1.1]) occurred in 97 patients (70.3%), prolonged prothrombin time (13.0 seconds [IQR, 12.3-13.7]) in 80 patients (58%), and elevated lactate dehydrogenase (261 U/L [IQR, 182-403]) in 55 patients (39.9%). Chest computed tomographic scans showed bilateral patchy shadows or ground glass opacity in the lungs of all patients. Most patients received antiviral therapy (oseltamivir, 124 [89.9%]), and many received antibacterial therapy (moxifloxacin, 89 [64.4%]; ceftriaxone, 34 [24.6%]; azithromycin, 25 [18.1%]) and glucocorticoid therapy (62 [44.9%]). Thirty-six patients (26.1%) were transferred to the intensive care unit (ICU) because of complications, including acute respiratory distress syndrome (22 [61.1%]), arrhythmia (16 [44.4%]), and shock (11 [30.6%]). The median time from first symptom to dyspnea was 5.0 days, to hospital admission was 7.0 days, and to ARDS was 8.0 days. Patients treated in the ICU (n = 36), compared with patients not treated in the ICU (n = 102), were older (median age, 66 years vs 51 years), were more likely to have underlying comorbidities (26 [72.2%] vs 38 [37.3%]), and were more likely to have dyspnea (23 [63.9%] vs 20 [19.6%]), and anorexia (24 [66.7%] vs 31 [30.4%]). Of the 36 cases in the ICU, 4 (11.1%) received high-flow oxygen therapy, 15 (41.7%) received noninvasive ventilation, and 17 (47.2%) received invasive ventilation (4 were switched to extracorporeal membrane oxygenation). As of February 3, 47 patients (34.1%) were discharged and 6 died (overall mortality, 4.3%), but the remaining patients are still hospitalized. Among those discharged alive (n = 47), the median hospital stay was 10 days (IQR, 7.0-14.0). Conclusions and Relevance: In this single-center case series of 138 hospitalized patients with confirmed NCIP in Wuhan, China, presumed hospital-related transmission of 2019-nCoV was suspected in 41% of patients, 26% of patients received ICU care, and mortality was 4.3%.

7.
Mil Med Res ; 7(1): 4, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-32029004

RESUMO

In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named "2019 novel coronavirus (2019-nCoV)" by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world's attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Infecção Hospitalar , Controle de Infecções , Programas de Rastreamento , Equipamento de Proteção Individual , Pneumonia Viral , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/isolamento & purificação , Betacoronavirus/patogenicidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Infecções por Coronavirus/transmissão , Infecção Hospitalar/prevenção & controle , Diagnóstico Diferencial , Medicamentos de Ervas Chinesas , Medicina Baseada em Evidências , Hidratação , Humanos , Controle de Infecções/normas , Pulmão/diagnóstico por imagem , Epidemiologia Molecular , Cuidados de Enfermagem , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/etiologia , Pneumonia Viral/terapia , Pneumonia Viral/transmissão
8.
Mol Med Rep ; 21(1): 320-328, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31939614

RESUMO

Cortex Mori Radicis extract (CMR) has various pharmacological properties, such as anti­inflammatory, anti­allergic and anti­hyperglycemic effects. However, the effects and mechanisms of CMR in the neuroregeneration of diabetic peripheral neuropathy (DPN) are unclear. In the present study, the effects of CMR on neurite outgrowth of dorsal root ganglia (DRG) neurons in diabetic rats were investigated and its underlying mechanisms were explored. SD rats were subjected to a high­fat diet with low­dose streptozotocin to induce a Type II diabetes model with peripheral neuropathy. CMR was then applied for four weeks continuously with or without injection of small interfere (si)RNA targeting the transient receptor potential canonical channel 1 (TRPC1) via the tail vein. Blood glucose levels, the number of Nissl bodies, neurite outgrowth and growth cone turning in DRG neurons were evaluated. The expression of TRPC1 protein, Ca2+ influx and activation of the PI3K/AKT signaling pathway were also investigated. The results of the present study showed that CMR significantly lowered blood glucose levels, reversed the loss of Nissl bodies, induced neurite outgrowth and restored the response of the growth cone of DRG neurons in diabetic rats. CMR exerted neurite outgrowth­promoting effects by increasing TRPC1 expression, reducing Ca2+ influx and enhancing AKT phosphorylation. siRNA targeting TRPC1 in the CMR group abrogated its anti­diabetic and neuroregenerative effects, suggesting the involvement of TRPC1 in the biological effects of CMR on DPN.

9.
J Biol Chem ; 295(6): 1575-1586, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31914403

RESUMO

Sterile alpha motif and HD domain-containing protein 1 (SAMHD1) is a deoxynucleoside triphosphohydrolase (dNTPase) with a nuclear localization signal (NLS). SAMHD1 suppresses innate immune responses to viral infection and inflammatory stimuli by inhibiting the NF-κB and type I interferon (IFN-I) pathways. However, whether the dNTPase activity and nuclear localization of SAMHD1 are required for its suppression of innate immunity remains unknown. Here, we report that the dNTPase activity, but not nuclear localization of SAMHD1, is important for its suppression of innate immune responses in differentiated monocytic cells. We generated monocytic U937 cell lines stably expressing WT SAMHD1 or mutated variants defective in dNTPase activity (HD/RN) or nuclear localization (mNLS). WT SAMHD1 in differentiated U937 cells significantly inhibited lipopolysaccharide-induced expression of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) mRNAs, as well as IFN-α, IFN-ß, and TNF-α mRNA levels induced by Sendai virus infection. In contrast, the HD/RN mutant did not exhibit this inhibition in either U937 or THP-1 cells, indicating that the dNTPase activity of SAMHD1 is important for suppressing NF-κB activation. Of note, in lipopolysaccharide-treated or Sendai virus-infected U937 or THP-1 cells, the mNLS variant reduced TNF-α or IFN-ß mRNA expression to a similar extent as did WT SAMHD1, suggesting that SAMHD1-mediated inhibition of innate immune responses is independent of SAMHD1's nuclear localization. Moreover, WT and mutant SAMHD1 similarly interacted with key proteins in NF-κB and IFN-I pathways in cells. This study further defines the role and mechanisms of SAMHD1 in suppressing innate immunity.

10.
Chemosphere ; 246: 125776, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31918093

RESUMO

The impairments of gestational cadmium (Cd) exposure on testicular development and male fertility in offspring have been reported. Here, we investigated the effect of paternal low-concentration cadmium exposure on testicular development and spermatogenesis in offspring. Five-week-old male mice were exposed to cadmium chloride (100 mg/L) in drinking water for 20 weeks. Results presented that Cd did not affect the testicular histology and sperm count in mice. After mating with untreated females, pregnant mice and pups were then evaluated. No significant difference in the rate for successful pregnancy and the body weight of pups was observed in Cd-exposed mice compared to the controls. Male offspring were given with a chow and high-fat diet from postnatal day (PND) 35 to PND70. Our data indicated that high-fat diet obviously decreased No. of sperm in epididymides of adult offspring due to paternal Cd exposure. Testicular histology revealed that the percentage of seminiferous tubules in stages IX-XII and the atypical residual bodies positive tubules in CdH (paternal cadmium exposure and pubertal high-fat diet) group were higher than these in CdC (paternal cadmium exposure and pubertal chow diet) group. Further analysis demonstrated that high-fat diet markedly accelerated testicular apoptosis, as determined by TUNEL assay and immunostaining for cleaved caspase-3, in male offspring due to paternal Cd exposure. Collectively, high-fat diet exacerbates the damage of testicular development and spermatogenesis in offspring due to paternal cadmium exposure.

11.
J Virol ; 94(7)2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-31941773

RESUMO

The cellular protein SERINC5 inhibits the infectivity of diverse retroviruses, and its activity is counteracted by the glycosylated Gag (glycoGag) protein of murine leukemia virus (MLV), the S2 protein of equine infectious anemia virus (EIAV), and the Nef protein of human immunodeficiency virus type 1 (HIV-1). Determining the regions within SERINC5 that provide restrictive activity or Nef sensitivity should inform mechanistic models of the SERINC5/HIV-1 relationship. Here, we report that deletion of the conserved sequence EDTEE, which is located within a cytoplasmic loop of SERINC5 and which is reminiscent of an acidic-cluster membrane trafficking signal, increases the sensitivity of SERINC5 to antagonism by Nef, while it has no effect on the intrinsic activity of the protein as an inhibitor of infectivity. These effects correlated with enhanced removal of the ΔEDTEE mutant relative to that of wild-type SERINC5 from the cell surface and with enhanced exclusion of the mutant protein from virions by Nef. Mutational analysis indicated that the acidic residues, but not the threonine, within the EDTEE motif are important for the relative resistance to Nef. Deletion of the EDTEE sequence did not increase the sensitivity of SERINC5 to antagonism by the glycoGag protein of MLV, suggesting that its virologic role is Nef specific. These results are consistent with the reported mapping of the cytoplasmic loop that contains the EDTEE sequence as a general determinant of Nef responsiveness, but they further indicate that sequences inhibitory to as well as supportive of Nef activity reside in this region. We speculate that the EDTEE motif might have evolved to mediate resistance against retroviruses that use Nef-like proteins to antagonize SERINC5.IMPORTANCE Cellular membrane proteins in the SERINC family, especially SERINC5, inhibit the infectivity of retroviral virions. This inhibition is counteracted by retroviral proteins, specifically, HIV-1 Nef, MLV glycoGag, and EIAV S2. One consequence of such a host-pathogen "arms race" is a compensatory change in the host antiviral protein as it evolves to escape the effects of viral antagonists. This is often reflected in a genetic signature, positive selection, which is conspicuously missing in SERINC5 Here we show that despite this lack of genetic evidence, a sequence in SERINC5 nonetheless provides relative resistance to antagonism by HIV-1 Nef.

12.
Elife ; 92020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31958059

RESUMO

Typhoid toxin is a virulence factor for the bacterial pathogen Salmonella Typhi, which causes typhoid fever in humans. After its synthesis by intracellular bacteria, typhoid toxin is secreted into the lumen of the Salmonella-containing vacuole by a secretion mechanism strictly dependent on TtsA, a specific muramidase that facilitates toxin transport through the peptidoglycan layer. Here we show that substrate recognition by TtsA depends on a discrete domain within its carboxy terminus, which targets the enzyme to the bacterial poles to recognize YcbB-edited peptidoglycan. Comparison of the atomic structures of TtsA bound to its substrate and that of a close homolog with different specificity identified specific determinants involved in substrate recognition. Combined with structure-guided mutagenesis and in vitro and in vivo crosslinking experiments, this study provides an unprecedented view of the mechanisms by which a muramidase recognizes its peptidoglycan substrate to facilitate protein secretion.

13.
Planta Med ; 86(3): 205-211, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31918446

RESUMO

Three phenylpropanoid glucosides (1:  - 3: ) and one iridoid glucoside (11: ), together with eleven known glucosides, were isolated from the ethanol extract of the whole plant of Hemiphragma heterophyllum. Their structures were elucidated by means of 1D and 2D NMR spectroscopy, HRMS, and chemical methods. All compounds except 11: and 13:  - 15: showed varying degrees of α-glucosidase inhibitory activity. Compounds 5, 9: , and 12: were marginally active in the bioassay, while compounds 1:  - 4: , 6:  - 8: , and 10: exhibited appreciable inhibitory activity with an IC50 value of 33.6 ~ 83.1 µM, which was much lower than that of the positive control acarbose (IC50 = 310.8 µM).


Assuntos
Glucosídeos Iridoides , alfa-Glucosidases , Glucosídeos , Inibidores de Glicosídeo Hidrolases , Iridoides , Estrutura Molecular , Extratos Vegetais
14.
Proc Natl Acad Sci U S A ; 117(3): 1648-1657, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31919279

RESUMO

Programmed death-1 homolog (PD-1H), a CD28/B7 family molecule, coinhibits T cell activation and is an attractive immunotherapeutic target for cancer and inflammatory diseases. The molecular basis of its function, however, is unknown. Bioinformatic analyses indicated that PD-1H has a very long Ig variable region (IgV)-like domain and extraordinarily high histidine content, suggesting that unique structural features may contribute to coinhibitory mechanisms. Here we present the 1.9-Å crystal structure of the human PD-1H extracellular domain. It reveals an elongated CC' loop and a striking concentration of histidine residues, located in the complementarity-determining region-like proximal half of the molecule. We show that surface-exposed histidine clusters are essential for robust inhibition of T cell activation. PD-1H exhibits a noncanonical IgV-like topology including an extra "H" ß-strand and "clamping" disulfide, absent in known IgV-like structures, that likely restricts its orientation on the cell surface differently from other IgV-like domains. These results provide important insight into a molecular basis of T cell coinhibition by PD-1H.

15.
J Clin Nurs ; 29(3-4): 535-544, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31737968

RESUMO

AIMS AND OBJECTIVES: To explore the regulation role of work resources in male nurses' job burnout and job demands. BACKGROUND: Burnout syndrome affects a wide range of nurses. Although burnout and turnover rate have drawn many researchers' attention, little is known of work characteristics that may cause a high burnout and turnover rate in male nurses. DESIGN: A survey design was used. METHOD: A total of 366 male nurses in Guangzhou hospitals were included in this survey using the Burnout Scale (MBI-GS) and the Job demands Resources Scale. Data were processed by hierarchical regression analysis. (Followed the STROBE checklist) RESULTS: The male nurse's MBI score was (2.72 ± 1.02). Job demands affected the severity of male nurses' job burnout. Work resources are in a low level, especially at the social support, reward and skill diversity. The regression coefficients ß of job demands, work resources and interaction items of job demands and work resources were 0.277, 0.314 and -0.006, respectively, and both passed the significance test (p < .01).). The new explanatory quantity ΔR2 after introducing the interaction between job demands and working resources was also statistically significant (ΔR2  = 0.254, p < .01). CONCLUSION: Male nurses are at a mild level of job burnout, and work resources are in shortage. Work resources play a regulating role in job demands and burnout. RELEVANCE TO CLINICAL PRACTICE: The mild burnout may be a surface phenomenon or was a sign of trend of male nurses' intention to leave the job. Managers should pay attention to the emotional needs and mental health problems of male nurses' work environment.

16.
Phys Chem Chem Phys ; 22(2): 422-429, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31793961

RESUMO

The use of the molecular spin state as a quantum of next-generation information technology is receiving impressive research attention, within which the fundamental issues include manipulating the phase transition between the spin-up and -down states and generating spin polarized current. The spinterface between ferromagnetic electrodes and a molecular bridge represents one of the most intriguing elements in this context. Herein, by means of the celebrated numerical renormalization group technique, we present an original way to realize spin reversal in a monomeric dimer. Our scheme is based on the exchange interactions between electronic spins on one monomer and those on the other one or on the electrodes, which could be easily controlled through purely electronic technology. Through a careful engineering of the interfacial parameters, one of the monomers is devoted to the spin reversing, whereas the other one contributes to the spin selecting. The charge numbers of spin-up and -down electrons swap their respective occupancies at some particular points, indicating charge sensing between different spins. The competition between the spinterface and the molecular energy level results in charge oscillating in a single spin channel, which is unfavorable to the spin selecting. The observation may provide a prospective example for a multifunctional magnetoelectronics molecular device, which works without any external magnetic field.

17.
J Viral Hepat ; 27(2): 127-134, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31571343

RESUMO

The aim of this retrospective study was to observe hepatitis B surface antigen (HBsAg) seroclearance and explore predictors of HBsAg loss in HIV/HBV-co-infected patients receiving long-term lamivudine or both tenofovir and lamivudine containing therapies. Quantification of HBsAg, hepatitis B e antigen and HBV DNA before and after initiation of HBV-active antiretroviral therapy in a total of 268 HIV/HBV-co-infected patients started treatment between 2005 and 2017 were performed. Over a median of 65.63 months of follow-up, 10 (3.7%) were observed HBsAg loss and the quantification of HBsAg in 7 (2.6%) patients were less than 50 IU/mL. With the prolongation of antiretroviral therapy duration time, the rates of HBsAg seroclearance tended to increase gradually, rising from 1.8% (3/163) during 2-4 years treatment to 29.4% (10/34) after antiretroviral therapy for up to 10 years. Lower baseline qHBsAg and HBV DNA levels and strong 12-month declines in qHBsAg were significantly associated with HBsAg seroclearance. The event of HBsAg seroclearance is uncommon among Chinese individuals with HIV/HBV co-infection who have been treated with anti-HBV containing antiretroviral therapy, and lifelong therapy for HBV is needed for HIV/HBV co-infected patients. Baseline qHBsAg and HBV DNA levels and qHBsAg decline rate were predictors for HBsAg seroclearance.

18.
Ecotoxicol Environ Saf ; 187: 109879, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31677567

RESUMO

Cadmium (Cd) is a major environmental pollutant. Maternal Cd exposure throughout pregnancy caused fetal growth restriction (FGR). However, the pivotal time window of Cd-evoked FGR and its mechanism are unknown. Here, we will establish a murine model to explore the effects of maternal Cd exposure at different stages of gestation on fetal growth and placental progesterone biosynthesis. Pregnant mice were randomly divided into four groups. For Cd groups, mice were given with CdCl2 (150 mg/L) through drinking water at early (GD0-GD6), middle (GD7-GD12) and late (GD13-GD17) gestation, respectively. The controls received reverses osmosis (RO) water. Results showed that maternal cadmium exposure only in late gestation lowered fetal weight and length. Correspondingly, placental Cd level in late gestational Cd exposure is the highest among three different gestational stages. Although gestational Cd exposure had few adverse effects in the weight and diameter of mouse placenta, placental vascular development, as determined by H&E staining and cluster of differentiation-34 (CD-34) immunostaining, was impaired in mice exposed to Cd during late pregnancy. Additionally, late gestational exposure to cadmium markedly reduced progesterone level in maternal serum and placenta. In line, the expression of key progesterone synthetases, including steroidogenic acute regulatory protein (StAR) and 3ß-hydroxyl steroid dehydrogenase (3ß-HSD), was obviously downregulated in placenta from mice was exposed Cd during late pregnancy. These data suggest that maternal Cd exposure during late pregnancy, but not early and middle pregnancy, induces fetal growth restriction partially via inhibiting placental progesterone synthesis.


Assuntos
Cádmio/toxicidade , Poluentes Ambientais/toxicidade , Retardo do Crescimento Fetal/induzido quimicamente , Exposição Materna/efeitos adversos , Placenta/efeitos dos fármacos , Progesterona/biossíntese , Animais , Cádmio/sangue , Regulação para Baixo , Poluentes Ambientais/sangue , Feminino , Idade Gestacional , Humanos , Camundongos , Placenta/metabolismo , Gravidez , Resultado da Gravidez , Progesterona/antagonistas & inibidores , Distribuição Aleatória
19.
Nat Struct Mol Biol ; 26(12): 1176-1183, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31792451

RESUMO

HIV-1 virion infectivity factor (Vif) promotes degradation of the antiviral APOBEC3 (A3) proteins through the host ubiquitin-proteasome pathway to enable viral immune evasion. Disrupting Vif-A3 interactions to reinstate the A3-catalyzed suppression of human immunodeficiency virus type 1 (HIV-1) replication is a potential approach for antiviral therapeutics. However, the molecular mechanisms by which Vif recognizes A3 proteins remain elusive. Here we report a cryo-EM structure of the Vif-targeted C-terminal domain of human A3F in complex with HIV-1 Vif and the cellular cofactor core-binding factor beta (CBFß) at 3.9-Å resolution. The structure shows that Vif and CBFß form a platform to recruit A3F, revealing a direct A3F-recruiting role of CBFß beyond Vif stabilization, and captures multiple independent A3F-Vif interfaces. Together with our biochemical and cellular studies, our structural findings establish the molecular determinants that are critical for Vif-mediated neutralization of A3F and provide a comprehensive framework of how HIV-1 Vif hijacks the host protein degradation machinery to counteract viral restriction by A3F.


Assuntos
Citosina Desaminase/química , HIV-1/química , Produtos do Gene vif do Vírus da Imunodeficiência Humana/química , Subunidade beta de Fator de Ligação ao Core/química , Microscopia Crioeletrônica , Citosina Desaminase/antagonistas & inibidores , Citosina Desaminase/ultraestrutura , Humanos , Evasão da Resposta Imune , Modelos Moleculares , Conformação Proteica , Domínios Proteicos , Mapeamento de Interação de Proteínas , Proteólise , Relação Estrutura-Atividade , Produtos do Gene vif do Vírus da Imunodeficiência Humana/farmacologia , Produtos do Gene vif do Vírus da Imunodeficiência Humana/ultraestrutura
20.
Sci Rep ; 9(1): 18829, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31827152

RESUMO

Functional exhaustion of immune cells is a defining characteristic of HIV-1 chronic infections, exhibiting dysregulation of cellular immune responses and expression of co-inhibitory receptors. Although the molecular mechanisms controlling immune-cell exhaustion retains largely unknown, immune checkpoint blockade strategy has shown inspiring potential to reinvigorate T cell functions in chronic infections. In this study, we investigated peripheral blood mononuclear cells (PBMCs) exhaustion markers from 109 chronic HIV-1-infected patients and found they correlated positively with microRNA-146a, which was inversely correlated with CD4+ T cell count. Intriguingly, ex vivo neutralization of miR-146a in PBMCs from chronic HIV-1 infection exhibited an elevated antiviral cytokines production as well as the expression of GZMB and perforin, while simultaneously, decreased the inhibitory receptors expression such as PD-1, CTLA-4, TIM-3 and LAG-3. These results highlight the importance of miR-146a to HIV-1 induced immune cell exhaustion, and uncover a novel layer of HIV/AIDS pathogenesis and provide potential targets for improved immune intervention.

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