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1.
Mol Immunol ; 134: 183-191, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33812250

RESUMO

Interferon regulatory factor 7 (IRF7) is a crucial regulator of type I interferons (IFNs) against pathogen infections and plays a significant role in the endosomal Toll-like receptor signaling (namely, TLR7 and TLR9) in plasmacytoid dendritic cells (pDCs). In this study, we identify MEKK3, one of the MAP3K kinase, as a potent stimulator of IRF7 upon cellular activation of the TLR7/9 signaling pathways to induce various type I IFNs. The knockdown of MEKK3 in vivo substantially impairs type I IFN induction and increases susceptibility to HSV-1 infection in mice. Overexpression of MEKK3 significantly activates IRF7 to trigger strong induction of type I IFNs, while cells deficient in MEKK3 expression show abrogated innate immune responses to TLR7/TLR9 ligands stimulation. We confirmed that the IFNs' induction is due to a MEKK3 and IRF7 interaction; it leads to the phosphorylation of IRF7 at multiple sites. Moreover, endogenous MEKK3 can bind and phosphorylate IRF7 after TLR9 activation by its specific ligand CpG DNA. It is the first time to report the role of MEKK3 on type I IFN, which indicates crosstalk between MAP3K activation and type I IFNs' induction in the endosomal Toll-like receptor pathways.

2.
Phytopathology ; 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33822646

RESUMO

Ralstonia solanacearum species complex (RSSC) contains a group of destructive plant pathogenic bacteria, causing bacterial wilt of over 200 species of crops and trees, such as Casuarina equisetifolia, worldwide. RSSC can survive in the soil environment for a long time and start infection after activated by host plants. This study conducted a transcriptome analysis on the expression pattern of the pathogenicity-related genes of a new isolated RSSC strain YQ (Ralstonia pseduosolanacearum phylotype I-16) in response to C. equisetifolia cladophyll (a branch of a stem that resembles and functions as a leaf) and root debris under in vitro culture. The cladophyll debris induced more genes upregulated than the root debris, including pathogenicity-related genes involved in motility, effectors, type III secretion systems, quorum sensing, and plant cell wall degradation. Besides, many differentially expressed genes were related to transcriptional regulator such as cyclic dimeric guanosine monophosphate. Moreover, the cultures with cladophyll debris induced a faster wilting in bioassays, and the cell swimming was enhanced by cladophyll exudate. C. equisetifolia cladophylls could activate the expression of pathogenicity-related genes of strain YQ and accelerate infection. Our findings suggest that litterfall management in C. equisetifolia forests, or even other plantations, should receive attention to prevent the induction of bacterial wilt disease caused by RSSC.

4.
Dev Cell ; 56(7): 1030-1042.e6, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33756107

RESUMO

Invasive or penetrative growth is critical for developmental and reproductive processes (e.g., pollen tube penetration of pistils) and disease progression (e.g., cancer metastasis and fungal hyphae invasion). The invading or penetrating cells experience drastic changes in mechanical pressure from the surroundings and must balance growth with cell integrity. Here, we show that Arabidopsis pollen tubes sense and/or respond to mechanical changes via a cell-surface receptor kinase Buddha's Paper Seal 1 (BUPS1) while emerging from compressing female tissues. BUPS1-defective pollen tubes fail to maintain cell integrity after emergence from these tissues. The mechano-transduction function of BUPS1 is established by using a microfluidic channel device mimicking the mechanical features of the in vivo growth path. BUPS1-based mechano-transduction activates Rho-like GTPase from Plant 1 (ROP1) GTPase to promote exocytosis that facilitates secretion of BUPS1's ligands for mechanical signal amplification and cell wall rigidification in pollen tubes. These findings uncover a membrane receptor-based mechano-transduction system for cells to cope with the physical challenges during invasive or penetrative growth.

5.
Eur J Radiol ; 138: 109623, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33711573

RESUMO

PURPOSE: To determine the risk factors and patterns of recurrence after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) meeting the up-to-seven criteria and to develop a nomogram to predict the recurrence free survival (RFS). MATERIALS AND METHODS: This retrospective study included 481 HCC patients meeting the up-to-seven criteria and who received RFA as the primary therapy at three Chinese hospitals from January 2013 to December 2016. All clinical variables were assessed by univariate and multivariate Cox regression analyses and a nomogram was constructed to predict the probability of RFS. RESULTS: The recurrence rate was 50.7 % (244/481). Age > 60 years, male gender, and multiple tumors were independent risk factors of recurrence. The incidence of early and late recurrence was 68.03 % (n = 166) and 31.97 % (n = 78), respectively. Seven patterns of spatial recurrence were identified: local tumor progression (LTP) alone (n = 18, 7.38 %), intrahepatic distant recurrence (IDR) alone (n = 136, 55.74 %), extrahepatic recurrence (ER) alone (n = 21, 8.61 %), IDR + ER (n = 45, 18.44 %), LTP + IDR (n = 16, 6.56 %), LTP + ER (n = 4, 1.64 %) and LTP + IDR + ER (n = 4, 1.64 %). The 1-, 2-, and 3-year RFS rates were 79.63 %, 65.23 %, and 51.03 %, respectively. A well-discriminated and calibrated nomogram was constructed. CONCLUSIONS: The factors affecting recurrence after RFA were age, gender, and the number of tumors. IDR was the most common type of recurrence after complete ablation.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33715114

RESUMO

Atrazine (ATZ), as a widely used triazine herbicide, is an environmental endocrine disruptor (EDC) that can cause many health problems. Therefore, we conducted this study based on the evidence of rats and mice to figure out the characteristics of ATZ damage to the reproductive system and further evaluate its health effects on the human. PRISMA's guidelines were followed according to the principles recommended by the Cochrane Handbook for Systematic Review. Health assessment was performed using the OHAT approach. Our new data were obtained from randomized controlled trials in rats designed in accordance with toxicological guidelines. Exposure to ATZ was significantly associated with decreased testosterone production (SMD = - 0.90, 95% CI - 1.27 to - 0.53), and reduced absolute weights of testis (SMD = - 0.41, 95% CI - 0.61 to - 0.22) and other reproductive organs. The damaging effect of sperm quality was also observed clearly, which included reduction of sperm count both in epididymis (SMD = - 2.32, 95% CI - 2.83 to - 1.81) and testis (SMD = - 1.01, 95% CI - 1.37 to - 0.64), decrease in sperm motility (SMD = - 8.86, 95% CI - 10.88 to - 6.83), and increase in sperm abnormality. Subgroup analysis revealed consistency across different species, life stage, and dosage. In addition, we found that ATZ exposure at a daily dose of 120 mg/kg during adolescence could cause decrease in weight gain and histological damage to the testis. The gene expression levels of Nrf2/HO-1 and Bcl-2/caspase signaling pathways in testis tissues were changed significantly. The results of this SR indicated that exposure to ATZ was associated with impairment of male reproductive system in rodents regardless of species, exposure life stage, and dosage. It is believed that ATZ exposure may have similar effects on male reproductive system of human beings. Pathways related to oxidative stress and apoptosis may be the mechanism leading to testicular damage in rats treated with ATZ.

7.
Biosci Rep ; 41(3)2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33704390

RESUMO

BACKGROUND: Little research has been done on clinicopathological characteristics and human papillomavirus (HPV) status of anogenital and oropharyngeal squamous cell carcinomas (SCC) with a strong expression of programmed death ligand 1 (PD-L1) in tumor cells. Therefore, we conducted this meta-analysis. METHODS: We performed a comprehensive research in PubMed, Embase and Cochrane databases up to 30 September 2020. The effect size was hazard ratio (HR) with 95% confidence interval (CI) for overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS). The pooled odds ratio (OR) with 95% CI were used to assess the association between PD-L1 expression and clinicopathological features along with HPV status. RESULTS: A total of 2003 cases (944 anogenital and 1059 oropharynx SCC patients) were included. High PD-L1 expression in anogenital SCC cases were associated with advanced age (OR = 1.63, 95% CI: 1.04-2.58) and HPV negativity (OR = 0.47, 95% CI: 0.31-0.71). Besides, PD-L1 positive anogenital SCC cases held a significantly declined OS (HR = 2.18, 95% CI: 1.37-3.47) and CSS (HR = 2.45, 95% CI: 1.30-4.65). For oropharynx SCC, PD-L1 was more frequent in younger and HPV positive patients (OR = 0.60, 95% CI: 0.37-0.98; OR = 3.01, 95% CI: 1.78-5.09) and PD-L1 expression was relevant to better OS and DFS (HR = 0.76, 95% CI: 0.60-0.97; HR = 0.50, 95% CI: 0.33-0.75). CONCLUSIONS: The meta-analysis demonstrated that in anogenital SCC, PD-L1 positivity had to do with a worse outcome, which might attribute to advanced age, higher tumor grade, lymph node metastasis and HPV negativity, while in oropharynx cancer, PD-L1 expression was related to better prognosis for the reason that PD-L1 was less frequent in the aged and negative HPV status.

8.
Clin Epigenetics ; 13(1): 55, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33726838

RESUMO

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality among US adults. African Americans have higher burden of CVD morbidity and mortality compared to any other racial group. Identifying biomarkers for clinical risk prediction of CVD offers an opportunity for precision prevention and earlier intervention. RESULTS: Using linear mixed models, we investigated the cross-sectional association between four measures of epigenetic age acceleration (intrinsic (IEAA), extrinsic (EEAA), PhenoAge (PhenoAA), and GrimAge (GrimAA)) and ten cardiometabolic markers of hypertension, insulin resistance, and dyslipidemia in 1,100 primarily hypertensive African Americans from sibships in the Genetic Epidemiology Network of Arteriopathy (GENOA). We then assessed the association between epigenetic age acceleration and time to self-reported incident CVD using frailty hazard models and investigated CVD risk prediction improvement compared to models with clinical risk scores (Framingham risk score (FRS) and the atherosclerotic cardiovascular disease (ASCVD) risk equation). After adjusting for sex and chronological age, increased epigenetic age acceleration was associated with higher systolic blood pressure (IEAA), higher pulse pressure (EEAA and GrimAA), higher fasting glucose (PhenoAA and GrimAA), higher fasting insulin (EEAA), lower low density cholesterol (GrimAA), and higher triglycerides (GrimAA). A five-year increase in GrimAA was associated with CVD incidence with a hazard ratio of 1.54 (95% CI 1.22-2.01) and remained significant after adjusting for CVD risk factors. The addition of GrimAA to risk score models improved model fit using likelihood ratio tests (P = 0.013 for FRS and P = 0.008 for ASCVD), but did not improve C statistics (P > 0.05). Net reclassification index (NRI) showed small but significant improvement in reassignment of risk categories with the addition of GrimAA to FRS (NRI: 0.055, 95% CI 0.040-0.071) and the ASCVD equation (NRI: 0.029, 95% CI 0.006-0.064). CONCLUSIONS: Epigenetic age acceleration measures are associated with traditional CVD risk factors in an African-American cohort with a high prevalence of hypertension. GrimAA was associated with CVD incidence and slightly improved prediction of CVD events over clinical risk scores.

9.
Reprod Toxicol ; 101: 124-136, 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33757772

RESUMO

The effect of post-adolescence bisphenol A (BPA) exposure on the reproductive system is not well-defined. We therefore performed this meta-analysis to elucidate the associations between post-adolescence BPA exposure and reproductive-related outcomes. A search was performed on the PubMed, EMBASE, and Web of science databases to identify relevant literature. The standardized mean differences (SMDs) and the 95 % confidence intervals (CIs) were measured by fixed-effects or random-effects models. Publication bias was assessed using funnel plots and Egger's regression test. A total of 40 studies were included in the final analysis. The results showed that post-adolescence BPA exposure was negatively associated with reproductive-related organ weighty (Testis weight: SMD: -0.61; 95 % Cl: -0.85, -0.36; epididymis weight; SMD: -0.43; 95 % Cl: -0.69, -0.17; seminal vesicles weight; SMD: -0.77; 95 % Cl: -1.05, -0.49) and sperm parameters (Sperm motility: SMD: -1.44; 95 % Cl: -1.95, -0.93; epididymal sperm concentration: SMD: -2.26; 95 % Cl: -2.79, -1.72; and abnormal sperm morphology: SMD: 2.41; 95 % Cl: 1.41, 2.86). Moreover, BPA exposure decreased the level of testosterone (T) and superoxide dismutase (SOD), but increased the ratio of serum estradiol (E2) to T. This systematic review demonstrates that post-adolescence exposure to BPA may adversely affect reproductive functions in male rodents.

10.
Bull Entomol Res ; : 1-12, 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33691812

RESUMO

Crematogaster rogenhoferi (Hymenoptera: Formicidae), an omnivorous ant, is one of the dominant predatory natural enemies of a soft scale pest, Parasaissetia nigra Nietner (Homoptera: Coccidae), and can effectively control P. nigra populations in rubber forests. Olfaction plays a vital role in the process of predation. However, the information about the molecular mechanism of olfaction-evoked behaviour in C. rogenhoferi is limited. In this study, we conducted antennal transcriptome analysis to identify candidate olfactory genes. We obtained 53,892 unigenes, 16,185 of which were annotated. Based on annotations, we identified 49 unigenes related to chemoreception, including four odourant-binding proteins, three chemosensory proteins, 37 odourant receptors, two odourant ionotropic receptors and three sensory neuron membrane proteins. This is the first report on the molecular basis of the chemosensory system of C. rogenhoferi. The findings provide a basis for elucidating the molecular mechanisms of the olfactory-related behaviours of C. rogenhoferi, which would facilitate a better application of C. rogenhoferi as a biological control agent.

12.
J Nurs Manag ; 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33706409

RESUMO

AIM: To test the influence of humble leadership, job embeddedness, and affective commitment on the voice behavior of nurses. BACKGROUND: A nurse's voice behavior is regarded as an important measure to identify and solve problems in medical institutions, and improve patients satisfaction. It is urgent to pay sufficient attention to nurses' advice to determine which factors can stimulate enthusiasm in this area. METHODS: This study is a cross-sectional study involving 598 nurses. RESULTS: The results showed that humble leadership, job embeddedness, affective commitment, and voice behavior were significantly positively correlated. Job embeddedness played a partial mediating role in humble leadership and affective commitment; meanwhile, affective commitment also partially mediated the influence of job embeddedness on voice behavior. CONCLUSIONS: Humble leadership was the key to improve the voice behavior of nurses; as a mediating mechanism, job embeddedness and affective commitment further explained how humble leadership promoted the voice behavior of nurses. IMPLICATIONS FOR NURSING MANAGEMENT: The effects of humble leadership, job embeddedness, and affective commitment to voice behavior could be used to guide the management of clinical nurses. In particular, the humble leadership style perceived by nurses and the enhanced emotional connection with the organization would contribute to the generation of voice behavior.

13.
Int J Hyperthermia ; 38(1): 437-446, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33724137

RESUMO

OBJECTIVE: To define an optimal cutoff time to distinguish early and late recurrence in hepatocellular carcinoma (HCC) patients after radiofrequency ablation (RFA), and to determine the risk factors and patterns of early recurrence. MATERIALS AND METHODS: This retrospective study included HCC patients who developed recurrence after RFA as the primary therapy at three Chinese hospitals from January 2011 to December 2016. The best cutoff time to define early and late recurrence was determined based on differences in post recurrence survival (PRS). The clinical variables were assessed by univariate and multivariate logistic regression analyses. RESULTS: A total of 279 eligible patients were included. The optimal cutoff time interval after RFA to differentiate early and late recurrence was identified as 12 months (p = 0.029). The independent risk factors of early recurrence were multiple tumors, alpha fetoprotein (AFP) levels, gamma-glutamyl transferase (γ-GT), and serum albumin (ALB) levels. A well-discriminated nomogram was constructed to predict risk of early recurrence. The incidence of intrahepatic distant recurrence (IDR) alone and IDR + extrahepatic recurrence (ER) in early recurrence group was significantly higher than those in late recurrence group (80.73% vs. 66.47%, p = 0.009). CONCLUSION: Twelve months was determined as the optimal cutoff time for differentiating early and late recurrence after RFA for HCC patients. The factors affecting early recurrence after RFA were multiple tumors, AFP levels, ALB level, and γ-GT level. Patients in early recurrence cohort were more likely to develop IDR alone or IDR + ER.

14.
Mol Cancer ; 20(1): 45, 2021 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-33658012

RESUMO

BACKGROUND: The tumor suppressor FBW7 is the substrate recognition component of the SCF E3-ubiquitin ligase complex that mediates proteolytic degradation of various oncogenic proteins. However, the role of FBW7 in ovarian cancer progression remains inadequately understood. METHODS: IP-MASS, co-IP, immunohistochemistry, and western blotting were used to identify the potential substrate of FBW7 in ovarian cancer. The biological effects of FBW7 were investigated using in vitro and in vivo models. LC/MS was used to detect the m6A levels in ovarian cancer tissues. MeRIP-Seq and RNA-Seq were used to assess the downstream targets of YTHDF2. RESULTS: We unveil that FBW7 is markedly down-regulated in ovarian cancer tissues and its high expression is associated with favorable prognosis and elevated m6A modification levels. Consistently, ectopic FBW7 inhibits ovarian cancer cell survival and proliferation in vitro and in vivo, while ablation of FBW7 empowers propagation of ovarian cancer cells. In addition, the m6A reader protein, YTHDF2, is identified as a novel substrate for FBW7. FBW7 counteracts the tumor-promoting effect of YTHDF2 by inducing proteasomal degradation of the latter in ovarian cancer. Furthermore, YTHDF2 globally regulates the turnover of m6A-modified mRNAs, including the pro-apoptotic gene BMF. CONCLUSIONS: Our study has demonstrated that FBW7 suppresses tumor growth and progression via antagonizing YTHDF2-mediated BMF mRNA decay in ovarian cancer.

15.
J Virol ; 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33658348

RESUMO

Glycoprotein B (gB) is an essential fusion protein for the Epstein-Barr virus (EBV) infection of both B cells and epithelial cells and is thus a promising target antigen for a prophylactic vaccine to prevent or reduce EBV-associated disease. T cell responses play key roles in the control of persistent EBV infection and in the efficacy of a vaccine. However, to date, T cell responses to gB have been characterized for only a limited number of human leukocyte antigen (HLA) alleles. Here, we screened gB T cell epitopes in 23 healthy EBV carriers and ten patients with nasopharyngeal cancer (NPC) using a peptide library spanning the entire gB sequence. We identified twelve novel epitopes in the context of seven new HLA restrictions that are common in Asian populations. Two epitopes, gB214-223 and gB840-849, restricted by HLA-B*58:01 and B*38:02, respectively, elicited specific CD8+ T cell responses to inhibit EBV-driven B cell transformation. Interestingly, gB-specific CD8+ T cells were more frequent in healthy viral carriers with EBV reactivation than in those without EBV reactivation, indicating that EBV reactivation in vivo stimulates both humoral (VCA-gp125-IgA) and cellular responses to gB. We further found that most gB epitopes are conserved among different EBV strains. Our study broadens the diversity and HLA restrictions of gB epitopes and suggests that gB is a common target of T cell responses in healthy viral carriers with EBV reactivation. In particular, the precisely mapped and conserved gB epitopes provide valuable information for prophylactic vaccine development.ImportanceT cells are crucial for the control of persistent EBV infection and the development of EBV-associated diseases. The EBV gB protein is essential for virus entry into B cells and epithelial cells and is thus a target antigen for vaccine development. Understanding T cell responses to gB is important for subunit vaccine design. Herein, we comprehensively characterized T cell responses to full-length gB. Our results expand the available gB epitopes and HLA restrictions, particularly those common in Asian populations. Furthermore, we showed that gB-specific CD8+ T cells inhibit B cell transformation ex vivo and that gB-specific CD8+ T cell responses in vivo may be associated with intermittent EBV reactivation in asymptomatic viral carriers. These gB epitopes are highly conserved among geographically separated EBV strains. Precisely mapped and conserved T cell epitopes may contribute to immune monitoring and to the development of a gB subunit vaccine.

16.
J Cell Mol Med ; 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33759345

RESUMO

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic worldwide. Long non-coding RNAs (lncRNAs) are a subclass of endogenous, non-protein-coding RNA, which lacks an open reading frame and is more than 200 nucleotides in length. However, the functions for lncRNAs in COVID-19 have not been unravelled. The present study aimed at identifying the related lncRNAs based on RNA sequencing of peripheral blood mononuclear cells from patients with SARS-CoV-2 infection as well as health individuals. Overall, 17 severe, 12 non-severe patients and 10 healthy controls were enrolled in this study. Firstly, we reported some altered lncRNAs between severe, non-severe COVID-19 patients and healthy controls. Next, we developed a 7-lncRNA panel with a good differential ability between severe and non-severe COVID-19 patients using least absolute shrinkage and selection operator regression. Finally, we observed that COVID-19 is a heterogeneous disease among which severe COVID-19 patients have two subtypes with similar risk score and immune score based on lncRNA panel using iCluster algorithm. As the roles of lncRNAs in COVID-19 have not yet been fully identified and understood, our analysis should provide valuable resource and information for the future studies.

17.
BMC Anesthesiol ; 21(1): 86, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33740886

RESUMO

BACKGROUND: To investigate the optimal target e of lactate kinetics at different time during the resuscitation, the factors that influence whether the kinetics achieve the goals, and the clinical implications of different clinical phenotypes. METHODS: Patients with hyperlactatemia between May 1, 2013 and December 31, 2018 were retrospectively analyzed. Demographic data, basic organ function, hemodynamic parameters at ICU admission (T0) and at 6 h, 12 h, 24 h, 48 h, and 72 h, arterial blood lactate and blood glucose levels, cumulative clinical treatment conditions at different time points and final patient outcomes were collected. RESULTS: A total of 3298 patients were enrolled, and the mortality rate was 12.2%. The cutoff values of lactate kinetics for prognosis at 6 h, 12 h, 24 h, 48 h, and 72 h were 21%, 40%, 57%, 66%, and 72%. The APACHE II score, SOFA score, heart rate (HR), and blood glucose were risk factors that correlated with whether the lactate kinetics attained the target goal. Based on the pattens of the lactate kinetics, eight clinical phenotypes were proposed. The odds ratios of death for clinical phenotypes VIII, IV, and II were 4.39, 4.2, and 5.27-fold of those of clinical phenotype I, respectively. CONCLUSION: Stepwise recovery of lactate kinetics is an important resuscitation target for patients with hyperlactatemia. The APACHE II score, SOFA score, HR, and blood glucose were independent risk factors that influenced achievement of lactate kinetic targets. The cinical phenotypes of stepwise lactate kinetics are closely related to the prognosis.

18.
Eur J Med Res ; 26(1): 27, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33741043

RESUMO

BACKGROUND: Compliance with the surviving sepsis campaign (SSC) guidelines (Cssc) is a key factor affecting the effects of sepsis treatment. We designed this study to investigate the relationships of the structure indicators of ICU on 3 and 6-h Cssc in China. METHODS: A total of 1854 hospitals were enrolled in a survey, led by the China National Critical Care Quality Control Center (China-NCCQC) from January 1, 2018, through December 31, 2018. We investigated the 1854 hospitals' 3 and 6-h Cssc, including compliance with each specific measure of the 3-h and 6-h SSC bundles. We also investigated the actual level of the structure indicators of ICU, released by China-NCCQC in 2015.The outcomes were in adherence with the SSC guidelines (2016). Monitoring indicators included 3 and 6-h Cssc. RESULTS: In the subgroup, the rate of broad-spectrum antibiotic therapy was the highest, and the rate of CVP and ScvO2 measurement was the lowest among the items of 3 and 6-h Cssc. Structure indicators related to 3 and 6-h Cssc include the predicted mortality rate and the standardized mortality ratio (SMR). The relationships between 3 and 6-h Cssc and the proportion of ICU in total inpatient bed occupancy, the proportion of acute physiology and chronic health evaluation (APACHE) II score ≥ 15 in all ICU patients were uncertain. There was no relationship of 3 and 6-h Cssc with the proportion of ICU patients among total inpatients. CONCLUSIONS: Structure indicators influencing 3 and 6-h Cssc in China are the predicted mortality rate and the standardized mortality rate.

19.
Cell Death Dis ; 12(2): 204, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33627621

RESUMO

Apoptosis related protein in TGF-ß signaling pathway (ARTS) was originally discovered in cells undergoing apoptosis in response to TGF-ß, but ARTS also acts downstream of many other apoptotic stimuli. ARTS induces apoptosis by antagonizing the anti-apoptotic proteins XIAP and Bcl-2. Here we identified the pro-apoptotic Sept4/ARTS gene as a p53-responsive target gene. Ectopic p53 and a variety of p53-inducing agents increased both mRNA and protein levels of ARTS, whereas ablation of p53 reduced ARTS expression in response to multiple stress conditions. Also, γ-irradiation induced p53-dependent ARTS expression in mice. Consistently, p53 binds to the responsive DNA element on the ARTS promoter and transcriptionally activated the promoter-driven expression of a luciferase reporter gene. Interestingly, ARTS binds to and sequesters p53 at mitochondria, enhancing the interaction of the latter with Bcl-XL. Ectopic ARTS markedly augments DNA damage stress- or Nutlin-3-triggered apoptosis, while ablation of ARTS preferentially impairs p53-induced apoptosis. Altogether, these findings demonstrate that ARTS collaborates with p53 in mitochondria-engaged apoptosis.

20.
Sci Adv ; 7(9)2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33637528

RESUMO

The innate immune response influences neural repair after spinal cord injury (SCI). Here, we combined myeloid-specific transcriptomics and single-cell RNA sequencing to uncover not only a common core but also temporally distinct gene programs in injury-activated microglia and macrophages (IAM). Intriguingly, we detected a wide range of microglial cell states even in healthy spinal cord. Upon injury, IAM progressively acquired overall reparative, yet diversified transcriptional profiles, each comprising four transcriptional subtypes with specialized tasks. Notably, IAM have both distinct and common gene signatures as compared to neurodegeneration-associated microglia, both engaging phagocytosis, autophagy, and TyroBP pathways. We also identified an immediate response microglia subtype serving as a source population for microglial transformation and a proliferative subtype controlled by the epigenetic regulator histone deacetylase 3 (HDAC3). Together, our data unveil diversification of myeloid and glial subtypes in SCI and an extensive influence of HDAC3, which may be exploited to enhance functional recovery.

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