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1.
FASEB J ; 36 Suppl 12022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35554034

RESUMO

Protein SUMOylation plays an essential role in maintaining cellular homeostasis when cells are under stress. However, how SUMOylation is regulated, and a molecular mechanism linking cellular stress to SUMOylation remains elusive. We hypothesized that cAMP, a major stress-response second messenger, acts through exchange protein directly activated by cAMP (Epac1) to regulate cellular SUMOylation. Proteomic analysis reveals that Epac1 associated proteome is highly-enriched with major components of the SUMOylation machinery and well-known SUMO target proteins. Activation of Epac1 by intracellular cAMP in Human Umbilical Vein Endothelial Cells (HUVECs) promotes cellular SUMOylation and activates cellular SUMO-activating enzyme E1 (AOS1/UBA2). Conversely, silencing Epac1 leads to a reduced cellular SUMOylation and SUMO E1 activation. However, in vitro SUMOylation assay using purified recombinant components of SUMOylation machinery shows that Epac1 does not directly activate SUMO E1 and SUMO-conjugating enzyme E2 (UBC9). Moreover, Epac1-mediated cellular SUMOylation is independent on its guanine nucleotide exchange activity, suggesting that Epac1 promotes cellular SUMOylation through an unconventional mechanism. Co-immunofluorescence staining and Structured Illumination Microscopy (SIM) super-resolution imaging analyses reveal that Epac1 activation promotes the formation of Epac1 nuclear condensates that co-localize with nuclear UBA2/UBC9/SUMO2/3. The discovery of Epac1-based biomolecular condensates is consistent with the facts that Epac1 contains intrinsically disordered regions (IDRs) and undergoes salt- and cAMP-dependent phase separation (PS). Importantly, the formation of Epac1 nuclear condensates is required for Epac1-mediated cellular SUMOylation, as a Δ (1-148) Epac1 mutant incapable of PS and forming nuclear condensates fails to promote cellular SUMOylation. Furthermore, genetic knockout of Epac1 obliterates oxidized low-density lipoprotein (oxLDL) induced cellular SUMOylation in macrophages, leading to suppression of foam cell formation. Our findings represent a major conceptual advance in our understanding of cell stress responses by providing a direct connection between protein SUMOylation and cAMP/Epac1 signaling pathway, two major cellular stress processes. The ability of cAMP to directly modulate the dynamics of cellular condensate provides the first experimental evidence that protein phase separation can be regulated by an endogenous ligand.

2.
Sleep ; 45(5)2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35554576
3.
Front Cell Infect Microbiol ; 12: 726256, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35558102

RESUMO

Rationale and Objective: Gut microbiota have been targeted by alternative therapies for non-communicable diseases. We examined the gut microbiota of a healthy Taiwanese population, identified various bacterial drivers in different demographics, and compared them with dialysis patients to associate kidney disease progression with changes in gut microbiota. Study Design: This was a cross-sectional cohort study. Settings and Participants: Fecal samples were obtained from 119 healthy Taiwanese volunteers, and 16S rRNA sequencing was done on the V3-V4 regions to identify the bacterial enterotypes. Twenty-six samples from the above cohort were compared with fecal samples from 22 peritoneal dialysis and 16 hemodialysis patients to identify species-level bacterial biomarkers in the dysbiotic gut of chronic kidney disease (CKD) patients. Results: Specific bacterial species were identified pertaining to different demographics such as gender, age, BMI, physical activity, and sleeping habits. Dialysis patients had a significant difference in gut microbiome composition compared to healthy controls. The most abundant genus identified in CKD patients was Bacteroides, and at the species level hemodialysis patients showed significant abundance in B. ovatus, B. caccae, B. uniformis, and peritoneal dialysis patients showed higher abundance in Blautia producta (p ≤ 0.05) than the control group. Pathways pertaining to the production of uremic toxins were enriched in CKD patients. The abundance of the bacterial species depended on the type of dialysis treatment. Conclusion: This study characterizes the healthy gut microbiome of a Taiwanese population in terms of various demographics. In a case-control examination, the results showed the alteration in gut microbiota in CKD patients corresponding to different dialysis treatments. Also, this study identified the bacterial species abundant in CKD patients and their possible role in complicating the patients' condition.

4.
Front Pharmacol ; 13: 886377, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35548363

RESUMO

Adverse drug reactions (ADR) remain the major problems in healthcare. Most severe ADR are unpredictable, dose-independent and termed as type B idiosyncratic reactions. Recent pharmacogenomic studies have demonstrated the strong associations between severe ADR and genetic markers, including specific HLA alleles (e.g., HLA-B*15:02/HLA-B*57:01/HLA-A*31:01 for carbamazepine-induced severe cutaneous adverse drug reactions [SCAR], HLA-B*58:01 for allopurinol-SCAR, HLA-B*57:01 for abacavir-hypersensitivity, HLA-B*13:01 for dapsone/co-trimoxazole-induced SCAR, and HLA-A*33:01 for terbinafine-induced liver injury), drug metabolism enzymes (such as CYP2C9*3 for phenytoin-induced SCAR and missense variant of TPMT/NUDT15 for thiopurine-induced leukopenia), drug transporters (e.g., SLCO1B1 polymorphism for statin-induced myopathy), and T cell receptors (Sulfanilamide binding into the CDR3/Vα of the TCR 1.3). This mini review article aims to summarize the current knowledge of pharmacogenomics of severe ADR, and the potentially clinical use of these genetic markers for avoidance of ADR.

5.
Polymers (Basel) ; 14(9)2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35567013

RESUMO

In this study, we determined the effects of design and processing parameters of precision injection molding (PIM) to minimize warpage phenomena of micro-sized parts using various plastics (polyoxymethylene (POM), acrylonitrile-butadiene-styrene (ABS), polypropylene (PP), polyamide (PA), and ABS+ polycarbonate (PC)). We applied a numerical simulation (Moldflow) to determine the runner's balance in multi-cavities of the micro-sized part and simulate the warpage phenomenon of micro-parts with PIM. We used simulation data to fabricate a steel mold by computer numerical control (CNC) machining. In this, we study manufactured a micro-sized part and measured its warpage value using various PIM process parameters (melt temperature, mold temperature, injection pressure, and filling time). In order to obtain optimal results (i.e., minimum warpage), we employed the Taguchi method and grey theory to discern the influence of each process parameter on PIM. Finally, we determined that the most significant PIM process parameter influencing the warpage phenomenon of micro-sized parts was the mold temperature, regardless of whether in terms of the experimental results, numerical simulations, or grey theory. The PA material had the most suitable properties for application for micro-sized parts, regardless of whether in terms of experimental results, numerical simulations, or grey theory for PIM. This study also illustrates that micro-sized parts can be fabricated by PIM without the use of micro-injection molding, and we determined that the mold temperature required for molding does not need to be higher than the glass-transition temperature of the material.

6.
Front Genet ; 13: 874379, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35571010

RESUMO

Na+-taurocholate cotransporting polypeptide deficiency (NTCPD) is an autosomal recessive disorder arising from biallelic SLC10A1 mutations. As a newly-described inborn error of bile acid metabolism, the epidemiology of this condition remains largely unclear in Chinese population so far. In this study, a total of 2,828 peripheral blood samples were collected from 12 cities in Guangdong, a province with the largest population in China, and the four prevalent SLC10A1 variants c.800C > T (p.Ser267Phe), c.263T > C (p.Ile88Thr), c.595A > C (p.Ser199Arg) and c.665T > C (p.Leu222Ser) were screened for by using polymerase chain reaction (PCR)- restriction fragment length polymorphism (RFLP). As a result, 663 mutated SLC10A1 alleles were detected, and the mutated allele frequency was calculated to be 11.72% (663/5,656), with a carrier frequency 20.69% (1/5) and a theoretical morbidity rate 1.37% (1/73) of NTCPD in Guangdong province. The variant c.800C > T (p.Ser267Phe) exhibited highest allele frequency among the four prevalent variants (χ2 = 1501.27, p < 0.0001) as well as higher allele frequency in the peripheral region than that within the Pearl River Delta (χ2 = 4.834, p < 0.05). The results suggested that NTCPD might be a disorder rather common in Guangdong province. The findings depicted the molecular epidemiologic features of NTCPD, providing preliminary but significant laboratory evidences for the subsequent NTCPD diagnosis and management in Guangdong population.

7.
Ann Transl Med ; 10(8): 431, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35571412

RESUMO

Background: Fibroblast-like synoviocytes (FLSs) play a critical role in promoting synovial aggression and joint destruction in rheumatoid arthritis (RA). Cyclic GMP-AMP synthase (cGAS)/stimulator of interferon gene (STING) signaling plays an important role in controlling a series of cellular biological processes. However, it is still unclear whether cGAS/STING signaling regulates rheumatoid synovial aggression. Methods: Cell migration and invasion were detected using a Transwell chamber. Gene expression was measured using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and protein expression was detected by western blotting. Reactive oxygen species (ROS) levels were measured by 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) probe. F-actin staining and immunofluorescence assays were used to investigate lamellipodia formation and nuclear translocation, respectively. A severe combined immunodeficiency (SCID) mouse model was established to observe the migration and invasion of RA FLSs in vivo. Results: Our results showed that cytosolic double-stranded DNA (dsDNA)-induced cGAS/STING activation promoted the in vitro migration and invasion of RA FLSs. Moreover, RA FLSs treated with cGAS or STING short hairpin RNA (shRNA) exhibited reduced invasion into cartilage in the SCID model. Mechanistically, we determined that cGAS/STING activation leads to increased mitochondrial ROS levels, and thereby increases phosphorylation of mammalian sterile 20-like kinase 1 (MST1), a core component of the Hippo pathway, subsequently promoting activation of forkhead box1 (FOXO1). MST1 and FOXO1 knockdown also diminished the migration and invasion of RA FLSs. Conclusions: Our findings suggest that cGAS/STING signaling has an important role in regulating rheumatoid synovial aggression and that targeting cGAS/STING may represent a novel potential therapy for RA.

8.
Natl Sci Rev ; 9(4): nwab228, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35571607

RESUMO

Recent investigations have revealed that dynamics of complex networks and systems are crucially dependent on the temporal structures. Accurate detection of the time instant at which a system changes its internal structures has become a tremendously significant mission, beneficial to fully understanding the underlying mechanisms of evolving systems, and adequately modeling and predicting the dynamics of the systems as well. In real-world applications, due to a lack of prior knowledge on the explicit equations of evolving systems, an open challenge is how to develop a practical and model-free method to achieve the mission based merely on the time-series data recorded from real-world systems. Here, we develop such a model-free approach, named temporal change-point detection (TCD), and integrate both dynamical and statistical methods to address this important challenge in a novel way. The proposed TCD approach, basing on exploitation of spatial information of the observed time series of high dimensions, is able not only to detect the separate change points of the concerned systems without knowing, a priori, any information of the equations of the systems, but also to harvest all the change points emergent in a relatively high-frequency manner, which cannot be directly achieved by using the existing methods and techniques. Practical effectiveness is comprehensively demonstrated using the data from the representative complex dynamics and real-world systems from biology to geology and even to social science.

9.
Front Oncol ; 12: 791620, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35574295

RESUMO

Purpose: This study aimed to compare the oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) without clinical lymph node metastasis (cN0) undergoing lymph node dissection (LND) during radical nephroureterectomy (NU). Methods: From the updated data of the Taiwan UTUC Collaboration Group, a total of 2726 UTUC patients were identified. We only include patients with ≥ pT2 stage and enrolled 658 patients. The Kaplan-Meier estimator and Cox proportional hazards model were used to analyze overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and bladder recurrence-free survival (BRFS) in LND (+) and LND (-) groups. Results: A total of 658 patients were included and 463 patients without receiving LND and 195 patients receiving LND. From both univariate and multivariate survival analysis, there are no significant difference between LND (+) and LND (-) group in survival rate. In LND (+) group, 18.5% patients have pathological LN metastasis. After analyzing pN+ subgroup, it revealed worse CSS (p = 0.010) and DFS (p < 0.001) compared with pN0 patients. Conclusions: We found no significant survival benefit related to LND in cN0 stage, ≥ pT2 stage UTUC, irrespective of the number of LNs removed, although pN+ affected cancer prognosis. However, from the result of pN (+) subgroup of LND (+) cohort analysis, it may be reasonable to not perform LND in patients with cT2N0 stage due to low positive predictive value of pN (+). In addition, performing LND may be considered for ureter cancer, which tends to cause lymphatic and hematogenous tumor spreading. Further large prospective studies are needed to validate our findings.

10.
Front Oncol ; 12: 878482, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35574398

RESUMO

Objective: This study was to explore the difference and significance of parietal pleura invasion and rib invasion in pathological T classification with non-small cell lung cancer. Methods: A total of 8681 patients after lung resection were selected to perform analyses. Multivariable Cox analysis was used to identify the mortality differences in patients between parietal pleura invasion and rib invasion. Eligible patients with chest wall invasion were re-categorized according to the prognosis. Cancer-specific survival curves for different pathological T (pT) classifications were presented. Results: There were 466 patients considered parietal pleura invasion, and 237 patients served as rib invasion. Cases with rib invasion had poorer survival than those with the invasion of parietal pleura (adjusted hazard ratio [HR]= 1.627, P =0.004). In the cohort for parietal pleura invasion, patients with tumor size ≤5cm reached more satisfactory survival outcomes than patients with tumor size >5cm (unadjusted HR =1.598, P =0.006). However, there was no predictive difference in the cohort of rib invasion. The results of the multivariable analysis revealed that the mortality with parietal pleura invasion plus tumor size ≤5cm were similar to patients with classification pT3 (P =0.761), and patients for parietal pleura invasion plus tumor size >5cm and pT4 had no stratified survival outcome (P =0.809). Patients identified as rib invasion had a poorer prognosis than patients for pT4 (P =0.037). Conclusions: Rib invasion has a poorer prognosis than pT4. Patients with parietal pleura invasion and tumor size with 5.1-7.0cm could be appropriately up-classified from pT3 to pT4.

11.
Inquiry ; 59: 469580221096278, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35532315

RESUMO

OBJECTIVE: The COVID-19 pandemic has increased psychological distress among common people and has caused health care providers, such as nurses, to experience tremendous stress. METHODS: This prospective cross-sectional study assessed the psychological impacts on nurses in a community hospital in Taiwan, including major depressive disorder (MDD), posttraumatic stress (PTS), and pessimism. According to transactional theory, coping strategies and personal factors have psychological impacts. We hypothesized that behavioral responses to COVID-19 (problem-focused coping) are more effective in reducing psychological impacts than emotional responses to COVID-19 (emotion-focused coping). Independent variables were the use of behavioral and emotional coping strategies for COVID-19 and 3 personal factors, namely sleep disturbance, physical component summary (PCS-12), and mental component summary (MCS-12) of the 12-Item Short Form Health Survey (SF-12) obtained from the Medical Outcomes Study. Dependent variables comprised 3 psychological impacts, namely MDD, PTS, and pessimism. RESULTS: We determined that behavioral coping strategies had significant negative effects on PTS and pessimism; however, emotional coping strategies had significantly positive effects on PTS and pessimism. Sleep disturbance was significantly associated with increased MDD and pessimism. PCS-12 had a significant negative effect on PTS, whereas MCS-12 was not significantly associated with any of the 3 psychological impacts. CONCLUSIONS: Nurses who adopted protective behavior against COVID-19, such as washing hands, wearing masks, avoiding touching eyes, and mouth, and avoiding personal contact, were associated with less posttraumatic stress and pessimism. Healthcare providers should consider strategies for improving preventive behaviors to help ease their worries and fears concerning COVID-19.


Assuntos
COVID-19 , Transtorno Depressivo Maior , Adaptação Psicológica , Estudos Transversais , Humanos , Pandemias , Estudos Prospectivos , Inquéritos e Questionários , Taiwan/epidemiologia
12.
Artigo em Inglês | MEDLINE | ID: mdl-35512604

RESUMO

BACKGROUND: The extent of interstitial fibrosis in the kidney not only correlates with renal function at the time of biopsy but also predicts future renal outcome. However, its assessment by pathologists lacks good agreement. The aim of this study is to construct a machine learning-based model that enables automatic and reliable assessment of interstitial fibrosis in human kidney biopsies. METHODS: Validated cortex, glomerulus, and tubule segmentation algorithms were incorporated into a single model to assess the extent of interstitial fibrosis. The model performances were compared with expert renal pathologists and correlated with patients' renal functional data. RESULTS: Compared with human raters, the model had the best agreement (intraclass correlation coefficient; ICC 0.90) to the reference in 50 test cases. The model also had a low mean bias and the narrowest 95% limits of agreement. The model was robust against colour variation on images obtained at different times, through different scanners, or from outside institutions with excellent ICCs of 0.92 to 0.97. The model showed significantly better test-retest reliability (ICC 0.98) than humans (ICC 0.76 to 0.94), and the amount of interstitial fibrosis inferred by the model strongly correlated with 405 patients' serum creatinine (r = 0.65 to 0.67) and eGFR (r = -0.74 to -0.76). CONCLUSIONS: This study demonstrated that a trained machine learning-based model can faithfully simulate the whole process of interstitial fibrosis assessment, which traditionally can only be carried out by renal pathologists. Our data suggested that such a model may provide more reliable results, thus enabling precision medicine.

13.
J Chin Med Assoc ; 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35507042

RESUMO

BACKGROUND: The effects of endoscopic sinus surgery (ESS) on the symptom burden of Eustachian tube dysfunction (ETD) in chronic rhinosinusitis (CRS) patients were investigated. METHODS: Ninety-two patients with CRS following ESS were prospectively enrolled and followed up every 3 months for 1 year. The 7-item Eustachian Tube Dysfunction Questionnaire (ETDQ-7) and 22-item Sino-Nasal Outcome Test (SNOT-22) were administered before ESS and at each visit following ESS. RESULTS: Before surgery, 25% patients reported ETDQ-7 scores ≥ 14.5, indicating the presence of ETD. The mean preoperative ETDQ-7 and SNOT-22 scores were 13.3 and 40.0, respectively. The mean ETDQ-7 and SNOT-22 scores were significantly decreased to 8.2 and 17.0 at 1-year following ESS, respectively. Most patients reported alleviation of their symptoms within the first 3 months, and the prevalence of ETD had decreased to 3.3% at 1 year. Patients who received revision surgery had higher ETDQ-7 scores during the follow-up period. Additionally, 5.4% of patients reported worsening of their symptoms. CONCLUSION: ETD symptoms can be effectively alleviated in most patients within 3 months following ESS. However, 5.4% of patients reported worsening of their symptoms at the 1-year follow-up. Additional objective studies should be conducted to evaluate Eustachian tube function thoroughly in CRS patients.Supplemental files will be available at http://links.lww.com/JCMA/A148.

14.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 47(2): 211-218, 2022 Feb 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-35545411

RESUMO

OBJECTIVES: Platelet-to-lymphocyte ratio (PLR) has recently been investigated as a new inflammatory marker in many inflammatory diseases, including systemic lupus erythematosus and immunoglobulin A vasculitis. However, there were very few reports regarding the clinical role of PLR in patients with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis. This study was thus undertaken to investigate the relationship between inflammatory response and disease activity in Chinese patients with myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA) associated vasculitis. Furthermore, we evaluated whether PLR predicts the progression of end stage of renal disease (ESRD) and all-cause mortality. METHODS: The clinical, laboratory and pathological data, and the outcomes of MPO-ANCA associated vasculitis patients were collected. The Spearman correlation coefficient was computed to examine the association between 2 continuous variables. Cox regression analysis was used to estimate the association between PLR and ESRD or all-cause mortality. RESULTS: A total of 190 consecutive patients with MPO-ANCA associated vasculitis were included in this study. Baseline PLR was positively correlated with CRP (r=0.333, P<0.001) and ESR (r=0.218, P=0.003). PLR had no obvious correlation with Birmingham Vasculitis Activity Score (BVAS). Patients having PLR≥330 exhibited better cumulative renal survival rates than those having PLR<330 (P=0.017). However, there was no significant difference in the cumulative patient survival rates between patients with PLR≥330 and those with PLR<330 at diagnosis (P>0.05). In multivariate analysis, PLR is associated with the decreased risk of ESRD (P=0.038, HR=0.518, 95% CI 0.278 to 0.963). We did not find an association between PLR with all-cause mortality using multivariate analysis (HR=1.081, 95% CI 0.591 to 1.976, P=0.801). CONCLUSIONS: PLR is positively correlated with CRP and ESR. Furthermore, PLR may independently predict the risk of ESRD.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Falência Renal Crônica , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Anticorpos Anticitoplasma de Neutrófilos/análise , China/epidemiologia , Feminino , Humanos , Falência Renal Crônica/complicações , Linfócitos , Masculino , Peroxidase , Estudos Retrospectivos
15.
Front Oncol ; 12: 843715, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35530335

RESUMO

Background: The advantage of adjuvant chemotherapy for upper urinary tract urothelial cancer (UTUC) has been reported, whereas its impact on upper tract cancer with variant histology remains unclear. We aimed to answer the abovementioned question with our real-world data. Design Setting and Participants: Patients who underwent radical nephroureterectomy (RNU) and were confirmed to have variant UTUC were retrospectively evaluated for eligibility of analysis. In the Taiwan UTUC Collaboration database, we identified 245 patients with variant UTUC among 3,109 patients with UTUC who underwent RNU after excluding patients with missing clinicopathological information. Intervention: Those patients with variant UTUC were grouped based on their history of receiving adjuvant chemotherapy or not. Outcome Measurements and Statistical Analysis: Propensity score matching was used to reduce the treatment assignment bias. Multivariable Cox regression model was used for the analysis of overall, cancer-specific, and disease-free survival. Results and Limitations: For the patients with variant UTUC who underwent adjuvant chemotherapy compared with those without chemotherapy, survival benefit was identified in overall survival in univariate analysis (hazard ratio (HR), 0.527; 95% confidence interval (CI), 0.285-0.973; p = 0.041). In addition, in multivariate analysis, patients with adjuvant chemotherapy demonstrated significant survival benefits in cancer-specific survival (OS; HR, 0.454; CI, 0.208-0.988; p = 0.047), and disease-free survival (DFS; HR, 0.324; 95% CI, 0.155-0.677; (p = 0.003). The main limitations of the current study were its retrospective design and limited case number. Conclusions: Adjuvant chemotherapy following RNU significantly improved cancer-related survivals in patients with UTUC with variant histology.

16.
Genetica ; 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35536451

RESUMO

Breast cancer is a devastating malignancy, among which the luminal A (LumA) breast cancer is the most common subtype. In the present study, we used a comprehensive bioinformatics approach in the hope of identifying novel prognostic biomarkers for LumA breast cancer patients. Transcriptomic profiling of 611 LumA breast cancer patients was downloaded from TCGA database. Differentially expressed genes (DEGs) between tumor samples and controls were first identified by differential expression analysis, before being used for the weighted gene co-expression network analysis. The subsequent univariate Cox regression and LASSO algorithm were used to uncover key prognostic genes for constructing multivariate Cox regression model. Patients were stratified into high-risk and low-risk groups according to the risk score, and subjected to multiple downstream analyses including survival analysis, gene set enrichment analysis (GSEA), inference on immune cell infiltration and analysis of mutation burden. Receiving operator curve analysis was also performed. A total of 7071 DEGs were first identified by edgeR package, pink module was found significantly associated with invasive lobular carcinoma (ILC). 105 prognostic genes and 9 predictors were identified, allowing the identification of a 5-key prognostic genes (LRRC77P, CA3, BAMBI, CABP1, ATP8A2) after intersection. These 5 genes, and the resulting Cox model, displayed good prognostic performance. Furthermore, distinct differences existed between two risk-score stratified groups at various levels. The identified 5-gene prognostic model will help deepen the understanding of the molecular and immunological mechanisms that affect the survival of LumA-ILC patients and guide and proper monitoring of these patients.

17.
Proc Natl Acad Sci U S A ; 119(22): e2202913119, 2022 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-35605116

RESUMO

SignificanceHydrogen peroxide is a highly competitive ready-to-use product for solar energy transformation. Nevertheless, the contemporary photosynthetic systems are not efficient enough, due to severe charge recombination caused by high activation energy and binding energy of the exciton. Herein, we achieve spontaneous exciton dissociation at room temperature. Moreover, the photosynthesis of H2O2 reaches between 9,366 and 12,324 µmol·g-1 from 9 AM to 4 PM in ambient conditions, that is, sunlight irradiation, real water including fresh water and seawater, room temperature, and open air. The ultrahigh photocatalytic efficiency in ambient conditions allows the solar-to-chemical conversion in a real cost-effective and sustainable way, which represents an important step toward real applications.

18.
Artigo em Inglês | MEDLINE | ID: mdl-35564722

RESUMO

Peat is a nonrenewable resource that we are using at alarming rates. Development of peat alternative from pruning waste (PW) could be a cost- and environment-friendly way of disposal. Steam explosion (SE) is a commonly used pretreatment of lignocellulosic biomass, but its impact on the properties of PW as a growing substrate is largely unknown. To address this issue, PW was treated using five SE temperatures (160, 175, 190, 205 and 220 °C) and three retention times (1, 3 and 5 min) and evaluated for key traits of growing substrate. Results indicate that bulk density, total porosity, EC, total carbon, and concentration of phytotoxins including phenol, flavonoid, and alkaloid significantly increased or tended to increase with increasing temperature and/or retention time. A reversed trend was observed for water-holding capacity, pH, content of hemicellulose and lignin, and germination index. Cation exchange capacity and total N showed minimal response to SE. Steam explosion had inconsistent impacts on acid soluble nutrients. Phytotoxicity was a major factor limiting the use of SE-treated PW as growing substrate. Higher pretreatment severity led to higher phytotoxicity but also facilitated subsequent phytotoxicity removal by torrefaction. Pruning waste treated by SE and torrefaction under certain conditions may be used as peat substitute for up to 40% (v/v).

19.
BMC Womens Health ; 22(1): 169, 2022 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-35568870

RESUMO

BACKGROUND: Little research has been conducted to explore variables associated with the healthcare providers' (HCPs) understanding and recommendation of human papillomavirus vaccine (HPV) since the vaccine was approved for use in China. METHODS: A large-scale cross-sectional survey was conducted in southern China covering Guangdong, Guangxi, and Hainan provinces between April 2019 and October 2019. Firstly, descriptive analysis was used to access awareness, knowledge, barriers, and recommendations toward HPV vaccine among all participants. Multi-variable logistic regression was further applied to explore potential factors associated with awareness, acknowledgment of HPV vaccine, and recommendation behaviors toward HPV vaccine. RESULTS: 2075 questionnaires were collected, and 2054 were included in the final analysis. In total, 77.9% of participants have heard of HPV vaccine and obtained sub-optimal HPV/HPV vaccine knowledge scores with a mean (SD) of 13.8 (3.5) out of a maximum score of 23. 68.1% HCPs reported that they have recommended HPV vaccine to others. Province and profession were the most significant characteristics associated with awareness, knowledge score, and recommendation behavior toward HPV vaccine. HCPs in Guangdong obtained a much better knowledge score [Mean (SD) = 15.5 (3.0)] and reported higher recommendation behavior (82.8%). Compare with HCPs from the Division of Expanded Program on Immunization (DEPI), Community Health Center (CHC), and obstetrician-gynecologists, other non-HPV closely related professions showed a less competent knowledge of HPV and HPV vaccine [Mean (SD) = 12.5 (3.0)] and lower frequency of recommendation behavior on vaccination (58.1%). The difference in HPV vaccine knowledge among different professions was concentrating on the items about clinical pathology of HPV and the practical aspects of HPV vaccine. Educational level and title were also closely associated with their knowledge of HPV and its vaccine. Besides, knowledge scores independently determined with recommendation behavior (OR = 1.18, 95% CI 1.13-1.23). CONCLUSION: Knowledge level of HPV and HPV vaccine as well as recommendation behavior toward HPV vaccine were relatively lower in southern China and differed significantly between provinces. Profession-specific gaps on the knowledge level of HPV and HPV vaccine emphasized the need for targeted education and training to improve HCPs' engagement in the promotion of the HPV vaccine.

20.
Artigo em Inglês | MEDLINE | ID: mdl-35579014

RESUMO

BACKGROUND: This meta-analysis of randomized controlled trials (RCTs) investigated the clinical efficacy and safety of favipiravir for patients with mild-to-critical COVID-19. METHODS: PubMed, Web of Science, Ovid Medline, Embase, and Cochrane Central Register of Controlled Trials were searched for RCTs published before October 30, 2021. Only RCTs that compared the clinical efficacy and safety of favipiravir -based antiviral regimens (study group) with other alternative treatments or placebos (control group) in patients with COVID-19 were included. RESULTS: Overall, the clinical improvement rate was significantly higher in the study group than in the control group at the assessment conducted after 14 days (OR, 1.83; 95% CI, 1.12-2.98). The rate of virological eradication was significantly higher in the study group than in the control group at the assessment conducted after 28 days (OR, 2.09; 95% CI, 1.15-3.78). No significant difference was observed in the rates of invasive mechanical ventilation requirement or ICU admission, mortality, or risk of an adverse event between the study and control groups. CONCLUSIONS: Except the clinical improvement rate within 14 days and the virological eradication rate within 28 days, favipiravir-based treatment did not provide significantly additional benefit for patients with COVID-19. Therefore, more evidence is necessary.

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