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2.
Cell Biol Int ; 46(4): 599-610, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34957655

RESUMO

In most cases of cervical cancer, the high risk of the disease is caused by the human papilloma virus (HPV). Surgery or radiation usually benefits patients with early cervical cancer, while the metastatic one is uncurable and new therapeutic strategies and approaches are required. In this study, HPV16 E6 silence or overexpression were carried out to evaluate the possible mechanisms of HPV16 E6 function in cervical cancer cells with different HPV16 E6 expression background. HPV16 E6-positive cervical cancer cell Siha exerts significantly stronger cell invasion and migration potentials than the HPV16 E6-negative C33A cells. HPV16 E6 silence significantly weakened the potentials of cell invasion and migration, cell proliferation and stemness characteristic in Siha cells. Meanwhile, the overexpression of HPV16 E6 effectively promoted the cell proliferation and stemness characteristic in C33A cells. Our data also indicated a positive association between HPV16 E6 and the levels of epithelial to mesenchymal transition (EMT), and cell stemness. The ectopic expression of OCT4 could effectively reverse the inhibitory roles of HPV16 E6 silence on cell migration, invasion, and stemness in Siha cells. More interestingly, we found that HPV16 E6 might promote the OCT4 expression by impairing the direct binding of p53 on the promoter and activate its transcription. Taken together, our results indicated that HPV16 E6 could promoted the potential cell proliferation, migration, and invasion of human cervical cancer cells by modulating EMT and cell stemness. Our data provide a novel mechanism for how HPV16 E6 acts as a key risk factor for cervical cancer development and progression.


Assuntos
Neoplasias do Colo do Útero , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Feminino , Papillomavirus Humano 16/metabolismo , Humanos , Neoplasias do Colo do Útero/metabolismo
3.
Langmuir ; 38(13): 4129-4137, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35313108

RESUMO

Designing electrical insulation materials with excellent surface flashover strength in a vacuum environment is crucial for high-power equipment and aerospace devices. In the present paper, the effect of two types of electronegative groups, the halogen-phenyl groups and the aromatic π-conjugated naphthyl groups, is used to greatly improve the vacuum flashover characteristics of polystyrene (PS), a commonly used polymer dielectric material in high-power devices. By polymerization of the monomers containing these electronegative groups, the bulk insulation material as a whole is modified expediently. In comparison to the base polymer PS, the electron affinity of the structures containing strong electronegative groups is studied with first-principles calculations based on the density functional theory. The nanosecond pulsed vacuum flashover testing results show that the vacuum flashover strength is increased by 10% after replacing the PS pendant phenyl groups with fluorophenyl groups and increased by 44% when replaced with the naphthyl groups. Furthermore, the thermally stimulated current and secondary electron emission yield spectroscopies are measured, to study the influence of strong electronegative groups on the trapping characteristics and further the electron-emitting features of the polymer dielectrics, which are closely related to the charged particle multiplication process during the vacuum flashover. The results prove that introducing strong electronegative groups can inhibit the triggering of vacuum flashover, suppress the electron emission, delay the flashover process, and thus greatly increase the vacuum flashover voltage. The study of this paper not only puts forward two groups of easily processable polymers with excellent vacuum flashover strength but also paves ways for the future material design of special insulation polymers.

4.
Front Pediatr ; 10: 947876, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36090570

RESUMO

Objective: Cystic biliary atresia (CBA) is a rare and peculiar type of biliary atresia (BA) that is easily confused with infantile choledochal cysts (CCs). This study explored information for early CBA diagnosis and treatment. Method: The authors retrospectively analyzed the clinical data of 32 children with hilar cysts from January 2013 to May 2021. According to the diagnosis, they were divided into the CBA (n = 12) and CC (n = 20) groups. Patient features, biochemical indexes, preoperative ultrasound characteristics, cholangiography features, and intraoperative findings were analyzed and compared between the two groups. Results: The alanine aminotransferase, aspartate aminotransferase, total bilirubin, and direct bilirubin levels in the CBA group were higher than in the CCs group (P < 0.05). Additionally, B-mode ultrasound showed a cystic mass in front of the hepatic hilum, and the cyst size was much smaller in the CBA group compared with the CC group (2.2 ± 1.3 cm vs. 6.0 ± 2.2 cm, P < 0.001). Among all of the parameters, cyst width was the most accurate for identifying CBA and CCs. A cutoff value of 2.5 cm (area under the curve, 0.98, P < 0.001) showed 90.9% sensitivity and 95% specificity for cyst size. Conclusion: For children with early-onset severe jaundice, and if the width of the cystic mass was ≤2.5 cm, a diagnosis of CBA was highly likely. Early cholangiography and surgical treatment are necessary for the effective treatment of these infants.

5.
Front Physiol ; 13: 937899, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091396

RESUMO

Exercise affects the expression of microRNAs (miR/s) and muscle-derived extracellular vesicles (EVs). To evaluate sarcoplasmic and secreted miR expression in human skeletal muscle in response to exercise-mimetic contractile activity, we utilized a three-dimensional tissue-engineered model of human skeletal muscle ("myobundles"). Myobundles were subjected to three culture conditions: no electrical stimulation (CTL), chronic low frequency stimulation (CLFS), or intermittent high frequency stimulation (IHFS) for 7 days. RNA was isolated from myobundles and from extracellular vesicles (EVs) secreted by myobundles into culture media; miR abundance was analyzed by miRNA-sequencing. We used edgeR and a within-sample design to evaluate differential miR expression and Pearson correlation to evaluate correlations between myobundle and EV populations within treatments with statistical significance set at p < 0.05. Numerous miRs were differentially expressed between myobundles and EVs; 116 miRs were differentially expressed within CTL, 3 within CLFS, and 2 within IHFS. Additionally, 25 miRs were significantly correlated (18 in CTL, 5 in CLFS, 2 in IHFS) between myobundles and EVs. Electrical stimulation resulted in differential expression of 8 miRs in myobundles and only 1 miR in EVs. Several KEGG pathways, known to play a role in regulation of skeletal muscle, were enriched, with differentially overrepresented miRs between myobundle and EV populations identified using miEAA. Together, these results demonstrate that in vitro exercise-mimetic contractile activity of human engineered muscle affects both their expression of miRs and number of secreted EVs. These results also identify novel miRs of interest for future studies of the role of exercise in organ-organ interactions in vivo.

6.
Front Bioeng Biotechnol ; 10: 990507, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091442

RESUMO

Adverse events of diabetes mellitus (DM) include bone damages, such as the increased incidence of osteoporosis and bone fractures, which are known as diabetic osteopathy. The pathogenic mechanism of diabetic osteopathy is complex, and hyperglycemia is a vital cause involved in it. Bone marrow mesenchymal stem cells (BMSCs) exert a significant effect on bone formation. Therefore, in this paper, transcriptomic changes of BMSCs cultured in high glucose (35 mM) for 30 days are mainly investigated. In addition, 794 up-regulated genes and 1,162 down-regulated genes were identified. Then, biological functions of the differentially expressed genes in the high glucose microenvironment were investigated by two kinds of functional analyses. Gene Set Enrichment Analysis was also applied to focus on the significant gene sets and it is found that Wnt10b expression witnessed a remarkable decrease in BMSCs under the high glucose microenvironment. At last, in vitro experiments revealed that oleuropein effectively reversed high glucose-induced osteogenic inhibition via activating Wnt10b in BMSCs.

7.
Artigo em Inglês | MEDLINE | ID: mdl-36091601

RESUMO

Objective: The aim of this study was to analyze the clinical effect of the proximal femoral nail on elderly patients with unstable intertrochanteric fracture and the effect of the proximal femoral nail on serum levels of matrix metalloproteinases (MMPs) and osteoprotegerin (OPG). Methods: The elderly patients with unstable intertrochanteric fracture of the femur admitted to our hospital from January 2017 to January 2021 were studied. 100 patients were randomly divided into two groups: the control group (n = 50) and the observation group (n = 50). The patients in the control group were treated with a proximal femoral locking compression plate. The patients in the observation group were treated with the proximal femoral antirotation intramedullary nail. The clinical therapeutic effects of the two groups and the changes in serum MMPs and OPG levels before and after treatment were analyzed. Results: Compared with the control group, the operation time, postoperative landing time, and fracture healing time of the observation group were significantly shortened, and intraoperative blood loss was significantly reduced (P < 0.05). Compared with the control group, the total effective rate of patients in the observation group was significantly higher (P < 0.05). After treatment, the levels of CRP, IL1ß, IL2, MMP-2, MMP-6, TIMP-1, and RANKL decreased significantly in both groups (P < 0.05), while the levels of OPG increased significantly (P < 0.05). Compared with the control group, the changes in the above indexes were more obvious in the observation group (P < 0.05). Conclusion: The proximal femoral antirotation intramedullary nail has a better therapeutic effect on elderly patients with unstable intertrochanteric fracture, and the level of MMPs and OPG may be related to the treatment process.

8.
Front Pharmacol ; 13: 937581, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091763

RESUMO

In this study, three acidic polysaccharides from different plant parts of Codonopsis pilosula var. Modesta (Nannf.) L. T. Shen were obtained by ion exchange chromatography and gel filtration chromatography, and the yields of these three polysaccharides were different. According to the preliminary experimental results, the antioxidant activities of the polysaccharides from rhizomes and fibrous roots (CLFP-1) were poor, and was thus not studied further. Due to this the structural features of polysaccharides from roots (CLRP-1) and aerial parts (CLSP-1) were the object for this study and were structurally characterized, and their antioxidant activities were evaluated. As revealed by the results, the molecular weight of CLRP-1and CLSP-1 were 15.9 kDa and 26.4 kDa, respectively. The monosaccharide composition of CLRP-1 was Ara, Rha, Fuc, Xyl, Man, Gal, GlcA, GalA in a ratio of 3.8: 8.4: 1.0: 0.8: 2.4: 7.4: 7.5: 2.0: 66.7, and Ara, Rha, Gal, GalA in a ratio of 5.8: 8.9: 8.0: 77.0 in for CLSP-1. The results of structural elucidation indicated that both CLRP-1 and CLSP-1 were pectic polysaccharides, mainly composed of 1, 4-linked galacturonic acid with long homogalacturonan regions. Arabinogalactan type I and arabinogalactan type II were presented as side chains. The antioxidant assay in IPEC-J2 cells showed that both CLRP-1 and CLSP-1 promoted cell viability and antioxidant activity, which significantly increase the level of total antioxidant capacity and the activity of superoxide dismutase, catalase, and decrease the content of malondialdehyde. Moreover, CLRP-1 and CLSP-1 also showed powerful antioxidant abilities in Caenorhabditis elegans and might regulate the nuclear localization of DAF-16 transcription factor, induced antioxidant enzymes activities, and further reduced reactive oxygen species and malondialdehyde contents to increase the antioxidant ability of Caenorhabditis elegans. Thus, these finding suggest that CLRP-1 and CLSP-1 could be used as potential antioxidants.

9.
Oxid Med Cell Longev ; 2022: 7957255, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092168

RESUMO

Abdominal or pelvic radiotherapy (RT) often results in small intestinal injury, such as apoptosis of epithelial cells and shortening of the villi. Atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has many biological effects including cholesterol reduction, protection from cell damage, and autophagy activation. To reduce the extent of radiotherapy- (RT-) induced enteritis, we investigated the protective effects of atorvastatin against RT-induced damage of the intestinal tract. In this study, C57BL/6 mice were randomly distributed into the following groups (n = 8 per group): (1) control group: mice were fed water only, (2) atorvastatin group (Ator): mice were administered atorvastatin, (3) irradiation group (IR): mice received abdominal RT, (4) Ator+IR group: mice received abdominal RT following atorvastatin administration, and (5) Ator+IR+3-MA group: abdominal RT following atorvastatin and 3-methyladenine (an autophagy inhibitor) administration. Based on the assessment of modified Chiu's injury score and villus/crypt ratio, we found that atorvastatin administration significantly reduced intestinal mucosal damage induced by RT. Atorvastatin treatment reduced apoptosis (cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase), DNA damage (γH2AX and 53BP1), oxidative stress (OS, 4-hydroxynonenal), inflammatory molecules (phospho-NF-κB p65 and TGF-ß), fibrosis (collagen I and collagen III), barrier leakage (claudin-2 and fluorescein isothiocyanate-dextran), disintegrity (fatty acid-binding protein 2), and dysfunction (lipopolysaccharide) caused by RT in small intestinal tissue. In addition, atorvastatin upregulated the expression of autophagy-active molecules (LC3B), antioxidants (heme oxygenase 1 and thioredoxin 1), and tight junction proteins (occludin and zonula occludens 1). However, the biological functions of atorvastatin in decreasing RT-induced enteritis were reversed after the administration of 3-MA; the function of antioxidant molecules and activity of thioredoxin reductase were independent of autophagy activation. Our results indicate that atorvastatin can effectively relieve RT-induced enteritis through autophagy activation and associated biological functions, including maintaining integrity and function and decreasing apoptosis, DNA damage, inflammation, OS, and fibrosis. It also acts via its antioxidative capabilities.


Assuntos
Antioxidantes , Autofagia , Animais , Antioxidantes/farmacologia , Atorvastatina/farmacologia , Atorvastatina/uso terapêutico , Fibrose , Camundongos , Camundongos Endogâmicos C57BL
10.
Front Genet ; 13: 964098, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092864

RESUMO

Background: Lethal multiple pterygium syndrome (LMPS) is a rare autosomal recessive inherited disorder typically characterized by intrauterine growth retardation, multiple pterygia, and flexion contractures. Case presentation: We herein report a Chinese case with a history of three adverse pregnancies demonstrating the same ultrasonic phenotypes, including increased nuchal translucency, edema, fetal neck cystoma, reduced movement, joint contractures, and other congenital features. Whole-exome sequencing (WES) revealed novel compound heterozygous variants in the CHRNA1 gene NM_000079.4: c.[1128delG (p.Pro377LeufsTer10)]; [505T>C (p.Trp169Arg)] in the recruited individual, and subsequent familial segregation showed that both parents transmitted their respective mutation. Conclusion: For the first time, we identified an association between the CHRNA1 gene and the recurrent lethal multiple pterygium syndrome (LMPS) in a Chinese family. This finding may also enrich the mutation spectrum of the CHRNA1 gene and promote the applications of WES technology in etiologic diagnosis of ultrasound anomalies in prenatal examination.

11.
Transl Cancer Res ; 11(8): 2936-2939, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36093527

RESUMO

Background: Bevacizumab has gradually become an important adjuvant therapy for many advanced tumors including lung cancer. Although it can improve the survival of many cancer patients, it also brings many adverse reactions, including fistula formation. However, vesicovaginal fistula in the absence of pelvic lesions and radiation history has not been reported before. Case Description: We diagnosed an advanced non-small cell lung cancer patient with left pleural, bone and liver metastases in February 2017. She then received Gefitinib-targeted therapy. Ten months later, liver metastases achieved complete remission and the remaining metastases partial response. Then she received whole brain radiotherapy (30 Gy/10 F) for new brain metastases, and Oxitinib was used to replace Gefitinib. In March 2018, the patient underwent TVT-O sling surgery for stress urinary incontinence, and recovered well after the operation. The patient was treated with Bevacizumab at 400 mg once every 3 weeks in March 2019 because of the poor efficacy of Oxitinib. After using bevacizumab for 3 months, the patient complained about frequent urination, urgency, dysuria, and vaginal leakage. The presence of vesicovaginal fistula was confirmed by color Doppler ultrasound and positron emission tomography/computed tomography (PET-CT). After discontinuation of Bevacizumab, urine leakage was disappeared. Conclusions: Bevacizumab can also cause vesicovaginal fistula, even without pelvic lesions and radiotherapy. Previous pelvic surgery and foreign materials implantation may be factors that promote the formation of vesicovaginal fistula.

12.
Am J Clin Nutr ; 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36095141

RESUMO

OBJECTIVES: Many studies have investigated the effects of soy isoflavones on weight control, but few have focused on the role of equol, a gut-derived metabolite of daidzein with greater bioavailability than other soy isoflavones. This study examined the association of equol production with obesity and explored the mediating roles of equol-related gut microbiota and microbial carnitine metabolites. METHODS: This 6.6-year prospective study included 2958 Chinese adults (2011 females and 947 males) aged 60.6 ± 6.0 years. Urinary equol and isoflavones were measured using HPLC-MS/MS. Body mass index (BMI), fat mass (%FM), and serum triglycerides (TG) were assessed every three years. Metagenomics sequencing and assessment of carnitine metabolites in feces were performed in a subsample of 897 participants. RESULTS: Urinary equol, but not daidzein and genistein, was independently and inversely associated with obesity-related indicators of BMI, %FM, and biomarkers (TG). Equol producers (EP) had lower odds of adiposity conditions and a reduced risk of 6.6-year obesity progression than non-EP among total participants. Gut microbial analyses indicated that EP had higher microbiome species richness (P = 3.42 × 10-5) and significantly different beta-diversity of gut microbiota compared to the non-EP groups (P = 0.001), with 20 of 162 species differing significantly. EP (vs. non-EP) had higher abundances of Alistipes senegalensis and Coprococcus catus but lower abundances of Ruminococcus gnavus (FDR < 0.05). Among the seven determined fecal acylcarnitine metabolites, palmitoylcarnitine, oleylcarnitine C18:1, and stearylcarnitine were inversely associated with EP but positively correlated with obesity conditions and progression. Path analyses indicated that the beneficial association between equol and obesity might be mediated by gut microbiota and decreased production of 3 acylcarnitines in feces. CONCLUSIONS: This study suggests a beneficial association between equol and obesity that mediated by the gut microbiome and acylcarnitine in adults.

13.
J Hazard Mater ; 439: 129626, 2022 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-36104896

RESUMO

Arsenic (As) pollution in paddy fields is a major threat to rice safety. Existing As remediation techniques are costly, require external chemical addition and degrade soil properties. Here, we report the use of plastic tubes as a recyclable tool to precisely extract As from contaminated soils. Following insertion into flooded paddy soils, polyethylene tube walls were covered by thin but massive Fe coatings of 76.9-367 mg Fe m-2 in 2 weeks, which adsorbed significant amounts of As. The formation of tube-wall Fe oxides was driven by local Fe-oxidizing bacteria with oxygen produced by oxygenic phototrophs (e.g., Cyanobacteria) or diffused from air through the tube wall. The tubes with As-bound Fe oxides can be easily separated from soil and then washed and reused. We tested the As removal efficiency in a pot experiment to remove As from ~ 20 cm depth/40 kg soils in a 2-year experiment and achieved an overall removal efficiency of 152 mg As m-2 soil year-1, comparable to phytoremediation with the As hyperaccumulator Pteris vittata. The cost of Fe hooks was estimated at 8325 RMB ha-1 year-1, and the profit of growing rice (around 16080 RMB ha-1 year-1 can be still maintained. The As accumulated in rice tissues was markedly decreased in the treatment (>11.1 %). This work provides a low-cost and sustainable soil remediation method for the targeted removal of As from soils and a useful tool for the study and management of the biogeochemical Fe cycle in paddy soils.


Assuntos
Arsênio , Oryza , Poluentes do Solo , Arsênio/metabolismo , Biodegradação Ambiental , Compostos Férricos , Ferro/química , Oryza/metabolismo , Óxidos/metabolismo , Plásticos/metabolismo , Solo/química , Poluentes do Solo/metabolismo
14.
Front Public Health ; 10: 973887, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36111192

RESUMO

Background: Trace metals are essential trace elements for the human body, but insufficient or excessive levels of metal ions can lead to the development of disease. The purpose of this study was to examine the relationship between dietary intake of copper and the prevalence of kidney stones in U.S. adult population. Methods: We included data on dietary intake of trace metals from 28,623 adult participants in the National Health and Nutrition Examination Survey (NHANES) database between 2007 and 2018. Multivariate logistic regression and restricted cubic spline (RCS) dose-response curves were used to explore the association between trace metals and kidney stones, and 1:1 propensity score matching (PSM) was performed between the stone formers and non-stone formers to test the validity of the results. Results: Dose-response curves showed a non-linear negative association between dietary copper intake and kidney stones, and an increase in copper intake reduced the risk of kidney stones. Multivariate logistic regression analysis showed that the odds ratio (95% confidence interval) for kidney stones in each quartile of copper intake compared to the lowest quartile were 0.905 (0.808-1.011, p = 0.075), 0.880 (0.785-0.987, p = 0.028) and 0.853 (0.756-0.959, p = 0.009). In addition, similar conclusions were reached after analysis of PSM in the stone formers and non-stone formers groups. Conclusion: Dietary copper intake was negatively and non-linearly correlated with kidney stones, which is worthy of further research and application in clinical practice.


Assuntos
Cobre , Cálculos Renais , Adulto , Humanos , Cálculos Renais/epidemiologia , Cálculos Renais/etiologia , Inquéritos Nutricionais , Prevalência , Pontuação de Propensão , Estados Unidos/epidemiologia
15.
Comput Biol Chem ; 101: 107765, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36113329

RESUMO

BACKGROUND: RNA Secondary Structure (RSS) has drawn growing concern, both for their pivotal roles in RNA tertiary structures prediction and critical effect in penetrating the mechanism of functional non-coding RNA. Computational techniques that can reduce the in vitro and in vivo experimental costs have become popular in RSS prediction. However, as an NP-hard problem, there is room for improvement that the validity of the prediction RSS with pseudoknots in traditional machine learning predictors. RESULTS: In this essay, by integrating the bidirectional GRU (Gated Recurrent Unit) with the attention, we propose a multilayered neural network called BAT-Net to predict RSS. Different from the state-of-the-art works, BAT-Net can not only make full use of the information about the direct predecessor and direct successor of the predicted base in the RNA sequence but also dynamically adjust the corresponding loss function. The experimental results on five representative datasets extracted from the RNA STRAND database show that the sensitivity, precision, accuracy, and MCC (Matthews Correlation Coefficient) of the BAT-Net have improved by 8.52%, 8.28%, 5.66% and 9.82%, respectively, compared with the benchmark approaches on the best averages. CONCLUSIONS: BAT-Net can provide users with more credible RSS results since it has further utilized the source information of the dataset. Comparative results show that the proposed BAT-Net is superior to the other existing methods on the relevant indicators.

16.
Artigo em Inglês | MEDLINE | ID: mdl-36121452

RESUMO

BACKGROUND: Immunotherapy has largely improved clinical outcome of patients with esophageal squamous cell carcinoma (ESCC). However, a proportion of patients still fail to benefit. Thus, biomarkers predicting therapeutic resistance and underlying mechanism needs to be investigated. METHODS: Transcriptomic profiling was applied in FFPE tissues from 103 ESCC patients, including surgical samples from 66 treatment-naïve patients with long-term follow-up, and endoscopic biopsies from 37 local advanced ESCC cases receiving neoadjuvant immunotherapy plus chemotherapy. Unsupervised clustering indicated an aggressive phenotype with mesenchymal character in 66 treatment-naïve samples. Univariant logistic regression was applied to identify candidate biomarkers potentially predicted resistance to neoadjuvant immunotherapy within the range of mesenchymal phenotype enriched genes. These biomarkers were further validated by immunohistochemistry. Putative mechanisms mediating immunotherapy resistance, as indicated by microenvironment and immune cell infiltration, were evaluated by transcriptomic data, and validated by multiplex immunofluorescence. RESULTS: PLEK2 and IFI6, highly expressed in mesenchymal phenotype, were identified as novel biomarkers relating to non-MPR in neoadjuvant immunotherapy cohort [PLEK2high, OR (95% CI): 2.15 (1.07-4.33), P = 0.032; IFI6high, OR (95% CI): 2.21 (1.16-4.23), P = 0.016). PLEK2high and IFI6 high ESCC patients (versus low expressed patients) further exhibit higher chance of non-major pathological remissions (90%, P = 0.004) in neoadjuvant immunotherapy cohort and high mortality (78.9%, P = 0.05), poor prognosis in retrospective cohort. PLEK2high/IFI6high ESCC recapitulated mesenchymal phenotype, characterized by extracellular matrix composition and matrix remodeling. In addition, PLEK2high or IFI6high ESCC displayed an immune-unfavored microenvironment, represented by positive correlating with regulatory T cells, Helper 2 T cell as well as less infiltration of B cells, effector T cells and mast cells. CONCLUSIONS: PLEK2 and IFI6 was discovered of first time to identify a distinct ESCC subpopulation cannot be benefited from neoadjuvant immunotherapy and present a poor survival, which putatively associated with mesenchymal and immune-suppressive microenvironment.

17.
PLoS One ; 17(9): e0271239, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36107934

RESUMO

Market competition is considered to have a significant impact on product diversification, but related issues are rarely discussed on a city scale. To analyze the diversification of export commodities and export market of 270 Chinese cities, this study uses data from 2000 to 2017 based on the commodity concentration index, market concentration index, export similarity index, spatial stratified heterogeneity, and the Almon lag model. The study's findings are: (1) The diversification of exports in most Chinese cities increased, which was higher in more developed cities in the southeast than in less developed ones in the northwest. With time, the degree of commodity and market diversification in some developed southeast Chinese cities (e.g., Shanghai) declined. This indicates the difference in and complexity of the evolution of export development in hundreds of Chinese cities between 2000 and 2017. (2) The export competition between cities became increasingly fierce, which effectively urged most of them to improve their export diversification levels. Facing increasing export competition pressure, 81.11% of the total number of cities will enhance the diversification of export commodities to cope with challenges posed by other cities. But only 56.67% will further expand the export market when the pressure of export competition increases. The biggest contribution of this study is the finding that for most Chinese cities, when export competition from other domestic cities increases, increasing diversification of products becomes a wise choice. However, the influence of competition on the diversification degree of the city's export market is relatively weak. This study provides not only a new perspective for existing research on urban export trade, but also valuable information for cities to form a more profitable and robust trading system.


Assuntos
Reforma Urbana , China , Cidades
18.
BMC Gastroenterol ; 22(1): 425, 2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36115934

RESUMO

BACKGROUND: New direct-acting antiviral therapies have revolutionized hepatitis C virus (HCV) infection therapy. Nonetheless, once liver cirrhosis is established, the risk of hepatocellular carcinoma (HCC) still exists despite virus eradication. Late HCV diagnosis hinders timely access to HCV treatment. Thus, we determined trends and risk factors associated with late HCV among patients with a diagnosis of HCC in Taiwan. METHODS: We conducted a population-based unmatched case-control study. 2008-2018 Claims data were derived from the Taiwan National Health Insurance Research Database. Individuals with an initial occurrence of liver cancer between 2012 and 2018 were included. The late HCV group were referred as individuals who were diagnosed with HCC within 3 years after HCV diagnosis. The control group were referred as individuals who were diagnosed more than 3 years after the index date. We used multivariable logistic models to explore individual- and provider-level risk factors associated with a late HCV diagnosis. RESULTS: A decreasing trend was observed in the prevalence of late HCV-related HCC diagnosis between 2012 and 2018 in Taiwan. On an individual level, male, elderly patients, patients with diabetes mellitus (DM), and patients with alcohol-related disease had significantly higher risks of late HCV-related HCC diagnosis. On a provider level, patients who were mainly cared for by male physicians, internists and family medicine physicians had a significantly lower risk of late diagnosis. CONCLUSIONS: Elderly and patients who have DM and alcohol related disease should receive early HCV screening. In addition to comorbidities, physician factors also matter. HCV screening strategies shall take these higher risk patients and physician factors into consideration to avoid missing opportunities for early intervention.


Assuntos
Carcinoma Hepatocelular , Diabetes Mellitus , Hepatite C Crônica , Hepatite C , Neoplasias Hepáticas , Idoso , Antivirais , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , Diagnóstico Tardio/efeitos adversos , Hepacivirus , Hepatite C/complicações , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/etiologia , Masculino
19.
Microbiol Spectr ; : e0207222, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36129287

RESUMO

The emergence and spread of antibiotic resistance pose serious environmental and health challenges. Attention has been drawn to phage therapy as an alternative approach to combat antibiotic resistance with immense potential. However, one of the obstacles to phage therapy is phage resistance, and it can be acquired through genetic mutations, followed by consequences of phenotypic variations. Therefore, understanding the mechanisms underlying phage-host interactions will provide us with greater detail on how to optimize phage therapy. In this study, three lytic phages (phipa2, phipa4, and phipa10) were isolated to investigate phage resistance and the potential fitness trade-offs in Pseudomonas aeruginosa. Specifically, in phage-resistant mutants phipa2-R and phipa4-R, mutations in conferring resistance occurred in genes pilT and pilB, both essential for type IV pili (T4P) biosynthesis. In the phage-resistant mutant phipa10-R, a large chromosomal deletion of ~294 kb, including the hmgA (homogentisate 1,2-dioxygenase) and galU (UTP-glucose-1-phosphate uridylyltransferase) genes, was observed and conferred phage phipa10 resistance. Further, we show examples of associated trade-offs in these phage-resistant mutations, e.g., impaired motility, reduced biofilm formation, and increased antibiotic susceptibility. Collectively, our study sheds light on resistance-mediated genetic mutations and their pleiotropic phenotypes, further emphasizing the impressive complexity and diversity of phage-host interactions and the challenges they pose when controlling bacterial diseases in this important pathogen. IMPORTANCE Battling phage resistance is one of the main challenges faced by phage therapy. To overcome this challenge, detailed information about the mechanisms of phage-host interactions is required to understand the bacterial evolutionary processes. In this study, we identified mutations in key steps of type IV pili (T4P) and O-antigen biosynthesis leading to phage resistance and provided new evidence on how phage predation contributed toward host phenotypes and fitness variations. Together, our results add further fundamental knowledge on phage-host interactions and how they regulate different aspects of Pseudomonas cell behaviors.

20.
Inorg Chem ; 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36122376

RESUMO

The electrocatalytic nitrate reduction reaction (NO3--ERR) to ammonia (NH3) is a promising strategy for NH3 production. Cu-based nanomaterials have been regarded as a kind of effective NO3--ERR catalysts. In this work, high-quality hollow Cu2O nanocubes (Cu2O h-NCs) are facilely synthesized by a simple one-step reduction method. The as-prepared Cu2O h-NCs reveal high selectivity and activity for NO3--ERR, which is ascribed to abundant oxygen vacancies, high surface area, hollow architecture, low mass transfer resistance, and strong adsorbing ability toward NO3-. In fact, Cu2O h-NCs can achieve a Faradic efficiency of 92.9% and an NH3 yield of 56.2 mg h-1 mgcat-1 for NH3 production at -0.85 V (vs RHE) potential, which exceeds those of other transition-metal-based NO3--ERR electrocatalysts.

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