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1.
Cell ; 181(5): 997-1003.e9, 2020 05 28.
Artículo en Inglés | MEDLINE | ID: mdl-32359424

RESUMEN

Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2 infection and was first reported in central China in December 2019. Extensive molecular surveillance in Guangdong, China's most populous province, during early 2020 resulted in 1,388 reported RNA-positive cases from 1.6 million tests. In order to understand the molecular epidemiology and genetic diversity of SARS-CoV-2 in China, we generated 53 genomes from infected individuals in Guangdong using a combination of metagenomic sequencing and tiling amplicon approaches. Combined epidemiological and phylogenetic analyses indicate multiple independent introductions to Guangdong, although phylogenetic clustering is uncertain because of low virus genetic variation early in the pandemic. Our results illustrate how the timing, size, and duration of putative local transmission chains were constrained by national travel restrictions and by the province's large-scale intensive surveillance and intervention measures. Despite these successes, COVID-19 surveillance in Guangdong is still required, because the number of cases imported from other countries has increased.


Asunto(s)
Betacoronavirus/genética , Infecciones por Coronavirus/epidemiología , Neumonía Viral/epidemiología , Teorema de Bayes , COVID-19 , China/epidemiología , Infecciones por Coronavirus/virología , Monitoreo Epidemiológico , Humanos , Funciones de Verosimilitud , Pandemias , Neumonía Viral/virología , SARS-CoV-2 , Viaje
2.
BMC Genomics ; 25(1): 37, 2024 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-38184538

RESUMEN

BACKGROUND: Citrus is one of the most valuable fruits worldwide and an economic pillar industry in southern China. Nevertheless, it frequently suffers from undesirable environmental stresses during the growth cycle, which severely restricts the growth, development and yield of citrus. In plants, the growth-regulating factor (GRF) family of transcription factors (TF) is extensively distributed and plays an vital part in plant growth and development, hormone response, as well as stress adaptation. However, the systematic identification and functional analysis of GRF TFs in citrus have not been reported. RESULTS: Here, a genome-wide identification of GRF TFs was performed in Citrus sinensis, 9 members of CsGRFs were systematically identified and discovered to be scattered throughout 5 chromosomes. Subsequently, physical and chemical properties, phylogenetic relationships, structural characteristics, gene duplication events, collinearity and cis-elements of promoter were elaborately analyzed. In particular, the expression patterns of the CsGRF genes in response to multiple phytohormone and abiotic stress treatments were investigated. Predicated on this result, CsGRF04, which exhibited the most differential expression pattern under multiple phytohormone and abiotic stress treatments was screened out. Virus-induced gene silencing (VIGS) technology was utilized to obtain gene silenced plants for CsGRF04 successfully. After the three stress treatments of high salinity, low temperature and drought, the CsGRF04-VIGS lines showed significantly reduced resistance to high salinity and low temperature stresses, but extremely increased resistance to drought stress. CONCLUSIONS: Taken together, our findings systematically analyzed the genomic characterization of GRF family in Citrus sinensis, and excavated a CsGRF04 with potential functions under multiple abiotic stresses. Our study lay a foundation for further study on the function of CsGRFs in abiotic stress and hormone signaling response.


Asunto(s)
Citrus sinensis , Citrus , Citrus sinensis/genética , Filogenia , Reguladores del Crecimiento de las Plantas/farmacología , Péptidos y Proteínas de Señalización Intercelular , Hormonas
3.
Clin Immunol ; 265: 110296, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38914361

RESUMEN

Proliferative lupus nephritis (PLN) is a serious organ-threatening manifestation of systemic lupus erythematosus (SLE) that is associated with high mortality and renal failure. Here, we analyzed data from 1287 SLE patients with renal manifestations, including 780 of which were confirmed as proliferative or non-proliferative LN patients by renal biopsy, divided into a training cohort (547 patients) and a validation cohort (233 patients). By applying a least absolute shrinkage and selection operator (LASSO) regression approach combined with multivariate logistic regression analysis to build a nomogram for prediction of PLN that was then assessed by receiver operating characteristic (ROC) curves, calibration curves, and clinical decision curves (DCA) in both the training and validation cohorts. The area under the ROC curve (AUC) of the model in the training cohort was 0.921 (95% confidence interval (CI): 0.895-0.946), the AUC of internal validation in the training cohort was 0.909 and the AUC of external validation was 0.848 (95% CI: 0.796-0.900). The nomogram showed good performance as evaluated using calibration and DCA curves. Taken together, our results indicate that our nomogram that comprises 12 significantly relevant variables could be clinically valuable to prognosticate on the risk of PLN in SLE, so as to improve patient prognoses.


Asunto(s)
Lupus Eritematoso Sistémico , Nefritis Lúpica , Nomogramas , Humanos , Femenino , Masculino , Adulto , Lupus Eritematoso Sistémico/complicaciones , Riñón/patología , Curva ROC , Persona de Mediana Edad , Pronóstico , Adulto Joven , Estudios de Cohortes , Factores de Riesgo
4.
Antimicrob Agents Chemother ; : e0112624, 2024 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-39431818

RESUMEN

This study aims to describe the distribution characteristics of voriconazole (VRC) plasma trough concentrations (Ctrough) in patients with liver dysfunction, identify factors influencing VRC Ctrough, and provide recommendations for the use of VRC in this population. We retrospectively collected medical records of hospitalized patients with liver dysfunction who used VRC and underwent therapeutic drug monitoring (TDM) at the First Hospital of Changsha. The severity of liver dysfunction was assessed by the Child-Pugh (CP) score. Multiple linear regression was employed to explore factors affecting VRC Ctrough in these patients. A total of 147 Ctrough from 102 patients with liver dysfunction were analyzed. Patients were categorized into a control group (n = 40), CP-A (n = 39), CP-B (n = 11), and CP-C group (n = 12). The initial probability of target attainment of Ctrough was 70.6%, with 6.9% of patients obtaining subtherapeutic Ctrough and 22.5% obtaining supertherapeutic Ctrough. The initial Ctrough in CP-A and B were 5.05 (0.64-9.57) mg/L and 5.37 (0.26-10.01) mg/L, respectively, significantly higher than the control group (P = 0.021 and P = 0.010). The proportion of VRC Ctrough of >5.5 mg/L in CP-A and B was 33.3% and 45.5%, respectively. Multiple linear regression analysis revealed that factors such as age ≥70 years, CP class, C-reactive protein (CRP), and direct bilirubin were significantly related to the initial VRC Ctrough. Among all measurements, patients with severe inflammation (CRP >100 mg/L), aged ≥70 years, and albumin levels of <30 or <25 g/L had significantly higher VRC Ctrough. The treatment success rate of VRC was 69.6% (71 of 102), and the rate of VRC-related adverse drug reactions was 29.4% (30 of 102). The recommended half-maintenance dose may lead to elevated VRC Ctrough in patients with CP-A and CP-B. TDM is essential for patients with advanced age, severe infections, or hypoalbuminemia to prevent excessive VRC trough levels.

5.
Oncologist ; 29(9): e1120-e1131, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-38760956

RESUMEN

OBJECTIVE: Patients with radioiodine-refractory (RAIR) differentiated thyroid carcinoma (DTC; RAIR-DTC) have a poor prognosis. The aim of this study was to provide new insights and possibilities for the diagnosis and treatment of RAIR-DTC. METHODS: The metabolomics of 24 RAIR-DTC and 18 non-radioiodine-refractory (NonRAIR) DTC patients samples were analyzed by liquid chromatograph-mass spectrometry. Cellular radioiodine uptake was detected with γ counter. Sodium iodide symporter (NIS) expression and thyroid stimulating hormone receptor (TSHR) were measured by Western blot analysis. CCK8 and colony formation assays were used to measure cellular proliferation. Scratch and transwell assays were performed to assess cell migration and invasion. Annexin V/PI staining was used to detect cell apoptosis. Cell growth in vivo was evaluated by a tumor xenograft model. The acetoacetate (AcAc) level was measured by ELISA. Pathological changes, Ki67, NIS, and TSHR expression were investigated by immunohistochemistry. RESULTS: The metabolite profiles of RAIR could be distinguished from those of NonRAIR, with AcAc significantly lower in RAIR. The significantly different metabolic pathway was ketone body metabolism. AcAc increased NIS and TSHR expression and improved radioiodine uptake. AcAc inhibited cell proliferation, migration, and invasion, and as well promoted cell apoptosis. Ketogenic diet (KD) elevated AcAc levels and significantly suppressed tumor growth, as well as improved NIS and TSHR expression. CONCLUSION: Significant metabolic differences were observed between RAIR and NonRAIR, and ketone body metabolism might play an important role in RAIR-DTC. AcAc improved cellular iodine uptake and had antitumor effects for thyroid carcinoma. KD might be a new therapeutic strategy for RAIR-DTC.


Asunto(s)
Dieta Cetogénica , Metabolómica , Neoplasias de la Tiroides , Humanos , Neoplasias de la Tiroides/dietoterapia , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/radioterapia , Neoplasias de la Tiroides/metabolismo , Dieta Cetogénica/métodos , Animales , Metabolómica/métodos , Femenino , Masculino , Ratones , Proliferación Celular , Radioisótopos de Yodo/uso terapéutico , Persona de Mediana Edad , Apoptosis , Simportadores/metabolismo , Adulto , Línea Celular Tumoral , Movimiento Celular
6.
Anal Chem ; 96(24): 9917-9926, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38837181

RESUMEN

Two-dimensional (2D) materials have been extensively implemented as surface-enhanced Raman scattering (SERS) substrates, enabling trace-molecule detection for broad applications. However, the accurate understanding of the mechanism remains elusive because most theoretical explanations are still phenomenological or qualitative based on simplified models and rough assumptions. To advance the development of 2D material-assisted SERS, it is vital to attain a comprehensive understanding of the enhancement mechanism and a quantitative assessment of the enhancement performance. Here, the microscopic chemical mechanism of 2D material-assisted SERS is quantitatively investigated. The frequency-dependent Raman scattering cross sections suggest that the 2D materials' SERS performance is strongly dependent on the excitation wavelengths and the molecule types. By analysis of the microscopic Raman scattering processes, the comprehensive contributions of SERS can be revealed. Beyond the widely postulated charge transfer mechanisms, the quantitative results conclusively demonstrate that the resonant transitions within 2D materials alone are also capable of enhancing the molecular Raman scattering through the diffusive scattering of phonons. Furthermore, all of these scattering routines will interfere with each other and determine the final SERS performance. Our results not only provide a complete picture of the SERS mechanisms but also demonstrate a systematic and quantitative approach to theoretically understand, predict, and promote the 2D materials SERS toward analytical applications.

7.
Cancer Cell Int ; 24(1): 6, 2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-38172873

RESUMEN

BACKGROUND: Gastric cancer at different locations has distinct prognoses and biological behaviors, but the specific mechanism is unclear. METHODS: Non-targeted metabolomics was performed to examine the differential metabolite phenotypes that may be associated with the effects of tumor location on the prognosis of gastric cancer. And silencing of the rate-limiting enzyme to evaluate the effect of abnormal changes in metabolic pathway on the functional biological assays of gastric cancer cells HGC-27 and MKN28. RESULTS: In a retrospective study of 94 gastric cancer patients, the average survival time of patients with gastric cancer in the middle third of the stomach was significantly lower than that of patients with gastric cancer in other locations (p < 0.05). The middle third location was also found to be an independent risk factor for poor prognosis (HR = 2.723, 95%CI 1.334-5.520), which was closely associated with larger tumors in this location. Non-targeted metabolomic analysis showed that the differential metabolites affected 16 signaling pathways including arginine synthesis, retrograde endocannabinoid signaling, arginine biosynthesis, and alanine and aspartate and glutamate metabolism between gastric cancer and normal tissue, as well as between tumors located in the middle third of the stomach and other locations. Argininosuccinate synthetase 1 (ASS1), the rate-limiting enzyme of the arginine biosynthesis pathway, catalyzes the production of argininosuccinic acid. Here, knockdown of ASS1 significantly inhibited the proliferation, colony formation, and migration/invasion of gastric cancer cells, and promoted apoptosis. CONCLUSIONS: Our study suggests that abnormal arginine synthesis may lead to larger tumor size and worse prognosis in gastric cancer located in the middle third position of the stomach. These findings may provide the basis for the stratification and targeted treatment of gastric cancer in different locations.

8.
BMC Cancer ; 24(1): 1184, 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39334028

RESUMEN

INTRODUCTION: This study analyzed and discussed the characteristics of peripheral blood lymphocytes (PBLs) in patients with endometrial carcinoma (EC) to explore the PBLs' clinical application value. METHODS: This single-center case‒control study analyzed the clinical data of patients with EC and uterine fibroids who underwent surgery at the First Affiliated Hospital of Chongqing Medical University between October 2018 and October 2023 retrospectively. The Center for Clinical Molecular Medical Detection of our hospital performed PBLs detection using flow cytometry, and recorded the detection results in the electronic medical records system. Between-group and subgroup comparisons of PBLs in patients with EC were analyzed using t-test or Mann-Whitney U test. The effect of surgery on PBLs in patients with EC was assessed using a paired t-test or the Wilcoxon signed rank test. RESULTS: The immune function of patients with EC was significantly lower than that of healthy people (P < 0.05) and those with benign uterine diseases (P < 0.05) and was related to body mass index (BMI), hypertension, diabetes, and blood lipids (P < 0.05). In patients with EC, the PBLs counts decreased significantly after surgery (P < 0.05) and more kinds of lymphocytes were affected in the laparoscopic surgery group than in the open surgery group. CONCLUSIONS: With the decrease of PBLs counts, the immune status of patients with EC is impaired. Metabolic syndrome (Mets), including obesity, hypertension, diabetes, and high blood lipids, also affects the immune function of patients with EC. And for EC patients, the effect of laparoscopic surgery is greater than that of open surgery. PBLs has the potential to be one of indicator during the diagnosis and treatment of EC. TRIAL REGISTRATION: This study was retrospectively registered by the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University (approval number K2023-578).


Asunto(s)
Neoplasias Endometriales , Linfocitos , Humanos , Femenino , Neoplasias Endometriales/sangre , Neoplasias Endometriales/cirugía , Neoplasias Endometriales/patología , Persona de Mediana Edad , Estudios de Casos y Controles , Estudios Retrospectivos , Adulto , Recuento de Linfocitos , Anciano , Citometría de Flujo , Leiomioma/sangre , Leiomioma/cirugía , Leiomioma/patología , Laparoscopía , Índice de Masa Corporal
9.
Appl Microbiol Biotechnol ; 108(1): 170, 2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38265689

RESUMEN

The deep-sea environment is an extremely difficult habitat for microorganisms to survive in due to its intense hydrostatic pressure. However, the mechanisms by which these organisms adapt to such extreme conditions remain poorly understood. In this study, we investigated the metabolic adaptations of Microbacterium sediminis YLB-01, a cold and stress-tolerant microorganism isolated from deep-sea sediments, in response to high-pressure conditions. YLB-01 cells were cultured at normal atmospheric pressure and 28 ℃ until they reached the stationary growth phase. Subsequently, the cells were exposed to either normal pressure or high pressure (30 MPa) at 4 ℃ for 7 days. Using NMR-based metabolomic and proteomic analyses of YLB-01 cells exposed to high-pressure conditions, we observed significant metabolic changes in several metabolic pathways, including amino acid, carbohydrate, and lipid metabolism. In particular, the high-pressure treatment stimulates cell division and triggers the accumulation of UDP-glucose, a critical factor in cell wall formation. This finding highlights the adaptive strategies used by YLB-01 cells to survive in the challenging high-pressure environments of the deep sea. Specifically, we discovered that YLB-01 cells regulate amino acid metabolism, promote carbohydrate metabolism, enhance cell wall synthesis, and improve cell membrane fluidity in response to high pressure. These adaptive mechanisms play essential roles in supporting the survival and growth of YLB-01 in high-pressure conditions. Our study offers valuable insights into the molecular mechanisms underlying the metabolic adaptation of deep-sea microorganisms to high-pressure environments. KEY POINTS: • NMR-based metabolomic and proteomic analyses were conducted on Microbacterium sediminis YLB-01 to investigate the significant alterations in several metabolic pathways in response to high-pressure treatment. • YLB-01 cells used adaptive strategies (such as regulated amino acid metabolism, promoted carbohydrate metabolism, enhanced cell wall synthesis, and improved cell membrane fluidity) to survive in the challenging high-pressure environment of the deep sea. • High-pressure treatment stimulated cell division and triggered the accumulation of UDP-glucose, a critical factor in cell wall formation, in Microbacterium sediminis YLB-01 cells.


Asunto(s)
Actinomycetales , Proteómica , Aminoácidos , Glucosa , Uridina Difosfato , Microbacterium
10.
Ultrason Imaging ; 46(6): 312-319, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39189365

RESUMEN

Sm-doped Pb(Mg1/3Nb2/3)O3-0.28PbTiO3 (PMN-0.28PT) ceramic has been reported to exhibit very large piezoelectric response (d33~1300 pC/N) that can be comparable with PMN-0.30PT single crystal. Based on the Sm-doped PMN-0.28PT ceramics, a high frequency ultrasound transducer with the center frequency above 30 MHz has been designed and fabricated for intravascular ultrasound imaging, and the performance of the transducer was investigated via ultrasound pulse-echo tests. Further, for a porcine vessel wall, the 2D and 3D ultrasound images were constructed using signal acquisition and processing from the fabricated high-frequency transducer. The obtained details of the vessel wall by the IVUS transducer indicate that Sm-doped PMN-0.28PT ceramic is a promising candidate for high frequency transducers.


Asunto(s)
Cerámica , Diseño de Equipo , Plomo , Transductores , Ultrasonografía Intervencional , Porcinos , Animales , Ultrasonografía Intervencional/métodos , Titanio , Imagenología Tridimensional/métodos
11.
J Environ Manage ; 370: 122911, 2024 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-39405891

RESUMEN

River water quality continues to deteriorate under the coupled effects of climate change and human activities. Machine learning (ML) is a promising approach for analyzing water quality. Nevertheless, the spatiotemporal dynamics of river water quality and their potential mechanisms in changing environments remain incomprehensively understood through available ML-based researches. Here, we developed a ML-based framework integrating a self-organizing map (SOM) model with a random forest (RF) model. This framework was applied to simultaneously investigate the spatiotemporal patterns and potential drivers of river permanganate (CODMn), ammonia nitrogen (NH3-N), and total phosphorus (TP) dynamics across 34 sites from 2010 to 2020 in a coastal city threatened by deteriorating water environment in southeastern China. The sites were divided into two clusters in the spatial context with different water quality conditions. The year of 2015 for NH3-N and 2018 for CODMn and TP were identified as the key turning points of water quality variations. Features including sewage discharge, population dynamics, percentage of cultivated land, and fertilizer application contributed greatly to water quality deterioration. The increase in forest vegetation reflected by percentage of forest and leaf area index may improve water quality. The ML-based modeling framework demonstrated a promising way to address the spatiotemporal dynamics of river water quality, and provided insights for water management in a coastal city with intensifying human-nature interactions.

12.
Geriatr Nurs ; 55: 79-88, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37976559

RESUMEN

OBJECTIVE: The study investigates the impact of preoperative rehabilitation on the surgical prognosis of frail older patients. METHOD: The effect sizes of all studies retrieved and included by the nine databases were analyzed and expressed as RR and WMD. RESULTS: 8 studies with 902 participants met the criteria for inclusion. A significant reduction in total complications (RR = 0.84, 95 % CI = 0.73 to 0.97, P = 0.021) and the 6MWT after surgery (WMD = 74.76, 95 % CI = 44.75 to 104.77, P = 0.000) was observed in the prehabilitation group. But it had no differences in mortality(RR = 1.89, 95 % CI = 0.75 to 4.72, P = 0.176), readmission rates(RR = 1.04, 95 % CI = 0.56 to 1.91, P = 0.906) and LOS(WMD = -0.24, 95 % CI = -1.00 to 0.52, P = 0.540). CONCLUSIONS: Prehabilitation had positive effect on postoperative complications and functional recovery in frail older patients.


Asunto(s)
Anciano Frágil , Ejercicio Preoperatorio , Humanos , Anciano , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Pronóstico , Recuperación de la Función
13.
Geriatr Nurs ; 59: 581-589, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39154507

RESUMEN

AIMS: To systematically evaluate the predictive efficacy of clinical frailty scale (CFS) for postoperative mortality older surgical patients, and to evaluate the prevalence of frailty in the included studies. DESIGN: A systematic review and meta-analysis of observational studies was conducted, utilizing the MOOSE guidelines for the evaluation of both. Quality assessment of the articles was also performed. DATA SOURCES: The protocol was registered (CRD42023423552). Relevant English and Chinese language studies published until October 20th, 2023 were retrieved from PubMed, Web of Science, Embase, Medline, CINAHL,Cochrane, WAN FANG DATA, VIP Information, CNKI, and SinoMed databases. REVIEW METHODS: Study were included in which frailty was measured by the CFS and postoperative mortality was reported for older surgery patients. A meta-analysis to predict postoperative mortality and frailty prevalence was performed using STATA 17.0 software. RESULTS: Sixteen cohort studies were included (5,864 participants) from 1,513 records. All studies' Newcastle-Ottawa Scale (NOS) scores were above 6 points. It was found that the prevalence of surgical frailty in the older was 0.36(CI 0.20-0.52). Patients assessed as frail by the CFS were associated with higher all-cause mortality (OR:4.01; CI 2.59-6.23). Subgroup analysis shows that frailty was associated with1-month mortality (OR:3.85; CI 1.11-13.45) and 1-year mortality (OR:4.43; CI 2.18-8.99). CONCLUSIONS: The prevalence of frailty is high in older surgical patients, and CFS can effectively predict the mortality of older surgical patients with frailty.


Asunto(s)
Fragilidad , Anciano , Humanos , Anciano Frágil/estadística & datos numéricos , Fragilidad/diagnóstico , Fragilidad/epidemiología , Evaluación Geriátrica , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/mortalidad , Periodo Posoperatorio , Prevalencia
14.
J Infect Dis ; 228(10): 1375-1384, 2023 11 11.
Artículo en Inglés | MEDLINE | ID: mdl-37170968

RESUMEN

BACKGROUND: The impact of hepatitis B surface antigen (HBsAg)-negative/hepatitis B virus (HBV) DNA-positive occult HBV infection (OBI) on the severity of liver fibrosis remains unclear. METHODS: A total of 1772 patients negative for HBsAg but positive for antibody to hepatitis B core antigen (HBcAg), stratified by the presence or absence of OBI, were selected for long-term carriage leading to elevation of ≥2 of 4 liver fibrosis indexes-hyaluronic acid (HA), laminin, type III procollagen peptide (PCIII), and type IV collagen (CIV)-at testing in a Chinese hospital. Patients were tested for serum viral load, HBV markers, and histopathological changes in liver biopsy specimens. RESULTS: OBI was identified in 148 patients with liver fibrosis (8.4%), who had significantly higher levels of HA, laminin, PCIII, and CIV than 1624 fibrotic patients without OBI (P < .05). In 36 patients with OBI who underwent liver biopsy, significant correlations were observed between OBI viral load and serum HA levels (P = .01), PCIII levels (P = .01), and pathological histological activity index (HAI) scores (P < .001), respectively; HAI scores and PCIII levels (P = .04); HBcAg immunohistochemical scores and HA levels (P < .001); and HBcAg immunohistochemical scores and PCIII levels (P = .03). Positive fluorescent in situ hybridization results were significantly more frequent in patients with OBIs (80.6% vs 37.5% in those without OBIs). Among patients with OBIs, HBcAg was detected in the liver tissue in 52.8% and HBsAg in 5.6%. CONCLUSIONS: OBI status appears to be associated with liver fibrosis severity.


Asunto(s)
Hepatitis B Crónica , Hepatitis B , Humanos , Virus de la Hepatitis B , Antígenos de Superficie de la Hepatitis B , Antígenos del Núcleo de la Hepatitis B , Laminina , Hibridación Fluorescente in Situ , Hepatitis B/complicaciones , Cirrosis Hepática/patología , Ácido Hialurónico
15.
Kidney Int ; 104(4): 769-786, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37482091

RESUMEN

Tubulointerstitial fibrosis is considered the final convergent pathway of progressive chronic kidney diseases (CKD) regardless of etiology. However, mechanisms underlying kidney injury-induced fibrosis largely remain unknown. Recent studies have indicated that transcriptional intermediary factor 1γ (TIF1γ) inhibits the progression of fibrosis in other organs. Here, we found that TIF1γ was highly expressed in the cytoplasm and nucleus of the kidney proximal tubule. Interestingly, we found tubular TIF1γ expression was decreased in patients with CKD, including those with diabetes, hypertension, and IgA nephropathy, and in mouse models with experimental kidney fibrosis (unilateral ureteral obstruction [UUO], folic acid nephropathy [FAN], and aristolochic acid-induced nephrotoxicity). Tubule-specific knock out of TIF1γ in mice exacerbated UUO- and FAN-induced tubular cell polyploidy and subsequent fibrosis, whereas overexpression of kidney TIF1γ protected mice against kidney fibrosis. Mechanistically, in tubular epithelial cells, TIF1γ exerted an antifibrotic role via transforming growth factor-ß (TGF-ß)-dependent and -independent signaling. TIF1γ hindered TGF-ß signaling directly by inhibiting the formation and activity of the transcription factor Smad complex in tubular cells, and we discovered that TIF1γ suppressed epidermal growth factor receptor (EGFR) signaling upstream of TGF-ß signaling in tubular cells by ubiquitylating EGFR at its lysine 851/905 sites thereby promoting EGFR internalization and lysosomal degradation. Pharmacological inhibition of EGFR signaling attenuated exacerbated polyploidization and the fibrotic phenotype in mice with tubule deletion of TIF1γ. Thus, tubular TIF1γ plays an important role in kidney fibrosis by suppressing profibrotic EGFR and TGF-ß signaling. Hence, our findings suggest that maintaining homeostasis of tubular TIF1γ may be a new therapeutic option for treating tubulointerstitial fibrosis and subsequent CKD.


Asunto(s)
Insuficiencia Renal Crónica , Obstrucción Ureteral , Animales , Humanos , Ratones , Células Epiteliales/metabolismo , Receptores ErbB/genética , Fibrosis , Riñón/metabolismo , Análisis de Mediación , Insuficiencia Renal Crónica/genética , Insuficiencia Renal Crónica/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Obstrucción Ureteral/complicaciones , Obstrucción Ureteral/genética , Obstrucción Ureteral/metabolismo
16.
Brief Bioinform ; 22(5)2021 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-33866367

RESUMEN

Although synonymous mutations do not alter the encoded amino acids, they may impact protein function by interfering with the regulation of RNA splicing or altering transcript splicing. New progress on next-generation sequencing technologies has put the exploration of synonymous mutations at the forefront of precision medicine. Several approaches have been proposed for predicting the deleterious synonymous mutations specifically, but their performance is limited by imbalance of the positive and negative samples. In this study, we firstly expanded the number of samples greatly from various data sources and compared six undersampling strategies to solve the problem of the imbalanced datasets. The results suggested that cluster centroid is the most effective scheme. Secondly, we presented a computational model, undersampling scheme based method for deleterious synonymous mutation (usDSM) prediction, using 14-dimensional biology features and random forest classifier to detect the deleterious synonymous mutation. The results on the test datasets indicated that the proposed usDSM model can attain superior performance in comparison with other state-of-the-art machine learning methods. Lastly, we found that the deep learning model did not play a substantial role in deleterious synonymous mutation prediction through a lot of experiments, although it achieves superior results in other fields. In conclusion, we hope our work will contribute to the future development of computational methods for a more accurate prediction of the deleterious effect of human synonymous mutation. The web server of usDSM is freely accessible at http://usdsm.xialab.info/.


Asunto(s)
Algoritmos , Biología Computacional/métodos , Aprendizaje Automático , Modelos Genéticos , Proteínas/genética , Mutación Silenciosa , Humanos , Proteínas/química , Reproducibilidad de los Resultados
17.
Nanotechnology ; 35(5)2023 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-37879318

RESUMEN

Achieving high sensitivity in gas sensors is crucial for the precise detection of toxic agents. However, this can be challenging as it requires gas sensors to possess both a high response signal and low electrical noise simultaneously, which seems controversial as it necessitates adopting semiconductors with different bandgaps. Herein, we demonstrate the superior sensitivity of 2D molybdenum disulfide (MoS2)/tellurium (Te) van der Waals heterostructure (vdWH) gas sensors fabricated by combining narrow-bandgap (Te) and wide-bandgap (MoS2) semiconductors. The as-fabricated MoS2/Te vdWH gas sensors exhibit excellent sensitivity that is unavailable for sensors based on its individual counterparts. The response toward 50 ppm NH3is improved by two and six times compared to the individual MoS2and Te gas sensors, respectively. In addition, a high signal-to-noise ratio of ∼350 and an ultralow limit of detection of ∼2 ppb are achieved. These results outperform most previously reported gas sensors due to the efficient modulation of the barrier height of the MoS2/Te p-n junction as well as the synergistic effect benefiting from the low electric noise of the narrow-bandgap Te and high response signal of the wide-bandgap MoS2. Our work provides an insight into utilizing vdWHs based on narrow-wide bandgap semiconductors for developing highly sensitive gas sensors.

18.
Environ Sci Technol ; 57(10): 4253-4265, 2023 03 14.
Artículo en Inglés | MEDLINE | ID: mdl-36862939

RESUMEN

Bacterial communication plays an important role in coordinating microbial behaviors in a community. However, how bacterial communication organizes the entire community for anaerobes to cope with varied anaerobic-aerobic conditions remains unclear. We constructed a local bacterial communication gene (BCG) database comprising 19 BCG subtypes and 20279 protein sequences. BCGs in anammox-partial nitrification consortia coping with intermittent aerobic and anaerobic conditions as well as gene expressions of 19 species were inspected. We found that when suffering oxygen changes, intra- and interspecific communication by a diffusible signal factor (DSF) and bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) changed first, which in turn induced changes of autoinducer-2 (AI-2)-based interspecific and acyl homoserine lactone (AHLs)-based intraspecific communication. DSF and c-di-GMP-based communication regulated 455 genes, which covered 13.64% of the genomes and were mainly involved in antioxidation and metabolite residue degradation. For anammox bacteria, oxygen influenced DSF and c-di-GMP-based communication through RpfR to upregulate antioxidant proteins, oxidative damage-repairing proteins, peptidases, and carbohydrate-active enzymes, which benefited their adaptation to oxygen changes. Meanwhile, other bacteria also enhanced DSF and c-di-GMP-based communication by synthesizing DSF, which helped anammox bacteria survive at aerobic conditions. This study evidences the role of bacterial communication as an "organizer" within consortia to cope with environmental changes and sheds light on understanding bacterial behaviors from the perspective of sociomicrobiology.


Asunto(s)
Proteínas Bacterianas , Bacterias/genética , Bacterias/metabolismo , Proteínas Bacterianas/genética , GMP Cíclico/metabolismo
19.
Genet Sel Evol ; 55(1): 43, 2023 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-37386365

RESUMEN

BACKGROUND: Currently, meat cut traits are integrated in pig breeding objectives to gain extra profit. However, little is known about the heritability of meat cut proportions (MCP) and their correlations with other traits. The aims of this study were to assess the heritability and genetic correlation of MCP with carcass and meat quality traits using single nucleotide polymorphism chips and conduct a genome-wide association study (GWAS) to identify candidate genes for MCP. RESULTS: Seventeen MCP, 12 carcass, and seven meat quality traits were measured in 2012 pigs from four populations (Landrace; Yorkshire; Landrace and Yorkshire hybrid pigs; Duroc, and Landrace and Yorkshire hybrid pigs). Estimates of the heritability for MCP ranged from 0.10 to 0.55, with most estimates being moderate to high and highly consistent across populations. In the combined population, the heritability estimates for the proportions of scapula bone, loin, back fat, leg bones, and boneless picnic shoulder were 0.44 ± 0.04, 0.36 ± 0.04, 0.44 ± 0.04, 0.38 ± 0.04, and 0.39 ± 0.04, respectively. Proportion of middle cuts was genetically significantly positively correlated with intramuscular fat content and backfat depth. Proportion of ribs was genetically positively correlated with carcass oblique length and straight length (0.35 ± 0.08 to 0.45 ± 0.07) and negatively correlated with backfat depth (- 0.26 ± 0.10 to - 0.45 ± 0.10). However, weak or nonsignificant genetic correlations were observed between most MCP, indicating their independence. Twenty-eight quantitative trait loci (QTL) for MCP were detected by GWAS, and 24 new candidate genes related to MCP were identified, which are involved with growth, height, and skeletal development. Most importantly, we found that the development of the bones in different parts of the body may be regulated by different genes, among which HMGA1 may be the strongest candidate gene affecting forelimb bone development. Moreover, as previously shown, VRTN is a causal gene affecting vertebra number, and BMP2 may be the strongest candidate gene affecting hindlimb bone development. CONCLUSIONS: Our results indicate that breeding programs for MCP have the potential to enhance carcass composition by increasing the proportion of expensive cuts and decreasing the proportion of inexpensive cuts. Since MCP are post-slaughter traits, the QTL and candidate genes related to these traits can be used for marker-assisted and genomic selection.


Asunto(s)
Carne Roja , Porcinos , Animales , Porcinos/genética , Genotipo , Estudio de Asociación del Genoma Completo , Calidad de los Alimentos , Sitios de Carácter Cuantitativo
20.
Phys Chem Chem Phys ; 25(11): 7711-7718, 2023 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-36876861

RESUMEN

Optical microscopy with a diffraction limit cannot distinguish nanowires with sectional dimensions close to or smaller than the optical resolution. Here, we propose a scheme to retrieve the subwavelength cross-section of nanowires based on the asymmetric excitation of Bloch surface waves (BSWs). Leakage radiation microscopy is used to observe the propagation of BSWs at the surface and to collect far-field scattering patterns in the substrate. A model of linear dipoles induced by tilted incident light is built to explain the directional imbalance of BSWs. It shows the potential capability in precisely resolving the subwavelength cross-section of nanowires from far-field scattering without the need for complex algorithms. Through comparing the nanowire widths measured by this method and those measured by scanning electron microscopy (SEM), the transverse resolutions of the widths of two series of nanowires with heights 55 nm and 80 nm are about 4.38 nm and 6.83 nm. All results in this work demonstrate that the new non-resonant far-field optical technology has potential application in metrology measurements with high precision by taking care of the inverse process of light-matter interaction.

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