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1.
Mol Ther Methods Clin Dev ; 27: 431-449, 2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36419469

RESUMO

With the aim of expediting drug target discovery and validation for respiratory diseases, we developed an optimized method for in situ somatic gene disruption in murine lung epithelial cells via AAV6-mediated CRISPR-Cas9 delivery. Efficient gene editing was observed in lung type II alveolar epithelial cells and distal airway cells following assessment of single- or dual-guide AAV vector formats, Cas9 variants, and a sequential dosing strategy with combinatorial guide RNA expression cassettes. In particular, we were able to demonstrate population-wide gene disruption within distinct epithelial cell types for separate targets in Cas9 transgenic animals, with minimal to no associated inflammation. We also observed and characterized AAV vector integration events that occurred within directed double-stranded DNA break sites in lung cells, highlighting a complicating factor with AAV-mediated delivery of DNA nucleases. Taken together, we demonstrate a uniquely effective approach for somatic engineering of the murine lung, which will greatly facilitate the modeling of disease and therapeutic intervention.

2.
Opt Lett ; 47(18): 4786-4789, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36107090

RESUMO

In this work, an ultra-low loss silicon nitride (SiN) edge coupler was designed and fabricated to interface with a single-mode fiber (SMF). Unlike other works that focus on the core structure, this work focuses on the cladding structure. First, it is demonstrated that the cladding structure ultimately determines the size and shape of the mode when the taper tip width is small enough. Then, the thickness of the up-cladding is optimized to provide enough space for mode expansion in the vertical direction. Air trenches are added to confine the mode laterally. In addition, the refractive index (RI) of the up-cladding layer is slightly increased to prevent light from leaking into the Si substrate. This edge coupler is then fabricated on the SiN platform at Chongqing United Microelectronics Center. For the TE mode at 1630 nm, a coupling loss of 0.67 dB/facet was obtained. At 1550 nm, 0.85 dB/facet and 1.09 dB/facet were measured for the TE and TM modes, respectively, which means that the polarization-dependent loss is 0.24 dB. Although the design method and the structure are based on a pure SiN platform, they are applicable to a silicon-on-insulator platform as well.

3.
Sci Transl Med ; 14(663): eabo5959, 2022 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-36130016

RESUMO

ESR1 (estrogen receptor 1) hotspot mutations are major contributors to therapeutic resistance in estrogen receptor-positive (ER+) breast cancer. Such mutations confer estrogen independence to ERα, providing a selective advantage in the presence of estrogen-depleting aromatase inhibitors. In addition, ESR1 mutations reduce the potency of tamoxifen and fulvestrant, therapies that bind ERα directly. These limitations, together with additional liabilities, inspired the development of the next generation of ERα-targeted therapeutics, of which giredestrant is a high-potential candidate. Here, we generated Esr1 mutant-expressing mammary gland models and leveraged patient-derived xenografts (PDXs) to investigate the biological properties of the ESR1 mutations and their sensitivity to giredestrant in vivo. In the mouse mammary gland, Esr1 mutations promote hypersensitivity to progesterone, triggering pregnancy-like tissue remodeling and profoundly elevated proliferation. These effects were driven by an altered progesterone transcriptional response and underpinned by gained sites of ERα-PR (progesterone receptor) cobinding at the promoter regions of pro-proliferation genes. PDX experiments showed that the mutant ERα-PR proliferative program is also relevant in human cancer cells. Giredestrant suppressed the mutant ERα-PR proliferation in the mammary gland more so than the standard-of-care agents, tamoxifen and fulvestrant. Giredestrant was also efficacious against the progesterone-stimulated growth of ESR1 mutant PDX models. In addition, giredestrant demonstrated activity against a molecularly characterized ESR1 mutant tumor from a patient enrolled in a phase 1 clinical trial. Together, these data suggest that mutant ERα can collaborate with PR to drive protumorigenic proliferation but remain sensitive to inhibition by giredestrant.


Assuntos
Neoplasias da Mama , Receptor alfa de Estrogênio , Animais , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carbolinas , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Estrogênios , Feminino , Fulvestranto/farmacologia , Fulvestranto/uso terapêutico , Humanos , Camundongos , Mutação/genética , Progesterona/farmacologia , Receptores de Estrogênio/genética , Receptores de Progesterona/genética , Receptores de Progesterona/uso terapêutico , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico
4.
Molecules ; 27(16)2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-36014538

RESUMO

Oxyfunctionalization of toluene to value-added benzaldehyde, benzyl alcohol and benzoic acid is of great significance. In this work, Co-Schiff bases were immobilized on commercial silica gel by covalent anchoring, and resulting catalysts were used to catalyze the oxidation of toluene in the presence of the cocatalyst N-hydroxyphthalimide (NHPI). The catalysts exhibited excellent textural and structural properties, reliable bonding and a predomination of the cobaltous ions. The catalyst synthesized by diethylamino salicylaldehyde (EASA) possessed a grafting density of 0.14 mmol/g and exhibited a toluene conversion of 37.5%, with predominant selectivities to benzaldehyde, benzyl alcohol and benzoic acid under solvent-free conditions. It is concluded that the effect of ligands on their catalytic performance might be related to their electron-donating or -withdrawing properties.


Assuntos
Bases de Schiff , Tolueno , Benzaldeídos , Ácido Benzoico/química , Álcool Benzílico/química , Tolueno/química
5.
Front Oncol ; 12: 913731, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36016629

RESUMO

Background: Inflammation, immunity, and nutrition status play important roles in tumorigenesis, progression, and metastasis. This study aimed to evaluate the prognostic value of Inflammation-Immunity-Nutrition Score (IINS) for overall survival (OS) and progression-free survival (PFS) in patients with hepatocellular carcinoma (HCC) undergoing radical surgery. Methods: A total of 204 HCC patients who met the criteria were included in this retrospective study: 144 in the prediction model and 60 in the validation model. IINS was constructed based on the sum of classification scores of preoperative high-sensitivity C-reactive protein (hsCRP), lymphocyte (LYM), and albumin (ALB). The associations between the IINS group and the clinicopathologic characteristics were analyzed using Pearson's χ2 test or Fisher's exact test. Multivariate Cox regression analysis was used to evaluate variables significant on univariate analysis. Kaplan-Meier survival curves were conducted to investigate the prognostic values of IINS, Alpha-fetoprotein (AFP) and IINS-AFP classification. The prognostic performances of all the potential prognostic factors were further compared by receiver operating characteristic (ROC) curve, and time-dependent ROC curve. The internal validation and external validation were used to ensure the credibility of this prediction model. Results: The patients were divided into low and high IINS groups according to the median of IINS. According to multivariate Cox regression analyses, the Barcelona Clinic Liver Cancer (BCLC) Stage (P=0.003), AFP (P=0.013), and IINS (P=0.028) were independent prognostic factors for OS, and BCLC Stage (P=0.009), microvascular invasion (P=0.030), and IINS (P=0.031) were independent prognostic factors for PFS. High IINS group were associated with significantly worse OS and PFS compared with low IINS group (P<0.001; P=0.004). In terms of clinical prognosis, IINS-AFP classification was good in group I, moderate in group II, and poor in group III. Group I had a longer OS (P<0.001) and PFS (P=0.008) compared with group II and III. ROC analysis revealed that IINS-AFP classification had a better prognostic performance for OS (AUC: 0.767) and PFS (AUC: 0.641) than other predictors, excluding its slightly lower predictive power for PFS than IINS. The time-dependent ROC curves also showed that both IINS (12-month AUC: 0.650; 24-month AUC: 0.670; 36-month AUC: 0.880) and IINS-AFP classification (12-month AUC: 0.720; 24-month AUC: 0.760; 36-month AUC: 0.970) performed well in predicting OS for HCC patients. Furthermore, the internal validation and external validation proved that IINS had good predictive performance, strong internal validity and external applicability, and could be used to establish the prediction model. Conclusion: Inflammation-immunity-nutrition score could be a powerful clinical prognostic indicator in HCC patients undergoing radical surgery. Furthermore, IINS-AFP classification presents better prognostic performance than IINS or AFP alone, and might serve as a practical guidance to help patients adjust treatment and follow-up strategies to improve future outcomes.

6.
Ultrason Sonochem ; 88: 106092, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35878510

RESUMO

The sonoprocessing of droplet spreading during the wetting process of molten aluminum droplets on SiC ceramic substrates at 700 °C is investigated in this paper. When wetting is assisted by a 20 kHz frequency ultrasonic field, the wettability of liquid metal gets enhanced, which has been determined by the variations in thermodynamic energy and wetting kinetics. Wetting kinetic characteristics are divided into two stages according to pinning and depinning states of substrate/droplet contact lines. The droplet is static when the contact line is pinning, while it is forced to move when the contact line is depinning. When analyzing the pinning stage, high-speed photography reveals the evidence of oxide films being rapidly crushed outside the aluminum droplet. In this work, atomic models of spherical Al core being wrapped by alumina shell are tentatively built, whose dioxide microstructures are being transformed from face-centered cubic into liquid at the atomic scale. At the same time, the wetting experiment reveals that the oxide films show changes in the period of sonoprocessing from 3rd to 5th second. During the ultrasonic spreading behavior in the late stage, there is a trend of evident expansion of the base contact area. The entire ultrasonic process lasts for no longer than 10 s. With the aid of ultrasonic sinusoidal waves, the wettability of metal Al gets a rapid improvement. Both molecular dynamic (MD) investigations and the experiments results reveal that the precursor film phenomenon is never found unless wetting is assisted by ultrasonic treatments. However, the precursor film appears near the triple line after using ultrasonics in the droplet wetting process, whose formation is driven by ultrasonic oscillations. Due to the precursor film, the ultrasonic wetting contact angle is lower than the non-ultrasonic contact angle. In addition, the time-variant effective ultrasonic energy has been quantitatively evaluated. The numerical expressions of thermodynamic variables are well verified by former ultrasonic spreading test results, which altogether provide an intrinsic explanation of the fast-decreasing contact angle of Al/SiC.

7.
Int J Food Microbiol ; 378: 109824, 2022 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-35797894

RESUMO

Ultraviolet C (UVC) radiation is a widely used technology for the disinfection of surfaces, air flows, water and other liquids. Although extensive research has been conducted on the UV tolerance of bacteriophages used as surrogates for waterborne viruses, limited information is available on phages relevant to food processing. Phages of dairy starters may reach high numbers in dairy facilities and cause fermentation failure with great economic losses for the dairy industry. Here, the UV tolerance of virulent phages, belonging to the 936-group (Skunavirus) of Lactococcus lactis subsp. diacetylactis F7/2, was assessed, employing both host infectivity loss and qPCR assays. A highly heat-tolerant phage (P680) and a less heat-tolerant phage (P008) were exposed to UV radiation at 265 nm (UVC), 285 nm (UVB) and 365 nm (UVA), respectively, in an aqueous suspension, using UV Light-Emitting-Diodes (LEDs) in a static set-up. UVC at 265 nm achieved the highest total inactivation, leading to a 4 log10 reduction of the phage titer at a UV dose of 327 and 164 mJ/cm2 for P680 and P008, respectively. UVB at 285 nm achieved similar inactivation levels, while UVA at 365 nm did not cause major reductions. Phages were also suspended in yoghurt serum of pH 5.5 and pH 7.0 and exposed to UVC radiation at 265 nm. The heat-tolerant phage P680 was more UV tolerant for all wavelengths, matrices and pH values tested. A higher aggregation degree together with less DNA damage was observed for both phages at pH 5.5, especially for phage P680, indicating a UV light-shielding effect. Interestingly, there were indications of some phage survivors exhibiting higher UV tolerance on re-exposure, pointing out a need for further investigation. Our results show that UV LEDs emitting at 265 nm and 285 nm are efficient in reducing the phage population significantly, but also underline that 936-type phages are relatively UV resistant. A further understanding of the main factors influencing UV efficiency could enable future use of the UV technology as an alternative or complement to thermal treatment for phage inactivation.


Assuntos
Bacteriófagos , Lactococcus lactis , Siphoviridae , Bacteriófagos/genética , Desinfecção/métodos , Concentração de Íons de Hidrogênio , Raios Ultravioleta
8.
BMC Gastroenterol ; 22(1): 297, 2022 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35701742

RESUMO

BACKGROUND: A precise evaluation of liver reserve function in patients with hepatic alveolar echinococcosis (HAE) prior to hepatectomy could substantially increase the success rate of the operation and reduce the incidence of postoperative complications. The present study aimed to investigate the significance of the indocyanine green retention test at 15 min (ICG-R15) and the Albumin-Indocyanine Green Evaluation (ALICE) grading system in predicting severe posthepatectomy liver failure (PHLF) and postoperative mortality in HAE patients undergoing liver resection. METHODS: A total of 105 HAE patients undergoing hepatectomy were enrolled in this study. The value of each variable in predicting severe PHLF was evaluated by univariate and multivariate logistic regression analyses. The area under the receiver operating characteristic (ROC) curves (AUC) were calculated to evaluate the predictive ability of the Child-Pugh grade, ICG-R15, and ALICE grading system. Also, patients were classified using the optimal cutoff value for ICG-R15 and different ALICE grades, and the incidence of severe PHLF and postoperative mortality were compared with the predicted values. RESULTS: Out of the 105 HAE patients enrolled in this study, 34 patients (32.4%) developed severe PHLF. The ALICE grade and operative time were identified as independent predictors of severe PHLF. According to ROC analysis, the AUCs of the Child-Pugh grade, ICG-R15, and ALICE grade for predicting severe PHLF were 0.733 (95% confidence interval (CI), 0.637-0.814), 0.823 (95% CI, 0.737-0.891), 0.834 (95% CI, 0.749-0.900). The incidence of severe PHLF and postoperative 90-day mortality in patients with ICG-R15 > 7.2% were significantly higher than those with ICG-R15 ≤ 7.2% (P < 0.001; P = 0.008). Likewise, the incidence of severe PHLF and postoperative 90-day mortality in patients with ALICE grade 2 were higher than those with ALICE grade 1 within the Child-Pugh grade A (P < 0.001; P = 0.083). CONCLUSION: ICG-R15 and ALICE grading system are powerful predictors of severe PHLF and postoperative mortality among HAE patients undergoing hepatectomy. Furthermore, a combination of the preoperative Child-Pugh grade and ALICE grading system may provide an even more precise and objective guidance and facilitate surgical decision-making for HAE patients.


Assuntos
Carcinoma Hepatocelular , Equinococose Hepática , Falência Hepática , Neoplasias Hepáticas , Albuminas , Carcinoma Hepatocelular/complicações , Equinococose Hepática/cirurgia , Hepatectomia/efeitos adversos , Humanos , Verde de Indocianina , Falência Hepática/etiologia , Falência Hepática/cirurgia , Testes de Função Hepática , Neoplasias Hepáticas/cirurgia , Estudos Retrospectivos
9.
J Immunol ; 208(12): 2632-2642, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35675956

RESUMO

Genetic and environmental cues shape the evolution of the B cell Ig repertoire. Activation-induced cytidine deaminase (AID) is essential to generating Ig diversity through isotype class switching and somatic mutations, which then directly influence clonal selection. Impaired B cell development in AID-knockout mice has made it difficult to study Ig diversification in an aging repertoire. Therefore, in this report, we used a novel inducible AID-knockout mouse model and discovered that deleting AID in adult mice caused spontaneous germinal center formation. Deep sequencing of the IgH repertoire revealed that Ab diversification begins early in life and evolves over time. Our data suggest that activated B cells form germinal centers at steady state and facilitate continuous diversification of the B cell repertoire. In support, we identified shared B cell lineages that were class switched and showed age-dependent rates of mutation. Our data provide novel context to the genesis of the B cell repertoire that may benefit the understanding of autoimmunity and the strength of an immune response to infection.


Assuntos
Citidina Desaminase , Switching de Imunoglobulina , Animais , Linfócitos B , Citidina Desaminase/genética , Centro Germinativo , Switching de Imunoglobulina/genética , Camundongos , Camundongos Knockout , Hipermutação Somática de Imunoglobulina
10.
Front Genet ; 13: 848391, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35601487

RESUMO

Background: Pancreatic adenocarcinoma (PAAD) is among the most common types of cancer with a poor prognosis. Transmembrane protein 170B (TMEM170B) has been reported to suppress breast cancer proliferation, metastasis, and tumorigenesis and is related to prognosis. However, its role in PAAD and the underlying molecular mechanisms are yet to be investigated. Patients and methods: We performed a comprehensive analysis of RNA sequencing data obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases to determine TMEM170B expression. Immunostaining and real-time polymerase chain reaction (RT-PCR) were done to determine TMEM170B expression in human pancreatic cancer cell lines and tissue specimens. Furthermore, the correlation of TMEM170B with clinicopathological features and PAAD prognosis was investigated, and the mechanisms were explored through enrichment analysis and immune cell infiltration analysis. Results: TCGA and GEO dataset analysis revealed that TMEM170B expression in PAAD tissue samples was significantly lower than that in non-tumorous tissues, which was further confirmed by immunohistochemistry and RT-PCR. Low TMEM170B expression was associated with poor differentiation (p = 0.014). Multivariate analysis identified that TMEM170B is an independent indicator for overall survival [hazard ratio (HR) = 0.116, 95% confidence interval (CI) = 0.014-0.995; p = 0.049] and disease-free survival (HR = 0.19, 95% CI = 0.04-0.910; p = 0.038) in patients with PAAD. Additionally, TMEM170B was involved in immune-related gene sets, including those related to chemokine signaling pathways and innate and adaptive immunity. High TMEM170B expression was linked to antitumor immune microenvironment with a high infiltration of B cells, T cells, dendritic cells, monocytes, M1 macrophages, neutrophil, and natural killer cells and a low infiltration of Tregs and myeloid-derived suppressor cells (all p < 0.05). Plain Language Summary: There is an urgent need to identify clinical prognostic biomarkers and targeted drugs for pancreatic cancer treatment. In this study, the expression status and prognostic value of transmembrane protein 170B (TMEM170B) in pancreatic adenocarcinoma were elucidated. Furthermore, TMEM170B, as a tumor suppressor gene, induced antitumor immune effects, including increased tumor infiltration of immune effector cells and reduced levels of inhibitory immune molecules and regulatory cells. Therefore, TMEM170B could be regarded as a novel target in preventing the progression of pancreatic cancer. Conclusion: The findings suggest that low TMEM170B expression is remarkably correlated with poor PAAD prognosis, which might provide a therapeutic target for PAAD.

11.
Sci Transl Med ; 14(641): eabl8146, 2022 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-35442706

RESUMO

Asthma and inflammatory airway diseases restrict airflow in the lung, compromising gas exchange and lung function. Inhaled corticosteroids (ICSs) can reduce inflammation, control symptoms, and improve lung function; however, a growing number of patients with severe asthma do not benefit from ICS. Using bronchial airway epithelial brushings from patients with severe asthma or primary human cells, we delineated a corticosteroid-driven fibroblast growth factor (FGF)-dependent inflammatory axis, with FGF-responsive fibroblasts promoting downstream granulocyte colony-stimulating factor (G-CSF) production, hyaluronan secretion, and neutrophilic inflammation. Allergen challenge studies in mice demonstrate that the ICS, fluticasone propionate, inhibited type 2-driven eosinophilia but induced a concomitant increase in FGFs, G-CSF, hyaluronan, and neutrophil infiltration. We developed a model of steroid-induced neutrophilic inflammation mediated, in part, by induction of an FGF-dependent epithelial-mesenchymal axis, which may explain why some individuals do not benefit from ICS. In further proof-of-concept experiments, we found that combination therapy with pan-FGF receptor inhibitors and corticosteroids prevented both eosinophilic and steroid-induced neutrophilic inflammation. Together, these results establish FGFs as therapeutic targets for severe asthma patients who do not benefit from ICS.


Assuntos
Asma , Fatores de Crescimento de Fibroblastos , Corticosteroides/farmacologia , Corticosteroides/uso terapêutico , Animais , Fluticasona/farmacologia , Fluticasona/uso terapêutico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Ácido Hialurônico , Inflamação/tratamento farmacológico , Camundongos
12.
J Clin Lab Anal ; 36(5): e24336, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35312116

RESUMO

BACKGROUND: There are no validated biomarkers that can predict the clinical benefit of immune checkpoint blockers against the programmed cell death protein 1 (PD-1) treatments in hepatocellular carcinoma (HCC). This study aimed to investigate the prognostic value of inflammation-immunity-nutrition score (IINS) in patients with HCC treated with anti-PD-1 therapy. METHODS: A consecutive series of 101 HCC patients treated with PD-1 inhibitors in Sichuan Provincial People's Hospital between January 2018 and August 2020 were enrolled in the retrospective study. IINS (0-6) was constructed based on pretreatment high-sensitivity C-reactive protein (hsCRP), lymphocyte (LYM), and albumin (ALB). The patients were divided into high and low IINS groups according to IINS values. Prognostic values of each variable were evaluated with univariate and multivariate time-dependent Cox regression analyses. Survival curves were calculated and compared using the Kaplan-Meier method and log-rank test. The prognostic performance of IINS was further compared with that of other traditional prognostic indicators by receiver operating characteristic (ROC) curve and the areas under the ROC curve. RESULTS: Patients with low IINS had longer overall survival (OS) (HR: 4.711, 95% CI: 1.80-12.37, p = .001) and progression-free survival (HR: 3.411, 95% CI: 1.79-6.51, p < .0001) than those with high IINS. The multivariate analysis identified IINS (HR: 3.746, 95% CI: 1.05-13.38, p = .042) and tumor number (HR: 5.111, 95% CI: 1.075-24.299, p = .04) as independent prognostic factors. According to ROC analysis, IINS (AUC =0.729, 95% CI: 0.597-0.861, p = .002) presented better prognostic performance than other traditional prognostic indicators. The area of the IINS-CA19-9 under the ROC curve (AUC) was higher than that of the IINS or CA19-9 levels for the prediction of OS. CONCLUSION: The results suggest that IINS may be an independent prognostic indicator for HCC patients treated with anti-PD-1 therapy. IINS-CA19-9 classification may be more effective in predicting clinical benefit of anti-PD-1 therapy in HCC patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Antígeno CA-19-9 , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Inflamação/patologia , Neoplasias Hepáticas/tratamento farmacológico , Prognóstico , Curva ROC , Estudos Retrospectivos
13.
J Relig Health ; 61(4): 2726-2742, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35347576

RESUMO

Effects of religion, spirituality and supernatural beliefs (RSS) upon health in mainland China remain poorly understood, despite strong RSS beliefs influencing Chinese society. We conducted a Chinese-English bilingual systematic review to summarize the state of RSS-health research in mainland China. Study quality was assessed using the Critical Appraisal Skills Program tool. We screened 1858 studies, 162 of which were included in the review. From 2000-2004 to 2015-2019, the number of RSS-health studies in China increased from five to 73. However, only 7% of studies were rated as higher quality. Cross-sectional and case-control studies represented the vast majority of study designs (94%) and religious affiliation was the only RSS measure for 58% of studies. Higher, moderate, and lower quality studies indicated that RSS has both beneficial and adverse health implications. RSS-health research in China has accelerated rapidly in the last 20 years, but fundamental gaps in knowledge remain. Longitudinal study designs and nuanced RSS measures are needed to advance understanding of RSS health effects in China.


Assuntos
Terapias Espirituais , Espiritualidade , Estudos Transversais , Humanos , Estudos Longitudinais , Religião
14.
Anal Chem ; 94(7): 3056-3064, 2022 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-35142221

RESUMO

Stimulated emission depletion (STED) nanoscopy is an emerging super-resolution imaging platform for the study of the cellular structure. Developing suitable fluorescent probes of small size, good photostability, and easy functionalization is still in demand. Herein, we introduce a new type of surface-engineered gold nanoclusters (Au NCs) that are ultrasmall (1.7 nm) and ultrabright (QY = 60%) for STED bioimaging. A rigid shell formed by l-arginine (l-Arg) and 6-aza-2-thiothymine (ATT) on the Au NC surface enables not only its strong fluorescence in aqueous solution but also its easy chemical modification for specific biomolecule labeling. Au NCs show remarkable performance as STED nanoprobes, including high depletion efficiency, good photobleaching resistance, and low saturation intensity. Super-resolution imaging has been achieved with these Au NCs, and targeted nanoscopic imaging of cellular tubulin has been demonstrated. Moreover, the circular structure of lysosomes in live cells has been revealed. As a Au NC is also an ideal probe for electron microscopy, dual imaging of Aß42 aggregates with the single labeling probe of Au NCs has been realized in correlative light and electron microscopy (CLEM). This work reports, for the first time, the application of Au NCs as a novel probe in STED and CLEM imaging. With their excellent properties, Au NCs show promising potential for nanoscale bioimaging.


Assuntos
Ouro , Nanopartículas Metálicas , Corantes Fluorescentes/química , Ouro/química , Nanopartículas Metálicas/química , Microscopia Eletrônica , Fotodegradação
15.
Psychol Rep ; 125(4): 2274-2291, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34034570

RESUMO

The 10-item Connor-Davidson Resilience Scale (CD-RISC-10) is a self-report instrument widely used to assess resilience in particular demographics. This study aimed to evaluate the validity and measurement invariance (MI) of the CD-RISC-10 in Chinese left-behind children. A total of 968 children from three middle schools in Guizhou Province participated in this study, with the CD-RISC-10 used twice, at the base line time point and again after six months. The Ego-resilience Scale (ERS), and General Self-efficiency Scale (GSES-10) were also used as criteria-related validity instruments. Confirmatory factor analysis (CFA) was carried out to examine the one-factor model and the MI with regards to gender and left-behind status, as well as the longitudinal measurement invariance (LMI). The study proved satisfactory reliability and validity of the CD-RISC-10, with good criterion validity with the ERS and GSES-10. CFA results showed that the satisfactory model fit for the one-factor structure was supported in all groups (e.g., CFI = .942, TLI = .925, RMSEA = .057). The strict MI was evident across genders, as well as both the left-behind and non-left-behind groups. Additionally, the LMI of the CD-RISC-10 was also adequately supported. Generally speaking, these findings demonstrate that the CD-RISC-10 can effectively measure the resilience level of left-behind children - boys as well as girls - in China.


Assuntos
Resiliência Psicológica , Criança , China , Análise Fatorial , Feminino , Humanos , Masculino , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários
16.
Eur J Med Res ; 26(1): 147, 2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34920757

RESUMO

BACKGROUND: The outbreak of novel coronavirus disease 2019 (COVID-19) has become a public health emergency of international concern. Quantitative testing of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus is demanded in evaluating the efficacy of antiviral drugs and vaccines and RT-PCR can be widely deployed in the clinical assay of viral loads. Here, we developed a quantitative RT-PCR method for SARS-CoV-2 virus detection in this study. METHODS: RT-PCR kits targeting E (envelope) gene, N (nucleocapsid) gene and RdRP (RNA-dependent RNA polymerase) gene of SARS-CoV-2 from Roche Diagnostics were evaluated and E gene kit was employed for quantitative detection of COVID-19 virus using Cobas Z480. Viral load was calculated according to the standard curve established by series dilution of an E-gene RNA standard provided by Tib-Molbiol (a division of Roche Diagnostics). Assay performance was evaluated. RESULTS: The performance of the assay is acceptable with limit of detection (LOD) below 10E1 copies/µL and lower limit of quantification (LLOQ) as 10E2 copies/µL. CONCLUSION: A quantitative detection of the COVID-19 virus based on RT-PCR was established.


Assuntos
COVID-19/diagnóstico , Proteínas do Envelope de Coronavírus/genética , Proteínas do Nucleocapsídeo de Coronavírus/genética , RNA-Polimerase RNA-Dependente de Coronavírus/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Humanos , Limite de Detecção , Fosfoproteínas/genética , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Carga Viral/métodos
17.
Front Psychol ; 12: 678979, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630200

RESUMO

The Fear of COVID-19 Scale (FCV-19S) is a new one-dimensional scale used to measure fear of an individual about the COVID-19. Given the seriousness of the COVID-19 situation in China when our study was taking place, our aim was to translate and examine the applicability of the FCV-19S in Chinese students. The sample used for validation comprised 2,445 Chinese students. The psychometrical characteristics of the Chinese FCV-19S (FCV-19S-C) were tested using Rasch analysis. Principal component analysis (PCA) proved the unidimensional structure of the model. Both infit and outfit mean square (MNSQ) values (0.69-1.31) and point-measure correlations (0.82-0.86) indicated a good model fit. Person-item separation and reliability values indicated good reliability of the scale. The person-item map revealed an acceptable level of match between the persons and the items. Differential item functioning of the FCV-19S-C showed no differences with respect to age or gender. FCV-19S-C scores were significantly associated with anxiety, stress, depression, ego-resilience, and general health. The FCV-19S-C was proven to be effective in measuring fear of Chinese students about the COVID-19.

18.
Cell Host Microbe ; 29(10): 1521-1530.e10, 2021 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-34492225

RESUMO

The pore-forming protein gasdermin D (GSDMD) executes lytic cell death called pyroptosis to eliminate the replicative niche of intracellular pathogens. Evolution favors pathogens that circumvent this host defense mechanism. Here, we show that the Shigella ubiquitin ligase IpaH7.8 functions as an inhibitor of GSDMD. Shigella is an enteroinvasive bacterium that causes hemorrhagic gastroenteritis in primates, but not rodents. IpaH7.8 contributes to species specificity by ubiquitinating human, but not mouse, GSDMD and targeting it for proteasomal degradation. Accordingly, infection of human epithelial cells with IpaH7.8-deficient Shigella flexneri results in increased GSDMD-dependent cell death compared with wild type. Consistent with pyroptosis contributing to murine disease resistance, eliminating GSDMD from NLRC4-deficient mice, which are already sensitized to oral infection with Shigella flexneri, leads to further enhanced bacterial replication and increased disease severity. This work highlights a species-specific pathogen arms race focused on maintenance of host cell viability.


Assuntos
Proteínas de Bactérias/metabolismo , Disenteria Bacilar/metabolismo , Proteínas de Ligação a Fosfato/metabolismo , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Shigella flexneri/enzimologia , Ubiquitina-Proteína Ligases/metabolismo , Animais , Proteínas de Bactérias/genética , Disenteria Bacilar/genética , Disenteria Bacilar/microbiologia , Células Epiteliais/metabolismo , Células Epiteliais/microbiologia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Camundongos , Camundongos Knockout , Proteínas de Ligação a Fosfato/genética , Proteínas Citotóxicas Formadoras de Poros/genética , Proteólise , Shigella flexneri/genética , Shigella flexneri/fisiologia , Ubiquitina-Proteína Ligases/genética
19.
J Med Microbiol ; 70(8)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34397349

RESUMO

Introduction. Lactococcus petauri LZys1 (L. petauri LZys1) is a type of lactic acid bacteria (LAB), which was initially isolated from healthy human gut.Hypothesis/Gap Statement. It was previously anticipated that L. petauri LZys1 has potential characteristics of probiotic properties. The genetic structure and the regulation functions of L. petauri LZys1 need to be better revealed.Aim. The aim of this study was to detect the probiotic properties L. petauri LZys1 and to reveal the genome information related to its genetic adaptation and probiotic profiles.Methodology. Multiple in vitro experiments were carried out to evaluate its lactic acid-producing ability, resistance to pathogenic bacterial strains, auto-aggregation and co-aggregation ability, and so on. Additionally, complete genome sequencing, gene annotation, and probiotic associated gene analysis were performed.Results. The complete genome of L. petauri LZys1 comprised of 1 985 765 bp, with a DNA G+C content of 38.07 %, containing 50 tRNA, seven rRNA, and four sRNA. A total of 1931 genes were classified into six functional categories by Kyoto Encyclopaedia of Genes and Genomes (KEGG) database. The neighbour-joining phylogeny tree based on the whole genome of L. petauri LZys1 and other probiotics demonstrated that L. petauri LZys1 has a significant similarity to Lactococcus garvieae. The functional genes were detected to expound the molecular mechanism and biochemical processes of its potential probiotic properties, such as atpB gene.Conclusion. All the results described in this study, together with relevant information previously reported, made L. prtauri LZys1 a very interesting potential strain to be considered as a prominent candidate for probiotic use.


Assuntos
Trato Gastrointestinal/microbiologia , Genoma Bacteriano , Lactococcus , Probióticos , Animais , Bactérias/crescimento & desenvolvimento , Bactérias/patogenicidade , Sequência de Bases , Fezes/microbiologia , Genes Bacterianos , Humanos , Lactococcus/citologia , Lactococcus/genética , Lactococcus/isolamento & purificação , Lactococcus/fisiologia , Masculino , Anotação de Sequência Molecular , Mariposas/microbiologia , Filogenia , Polissacarídeos Bacterianos/biossíntese , Polissacarídeos Bacterianos/genética , Sequenciamento Completo do Genoma , Adulto Jovem
20.
Nature ; 596(7870): 97-102, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34290404

RESUMO

Infection-induced aversion against enteropathogens is a conserved sickness behaviour that can promote host survival1,2. The aetiology of this behaviour remains poorly understood, but studies in Drosophila have linked olfactory and gustatory perception to avoidance behaviours against toxic microorganisms3-5. Whether and how enteric infections directly influence sensory perception to induce or modulate such behaviours remains unknown. Here we show that enteropathogen infection in Drosophila can modulate olfaction through metabolic reprogramming of ensheathing glia of the antennal lobe. Infection-induced unpaired cytokine expression in the intestine activates JAK-STAT signalling in ensheathing glia, inducing the expression of glial monocarboxylate transporters and the apolipoprotein glial lazarillo (GLaz), and affecting metabolic coupling of glia and neurons at the antennal lobe. This modulates olfactory discrimination, promotes the avoidance of bacteria-laced food and increases fly survival. Although transient in young flies, gut-induced metabolic reprogramming of ensheathing glia becomes constitutive in old flies owing to age-related intestinal inflammation, which contributes to an age-related decline in olfactory discrimination. Our findings identify adaptive glial metabolic reprogramming by gut-derived cytokines as a mechanism that causes lasting changes in a sensory system in ageing flies.


Assuntos
Envelhecimento/metabolismo , Citocinas/metabolismo , Drosophila melanogaster/metabolismo , Intestinos , Neuroglia/metabolismo , Olfato/fisiologia , Animais , Aprendizagem da Esquiva , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/microbiologia , Feminino , Inflamação/metabolismo , Inflamação/microbiologia , Intestinos/microbiologia , Janus Quinases/metabolismo , Ácido Láctico/metabolismo , Metabolismo dos Lipídeos , Neurônios/metabolismo , Pectobacterium carotovorum , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais , Taxa de Sobrevida , Fatores de Transcrição/metabolismo
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