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1.
Nat Commun ; 13(1): 192, 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35017482

RESUMO

A key challenge in analyzing single cell RNA-sequencing data is the large number of false zeros, where genes actually expressed in a given cell are incorrectly measured as unexpressed. We present a method based on low-rank matrix approximation which imputes these values while preserving biologically non-expressed genes (true biological zeros) at zero expression levels. We provide theoretical justification for this denoising approach and demonstrate its advantages relative to other methods on simulated and biological datasets.

2.
Target Oncol ; 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35020119

RESUMO

BACKGROUND: Afatinib has been shown as a suitable option for the treatment of epidermal growth factor receptor mutation-positive (EGFRm+) non-small-cell lung cancer (NSCLC) in randomized controlled trials. However, patients treated in real-world clinical practice, including elderly patients, and those with brain metastases or poor Eastern Cooperative Oncology Group (ECOG) performance statuses, are often excluded from these studies. OBJECTIVE: To report the final results, with a particular focus on patients enrolled in China, from a prospective phase IIIb, "near real-world" study of afatinib in tyrosine kinase inhibitor (TKI)-naïve Asian patients with EGFRm+ NSCLC. PATIENTS AND METHODS: NCT01953913 was conducted at 34 centers across Asia. Entry criteria were broad to reflect real-world settings. Patients received afatinib 40 mg/day until tumor progression, lack of clinical benefit, or poor tolerability. Assessments included safety, time to symptomatic progression (TTSP), and progression-free survival (PFS). RESULTS: 541 patients were treated, of whom 412 were enrolled in China. Dose reductions were implemented in 28.7% of patients overall, and 17.7% of patients from China. Safety findings were consistent with phase III studies of afatinib. Median TTSP in all patients was 14.0 months (95% CI 12.9-15.9), and median PFS was 12.1 months (95% CI 11.0-13.6). Median TTSP (13.8 months, 95% CI 12.7-16.1) and PFS (11.4 months, 95% CI 10.9-13.7) were similar in patients from China to the overall population. Among patients from China who had dose reductions, TTSP was numerically longer than in those who did not (16.4 vs. 13.8 months; P = 0.0703), while PFS was significantly longer (13.9 vs. 11.1 months; P = 0.0275). Among patients from China with brain metastases, TTSP was numerically shorter than in those without (11.0 vs. 14.4 months; P = 0.0869), whereas PFS was significantly shorter (9.2 vs. 12.9 months; P = 0.0075). CONCLUSIONS: Safety data for afatinib when used in a "near real-world" setting in patients with EGFRm+ NSCLC was consistent with the known safety profile of afatinib. Supporting efficacy data of afatinib were provided in all patients, and in those enrolled in China. Tolerability-guided afatinib dose reduction allowed patients to remain on treatment and continue to experience clinical benefit. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: NCT01953913 (1 October 2013).

3.
Vet Med Sci ; 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34981892

RESUMO

BACKGROUND: Hepatitis E virus (HEV) is an important zoonotic pathogen, Genotypes 3 and 4 are the main zoonotic genotype. Due to the lack of mature and effective culture cell lines, researches on genotype IV swine HEV (SHEV-4) infection and pathogenic mechanism have been carried out in pigs, gerbils and non-human primate models. OBJECTIVES: The aim of this study was to establish a rat infection model by intra-peritoneal infection with SHEV-4, which provided a new research idea and scientific basis for further revealing the mechanism of HEV infection and preventing HEV infection. METHODS: SHEV-4 virus was administered intra-peritoneally to 6- to 8-week-old mice to observe the serological changes and virus release. RESULTS: According to the results of the rat serum HEV IgG, ALT and AST levels, swine HEV, minus-strand HEV RNA can infect Sprague-Dawley rats across species, and there are no obvious clinical symptoms after infection. HEV RNA was detected in most tissues and organs after infection, but the viral load was low. The liver had pathological changes of chronic hepatitis. CONCLUSIONS: We found that the rat model of porcine HEV infection is a small animal model suitable for the study of HEV infection.

4.
Lancet Oncol ; 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35038429

RESUMO

BACKGROUND: A substantial proportion of patients with unresectable stage III non-small-cell lung cancer (NSCLC) cannot either tolerate or access concurrent chemoradiotherapy, so sequential chemoradiotherapy is commonly used. We assessed the efficacy and safety of sugemalimab, an anti-PD-L1 antibody, in patients with stage III NSCLC whose disease had not progressed after concurrent or sequential chemoradiotherapy. METHODS: GEMSTONE-301 is a randomised, double-blind, placebo-controlled, phase 3 trial in patients with locally advanced, unresectable, stage III NSCLC, done at 50 hospitals or academic research centres in China. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 who had not progressed after concurrent or sequential chemoradiotherapy. We randomly assigned patients (2:1, using an interactive voice-web response system) to receive sugemalimab 1200 mg or matching placebo, intravenously every 3 weeks for up to 24 months. Stratification factors were ECOG performance status, previous chemoradiotherapy, and total radiotherapy dose. The investigators, trial coordination staff, patients, and study sponsor were masked to treatment allocation. The primary endpoint was progression-free survival as assessed by blinded independent central review (BICR) in the intention-to-treat population. Safety was assessed in all participants who received at least one dose of assigned study treatment. The study has completed enrolment and the results of a preplanned analysis of the primary endpoint are reported here. The trial is registered with ClinicalTrials.gov, NCT03728556. FINDINGS: Between Aug 30, 2018 and Dec 30, 2020, we screened 564 patients of whom 381 were eligible. Study treatment was received by all patients randomly assigned to sugemalimab (n=255) and to placebo (n=126). At data cutoff (March 8, 2021), median follow-up was 14·3 months (IQR 6·4-19·4) for patients in the sugemalimab group and 13·7 months (7·1-18·4) for patients in the placebo group. Progression-free survival assessed by BICR was significantly longer with sugemalimab than with placebo (median 9·0 months [95% CI 8·1-14·1] vs 5·8 months [95% CI 4·2-6·6]; stratified hazard ratio 0·64 [95% CI 0·48-0·85], p=0·0026). Grade 3 or 4 treatment-related adverse events occurred in 22 (9%) of 255 patients in the sugemalimab group versus seven (6%) of 126 patients in the placebo group, the most common being pneumonitis or immune-mediated pneumonitis (seven [3%] of 255 patients in the sugemalimab group vs one [<1%] of 126 in the placebo group). Treatment-related serious adverse events occurred in 38 (15%) patients in the sugemalimab group and 12 (10%) in the placebo group. Treatment-related deaths were reported in four (2%) of 255 patients (pneumonia in two patients, pneumonia with immune-mediated pneumonitis in one patient, and acute hepatic failure in one patient) in the sugemalimab group and none in the placebo group. INTERPRETATION: Sugemalimab after definitive concurrent or sequential chemoradiotherapy could be an effective consolidation therapy for patients with stage III NSCLC whose disease has not progressed after sequential or concurrent chemoradiotherapy. Longer follow-up is needed to confirm this conclusion. FUNDING: CStone Pharmaceuticals and the National Key Research and Development Program of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

5.
Genes Genomics ; 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34985712

RESUMO

BACKGROUND: Acetyl-CoA acyltransferase 1 (ACAT1) is a key enzyme catalyzing the production of mitochondrial ketone bodies. We have shown that ACAT1 is down-regulated in kidney renal clear cell carcinoma (KIRC) previously. OBJECTIVE: To investigate the reasons for downregulation of ACAT1 in KIRC and explore the underlying mechanisms involved in metastatic inhibition regulated by ACAT1. METHODS: The Gene Expression Omnibus (GEO) database was queried for meta-analysis of ACAT1 mRNA expression in KIRC. The UALCAN website was used to compare the methylation levels of the ACAT1 promoter region in KIRC and normal tissues. RT-qPCR was used to quantitate ACAT1 transcription levels. The GCBI and Tarbase V.8 databases were used to predict miRNAs that may target the mRNA of ACAT1. The correlation between mRNA expression of ACAT1, MMP7 (matrix metallopeptidase 7), CDH1 (E-cadherin), EpCAM (epithelial cell adhesion molecule), and VIM (vimentin) was analyzed. Extracellular MMP7 protein was quantitated using an ELISA assay. RESULTS: The methylation level of the ACAT1 promoter region in KIRC was significantly higher than that in the normal kidney tissues. The ACAT1 mRNA expression in the KIRC cell lines was restored after treatment with 5-aza-dC (p < 0.05). MiR-21-5p is a conserved microRNA targeting ACAT1. It is expressed at a significantly higher level in KIRC than in normal tissues (p < 0.001). MiR-21-5p miRNA expression negatively correlates with ACAT1 mRNA expression. The expression of miR-21-5p is higher at the T3-T4 stages and in the histologic grades G3-G4. Patients with high miR-21-5p expression tended to have lower overall survival, suggesting that miR-21-5p could serve as a potentially valuable diagnostic biomarker for KIRC (AUC = 0.957; p < 0.001). A mimetic of miR-21-5p inhibited the expression of ACAT1 mRNA and protein. In addition, ACAT1 mRNA expression positively correlates with CDH1 and EpCAM but is negatively correlated with VIM. Overexpression of ACAT1 suppresses the secretion of MMP7 in KIRC cells. CONCLUSION: Expression of ACAT1 in KIRC is controlled at two levels, firstly by the hypermethylation of the ACAT1 promoter region and secondly by overexpression of miR-21-5p. Downregulation of ACAT1 expression correlates with epithelial-mesenchymal transition (EMT).

6.
Med Phys ; 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35043971

RESUMO

PURPOSE: To propose a clinically feasible automatic planning solution for external beam intensity-modulated radiotherapy (IMRT) including dose prediction via a deep learning and voxel-based optimization strategy. MATERIALS AND METHODS: The dose distribution of patients was predicted using a U-Net-based deep learning network based on the patient's anatomy information. One hundred seventeen patients with nasopharyngeal cancer (NPC) and 200 patients with rectal cancer were enrolled in this study. For NPC cases, 94 cases were included in the training dataset, 13 in the validation dataset and 10 in the testing dataset. For rectal cancer cases, 172 cases were included in the training set, 18 in the validation set and 10 in the testing set. A voxel-based optimization strategy, "Voxel", was proposed to achieve treatment planning optimization by dividing body voxels into two parts: inside planning target volumes (PTVs) and outside PTVs. Fixed dose-volume objectives were attached to the total objective function to realize individualized planning intended as the "hybrid" optimizing strategy. Automatically generated plans were compared with clinically approved plans to evaluate clinical gains, according to dosimetric indices and dose-volume histograms (DVHs). RESULTS: Similarities were found between the DVH of the predicted dose and clinical plan, although significant differences were found in some organs at risk (OARs). Better organ sparing and suboptimal PTV coverage were shown using the voxel strategy; however, the deviation in homogeneity indices (HI) and conformity indices (CI) of the PTV between automatically generated plans and manual plans were reduced by the hybrid strategy ((Manual plans)/(Voxel plans)/(Hybrid plans): HI of PTV70 (1.06/1.12/1.02), CI of PTV70 (0.79/0.58/0.76)). The optimization time for each patient was within 1 minute and included fluence map optimization, leaf sequencing and control point optimization. All the generated plans (voxel & hybrid strategy) could be delivered on uRT-linac 506c (United Imaging Health care, Shanghai, China). CONCLUSION: Deliverable plans can be generated by incorporating a voxel-based optimization strategy into a commercial TPS. The hybrid optimization method shows the benefit and clinical feasibility in generating clinically acceptable plans. This article is protected by copyright. All rights reserved.

7.
Geriatr Nurs ; 44: 24-29, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35007867

RESUMO

Surveys based on western populations have identified many risk factors for dysphagia in older people, but the potential risk factors consistent with the demographic characteristics of older, hospitalized Chinese patients require further study. This single-center prospective study aimed to determine the incidence of dysphagia in western China, and to develop and validate a model to predict the risk of dysphagia among older patients. A total of 343 inpatients (aged ≥ 65 years without dysphagia and cognitive impairment) were included. A score ≥ 2 on the Eating Assessment Tool-10 was defined as dysphagia. After a six-month follow-up, 70 (20.4%) patients were found to have dysphagia. The final model included age, wearing dentures, activities of daily living, cerebral vascular disease, coronary heart disease, and malignancy. The developed model has high predictive accuracy and can be easily implemented in daily practice.

8.
Elife ; 112022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35023829

RESUMO

Congenital cataract, an ocular disease predominantly occurring within the first decade of life, is one of the leading causes of blindness in children. However, the molecular mechanisms underlying the pathogenesis of congenital cataract remain incompletely defined. Through whole-exome sequencing of a Chinese family with congenital cataract, we identified a potential pathological variant (p.G1943E) in PIKFYVE, which is located in the PIP kinase domain of the PIKFYVE protein. We demonstrated that heterozygous/homozygous disruption of PIKFYVE kinase domain, instead of overexpression of PIKFYVEG1943E in zebrafish mimicked the cataract defect in human patients, suggesting that haploinsufficiency, rather than dominant-negative inhibition of PIKFYVE activity caused the disease. Phenotypical analysis of pikfyve zebrafish mutants revealed that loss of Pikfyve caused aberrant vacuolation (accumulation of Rab7+Lc3+ amphisomes) in lens cells, which was significantly alleviated by treatment with the V-ATPase inhibitor bafilomycin A1 (Baf-A1). Collectively, we identified PIKFYVE as a novel causative gene for congenital cataract and pinpointed the potential application of Baf-A1 for the treatment of congenital cataract caused by PIKFYVE deficiency.

9.
Appl Intell (Dordr) ; : 1-15, 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35039715

RESUMO

Deep convolutional networks have been widely used for various medical image processing tasks. However, the performance of existing learning-based networks is still limited due to the lack of large training datasets. When a general deep model is directly deployed to a new dataset with heterogeneous features, the effect of domain shifts is usually ignored, and performance degradation problems occur. In this work, by designing the semantic consistency generative adversarial network (SCGAN), we propose a new multimodal domain adaptation method for medical image diagnosis. SCGAN performs cross-domain collaborative alignment of ultrasound images and domain knowledge. Specifically, we utilize a self-attention mechanism for adversarial learning between dual domains to overcome visual differences across modal data and preserve the domain invariance of the extracted semantic features. In particular, we embed nested metric learning in the semantic information space, thus enhancing the semantic consistency of cross-modal features. Furthermore, the adversarial learning of our network is guided by a discrepancy loss for encouraging the learning of semantic-level content and a regularization term for enhancing network generalization. We evaluate our method on a thyroid ultrasound image dataset for benign and malignant diagnosis of nodules. The experimental results of a comprehensive study show that the accuracy of the SCGAN method for the classification of thyroid nodules reaches 94.30%, and the AUC reaches 97.02%. These results are significantly better than the state-of-the-art methods.

10.
Clin Lab ; 68(1)2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35023696

RESUMO

BACKGROUND: Since December 2019, there has been a global outbreak of COVID-19. As of the end of July 2020, more than 600,000 deaths had been reported globally. The purpose of this paper is to further explore the application of non-invasive ventilation in severe COVID-19 patients. METHODS: A retrospective study was conducted to included 57 confirmed COVID-19 patients, among which 36 cases were severe. According to different oxygen inhalation methods, they were divided into non-invasive ventilator assisted ventilation group with 21 cases (group A) and 15 cases of nasal catheter oxygen inhalation group (group B). The data of respiration (RR), heart rate (HR), partial arterial pressure of oxygen (PaO2), partial arterial pressure of carbon dioxide (PaCO2), and oxygenation index (OI) before the treatment of noninvasive ventilator assisted ventilation or nasal catheter oxygen treatment at 24, 48, and 72 hours of treatment of the 2 groups were collected and analyzed to determine whether the above indicators were statistically different in each time period. RESULTS: After 24 hours of treatment with noninvasive ventilator assisted ventilation in group A, RR gradually decreased, PaO2 and OI were significantly higher than before treatment, while after 24 hours of treatment, PaO2, RR, HR and other indexes in group B showed no significant improvement, and OI increased gradually after 48 hours of treatment, with statistically significant difference compared with that before treatment. CONCLUSIONS: Early adoption of non-invasive ventilation can effectively improve the hypoxic state of patients with severe COVID-19. The combination of underlying diseases will not prolong the use of non-invasive ventilation.


Assuntos
COVID-19 , Humanos , Respiração Artificial , Estudos Retrospectivos , SARS-CoV-2 , Ventiladores Mecânicos
11.
BMC Musculoskelet Disord ; 23(1): 67, 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35042504

RESUMO

OBJECTIVE: This study aimed to identify key diagnostic markers and immune infiltration of (SONFH) by bioinformatics analysis. METHODS: Related SONFH datasets were downloaded from the Gene Expression Omnibus (GEO) database. First, we identified the differentially expressed genes (DEGs) and performed the functional enrichment analysis. Then weighted correlation network analysis (WGCNA) and the MCODE plug-in in Cytoscape were used to identify the diagnostic markers of SONFH. Finally, CIBERSORT was used to analyze the immune infiltration between SONFH and healthy controls, and the correlation between infiltrating immune cells and diagnostic markers was analyzed. RESULTS: TYROBP, TLR2, P2RY13, TLR8, HCK, MNDA, and NCF2 may be key diagnostic markers of SONFH. Immune cell infiltration analysis revealed that Memory B cells and activated dendritic cells may be related to the SONFH process. Moreover, HCK was negatively correlated with CD8 T cells, and neutrophils were positively correlated with those key diagnostic markers. CONCLUSIONS: TYROBP, TLR2, P2RY13, TLR8, HCK, MNDA, and NCF2 may be used as diagnostic markers of SONFH, and immune-related mechanism of SONFH and the potential immunotherapy are worthy of further study.

12.
Int J Biol Macromol ; 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35007636

RESUMO

Taraxacum mongolicum polysaccharide (TMP) exhibits anti-inflammatory and antioxidant activity, making it an attractive candidate for aquatic-product-safety applications. Here, this study was aimed to investigate the effects of dietary TMP on the growth, nutritional composition, antioxidant capacity, bioaccumulation and inflammation in Channa asiatica under hexavalent chromium stress. The C. asiatica was randomly distributed into five groups: The first group served as the blank control group (CK), the subsequent groups were fed TMP-supplemented feed (0, 0.5, 1.0 and 2.0 g/kg), respectively, and exposed to waterborne Cr6+ for 28 days. Our results indicated that the TMP effectively increased (P < 0.05) C. asiatica muscle flavour amino acid, total free amino acids, monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), and EPA + DHA contents, enhanced positively antioxidant enzyme activity (GPX, SOD, CAT, T-AOC), reduced oxidative stress parameters (MDA, PC), and up-regulated antioxidant-related genes mRNA expression. Meanwhile, the appropriate amount of TMP supplementation also inhibited the bioaccumulation of Cr6+ in tissues and alleviated the inflammatory response (P < 0.05). Furthermore, sensory evaluation implied that the overall score of sashimi and cooked fillet in the 2.0 g/kg TMP group was the highest in the experimental group, second only to CK. In brief, these results elucidate that TMP-supplemented diets excellently ameliorated the growth, enriched nutritional composition and antioxidant capacity, and inhibited bioaccumulation and inflammation in C. asiatica exposed to waterborne Cr6+.

13.
Artigo em Inglês | MEDLINE | ID: mdl-35031812

RESUMO

PURPOSE: Respiratory motion causes mismatches between PET images of the myocardium and the corresponding cardiac MR images in cardiac integrated PET/MR. The mismatch may affect the attenuation correction and the diagnosis of non-ischemic cardiomyopathies. In this study, we present a two-stage cardiac PET and MR late gadolinium enhancement (LGE) co-registration method, which seeks to improve diagnostic accuracy of non-ischemic cardiomyopathies via better image co-registration using an integrated whole-body PET/MR system. METHODS: The proposed PET and LGE two-stage co-registration method was evaluated through comparison with one-stage direct co-registration and no-registration. One hundred and ninety-one slices of LGE and forty lesions were studied. Two trained nuclear medicine physicians independently assessed the displacement between LGE and PET to qualitatively evaluate the co-registration quality. The changes of the mean SUV in the normal myocardium and the LGE-enhanced lesions before and after image co-registration were measured to quantitatively evaluate the accuracy and value of image co-registration. RESULTS: The two-stage method had an improved image registration score (4.93 ± 0.89) compared with the no-registration method (3.49 ± 0.84, p value < 0.001) and the single-stage method (4.23 ± 0.81, p value < 0.001). Furthermore, the two-stage method led to increased SUV value in the myocardium (3.87 ± 2.56) compared with the no-registration method (3.14 ± 1.92, p value < 0.001) and the single-stage method (3.32 ± 2.16, p value < 0.001). The mean SUV in the LGE lesion significantly increased from 2.51 ± 2.09 to 2.85 ± 2.35 (p value < 0.001) after the two-stage co-registration. CONCLUSION: The proposed two-stage registration method significantly improved the co-registration between PET and LGE in integrated PET/MR imaging. The technique may improve diagnostic accuracy of non-ischemic cardiomyopathies via better image co-registration. REGISTERED NO: DF-2020-085,2020.04.30.

14.
Int J Cancer ; 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35020946

RESUMO

APOBEC3-related somatic mutations are predominant in biliary tract cancers (BTCs). We aimed to elucidate the roles of APOBEC3A/3B functional polymorphisms and their influencing factors on the development of cholangiocarcinoma and gallbladder cancer (GBC). Polymorphisms at the promoter regions of APOBEC3A and APOBEC3B were genotyped in 3231 participants using quantitative PCR. Dual-luciferase reporter assay was applied to investigate the promoter activity. The difference in gene accessibility between cholangiocarcinoma cells and GBC cells was analyzed through single-cell transposase accessible chromatin sequencing. The effect of APOBEC3A on apoptosis was examined by cytometry. It's found that rs2267401-G at the APOBEC3B promoter decreases cholangiocarcinoma risk (age-, gender-adjusted odds ratio [AOR], 0.69; 95% confidence interval [CI], 0.51-0.94) but increases GBC risk (AOR, 2.04; 95% CI, 1.35-3.10). rs2267401-G confers a decreased APOBEC3B promoter activity in cholangiocarcinoma cells but an increased activity in GBC cells, possibly because the transcriptional repressor TFAP2A is over-expressed in cholangiocarcinoma. Tumor necrosis factor-α (TNF-α) increases the level of APOBEC3B via inhibiting TFAP2A expression rather than directly increasing the accessibility of APOBEC3B promoter. APOBEC3A promoter rs12157810-C decreased the risks of cholangiocarcinoma and GBC, with an AOR (95% CI) of 0.80 (0.66-0.97) and 0.75 (0.59-0.95), respectively. rs12157810-C upregulated the promoter activity in both cholangiocarcinoma and GBC cells. TNF-α upregulated the activity of the APOBEC3A promoter with rs12157810-C via increasing the accessibility of Ets-1 p68. APOBEC3A overexpression attenuates cancer evolution by causing apoptosis, in contrast to APOBEC3B. The heterogeneity in the transcriptional regulation of APOBEC3B affects the evolutionary potential of cancer cells in the inflammatory microenvironment. This article is protected by copyright. All rights reserved.

15.
BMC Vet Res ; 18(1): 16, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34983523

RESUMO

BACKGROUND: Porcine deltacoronavirus (PDCoV) is a new pathogenic porcine intestinal coronavirus, which has appeared in many countries since 2012. PDCoV disease caused acute diarrhea, vomiting, dehydration and death in piglets, resulted in significant economic loss to the pig industry. However, there is no commercially available vaccine for PDCoV. In this study, we constructed recombinant pseudorabies virus (rPRVXJ-delgE/gI/TK-S) expressing PDCoV spike (S) protein and evaluated its safety and immunogenicity in mice. RESULTS: The recombinant strain rPRVXJ-delgE/gI/TK-S obtained by CRISPR/Cas gE gene editing technology and homologous recombination technology has genetic stability in baby hamster syrian kidney-21 (BHK-21) cells and is safe to mice. After immunizing mice with rPRVXJ-delgE/gI/TK-S, the expression levels of IFN-γ and IL-4 in peripheral blood of mice were up-regulated, the proliferation of spleen-specific T lymphocytes and the percentage of CD4+ and CD8+ lymphocytes in mice spleen was increased. rPRVXJ-delgE/gI/TK-S showed good immunogenicity for mice. On the seventh day after booster immunity, PRV gB and PDCoV S specific antibodies were detected in mice, and the antibody level continued to increase, and the neutralizing antibody level reached the maximum at 28 days post- immunization (dpi). The recombinant strain can protect mice with 100% from the challenge of virulent strain (PRV XJ) and accelerate the detoxification of PDCoV in mice. CONCLUSION: The recombinant rPRVXJ-delgE/gI/TK-S strain is safe and effective with strong immunogenicity and is expected to be a candidate vaccine against PDCoV and PRV.

16.
Nucleic Acids Res ; 50(D1): D402-D412, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34986601

RESUMO

Transcription factors (TFs) play key roles in biological processes and are usually used as cell markers. The emerging importance of TFs and related markers in identifying specific cell types in human diseases increases the need for a comprehensive collection of human TFs and related markers sets. Here, we developed the TF-Marker database (TF-Marker, http://bio.liclab.net/TF-Marker/), aiming to provide cell/tissue-specific TFs and related markers for human. By manually curating thousands of published literature, 5905 entries including information about TFs and related markers were classified into five types according to their functions: (i) TF: TFs which regulate expression of the markers; (ii) T Marker: markers which are regulated by the TF; (iii) I Marker: markers which influence the activity of TFs; (iv) TFMarker: TFs which play roles as markers and (v) TF Pmarker: TFs which play roles as potential markers. The 5905 entries of TF-Marker include 1316 TFs, 1092 T Markers, 473 I Markers, 1600 TFMarkers and 1424 TF Pmarkers, involving 383 cell types and 95 tissue types in human. TF-Marker further provides a user-friendly interface to browse, query and visualize the detailed information about TFs and related markers. We believe TF-Marker will become a valuable resource to understand the regulation patterns of different tissues and cells.

17.
Eur J Cancer ; 161: 119-127, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34911640

RESUMO

AIM: The lung is the most common site of metastasis for gestational trophoblastic neoplasia (GTN). However, the level of influence of lung metastases on the prognosis of GTN and the degree to which lung metastases are considered in assessments of disease treatment options are unclear. Moreover, it is unclear which characteristics of lung metastases impact the disease. In this study, we evaluated the influence of lung metastases on the clinical course of GTN and identified lung imaging characteristics that impact treatment outcomes. METHODS: A retrospective cohort study was conducted on GTN patients treated at Peking Union Medical College Hospital between 2002 and 2018. The baseline characteristics, first-line treatment outcomes and final outcomes of patients with lung metastases (Group 1) and those without lung metastases (Group 2) were compared. RESULTS: The emergence of resistance occurred significantly more frequently in Group 1 (n = 994) than in Group 2 (n = 570) (19.52% versus 14.56%, p = 0.019), and the death rate was higher in Group 1 (0.91% versus 0%, p = 0.031). Among the patients treated with multi-agent chemotherapy, the rate of resistance and the number of treatment courses were significantly higher in Group 1 than in Group 2 (p = 0.002 and < 0.001, respectively). The lung imaging characteristics that impacted prognosis included the number of nodules, whether there were multiple nodules or a single nodule, and the number of nodules sized >1 cm. Multivariate analysis showed that a nodule measuring ≥1.8 cm was an independent risk factor for first-line treatment resistance and recurrence. CONCLUSION: Although pulmonary metastases do not affect overall survival in GTN patients, the presence of lung metastases before treatment is associated with increased risk of disease recurrence and resistance to first-line multidrug chemotherapy, especially when pulmonary nodules are larger than 1.8 cm. CLINICAL TRIAL REGISTRATION: N.A.

18.
J Clin Neurosci ; 95: 38-43, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34929649

RESUMO

Posterior reversible encephalopathy syndrome (PRES) is a neurological disorder characterized by headache, seizures, confusion and visual disturbances, as well as potentially reversible neuroimaging findings in most patients after proper treatment. Seizures is one of the most common clinical presentations of PRES. This review summarizes the potential pathophysiology and clinical features of PRES, as well as a multimodal approach to imaging and also briefly discusses the phenomenon of seizures in paediatric population.


Assuntos
Síndrome da Leucoencefalopatia Posterior , Criança , Cefaleia , Humanos , Imageamento por Ressonância Magnética , Neuroimagem , Síndrome da Leucoencefalopatia Posterior/diagnóstico por imagem , Convulsões/diagnóstico por imagem , Convulsões/etiologia
19.
Nano Lett ; 22(1): 411-418, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-34941277

RESUMO

The very high ionic conductivity of Li10GeP2S12 (LGPS) solid electrolyte (SE) makes it a promising candidate SE for solid-state batteries in electrical vehicles. However, chemomechanical failure, whose mechanism remains unclear, has plagued its widespread applications. Here, we report in situ imaging lithiation-induced failure of LGPS SE. We revealed a strong size effect in the chemomechanical failure of LGPS particles: namely, when the particle size is greater than 3 µm, fracture/pulverization occurred; when the particle size is between 1 and 3 µm, microcracks emerged; when the particle size is less than 1 µm, no chemomechanical failure was observed. This strong size effect is interpreted by the interplay between elastic energy storage and dissipation. Our finding has important implications for the design of high-performance LGPS SE, for example, by reducing the particle size to less than 1 µm the chemomechanical failure of LGPS SE can be mitigated.

20.
Food Chem ; 366: 130583, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34303203

RESUMO

Terpenoid metabolism at different developmental stages of Carya cathayensis was elucidated based on LC-MS/MS analysis and multi-omics. Terpenoid metabolites 2-hydroxy-1,4-naphoquinone and 3-hydroxybenzoic acid reached the maximum at 105 days after pollination (DAP) (P2 stage). To reveal the complex mechanism of C. cathayensis embryogenesis in relation to terpenoid metabolites (90-165 DAP), a metabolomic and transcriptional co-expression analysis was conducted. Based on RNA-Seq analysis, 679 genes of 1144 terpenoid biosynthesis were differentially expressed. Six terpenoid metabolites and 86 differentially expressed genes related to terpenoquinone metabolism were identified. Comprehensive analysis of metabolome and transcriptional data revealed that terpenoquinone accumulated in the early phase was active in the later phase. Overall, we profiled the transcriptome and metabolome changes in C. cathayensis during the developmental phase to investigate the metabolic pathways and candidate genes underlying the changes at different growth stages.


Assuntos
Carya , Cromatografia Líquida , Perfilação da Expressão Gênica , Espectrometria de Massas em Tandem , Terpenos , Transcriptoma
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