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1.
Pediatr Rheumatol Online J ; 19(1): 79, 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34078391

##### RESUMO

BACKGROUND: The present study focuses on the associations of streptococcal infection with the clinical phenotypes, relapse/recurrence and renal involvement in Henoch-Schönlein purpura (HSP) children. METHODS: Two thousand seventy-four Chinese children with HSP were recruited from January 2015 to December 2019. Patients' histories associated with HSP onset were obtained by interviews and questionnaires. Laboratory data of urine tests, blood sample and infectious agents were collected. Renal biopsy was performed by the percutaneous technique. RESULTS: (1) Streptococcal infection was identified in 393 (18.9%) HSP patients, and served as the most frequent infectious trigger. (2) Among the 393 cases with streptococcal infection, 43.0% of them had arthritis/arthralgia, 32.1% had abdominal pain and 29.3% had renal involvement. (3) 26.1% of HSP patients relapsed or recurred more than 1 time within a 5-year observational period, and the relapse/recurrence rate in streptococcal infectious group was subjected to a 0.4-fold decrease as compared with the non-infectious group. (4) No significant differences in renal pathological damage were identified among the streptococcal infectious group, the other infectious group and the non-infectious group. CONCLUSIONS: Streptococcal infection is the most frequent trigger for childhood HSP and does not aggravate renal pathological damage; the possible elimination of streptococcal infection helps relieve the relapse/recurrence of HSP.

2.
Cancer Med ; 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34076352

##### RESUMO

AIMS: Prognosis of patients for human epidermal growth factor receptor 2 (HER2)-negative breast cancer post neoadjuvant chemotherapy is not well understood. The aim of this study was to develop a novel pharmacophore-based signature to better classify and predict the risk of HER2-negative patients after anthracycline-and/or taxane-based neoadjuvant chemotherapy (NACT). MAIN METHODS: Anthracycline and taxane pharmacophore-based genes were obtained from PharmMapper. Drug-targeted genes (DTG) related clinical and bioinformatic analyses were undertaken in four GEO datasets. KEY FINDINGS: We used 12 genes from the pharmacophore to develop a DTG score (DTG-S). The DTG-S classification exhibited significant prognostic ability with respect to disease free survival (DFS) for HER2-negative patients who receive at least one type of neoadjuvant chemotherapy that included anthracycline and/or taxane. DTG-S associated with a high predictive ability for pathological complete response (pCR) as well as for prognosis of breast cancer. Using the DTG-S classification in other prediction models may improve the reclassification accuracy for DFS. Combining the DTG-S with other clinicopathological factors may further improve its predictive ability of patients' outcomes. Gene ontology and KEGG pathway analysis showed that the biological processes of DTG-S high group were associated with the cell cycle, cell migration, and cell signal transduction pathways. Targeted drug analysis shows that some CDK inhibitors and PI3K-AKT pathway inhibitors may be useful for high DTG-S patients. SIGNIFICANCE: The DTG-S classification adds prognostic and predictive information to classical parameters for HER2-negative patients who receive anthracycline-and/or taxane-based NACT, which could improve the patients' risk stratification and may help guide adjuvant treatment.

3.
Cell Rep ; 35(9): 109188, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34077723

##### RESUMO

During germinal center (GC) reactions, activated B cells undergo clonal expansion and functional maturation to produce high-affinity antibodies and differentiate into plasma and memory cells, accompanied with class-switching recombination (CSR) and somatic hypermutation (SHM). Activation-induced cytidine deaminase (AID) is responsible for both CSR and SHM in GC B cells. Transcriptional mechanisms underlying AID regulation and GC B cell reactions are still not well understood. Here, we show that expression of Ascl2 transcription factor is upregulated in GC B cells. Ectopic expression of Ascl2 promotes GC B cell development and enhances antibody production and affinity maturation. Conversely, deletion of Ascl2 in B cells impairs the GC response. Genome-wide analysis reveals that Ascl2 directly regulates GC B cell-related genes, including AID; ectopic expression of AID in Ascl2-deficient B cells rescues their antibody defects. Thus, Ascl2 regulates AID transcription and promotes GC B cell responses.

4.
Opt Lett ; 46(11): 2762-2765, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34061107

##### RESUMO

We demonstrate a high sensitivity all-fiber spectroscopic methane sensor based on photothermal interferometry. With a 2.4-m-long anti-resonant hollow-core fiber, a 1654 nm distributed feedback laser, and a Raman fiber amplifier, a noise-equivalent concentration of ${\sim}{4.3}\;{\rm ppb}$ methane is achieved at the room temperature and pressure of ${\sim}{1}\;{\rm bar}$. The effects of temperature on the photothermal phase modulation as well as the stability of the interferometer are studied. By introducing a temperature-dependent compensation factor and stabilizing the interferometer at quadrature, signal instability of ${\sim}{2.1}\%$ is demonstrated for temperature variation from 296 to 373 K.

5.
Zhongguo Yi Liao Qi Xie Za Zhi ; 45(3): 261-265, 2021 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-34096232

##### RESUMO

Based on the clinical application data of medical X-ray computed tomography (CT) in the Shanghai Sixth People's Hospital, this study transformed it into the product reliability index requirements, and took the mechanical representative component-examination table (hereinafter referred to as "patient table") and the electronic representative component-DCB (data control board) as examples. Based on the relationship between failure characteristics and clinical application data, a complete set of closed-loop implementation methods from reliability index requirements to reliability design and verification are discussed.

##### Assuntos
6.
Signal Transduct Target Ther ; 6(1): 219, 2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34083505
7.
Zhongguo Zhen Jiu ; 41(6): 691-8, 2021 Jun 12.
Artigo em Chinês | MEDLINE | ID: mdl-34085491

##### RESUMO

OBJECTIVE: To review systematically the effectiveness and safety of tuina (Chinese massage)in treatment of functional constipation. METHODS: The articles on functional constipation treated with tuina were collected by computer retrieval from 7 databases from the date of establishment to March 28, 2020, including Chinese biomedical literature database (SinoMed), China journal full-text database (CNKI), full-text database of Wanfang academic journals (Wanfang), VIP Chinese science and technology journal database(VIP), PubMed, Dutch medical literature database (EMbase) and the Cochrane Library. After data extraction and quality evaluation of the included articles, Meta analysis was conducted with RevMan5.3 software. RESULTS: A total of 16 articles were included, with 1424 cases involved. Meta analysis results showed: â The total effective rate in the treatment group was higher than that in the control group (RR=1.28, 95%CI: 1.16-1.42, P<0.000 01). â¡The effective rate for the symptoms of functional constipation in traditional Chinese medicine in the treatment group was higher than that in the control group (RR=1.38, 95%CI :1.25-1.52, Z=6.31, P<0.000 01). â¢Adverse reactions in the treatment group in the treatment of functional constipation were less than those in the control group (RR=0.10, 95%CI: 0.02-0.49, Z=2.81, P=0.005).â£The effective rate of functional constipation treated on the base of syndrome differentiation in the treatment group was higher than that of the control group (RR=1.50, 95%CI: 1.08-2.10, Z=2.39, P=0.02).â¤The improvements in fecal characteristics, defecation time and defecation frequency of the patients with functional constipation in the treatment group were better than those in the control group (P<0.05). CONCLUSION: Tuina therapy presents a certain advantages on its curative effect on functional constipation, has less adverse reactions and relieves the relevant symptoms of functional constipation. But more randomized controlled trials with high quality and large sample are required to provide further verification of its effect.

##### Assuntos
Constipação Intestinal , Medicina Tradicional Chinesa , China , Constipação Intestinal/terapia , Humanos , Massagem
8.
J Neuroinflammation ; 18(1): 133, 2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34118948

##### RESUMO

BACKGROUND: Brain ischemia compromises natural killer (NK) cell-mediated immune defenses by acting on neurogenic and intracellular pathways. Less is known about the posttranscriptional mechanisms that regulate NK cell activation and cytotoxicity after ischemic stroke. METHODS: Using a NanoString nCounter® miRNA array panel, we explored the microRNA (miRNA) profile of splenic NK cells in mice subjected to middle cerebral artery occlusion. Differential gene expression and function/pathway analysis were applied to investigate the main functions of predicted miRNA target genes. miR-1224 inhibitor/mimics transfection and passive transfer of NK cells were performed to confirm the impact of miR-1224 in NK cells after brain ischemia. RESULTS: We observed striking dysregulation of several miRNAs in response to ischemia. Among those miRNAs, miR-1224 markedly increased 3 days after ischemic stroke. Transfection of miR-1224 mimics into NK cells resulted in suppression of NK cell activity, while an miR-1224 inhibitor enhanced NK cell activity and cytotoxicity, especially in the periphery. Passive transfer of NK cells treated with an miR-1224 inhibitor prevented the accumulation of a bacterial burden in the lungs after ischemic stroke, suggesting an enhanced immune defense of NK cells. The transcription factor Sp1, which controls cytokine/chemokine release by NK cells at the transcriptional level, is a predicted target of miR-1224. The inhibitory effect of miR-1224 on NK cell activity was blocked in Sp1 knockout mice. CONCLUSIONS: These findings indicate that miR-1224 may serve as a negative regulator of NK cell activation in an Sp1-dependent manner; this mechanism may be a novel target to prevent poststroke infection specifically in the periphery and preserve immune defense in the brain.

9.
Microbiome ; 9(1): 137, 2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34118976

##### RESUMO

BACKGROUND: Gastrointestinal tract (GIT) microbiomes in ruminants play major roles in host health and thus animal production. However, we lack an integrated understanding of microbial community structure and function as prior studies. are predominantly biased towards the rumen. Therefore, to acquire a microbiota inventory of the discrete GIT compartments, In this study, we used shotgun metagenomics to profile the microbiota of 370 samples that represent 10 GIT regions of seven ruminant species. RESULTS: Our analyses reconstructed a GIT microbial reference catalog with > 154 million nonredundant genes and identified 8745 uncultured candidate species from over 10,000 metagenome-assembled genomes. The integrated gene catalog across the GIT regions demonstrates spatial associations between the microbiome and physiological adaptations, and 8745 newly characterized genomes substantially expand the genomic landscape of ruminant microbiota, particularly those from the lower gut. This substantially expands the previously known set of endogenous microbial diversity and the taxonomic classification rate of the GIT microbiome. These candidate species encode hundreds of enzymes and novel biosynthetic gene clusters that improve our understanding concerning methane production and feed efficiency in ruminants. Overall, this study expands the characterization of the ruminant GIT microbiota at unprecedented spatial resolution and offers clues for improving ruminant livestock production in the future. CONCLUSIONS: Having access to a comprehensive gene catalog and collections of microbial genomes provides the ability to perform efficiently genome-based analysis to achieve a detailed classification of GIT microbial ecosystem composition. Our study will bring unprecedented power in future association studies to investigate the impact of the GIT microbiota in ruminant health and production. Video abstract.

10.
Aging (Albany NY) ; 132021 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-34120890

##### RESUMO

Hepatocellular carcinoma (HCC) serves as a prevailing global malignancy with severe mortality and extremely unsatisfactory prognosis, in which autophagy is a fundamental process in liver cancer pathogenesis, but the mechanisms are poorly understood. MicroRNAs (miRNAs) serve as a type of well-recognized non-coding regulators and contribute to the modulation of liver cancer development, from the aspects of diagnosis, progression, and therapy. Here, we aimed to investigate the function of hsa_microRNA-513b-5p (miR-513b-5p) in regulating autophagy during HCC progression. Specifically, our data showed that miR-513b-5p mimic reduced the LC3-II and beclin1 expression but enhanced p62 expression in HCC cells. MiR-513b-5p repressed liver cancer cell proliferation, migration/invasion, and induced apoptosis in vitro. Crucially, miR-513b-5p attenuated tumor growth of liver cancer cells in vivo. In the mechanical investigation, we identified that PIK3R3 mRNA 3'UTR was targeted by miR-513b-5p and miR-513b-5p suppressed PIK3R3 expression. PIK3R3 overexpression partly reversed miR-513b-5p-mediated autophagy, proliferation, and apoptosis of liver cancer cells. Consequently, we concluded that miR-513b-5p repressed autophagy during the malignant progression of HCC by targeting PIK3R3. MiR-513b-5p may be applied as a therapeutic target for HCC.

11.
Biomed Eng Online ; 20(1): 56, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34090428

##### RESUMO

BACKGROUND: To predict placental invasion (PI) and determine the subtype according to the degree of implantation, and to help physicians develop appropriate therapeutic measures, a prenatal prediction and typing of placental invasion method using MRI deep and radiomic features were proposed. METHODS: The placental tissue of abdominal magnetic resonance (MR) image was segmented to form the regions of interest (ROI) using U-net. The radiomic features were subsequently extracted from ROI. Simultaneously, a deep dynamic convolution neural network (DDCNN) with codec structure was established, which was trained by an autoencoder model to extract the deep features from ROI. Finally, combining the radiomic features and deep features, a classifier based on the multi-layer perceptron model was designed. The classifier was trained to predict prenatal placental invasion as well as determine the invasion subtype. RESULTS: The experimental results show that the average accuracy, sensitivity, and specificity of the proposed method are 0.877, 0.857, and 0.954 respectively, and the area under the ROC curve (AUC) is 0.904, which outperforms the traditional radiomic based auxiliary diagnostic methods. CONCLUSIONS: This work not only labeled the placental tissue of MR image in pregnant women automatically but also realized the objective evaluation of placental invasion, thus providing a new approach for the prenatal diagnosis of placental invasion.

12.
Sci Total Environ ; 790: 148030, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34091342

##### RESUMO

Due to the spread of coronavirus disease 2019 (COVID-19), large amounts of antivirals were consumed and released into wastewater, posing risks to the ecosystem and human health. Ozonation is commonly utilized as pre-oxidation process to enhance the disinfection of hospital wastewater during COVID-19 spread. In this study, the transformation of ribavirin, antiviral for COVID-19, during ozone/PMS­chlorine intensified disinfection process was investigated. â¢OH followed by O3 accounted for the dominant ribavirin degradation in most conditions due to higher reaction rate constant between ribavirin and â¢OH vs. SO4â¢- (1.9 × 109 vs. 7.9 × 107 M-1 s-1, respectively). During the O3/PMS process, ribavirin was dehydrogenated at the hydroxyl groups first, then lost the amide or the methanol group. Chloride at low concentrations (e.g., 0.5- 2 mg/L) slightly accelerated ribavirin degradation, while bromide, iodide, bicarbonate, and dissolved organic matter all reduced the degradation efficiency. In the presence of bromide, O3/PMS process resulted in the formation of organic brominated oxidation by-products (OBPs), the concentration of which increased with increasing bromide dosage. However, the formation of halogenated OBPs was negligible when chloride or iodide existed. Compared to the O3/H2O2 process, the concentration of brominated OBPs was significantly higher after ozonation or the O3/PMS process. This study suggests that the potential risks of the organic brominated OBPs should be taken into consideration when ozonation and ozone-based processes are used to enhance disinfection in the presence of bromide amid COVID-19 pandemic.

13.
Biometrics ; 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34145900

##### RESUMO

Although combination antiretroviral therapy (ART) with three or more drugs is highly effective in suppressing viral load for people with HIV, many ART agents may exacerbate mental health-related adverse effects including depression. Therefore, understanding the effects of combination ART on mental health can help clinicians personalize medicine with less adverse effects to avoid undesirable health outcomes. The emergence of electronic health records offers researchers unprecedented access to HIV data including individuals' mental health records, drug prescriptions, and clinical information over time. However, modeling such data is challenging due to high-dimensionality of the drug combination space, the individual heterogeneity, and sparseness of the observed drug combinations. To address these challenges, we develop a Bayesian nonparametric approach to learn drug combination effect on mental health in people with HIV adjusting for socio-demographic, behavioral, and clinical factors. The proposed method is built upon the subset-tree kernel that represents drug combinations in a way that synthesizes known regimen structure into a single mathematical representation. It also utilizes a distance-dependent Chinese restaurant process to cluster heterogeneous populations while considering individuals' treatment histories. We evaluate the proposed approach through simulation studies, and apply the method to a dataset from the Women's Interagency HIV Study, showing the clinical utility of our model in guiding clinicians to prescribe informed and effective personalized treatment based on individuals' treatment histories and clinical characteristics.

14.
Preprint | bioRxiv | ID: ppbiorxiv-447982

##### RESUMO

T follicular helper (Tfh) cells are the conventional drivers of protective, germinal center (GC)-based antiviral antibody responses. However, loss of Tfh cells and GCs has been observed in patients with severe COVID-19. As T cell-B cell interactions and immunoglobulin class switching still occur in these patients, non-canonical pathways of antibody production may be operative during SARS-CoV-2 infection. We found that both Tfh-dependent and -independent antibodies were induced against SARS-CoV-2 as well as influenza A virus. Tfh-independent responses were mediated by a population we call lymph node (LN)-Th1 cells, which remain in the LN and interact with B cells outside of GCs to promote high-affinity but broad-spectrum antibodies. Strikingly, antibodies generated in the presence and absence of Tfh cells displayed similar neutralization potency against homologous SARS-CoV-2 as well as the B.1.351 variant of concern. These data support a new paradigm for the induction of B cell responses during viral infection that enables effective, neutralizing antibody production to complement traditional GCs and even compensate for GCs damaged by viral inflammation. One-Sentence SummaryComplementary pathways of antibody production mediate neutralizing responses to SARS-CoV-2.

15.
Mol Med Rep ; 24(1)2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34036384

##### RESUMO

Pulmonary fibrosis is the primary reason for mortality in patients with paraquat (PQ) poisoning. Our previous study demonstrated that epithelial­mesenchymal transition (EMT) had a role in PQ­induced pulmonary fibrosis. However, the role of endoplasmic reticulum (ER) stress in PQ­induced EMT remains clear. The present study aimed to determine the role of ER stress in EMT in PQ­induced pulmonary fibrosis. A549 and RLE­6TN cells were incubated with LY294002 (a PI3K inhibitor) or transfected with protein kinase RNA­like ER kinase (PERK) small interfering RNA (si) for 24 h prior to being exposed to PQ. Next, the expression levels of ER stress­related proteins, PI3K/AKT/GSK­3ß signaling pathway­related proteins and EMT­related markers were analyzed by performing western blotting, reverse transcription­quantitative PCR and immunofluorescence assays. The results of the present study revealed that the protein expression levels of PERK, phosphorylated (p)­PERK, p­eukaryotic initiation factor 2 (eIF2)α were significantly upregulated in the PQ group, whereas p­PI3K, p­AKT and p­GSK­3ß were significantly upregulated in the sicontrol + PQ group compared with the sicontrol group. In vitro, following transfection with siPERK or treatment with the PI3K inhibitor, the protein expression levels of E­cadherin (an epithelial marker) were upregulated, whereas the protein expression levels of α­SMA (a mesenchymal marker) were downregulated. Immunofluorescence analysis revealed that the levels of E­cadherin were markedly upregulated, whereas the levels of α­SMA were notably downregulated following transfection with siPERK compared with the sicontrol group. The results of wound healing assay demonstrated that cell migration in the siPERK + PQ group was markedly decreased compared with the sicontrol + PQ group. These indicated that PQ­induced EMT was suppressed after silencing PERK. The expression levels of p­GSK­3ß, p­AKT and p­PI3K were also markedly downregulated in the siPERK + PQ group compared with the sicontrol + PQ group. In conclusion, the findings of the present study suggested that ER stress may promote EMT through the PERK signaling pathway in PQ­induced pulmonary fibrosis. Thus, ER stress may represent a potential therapeutic target for PQ­induced pulmonary fibrosis.

16.
Eur J Radiol ; 140: 109746, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33992979

##### RESUMO

PURPOSE: To evaluate computed tomography (CT) features and establish a predictive model for the clinical diagnosis and prognosis of tracheal adenoid cystic carcinoma (ACC). METHOD: From January 2010 to December 2018, 82 patients with tracheal tumors, including 46 patients with ACC confirmed by surgery and histopathology, were enrolled in this study. These patients' clinicopathologic information, CT features and survival outcomes were recorded and analyzed. Independent predictors of diagnosis and prognosis of tracheal ACC were determined by both univariate and multivariate analyses. RESULTS: Compared with tracheal non-ACC patients, univariate analysis showed that ACC patients were more likely to have extensive longitudinal length (p < 0.001) and to appear as annular wall thickening (p = 0.001), transmural growth (p = 0.036), poorly defined border (p = 0.003) and mild enhancement (p = 0.001). Multivariate logistic analysis showed that longitudinal length and enhancement degree were independent predictors of tracheal ACC. The 3-year and 5-year disease-free survival (DFS) were 75.7 % and 64.5 %, respectively. Longitudinal length (≥ 34â¯mm), transverse length (≥ 20â¯mm) and transmural growth were associated with poor DFS in univariate analysis. After multivariate adjustment, only transverse length (≥ 20â¯mm) was an adverse prognostic factor for DFS (hazard ratioâ¯=â¯4.594, 95 % confidence intervalâ¯=â¯1.240-17.017; p = 0.022). CONCLUSIONS: CT longitudinal length and enhancement degree of tumors showed satisfactory discrimination for tracheal ACC. Excessive CT transverse length might be an unfavorable indicator for ACC recurrence and could be helpful for predicting the survival outcomes of ACC at the initial diagnosis.

##### Assuntos
Carcinoma Adenoide Cístico , Neoplasias da Traqueia , Carcinoma Adenoide Cístico/diagnóstico por imagem , Humanos , Recidiva Local de Neoplasia , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Neoplasias da Traqueia/diagnóstico por imagem
17.
J Mol Histol ; 2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34050851

##### RESUMO

Accumulating evidence suggested that many long noncoding RNAs (lncRNAs) were widely involved in the development and progression of non-small cell lung cancer (NSCLC). However, the roles of lncRNA homeobox A11 antisense (HOXA11-AS) and its underlying mechanism in NSCLC remains largely unknown. The expression levels of HOXA11-AS, miR-3619-5p and sal-like protein 4 (SALL4) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot analysis was used to measure the protein levels of hexokinase II (HK2) and SALL4. Cell proliferation, apoptosis, migration and invasion were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry and transwell assay, respectively. The glucose consumption and lactate production were measured using glucose assay kit and lactate assay kit, respectively. The potential binding sites between miR-3619-5p and HOXA11-AS or SALL4 were predicted by online software and verified by luciferase report assay. A xenograft tumor model was established to confirm the function of HOXA11-AS in NSCLC in vivo. HOXA11-AS and SALL4 were upregulated while miR-3619-5p was downregulated in NSCLC tissues and cells. HOXA11-AS knockdown suppressed cell proliferation, migration, invasion, and glycolysis but promoted apoptosis in NSCLC cells. Moreover, miR-3619-5p could directly bind to HOXA11-AS and its inhibition attenuated the inhibitory effect of HOXA11-AS knockdown on progression of NSCLC cells. Furthermore, SALL4 was a direct target of miR-3619-5p and its overexpression reversed the anti-tumor role of miR-3619-5p in NSCLC cells. Besides, HOXA11-AS modulated SALL4 expression via sponging miR-3619-5p. Additionally, silencing HOXA11-AS inhibited tumor growth though upregulating miR-3619-5p and downregulating SALL4. Collectively, HOXA11-AS knockdown inhibited the progression of NSCLC by regulating miR-3619-5p/SALL4 axis, which might offer a novel avenue for interpreting the mechanism of NSCLC development.

18.
Front Immunol ; 12: 690565, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34054880

##### RESUMO

Immunotherapy has become an indispensable part of the comprehensive treatment of hepatocellular carcinoma (HCC). Immunotherapy has proven effective in patients with early HCC, advanced HCC, or HCC recurrence after liver transplantation. Clinically, the most commonly used immunotherapy is immune checkpoint inhibition using monoclonal antibodies, such as CTLA-4 and PD-1. However, it cannot fundamentally solve the problems of a weakened immune system and inactivation of immune cells involved in killing tumor cells. T cells can express tumor antigen-recognizing T cell receptors (TCRs) or chimeric antigen receptors (CARs) on the cell surface through gene editing to improve the specificity and responsiveness of immune cells. According to previous studies, TCR-T cell therapy is significantly better than CAR-T cell therapy in the treatment of solid tumors and is one of the most promising immune cell therapies for solid tumors so far. However, its application in the treatment of HCC is still being researched. Technological advancements in induction and redifferentiation of induced pluripotent stem cells (iPSCs) allow us to use T cells to induce T cell-derived iPSCs (T-iPSCs) and then differentiate them into TCR-T cells. This has allowed a convenient strategy to study HCC models and explore optimal treatment strategies. This review gives an overview of the major advances in the development of protocols to generate neoantigen-specific TCR-T cells from T-iPSCs. We will also discuss their potential and challenges in the treatment of HCC.

19.
Proc Natl Acad Sci U S A ; 118(20)2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-33941644

##### RESUMO

How coniferous forests evolved in the Northern Hemisphere remains largely unknown. Unlike most groups of organisms that generally follow a latitudinal diversity gradient, most conifer species in the Northern Hemisphere are distributed in mountainous areas at middle latitudes. It is of great interest to know whether the midlatitude region has been an evolutionary cradle or museum for conifers and how evolutionary and ecological factors have driven their spatiotemporal evolution. Here, we investigated the macroevolution of Pinus, the largest conifer genus and characteristic of northern temperate coniferous forests, based on nearly complete species sampling. Using 1,662 genes from transcriptome sequences, we reconstructed a robust species phylogeny and reestimated divergence times of global pines. We found that â¼90% of extant pine species originated in the Miocene in sharp contrast to the ancient origin of Pinus, indicating a Neogene rediversification. Surprisingly, species at middle latitudes are much older than those at other latitudes. This finding, coupled with net diversification rate analysis, indicates that the midlatitude region has provided an evolutionary museum for global pines. Analyses of 31 environmental variables, together with a comparison of evolutionary rates of niche and phenotypic traits with a net diversification rate, found that topography played a primary role in pine diversification, and the aridity index was decisive for the niche rate shift. Moreover, fire has forced diversification and adaptive evolution of Pinus Our study highlights the importance of integrating phylogenomic and ecological approaches to address evolution of biological groups at the global scale.

20.
Environ Pollut ; 285: 117237, 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33957515

##### RESUMO

Methane emitted by insects is considered to be an important source of atmospheric methane. Here we report the stimulation of methane emission in the cockroach Periplaneta americana and termite Coptotermes chaohuensis, insects with abundant methanogens, by neonicotinoids, insecticides widely used to control insect pests. Cycloxaprid (CYC) and imidacloprid (IMI) caused foregut expansion in P. americana, and increased the methane emission. Antibiotics mostly eliminated the effects. In P. americana guts, hydrogen levels increased and pH values decreased, which could be significantly explained by the gut bacterium community change. The proportion of several bacterium genera increased in guts following CYC treatment, and two genera from four could generate hydrogen. Hydrogen is a central intermediate in methanogenesis. All increased methanogens in both foregut and hindgut used hydrogen as electron donor to produce methane. Besides, the up-regulation of mcrA, encoding the enzyme for the final step of methanogenesis suggested the enhanced methane production ability in present methanogens. In the termite, hydrogen levels in gut and methane emission also significantly increased after neonicotinoid treatment, which was similar to the results in P. americana. In summary, neonicotinoids changed bacterium community in P. americana gut to generate more hydrogen, which then stimulated gut methanogens to produce and emit more methane. The finding raised a new concern over neonicotinoid applications, and might be a potential environmental risk associated with atmospheric methane.

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