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1.
Cell Death Dis ; 13(9): 813, 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36138018

RESUMO

A common stage of advanced prostate cancer is castration-resistant prostate cancer (CRPC), greater understanding of which is required in order to address and solve the clinically difficult challenge. Cathepsin K (CTSK) is a cysteine protease that usually has a strong activity of degrading extracellular matrix and is related to osteoclast-mediated bone destruction. However, the mechanism of CTSK-regulation in CRPC is still unclear to us. The current study aimed to analyze the expression of differentially expressed genes (DEGs) in patient samples (from localized PC and CRPC). Interestingly, we found that CTSK to be significantly up-regulated in CRPC. Through further signal pathway enrichment analysis, we found that the IL-17 signaling pathway to be highly correlated with CTSK. The oncogenic functions of CTSK and IL-17 in CRPC were proven by a series of in vivo and in vitro experiments. Possible downstream molecules of CTSK were investigated, which could serve as control elements to regulate the expression of EMT, thereby facilitating the metastasis and excessive proliferation of PC cells. Expression of CTSK was related to high concentration of M2 tumor-associated macrophages (TAMs) M2 in CRPC. A CTSK-mediated feedback circuit between TAMs and CRPC tissues was indicated in the process of transfer, proving the possibility of CTSK could be use as an available therapeutic target for CRPC.

2.
Eur Urol ; 2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36050131

RESUMO

BACKGROUND: Rhabdomyosarcoma (RMS) is the most common paediatric soft-tissue sarcoma. Approximately 15-20% of RMS cases arise from the bladder and prostate (B/P). The optimal treatment strategy for B/P RMS remains unclear. OBJECTIVE: To retrospectively evaluate the applicability of our procedure performed to treat paediatric patients with B/P RMS. DESIGN, SETTING, AND PARTICIPANTS: This is a retrospective analysis from a single tertiary referral hospital. From August 2003 to March 2021, 62 children pathologically diagnosed with B/P RMS underwent radical cystectomy and orthotopic detaenial sigmoid neobladder reconstruction in our centre. SURGICAL PROCEDURE: Surgical procedures included laparoscopic radical cystectomy and detaenial sigmoid neobladder reconstruction, which is demonstrated in the accompanying video. MEASUREMENTS: Demographic, clinical, and follow-up data were collected. Perioperative and long-term oncological and functional outcomes were reported. A logistic regression analysis was also performed. RESULTS AND LIMITATIONS: All surgeries, including three intracorporeal laparoscopic surgeries, were completed successfully. Of the 62 patients, 54 were alive without evidence of disease recurrence or metastasis at the last follow-up. Five of the 14 >12-yr-old boys reported that they experienced erections. Two female patients >12 yr old reported that they menstruated. However, this was a retrospective study conducted at a single centre with limited surgeon experience. CONCLUSIONS: Our results confirmed the safety and feasibility of primary orthotopic sigmoid neobladder reconstruction after radical cystectomy for paediatric patients with B/P RMS. Good outcomes in terms of oncological control and functional recovery were achieved. The high histocompatibility and tissue adaptability of children are inspiring. PATIENT SUMMARY: We describe our stepwise technique of radical cystectomy and detaenial sigmoid neobladder reconstruction for paediatric patients with bladder and prostate rhabdomyosarcoma. With this technique, we were able to achieve good functional recovery without compromising cancer control and significantly increasing complications.

3.
Annu Int Conf IEEE Eng Med Biol Soc ; 2022: 1314-1318, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36086121

RESUMO

Electrocardiogram (ECG) signal provides a graphical representation of cardiac activity and is the most commonly adopted clinical tool for cardiac abnormalities detection. Heartbeat detection, as the first step in analyzing ECG signals, is required for an accurate diagnosis. Stationary wavelet transform (SWT) as a commonly used algorithm for heartbeat detection has a disadvantage of phase shift regarding the original signal. This work addresses this issue by presenting a new method that incorporates an SWT-based zero-phase filter bank with a voting scheme. Our results indicated that a superior performance in heartbeat detection was achieved from the upper arm compared to conventional SWT with a more accurate localization. We achieved sensitivity (SE) and positive predictive value (PPV) of 0.98±0.04 and 0.95±0.09 with the most distance of 50 ms from the actual heartbeats. The SE and PPV changed to 0.75±0.15 and 0.73±0.16, respectively for the distance of 20 ms. Clinical Relevance- The proposed method can be later implemented in wearable devices for convenient cardiac activity monitoring from upper arm or other none-conventional sites.


Assuntos
Braço , Análise de Ondaletas , Frequência Cardíaca , Política , Processamento de Sinais Assistido por Computador
4.
Neuroscience ; 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36067951

RESUMO

MicroRNAs (miRNAs) are widely acknowledged to play a unique role in cerebrovascular disease. This research investigates the function of microRNAs in ischemic stroke via a middle cerebral artery occlusion (MCAO) model. Four differentially expressed microRNAs in rat brains were identified by bioinformatics analysis, and qRT-PCR showed that miR-423-5p exhibited the highest expression in cerebral ischemia/reperfusion injury in rats, with peak levels observed at 24 hours. After microRNA inhibitors and mimics were administrated in the rat model of MCAO, the neurological scores and brain water content were detected, and triphenyltetrazolium chloride (TTC), Hematoxylin and Eosin (H&E), and Nissl staining were conducted to explore the influence of miR-423-5p on ischemic stroke. Subsequently, western blot, ELISA, MPO, TUNEL and commercial assay kits were applied to assess the influence of miR-423-5p on NLRP3 inflammasome, apoptosis, and oxidative stress levels in ischemic penumbra tissue. The results showed that miR-423-5p knockdown could effectively improve neurological indicators, such as cerebral infarct volume, brain water content, neurological scores, and nerve tissue damage, and inhibit the NLRP3 inflammasome, apoptosis, and oxidative stress. In contrast, the miR-423-5p mimic yielded opposite results. In conclusion, inhibition of miR-423-5p expression could effectively attenuate ischemic stroke and might be considered a promising target for stroke.

5.
Front Plant Sci ; 13: 978951, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061782

RESUMO

Fusarium oxysporum is a main causative agent of tobacco root rot, severely affecting tobacco growth. Here, 200 F. oxysporum strains were isolated and examined for their virulence toward tobacco plants. These strains were divided into disease class 1-3 (weak virulence), 4-6 (moderate virulence), and 7-9 (strong virulence). To understand the virulence mechanism of F. oxysporum, a comparative transcriptome study was performed using weak, moderate, and strong virulence-inducing strains. The results showed that expression levels of 1,678 tobacco genes were positively correlated with virulence levels, while expression levels of 3,558 genes were negatively associated with virulence levels. Interestingly, the expression levels of ATP synthase genes were positively correlated with F. oxysporum virulence. To verify whether ATP synthase gene expression is associated with F. oxysporum virulence, 5 strains each of strong, moderate, and weak virulence-inducing strains were tested using qRT-PCR. The results confirmed that ATP synthase gene expression is positively correlated with virulence levels. Knock-out mutants of ATP synthase genes resulted in a relatively weak virulence compared to wild-type as well as the inhibition of F. oxysporum-mediated suppression of NtSUC4, NtSTP12, NtHEX6, and NtSWEET, suggesting that ATP synthase activity is also associated with the virulence. Taken together, our analyses show that ATP synthases are key genes for the regulation of F. oxysporum virulence and provide important information for understanding the virulence mechanism of F. oxysporum in tobacco root rot.

6.
Endocrine ; 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36070051

RESUMO

OBJECTIVE: The aim of this study was to construct a collagen-related prognostic model for thyroid cancer and to investigate prognostic value of collagen family genes for thyroid cancer. METHODS: A LASSO Cox regression model for thyroid cancer was developed based on the expression profiles of collagen-related genes. Kaplan-Meier survival analysis was performed for high and low risk groups. The ROC method was used to assess its predictive performance. Predictive independence was verified by multivariate Cox regression analysis. The relationship between this feature and immune cell infiltration was analyzed by tumor microenvironment. COL18A1 was validated by immunohistochemistry and RT-PCR in thyroid cancer tissues. The effect of COL18A1 on cell proliferation, migration and invasion ability of tumor cells were further valuated by CCK-8 assay and transwell assay. The effect of COL18A1 on the immune escape ability of tumor cells was further valuated by cytotoxicity assays. RESULTS: A model including 4 collagen family genes was developed to predict thyroid cancer prognosis. Patients with high-risk score had a poorer prognosis than those with low-risk scores for 1-, 2-, 3-, and 5- year survival. The model independently predicted prognosis after adjusting for other prognostic factors. A nomogram combining risk score and age was constructed with high sensitivity and specificity. This feature was significantly associated with immune cell infiltration. COL18A1 was aberrantly over-expressed in thyroid cancer compared with control tissues and significantly increased proliferative capacity, migration capacity, invasion capacity, and immune escape ability of tumor cells. CONCLUSION: Our findings establish a signature associated with collagen family genes that can be a promising tool to predict the prognosis of thyroid cancer. High COL18A1 expression significantly correlates with the poor prognosis of patients and enhances the immune escape ability of tumor cells.

7.
Front Pharmacol ; 13: 890330, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105220

RESUMO

Chronic restraint stress (CRS) is a classic animal model of stress that can lead to various physiological and psychological dysfunctions, including systemic neuroinflammation and memory deficits. Fresh Gastrodia elata Blume (FG), the unprocessed raw tuber of Gastrodia elata Blume, has been reported to alleviate the symptoms of headache, convulsions, and neurodegenerative diseases, while the protective effects of FG on CRS-induced cognitive deficits remain unclear. This work aimed to evaluate the effects of FG on CRS-induced cognitive deficits through multiplex animal behavior tests and to further explore the related mechanism by observing the expression of mitochondrial apoptosis-related proteins in the mouse hippocampus. In in vivo experiments, mice were subjected to the object location recognition test (OLRT), new object recognition test (NORT), Morris water maze test (MWMT), and passive avoidance test (PAT) to evaluate the learning and memory ability. In in vitro experiments, the expression of the AKT/CREB pathway, the fission- and apoptosis-related proteins (Drp1, Cyt C, and BAX), and the proinflammatory cytokines' (TNF-α and IL-1ß) level in the hippocampus was examined. Our results demonstrated that in spontaneous behavior experiments, FG significantly improved the cognitive performance of CRS model mice in OLRT (p < 0.05) and NORT (p < 0.05). In punitive behavior experiments, FG shortened the escape latency in long-term spatial memory test (MWMT, p < 0.01) and prolonged the latency into the dark chamber in non-spatial memory test (PAT, p < 0.01). Biochemical analysis showed that FG treatment significantly suppressed CRS-induced Cyt C, Drp1, and BAX activation (p < 0.001, p < 0.01 and p < 0.05), promoted the CREB, p-CREB, AKT, and p-AKT level (p < 0.05, p < 0.01 and p < 0.001), and inhibited the CRS-induced proinflammatory cytokines (TNF-α and IL-1ß, p < 0.05 and p < 0.001) level in the hippocampus. Taken together, these results suggested that FG could attenuate cognitive deficits induced by CRS on multiple learning and memory behavioral tests.

8.
J Biol Chem ; : 102490, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36115458

RESUMO

Branching morphogenesis is a key process essential for lung and other organ development in which cellular and tissue architecture branch out to maximize surface area. While this process is known to be regulated by differential gene expression of ligands and receptors, how chromatin remodeling regulates this process remains unclear. Znhit1, acting as a chromatin remodeler, has previously been shown to control the deposition of the histone variant H2A.Z. Here, we demonstrate that Znhit1 also plays an important role in regulating lung branching. Using Znhit1 conditional knockout mice, we show that Znhit1 deficiency in the embryonic lung epithelium leads to failure of branching morphogenesis and neonatal lethality, which is accompanied by reduced cell proliferation and increased cell apoptosis of the epithelium. The results from the transcriptome and the ChIP assay reveal that this is partially regulated by the derepression of Bmp4, encoding bone morphogenetic protein 4, which is a direct target of H2A.Z. Furthermore, we show that inhibition of BMP signaling by the protein inhibitor Noggin rescues the lung branching defects of Znhit1 mutants ex vivo. Taken together, our study identifies the critical role of Znhit1/H2A.Z in embryonic lung morphogenesis via the regulation of BMP signaling.

9.
Methods Mol Biol ; 2574: 183-208, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36087202

RESUMO

Linking antigen specificity to T cell receptor (TCR) sequences is critical, albeit challenging, to both understanding T cell biology and developing T cell-based therapeutics. Here, we describe in detail tetramer-associated TCR sequencing (TetTCR-Seq), a novel approach to tackling this challenge. TetTCR-Seq is accomplished by multiplexing DNA-barcoded peptide-MHC (pMHC) tetramers, allowing for simultaneous recall of antigen specificity and TCR sequences after single cell sequencing. Additionally, TetTCR-Seq simplifies labor and cuts cost by taking advantage of in vitro transcription and translation (IVTT) to generate peptide libraries and DNA barcodes, in parallel, from the same template. Thus, TetTCR-Seq is a powerful technology capable of quickly and affordably surveying the T cell repertoire for hundreds of antigen specificities in a single experiment.


Assuntos
Receptores de Antígenos de Linfócitos T , Linfócitos T , Sequenciamento de Nucleotídeos em Larga Escala , Receptores de Antígenos de Linfócitos T/genética
10.
Arch Microbiol ; 204(9): 596, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36056268

RESUMO

Strain DKSPLA3T, a novel Gram-negative, catalase-positive, oxidase-positive, non-spore-forming, aerobic, non-nitrogen-fixing, non-motile bacterium was isolated from Quercus variablis leaf, in Zunyi, Guizhou, China. Growth occurred at 4-37 °C (optimum 28 °C), pH 4.0-9.0 (optimum pH 7.0) and up to 4.0% (w/v) NaCl (optimum under 2.0%, w/v). Phylogeny based on 16S rRNA gene indicated that strain DKSPLA3T was a novel species in the genus Rhizobium, which was supported by average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values. The predominant fatty acids of strain DKSPLA3T were C16:0, C18:1 ω7c and/or C18:1 ω6c and C18:1 ω7c 11-methyl. The major respiratory quinone was Q-10. Major polar lipids were diphosphatidyl glycerol (DPG), phosphatidyl glycerol (PG), phosphatidylethanolamine (PE), phosphatidylmonomethylethanolamine (PME), phosphatidylcholine (PC), two unidentified phospholipids (PL) and nine unidentified lipids (L). The genomic G + C content was 64.47 mol%. Based on the phenotypic, phylogenetic and genotypic data, DKSPLA3T should be classified as a novel species in the genus Rhizobium, for which the name Rhizobium quercicola sp. nov. (KCTC 82843T = CFCC 16,707T) is proposed.


Assuntos
Quercus , Rhizobium , Técnicas de Tipagem Bacteriana , China , DNA Bacteriano/genética , Ácidos Graxos/química , Fosfolipídeos/química , Filogenia , Folhas de Planta , Quercus/genética , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
11.
Food Res Int ; 160: 111708, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36076457

RESUMO

Fungal chemicals are vital in processes recognizing damage- and microbe-associated molecules (DAMPs/MAMPs) that trigger defense responses in fungi. Pleurotus ostreatus is a widely cultivated edible fungus that is prone to attack from fungivorous insects and mites. Yet P. ostreatus has evolved an elegant defense system against fungivore attacks. In this study, we investigated how the oyster mushroom responds to the fungivory and mechanical wounding by conducting transcriptome, proteome, and secondary metabolic analyses. The profiling analysis revealed a total of 11,495 transcripts and 866 proteins, 4416 differentially expressed genes (DEGs), and 62 differentially expressed proteins (DEPs) were identified in response to the mite Tyrophagus putrescentiae feeding and mechanical wounding. In comparing the responses induced by mechanical wounding, some genes, proteins, and metabolites were uniquely induced or repressed by the mite. At the transcript level, nine pathways were activated by the mite feeding, including those of "MAPK signaling pathway-yeast", "Phenylalanine metabolism", and "Biotin metabolism", among others, while both enrichment of "Ribosome", "Ribosome biogenesis in eukaryotes", and "Regulation of Mitophagy in Yeast" demonstrated the common effects upon fungal secretory protein synthesis and processing induced by fungivory and mechanical wounding. Fungivory also stimulated the synthesis of C8-aryl compounds and sesquiterpenes (especially1-octen-3-ol and α-/ß-bisabolene), and these compounds repellent to T. putrescentiae. Both jasmonic acid (JA) and jasmonic acid methyl ester (MeJA) were specifically regulated by mite feeding and mechanical wounding. The terpene synthase gene transcription was significantly increased induced by the exogenous addition of MeJA, resulting in defensive sesquiterpene production against the mite. These findings are the first to demonstrate that the reactive oxygen species (ROS)/MAPK signaling pathway, JA regulation, specific gene expression, and protein synthesis, and anti-mite substance metabolism are all involved in coordinated inducible chemical-based defense responses in P. ostreatus, which could be especially effective the mite T. putrescentiae.


Assuntos
Acaridae , Pleurotus , Animais , Mecanismos de Defesa , Proteínas Fúngicas , Micélio , Pleurotus/genética
12.
Front Genet ; 13: 955133, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36118857

RESUMO

Objective: Neuroendocrine prostate cancer (NEPC) is an aggressive variant of prostate cancer (PC) that may arise de novo or in patients previously treated with hormonal therapies for prostate adenocarcinoma as a mechanism of resistance. In our investigation, there appeared to be a strong correlation between neuroendocrine differentiation prostate cancer (NEDPC) and NEPC. The objectives of this study included exploring whether NEDPC is an intermediate stage in the progression of high-risk prostate cancer (HRPC) to NEPC and identifying risk factors and new targets associated with survival in the treatment of NEPC. Methods: The selected prostate cancer patients were progressed to high-risk and characterized by neuroendocrine. We collected the clinical data and characteristics of patients with three types of cancer: the incidence of metastasis, site and time of metastasis, recurrence rate, related treatment methods, etc. The similarity and differences of the three groups were compared through experiment and database. Results: By analyzing the clinical data and immunohistochemical results, we found that there seems to be a clinical feature of neuroendocrine differentiation (NED) status in between when patients progress from PC to NEPC. Finding novel treatment targets would therefore be beneficial by taking into account NEDPC as the stage of PC progression prior to NEPC. The metastasis-free survival curve and the immunohistochemical results are informing us that NEDPC can be a pre-state for diagnosing NEPC. Conclusion: NEPC is a late PC symptom that is frequently disregarded and has a bad prognosis. Finding novel treatment targets would therefore be beneficial by taking into account NEDPC as the stage of PC progression prior to NEPC.

13.
Plant Dis ; 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35971260

RESUMO

Tobacco is one of the most significant non-food cash crops (Lu et al. 2020). In March 2022, cigar tobacco plants showing characteristic symptoms of vascular discoloration, stem rotting, leaf wilting and rotting were observed in Tengchong city (N 25°3'26″, E 98°25'6″) of Yunnan province, China (Fig. S1). The disease incidence was about 5% on cultivar Yunxue 6 in a 33-ha field. Infected stems were collected from Tengchong for pathogen isolation and 16S rDNA sequence analysis was performed as previously described (Lu et al. 2021). Sequence analysis showed that tobacco isolates (GenBank accession numbers: ON795108, ON795107 and ON795106) had an identical sequence with that of the species type strain of Pectobacterium versatile CFBP 6051T and shared the sequence identities of 99.55% and 99.47% with P. carotovorum DSM 30168T and P. parvum s0421T, respectively. Furthermore, phylogenetic analysis showed that tobacco strains were clustered with Pectobacterium versatile CFBP 6051T (Fig. S2a). In API assays, strain 22TC1 was positive for ß-galactosidase activity, reduction of nitrates to nitrites, fermentation of glucose, hydrolysis of esculin and gelatin, assimilation of D-glucose, L-arabinose, D-mannose, D-mannitol, N-acetylglucosamine, malic acid and trisodium citrate; positive for the enzymatic substrates of alkaline phosphatase, leucine arylamidase, acid phosphatase, naphthol-AS-BI-phosphohydrolase, α-galactosidase, ß-galactosidase and α-glucosidase. Furthermore, the average nucleotide identity (ANI) analysis (Richter et al. 2015) showed that strain 22TC1 (GenBank accession number: JAMWYQ000000000) had the highest ANIb score of 96.76% and ANIm value of 97.19% with P. versatile CFBP 6051T. Similarly, in silico DNA-DNA hybridization (isDDH) value was 74.5% compared to P. versatile CFBP 6051T, isDDH values were 35.5-63.7% with the other Pectobacterium species, which below the 70% threshold value for species delineation (Meier-Kolthoff et al. 2021). The phylogenomic analysis also showed that strain 22TC1 was clustered with the species type strain of P. versatile CFBP 6051T. For pathogenicity tests, cell suspension with ten-fold dilution (approx. 1 x 108 CFU/ml) was injected into the leaf axils of two 2-month-old tobacco stems (cv. Yunyan 87). As a control, tobacco seedlings were inoculated with sterile distilled water. The plants were sealed in plastic bags and maintained in a growth chamber at 28°C for 2 d. The symptoms of water-soaked decay were observed within 24 h of inoculation. Whole-plant decay was at 2 days after injection. No symptoms were developed in the controls. Reisolation was performed on diseased stems and the identity of isolated bacteria was confirmed by PCR and sequencing of 16S rRNA. Similar results were obtained in two independent experiments. Based on the above-described data, the causal pathogen of stem rot on cigar tobacco in Tengchong was identified as P. versatile. To our knowledge, this is the first time that P. versatile is found to cause stem rot on tobacco. Pectobacterium species have been reported to cause seed-borne diseases on tobacco seedlings in the floating tray system and soil-borne diseases in tobacco fields (Wang et al. 2017; Xia and Mo 2007). Therefore, studying the possible transmission of the P. versatile to tobacco plants is necessary.

14.
Infect Drug Resist ; 15: 4563-4573, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35999831

RESUMO

Purpose: Carbapenem-resistant organisms (CROs) have posed a great threat to antibiotic use and induce multi-drug resistance. Contamination of the hospital environment and infection of healthcare workers (HCWs) are reported as sources of nosocomial infections. Here, we performed a comprehensive environment sampling and timely epidemiological investigation during outbreaks to investigate the role of the environment and HCWs in CRO transmission. Patients and Methods: We enrolled carbapenem-resistant organism outbreaks in ICU-1 of Huashan Hospital from January 2019 to March 2019, and ICU-2 located at west branch of Huashan Hospital from October 2019 to November 2019. Carbapenem-resistant Klebsiella pneumoniae (CRKP) and carbapenem-resistant Acinetobacter baumannii (CRAB) isolates were collected from the patients. We performed a real-time comprehensive environmental and HCW sampling in the two ICUs. Isolated strains from patients and the positive colonies from the screening were sent for whole-genome sequencing. Finally, phylogenetic trees were constructed. Results: CRAB and CRKP outbreaks simultaneously occurred in ICU-1; the outbreak involved 13 patients. Meanwhile, the CRKP outbreak in ICU-2 included 11 patients. Twelve out of 146 environment and HCWs samples in ICU-1 were carbapenem-resistant bacteria, including six CRKP and six CRAB strains. For ICU-2, hospital surfaces and HCWs were negative for CRKP. Phylogenetic analyses showed that CRKP strains in ICU-1 were classified into two clades: Clade 1 and Clade 2, sharing a high similarity of isolates from the environment and HCWs. The same phenomenon was observed in CRAB. Conclusion: A timely comprehensive sampling combined with genome-based investigation may aid in tracking the transmission route of and controlling the infections. The environment and HCWs could be contaminated during CRO transmission, which calls for strengthened prevention and control measures.

16.
Folia Neuropathol ; 60(2): 195-209, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35950472

RESUMO

This study was designed to elucidate the relationship of miR-211-3p and rhomboid domain containing 1 (RHBDD1) in glioma. Here, we first observed that miR-211-3p directly targets the 3˘-UTR of RHBDD1 in glioma cells using dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and Western blot analysis. Pearson's correlation analysis showed that miR-211-3p expression was negatively correlated with RHBDD1 expression in glioma tissues. CCK-8 assay, flow cytometry, and transwell assay were applied to assess cell proliferation, cell cycle distribution, migration, and invasion. The results showed that RHBDD1 knockdown inhibited cell proliferation, cell cycle G1/S transition, migration, and invasion in two glioma cell lines (U87 and LN-229). Knockdown of miR-211-3p obtained opposite results. Moreover, overexpression of RHBDD1 counteracted suppressive effects of miR-211-3p on glioma cells. Furthermore, decreased expression of CDK4, cyclin D1, N-cadherin, and vimentin as well as increased E-cadherin expression induced by miR-211-3p was reversed by RHBDD1 overexpression. Our results suggested that targeting miR-211-3p/RHBDD1 axis might be a novel effective therapeutic target for glioma treatment.


Assuntos
Glioma , MicroRNAs , Linhagem Celular Tumoral , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/genética , Glioma/genética , Glioma/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismo
17.
Polymers (Basel) ; 14(15)2022 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-35956613

RESUMO

This work focused on the effects of the hydrothermal environment on the aging of all-steel radial tire (ASRT) composites. Composite specimens were conditioned by immersion in deionized water at 30, 60 and 90 °C. Its water absorption, thermal and mechanical properties (tensile strength, elasticity modulus, elongation at break and interfacial shear strength), morphological structure, as well as molecular cross-linking reaction were investigated before and after aging. Results indicated that there was no dynamic equilibrium of water absorption of ASRT composites after deviating from the Fickian model. The molecular cross-linking density of the rubber matrix showed an increase in the early stage of aging. Then, the mechanical properties suffered of a drop due to the degradation of the rubber matrix and the poor interface between the steel fiber and rubber matrix. Additionally, a systematic hygrothermal aging mechanism was proposed.

18.
Plant J ; 2022 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-35959634

RESUMO

Sacred lotus (Nelumbo nucifera Gaertn.) is a basal eudicot plant with a unique lifestyle, physiological features, and evolutionary characteristics. Here we report the unique profile of transposable elements (TEs) in the genome, using a manually curated repeat library. TEs account for 59% of the genome, and hAT (Ac/Ds) elements alone represent 8%, more than in any other known plant genome. About 18% of the lotus genome is comprised of Copia LTR retrotransposons, and over 25% of them are associated with non-canonical termini (non-TGCA). Such high abundance of non-canonical LTR retrotransposons has not been reported for any other organism. TEs are very abundant in genic regions, with retrotransposons enriched in introns and DNA transposons primarily in flanking regions of genes. The recent insertion of TEs in introns has led to significant intron size expansion, with a total of 200 Mb in the 28 455 genes. This is accompanied by declining TE activity in intergenic regions, suggesting distinct control efficacy of TE amplification in different genomic compartments. Despite the prevalence of TEs in genic regions, some genes are associated with fewer TEs, such as those involved in fruit ripening and stress responses. Other genes are enriched with TEs, and genes in epigenetic pathways are the most associated with TEs in introns, indicating a dynamic interaction between TEs and the host surveillance machinery. The dramatic differential abundance of TEs with genes involved in different biological processes as well as the variation of target preference of different TEs suggests the composition and activity of TEs influence the path of evolution.

19.
Front Immunol ; 13: 896685, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35924243

RESUMO

Cell therapy is a distinguished targeted immunotherapy with great potential to treat solid tumors in the new era of cancer treatment. Cell therapy products include genetically engineered cell products and non-genetically engineered cell products. Several recent cell therapies, especially chimeric antigen receptor (CAR)-T cell therapies, have been approved as novel treatment strategies for cancer. Many clinical trials on cell therapies, in the form of cell therapy alone or in combination with other treatments, in solid tumors, have been conducted or ongoing. However, there are still challenges since adverse events and the limited efficacy of cell therapies have also been observed. Here, we concisely summarize the clinical milestones of the conducted and ongoing clinical trials of cell therapy, introduce the evolution of CARs, discuss the challenges and limitations of these therapeutic modalities taking CAR-T as the main focus, and analyze the disparities in the regulatory policies in different countries.


Assuntos
Neoplasias , Receptores de Antígenos Quiméricos , Terapia Baseada em Transplante de Células e Tecidos , Humanos , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos Quiméricos/genética , Linfócitos T
20.
G3 (Bethesda) ; 2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-35976112

RESUMO

The majority of sequenced genomes in the monocots are from species belonging to Poaceae, which include many commercially important crops. Here, we expand the number of sequenced genomes from the monocots to include the genomes of four related cyperids: Carex cristatella and Carex scoparia from Cyperaceae and Juncus effusus and Juncus inflexus from Juncaceae. The high-quality, chromosome-scale genome sequences from these four cyperids were assembled by combining whole-genome shotgun sequencing of Nanopore long reads, Illumina short reads and Hi-C sequencing data. Some members of the Cyperaceae and Juncaceae are known to possess holocentric chromosomes. We examined the repeat landscapes in our sequenced genomes to search for potential repeats associated with centromeres. Several large satellite repeat families, comprising 3.2% to 9.5% of our sequenced genomes, showed dispersed distribution of large satellite repeat clusters across all Carex chromosomes, with few instances of these repeats clustering in the same chromosomal regions. In contrast, most large Juncus satellite repeats were clustered in a single location on each chromosome, with sporadic instances of large satellite repeats throughout the Juncus genomes. Recognizable transposable elements account for about 20% of each of the four genome assemblies, with the Carex genomes containing more DNA transposons than retrotransposons while the converse is true for the Juncus genomes. These genome sequences and annotations will facilitate better comparative analysis within monocots.

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