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1.
J Virol ; 98(5): e0195923, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38634598

RESUMO

The role of Culex mosquitoes in the transmission of Japanese encephalitis virus (JEV) is crucial, yet the mechanisms of JEV infection in these vectors remain unclear. Previous research has indicated that various host factors participate in JEV infection. Herein, we present evidence that mosquito sialic acids enhance JEV infection both in vivo and in vitro. By treating mosquitoes and C6/36 cells with neuraminidase or lectin, the function of sialic acids is effectively blocked, resulting in significant inhibition of JEV infection. Furthermore, knockdown of the sialic acid biosynthesis genes in Culex mosquitoes also leads to a reduction in JEV infection. Moreover, our research revealed that sialic acids play a role in the attachment of JEV to mosquito cells, but not in its internalization. To further explore the mechanisms underlying the promotion of JEV attachment by sialic acids, we conducted immunoprecipitation experiments to confirm the direct binding of sialic acids to the last α-helix in JEV envelope protein domain III. Overall, our study contributes to a molecular comprehension of the interaction between mosquitoes and JEV and offers potential strategies for preventing the dissemination of flavivirus in natural environments.IMPORTANCEIn this study, we aimed to investigate the impact of glycoconjugate sialic acids on mosquito infection with Japanese encephalitis virus (JEV). Our findings demonstrate that sialic acids play a crucial role in enhancing JEV infection by facilitating the attachment of the virus to the cell membrane. Furthermore, our investigation revealed that sialic acids directly bind to the final α-helix in the JEV envelope protein domain III, thereby accelerating virus adsorption. Collectively, our results highlight the significance of mosquito sialic acids in JEV infection within vectors, contributing to a better understanding of the interaction between mosquitoes and JEV.


Assuntos
Culex , Vírus da Encefalite Japonesa (Espécie) , Encefalite Japonesa , Ácidos Siálicos , Ligação Viral , Animais , Camundongos , Linhagem Celular , Culex/virologia , Culex/metabolismo , Vírus da Encefalite Japonesa (Espécie)/fisiologia , Vírus da Encefalite Japonesa (Espécie)/metabolismo , Encefalite Japonesa/virologia , Encefalite Japonesa/metabolismo , Mosquitos Vetores/virologia , Neuraminidase/metabolismo , Neuraminidase/genética , Ácidos Siálicos/metabolismo , Proteínas do Envelope Viral/metabolismo , Proteínas do Envelope Viral/genética , Internalização do Vírus
2.
Small ; 20(23): e2310614, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38200684

RESUMO

Musculoskeletal (MSK) disorders significantly burden patients and society, resulting in high healthcare costs and productivity loss. These disorders are the leading cause of physical disability, and their prevalence is expected to increase as sedentary lifestyles become common and the global population of the elderly increases. Proper innervation is critical to maintaining MSK function, and nerve damage or dysfunction underlies various MSK disorders, underscoring the potential of restoring nerve function in MSK disorder treatment. However, most MSK tissue engineering strategies have overlooked the significance of innervation. This review first expounds upon innervation in the MSK system and its importance in maintaining MSK homeostasis and functions. This will be followed by strategies for engineering MSK tissues that induce post-implantation in situ innervation or are pre-innervated. Subsequently, research progress in modeling MSK disorders using innervated MSK organoids and organs-on-chips (OoCs) is analyzed. Finally, the future development of engineering innervated MSK tissues to treat MSK disorders and recapitulate disease mechanisms is discussed. This review provides valuable insights into the underlying principles, engineering methods, and applications of innervated MSK tissues, paving the way for the development of targeted, efficacious therapies for various MSK conditions.


Assuntos
Doenças Musculoesqueléticas , Engenharia Tecidual , Engenharia Tecidual/métodos , Humanos , Animais , Doenças Musculoesqueléticas/terapia , Medicina Regenerativa/métodos , Ortopedia
3.
Plant Cell ; 33(8): 2685-2700, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34003932

RESUMO

MEIOSIS ARRESTED AT LEPTOTENE1 (MEL1), a rice (Oryza sativa) Argonaute (AGO) protein, has been reported to function specifically at premeiotic and meiotic stages of germ cell development and is associated with a novel class of germ cell-specific small noncoding RNAs called phased small RNAs (phasiRNAs). MEL1 accumulation is temporally and spatially regulated and is eliminated after meiosis. However, the metabolism and turnover (i.e. the homeostasis) of MEL1 during germ cell development remains unknown. Here, we show that MEL1 is ubiquitinated and subsequently degraded via the proteasome pathway in vivo during late sporogenesis. Abnormal accumulation of MEL1 after meiosis leads to a semi-sterile phenotype. We identified a monocot-specific E3 ligase, XBOS36, a CULLIN RING-box protein, that is responsible for the degradation of MEL1. Ubiquitination at four K residues at the N terminus of MEL1 by XBOS36 induces its degradation. Importantly, inhibition of MEL1 degradation either by XBOS36 knockdown or by MEL1 overexpression prevents the formation of pollen at the microspore stage. Further mechanistic analysis showed that disrupting MEL1 homeostasis in germ cells leads to off-target cleavage of phasiRNA target genes. Our findings thus provide insight into the communication between a monocot-specific E3 ligase and an AGO protein during plant reproductive development.


Assuntos
Oryza/fisiologia , Proteínas de Plantas/metabolismo , Esporos/crescimento & desenvolvimento , Ubiquitina/metabolismo , Proteínas Argonautas/genética , Proteínas Argonautas/metabolismo , Regulação da Expressão Gênica de Plantas , Lisina/metabolismo , Meiose , Oryza/genética , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas , Pólen/genética , Pólen/crescimento & desenvolvimento , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , RNA de Plantas/genética , RNA de Plantas/metabolismo , Pequeno RNA não Traduzido/genética , Pequeno RNA não Traduzido/metabolismo , Esporos/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
4.
Artigo em Inglês | MEDLINE | ID: mdl-38695865

RESUMO

A novel Gram-staining-positive actinobacterium with antimicrobial activity, designated CFH 90308T, was isolated from the sediment of a salt lake in Yuncheng, Shanxi, south-western China. The isolate exhibited the highest 16S rRNA gene sequence similarities to Microbacterium yannicii G72T, Microbacterium hominis NBRC 15708T and Microbacterium xylanilyticum S3-ET (98.5, 98.4 and 98.2 %, respectively), and formed a separate clade with M. xylanilyticum S3-ET in phylogenetic trees. The strain grew at 15-40 ºC, pH 6.0-8.0 and could tolerate NaCl up to a concentration of 15 % (w/v). The whole genome of strain CFH 90308T consisted of 4.33 Mbp and the DNA G+C content was 69.6 mol%. The acyl type of the peptidoglycan was glycolyl and the whole-cell sugars were galactose and mannose. The cell-wall peptidoglycan mainly contained alanine, glycine and lysine. The menaquinones of strain CFH 90308T were MK-12, MK-13 and MK-11. Strain CFH 90308T contained anteiso-C15:0, anteiso-C17:0, iso-C16:0 and iso-C15:0 as the predominant fatty acids. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between CFH 90308T and the other species of the genus Microbacterium were found to be low (ANIb <81.3 %, dDDH <25.6 %). The secondary metabolite produced by strain CFH 90308T showed antibacterial activities against Bacillus subtilis, Pseudomonas syringae, Aeromonas hydrophila and methicillin-resistant Staphylococcus aureus. Based on genotypic, phenotypic and chemotaxonomic results, the isolate is considered to represent a novel species of the genus Microbacterium, for which the name Microbacterium salsuginis sp. nov. is proposed. The type strain is CFH 90308T (=DSM 105964T=KCTC 49052T).


Assuntos
Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Sedimentos Geológicos , Microbacterium , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , Vitamina K 2 , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , China , Vitamina K 2/análogos & derivados , Sedimentos Geológicos/microbiologia , Peptidoglicano , Lagos/microbiologia , Hibridização de Ácido Nucleico , Cloreto de Sódio/metabolismo , Genoma Bacteriano
5.
J Chem Inf Model ; 64(3): 1066-1080, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38238993

RESUMO

Ovarian cancer (OC) is a highly heterogeneous disease, with patients at different tumor staging having different survival times. Metabolic reprogramming is one of the key hallmarks of cancer; however, the significance of metabolism-related genes in the prognosis and therapy outcomes of OC is unclear. In this study, we used weighted gene coexpression network analysis and differential expression analysis to screen for metabolism-related genes associated with tumor staging. We constructed the metabolism-related gene prognostic index (MRGPI), which demonstrated a stable prognostic value across multiple clinical trial end points and multiple validation cohorts. The MRGPI population had its distinct molecular features, mutational characteristics, and immune phenotypes. In addition, we investigated the response to immunotherapy in MRGPI subgroups and found that patients with low MRGPI were prone to benefit from anti-PD-1 checkpoint blockade therapy and exhibited a delayed treatment effect. Meanwhile, we identified four candidate therapeutic drugs (ABT-737, crizotinib, panobinostat, and regorafenib) for patients with high MRGPI, and we evaluated the pharmacokinetics and safety of the candidate drugs. In summary, the MRGPI was a robust clinical feature that could predict patient prognosis, immunotherapy response, and candidate drugs, facilitating clinical decision making and therapeutic strategy of OC.


Assuntos
Imunoterapia , Neoplasias Ovarianas , Humanos , Feminino , Prognóstico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Reprogramação Metabólica , Mutação
6.
J Biochem Mol Toxicol ; 38(2): e23648, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38348705

RESUMO

Chronic liver diseases caused by various factors may develop into liver fibrosis (LF). Early stage of LF could be reversible. Tanshinone IIA (Tan IIA), an extract from Salvia miltiorrhiza, has been reported to be hepatoprotective. However, the potential targets and mechanism of Tan IIA in the treatment of LF are still unclear. Our study aims at the anti-LF mechanism of Tan IIA through network pharmacological analysis combined with LF-related experiments. Serum biochemical indicators and histopathological examination showed that Tan IIA could ameliorate the process of LF in the CCl4 -induced mouse model. Western blot and immunohistochemical assays showed that Tan IIA decreased the expression of Kirsten rat sarcoma viral oncogene homolog (KRAS), phosphatidylinositide 3-kinases/protein kinase B (PI3K/Akt), and nuclear factor erythroid 2-related factor/heme oxygenase-1 (Nrf2/HO-1). Compared with the model group, the Tan IIA groups increased the decreased superoxide dismutase activity and glutathione content, while decreasing the increased malondialdehyde content. These results indicate that Tan IIA may play an antioxidant role by inhibiting the expression of KRAS, PI3K/Akt, and Nrf2/HO-1 to ameliorate the progression of LF, which to some extent explains the pharmacological mechanism of Tan IIA in LF. In conclusion, our study demonstrates that Tan IIA could regulate LF via PI3K/Akt and Nrf2/HO-1 signaling pathways. It may be an effective therapeutic compound for the treatment of LF.


Assuntos
Abietanos , Fator 2 Relacionado a NF-E2 , Proteínas Proto-Oncogênicas c-akt , Animais , Camundongos , Heme Oxigenase (Desciclizante)/metabolismo , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Transdução de Sinais
7.
Nutr J ; 23(1): 47, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664726

RESUMO

PURPOSE: Whole grains have recently been promoted as beneficial to diabetes prevention. However, the evidence for the glycemic benefits of whole grains seems to conflict between the cohort studies and randomized control trials (RCTs). To fill the research gap, we conducted a meta-analysis to determine the effects of whole grains on diabetes prevention and to inform recommendations. METHODS: We searched PubMed, Clarivate Web of Science, and Cochrane Library until March 2024. We used the risk ratio (RR) of type 2 diabetes to represent the clinical outcomes for cohort studies, while the biomarkers, including fasting blood glucose and insulin, HbA1C, and HOMA-IR, were utilized to show outcomes for RCTs. Dose-response relationships between whole grain intakes and outcomes were tested with random effects meta-regression models and restricted cubic splines models. This study is registered with PROSPERO, CRD42021281639. RESULTS: Ten prospective cohort studies and 37 RCTs were included. Cohort studies suggested a 50 g/day whole grain intake reduced the risk of type 2 diabetes (RR = 0.761, 95% CI: 0.700 to 0.828, I2 = 72.39%, P < 0.001) and indicated a monotonic inverse relationship between whole grains and type 2 diabetes rate. In RCTs, whole grains significantly reduced fasting blood glucose (Mean difference (MD) = -0.103 mmol/L, 95% CI: -0.178 to -0.028; I2 = 72.99%, P < 0.01) and had modest effects on HbA1C (MD = -0.662 mmol/mol (-0.06%), 95% CI: -1.335 to 0.010; I2 = 64.55%, P = 0.05) and HOMA-IR (MD = -0.164, 95% CI: -0.342 to 0.013; I2 = 33.38%, P = 0.07). The intake of whole grains and FBG, HbA1C, and HOMA-IR were significantly dose-dependent. The restricted spline curves remained flat up to 150 g/day and decreased afterward. Subgroup analysis showed that interventions with multiple whole-grain types were more effective than those with a single type. CONCLUSION: Our study findings suggest that a daily intake of more than 150 g of whole grain ingredients is recommended as a population approach for diabetes prevention.


Assuntos
Glicemia , Diabetes Mellitus Tipo 2 , Controle Glicêmico , Ensaios Clínicos Controlados Aleatórios como Assunto , Grãos Integrais , Humanos , Diabetes Mellitus Tipo 2/prevenção & controle , Diabetes Mellitus Tipo 2/sangue , Controle Glicêmico/métodos , Glicemia/metabolismo , Estudos Prospectivos , Dieta/métodos , Dieta/estatística & dados numéricos , Hemoglobinas Glicadas/análise , Insulina/sangue
8.
Knee Surg Sports Traumatol Arthrosc ; 32(6): 1599-1606, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38678391

RESUMO

PURPOSE: The present study aimed to evaluate the functional outcomes of hip arthroscopy using a noninterportal capsulotomy technique to address labral tears in patients with borderline hip dysplasia (BHD). Additionally, we also compared these outcomes with those of patients with BHD who underwent the standard repaired interportal capsulotomy (RIPC) arthroscopy. METHODS: Data from patients with BHD were retrieved from a database of patients who underwent arthroscopic hip surgery with noninterportal capsulotomy or RIPC to treat labral tears between January 2014 and December 2020. Data collected included both pre- and postoperative patient-reported outcomes (PROs). RESULTS: A total of 58 patients (noninterportal capsulotomy, n = 37; RIPC, n = 21) with a mean age of 30.9 ± 5.6 and 28.6 ± 5.5 years, respectively, met the inclusion criteria. All of the patients underwent a minimal 2-year follow-up. The mean lateral centre-edge angle was 23.3 ± 1.2° in the noninterportal capsulotomy group and 23.7 ± 1.0° in the RIPC group, with no significant difference. The PROs improved from the preoperative to the latest follow-up, with a p < 0.001. There were no differences between the groups. CONCLUSION: Using strict patient selection criteria, hip arthroscopy with noninterportal capsulotomy demonstrated significant pre- to postoperative improvements in patients with BHD and achieved results comparable to those from hip arthroscopy with RIPC. LEVEL OF EVIDENCE: Level III.


Assuntos
Artroscopia , Cápsula Articular , Humanos , Artroscopia/métodos , Feminino , Masculino , Estudos Retrospectivos , Adulto , Seguimentos , Cápsula Articular/cirurgia , Medidas de Resultados Relatados pelo Paciente , Resultado do Tratamento , Luxação do Quadril/cirurgia , Articulação do Quadril/cirurgia , Adulto Jovem
9.
Mikrochim Acta ; 191(7): 422, 2024 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-38922459

RESUMO

Since 2017, an infectious goose gout disease characterized by urate precipitation in viscera, mainly caused by novel goose astrovirus (GoAstV) infection, has emerged in the main goose-producing region of China. The current challenge in managing goose gout disease is largely due to the absence of a rapid and efficient detection method for the GoAstV pathogen. Notably, the potential application of immunosensors in detecting GoAstV has not yet been explored. Herein, a label-free PEC immunosensor was fabricated by using purchased TiO2 as the photoactive material and antibody against GoAstV P2 proteins as the specific recognition element. First, we successfully expressed the capsid spike domain P2 protein of ORF2 from GoAstV CHSH01 by using the pET prokaryotic expression system. Meanwhile, the polyclonal antibody against GoAstV capsid P2 protein was produced by purified protein. To our knowledge, this is the first establishment and preliminary application of the label-free photoelectrochemical immunosensor method in the detection of AstV. The PEC immunosensor had a linear range of 1.83 fg mL-1 to 3.02 ng mL-1, and the limit of detection (LOD) was as low as 0.61 fg mL-1. This immunosensor exhibited high sensitivity, great specificity, and good stability in detecting GoAstV P2 proteins. To evaluate the practical application of the immunosensor in real-world sample detection, allantoic fluid from goose embryos was collected as test samples. The results indicated that of the eight positive samples, one false negative result was detected, while both negative samples were accurately detected, suggesting that the constructed PEC immunosensor had good applicability and practical application value, providing a platform for the qualitative detection of GoAstV.


Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , Limite de Detecção , Titânio , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Animais , Imunoensaio/métodos , Titânio/química , Gansos , Proteínas do Capsídeo/imunologia , Proteínas do Capsídeo/química , Avastrovirus/química , Avastrovirus/imunologia , Anticorpos Imobilizados/imunologia , Anticorpos Imobilizados/química , Anticorpos Antivirais/imunologia , Processos Fotoquímicos
10.
J Formos Med Assoc ; 123(1): 106-115, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37385933

RESUMO

BACKGROUND: Patients with locally advanced esophageal squamous cell carcinoma (ESCC) following neoadjuvant chemoradiotherapy (nCRT) may not always receive resection despite the possible achievement of a pathologic complete response (pCR) being associated with superior survival benefit. We aimed to compare outcomes among ESCC patients with or without pCR and those refusing surgery. METHODS: In total, 111 medically operable, non-cervical ESCC patients after the same protocol of nCRT (platinum/5-fluorouracil plus radiation 50Gy) were prospectively enrolled between 2011 and 2021. Eighty-three of them underwent esophagectomy comprising pCR (n = 32) and non-pCR (n = 51), while 28 operable patients declined surgery (refusal-of-surgery group). Predictors and survival data were analyzed. RESULTS: In terms of esophagectomy, 38.5% (32/83) patients achieved pCR. The pCR group exhibited better pretreatment performance status than the non-pCR group (adjusted odds ratio: 0.11, 95% confidence interval: 0.03-0.58; p = 0.01). Among pCR, non-pCR, and refusal-of-surgery groups, the 5-year overall survival (OS) rates were 56%, 29% and 50% (p = 0.08) and progression-free survival (PFS) rates were 52%, 28% and 36% (p = 0.07) respectively. The pCR group had significantly better OS and PFS than the non-PCR group (adjusted hazard ratio: 2.33 and 1.93, p = 0.02 and 0.049 respectively) but not the refusal-of-surgery group. CONCLUSION: Better pretreatment performance status is associated with higher chance of pCR. Consistent with previous studies, we found attainment of pCR confers the best OS and PFS. Suboptimal OS in the refusal-of-surgery group reflects some of them would have residual disease in addition to complete remission. Further studies are needed to identify prognostic factors of pCR to select candidates who could validly decline esophagectomy.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Neoplasias Esofágicas/tratamento farmacológico , Terapia Neoadjuvante/métodos , Estudos Prospectivos , Estadiamento de Neoplasias , Esofagectomia/métodos , Resultado do Tratamento , Quimiorradioterapia , Estudos Retrospectivos
11.
J Formos Med Assoc ; 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38824057

RESUMO

BACKGROUND: More than 50% of esophageal cancer patients are diagnosed with advanced diseases and commonly experience dysphagia, some of whom even have tracheoesophageal fistula. Self-expandable metal stent (SEMS) is one of the recommended palliative methods, although complications such as chest pain and stent migration are not uncommon. The goal of this study was to examine the predictors of stent migration. METHODS: We conducted a retrospective cohort study to include patients with esophageal cancer and dysphagia/tracheoesophageal fistula. Clinicopathological information, stent characteristics and patient outcomes were collected for analysis, while side-effects of SEMS were recorded, potential predictors were examined, and patients' nutritional outcomes were compared in the migration and non-migration groups. RESULTS: A total of 54 patients with esophageal cancer who received fully covered SEMS between 2013 and 2022 were included. We found tumor across the esophagogastric junction (adjusted odds ratio (OR) = 32.64, P = 0.01) and the female sex (adjusted OR = 12.5, P = 0.02) were significant predictors for stent migration. There was a decreasing tendency in body mass index/body weight in migration and non-migration groups, but the former had a steeper downslope. CONCLUSION: Fully covered SEMS is a safe and effective strategy to palliate dysphagia or fistula. Tumor across esophagogastric junction and the female sex were higher risk predictors of stent migration. A careful patient selection would optimize the effects of SEMS placement, especially in those with short-expected lifespan.

12.
Int Wound J ; 21(4): e14858, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38546006

RESUMO

Hypertension is a prevalent condition that poses significant challenges in the perioperative management of patients undergoing major non-cardiac surgery, particularly concerning wound healing and scar formation. This meta-analysis assesses the impact of long-term antihypertensive treatment on postoperative wound healing, examining data from seven studies involving patients who received such treatments compared to untreated controls. Our findings reveal that long-term antihypertensive therapy is associated with significantly improved wound healing outcomes, as indicated by lower REEDA scores (I2 = 96%, SMD = -25.71, 95% CI: [-33.71, -17.70], p < 0.01) 1 week post-surgery and reduced scar formation, demonstrated by lower Manchester Scar Scale scores (I2 = 93%, SMD = -37.29, 95% CI: [-44.93, -29.64], p < 0.01) 2 months post-surgery. These results underscore the potential benefits of antihypertensive treatment in enhancing surgical recovery and offer insights into optimising perioperative care for hypertensive patients.


Assuntos
Doenças Cardiovasculares , Hipertensão , Humanos , Cicatriz , Anti-Hipertensivos/uso terapêutico , Cicatrização , Hipertensão/tratamento farmacológico
13.
Medicina (Kaunas) ; 60(2)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38399524

RESUMO

Background and Objectives: Lung cancer is a leading cause of cancer mortality in Taiwan. With rapid advancement of targeted therapeutics in non-small cell lung cancers, next-generation sequencing (NGS) is becoming an important tool for biomarker testing. In this study, we describe institutional experience of NGS analysis in non-small cell carcinoma (NSCLC). Materials and Methods: A cohort of 73 cases was identified from the institutional pathology archive in the period between November 2020 and December 2022. Results: Adenocarcinoma was the most common histologic type (91.8%). Most patients presented with stage IIIB and beyond (87.7%). Twenty-nine patients (39.7%) were evaluated at the time of initial diagnosis, while the others had received prior chemotherapy or targeted therapy. The most frequently mutated gene was EGFR (63%), and this was followed by TP53 (50.7%), KRAS (13.7%), RB1 (13.7%), and CDKN2A (13.7%). Clinically actionable mutations associated with a guideline-suggested targeted therapy were identified in 55 cases (75.3%) overall, and in 47.1% of cases excluding EGFR TKI-sensitizing mutation. Biomarkers other than EGFR TKI-sensitizing mutations were compared. Cases without TKI-sensitizing EGFR mutation had more level 1 or 2 biomarkers (excluding EGFR TKI-sensitizing mutations) than cases with TKI-sensitizing EGFR mutations (47.1% versus 20.1%, p = 0.016). Progressive disease was associated with co-occurrence of clinically actionable mutations (20.5% versus 0%, p < 0.05). Eight of the nine cases with co-occurring actionable genetic alternations had an EGFR mutation. After an NGS test, 46.1% of actionable or potentially actionable genetic alternations led to patients receiving a matched therapy. Conclusions: Our study demonstrated that NGS analysis identifies therapeutic targets and may guide treatment strategies in NSCLC. NGS tests may be advantageous over multiple single-gene tests for optimization of treatment plans, especially for those with non-EGFR mutations or those with progressive disease.


Assuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Taiwan/epidemiologia , Receptores ErbB/genética , Mutação , Sequenciamento de Nucleotídeos em Larga Escala , Biomarcadores , Inibidores de Proteínas Quinases/uso terapêutico
14.
BMC Genomics ; 24(1): 568, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37749507

RESUMO

BACKGROUND: Mammals are potential hosts for many infectious diseases. However, studies on the viral communities of herbivorous mammals in the Northwest Plateau are limited. Here, we studied the viral communities of herbivorous mammals in the Northwest Plateau using virus metagenomic analysis to analyze and compare the viral community composition of seven animal species. RESULTS: By library construction and next-generation sequencing, contigs and singlets reads with similar viral sequences were classified into 24 viral families. Analyzed from the perspective of sampling areas, the virus community composition was relatively similar in two areas of Wuwei and Jinchang, Gansu Province. Analyzed from the perspective of seven animal species, the viral reads of seven animal species were mostly ssDNA and dominated by CRESS-DNA viruses. Phylogenetic analysis based on viral marker genes indicated that CRESS-DNA viruses and microviruses have high genetic diversity. In addition to DNA viruses, nodaviruses, pepper mild mottle viruses and picornaviruses were RNA viruses that we performed by phylogenetic analysis. The CRESS-DNA viruses and nodaviruses are believed to infect plants and insects, and microviruses can infect bacteria, identifying that they were likely from the diet of herbivorous mammals. Notably, two picornaviruses were identified from red deer and wild horse, showing that the picornavirus found in red deer had the relatively high similarity with human hepatitis A virus, and the picornavirus carried by wild horse could potentially form a new species within the Picornaviridae family. CONCLUSIONS: This study explored the herbivorous mammalian virus community in the Northwest Plateau and the genetic characteristics of viruses that potentially threaten human health. It reveals the diversity and stability of herbivorous mammalian virus communities in the Northwest Plateau and helps to expand our knowledge of various herbivorous mammalian potentially pathogenic viruses.


Assuntos
Brassicaceae , Cervos , Animais , Humanos , Filogenia , Verduras , Clonagem Molecular
15.
J Transl Med ; 21(1): 185, 2023 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-36895015

RESUMO

BACKGROUND: Circadian rhythm regulates complex physiological activities in organisms. A strong link between circadian dysfunction and cancer has been identified. However, the factors of dysregulation and functional significance of circadian rhythm genes in cancer have received little attention. METHODS: In 18 cancer types from The Cancer Genome Atlas (TCGA), the differential expression and genetic variation of 48 circadian rhythm genes (CRGs) were examined. The circadian rhythm score (CRS) model was created using the ssGSEA method, and patients were divided into high and low groups based on the CRS. The Kaplan-Meier curve was created to assess the patient survival rate. Cibersort and estimate methods were used to identify the infiltration characteristics of immune cells between different CRS subgroups. Gene Expression Omnibus (GEO) dataset is used as verification queue and model stability evaluation queue. The CRS model's ability to predict chemotherapy and immunotherapy was assessed. Wilcoxon rank-sum test was used to compare the differences of CRS among different patients. We use CRS to identify potential "clock-drugs" by the connective map method. RESULTS: Transcriptomic and genomic analyses of 48 CRGs revealed that most core clock genes are up-regulated, while clock control genes are down-regulated. Furthermore, we show that copy number variation may affect CRGs aberrations. Based on CRS, patients can be classified into two groups with significant differences in survival and immune cell infiltration. Further studies showed that patients with low CRS were more sensitive to chemotherapy and immunotherapy. Additionally, we identified 10 compounds (e.g. flubendazole, MLN-4924, ingenol) that are positively associated with CRS, and have the potential to modulate circadian rhythms. CONCLUSIONS: CRS can be utilized as a clinical indicator to predict patient prognosis and responsiveness to therapy, and identify potential "clock-drugs".


Assuntos
Relógios Circadianos , Neoplasias , Humanos , Relógios Circadianos/genética , Variações do Número de Cópias de DNA , Ritmo Circadiano/genética , Neoplasias/genética , Prognóstico
16.
Glob Chang Biol ; 29(24): 7159-7172, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37830780

RESUMO

The frequency and intensity of droughts worldwide are challenging the conservation of soil organic carbon (SOC) pool. Microbial necromass is a key component of SOC, but how it responds to drought at specific soil depths remains largely unknown. Here, we conducted a 3-year field experiment in a forest plantation to investigate the impacts of drought intensities under three treatments (ambient control [CK], moderate drought [30% throughfall removal], and intensive drought [50% throughfall removal]) on soil microbial necromass pools (i.e., bacterial necromass carbon, fungal necromass carbon, and total microbial necromass carbon). We showed that the effects of drought on microbial necromass depended on microbial groups, soil depth, and drought intensity. While moderate drought increased total (+9.1% ± 3.3%) and fungal (+13.5% ± 4.9%) necromass carbon in the topsoil layer (0-15 cm), intensive drought reduced total (-31.6% ± 3.7%) and fungal (-43.6% ± 4.0%) necromass in the subsoil layer (15-30 cm). In contrast, both drought treatments significantly increased the BNC in the topsoil and subsoil. Our results suggested that the effects of drought on the microbial necromass of the subsoil were more pronounced than those of the topsoil. This study highlights the complex responses of microbial necromass to drought events depending on microbial community structure, drought intensity and soil depth with global implications when forecasting carbon cycling under climate change.


Assuntos
Secas , Solo , Carbono , Florestas , Ciclo do Carbono , Microbiologia do Solo
17.
Opt Lett ; 48(16): 4364-4367, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37582033

RESUMO

We propose and demonstrate a new, to the best of our knowledge, technique to implement a high-speed and highly sensitive torsion sensor based on a coupled optoelectronic oscillator (COEO) incorporating nonlinear polarization rotation (NPR). The COEO consists of a mode-locked laser loop and an OEO loop. In the laser loop, the NPR effect effectively induces intensity- and wavelength-dependent loss, which acts as a Lyot birefringent fiber filter. When twisting the polarization-maintaining fiber (PMF), the transmission of the filter varies as well as the laser output wavelength. In the OEO loop, the optical source is provided by the output signal of the mode-locked laser. The variation in the optical carrier wavelength changes the time delay and the oscillation frequency of the OEO loop. The oscillation frequency shift is a linear function of the twist angle. Sensitivities of -60.006 Hz/deg over 360° for a 48 cm PMF and -180.996 Hz/deg over 92° for a 22 cm PMF are achieved.

18.
Langmuir ; 39(29): 10154-10162, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37342903

RESUMO

Water absorbed by epoxy resins from a humid atmosphere considerably influences their structure and properties. Examining the effects of absorbed water on epoxy resins at their interfaces with solid substrates is crucial because of their adhesive applications in various fields. The spatial distribution of absorbed water in epoxy resin thin films under high humidity was investigated in this study by neutron reflectometry. Water molecules were found to accumulate at the SiO2/epoxy resin interface after exposure at a relative humidity of 85% for 8 h. The formation of an ∼1-nm-thick condensed water layer was observed, and the thickness of this layer varied with curing conditions of epoxy systems. Furthermore, water accumulation at the interface was noted to be affected by high-temperature and high-humidity environments. The formation of the condensed water layer is presumed to be related to the features of the polymer layer near the interface. The construction of the interface layer of epoxy resin would be affected by the interface constraint effect on the cross-linked polymer chain during the curing reaction. This study provides essential information for understanding the factors influencing the accumulation of water at the interface in epoxy resins. In practical applications, the process of improving the construction of epoxy resins near the interface would be a reasonable solution to resist water accumulation in the interface.

19.
Inorg Chem ; 62(47): 19366-19374, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-37948416

RESUMO

Various Co-based perovskites are synthesized through thermally driving viscous fluids. In this process, rare earth salts, cobalt salts, and citric acid do not require homogeneous mixing but only need to be heated until they melt into a molten viscous slurry. The physicochemical properties of cobalt-based perovskites were examined using techniques such as X-ray diffraction (XRD), electron paramagnetic resonance (EPR), scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-Mapping-EDS), X-ray photoelectron spectroscopy (XPS), hydrogen temperature-programmed reduction (H2-TPR), oxygen temperature-programmed desorption (O2-TPD), and N2 adsorption-desorption. The results indicate that the surface-active species can be controlled by altering the A-site elements of cobalt-based perovskites. All catalysts synthesized through the thermal treatment of viscous mixtures exhibited a low activation temperature and a low apparent activation energy for the catalytic oxidation of toluene. Among all cobalt-based perovskites, LaCoO3 demonstrated the most outstanding catalytic activity, primarily attributed to its capacity to expose a larger number of surface-active sites and oxygen species, as well as its superior reducibility. Furthermore, the formation process of optimal LaCoO3 was monitored using thermogravimetric analysis-differential scanning calorimetry (TGA-DSC), and the byproducts of the low-temperature catalytic oxidation of toluene by the catalyst were identified using gas chromatography-mass spectrometry (GC-MS). The possible mechanism of toluene oxidation was inferred by in situ diffuse reflection infrared Fourier transform spectroscopy (DRIFTS). Moreover, LaCoO3 exhibits a predominant resistance to high-temperature hydrothermal conditions. This work provides a scalable and innovative approach to fabricating exceptionally effective catalysts for the efficient purification of VOCs.

20.
BMC Gastroenterol ; 23(1): 26, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36717769

RESUMO

BACKGROUND AND AIMS: To investigate the usefulness of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), protein C (PC), and thromboelastography (TEG) to serve as a predictor of portal vein thrombosis (PVT) in patients with liver cirrhosis. Additionally, we examined the clinical significance of the above indicators in terms of disease progression. METHODS: A total of 123 patients with liver cirrhosis were recruited from May 2021 to December 2021, according to the imaging findings. They were divided into the PVT group (n = 52) and the non-PVT group (n = 71). Furthermore, patients with PVT were divided into plasma transfusion groups (n = 13) and non-plasma transfusion groups (n = 39). The basic general information, past medical history, laboratory, and imaging examination data were collected and analyzed. RESULTS: In univariate analysis, there was no significant difference between the two groups in IL-6, PC, reaction time (R), alpha angle (Angle), maximum amplitude, or coagulation index (CI) (P > 0.05). TNF-α in the PVT group was significantly lower than that in the non-PVT group (P = 0.001). K-time (K) in the PVT group was significantly higher than that in the non-PVT group (P = 0.031). There was no significant difference in IL-6, TNF-α, PC, or TEG between different Child-Pugh classification groups (P > 0.05). There were no significant differences in TEG between the plasma transfusion group and the non-plasma transfusion group. In Binary logistic regression analysis, TNF-α (OR = 0.9881, 95%CI = 0.971, 0.990, P < 0.001), K(OR = 1.28, 95% = 1.053, 1.569, P = 0.014), activate partial thromboplastin time (APTT) (OR = 0.753, 95%CI = 0.656, 0.865, P < 0.001), portal vein diameter (OR = 1.310, 95%CI = 1.108, 1.549, P = 0.002)and the history of splenectomy or embolism (OR = 7.565, 95%CI = 1.514, 37.799, P = 0.014)were related to the formation of PVT. CONCLUSIONS: TNF-α, K, APTT, portal vein diameter, and splenectomy or embolism history were associated with PVT formation, but IL-6 was not.


Assuntos
Veia Porta , Trombose Venosa , Humanos , Veia Porta/patologia , Fatores de Risco , Fator de Necrose Tumoral alfa , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Trombose Venosa/complicações
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