Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 112
Filtrar
1.
Virus Evol ; 10(1): veae062, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39175838

RESUMO

Amphibians are an essential class in the maintenance of global ecosystem equilibrium, but they face serious extinction risks driven by climate change and infectious diseases. Unfortunately, the virus diversity harbored by these creatures has been rarely investigated. By profiling the virus flora residing in different tissues of 100 farmed black-spotted frogs (Rana nigromaculata) using a combination of DNA and RNA viromic methods, we captured 28 high-quality viral sequences covering at least 11 viral families. Most of these sequences were remarkably divergent, adding at least 10 new species and 4 new genera within the families Orthomyxoviridae, Adenoviridae, Nodaviridae, Phenuiviridae, and Picornaviridae. We recovered five orthomyxovirus segments, with three distantly neighboring two Chinese fish-related viruses. The recombination event of frog virus 3 occurred among the frog and turtle strains. The relative abundance and molecular detection revealed different tissue tropisms of these viruses, with the orthomyxovirus and adenoviruses being enteric and probably also neurotropic, but the new astrovirus and picornavirus being hepatophilic. These results expand the spectrum of viruses harbored by anurans, highlighting the necessity to continuously monitor these viruses and to investigate the virus diversity in a broader area with more diverse amphibian species.

2.
Nicotine Tob Res ; 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39083005

RESUMO

INTRODUCTION: In China, standard smoking cessation practices are rarely used by healthcare service providers (HSPs). WeChat, a popular social media app, has been widely used in China. METHODS: In this single-blind, randomized trial, undertaken in China with 8-week interventions and follow-up to 34 weeks, 1887 HSPs were randomly selected to the intervention (n=942) or control group (n=945) from Oct 2020 to Oct 2021. The intervention group received regular smoking cessation training program messages from the professional team for 8 weeks and followed for 34 weeks. The control group received thanks messages for 8 weeks, and follow-up to 34 weeks. Both groups received a hard copy of the manual after randomization. The primary outcome measure was the utilization rate of behavioral and pharmacotherapy interventions for smoking patients from 9 to 34 weeks. This trial is registered at ClinicalTrials.gov (number NCT03556774). RESULTS: HSPs in the intervention group demonstrated a better overall utilization rate of smoking cessation at 20-week follow-up compared to the control group (35.54% vs 31.41%, p=0.036). Additionally, both groups showed a significant increase in the adoption of various components of the 5A's model - including "Assess", "Assist: set a quit date", "Assist: recommend cessation program", "Assist: provide information", "Assist: recommend medication", and "Arrange" - at the 9-week follow-up relative to baseline. Notably, at the 20-week follow-up, the intervention group reported significantly enhanced utilization rates for all these components, except "Assist: set a quit date". CONCLUSIONS: The "Wechat Wequit" training program effectively enhanced smoking cessation intervention adoption among Chinese HSPs. IMPLICATION: 'WeChat WeQuit' training program was effective in increasing the provision of effective tobacco cessation interventions by Chinese-speaking HSPs to patients with cigarette smoking, which could provide valuable insights into bridging the gap between need and services for smoking cessation in China.

3.
Int J Biol Macromol ; 274(Pt 2): 133294, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38925188

RESUMO

Congenital heart disease (CHD) is a type of major defect that occurs during embryonic development. Although significant advances have been made in the treatment of CHD, its etiology and molecular mechanism remain unclear. To identify the critical role of SUMOylation in cardiac development, we generated SENP3 knockout mice and showed that SENP3 knockout mice die on embryonic day 8.5 with an open neural tube and reversed left-right cardiac asymmetry. Moreover, SENP3 knockout promoted apoptosis and senescence of H9C2 cells. Further studies showed that Nodal, a critical gene that forms left-right asymmetry, is regulated by SENP3 and that SENP3 regulates cell apoptosis and senescence in a Nodal-dependent manner. Furthermore, Nodal was hyper-SUMOylated after SENP3 knockout, and SUMOylation of Nodal inhibited its ubiquitination and ubiquitin-proteasome degradation pathway. Nodal overexpression enhanced cell apoptosis and senescence; however, the mutation at the SUMOylation site of Nodal reversed its effect on the apoptosis and senescence of H9C2 cells. More importantly, the SENP3-Nodal axis regulates cell senescence by inducing cell autophagy. These results suggest that the SENP3-Nodal signaling axis regulates cardiac senescence-autophagy homeostasis, which in turn affects cardiac development and results in the occurrence of CHD.


Assuntos
Apoptose , Cisteína Endopeptidases , Proteína Nodal , Transdução de Sinais , Sumoilação , Animais , Cisteína Endopeptidases/metabolismo , Cisteína Endopeptidases/genética , Camundongos , Apoptose/genética , Proteína Nodal/metabolismo , Proteína Nodal/genética , Coração/embriologia , Camundongos Knockout , Autofagia/genética , Senescência Celular/genética , Linhagem Celular
5.
Methods ; 228: 12-21, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38759908

RESUMO

Annotating cell types of single-cell RNA sequencing (scRNA-seq) data is crucial for studying cellular heterogeneity in the tumor microenvironment. Recently, large-scale pre-trained language models (PLMs) have achieved significant progress in cell-type annotation of scRNA-seq data. This approach effectively addresses previous methods' shortcomings in performance and generalization. However, fine-tuning PLMs for different downstream tasks demands considerable computational resources, rendering it impractical. Hence, a new research branch introduces parameter-efficient fine-tuning (PEFT). This involves optimizing a few parameters while leaving the majority unchanged, leading to substantial reductions in computational expenses. Here, we utilize scBERT, a large-scale pre-trained model, to explore the capabilities of three PEFT methods in scRNA-seq cell type annotation. Extensive benchmark studies across several datasets demonstrate the superior applicability of PEFT methods. Furthermore, downstream analysis using models obtained through PEFT showcases their utility in novel cell type discovery and model interpretability for potential marker genes. Our findings underscore the considerable potential of PEFT in PLM-based cell type annotation, presenting novel perspectives for the analysis of scRNA-seq data.


Assuntos
RNA-Seq , Análise de Célula Única , Análise de Célula Única/métodos , Humanos , RNA-Seq/métodos , Análise de Sequência de RNA/métodos , Biologia Computacional/métodos , Algoritmos , Anotação de Sequência Molecular/métodos , Software , Microambiente Tumoral/genética , Análise da Expressão Gênica de Célula Única
6.
Biosens Bioelectron ; 257: 116345, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38692247

RESUMO

Nitrite (NO2-) is present in a variety of foods, but the excessive intake of NO2- can indirectly lead to carcinogenic, teratogenic, mutagenicity and other risks to the human body. Therefore, the detection of NO2- is crucial for maintaining human health. In this study, an integrated array sensor for NO2- detection is developed based on molybdenum single atom material (IMSMo-SAC) using high-resolution electrohydrodynamic (EHD) printing technology. The sensor comprises three components: a printed electrode array, multichannels designed on polydimethylsiloxane (PDMS) and an electronic signal process device with bluetooth. By utilizing Mo-SAC to facilitate electron transfer during the redox reaction, rapid and efficient detection of NO2- can be achieved. The sensor has a wide linear range of 0.1 µM-107.8 mM, a low detection limit of 33 nM and a high sensitivity of 0.637 mA-1mM-1 cm-2. Furthermore, employing this portable array sensor allows simultaneously measurements of NO2- concentrations in six different foods samples with acceptable recovery rates. This array sensor holds great potential for detecting of small molecules in various fields.


Assuntos
Técnicas Biossensoriais , Desenho de Equipamento , Análise de Alimentos , Limite de Detecção , Molibdênio , Nitritos , Molibdênio/química , Técnicas Biossensoriais/instrumentação , Nitritos/análise , Análise de Alimentos/instrumentação , Humanos , Dimetilpolisiloxanos/química , Eletrodos , Técnicas Eletroquímicas/métodos , Técnicas Eletroquímicas/instrumentação , Contaminação de Alimentos/análise
9.
Bone Res ; 12(1): 15, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38433252

RESUMO

Osteoarthritis (OA) is a common degenerative disease worldwide and new therapeutics that target inflammation and the crosstalk between immunocytes and chondrocytes are being developed to prevent and treat OA. These attempts involve repolarizing pro-inflammatory M1 macrophages into the anti-inflammatory M2 phenotype in synovium. In this study, we found that phosphoglycerate mutase 5 (PGAM5) significantly increased in macrophages in OA synovium compared to controls based on histology of human samples and single-cell RNA sequencing results of mice models. To address the role of PGAM5 in macrophages in OA, we found conditional knockout of PGAM5 in macrophages greatly alleviated OA symptoms and promoted anabolic metabolism of chondrocytes in vitro and in vivo. Mechanistically, we found that PGAM5 enhanced M1 polarization via AKT-mTOR/p38/ERK pathways, whereas inhibited M2 polarization via STAT6-PPARγ pathway in murine bone marrow-derived macrophages. Furthermore, we found that PGAM5 directly dephosphorylated Dishevelled Segment Polarity Protein 2 (DVL2) which resulted in the inhibition of ß-catenin and repolarization of M2 macrophages into M1 macrophages. Conditional knockout of both PGAM5 and ß-catenin in macrophages significantly exacerbated osteoarthritis compared to PGAM5-deficient mice. Motivated by these findings, we successfully designed mannose modified fluoropolymers combined with siPGAM5 to inhibit PGAM5 specifically in synovial macrophages via intra-articular injection, which possessed desired targeting abilities of synovial macrophages and greatly attenuated murine osteoarthritis. Collectively, these findings defined a key role for PGAM5 in orchestrating macrophage polarization and provides insights into novel macrophage-targeted strategy for treating OA.


Assuntos
Osteoartrite , Fosfoglicerato Mutase , Humanos , Animais , Camundongos , beta Catenina , Osteoartrite/genética , Inflamação , Macrófagos , Fosfoproteínas Fosfatases , Proteínas Mitocondriais
10.
ACS Appl Mater Interfaces ; 16(11): 13828-13838, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38448219

RESUMO

Alluaudite sodium iron sulfate (NFS) exhibits great potential for use in sodium-ion battery cathodes due to its elevated operating potential and abundant element reserves. However, conventional solid-state methods demonstrate a low heating/cooling rate and sluggish reaction kinetics, requiring a long thermal treatment to effectively fabricate NFS cathodes. Herein, we propose a thermal shock (TS) strategy to synthesize alluaudite sodium iron sulfate cathodes using either hydrous or anhydrous raw materials. The analysis of the phase formation process reveals that TS treatment can significantly facilitate the removal of crystal water and decomposition of the intermediate phase Na2Fe(SO4)2 in the hydrous precursor. In the case of the anhydrous precursor, the kinetics of the combination reaction between Na2SO4 and FeSO4 can be also accelerated by TS treatment. Consequently, pure NFS phase formation can be completed after a substantially shorter time of post-sintering, thereby saving significant time and energy. The TS-treated NFS cathode derived from hydrous precursor exhibits higher retention after 200 cycles at 1C and better rate capability than the counterpart prepared by conventional long-term tube furnace sintering, demonstrating the great potential of this novel strategy.

11.
Tob Induc Dis ; 222024.
Artigo em Inglês | MEDLINE | ID: mdl-38482507

RESUMO

INTRODUCTION: Smoking prevalence is high in China, and healthcare workers are important for tobacco control. This study aimed to determine the smoking status, cognition of tobacco hazards, and smoking cessation-related knowledge among respiratory healthcare workers, and to explore their ability to provide smoking cessation assistance. METHODS: A cross-sectional study was conducted in 2021 among 1028 respiratory healthcare workers from 89 hospitals in Fujian Province, China. A self-designed electronic questionnaire was used to collect data on smoking status, knowledge of smoking hazards, and smoking cessation knowledge. Descriptive statistics were calculated for all questions. Logistic regression analysis was used to explore the relationship between awareness of the tobacco control goals of Healthy China 2030 and demographic characteristics. RESULTS: Among the healthcare workers surveyed, 3.4% were smokers, all of whom were male. Most respondents (99.4%) were aware of smoking as a cause of lung cancer, but awareness of smoking as a cause of non-respiratory cancer was lower. The awareness rate of smoking cessation support was high (>90%), but only 40.0% of participants were aware of the Healthy China 2030 tobacco control targets. Male (HR=2.16; 95% CI: 1.69-2.80) and participation in the cessation clinic (HR=1.47; 95% CI: 1.10-1.96) were associated with higher awareness of the targets. CONCLUSIONS: Respiratory healthcare workers in Fujian Province demonstrated a high level of awareness regarding behavioral and pharmacotherapy support for smoking cessation. In order to enable healthcare workers to play a more active role in tobacco control, there is a need to increase public awareness of smoking cessation services in Fujian Province.

12.
BMC Pulm Med ; 24(1): 36, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38233781

RESUMO

BACKGROUND: Chlamydia pneumoniae (Cpn) IgG and IgA has been strongly linked to lung cancer, but its impact on patients' quality of life remains unclear. Our objective was to investigate the relationship between pre-treatment Cpn IgG and IgA and time to deterioration (TTD) of the HRQoL in patients with primary lung cancer. METHODS: A prospective hospital-based study was conducted from June 2017 to December 2018, enrolling 82 patients with primary lung cancer admitted to the First Affiliated Hospital of Fujian Medical University for questionnaire surveys. Cpn IgG and IgA was detected by microimmunofluorescence method. HRQoL was assessed at baseline and during follow-up using the EORTC Quality of Life Questionnaire version 3.0 (EORTC QLQ-C30) and EORTC Quality of Life Questionnaire-Lung Cancer (EORTC QLQ-LC13). HRQoL scores were calculated using the QoLR package, and TTD events were determined (minimum clinically significant difference = 5 points). Cox regression analysis was used to evaluate the effect of Cpn IgG and IgA on HRQoL. RESULTS: We investigated the relationship between Cpn IgG and IgA and quality of life in patients with primary lung cancer. The study was found that 75.61% of cases were Cpn IgG + and 45.12% were Cpn IgA + . Cpn IgA + IgG + was 41.46%. For EORTC QLQ-C30, Physical function (PF) and Pain (PA) TTD events on the functional scale and Symptom scale were the most common during follow-up. After adjusting for gender and smoking status, Pre-treatment Cpn IgA + was found to signifcantly delay TTD of Physical functioning(HR = 0.539, 95% CI: 0.291-0.996, P = 0.048). In addition, Cpn IgG + before treatment significantly delayed TTD in Emotional functioning (HR = 0.310, 95% CI: 0.115-0.836, P = 0.021). For EORTC QLQ-LC13, deterioration of dyspnea (LC-DY) was the most common event. However, Cpn IgG and IgA before treatment had no effect on the TTD of EORTC QLQ-LC13 items. CONCLUSIONS: According to EORTC QLQ-C30 and EORTC QLQ-LC13, Cpn IgA delayed TTD in Physical functioning and Cpn IgG delayed TTD in Emotional functioning.


Assuntos
Infecções por Chlamydophila , Neoplasias Pulmonares , Humanos , Qualidade de Vida/psicologia , Neoplasias Pulmonares/terapia , Estudos Prospectivos , Infecções por Chlamydophila/complicações , Imunoglobulina A , Imunoglobulina G , Inquéritos e Questionários
13.
Quant Imaging Med Surg ; 14(1): 179-193, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38223045

RESUMO

Background: The application of high-intensity focused ultrasound (HIFU) in the treatment of uterine fibroids is becoming increasingly widespread, and postoperative collateral thermal damage to adjacent tissue has become a prominent subject of discussion. However, there is limited research related to bone injury. Therefore, the aim of this study was to investigate the potential factors influencing unintentional pelvic bone injury after HIFU ablation of uterine fibroids with magnetic resonance imaging (MRI). Methods: A total of 635 patients with fibroids treated with HIFU in the First Affiliated Hospital of Chongqing Medical University were enrolled. All patients underwent contrast-enhanced MRI (CE-MRI) pre- and post-HIFU. Based on the post-treatment MRI, the patients were divided into two groups: pelvic bone injury group and non-injury group, while the specific site of pelvic bone injury of each patient was recorded. The univariate and multivariate analyses were used to assess the correlations between the factors of fibroid features and treatment parameters and pelvic bone injury, and to further analyze the factors influencing the site of injury. Results: Signal changes in the pelvis were observed on CE-MRI in 51% (324/635) of patients after HIFU. Among them, 269 (42.4%) patients developed sacral injuries and 135 (21.3%) had pubic bone injuries. Multivariate analyses showed that patients with higher age [P=0.003; odds ratio (OR), 1.692; 95% confidence interval (CI): 1.191-2.404], large anterior side-to-skin distance of fibroid (P<0.001; OR, 2.297; 95% CI: 1.567-3.365), posterior wall fibroid (P=0.006; OR, 1.897; 95% CI: 1.204-2.989), hyperintensity on T2-weighted imaging (T2WI, P=0.003; OR, 2.125; 95% CI: 1.283-3.518), and large therapeutic dose (TD, P<0.001; OR, 3.007; 95% CI: 2.093-4.319) were at higher risk of postoperative pelvic bone injury. Further analysis of the factors influencing the site of the pelvic bone injury showed that some of the fibroid features and treatment parameters were associated with it. Moreover, some postoperative pain-related adverse events were associated with the pelvic bone injury. Conclusions: Post-HIFU treatment, patients may experience pelvic injuries to the sacrum, pubis, or a combination of both, and some of them experienced adverse events. Some fibroid features and treatment parameters are associated with the injury. Taking its influencing factors into full consideration preoperatively, slowing down treatment, and prolonging intraoperative cooling phase can help optimize treatment decisions for HIFU.

14.
Anim Biosci ; 37(2): 303-314, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37905323

RESUMO

OBJECTIVE: Rutin, also called vitamin P, is a flavonoids from plants. Previous studies have indicated that rutin can alleviate the injury of tissues and cells by inhibiting oxidative stress and ameliorating inflammation. There is no report on the protective effects of rutin on goat rumen epithelial cells (GRECs) at present. Hence, we investigated whether rutin can alleviate lipopolysaccharide (LPS)-induced damage in GRECs. METHODS: GRECs were cultured in basal medium or basal medium containing 1 µg/mL LPS, or 1 µg/mL LPS and 20 µg/mL rutin. Six replicates were performed for each group. After 3-h culture, the GRECs were harvested to detect the relevant parameters. RESULTS: Rutin significantly enhanced the cell activity (p<0.05) and transepithelial electrical resistance (TEER) (p<0.01) and significantly reduced the apoptosis rate (p<0.05) of LPSinduced GRECs. Rutin significantly increased superoxide dismutase, glutathione peroxidase, and catalase activity (p<0.01) and significantly decreased lactate dehydrogenase activity and reactive oxygen species and malondialdehyde (MDA) levels in LPS-induced GRECs (p<0.01). The mRNA and protein levels of interleukin 6 (IL-6), IL-1ß, and C-X-C motif chemokine ligand 8 (CXCL8) and the mRNA level of tumor necrosis factor-α (TNF-α) and chemokine C-C motif ligand 5 (CCL5) were significantly increased in LPS-induced GRECs (p<0.05 or p<0.01), while rutin supplementation significantly decreased the mRNA and protein levels of IL-6, TNF-α, and CXCL8 in LPS-induced GRECs (p<0.05 or p<0.01). The mRNA level of toll-like receptor 2 (TLR2), and the mRNA and protein levels of TLR4 and nuclear factor κB (NF-κB) was significantly improved in LPS-induced GRECs (p<0.05 or p<0.01), whereas rutin supplementation could significantly reduce the mRNA and protein levels of TLR4 (p<0.05 or p<0.01). In addition, rutin had a tendency of decreasing the protein levels of CXCL6, NF-κB, and inhibitor of nuclear factor kappa-B alpha (0.05< p<0.10). Rutin could significantly decreased interferon regulatory factor 3 mRNA expression in LPS-induced GRECs (p<0.05), whereas interferon induced protein with tetratricopeptide repeats 3 (IFIT3) and toll-interacting protein (TOLLIP) mRNA expression was not significantly different between the groups. LPS reduced the tight junction protein zonula occludin 1 (ZO-1) level in GRECs whereas rutin enhanced it. Rutin significantly improved tight junction protein Claudin-1 mRNA expression in LPS-induced GRECs (p<0.01), but could not affect tight junction protein Occludin mRNA expression. CONCLUSION: Rutin alleviated LPS-induced barrier damage in GRECs by improving oxidation resistance and anti-inflammatory activity, which may be related to TLR/NF-κB signaling pathway inhibition.

15.
Nucleic Acids Res ; 52(4): 1878-1895, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38153123

RESUMO

The exonuclease ISG20L2 has been initially characterized for its role in the mammalian 5.8S rRNA 3' end maturation, specifically in the cleavage of ITS2 of 12S precursor ribosomal RNA (pre-rRNA). Here, we show that human ISG20L2 is also involved in 18S pre-rRNA maturation through removing the ITS1 region, and contributes to ribosomal biogenesis and cell proliferation. Furthermore, we determined the crystal structure of the ISG20L2 nuclease domain at 2.9 Å resolution. It exhibits the typical αßα fold of the DEDD 3'-5' exonuclease with a catalytic pocket located in the hollow near the center. The catalytic residues Asp183, Glu185, Asp267, His322 and Asp327 constitute the DEDDh motif in ISG20L2. The active pocket represents conformational flexibility in the absence of an RNA substrate. Using structural superposition and mutagenesis assay, we mapped RNA substrate binding residues in ISG20L2. Finally, cellular assays revealed that ISG20L2 is aberrantly up-regulated in colon adenocarcinoma and promotes colon cancer cell proliferation through regulating ribosome biogenesis. Together, these results reveal that ISG20L2 is a new enzymatic member for 18S pre-rRNA maturation, provide insights into the mechanism of ISG20L2 underlying pre-rRNA processing, and suggest that ISG20L2 is a potential therapeutic target for colon adenocarcinoma.


Assuntos
Adenocarcinoma , Neoplasias do Colo , Animais , Humanos , RNA Ribossômico 18S/metabolismo , Precursores de RNA/genética , Precursores de RNA/metabolismo , Adenocarcinoma/genética , Neoplasias do Colo/genética , RNA Ribossômico/genética , RNA Ribossômico/metabolismo , Ribossomos/genética , Ribossomos/metabolismo , Processamento Pós-Transcricional do RNA , Exonucleases/genética , Exonucleases/metabolismo , RNA Ribossômico 5,8S/genética , Mamíferos/genética
16.
Asian J Surg ; 47(4): 1806-1808, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38155078

RESUMO

OBJECTIVE: To report a patient of pseudoaneurysm of carotid artery caused by brucellosis infection and improve the recognition, diagnosis and treatment of this disease. METHODS: The etiology, clinical data and treatment of false aneurysm were reviewed A 75-year-old man with a high probability of pseudoaneurysm of the left common carotid artery was found by enhanced CT. Open surgery was performed. Bacterial culture return was Brucella. After regular oral drug treatment, the patient recovered well. RESULTS: The patient recovered well after surgery and took oral medication regularly for 3 months without recurrence. CONCLUSION: Pseudoaneurysms of the carotid artery caused by brucella infection are very rare, and correct diagnosis and open surgery combined with drug therapy are the best choices.


Assuntos
Falso Aneurisma , Masculino , Humanos , Idoso , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/etiologia , Falso Aneurisma/cirurgia , Artéria Carótida Primitiva/diagnóstico por imagem , Artéria Carótida Primitiva/cirurgia , Artérias Carótidas
17.
Bioorg Chem ; 141: 106892, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37776681

RESUMO

Peptide-based drugs have garnered considerable attention in recent years owing to their increasingly crucial role in the treatment of diverse diseases. However, the limited pharmacokinetic properties of peptides have hindered their full potential. One prominent strategy for enhancing the druggability of peptides is N-methylation, which involves the addition of a methyl group to the nitrogen atom of the peptide backbone. This modification significantly improves the stability, bioavailability, receptor binding affinity and selectivity of peptide drug candidates. In this review, we provide a comprehensive overview of the advancements in synthetic methods for N-methylated peptide synthesis, as well as the associated limitations. Moreover, we explore the versatile effects of N-methylation on various aspects of peptide properties. Furthermore, we emphasize the efforts dedicated to N-methylated peptide pharmaceuticals that have successfully obtained marketing approval.


Assuntos
Desenvolvimento de Medicamentos , Peptídeos , Metilação , Peptídeos/química , Nitrogênio , Preparações Farmacêuticas
18.
BMC Plant Biol ; 23(1): 413, 2023 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-37674150

RESUMO

BACKGROUND: Chayote is an underutilized species of Cucurbitaceae. It is rich in nutrients such as protein, minerals, phenols and its extracts have anti-cardiovascular and anti-cancer effects, making it a versatile plant for both medicinal and culinary purposes. Although research on its root tuber is limited, they are rich in starch and have a structure similar to that of potatoes, cassava, and sweet potatoes. Therefore, they can serve as potential substitutes for potatoes and offer promising prospects as agricultural and industrial resources. However, the physiological and cellular mechanisms of chayote root tuber formation and development are still unclear. RESULTS: In this study, we observed the growth habit of 'Tuershao' (high yield of root tuber). The results revealed that the tuber enlargement period of 'Tuershao' lasts approximately 120 days, with the early enlargement phase occurring during 0-30 days, rapid enlargement phase during 30-90 days, and maturation phase during 90-120 days. Physiological indicators demonstrated a gradual increase in starch content as the tuber developed. The activities of sucrose synthase (SUS) and invertase (VIN) showed a consistent trend, reaching the highest level in the rapid expansion period, which was the key enzyme affecting tuber expansion. Moreover, the special petal like structure formed by the secondary phloem and secondary xylem of the tuber resulted in its enlargement, facilitating the accumulation of abundant starch within the thin-walled cells of this structure. Principal component analysis further confirmed that starch content, SUS and VIN activities, as well as the concentrations of calcium (Ca), iron (Fe), and selenium (Se), were the major factors influencing tuber development. Moreover, the low temperature environment not only promoted the growth of 'Tuershao' tubers but also enhanced the accumulation of nutritional substances. CONCLUSIONS: These findings contribute to a deeper understanding of the formation and developmental mechanisms of 'Tuershao' tubers, providing valuable guidance for cultivation practices aimed at improving crop yield.


Assuntos
Agricultura , Cucurbitaceae , Cálcio , Temperatura Baixa , Ferro
19.
Front Cardiovasc Med ; 10: 1139771, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37554367

RESUMO

Background: Commando procedure, the surgical replacement of the mitral and aortic valves combined with reconstruction of the fibrosa fibrous body, is a technical challenge in patients with small aortic and mitral annuli. In this study, we evaluated the safety and early outcomes of the "Chimney" modality of the Commando procedure, in patients with small aortic and mitral annuli, after prior valve surgery, using a self-assembled valved conduit. Methods: From April 2021 to April 2022, 30 consecutive cases of the "Chimney" Commando procedure, with a self-assembled valved conduit and other combined cardiac procedures, were fully performed for re-operative patients with small aortic roots. Data were obtained through a medical record review, at the Asian Heart Hospital in Wuhan, China. Results: The patient's mean age was 52.7 ± 13.53 years, with 93.3% females. All patients had a previous heart valve surgery, 90% of which had double valve replacement (DVR). Hospital death occurred in 3.3% (n = 1) of the patients, due to malignant arrhythmias and multiorgan failure. Postoperative echocardiogram exams showed that the sizes of the aortic and mitral valve prostheses were 24.23 ± 1.60 mm and 28.33 ± 1.21 mm, respectively. All patients had intact intervalvular fibrosa (IVF) repair and no patient had any aberration in the left heart chamber communication. With the exception of one postoperative sick sinus syndrome and one re-sternotomy for bleeding, there were no significant postoperative complications, such as mortality, renal failure requiring ongoing dialysis, or mediastinitis. Echocardiography exams in the sixth postoperative month showed that the mean gradients of the aortic and mitral valves were 16.26 ± 6.44 mmHg and 11.24 ± 4.90 mmHg, respectively. Conclusions: In comparison with the standard Commando operation, the early outcomes and safety of the "Chimney" Commando procedure proved to be a feasible therapeutic option for patients with small aortic and mitral annuli, after prior valve operations. This approach enables the enlargement of the aortic and mitral annuli and the implantation of the necessary valve prosthesis.

20.
World J Surg Oncol ; 21(1): 243, 2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37563730

RESUMO

BACKGROUND: Cancer stem cells may be the source of cancer-causing mutant cells and are closely related to the prognosis of cancer. Our study aimed to investigate the potential association between single-nucleotide polymorphisms (SNPs) of cancer stem cell-related genes and the prognosis of lung cancer patients. METHODS: The SNP loci were genotyped by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS), and the overall survival of subjects was analyzed by log-rank test after stratifying and adjusting their demographic data, clinical data, and genotypes. The correlation between survival time and quality of life of lung cancer under codominant, dominant, recessive, and additive genetic models was analyzed by the Cox regression model. The association between SNP polymorphism and the prognosis of lung cancer was analyzed by Stata16.0 software, and their heterogeneity was tested. Interaction analysis was performed using R software (version 4.2.0). RESULTS: Stratified analysis unveiled that rs3740535 had recessive AA genotype and additive GG genotype; Rs3130932 dominant GT + GG genotype, additive TT genotype; Rs13409 additive TT genotype; Rs6815391 recessive CC genotype and additional TT genotype were associated with increased risk of lung cancer death. Rs3130932 recessive GG genotype was associated with a reduced risk of lung cancer death. CONCLUSION: Rs3740535, rs3130932, rs13409, and rs6815391 are associated with the overall survival of lung cancer patients and may be valuable for the prognosis of lung cancer patients.


Assuntos
Neoplasias Pulmonares , Polimorfismo de Nucleotídeo Único , Humanos , Qualidade de Vida , Neoplasias Pulmonares/genética , Genótipo , Prognóstico , Predisposição Genética para Doença , Estudos de Casos e Controles
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA