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1.
J Am Chem Soc ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38717282

RESUMO

In this study, we investigated the role of aluminum cations in facilitating hydride transfer during the hydrogenation of imines within the context of Noyori-type metal-ligand cooperative catalysis. We propose a novel model involving aluminum cations directly coordinated with imines to induce activation from the lone pair electron site, a phenomenon termed σ-induced activation. The aluminum metal-hydride amidate complex ("HMn-NAl") exhibits a higher ability of hydride transfer in the hydrogenation of imines compared to its lithium counterpart ("HMn-NLi"). Density functional theory (DFT) calculations uncover that the aluminum cation efficiently polarizes unsaturated bonds through σ-electron-induced activation in the transition state of hydride transfer, thereby enhancing substrate electrophilicity more efficiently. Additionally, upon substrate coordination, aluminum's coordination saturation improves the hydride nucleophilicity of the HMn-NAl complex via the breakage of the Al-H coordination bond.

2.
EMBO J ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38769438

RESUMO

Energy stress, characterized by the reduction of intracellular ATP, has been implicated in various diseases, including cancer. Here, we show that energy stress promotes the formation of P-bodies in a ubiquitin-dependent manner. Upon ATP depletion, the E3 ubiquitin ligase TRIM23 catalyzes lysine-63 (K63)-linked polyubiquitination of HCLS1-associated protein X-1 (HAX1). HAX1 ubiquitination triggers its liquid‒liquid phase separation (LLPS) and contributes to P-bodies assembly induced by energy stress. Ubiquitinated HAX1 also interacts with the essential P-body proteins, DDX6 and LSM14A, promoting their condensation. Moreover, we find that this TRIM23/HAX1 pathway is critical for the inhibition of global protein synthesis under energy stress conditions. Furthermore, high HAX1 ubiquitination, and increased cytoplasmic localization of TRIM23 along with elevated HAX1 levels, promotes colorectal cancer (CRC)-cell proliferation and correlates with poor prognosis in CRC patients. Our data not only elucidate a ubiquitination-dependent LLPS mechanism in RNP granules induced by energy stress but also propose a promising target for CRC therapy.

3.
J Asian Nat Prod Res ; : 1-15, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38598409

RESUMO

A sensitive UPLC-HRMS method was developed and validated for simultaneous quantification of four active flavonoids from Chimonanthus nitens Leaf Granules (CNLG) in biological matrix. The method was utilized in pharmacokinetic study of the four flavonoids in rats as well as other evaluation assays in vitro. It was revealed that rutin, nicotiflorin, and astragalin had poor oral bioavailability in rats possibly due to low intestinal permeability and metabolism in intestinal flora. Kaempferol underwent rapid glucuronidation and sulphation in rat plasma with medium permeability coefficient. The results provided valuable data for future research and development of CNLG flavonoids.

4.
Radiol Imaging Cancer ; 6(3): e230167, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38607280

RESUMO

Purpose To investigate the association of tumor arterial burden (TAB) on preoperative MRI with transarterial chemoembolization refractoriness (TACER) and progression-free survival (PFS) in patients with hepatocellular carcinoma (HCC). Materials and Methods This retrospective study included patients with HCC who underwent repeated transarterial chemoembolization (TACE) treatments between January 2013 and December 2020. HCC was confirmed with pathology or imaging, and patients with other tumors, lost follow-up, or with a combination of other treatments were excluded. TACER was defined as viable lesions of more than 50% or increase in tumor number after two or more consecutive TACE treatments, continuous elevation of tumor markers, extrahepatic spread, or vascular invasion. TAB assessed with preoperative MRI was divided into high and low groups according to the median. A Cox proportional hazards model was used to determine the predictors of TACER and PFS. Results A total of 355 patients (median age, 61 years [IQR, 54-67]; 306 [86.2%] men, 49 [13.8%] women) were included. During a median follow-up of 32.7 months, the high TAB group had significantly faster TACER and decreased PFS than the low TAB group (all log-rank P < .001). High TAB was the strongest independent predictor of TACER and PFS in multivariable Cox regression analyses (hazard ratio [HR], 2.23 [95% CI: 1.51, 3.29]; HR, 2.30 [95% CI: 1.61, 3.27], respectively), especially in patients with Barcelona Clinic Liver Cancer stage A or a single tumor. The restricted cubic spline plot demonstrated that the HR of TACER and PFS continuously increased with increasing TAB. Conclusion High preoperative TAB at MRI was a risk factor for faster refractoriness and progression in patients with HCC treated with TACE. Keywords: Interventional-Vascular, MR Angiography, Hepatocellular Carcinoma, Transarterial Chemoembolization, Progression-free Survival, MRI Supplemental material is available for this article. © RSNA, 2024.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Prognóstico , Estudos Retrospectivos , Imageamento por Ressonância Magnética
5.
Noise Health ; 26(120): 37-43, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38570309

RESUMO

OBJECTIVE: Noise is a kind of perceived public nuisance that is closely related to people's subjective feelings and lives. This study explores the clinical application effect of comprehensive noise reduction technology in outpatients with vitiligo. METHODS: A total of 76 patients with vitiligo were selected in the Department of Dermatology at Baoding No. 2 Central Hospital from January 2020 to January 2021, as the control group (CG), receiving 5S management mode, and 80 patients with vitiligo from February 2021 to October 2022 were selected as the study group (SG), receiving comprehensive noise reduction technology combined with the 5S management mode for this retrospective study. The effects of different management modes on these patients were observed. RESULTS: SG had higher nursing quality scores in service attitude, service initiative, communication skills, environmental management and item management and overtly a lower noise level than CG (all P < 0.001). The Hamilton Anxiety Scale (HAMA) scores of the two groups at the end of treatment were significantly lower than those on admission (P < 0.05), with SG showing a lower score than CG (P < 0.001). Correlation analysis showed that noise levels and HAMA scores had a positive correlation (r = 0.423, P < 0.001). Patients with negative feelings about medical treatment caused by various noise sources in SG were obviously less than those in CG (P < 0.05). Both the groups had a statistical difference in overall satisfaction (P < 0.05). CONCLUSION: The investigation and data analysis demonstrated that comprehensive noise reduction in outpatients with vitiligo had a considerable effect. This technology can standardise the behaviour of medical staff, enhance nursing quality, reduce noise levels and alleviate patients' anxiety and improve their satisfaction. It has great benefits for the outpatient environment and patients.


Assuntos
Vitiligo , Humanos , Estudos Retrospectivos , Vitiligo/terapia , Pacientes Ambulatoriais , Inquéritos e Questionários , Satisfação do Paciente
6.
Artigo em Inglês | MEDLINE | ID: mdl-38583799

RESUMO

PURPOSE: This study aims to investigate the current status of affiliate stigma among parents of autistic children, analyze the influencing factors, explore the relationship among mindfulness, coping styles, and affiliate stigma, and verify the mediating role of coping styles between mindfulness and affiliate stigma in parents of children with autism in China. METHOD: Between February and April 2023, the Child Development Behaviour Centre of a public hospital in China recruited 345 parents of children with autism. These parents completed the General Information Questionnaire, the Mindful Attention Awareness Scale, the Affiliate Stigma Scale, and the Simple Coping Style Questionnaire. We then adapted the Hayes Process Macro and Bootstrap method to examine the mediating effects of coping styles between mindfulness and affiliate stigma. RESULTS: (1) The total affiliate stigma score of parents of children with autism was 48.53(SD, 10.74). Parents' age, monthly family income, duration of care, mindfulness, and coping styles were the influencing factors of parental affiliate stigma. (2) Mindfulness was positively correlated with positive coping style (r = .33, P < .01) and negatively correlated with negative coping style, affiliate stigma(r = -.38, -.39, P < .01), whereas affiliate stigma was negatively correlated with positive coping style (r = -.34, P < .01) and positively correlated with negative coping style(r = .41, P < .01). (3) Positive coping style and negative coping style play a parallel mediating role between mindfulness and affiliate stigma of parents of autistic children. CONCLUSION: Parents of children with autism experience significant levels of affiliate stigma. Mindfulness has a direct impact on associated stigma in parents of children with autism and also indirectly predicts associated stigma through the intermediary influence of positive and negative coping styles. Healthcare professionals could perform mindfulness interventions from an optimistic psychology viewpoint to boost parents' mindfulness and coping abilities, thereby accomplishing the objective of mitigating affiliate stigma.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38591775

RESUMO

A Gram-stain-negative, aerobic, rod-shaped and halotolerant bacterium, designated as strain ASW11-75T, was isolated from intertidal sediments in Qingdao, PR China, and identified using a polyphasic taxonomic approach. Growth of strain ASW11-75T occurred at 10-45 °C (optimum, 37 °C), pH 6.5-9.0 (optimum, pH 8.0) and 0.5-18.0 % NaCl concentrations (optimum, 2.5 %). Phylogenetic analyses based on 16S rRNA gene sequences and 1179 single-copy orthologous clusters indicated that strain ASW11-75T is affiliated with the genus Marinobacter. Strain ASW11-75T showed highest 16S rRNA gene sequence similarity to 'Marinobacter arenosus' CAU 1620T (98.5 %). The digital DNA-DNA hybridization and average nucleotide identity values between strain ASW11-75T and its closely related strains (Marinobacter salarius R9SW1T, Marinobacter similis A3d10T, 'Marinobacter arenosus' CAU 1620T, Marinobacter sediminum R65T, Marinobacter salinus Hb8T, Marinobacter alexandrii LZ-8T and Marinobacter nauticus ATCC 49840T) were 19.8-24.5 % and 76.6-80.7 %, respectively. The predominant cellular fatty acids were C16 : 0, C18 : 1 ω9c and C16 : 0 N alcohol. The polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, one unidentified aminophospholipid and two unidentified lipids. The major isoprenoid quinone was ubiquinone-9. The genomic DNA G+C content was 62.2 mol%. Based on genomic and gene function analysis, strain ASW11-75T had lower protein isoelectric points with higher ratios of acidic residues to basic residues and possessed genes related to ion transport and organic osmoprotectant uptake, implying its potential tolerance to salt. The results of polyphasic characterization indicated strain ASW11-75T represents a novel Marinobacter species, for which the name Marinobacter qingdaonensis sp. nov. with the type strain ASW11-75T is proposed. The type strain is ASW11-75T (=KCTC 82497T=MCCC 1K05587T).


Assuntos
Ácidos Graxos , Marinobacter , Ácidos Graxos/química , Fosfolipídeos/química , Água do Mar/microbiologia , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Composição de Bases , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana
8.
Front Neurosci ; 18: 1360935, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38686327

RESUMO

Objective: According to the World Alzheimer's Disease Report in 2015,there were 9.9 million new cases of dementia in the world every year. At present, the number of patients suffering from dementia in China has exceeded 8 million, and it may exceed 26 million by 2040.Mild cognitive impairment (MCI) refers to the pathological state of pre-dementia with the manifestation of the progressive decline of memory or other cognitive functions but without decline of activities of daily life. It is particularly important to prevent or prolong the development of MCI into dementia. Research showing effects of rhythmic auditory stimulation based-movement training(RASMT) interventions on cognitive function is also emerging. Therefore, the present meta-analysis briefly summarize findings regarding the impacts of RASMT programs on cognitive impairment. Methods: Data from Pubmed, Embase, and Cochrane Library were utilized. The impact of RASMT on cognitive functions was evaluated using indicators such as overall cognitive status, memory, attention, and executive functions. The REVMAN5.3 software was employed to analyze bias risks integrated into the study and the meta-analysis results for each indicator. Results: A total of 1,596 studies were retrieved, of which 1,385 non-randomized controlled studies and 48 repetitive studies were excluded. After reviewing titles and abstracts of the remaining 163 articles, 133 irrelevant studies were excluded, 30 studies were downloaded and read the full text. Among 30 articles, 18 articles that did not meet the inclusion criteria were excluded, the other 12 studies were included in this meta-analysis. Utilizing the Cochrane Collaborative Network Bias Risk Assessment Scale, it was found that 11 studies explained the method of random sequence generation, nine studies did not describe allocation concealment, four were single-blinded to all researchers, and eight reported single-blinding in the evaluation of experimental results. In the meta-analysis, the main outcomes showed statistically significant differences in overall cognitive status [MD = 1.19, 95%CI (0.09, 2.29), (p < 0.05)], attention [MD = -1.86, 95%CI (-3.53, -0.19), (p < 0.05)], memory [MD = 0.71, 95%CI (0.33, 1.09), (p < 0.01)], and executive function [MD = -0.23, 95% CI (-0.44, -0.02), (p < 0.05)]. Secondary outcomes indicated no statistically significant differences in verbal fluency [MD = -0.51, 95%CI (-1.30, 0.27), (p = 0.20)], while depression [MD = -0.29, 95% CI (-0.42, -0.16), (p < 0.01)] and anxiety [MD = 0.19, 95% CI (0.06, 0.32), (p < 0.01)] exhibited statistically significant differences. The GRADEpro GDT online tool assessed the quality of evidence for the outcome measures, revealing one low-quality outcome, two moderate-quality outcomes, and one high-quality outcome in this review. Conclusion: This study shows that RASMT can improve the general cognitive status, memory, attention and executive function of patients with cognitive impairment. The quality of evidence revealed that MMSE was low, attention and memory were moderate, and executive function was high. The RAMST program (type of exercise: play percussion instruments; time of exercise: 30-60 min; frequency of exercise: 2-3 times/week; duration of exercise: more than 12 weeks) was proved to be more effective in improving cognitive function. However, the sample size is relatively insufficient, the future needs further study. Systematic review registration: PROSPERO, identifier: CRD42023483561.

9.
Huan Jing Ke Xue ; 45(3): 1293-1303, 2024 Mar 08.
Artigo em Chinês | MEDLINE | ID: mdl-38471846

RESUMO

Electrification of bus fleets is an effective approach to reducing transportation-related pollution and carbon emissions. Evaluating the impact of electrification on existing bus fleets can provide valuable insights for promoting full electrification of public transportation in large cities. Utilizing the fuel life cycle method, we analyzed the CO2 and pollutant emissions of Zhengzhou's bus fleet before and after electrification and evaluated emissions under different electrification scenarios. Our results indicated that after electrification, the fuel life cycle CO2 and PM2.5 emissions increased by 32.6% and 42.6%, respectively, whereas CO, NOx, and VOC emissions decreased by 28%, 34%, and 25%, respectively. Optimizing the power generation structure is a critical factor in reducing CO2 and PM2.5 emissions during the electrification process. The best scenario for comprehensive electrification and power generation structure optimization could result in a 38.7% reduction in CO2, as well as reductions of 80.1% in CO, 84.4% in NOx, 92.2% in VOC, and 30.2% in PM2.5. Prioritizing electrification on long-distance routes is recommended during the replacement process. Additionally, replacing plug-in hybrid natural gas vehicles with pure electric vehicles has both advantages and disadvantages in terms of emission reduction. Achieving pollution reduction and carbon synergies requires advancing fleet replacement and power structure adjustments simultaneously.

10.
Bioorg Chem ; 145: 107236, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38402796

RESUMO

In this study, 16 new compounds, six bibenzyls (1-6) and 10 naphthalenes (7-13), including three pairs of naphthalene enantiomers and three known compounds (14-16), were isolated from Dendrobium chrysanthum. Structurally, compounds 1-5 are previously undescribed dimeric bibenzyls, uniquely linked by unusual carbon bonds. The structures of the compounds were determined using spectroscopy and X-ray crystallography. The screening results indicated that 1, 2, and 5 showed remarkable lipid-lowering activities in FFA-induced HepG2 cells, with EC50 values ranging from 3.13 to 6.57 µM. Moreover, 1, 2, and 5 significantly decreased both the mRNA and protein levels of the target SREBP-1c, and 5 also reduced PPARα mRNA and protein levels. Therefore, 1, 2, and 5 are potential drugs against hepatic steatosis by targeting PPARα or SREBP-1c.


Assuntos
Bibenzilas , Dendrobium , Fígado Gorduroso , Bibenzilas/farmacologia , Bibenzilas/química , Dendrobium/química , PPAR alfa , RNA Mensageiro , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Naftalenos/química , Naftalenos/farmacologia
11.
BMC Cancer ; 24(1): 217, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38360572

RESUMO

OBJECTIVE: The aim of this study was to compare the therapeutic value and treatment-related complications of radical hysterectomy with those of concurrent chemoradiotherapy (CCRT) for locally resectable (T1a2-T2a1) stage IIIC1r cervical cancer. METHODS: A total of 213 patients with locally resectable stage IIIC1r cervical cancer who had been treated at Jiangxi Maternal and Child Health Care Hospital between January 2013 and December 2021 were included in the study and classified into two groups: surgery (148 patients) and CCRT (65 patients). The disease-free survival (DFS) rate, overall survival (OS) rate, side effects, and economic costs associated with the two groups were compared. RESULTS: 43.9% (65/148) patients in the surgical group had no pelvic lymph node metastasis, and 21of them did not require supplementary treatment after surgery due to a low risk of postoperative pathology. The median follow-up time was 46 months (range: 7-108 months). The five-year DFS and OS rates of the surgery group were slightly higher than those of the CCRT group (80.7% vs. 75.1% and 81.6% vs. 80.6%, respectively; p > 0.05). The incidences of grade III-IV gastrointestinal reactions in the surgery and CCRT groups were 5.5% and 9.2%, respectively (p = 0.332). Grade III-IV myelosuppression was identified in 27.6% of the surgery group and 26.2% of the CCRT group (p = 0.836). The per capita treatment cost was higher for the surgery group than for the CCRT group (RMB 123, 918.6 0 vs. RMB 101, 880.90, p = 0.001). CONCLUSION: The therapeutic effects and treatment-related complications of hysterectomy and CCRT are equivalent in patients with locally resectable stage IIIC1r cervical cancer, but surgery can provide accurate lymph node information and benefit patients with unnecessary radiation.


Assuntos
Neoplasias do Colo do Útero , Feminino , Criança , Humanos , Neoplasias do Colo do Útero/patologia , Quimiorradioterapia/efeitos adversos , Linfonodos/patologia , Intervalo Livre de Doença , Excisão de Linfonodo , Estudos Retrospectivos , Estadiamento de Neoplasias , Histerectomia
12.
Sci Rep ; 14(1): 1982, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263420

RESUMO

Epidemiological studies have reported a positive association between chronic inflammation and cancer risk. However, the causal association between chronic inflammation and breast cancer (BC) risk remains unclear. Here, we performed a Mendelian randomization study to investigate the etiological role of chronic inflammation in BC risk. We acquired data regarding C-reactive protein (CRP), interleukin (IL)-1a, IL-1b, and IL-6 expression and BC related to single nucleotide polymorphisms (SNPs) from two larger consortia (the genome-wide association studies and the Breast Cancer Association Consortium). Next, we conducted the two-sample Mendelian randomization study to investigate the relationship of the abovementioned inflammatory factors with the incidence of BC. We found that genetically predicted CRP, IL-6, and IL-1a levels did not increase BC incidence (odds ratio (OR)CRP 1.06, 95% confidence interval (CI) 0.98-1.12, P = 0.2059, ORIL-6 1.05, 95% CI 0.95-1.16, P = 0.3297 and ORIL-1a 1.01, 95% CI 0.99-1.03, P = 0.2167). However, in subgroup analysis, genetically predicted IL-1b levels increased ER + BC incidence (OR 1.15, 95% CI 1.03-1.27, P = 0.0088). Our study suggested that genetically predicted IL-1b levels were found to increase ER + BC susceptibility. However, due to the support of only one SNP, heterogeneity and pleiotropy tests cannot be performed, which deserves further research.


Assuntos
Neoplasias Inflamatórias Mamárias , Interleucina-1alfa , Humanos , Interleucina-1beta , Proteína C-Reativa , Interleucina-6 , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Inflamação
13.
Cell Res ; 34(4): 281-294, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38200278

RESUMO

Plant survival requires an ability to adapt to differing concentrations of nutrient and toxic soil ions, yet ion sensors and associated signaling pathways are mostly unknown. Aluminum (Al) ions are highly phytotoxic, and cause severe crop yield loss and forest decline on acidic soils which represent ∼30% of land areas worldwide. Here we found an Arabidopsis mutant hypersensitive to Al. The gene encoding a leucine-rich-repeat receptor-like kinase, was named Al Resistance1 (ALR1). Al ions binding to ALR1 cytoplasmic domain recruits BAK1 co-receptor kinase and promotes ALR1-dependent phosphorylation of the NADPH oxidase RbohD, thereby enhancing reactive oxygen species (ROS) generation. ROS in turn oxidatively modify the RAE1 F-box protein to inhibit RAE1-dependent proteolysis of the central regulator STOP1, thus activating organic acid anion secretion to detoxify Al. These findings establish ALR1 as an Al ion receptor that confers resistance through an integrated Al-triggered signaling pathway, providing novel insights into ion-sensing mechanisms in living organisms, and enabling future molecular breeding of acid-soil-tolerant crops and trees, with huge potential for enhancing both global food security and forest restoration.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Alumínio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Íons , Solo , Regulação da Expressão Gênica de Plantas , Fatores de Transcrição/metabolismo
14.
IEEE J Biomed Health Inform ; 28(2): 1078-1088, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37948137

RESUMO

OBJECTIVE: The proliferation of wearable devices has escalated the standards for photoplethysmography (PPG) signal quality. This study introduces a lightweight model to address the imperative need for precise, real-time evaluation of PPG signal quality, followed by its deployment and validation utilizing our integrated upper computer and hardware system. METHODS: Multiscale Markov Transition Fields (MMTF) are employed to enrich the morphological information of the signals, serving as the input for our proposed hybrid model (HM). HM undergoes initial pre-training utilizing the MIMIC-III and UCI databases, followed by fine-tuning the Queensland dataset. Knowledge distillation (KD) then transfers the large-parameter model's knowledge to the lightweight hybrid model (LHM). LHM is subsequently deployed on the upper computer for real-time signal quality assessment. RESULTS: HM achieves impressive accuracies of 99.1% and 96.0% for binary and ternary classification, surpassing current state-of-the-art methods. LHM, with only 0.2 M parameters (0.44% of HM), maintains high accuracy despite a 2.6% drop. It achieves an inference speed of 0.023 s per image, meeting real-time display requirements. Furthermore, LHM attains a 97.7% accuracy on a self-created database. HM outperforms current methods in PPG signal quality accuracy, demonstrating the effectiveness of our approach. Additionally, LHM substantially reduces parameter count while maintaining high accuracy, enhancing efficiency and practicality for real-time applications. CONCLUSION: The proposed methodology demonstrates the capability to achieve high-precision and real-time assessment of PPG signal quality, and its practical validation has been successfully conducted during deployment. SIGNIFICANCE: This study contributes a convenient and accurate solution for the real-time evaluation of PPG signals, offering extensive application potential.


Assuntos
Processamento de Sinais Assistido por Computador , Dispositivos Eletrônicos Vestíveis , Humanos , Algoritmos , Fotopletismografia/métodos , Frequência Cardíaca , Artefatos
15.
Biomed Chromatogr ; 38(1): e5763, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37858975

RESUMO

Alisol B 23-acetate (AB23A) has been demonstrated to have beneficial effects on nonalcoholic steatohepatitis (NASH). However, the mechanisms of AB23A on NASH remain unclear. This study aimed to investigate the mechanisms underlying the metabolic regulatory effects of AB23A on NASH. We used AB23A to treat mice with NASH, which was induced by a methionine and choline deficient (MCD) diet. We initially investigated therapeutic effect and resistance to oxidation and inflammation of AB23A on NASH. Subsequently, we performed untargeted metabolomic analyses and relative validation assessments to evaluate the metabolic regulatory effects of AB23A. AB23A reduced lipid accumulation, ameliorated oxidative stress and decreased pro-inflammatory cytokines in the liver. Untargeted metabolomic analysis found that AB23A altered the metabolites of liver. A total of 55 differential metabolites and three common changed pathways were screened among the control, model and AB23A treatment groups. Further tests validated the effects of AB23A on modulating common changed pathway-involved factors. AB23A treatment can ameliorate NASH by inhibiting oxidative stress and inflammation. The mechanism of AB23A on NASH may be related to the regulation of alanine, aspartate and glutamate metabolism, d-glutamine and d-glutamate metabolism, and arginine biosynthesis pathways.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/metabolismo , Metionina/metabolismo , Metionina/farmacologia , Colina , Fígado/metabolismo , Racemetionina/metabolismo , Racemetionina/farmacologia , Dieta , Inflamação/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
16.
Mol Clin Oncol ; 20(1): 7, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38125742

RESUMO

Lenalidomide is a second-generation new immunomodulatory medication used to treat multiple myeloma (MM). Its mechanism of action involves affecting the expression of vascular endothelial growth factor, interleukin-6, cytochrome c, caspase-8, as well as other factors including immunological modulation and the direct killing of cells, among others, rendering it a fundamental medication, useful for the treatment of MM. Combining lenalidomide with other medications such dexamethasone, bortezomib, ixazomib, carfilzomib and daratumumab can markedly alleviate MM. When autologous-hematopoietic stem cell transplantation (ASCT) cannot be utilized to treat newly diagnosed individuals with MM (NDMM), monotherapy maintenance following lenalidomide and dexamethasone may be employed. Following ASCT, single-agent maintenance with lenalidomide can be performed as an additional treatment. The combination of bortezomib and lenalidomide has been demonstrated to be associated with favorable response rates, tolerable toxicity, and therapeutic benefits although caution is warranted to prevent the onset of peripheral neuropathy with its use. A new-generation oral drug with an excellent safety profile, ixazomib, is more practical and therapeutically applicable in relapsed refractory MM. However, the frequent occurrence of cardiovascular events, hematocrit, and infections with it require flexible adjustment in its clinical application. Carfilzomib produces a rapid and profound response in patients with NDMM eligible for transplantation, but its cardiovascular side effects need to be closely monitored. The primary aim of the present review was to examine the pharmacological properties and pharmacokinetics of lenalidomide, as well as the efficacy and safety of lenalidomide-based treatments with reference to data from clinical trials and real-world studies.

17.
Huan Jing Ke Xue ; 44(12): 6992-7003, 2023 Dec 08.
Artigo em Chinês | MEDLINE | ID: mdl-38098422

RESUMO

To explore the influences of chemical oxidation on the physiological and ecological functions of indigenous microorganisms during contaminated soil remediation, three oxidants, including KMnO4, Na2S2O8, and O3, were selected to investigate their remediation effects on PAHs and the responses to indigenous microorganisms under different liquid-solid ratios, in this study. The results showed that:when the ΣPAHs concentration was 679.1 mg·kg-1 and the dosage of KMnO4 and Na2S2O8 was 1%, the removal efficiency of ΣPAHs reached up to 96.9% and 95.7% under the liquid-solid ratio of 6:1; for the O3 treatment, the removal efficiency of ΣPAHs was the highest(82.3%) at the O3 dosage and the liquid-solid ratio of 72 mg·min-1 and 8:1, respectively. The removal efficiency of low ring(3-4 rings) PAHs was higher than that of high ring(5-6 rings) PAHs under different liquid-solid ratios. The highest removal efficiencies were observed for phenanthrene and acenaphthene, whereas for benzo[a]pyrene, only the KMnO4treatment provided an effective performance, showing the highest removal efficiency of 97.4%. The microbial quantity analysis indicated that the quantity of soil microorganisms in the soil dropped sharply after being treated with KMnO4, decreasing from 108 copies·g-1 to 105 copies·g-1, whereas it changed only slightly after being treated with Na2S2O8 and O3. The community structure analysis showed that Proteobacteria were predominant in the contaminated soil, with the relative abundance of 99.5%. The addition of KMnO4 and Na2S2O8 significantly increased the microbial diversity; in particular, the relative abundance of a variety of microorganisms(such as Ralstonia and Acinetobacter) that can degrade PAHs was remarkably increased. The analysis of microbial metabolic function pathways revealed that chemical oxidation could simultaneously increase the relative abundance of PAHs-degrading bacteria and improve the ability of organic metabolism. Overall, the KMnO4 treatment greatly altered the quantity of microorganisms and the structure of the microbial community and the relative abundance of PAHs-degrading microorganisms at the liquid-solid ratio of 6:1.


Assuntos
Coque , Hidrocarbonetos Policíclicos Aromáticos , Poluentes do Solo , Oxidantes/química , Hidrocarbonetos Policíclicos Aromáticos/análise , Coque/análise , Poluentes do Solo/análise , Biodegradação Ambiental , Solo/química , Microbiologia do Solo
18.
Huan Jing Ke Xue ; 44(11): 5946-5953, 2023 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-37973079

RESUMO

The waste sector is a significant source of greenhouse gas(GHG) emissions and clarifying its emission trends and characteristics is the premise for formulating GHG emission reduction strategies. Using the IPCC inventory model, the GHG emissions from the municipal solid waste(MSW) sector in China during 2010 to 2020 were estimated. The results showed that GHG emissions increased from 42.5 Mt in 2010 to 75.3 Mt in 2019, then decreased to 72.1 Mt in 2020. MSW landfills were the main source of GHG emissions. Further, with the increase in the proportion of waste incineration, the proportion of GHG incineration increased rapidly from 16.5% in 2010 to 60.1% in 2020. In terms of regional distribution, East and South China were the regions with the highest emissions, and Guangdong, Shandong, Jiangsu, and Zhejiang were the provinces with the largest GHG emissions. Implementing MSW classification, changing the MSW disposal modes from landfilling to incineration, improving the LFG collection efficiency of landfills, and using biological functional materials as the cover soil to strengthen the methane oxidation efficiency are the main measures to achieve GHG emission reduction in waste sectors.

19.
World J Gastrointest Surg ; 15(10): 2201-2210, 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37969722

RESUMO

BACKGROUND: Anastomotic leakage (AL) occurs frequently after sphincter-preserving surgery for rectal cancer and has a significant mortality rate. There are many factors that influence the incidence of AL, and each patient's unique circumstances add to this diversity. The early identification and prediction of AL after sphincter-preserving surgery are of great significance for the application of clinically targeted preventive measures. Developing an AL predictive model coincides with the aim of personalised healthcare, enhances clinical management techniques, and advances the medical industry along a more precise and intelligent path. AIM: To develop nomogram, decision tree, and random forest prediction models for AL following sphincter-preserving surgery for rectal cancer and to evaluate the predictive efficacy of the three models. METHODS: The clinical information of 497 patients with rectal cancer who underwent sphincter-preserving surgery at Jincheng People's Hospital of Shanxi Province between January 2017 and September 2022 was analyzed in this study. Patients were divided into two groups: AL and no AL. Using univariate and multivariate analyses, we identified factors influencing postoperative AL. These factors were used to establish nomogram, decision tree, and random forest models. The sensitivity, specificity, recall, accuracy, and area under the receiver operating characteristic curve (AUC) were compared between the three models. RESULTS: AL occurred in 10.26% of the 497 patients with rectal cancer. The nomogram model had an AUC of 0.922, sensitivity of 0.745, specificity of 0.966, accuracy of 0.936, recall of 0.987, and accuracy of 0.946. The above indices in the decision tree model were 0.919, 0.833, 0.862, 0.951, 0.994, and 0.955, respectively and in the random forest model were 1.000, 1.000, 1.000, 0.951, 0.994, and 0.955, respectively. The DeLong test revealed that the AUC value of the decision-tree model was lower than that of the random forest model (P < 0.05). CONCLUSION: The random forest model may be used to identify patients at high risk of AL after sphincter-preserving surgery for rectal cancer owing to its strong predictive effect and stability.

20.
Zhongguo Zhong Yao Za Zhi ; 48(17): 4722-4730, 2023 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-37802811

RESUMO

This study aims to investigate the regulatory effects of Astragalus polysaccharide(APS) and APS combined with 5-fluorouracil(5-FU) on indoleamine-2,3-dioxygenase(IDO1) in the colon tumor microenvironment. Sixty Balb/c mice were randomized into a blank group, a model group, an APS group, an APS + 5-FU group, an APS + low-dose 5-FU group, and a 5-FU group. A tumor model was established by subcutaneous transplantation with CT-26 mouse colon cancer cells in other groups except the blank group. After successful modeling, each group was treated with corresponding drugs for 7 days. The general condition, body weight, and tumor volume of the mice were observed and measured daily during the treatment period. The mice were sacrificed at the end of treatment, and the tumor suppression rate and spleen index of the mice were calculated. Western blot and fluorescence quantitative PCR were employed to determine the protein and mRNA levels, respectively, of IDO1 in the tumor tissue of mice. High performance liquid chromatography was employed to measure the levels of tryptophan(Trp) and kynurenine(Kyn) in the tumor tissue of mice. Hematoxylin-eosin(HE) staining was performed to observe the histological changes of the tumor tissue, and immunohistochemistry to detect the changes of CD4 and CD8 expression in the tumor tissue. Compared with that in the model group, the tumor volume of mice in each treatment group significantly reduced. The body weights of mice in APS + 5-FU group and 5-FU group significantly reduced from day 4 to day 7 of treatment. In addition, the APS + 5-FU group and 5-FU group showed significantly decreased spleen index. The protein and mRNA levels of IDO1 were significantly down-regulated in the APS, APS + 5-FU, and APS + low-dose 5-FU groups. The drug interventions significantly increased the Trp content and decreased the Kyn content. The APS + 5-FU group showed significantly reduced infiltration of CD4~+ T lymphocytes and increased infiltration of CD8~+ T lymphocytes. APS inhibited the expression of IDO1 in the colon tumor microenvironment to increase CD8~+ T lymphocyte infiltration, and the combination of APS with 5-FU demonstrated better effect.


Assuntos
Neoplasias do Colo , Microambiente Tumoral , Camundongos , Animais , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Fluoruracila/farmacologia , Polissacarídeos/farmacologia , Linfócitos T CD8-Positivos/metabolismo , RNA Mensageiro/metabolismo
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