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1.
Front Nutr ; 11: 1366525, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38953045

RESUMO

Objective: The objective of this study was to assess the global burden of disease for developmental and intellectual disabilities caused by iodine deficiency from 1990 to 2019. Methods: Using data from the global burden of disease (GBD) 2019, we conducted a cross-country inequity analysis to examine the worldwide burden of developmental and intellectual disabilities caused by the issue of iodine deficiency from 1990 to 2019. Absolute and relative inequality were assessed by the slope index of inequality and the concentration index, respectively. After summarising the latest evidence, we also projected the age-standardized prevalence and years lived with disability (YLD) rates up to 2030 using the BAPC and INLA packages in R statistical software. Results: In 2019, the global age-standardized prevalence and YLD rates for developmental and intellectual disabilities due to iodine deficiency were 22.54 per 100,000 population (95% UI 14.47 to 29.23) and 4.12 per 100,000 population (95% UI 2.25 to 6.4), respectively. From 1990 to 2019, the age-standardized prevalence and YLD rates of developmental and intellectual disabilities due to iodine deficiency decreased significantly. Geographic distribution showed that areas with lower socio-demographic indices (SDI) were the most affected. The correlation between higher SDI and lower prevalence highlights the role of economic and social factors in the prevalence of the disease. Cross-national inequity analysis shows that disparities persist despite improvements in health inequalities. In addition, projections suggest that the disease burden may decline until 2030. Conclusion: This research underscores the necessity for targeted interventions, such as enhancing iodine supplementation and nutritional education, especially in areas with lower SDI. We aim to provide a foundation for policymakers further to research effective preventative and potential alternative treatment strategies.

2.
Am J Transl Res ; 16(6): 2699-2710, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39006281

RESUMO

BACKGROUND: Evidence indicates that the risk of developing a secondary ovarian cancer (OC) is correlated with estrogen receptor (ER) status. However, the clinical significance of the relationship between ER-associated breast cancer (BC) and clear cell ovarian cancer (CCOC) remains elusive. METHODS: Independent single nucleotide polymorphisms (SNPs) strongly correlated with exposure were extracted, and those associated with confounders and outcomes were removed using the PhenoScanner database. SNP effects were extracted from the outcome datasets with minor allele frequency > 0.01 as the filtration criterion. Next, valid instrumental variables (IVs) were obtained by harmonizing exposure and outcome effects and further filtered based on F-statistics (> 10). Mendelian randomization (MR) assessment of valid IVs was carried out using inverse variance weighted (IVW), MR Egger (ME), weighted median (WM), and multiplicative random effects-inverse variance weighted (MRE-IVW) methods. For sensitivity analysis and visualization of MR findings, a heterogeneity test, a pleiotropy test, a leave-one-out test, scatter plots, forest plots, and funnel plots were employed. RESULTS: MR analyses with all four methods revealed that CCOC was not causally associated with ER-negative BC (IVW results: odds ratio (OR) = 0.89, 95% confidence interval (CI) = 0.66-1.20, P = 0.431) or ER-positive BC (IVW results: OR = 0.99, 95% CI = 0.88-1.12, P = 0.901). F-statistics were computed for each valid IV, all of which exceeded 10. The stability and reliability of the results were confirmed by sensitivity analysis. CONCLUSIONS: Our findings indicated that CCOC dids not have a causal association with ER-associated BC. The absence of a definitive causal link between ER-associated BC and CCOC suggested a minimal true causal influence of ER-associated BC exposure factors on CCOC. These results indicated that individuals afflicted by ER-associated BC could alleviate concerns regarding the developing of CCOC, thereby aiding in preserving their mental well-being stability and optimizing the efficacy of primary disease treatment.

3.
BMC Geriatr ; 24(1): 505, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849780

RESUMO

BACKGROUND: Depression is a prevalent issue among older adults, affecting their quality of life and overall well-being. Exercise is an effective means of relieving depressive symptoms in older adults, but the optimal dose for different exercise types remains unclear. As such, the aim of this meta-analysis was to examine the dose-response relationship between overall and specific types of exercise with depression symptoms in older adults. METHODS: This systematic review and network meta-analysis included a search of PubMed, Medline, Embase, PsycINFO, Cochrane library, and Web of Science for randomized controlled trials of exercise in older adults with depression symptoms from inception to 15 July 2023. Comprehensive data extraction covered dose, treatment regimen, demographics and study duration. Dosage metrics, encompassing METs-min/week, were scrutinized in correlation with the Minimal Clinically Importance Difference (MCID). RESULTS: A total of 47 studies involving 2895 participants and 7 kinds of exercise were included in the review. Without considering the dose, the results of our network meta-analysis indicated that Walking was the most effective in alleviating depression in older adults, in addition to Aerobic exercise (AE), Yoga, Qigong, Resistance training (RT), and Tai Chi (TC), which were equally effective. However, the results of the dose-response analysis found that Aerobic exercise was most effective at a dose of 1000 METs-min/week. It is noteworthy that Walking is significantly effective in alleviating depressive symptoms in older adults at very low doses. In terms of clinical benefits, we found that overall exercise doses in the range of 600 ~ 970 METs-min/week were clinically effective. Considering the specific types of exercise, Aerobic exercise, Resistance training, Walking, and Yoga were found to be effective at doses ranging from 820 ~ 1000 METs-min/week, 520 ~ 1000 METs-min/week, 650 ~ 1000 METs-min/week, 680 ~ 1000 METs-min/week, respectively. At the same time, we found that when the age exceeded 81 years, even when participating in exercise, it did not achieve the effect of alleviating depressive symptoms in older adults. CONCLUSIONS: In conclusion, including Walking, AE, Yoga, Qigong, RT, and TC, effectively alleviate depressive symptoms in older adults. Furthermore, we established statistically and clinically significant threshold doses for various exercise types. Early initiation of exercise is beneficial, but its efficacy diminishes from the age of 80, and beyond 81, exercise no longer significantly alleviates depressive symptoms.


Assuntos
Depressão , Metanálise em Rede , Humanos , Idoso , Depressão/terapia , Depressão/psicologia , Terapia por Exercício/métodos , Exercício Físico/fisiologia , Exercício Físico/psicologia , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos
4.
J Hazard Mater ; 474: 134701, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38824774

RESUMO

Coking wastewater (CWW) treatment is difficult due to its complex composition and high biological toxicity. Iron-carbon mediators was used to enhance the treatment of CWW through iron-carbon microelectrolysis (ICME). The results indicated that the removal rate of COD and phenolic compounds were enhanced by 24.1 % and 23.5 %, while biogas production and methane content were promoted by 50 % and 7 %. Microbial community analysis indicated that iron-carbon mediators had a transformative impact on the reactor's performance and dependability by enriching microorganisms involved in direct and indirect electron transfer, such as Anaerolineae and Methanothrix. The mediator also produced noteworthy gains in LB-EPS and TB-EPS, increasing by roughly 109.3 % and 211.6 %, respectively. PICRISt analysis demonstrated that iron-carbon mediators effectively augment the abundance of functional genes associated with metabolism, Citrate cycle, and EET pathway. This study provides a new approach for CWW treatment.


Assuntos
Reatores Biológicos , Carbono , Coque , Ferro , Águas Residuárias , Águas Residuárias/química , Ferro/metabolismo , Ferro/química , Carbono/química , Carbono/metabolismo , Metano/metabolismo , Eliminação de Resíduos Líquidos/métodos , Biocombustíveis , Análise da Demanda Biológica de Oxigênio , Resíduos Industriais , Poluentes Químicos da Água/metabolismo , Fenóis/metabolismo , Bactérias/metabolismo , Bactérias/genética
5.
Clin Oral Investig ; 28(7): 378, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38884808

RESUMO

OBJECTIVES: Peri-implant diseases, being the most common implant-related complications, significantly impact the normal functioning and longevity of implants. Experimental models play a crucial role in discovering potential therapeutic approaches and elucidating the mechanisms of disease progression in peri-implant diseases. This narrative review comprehensively examines animal models and common modeling methods employed in peri-implant disease research and innovatively summarizes the in vitro models of peri-implant diseases. MATERIALS AND METHODS: Articles published between 2015 and 2023 were retrieved from PubMed/Medline, Web of Science, and Embase. All studies focusing on experimental models of peri-implant diseases were included and carefully evaluated. RESULTS: Various experimental models of peri-implantitis have different applications and advantages. The dog model is currently the most widely utilized animal model in peri-implant disease research, while rodent models have unique advantages in gene knockout and systemic disease induction. In vitro models of peri-implant diseases are also continuously evolving to meet different experimental purposes. CONCLUSIONS: The utilization of experimental models helps simplify experiments, save time and resources, and promote advances in peri-implant disease research. Animal models have been proven valuable in the early stages of drug development, while technological advancements have brought about more predictive and relevant in vitro models. CLINICAL RELEVANCE: This review provides clear and comprehensive model selection strategies for researchers in the field of peri-implant diseases, thereby enhancing understanding of disease pathogenesis and providing possibilities for developing new treatment strategies.


Assuntos
Implantes Dentários , Modelos Animais de Doenças , Peri-Implantite , Animais , Humanos , Cães
6.
Plants (Basel) ; 13(11)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38891341

RESUMO

Deep sowing is an efficient strategy for maize to ensure the seedling emergence rate under adverse conditions such as drought or low temperatures. However, the genetic basis of deep-sowing tolerance-related traits in maize remains largely unknown. In this study, we performed a genome-wide association study on traits related to deep-sowing tolerance, including mesocotyl length (ML), coleoptile length (CL), plumule length (PL), shoot length (SL), and primary root length (PRL), using 255 maize inbred lines grown in three different environments. We identified 23, 6, 4, and 4 quantitative trait loci (QTLs) associated with ML, CL, PL, and SL, respectively. By analyzing candidate genes within these QTLs, we found a γ-tubulin-containing complex protein, ZmGCP2, which was significantly associated with ML, PL, and SL. Loss of function of ZmGCP2 resulted in decreased PL, possibly by affecting the cell elongation, thus affecting SL. Additionally, we identified superior haplotypes and allelic variations of ZmGCP2 with a longer PL and SL, which may be useful for breeding varieties with deep-sowing tolerance to improve maize cultivation.

7.
Foods ; 13(12)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38928896

RESUMO

The traditional Chinese Baijiu brewing process utilizes natural inoculation and open fermentation. The microbial composition and abundance in the microecology of Baijiu brewing often exhibit unstable characteristics, which directly results in fluctuations in Baijiu quality. The microbiota plays a crucial role in determining the quality of Baijiu. Analyzing the driving effect of technology and raw materials on microorganisms. Elucidating the source of core microorganisms and interactions between microorganisms, and finally utilizing single or multiple microorganisms to regulate and intensify the Baijiu fermentation process is an important way to achieve high efficiency and stability in the production of Baijiu. This paper provides a systematic review of the composition and sources of microbiota at different brewing stages. It also analyzes the relationship between raw materials, brewing processes, and brewing microbiota, as well as the steps involved in the implementation of brewing microbiota regulation strategies. In addition, this paper considers the feasibility of using Baijiu flavor as a guide for Baijiu brewing regulation by synthesizing the microbiota, and the challenges involved. This paper is a guide for flavor regulation and quality assurance of Baijiu and also suggests new research directions for regulatory strategies for other fermented foods.

8.
Neurochem Res ; 49(8): 2165-2178, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38824460

RESUMO

Patients suffering from hepatic ischemia-reperfusion injury (HIRI) frequently exhibit postoperative cognitive deficits. Our previous observations have emphasized the diurnal variation in hepatic ischemia-reperfusion injury-induced cognitive impairment, in which gut microbiota-associated hippocampal lipid metabolism plays an important role. Herein, we further investigated the molecular mechanisms involved in the process. Hepatic ischemia-reperfusion surgery was performed under morning (ZT0, 08:00) and evening (ZT12, 20:00). Fecal microbiota transplantation was used to associate HIRI model with pseudo-germ-free mice. The novel object recognition test and Y-maze test were used to assess cognitive function. 16S rRNA gene sequencing and analysis were used for microbial analysis. Western blotting was used for hippocampal protein analysis. Compared with the ZT0-HIRI group, ZT12-HIRI mice showed learning and short term memory impairment, accompanied by down-regulated expression of hippocampal CB1R, but not CB2R. Both gut microbiota composition and microbiota metabolites were significantly different in ZT12-HIRI mice compared with ZT0-HIRI. Fecal microbiota transplantation from the ZT12-HIRI was demonstrated to induce cognitive impairment behavior and down-regulated hippocampal CB1R and ß-arrestin1. Intraperitoneal administration of CB1R inhibitor AM251 (1 mg/kg) down-regulated hippocampal CB1R and caused cognitive impairment in ZT0-HIRI mice. And intraperitoneal administration of CB1R agonist WIN 55,212-2 (1 mg/kg) up-regulated hippocampal CB1R and improved cognitive impairment in ZT12-HIRI mice. In summary, the results suggest that gut microbiota may regulate the diurnal variation of HIRI-induced cognitive function by interfering with hippocampal CB1R.


Assuntos
Disfunção Cognitiva , Microbioma Gastrointestinal , Hipocampo , Receptor CB1 de Canabinoide , Traumatismo por Reperfusão , Animais , Microbioma Gastrointestinal/fisiologia , Hipocampo/metabolismo , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/etiologia , Traumatismo por Reperfusão/metabolismo , Receptor CB1 de Canabinoide/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ritmo Circadiano/fisiologia , Fígado/metabolismo , Transplante de Microbiota Fecal , Aprendizagem em Labirinto/fisiologia
9.
Ultrasonics ; 142: 107381, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38901150

RESUMO

During the ultrasound multi-layer focused scanning inspection process, the sequential images characterizing the defect morphology suffer from inter-layer contour information loss, which causes a reduction in the accuracy of defect 3D reconstruction, subsequently leading to errors in the characterization of the defect size and morphology. In order to address the above issues, a new method based on the Attention-based Residual Completion Network (ARC) is proposed for ultrasonic point cloud completion to characterize metal defects. Firstly, the ARC network extracts global contour morphological features and local edge detail features from the ultrasonic point cloud through consecutive residual convolutions. Subsequently, the two sets of features are concatenated and finally fed into a decoder based on self-attention, realizing the reconstruction of lost contour information and enhancing the 3D reconstruction accuracy of defects. In the experiment, an ultrasonic microscope was used to inspect actual steel plates. The internal defects were then completed using the ARC network, and the completion results were compared with the metallographic images of the defects. The experiment results indicated that, after completion, the characterization accuracy of defect morphology and sizes is enhanced by an average of 10.31 %. The ARC network provides a novel method for high-precision 3D characterization of internal defects in metal materials.

10.
J Nanobiotechnology ; 22(1): 290, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802884

RESUMO

Corneal neovascularization (CNV) is one of the common blinding factors worldwide, leading to reduced vision or even blindness. However, current treatments such as surgical intervention and anti-VEGF agent therapy still have some shortcomings or evoke some adverse effects. Recently, SU6668, an inhibitor targeting angiogenic tyrosine kinases, has demonstrated growth inhibition of neovascularization. But the hydrophobicity and low ocular bioavailability limit its application in cornea. Hereby, we proposed the preparation of SU6668 pure nanoparticles (NanoSU6668; size ~135 nm) using a super-stable pure-nanomedicine formulation technology (SPFT), which possessed uniform particle size and excellent aqueous dispersion at 1 mg/mL. Furthermore, mesenchymal stem cell membrane vesicle (MSCm) was coated on the surface of NanoSU6668, and then conjugated with TAT cell penetrating peptide, preparing multifunctional TAT-MSCm@NanoSU6668 (T-MNS). The T-MNS at a concentration of 200 µg/mL was treated for CNV via eye drops, and accumulated in blood vessels with a high targeting performance, resulting in elimination of blood vessels and recovery of cornea transparency after 4 days of treatment. Meanwhile, drug safety test confirmed that T-MNS did not cause any damage to cornea, retina and other eye tissues. In conclusion, the T-MNS eye drop had the potential to treat CNV effectively and safely in a low dosing frequency, which broke new ground for CNV theranostics.


Assuntos
Córnea , Neovascularização da Córnea , Nanopartículas , Soluções Oftálmicas , Neovascularização da Córnea/tratamento farmacológico , Animais , Nanopartículas/química , Soluções Oftálmicas/química , Córnea/metabolismo , Córnea/efeitos dos fármacos , Camundongos , Inibidores da Angiogênese/química , Inibidores da Angiogênese/uso terapêutico , Inibidores da Angiogênese/farmacologia , Tamanho da Partícula , Humanos , Masculino , Camundongos Endogâmicos C57BL , Coelhos
11.
Sci Total Environ ; 934: 173278, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38754509

RESUMO

BACKGROUND: Environmental factors like air pollution and temperature can trigger acute myocardial infarction (AMI). However, the link between large-scale weather patterns (synoptic types) and AMI admissions has not been extensively studied. This research aimed to identify the different synoptic air types in Beijing and investigate their association with AMI occurrences. METHODS: We analyzed data from Beijing between 2013 and 2019, encompassing 2556 days and 149,632 AMI cases. Using principal component analysis and hierarchical clustering, classification into distinct synoptic types was conducted based on weather and pollution measurements. To assess the impact of each type on AMI risk over 14 days, we employed a distributed lag non-linear model (DLNM), with the reference being the lowest risk type (Type 2). RESULTS: Four synoptic types were identified: Type 1 with warm, humid weather; Type 2 with warm temperatures, low humidity, and long sunshine duration; Type 3 with cold weather and heavy air pollution; and Type 4 with cold temperatures, dryness, and high wind speed. Type 4 exhibited the greatest cumulative relative risk (CRR) of 1.241 (95%CI: 1.150, 1.339) over 14 days. Significant effects of Types 1, 3, and 4 on AMI events were observed at varying lags: 4-12 days for Type 1, 1-6 days for Type 3, and 1-11 days for Type 4. Females were more susceptible to Types 1 and 3, while individuals younger than 65 years old showed increased vulnerability to Types 3 and 4. CONCLUSION: Among the four synoptic types identified in Beijing from 2013 to 2019, Type 4 (cold, dry, and windy) presented the highest risk for AMI hospitalizations. This risk was particularly pronounced for males and people under 65. Our findings collectively highlight the need for improved methods to identify synoptic types. Additionally, developing a warning system based on these synoptic conditions could be crucial for prevention.


Assuntos
Poluição do Ar , Hospitalização , Infarto do Miocárdio , Tempo (Meteorologia) , Infarto do Miocárdio/epidemiologia , Pequim/epidemiologia , Humanos , Hospitalização/estatística & dados numéricos , Masculino , Poluição do Ar/estatística & dados numéricos , Feminino , Idoso , Pessoa de Meia-Idade , Fatores de Risco , Poluentes Atmosféricos/análise
12.
Antioxidants (Basel) ; 13(4)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38671870

RESUMO

Dry eye disease (DED) is a multifactorial condition affecting the ocular surface. It is characterized by loss of tear film homeostasis and accompanied by ocular symptoms that may potentially result in damage to the ocular surface and even vision loss. Unmodifiable risk factors for DED mainly include aging, hormonal changes, and lifestyle issues such as reduced sleep duration, increased screen exposure, smoking, and ethanol consumption. As its prevalence continues to rise, DED has garnered considerable attention, prompting the exploration of potential new therapeutic targets. Recent studies have found that when the production of ROS exceeds the capacity of the antioxidant defense system on the ocular surface, oxidative stress ensues, leading to cellular apoptosis and further oxidative damage. These events can exacerbate inflammation and cellular stress responses, further increasing ROS levels and promoting a vicious cycle of oxidative stress in DED. Therefore, given the central role of reactive oxygen species in the vicious cycle of inflammation in DED, strategies involving antioxidants have emerged as a novel approach for its treatment. This review aims to enhance our understanding of the intricate relationship between oxidative stress and DED, thereby providing directions to explore innovative therapeutic approaches for this complex ocular disorder.

13.
Food Chem X ; 22: 101382, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38665634

RESUMO

In this study, a fortified Daqu (FF Daqu) was prepared using high cellulase-producing Bacillus subtilis, and the effects of in situ fortification on the physicochemical properties, flavor, active microbial community and metabolism of Daqu were analyzed. The saccharification power, liquefaction power, and cellulase activity of the FF Daqu were significantly increased compared with that of the traditional Daqu (CT Daqu). The overall differences in flavor components and their contents were not significant, but the higher alcohols were lower in FF Daqu. The relative abundance of dominant active species in FF Daqu was 85.08% of the total active microbiota higher than 63.42% in CT Daqu, and the biomarkers were Paecilomyces variotii and Aspergillus cristatus, respectively. The enzymes related to starch and sucrose metabolic pathways were up-regulated and expressed in FF Daqu. In the laboratory level simulation of baijiu brewing, the yield of baijiu was increased by 3.36% using FF Daqu.

14.
Front Nutr ; 11: 1366553, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38549751

RESUMO

Background: Numerous studies have already identified an association between excessive consumption of red meat and colorectal cancer (CRC). However, there has been a lack of detailed understanding regarding the disease burden linked to diet high in red meat and CRC. Objective: We aim to offer evidence-based guidance for developing effective strategies that can mitigate the elevated CRC burden in certain countries. Methods: We used the data from the Global Burden of Disease (GBD) Study 2019 to evaluate global, regional, and national mortality rates and disability-adjusted Life years (DALYs) related to diet high in red meat. We also considered factors such as sex, age, the socio-demographic index (SDI), and evaluated the cross-national inequalities. Furthermore, we utilized DALYs data from 204 countries and regions to measure cross-country inequalities of CRC by calculating the slope index of inequality and concentration index as standard indicators of absolute and relative inequalities. Discussion: The results show that globally, the age-standardized mortality rate (ASMR) and age-standardized disability adjusted life year rate (ASDR) related to CRC due to diet high in red meat have decreased, with estimated annual percent change (EAPCs) of -0.32% (95% CI -0.37 to -0.28) and-0.18% (95% CI -0.25 to -0.11). Notably, the burden was higher among males and the elderly. The slope index of inequality rose from 22.0 (95% CI 18.1 to 25.9) in 1990 to 32.9 (95% CI 28.3 to 37.5) in 2019 and the concentration index fell from 59.5 (95% CI 46.4 to 72.6) in 1990 to 48.9 (95% CI 34.6 to 63.1) in 2019. Also, according to our projections, global ASDR and ASMR might tend to increase up to 2030. Conclusion: ASMR and ASDR for CRC associated with high red meat diets declined globally from 1990 to 2019, but the absolute number of cases is still rising, with men and the elderly being more affected. CRC associated with diets high in red meat exhibits significant income inequality, placing a disproportionate burden on wealthier countries. Moreover, according to our projections, ASMR and ASDR are likely to increase globally by 2030. In order to address this intractable disease problem, understanding changes in global and regional epidemiologic trends is critical for policy makers and others.

15.
Lab Invest ; 104(5): 102042, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38431117

RESUMO

Esophageal squamous cell carcinoma stands as a notably aggressive malignancy within the digestive system. In cases of early esophageal cancer without lymph node metastasis, endoscopic surgical resection offers a viable alternative, often resulting in improved patient quality of life. However, the paucity of methods to preoperatively ascertain lymph node involvement complicates surgical planning. SOX4 gene was previously found to be highly associated with invasive metastasis in our work through single-cell RNA sequencing on 5 paired tumor/peritumor tissues. This research included the collection of 124 tissue samples from 106 patients (106 tumor and 18 lymph node specimens). Samples were methodically arranged into a tissue microarray and treated with immunohistochemical staining. Statistical analysis was conducted to assess the relationship between them. In the univariate analysis, 3 factors were identified as statistically significant in relation to lymph node metastasis: T category (P = .014), vascular invasion (P < .001), and SOX4 intensity (P = .001). Additionally, when evaluating SOX4 intensity alongside other clinical indicators, SOX4 was shown to independently influence lymph node metastasis. Further, the multivariate analysis revealed that vascular invasion (P < .001) and SOX4 intensity (P = .003) were significantly associated with lymph node metastasis, exhibiting hazard ratios of 10.174 and 7.142, respectively. The results of our study indicate that both SOX4 expression and vascular invasion serve as predictors of lymph node metastasis in patients diagnosed with category T1 esophageal squamous cell carcinoma, underscoring the potential utility of SOX4 in prognostic evaluations.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Metástase Linfática , Fatores de Transcrição SOXC , Humanos , Masculino , Fatores de Transcrição SOXC/metabolismo , Fatores de Transcrição SOXC/genética , Feminino , Pessoa de Meia-Idade , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/secundário , Carcinoma de Células Escamosas do Esôfago/cirurgia , Idoso , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Linfonodos/patologia , Linfonodos/metabolismo , Adulto , Prognóstico
16.
Org Lett ; 26(12): 2511-2516, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38506402

RESUMO

This work demonstrates the synthesis of a variety of perfluoroalkyl heterocycles via a visible-light-driven radical-polar crossover cyclization strategy. In this process, single-electron reduction/SNV-type/cyclization sequences follow the radical addition reaction of a diazoester, which differs from the current role of diazoesters as radical precursors/acceptors. This transformation demonstrates excellent functional group compatibility and allows for the modification of many bioactive molecules with diazoesters. Such a reaction could represent a novel approach to the photochemical transformation of diazo compounds.

17.
Front Immunol ; 15: 1295305, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38481990

RESUMO

Introduction: Ubiquitination is a crucial biological mechanism in humans, essential for regulating vital biological processes, and has been recognized as a promising focus for cancer therapy. Our objective in this research was to discover potential enzymes associated with ubiquitination that may serve as therapeutic targets for individuals with esophageal carcinoma (ESCA). Methods: To identify genes linked to the prognosis of ESCA, we examined mRNA sequencing data from patients with ESCA in the TCGA database. Further investigation into the role of the candidate gene in ESCA was conducted through bioinformatic analyses. Subsequently, we carried out biological assays to assess its impact on ESCA development. Results: Through univariate Cox regression analysis, we identified Ubiquitin Conjugating Enzyme E2 B (UBE2B) as a potential gene associated with the prognosis of ESCA. UBE2B exhibited significant upregulation and was found to be correlated with survival outcomes in ESCA as well as other cancer types. Additionally, UBE2B was observed to be involved in various biological pathways linked to the development of ESCA, including TNF-a signaling via NF-κB, epithelial-mesenchymal transition, inflammatory response, and hypoxia. Moreover, immune-related pathways like B cell activation (GO: 0042113), B cell receptor signaling pathway (GO: 0050853) and B cell mediated immunity (GO:0019724) were also involved. It was found that high expression of UBE2B was correlated with the increase of several kinds of T cells (CD8 T cells, Th1 cells) and macrophages, while effector memory T cell (Tem) and Th17 cells decreased. Furthermore, UBE2B showed potential as a prognostic biomarker for ESCA, displaying high sensitivity and specificity. Notably, proliferation and migration in ESCA cells were effectively suppressed when the expression of UBE2B was knocked down. Conclusions: To summarize, this study has made a discovery regarding the importance of gaining new insights into the role of UBE2B in ESCA. UBE2B might be an oncogene with good ability in predicting and diagnosing ESCA. Consequently, this discovery highlights the feasibility of targeting UBE2B as a viable approach for treating patients with ESCA.


Assuntos
Carcinoma , Neoplasias Esofágicas , Humanos , Prognóstico , Oncogenes , Linfócitos B , Neoplasias Esofágicas/genética , Biomarcadores , Enzimas de Conjugação de Ubiquitina/genética
18.
CNS Neurosci Ther ; 30(2): e14610, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38334013

RESUMO

AIMS: Hepatic ischemia-reperfusion injury (HIRI) resulting from hepatic inflow occlusion, which is a common procedure in liver surgery is inevitable. Previous research has confirmed that the cognitive dysfunction induced by HIRI is closely related to dysbiosis of the gut microbiota. This research aims to investigate the mechanisms underlying this complication. METHODS: C57BL/6 mice underwent hepatic ischemia experimentally through the occlusion of the left hepatic artery and portal vein. To assess the HDAC2-ACSS2 axis, gut microbiota transplantation. Enzyme-linked immunosorbent assay and LC/MS short-chain fatty acid detection were utilized. RESULTS: The findings indicated a notable decline in ACSS2 expression in the hippocampus of mice experiencing hepatic ischemia-reperfusion injury, emphasizing the compromised acetate metabolism in this particular area. Furthermore, the cognitive impairment phenotype and the dysregulation of the HDAC2-ACSS2 axis could also be transmitted to germ-free mice via fecal microbial transplantation. Enzyme-linked immunosorbent assay revealed reduced Acetyl-coenzyme A (acetyl-CoA) and Acetylated lysine levels in the hippocampus. CONCLUSION: These findings suggest that acetate metabolism is impaired in the hippocampus of HIRI-induced cognitive impairment mice and related to dysbiosis, leading to compromised histone acetylation.


Assuntos
Disfunção Cognitiva , Microbioma Gastrointestinal , Traumatismo por Reperfusão , Animais , Camundongos , Acetatos/metabolismo , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Disbiose/complicações , Fígado/metabolismo , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/metabolismo
19.
J Chem Neuroanat ; 136: 102397, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38331229

RESUMO

BACKGROUND: Ischemic stroke (IS) is a life-threatening neurological disease with various pathological mechanisms. Tetrahydropiperine (THP) is a natural alkaloid with protective effects against multiple diseases, such as seizure, and pain. This study was to examine the impact of THP on IS and investigate its potential mechanism. MATERIAL AND METHODS: We employed network pharmacology and molecular docking techniques to identify the target proteins of THP for intervention in IS. Adult male Sprague-Dawley rats were used to create a permanent middle cerebral artery occlusion model. PC-12 cells were chosen to establish an oxygen-glucose deprivation (OGD) cell model. Disease modeling followed by nimodipine (NIMO); 3-methyladenine (3-MA) and rapamycin (RAP) interventions. Open field test, Longa score, balance beam test, and forelimb grip test were used to measure motor and neurological functions. The degree of neurological damage recovery was assessed through behavioral analysis, and cerebral infarction volume was determined using TTC staining. Morphological changes were examined through HE and Nissl staining, and ultrastructural changes in neurons were observed using transmission electron microscopy. The protein expression of autophagy and related pathways was analyzed through Western blot (WB). The appropriate hypoxia time and drug concentration were determined using CCK-8 assay, which also measured cell survival rate. RESULTS: The network pharmacology findings indicated that the impact of THP on IS was enhanced in the PI3K/Akt signaling pathway. THP demonstrated robust docking capability with proteins associated with the autophagy and PI3K/Akt/mTOR, as indicated by the molecular docking outcomes. THP significantly improved behavioral damage, reduced the area of cerebral infarction, ameliorated histopathological damage from ischemia, increase neuronal survival, and alleviated ultrastructural damage in neurons (P < 0.05). THP enhanced the survival of PC-12 cells induced by OGD and ameliorated the morphological harm to the cells (P < 0.05). THP was found to elevate the quantities of P62, LC3-Ⅰ, PI3K, P-AKt/Akt, and P-mTOR/mTOR proteins while reducing the levels of Atg7 and Beclin1 proteins. The results of transmission electron microscopy showed no autophagosomes in the THP, 3-MA, and 3-MA + THP groups. CONCLUSION: The activation of the PI3K/Akt/mTOR signaling pathway by THP inhibits autophagy and provides relief from neurological damage in IS.


Assuntos
Alcaloides , Isquemia Encefálica , AVC Isquêmico , Fármacos Neuroprotetores , Ratos , Animais , Masculino , Ratos Sprague-Dawley , Proteínas Proto-Oncogênicas c-akt/metabolismo , AVC Isquêmico/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Fosfatidilinositol 3-Quinases/metabolismo , Simulação de Acoplamento Molecular , Serina-Treonina Quinases TOR/metabolismo , Infarto da Artéria Cerebral Média/tratamento farmacológico , Oxigênio , Isquemia Encefálica/tratamento farmacológico
20.
ACS Appl Mater Interfaces ; 16(6): 6988-6997, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38310560

RESUMO

Constructing a three-dimensional (3D) structure along with Zn (002) texture selective exposure is a promising strategy to tackle the issues faced by Zn metal anodes. Herein, for the first time, we proposed an electrochemical stripping strategy to achieve controlled modification of the texture and microstructure of zinc foils in one step, building a hierarchical structure with (002) texture preferred exposed Zn (SZ). The SZ with favorable zincophilic properties not only can reduce the concentration polarization at the interface but also allow Zn to grow horizontally on the edge of the (002) texture by guiding the adsorption sites for Zn2+. Moreover, the honeycomb-like structure is beneficial to rearrange the distribution of the Zn2+ flux as well as alleviating stress changes during cycling. Thus, the SZ||Cu cell exhibits excellent stability with a Coulombic efficiency of 99.76% over 1800 cycles. The SZ||NaV3O8·xH2O cell with inconspicuous self-discharge effect maintains a high areal capacity of 3.67 mA h cm-2 even after 700 cycles with a low N/P ratio of 3.6. This work achieves texture architecture and structure designing on Zn foils simultaneously by metallurgical electrochemical methods and opens up a potential strategy to implement the practicality of zinc metal anodes.

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