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1.
Inorg Chem ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39007761

RESUMO

Although organic-inorganic hybrid Mn2+ halides have advanced significantly, achieving high stability and narrow-band emission remains enormously challenging owing to the weak ionic nature and soft crystal lattice of the halide structure. To address these issues, we proposed a cationic engineering strategy of long-range cation π···π stacking and C-H···π interactions to simultaneously improve the crystal structural stability and rigidity. Herein, two organic zero-dimensional (0D) manganese halide hybrids of (BACQ)2MnX4 [BACQ = 4-(butylamino)-7-chloroquinolin-1-ium; X = Cl and Br] were synthesized. (BACQ)2MnX4 display strong green-light emissions with the narrowest full width at half-maximum (fwhm) of 39 nm, which is significantly smaller than those of commercial green phosphor ß-SiAlON:Eu2+ and most of reported manganese halides. Detailed Hirshfeld surface analyses demonstrate the rigid environment around the [MnX4]2- units originating from the interactions between [BACQ]+. The rigid crystal structure weakens the electron-phonon coupling and renders narrow fwhm of these manganese halides, which is further confirmed by temperature-dependent emission spectra. Remarkably, (BACQ)2MnX4 realizes outstanding structural and luminescence stabilities in various extreme environments. Benefiting from the excellent performance, these Mn2+ halides are used to assemble light-emitting diodes with a wide color gamut of 105% of the National Television System Committee 1931 standard, showcasing the advanced applications in liquid-crystal-display backlighting.

2.
J Med Chem ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38990190

RESUMO

The exploration of novel anticancer compounds based on natural cyclopeptides has emerged as a pivotal paradigm in the contemporary advancement of macrocyclic pharmaceuticals. Phakellistatin 13 is a cycloheptapeptide derived from the brown snubby sponge and exhibits remarkable antitumor activity. In this study, we have designed and synthesized a series of chiral cyclopeptides incorporating the rigid isoindolinone moiety at various sites within the natural cycloheptapeptide Phakellistatin 13, with the aim of investigating conformationally constrained cyclopeptides as potential antitumor agents. Cyclopeptide 3, comprising alternating l-/d-amino acid residues, exhibited promising antihepatocellular carcinoma effects. Detailed biological experiments have revealed that Phakellistatin 13 analogs effectively inhibit the proliferation of tumor cells and induce apoptosis and autophagy, while also causing cell cycle arrest through the modulation of the p53 and mitogen-activated protein kinase (MAPK) signaling pathway. This study not only provides valuable insights into chemical structural modifications but also contributes to a deeper understanding of the biological mechanisms underlying the development of natural cyclopeptide-based drugs.

3.
J Cancer Res Clin Oncol ; 150(7): 342, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38980538

RESUMO

BACKGROUND: Cholangiocarcinoma (CCA), characterized by high heterogeneity and extreme malignancy, has a poor prognosis. Doublecortin-like kinase 1 (DCLK1) promotes a variety of malignant cancers in their progression. Targeting DCLK1 or its associated regulatory pathways can prevent the generation and deterioration of several malignancies. However, the role of DCLK1 in CCA progression and its molecular mechanisms remain unknown. Therefore, we aimed to investigate whether and how DCLK1 contributes to CCA progression. METHODS: The expression of DCLK1 in CCA patients was detected using Immunohistochemistry (IHC). We established DCLK1 knockout and DCLK1 overexpression cell lines for Colony Formation Assay and Transwell experiments to explore the tumor-promoting role of DCLK1. RT-PCR, Western blot and multiple fluorescent staining were used to assess the association between DCLK1 and epithelial-mesenchymal transition (EMT) markers. RNA sequencing and bioinformatics analysis were performed to identify the underlying mechanisms by which DCLK1 regulates CCA progression and the EMT program. RESULTS: DCLK1 was overexpressed in CCA tissues and was associated with poor prognosis. DCLK1 overexpression facilitated CCA cell invasion, migration, and proliferation, whereas DCLK1 knockdown reversed the malignant tendencies of CCA cells, which had been confirmed both in vivo and in vitro. Furthermore, we demonstrated that DCLK1 was substantially linked to the advancement of the EMT program, which included the overexpression of mesenchymal markers and the downregulation of epithelial markers. For the underlying mechanism, we proposed that the PI3K/AKT/mTOR pathway is the key process for the role of DCLK1 in tumor progression and the occurrence of the EMT program. When administered with LY294002, an inhibitor of the PI3K/AKT/mTOR pathway, the tumor's ability to proliferate, migrate, and invade was greatly suppressed, and the EMT process was generally reversed. CONCLUSIONS: DCLK1 facilitates the malignant biological behavior of CCA cells through the PI3K/AKT/mTOR pathway. In individuals with cholangiocarcinoma who express DCLK1 at high levels, inhibitors of the PI3K/AKT/mTOR signaling pathway may be an effective therapeutic approach.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Quinases Semelhantes a Duplacortina , Peptídeos e Proteínas de Sinalização Intracelular , Fosfatidilinositol 3-Quinases , Proteínas Serina-Treonina Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Serina-Treonina Quinases TOR , Humanos , Colangiocarcinoma/patologia , Colangiocarcinoma/metabolismo , Colangiocarcinoma/genética , Colangiocarcinoma/tratamento farmacológico , Serina-Treonina Quinases TOR/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/metabolismo , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/tratamento farmacológico , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Fosfatidilinositol 3-Quinases/metabolismo , Masculino , Animais , Feminino , Camundongos , Transição Epitelial-Mesenquimal , Linhagem Celular Tumoral , Prognóstico , Pessoa de Meia-Idade , Proliferação de Células , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto , Regulação Neoplásica da Expressão Gênica
4.
J Affect Disord ; 361: 751-759, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38885845

RESUMO

BACKGROUND: Compared to monetary rewards, depressive symptoms are specifically associated with abnormal social reward processing. In addition, individuals with melancholic depression may exhibit more significant reward-related impairments. However, there is still limited understanding of the specific alterations in social reward processing in individuals with melancholic depression. METHODS: Forty patients with melancholic major depressive disorder (MDD), forty patients with non-melancholic MDD, and fifty healthy controls participated in the social incentive delay (SID) tasks with event-related potential (ERP) recording. We measured one anticipatory ERP(cue-N2) and two consummatory ERPs (FRN, fb-P3). Furthermore, we examined correlation between FRN and consummatory anhedonia. RESULTS: Melancholic MDD patients showed less anticipation of social rewards (cue-N2). Concurrently, melancholic individuals demonstrated diminished reception of social rewards, as evidenced by reduced amplitudes of FRN. Notably, the group x condition interaction effect on FRN was significant (F (2, 127) = 4.15, p = 0.018, η2ρ = 0.061). Melancholic MDD patients had similar neural responses to both gain and neutral feedback (blunted reward positivity), whereas non-melancholic MDD patients (t (39) = 3.09, p = 0.004) and healthy participants (t (49) = 5.25, p < 0.001) had smaller FRN amplitudes when receiving gain feedback relative to neutral feedback. In addition, there was a significant correlation between FRN and consummatory anhedonia in MDD patients. CONCLUSIONS: Our findings indicated that individuals with melancholic MDD exhibit attenuated neural responses to both anticipated and consumed social rewards. This suggests that aberrant processing of social rewards could serve as a potential biomarker for melancholic MDD.


Assuntos
Anedonia , Transtorno Depressivo Maior , Eletroencefalografia , Potenciais Evocados , Recompensa , Humanos , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/psicologia , Masculino , Feminino , Adulto , Potenciais Evocados/fisiologia , Anedonia/fisiologia , Pessoa de Meia-Idade , Motivação/fisiologia , Antecipação Psicológica/fisiologia , Comportamento Social , Sinais (Psicologia) , Adulto Jovem , Estudos de Casos e Controles
5.
Lancet Healthy Longev ; 5(7): e464-e479, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38945129

RESUMO

BACKGROUND: Parkinson's disease is the second most common neurodegenerative disorder, exhibiting an upward trend in prevalence. We aimed to investigate the prevalence of Parkinson's disease, temporal trends between 1980 and 2023, and variations in prevalence by location, age, sex, survey period, sociodemographic index (SDI), human development index (HDI), and study characteristics (sample size, diagnostic criteria, and data source). METHODS: In this systematic review and meta-analysis we searched PubMed, Cochrane, Web of Science, Embase, Scopus, and Global Health for observational studies that reported Parkinson's disease prevalence in the general population from database inception to Nov 1, 2023. We included studies if they were original observational investigations, had participants from the general population or community-based datasets, and provided numerical data on the prevalence of Parkinson's disease either with 95% CIs or with sufficient information to calculate 95% CIs. Studies were excluded if they were conducted in a specific population, had a sample size smaller than 1000, or were review articles, case reports, protocols, meeting abstracts, letters, comments, short communications, posters, and reports. The publication characteristics (first author and publication year), study location (countries, WHO regions, SDI, and HDI), survey period, study design, diagnostic criteria, data source, participant information, and prevalence data were extracted from articles using a standard form. Two authors independently evaluated eligibility, and discrepancies were resolved through discussion with the third author. We used random effect models to pool estimates with 95% CIs. Estimated annual percentage change (EAPC) was calculated to assess the temporal trend in prevalence of Parkinson's disease. The study was registered with PROSPERO, CRD42022364417. FINDINGS: 83 studies from 37 countries were eligible for analysis, with 56 studies providing all-age prevalence, 53 studies reporting age-specific prevalence, and 26 studies providing both all-age and age-specific prevalence. Global pooled prevalence of Parkinson's disease was 1·51 cases per 1000 (95% CI 1·19-1·88), which was higher in males (1·54 cases per 1000 [1·17-1·96]) than in females (1·49 cases per 1000 [1·12-1·92], p=0·030). During different survey periods, the prevalence of Parkinson's disease was 0·90 cases per 1000 (0·48-1·44; 1980-89), 1·38 cases per 1000 (1·17-1·61; 1990-99), 1·18 cases per 1000 (0·77-1·67; 2000-09), and 3·81 cases per 1000 (2·67-5·14; 2010-23). The EAPC of Parkinson's disease prevalence was significantly higher in the period of 2004-23 (EAPC 16·32% [95% CI 6·07-26·58], p=0·0040) than in the period of 1980-2003 (5·30% [0·82-9·79], p=0·022). Statistically significant disparities in prevalence were observed across six WHO regions. Prevalence increased with HDI or SDI. Considerable variations were observed in the pooled prevalence of Parkinson's disease based on different sample sizes or diagnostic criteria. Prevalence also increased with age, reaching 9·34 cases per 1000 (7·26-11·67) among individuals older than 60 years. INTERPRETATION: The global prevalence of Parkinson's disease has been increasing since the 1980s, with a more pronounced rise in the past two decades. The prevalence of Parkinson's disease is higher in countries with higher HDI or SDI. It is necessary to conduct more high-quality epidemiological studies on Parkinson's disease, especially in low SDI countries. FUNDING: National Nature Science Foundation of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Assuntos
Doença de Parkinson , Doença de Parkinson/epidemiologia , Humanos , Prevalência , Feminino , Masculino , Saúde Global/estatística & dados numéricos
6.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(6): 639-645, 2024 Jun 15.
Artigo em Chinês | MEDLINE | ID: mdl-38926382

RESUMO

OBJECTIVES: To explore the effects of iris xanthin on airway inflammation, airway remodeling, and the high mobility group box 1 protein (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway in asthmatic young mice. METHODS: Sixty male BALB/c young mice were randomly assigned into six groups: a blank group, a model group, a dexamethasone group, and low, medium, and high dose groups of iris xanthin, with ten mice per group. Asthma models were induced through intraperitoneal injections of a sensitizing agent [ovalbumin (OVA) 20 µg + aluminum hydroxide gel 2 mg], followed by 4% OVA aerosol inhalation. Lung function was measured using a pulmonary function tester to determine lung volume (LV), resting ventilation per minute (VE), and airway reactivity (Penh value). Hematoxylin-eosin (HE) staining was employed to examine and analyze airway remodeling. The contents of interleukin (IL)-1ß, IL-6, and tumor necrosis factor alpha (TNF-α) in bronchoalveolar lavage fluid were quantified using ELISA. Real-time fluorescence quantitative polymerase chain reaction and Western blot analysis were used to assess the expression of HMGB1/TLR4/NF-κB pathway-related mRNA and proteins in lung tissues. RESULTS: Compared to the model group, the dexamethasone and iris xanthin-treated groups (low, medium, and high doses) exhibited significant increases in LV and VE (P<0.05), with incremental dose-dependent increases observed in the iris xanthin groups. Additionally, Penh values, IL-1ß, IL-6, TNF-α, and airway remodeling indicators, along with mRNA levels of HMGB1, TLR4, and NF-κB p65 and protein levels of HMGB1, TLR4, and p-NF-κB p65, were all reduced (P<0.05) in a dose-dependent manner. When compared to the dexamethasone group, the low and medium dose iris xanthin groups showed decreases in LV and VE (P<0.05), whereas Penh values, IL-1ß, IL-6, TNF-α, and airway remodeling indicators, along with mRNA levels of HMGB1, TLR4, NF-κB p65 and protein levels of HMGB1, TLR4, and p-NF-κB p65, were increased (P<0.05). No significant differences were noted in these indices between the high dose iris xanthin group and the dexamethasone group (P>0.05). CONCLUSIONS: Iris xanthin can effectively alleviates airway inflammation and inhibits airway remodeling in asthmatic young mice, possibly through the suppression of the HMGB1/TLR4/NF-κB pathway.


Assuntos
Remodelação das Vias Aéreas , Asma , Proteína HMGB1 , Camundongos Endogâmicos BALB C , NF-kappa B , Transdução de Sinais , Receptor 4 Toll-Like , Animais , Remodelação das Vias Aéreas/efeitos dos fármacos , Asma/tratamento farmacológico , Asma/metabolismo , Masculino , Camundongos , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos
7.
Sensors (Basel) ; 24(11)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38894177

RESUMO

Visual simultaneous localization and mapping (VSLAM) enhances the navigation of autonomous agents in unfamiliar environments by progressively constructing maps and estimating poses. However, conventional VSLAM pipelines often exhibited degraded performance in dynamic environments featuring mobile objects. Recent research in deep learning led to notable progress in semantic segmentation, which involves assigning semantic labels to image pixels. The integration of semantic segmentation into VSLAM can effectively differentiate between static and dynamic elements in intricate scenes. This paper provided a comprehensive comparative review on leveraging semantic segmentation to improve major components of VSLAM, including visual odometry, loop closure detection, and environmental mapping. Key principles and methods for both traditional VSLAM and deep semantic segmentation were introduced. This paper presented an overview and comparative analysis of the technical implementations of semantic integration across various modules of the VSLAM pipeline. Furthermore, it examined the features and potential use cases associated with the fusion of VSLAM and semantics. It was found that the existing VSLAM model continued to face challenges related to computational complexity. Promising future research directions were identified, including efficient model design, multimodal fusion, online adaptation, dynamic scene reconstruction, and end-to-end joint optimization. This review shed light on the emerging paradigm of semantic VSLAM and how deep learning-enabled semantic reasoning could unlock new capabilities for autonomous intelligent systems to operate reliably in the real world.

8.
Immunol Invest ; : 1-12, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38900045

RESUMO

BACKGROUND: Interstitial lung disease (ILD) is a common pulmonary manifestation of rheumatoid arthritis (RA) and is associated with a poor prognosis. However, the role of blood biomarkers in RA-associated interstitial lung disease (RA-ILD) is ill-defined. We aim to evaluate the role of YKL-40 and Krebs von den Lungen-6 (KL-6) in the diagnosis and severity evaluation of RA-ILD. METHODS: 45 RA-non-ILD patients and 38 RA-ILD patients were included. The clinical data and the levels of YKL-40 and KL-6 were measured and collected for all patients. The risk factors for RA-ILD were analyzed and their correlation with relevant indicators and predictive value for RA-ILD was explored. RESULTS: The levels of YKL-40 and KL-6 in RA-ILD patients were higher than RA-non-ILD patients (p < .001). Both YKL-40 and KL-6 were correlated with the incidence of RA-ILD. The predictive power of combined KL-6 and YKL-40 for the presence of ILD was 0.789, with a sensitivity and specificity at 73.7% and 73.3%, respectively. In RA-ILD patients, both YKL-40 and KL-6 were positively correlated with the Scleroderma Lung Study (SLS) I score and negatively correlated with pulmonary function. CONCLUSIONS: KL-6 and YKL-40 might be a useful biomarker in the diagnosis and severity evaluation of RA-ILD.

9.
Hum Vaccin Immunother ; 20(1): 2341454, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38695296

RESUMO

Pertussis is a vaccine-preventable infectious disease; however, data on pertussis antibody levels in a nationwide population are still limited in China. We aimed to pool the seropositivity rates of IgG antibodies against pertussis toxin (PT-IgG) across the country. We systematically searched PubMed, Web of Science, Embase, and the China National Knowledge Infrastructure Database for studies published between January 1, 2010, and June 30, 2023. Studies reporting the seroprevalence of PT-IgG among a healthy Chinese population were included. Pooled estimates were obtained using random-effects meta-analyzes. The meta-analysis included 39 studies (47,778 participants) reporting anti-PT IgG seropositivity rates. The pooled rate for all ages was 7.06% (95% CI, 5.50%-9.07%). Subgroup analyzes showed rates ranging from 6.36% to 12.50% across different age groups. This meta-analysis indicated a low anti-PT IgG seropositivity rate in the Chinese population, particularly among school-aged children and young adults. This finding underscores the urgent need to refine immunization strategies.


Assuntos
Anticorpos Antibacterianos , Imunoglobulina G , Toxina Pertussis , Coqueluche , Humanos , Estudos Soroepidemiológicos , Toxina Pertussis/imunologia , Imunoglobulina G/sangue , Coqueluche/epidemiologia , Coqueluche/imunologia , Coqueluche/prevenção & controle , China/epidemiologia , Anticorpos Antibacterianos/sangue , Criança , Adulto , Adulto Jovem , Adolescente , Pré-Escolar , Pessoa de Meia-Idade , Vacina contra Coqueluche/imunologia , Vacina contra Coqueluche/administração & dosagem , População do Leste Asiático
10.
Plant Physiol Biochem ; 212: 108707, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38763002

RESUMO

Apple (Malus domestica Borkh.) is a widely cultivated fruit crop worldwide but often suffers from abiotic stresses such as salt and cold. Gibberellic acid (GA) plays a pivotal in controlling plant development, environmental adaptability, and secondary metabolism. The GA2-oxidase (GA2ox) is responsible for the deactivation of bioactive GA. In this study, seventeen GA2-oxidase genes were identified in the apple genome, and these members could be clustered into four clades based on phylogenetic relationships and conserved domain structures. MdGA2ox7 exhibited robust expression across various tissues, responded to cold and salt treatments, and was triggered in apple fruit peels via light-induced anthocyanin accumulation. Subcellular localization prediction and experiments confirmed that MdGA2ox7 was located in the cytoplasm. Overexpression of MdGA2ox7 in Arabidopsis caused a lower level of active GA and led to GA-deficient phenotypes, such as dwarfism and delayed flowering. MdGA2ox7 alleviated cold and salt stress damage in both Arabidopsis and apple in concert with melatonin (MT). Additionally, MdGA2ox7 enhanced anthocyanin biosynthesis in apple calli and activated genes involved in anthocyanin synthesis. These findings provide new insights into the functions of apple GA2ox in regulating development, stress tolerance, and secondary metabolism.


Assuntos
Antocianinas , Regulação da Expressão Gênica de Plantas , Malus , Proteínas de Plantas , Malus/genética , Malus/metabolismo , Antocianinas/metabolismo , Antocianinas/biossíntese , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Estresse Fisiológico , Arabidopsis/genética , Arabidopsis/metabolismo , Giberelinas/metabolismo , Filogenia , Plantas Geneticamente Modificadas , Melatonina/metabolismo
11.
Mol Carcinog ; 63(8): 1486-1499, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38780182

RESUMO

Lactate dehydrogenase A (LDHA) is known to promote the growth and invasion of various types of tumors, affects tumor resistance, and is associated with tumor immune escape. But how LDHA reshapes the tumor microenvironment and promotes the progression of renal cell carcinoma (RCC) remains unclear. In this study, we found that LDHA was highly expressed in clear cell RCC (ccRCC), and this high expression was associated with macrophage infiltration, while macrophages were highly infiltrated in ccRCC, affecting patient prognosis via M2-type polarization. Our in vivo and in vitro experiments demonstrated that LDHA and M2-type macrophages could enhance the proliferation, invasion, and migration abilities of ccRCC cells. Mechanistically, high expression of LDHA in ccRCC cells upregulated the expression of EPHA2 in exosomes derived from renal cancer. Exosomal EPHA2 promoted M2-type polarization of macrophages by promoting activation of the PI3K/AKT/mTOR pathway in macrophages, thereby promoting the progression of ccRCC. All these findings suggest that EPHA2 may prove to be a potential therapeutic target for advanced RCC.


Assuntos
Carcinoma de Células Renais , Progressão da Doença , Exossomos , Neoplasias Renais , Macrófagos , Receptor EphA2 , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/genética , Receptor EphA2/metabolismo , Receptor EphA2/genética , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/metabolismo , Neoplasias Renais/genética , Exossomos/metabolismo , Animais , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Linhagem Celular Tumoral , Proliferação de Células , L-Lactato Desidrogenase/metabolismo , L-Lactato Desidrogenase/genética , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Masculino , Microambiente Tumoral , Prognóstico , Serina-Treonina Quinases TOR/metabolismo , Feminino , Transdução de Sinais , Camundongos Nus , Proteínas Proto-Oncogênicas c-akt/metabolismo
12.
J Dig Dis ; 25(4): 248-254, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38808604

RESUMO

OBJECTIVES: Functional dyspepsia (FD) and irritable bowel syndrome (IBS) are prevalent functional gastrointestinal disorders (FGIDs). In this study we aimed to explore the causal association between physical activity or sedentary behavior and the risk of FD and IBS. METHODS: Mendelian randomization (MR) analysis was employed. Candidate genetic instruments for physical activity and sedentary behavior were retrieved from the latest published Genome-Wide Association Study (GWAS), which included up to 703 901 participants. Summary-level GWAS data for FD (8 875 cases and 320 387 controls) and IBS (9 323 cases and 301 931 controls) were obtained from the FinnGen study. The causal effects were mainly estimated by inverse variance weighted (IVW) method. Sensitivity analyses were implemented with Cochran's Q test, MR-Egger intercept test, leave-one-out analysis, and the funnel plot. RESULTS: No significant association of moderate-to-vigorous intensity physical activity (MVPA), leisure screen time (LST), sedentary behavior at work (SDW), and sedentary commuting (SDC) with the risk of FD was found. However, there was a suggestive correlation between MVPA and the decreased risk of FD (odds ratio [OR] 0.63, 95% confidence interval [CI] 0.39-0.99, P = 0.047). Genetically predicted MVPA decreased the risk of IBS (OR 0.58, 95% CI 0.40-0.84, P = 0.004), while increased LST was positively associated with IBS risk (OR 1.33, 95% CI 1.15-1.53, P < 0.001). No causal effects of SDW or SDC on IBS risk were observed. CONCLUSION: MVPA and LST are causally linked to the development of IBS, which will facilitate primary prevention of IBS.


Assuntos
Dispepsia , Exercício Físico , Estudo de Associação Genômica Ampla , Síndrome do Intestino Irritável , Análise da Randomização Mendeliana , Comportamento Sedentário , Humanos , Síndrome do Intestino Irritável/genética , Síndrome do Intestino Irritável/epidemiologia , Dispepsia/genética , Dispepsia/etiologia , Fatores de Risco , Feminino , Masculino , Polimorfismo de Nucleotídeo Único
13.
Bioconjug Chem ; 35(6): 826-842, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38722674

RESUMO

In clinical practice, the treatment of colon cancer is faced with the dilemma of metastasis and recurrence, which is related to immunosuppression and hypoxia. Immune checkpoint blockade (ICB) is a negative regulatory pathway of immunity. Immune checkpoint blockade (ICB) is an important immunotherapy method. However, inadequate immunogenicity reduces the overall response rate of ICB. In this study, a tumor microenvironment-responsive nanomedicine (Cu-FACD@MnO2@FA) was prepared to increase host immune response and increase intracellular oxygen levels. Cu-FACD@MnO2@FA preferentially enriched at the tumor site, combined with the immune checkpoint inhibitor alpha PD-L1, induced sufficient immunogenicity to treat colon cancer. Immunofluorescence detection of tumor cells and tissues showed that the expression of hypoxa-inducing factor 1α was significantly down-regulated after treatment and the expression of immunoactivity-related proteins was significantly changed. In vivo treatment in a bilateral tumor mouse model showed complete ablation of the primary tumor and efficient inhibition of the distal tumor. In this study, for the first time, the oxygenation effects of MnO2-coated Cu-doped carbon dots and chemodynamic therapy and a strategy of combining with immuno-blocking therapy were used for treating colon cancer.


Assuntos
Carbono , Neoplasias do Colo , Cobre , Ácido Fólico , Compostos de Manganês , Óxidos , Compostos de Manganês/química , Compostos de Manganês/farmacologia , Animais , Óxidos/química , Óxidos/farmacologia , Cobre/química , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Camundongos , Carbono/química , Humanos , Ácido Fólico/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Oxigênio/química , Pontos Quânticos/química , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Microambiente Tumoral/efeitos dos fármacos
14.
Nat Commun ; 15(1): 3691, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693179

RESUMO

Voltage-gated sodium (NaV) channels mediate a plethora of electrical activities. NaV channels govern cellular excitability in response to depolarizing stimuli. Inactivation is an intrinsic property of NaV channels that regulates cellular excitability by controlling the channel availability. The fast inactivation, mediated by the Ile-Phe-Met (IFM) motif and the N-terminal helix (N-helix), has been well-characterized. However, the molecular mechanism underlying NaV channel slow inactivation remains elusive. Here, we demonstrate that the removal of the N-helix of NaVEh (NaVEhΔN) results in a slow-inactivated channel, and present cryo-EM structure of NaVEhΔN in a potential slow-inactivated state. The structure features a closed activation gate and a dilated selectivity filter (SF), indicating that the upper SF and the inner gate could serve as a gate for slow inactivation. In comparison to the NaVEh structure, NaVEhΔN undergoes marked conformational shifts on the intracellular side. Together, our results provide important mechanistic insights into NaV channel slow inactivation.


Assuntos
Microscopia Crioeletrônica , Ativação do Canal Iônico , Canais de Sódio Disparados por Voltagem , Canais de Sódio Disparados por Voltagem/metabolismo , Canais de Sódio Disparados por Voltagem/química , Humanos , Animais , Células HEK293 , Modelos Moleculares
15.
Front Pharmacol ; 15: 1338471, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38698812

RESUMO

Objective: The aim of this study is to uncover the traditional Chinese medicine (TCM) treatments for chronic gastritis and their potential targets and pathways involved in the "inflammation-cancer" conversion in four stages. These findings can provide further support for future research into TCM and its active components. Materials and methods: The literature search encompassed PubMed, Web of Science, Google Scholar, CNKI, WanFang, and VIP, employing keywords such as "chronic gastritis", "gastric cancer", "traditional Chinese medicine", "medicinal herb", "Chinese herb", and "natural plant". Results: Herbal remedies may regulate the signaling pathways linked to the advancement of chronic gastritis. Under the multi-target and multi-pathway independent or combined reaction, the inflammatory microenvironment may be enhanced, leading to repair of damaged gastric mucosal cells, buffering the progress of mucosal atrophic degeneration via the decrease of inflammatory factor expression, inhibition of oxidative stress-induced damage, facilitation of microvascular neovascularization in the gastric mucosa and regulation of the processes of gastric mucosal cell differentiation and proliferation. Simultaneously, the decreased expression of inflammatory factors may impact the expression of associated oncogenes and regulate the malignant proliferation of cells, thereby achieving the treatment and prevention objectives of gastric cancer through the reduction of cell metastasis and apoptosis. Conclusion: Chinese medicine formulations and individual drugs can be utilised at various stages of the "inflammation-cancer" progression of chronic gastritis to prevent and treat gastric cancer in a multi-level, multi-targeted, and multi-directional fashion. This can provide guidance for the accurate application of medicines during different stages of "inflammation-cancer" transformation. New insights into the mechanism of inflammation-cancer transformation and the development of novel drugs for chronic gastritis can be gained through an extensive investigation of TCM treatment in this condition.

16.
J Colloid Interface Sci ; 668: 618-633, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38696990

RESUMO

Tumor metastasis and recurrence are closely related to immune escape and hypoxia. Chemodynamic therapy (CDT), photodynamic therapy (PDT), and photothermal therapy (PTT) can induce immunogenic cell death (ICD), and their combination with immune checkpoint agents is a promising therapeutic strategy. Iron based nanomaterials have received more and more attention, but their low Fenton reaction efficiency has hindered their clinical application. In this study, Fe3O4-carbon dots complex (Fe3O4-CDs) was synthesized, which was modified with ferrocenedicarboxylic acid by amide bond, and crosslinked into Fe3O4-CDs@Fc nano complex. The CDs catalyzed the Fenton reaction activity of Fe3O4 by helping to improve the electron transfer efficiency, extended the reaction pH condition to 7.4. The Fe3O4-CDs@Fc exhibit exceptional optical activity, achieving a thermal conversion efficiency of 56.43 % under 808 nm light and a photosensitive single-line state oxygen quantum yield of 33 % under 660 nm light. Fe3O4-CDs@Fc improved intracellular oxygen level and inhibited hypoxia-inducing factor (HIF-1α) by in-situ oxygen production based on Fenton reaction. The multimodal combination of Fe3O4-CDs@Fc (CDT/PDT/PTT) strongly induced immune cell death (ICD). The expression of immune-related protein and HIF-1α was investigated by immunofluorescence method. In vivo, Fe3O4-CDs@Fc combined with immune checkpoint blocker (antibody PD-L1, αPD-L1) effectively ablated primary tumors and inhibited distal tumor growth. Fe3O4-CDs@Fc is a promising immune-antitumor drug.


Assuntos
Carbono , Oxigênio , Pontos Quânticos , Camundongos , Animais , Pontos Quânticos/química , Carbono/química , Humanos , Catálise , Oxigênio/química , Imunoterapia , Tamanho da Partícula , Antineoplásicos/farmacologia , Antineoplásicos/química , Fotoquimioterapia , Camundongos Endogâmicos BALB C , Linhagem Celular Tumoral , Ferro/química , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/farmacologia , Propriedades de Superfície , Sobrevivência Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino
17.
Heliyon ; 10(10): e30855, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38774327

RESUMO

President Xi set a long-term mitigation target of carbon neutrality by 2060 in September 2020 to cut carbon emissions and improve environmental performance. As a result, the current study aims to investigate how green human resource management and green innovation affect environmental performance in pursuit of the ultimate objective of carbon neutrality. Furthermore, the research considers the potential mediating effect of a green competitive advantage to clarify the mechanisms by which GHRM and green innovation impact environmental performance. Data from 278 employees in the manufacturing industry of Heilongjiang Province were collected through a questionnaire, for which we used a quantitative random sampling technique. The study employed the Smart PLS-4 structural equation modeling technique and revealed that all three factors significantly influenced environmental performance: green HRM, innovation, and competitive advantage. Resource-based view (RBV) theory served as the theoretical foundation for the study. The study uniquely contributes to the literature on GHRM, green innovation, competitive advantage, and environmental performance.

18.
Angew Chem Int Ed Engl ; 63(25): e202404019, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38622071

RESUMO

Accelerating sulfur conversion catalysis to alleviate the shuttle effect has become a novel paradigm for effective Li-S batteries. Although nitrogen-coordinated metal single-atom (M-N4) catalysts have been investigated, further optimizing its utilization rate and catalytic activities is urgently needed for practical applications. Inspired by the natural alveoli tissue with interconnected structure and well-distributed enzyme catalytic sites on the wall for the simultaneously fast diffusion and in situ catalytic conversion of substrates, here, we proposed the controllable synthesis of bioinspired carbon cathode with interconnected porous structure and asymmetric coordinated V-S1N3 sites for efficient and stable Li-S batteries. The enzyme-mimetic V-S1N3 shows asymmetric electronic distribution and high tunability, therefore enhancing in situ polysulfide conversion activities. Experimental and theoretical results reveal that the high charge asymmetry degree and large atom radius of S in V-S1N3 result in sloping adsorption for polysulfide, thereby exhibiting low thermodynamic energy barriers and long-range stability (0.076 % decay over 600 cycles).

19.
Medicine (Baltimore) ; 103(15): e37778, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38608115

RESUMO

The impact of pulmonary rehabilitation (PR) on patients with different chronic respiratory diseases (CRDs) during hospitalization has not been thoroughly evaluated before. The objectives of the current research were to assess the effect of comprehensive PR management on inpatients' self-management skills, exercise capacity, nutrition assessment and mental health issues and explore whether impacts of PR vary in different CRDs. This retrospective study analyzed the clinical data from 272 inpatients with CRDs receiving PR management during hospitalization between October 2020 and March 2022 in Beijing Chao-Yang Hospital. Significant improvements were found in the patients' ability of daily living (ADL), dyspnea (assessed by modified medical research council dyspnea scale (MMRC)), handgrip strength, maximal inspiratory and expiratory pressure, anxiety (using the 7-item generalized anxiety disorder scale (GAD-7)) and depression (the 9-item patient health questionnaire score (PHQ-9)). There was no significant change in nutrition assessment pre-post PR management during hospitalization. The subgroup analyses were conducted on hospitalized patients with chronic obstructive pulmonary disease (COPD), bronchiectasis, asthma, interstitial lung diseases (ILDs) and other CRDs (e.g., lung cancer, diaphragm hemiparesis, obesity, etc.). The results showed that ADL, MMRC score, MIP, MEP, PHQ-9 score improved in all subgroups with CRDs. Handgrip strength of left hand was increased in COPD inpatients and anxiety was improved in all subgroups except for ILDs. Comprehensive PR management was necessary and beneficial for patients with different CRDs during hospitalization.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Transtornos Respiratórios , Humanos , Força da Mão , Estudos Retrospectivos , Hospitalização , Dispneia
20.
Curr Pharm Teach Learn ; 16(7): 102090, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38641484

RESUMO

BACKGROUND AND OBJECTIVES: The 1 + X certificate system, introduced in China in 2019, integrates academic credentials with vocational skill certificates to meet the heightened demand for skilled talents in the growing economy. This study aims to innovate and evaluate the vocational pharmaceutical education system under the 1 + X certificate framework, specifically addressing the gap between theoretical education and workplace requirements. MATERIALS AND METHODS: A retrospective observational approach analyzed 490 pharmacy students over two academic years. The 2021 cohort underwent 1 + X integrated education, while the 2020 cohort followed conventional education. We collaborated closely with industry partners to identify and compile typical job competencies, formulating work projects aligned with industry demands. Combining the skill level standards and assessment content of "1+X Pharmaceutical Purchasing and Sales" and "1+X Pharmaceutical Preparation", we revised the course standards, incorporating typical work projects into the 2021 pharmacy professional teaching curriculum. This constituted the fundamental content of the 1 + X education reform. Statistical analysis compared course scores and 1 + X certificate examination performance. RESULTS: The 2021 cohort, under the 1 + X educational model, demonstrated higher average scores in pharmacy courses, with significant improvements in pharmacology (1 + X vs. Traditional education: 58.40 ± 14.20 vs. 53.44 ± 14.67), clinical pharmacotherapy (72.74 ± 10.28 vs. 63.15 ± 11.03), and pharmaceutical distribution and marketing (79.34 ± 10.96 vs. 67.50 ± 15.82). 1 + X certificate pass rates and satisfaction with the model were also higher than the 2020 cohort. CONCLUSION: The 1 + X certificate system is useful for developing talent in Chinese vocational education, effectively integrating assessments with industry standards. Future research should aim at evaluating long-term outcomes and improving quantitative skills assessments for enhanced effectiveness.


Assuntos
Certificação , Educação em Farmácia , Humanos , China , Estudos Retrospectivos , Educação em Farmácia/métodos , Educação em Farmácia/normas , Educação em Farmácia/estatística & dados numéricos , Educação em Farmácia/tendências , Certificação/métodos , Certificação/estatística & dados numéricos , Certificação/normas , Certificação/tendências , Avaliação Educacional/métodos , Avaliação Educacional/estatística & dados numéricos , Currículo/tendências , Currículo/normas , Educação Vocacional/métodos , Educação Vocacional/normas
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