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1.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(7): 812-816, 2024 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-38946363

RESUMO

OBJECTIVE: To explore the clinical and genetic characteristics of two newborns with Central nuclear myopathy (CNM). METHODS: Two newborns with CNM diagnosed clinically at Wuhan Children's Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology in April 2019 and November 2021 were selected as the study subjects, and their clinical data was collected. Both newborns and their parents were subjected chromosomal karyotyping analysis and whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing. Pathogenicity of the candidate variants was evaluated based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). RESULTS: Patient 1 was a male neonate and Patient 2 was a 20-day-old male infant. Both newborns had featured difficulty in breathing and swallowing. WES revealed that both had harbored hemizygous variants of the MTM1 gene, which were verified by Sanger sequencing. Patient 1 had harbored a c.1261A>G variant. Based on the ACMG guidelines, it was rated as pathogenic (PVS1+PM2_Supporting+PP3). Patient 2 harbored a c.342delT variant, which was also rated as pathogenic (PVS1+PM2_Supporting+PP3). CONCLUSION: The c.1261A>G and c.342delT variants of the MTM1 gene probably underlay the pathogenesis of CNM in the two patients.


Assuntos
Miopatias Congênitas Estruturais , Humanos , Masculino , Miopatias Congênitas Estruturais/genética , Recém-Nascido , Mutação , Sequenciamento do Exoma , Proteínas Tirosina Fosfatases não Receptoras/genética , Testes Genéticos
2.
Br J Anaesth ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38969535

RESUMO

BACKGROUND: Postoperative delirium remains prevalent despite extensive research through randomised trials aimed at reducing its incidence. Understanding trial characteristics associated with interventions' effectiveness facilitates data interpretation. METHODS: Trial characteristics were extracted from eligible trials identified through two systematic literature searches. Multivariable meta-regression was used to investigate trial characteristics associated with effectiveness estimated using odds ratios. Meta-analysis was used to investigate pooled effectiveness. RESULTS: We identified 201 eligible trials. Compared with China, trials from the USA/Canada (ratio of odds ratio, 1.89; 95% confidence interval, 1.45-2.45) and Europe/Australia/New Zealand (1.67; 1.29-2.18) had an 89% and 67% higher odds ratio, respectively, suggesting reduced effectiveness. The effectiveness was enhanced when the incidence of postoperative delirium increased (0.85; 0.79-0.92, per 10% increase). Trials with concerns related to deviations from intended interventions reported increased effectiveness compared with those at low risk (0.69; 0.53-0.90). Compared with usual care, certain interventions appeared to have reduced the incidence of postoperative delirium in low-risk trials with low-to-moderate certainty of evidence. However, these findings should be considered inconclusive because of challenges in grouping heterogeneous interventions, the limited number of eligible trials, the prevalence of small-scale studies, and potential publication bias. CONCLUSIONS: The effectiveness of postoperative delirium trials varied based on the region of trial origin, the incidence of delirium, and the risk of bias. The limitations caution against drawing definitive conclusions from different bodies of evidence. These findings highlight the imperative need to improve the quality of research on a global scale. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42023413984).

3.
Nanotechnology ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38986449

RESUMO

In order to enhance stability of Raman reporters, trapping these reporters into metal organic frameworks (MOFs) exoskeleton which is grown and compressed on the Fe3O4@Au core-satellites has been performed so as to fabricate recyclable SERS nanotags. Furthermore, encapsulation of Raman reporters in assembled MOFs-based nanocomposites has been divided into two kinds of patterns, i.e., pre-enrichment and post-enrichment, for disentangling chemical enhancement of charge transfer (CT) from electromagnetic enhancement (EM) in surface enhanced Raman scattering (SERS). Hence, in order to demonstrate encapsulation effect, a typical non-thiolated Raman reporter, e.g., crystal violet (CV) trapped in core-satellites nanoassembly based-zeolitic imidazolate frameworks (ZIF-8) shell has been selected, and the results suggest that its stability and Raman intensity have been remarkably improved. Moreover, CV incorporation pattern into ZIF-8 shell with tunable shell thickness can contribute to promoting to disentangle CT effects from EM effects.

4.
BMC Med Educ ; 24(1): 738, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982322

RESUMO

BACKGROUND: The purpose of this study was to evaluate the effectiveness and efficiency of implementing a data-driven blended online-offline (DDBOO) teaching approach in the medicinal chemistry course. METHODS: A total of 118 third-year students majoring in pharmacy were enrolled from September 2021 to January 2022. The participants were randomly assigned to either the DDBOO teaching group or the traditional lecture-based learning (LBL) group for medicinal chemistry. Pre- and post-class quizzes were administered, along with an anonymous questionnaire distributed to both groups to assess students' perceptions and experiences. RESULTS: There was no significant difference in the pre-class quiz scores between the DDBOO and LBL groups (T=-0.637, P = 0.822). However, after class, the mean quiz score of the DDBOO group was significantly higher than that of the LBL group (T = 3.742, P < 0.001). Furthermore, the scores for learning interest, learning motivation, self-learning skill, mastery of basic knowledge, teamwork skills, problem-solving ability, innovation ability, and satisfaction, as measured by the questionnaire, were significantly higher in the DDBOO group than in the traditional group (all P < 0.05). CONCLUSION: The DDBOO teaching method effectively enhances students' academic performance and satisfaction. Further research and promotion of this approach are warranted.


Assuntos
Química Farmacêutica , Educação em Farmácia , Avaliação Educacional , Estudantes de Farmácia , Feminino , Humanos , Masculino , Adulto Jovem , Química Farmacêutica/educação , Instrução por Computador/métodos , Currículo , Educação a Distância , Educação em Farmácia/métodos , Inquéritos e Questionários
5.
Front Public Health ; 12: 1389026, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39022411

RESUMO

Artificial Intelligence (AI) is revolutionizing public health education through its capacity for intricate analysis of large-scale health datasets and the tailored dissemination of health-related information and interventions. This article conducts a profound exploration into the integration of AI within public health, accentuating its scientific foundations, prospective progress, and practical application scenarios. It underscores the transformative potential of AI in crafting individualized educational programs, developing sophisticated behavioral models, and informing the creation of health policies. The manuscript strives to thoroughly evaluate the extant landscape of AI applications in public health, scrutinizing critical challenges such as the propensity for data bias and the imperative of safeguarding privacy. By dissecting these issues, the article contributes to the conversation on how AI can be harnessed responsibly and effectively, ensuring that its application in public health education is both ethically grounded and equitable. The paper's significance is multifold: it aims to provide a blueprint for policy formulation, offer actionable insights for public health authorities, and catalyze the progression of health interventions toward increasingly sophisticated and precise approaches. Ultimately, this research anticipates fostering an environment where AI not only augments public health education but also does so with a steadfast commitment to the principles of justice and inclusivity, thereby elevating the standard and reach of health education initiatives globally.


Assuntos
Inteligência Artificial , Saúde Pública , Humanos , Saúde Pública/educação , Educação em Saúde , Empoderamento
6.
Abdom Radiol (NY) ; 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39023567

RESUMO

PURPOSE: To evaluate magnetic resonance elastography (MRE)-based liver stiffness measurement as a biomarker to predict the onset of cirrhosis in early-stage alcohol-related liver disease (ALD) patients, and the transition from compensated to decompensated cirrhosis in ALD. METHODS: Patients with ALD and at least one MRE examination between 2007 and 2020 were included in this study. Patient demographics, liver chemistries, MELD score (within 30 days of the first MRE), and alcohol abstinence history were collected from the electronic medical records. Liver stiffness and fat fraction were measured. Disease progression was assessed in the records by noting cirrhosis onset in early-stage ALD patients and decompensation in those initially presenting with compensated cirrhosis. Nomograms and cut-off values of liver stiffness, derived from Cox proportional hazards models were created to predict the likelihood of advancing to cirrhosis or decompensation. RESULTS: A total of 182 patients (132 men, median age 57 years) were included in this study. Among 110 patients with early-stage ALD, 23 (20.9%) developed cirrhosis after a median follow-up of 6.2 years. Among 72 patients with compensated cirrhosis, 33 (45.8%) developed decompensation after a median follow-up of 4.2 years. MRE-based liver stiffness, whether considered independently or adjusted for age, alcohol abstinence, fat fraction, and sex, was a significant and independent predictor for both future cirrhosis (Hazard ratio [HR] = 2.0-2.2, p = 0.002-0.003) and hepatic decompensation (HR = 1.2-1.3, p = 0.0001-0.006). Simplified Cox models, thresholds, and corresponding nomograms were devised for practical use, excluding non-significant or biased variables. CONCLUSIONS: MRE-based liver stiffness assessment is a useful predictor for the development of cirrhosis or decompensation in patients with ALD.

7.
Infect Drug Resist ; 17: 2913-2921, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39011343

RESUMO

Background: We aimed to describe the difference between Chlamydia psittaci pneumonia group and non C. psittaci bacterial pneumonia group in community acquired pneumonia in this single-center clinical study. Methods: We collected the data of 35 patients with C. psittaci pneumonia cases and 46 patients with non C. psittaci bacterial pneumonia cases diagnosed with metagenomic next-generation sequencing assays from February 2019 to December 2021 in Huaihua First People's Hospital in China. Results: In the C. psittaci pneumonia group, 35 patients (100%) had a chance of exposure to poultry or birds, and their body temperature was greater than or equal to 39.0°C. The other common symptoms were a slow pulse (68.6%), cough (65.7%), expectoration (54.3%), chills (51.4%) and a shortness of breath (37.1%). Laboratory tests showed that >90% of the cases had markedly elevated infection indicators, and 97.1% of the cases had markedly declined calcium. The most common imaging finding was patchy shadows (94.3%), pleural effusion (68.6%), bilateral in 54.3% (n = 19) and unilateral in 45.7% (n = 16) participants, and 51.4% (n = 18) of cases met the criteria for severe pneumonia. In the non C. psittaci bacterial pneumonia group, 18 patients (39.1%) had a chance of exposure to poultry or birds, and 11 patients (23.9%) body temperature was greater than or equal to 39.0°C. Laboratory tests showed that >67% of cases had a mildly elevated infection indicators, and mildly declined serum albumin. Conclusion: The following characteristics are more likely to help distinguish C. psittaci pneumonia from non C. psittaci bacterial pneumonia. Including had a chance of exposure to poultry or birds, high fever, exhibit chills, expectoration, relatively slow pulse, and progress into severe pneumonia. Percentage of neutrophils, C-reactive protein, procalcitonin, lactate dehydrogenase, and myoglobin levels are higher. Blood calcium and corrected calcium are lower. Chest CT showed pleural effusion, pericardial effusion, and mediastinal lymphadenopathy.

8.
Front Public Health ; 12: 1376993, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38947354

RESUMO

Introduction: This study explored the correlative factors of falls among the older adult with cognitive impairment, to provide distinct evidence for preventing falls in the older adult with cognitive impairment compared with the general older adult population. Methods: This study was based on a cross-sectional survey, with an older adult population of 124,124 was included. The data was sourced from the Elderly Care Unified Needs Assessment for Long-Term Care Insurance in Shanghai. Binary and multivariable logistic regression analyses were conducted sequentially on the correlative factors of falls. Multivariable logistic regression was performed on variables that were significant, stratified by cognitive function levels. Results: The incidence of fall in the past 90 days was 17.67% in this study. Specific variables such as gender (male), advanced age (≥80), residence with a elevator (or lift), mild or moderate disability, quality of sleep (acceptable/poor) were negatively correlated with falls, while higher education level, living alone, residence with indoor steps, unclean and untidy living environment, MCI or dementia, chronic diseases, restricted joints, impaired vision, and the use of diaper were positively correlative factors of falls. Comparing with older adult with normal cognitive functions, older adult with dementia faced a higher risk of falling due to accessibility barrier in the residence. For general older adults, less frequency of going outside and poor social interactions were positively correlated with falls, while for older adult with cognitive impairments, going outside moderately (sometimes) was found positively correlated with falls. Older adults with cognitive impairments have increased fall risks associated with chronic diseases, restricted joints, and the use of diaper. The risk of falling escalated with the greater number of chronic diseases. Discussion: For older adult with cognitive impairments, it is advisable to live with others. Additionally, creating an accessible living environment and maintaining the cleanness and tidiness can effectively reduce the risk of falls, particularly for those with MCI or dementia. Optimal outdoor activity plans should be developed separately based on the cognitive function of older adults. Older adult with dementia who have comorbidities should be paid special attention in fall prevention compared to the general older adult population.


Assuntos
Acidentes por Quedas , Disfunção Cognitiva , Humanos , Acidentes por Quedas/estatística & dados numéricos , Masculino , Feminino , Estudos Transversais , Idoso , Disfunção Cognitiva/epidemiologia , Idoso de 80 Anos ou mais , China/epidemiologia , Fatores de Risco , Incidência
9.
Front Immunol ; 15: 1344637, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962013

RESUMO

Disulfidptosis, a regulated form of cell death, has been recently reported in cancers characterized by high SLC7A11 expression, including invasive breast carcinoma, lung adenocarcinoma, and hepatocellular carcinoma. However, its role in colon adenocarcinoma (COAD) has been infrequently discussed. In this study, we developed and validated a prognostic model based on 20 disulfidptosis-related genes (DRGs) using LASSO and Cox regression analyses. The robustness and practicality of this model were assessed via a nomogram. Subsequent correlation and enrichment analysis revealed a relationship between the risk score, several critical cancer-related biological processes, immune cell infiltration, and the expression of oncogenes and cell senescence-related genes. POU4F1, a significant component of our model, might function as an oncogene due to its upregulation in COAD tumors and its positive correlation with oncogene expression. In vitro assays demonstrated that POU4F1 knockdown noticeably decreased cell proliferation and migration but increased cell senescence in COAD cells. We further investigated the regulatory role of the DRG in disulfidptosis by culturing cells in a glucose-deprived medium. In summary, our research revealed and confirmed a DRG-based risk prediction model for COAD patients and verified the role of POU4F1 in promoting cell proliferation, migration, and disulfidptosis.


Assuntos
Adenocarcinoma , Biomarcadores Tumorais , Neoplasias Colorretais , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/diagnóstico , Prognóstico , Adenocarcinoma/genética , Adenocarcinoma/mortalidade , Biomarcadores Tumorais/genética , Feminino , Linhagem Celular Tumoral , Masculino , Proliferação de Células/genética , Perfilação da Expressão Gênica , Transcriptoma , Nomogramas , Fator 3 de Transcrição de Octâmero/genética , Movimento Celular/genética
10.
Mar Pollut Bull ; 205: 116658, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38964192

RESUMO

Offshore coastal marine ranching ecosystems provide habitat for diverse and active bacterial communities. In this study, 16S rRNA gene sequencing and multiple bioinformatics methods were applied to investigate assembly dynamics and relationships in different habitats. The higher number of edges in the water network, more balanced ratio of positive and negative links, and more keystone species included in the co-occurrence network of water. Stochastic processes dominated in shaping gut and sediment community assembly (R2 < 0.5), while water bacterial community assembly were dominated by deterministic processes (R2 > 0.5). Dissimilarity-overlap curve model indicated that the communities in different habitats have general dynamics and interspecific interaction (P < 0.001). Bacterial source-tracking analysis revealed that the gut was more similar to the sediment than the water bacterial communities. In summary, this study provides basic data for the ecological study of marine ranching through the study of bacterial community dynamics.

11.
Med ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38964333

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) provide modest but unsatisfactory benefits for extensive-stage small cell lung cancer (ES-SCLC). Developing strategies for treating ES-SCLC is critical. METHODS: We preliminarily explored the outcomes of salvage low-dose radiotherapy (LDRT) plus ICI on refractory SCLC patients. Next, we evaluated the combinational efficacy in murine SCLC. The tumor immune microenvironment (TIME) was analyzed for mechanistic study. Subsequently, we conducted a multicenter, prospective phase II trial that administered concurrent thoracic LDRT plus chemoimmunotherapy to treatment-naive ES-SCLC patients (MATCH trial, NCT04622228). The primary endpoint was confirmed objective response rate (ORR), and the key secondary endpoints included progression-free survival (PFS) and safety. FINDINGS: Fifteen refractory SCLC patients treated with LDRT plus ICI were retrospectively reviewed. The ORR was 73.3% (95% confidence interval [CI], 44.9-92.2). We identified a specific dose of LDRT (15 Gy/5 fractions) that exhibited growth retardation and improved survival in murine SCLC when combined with ICIs. This combination recruited a special T cell population, TCF1+ PD-1+ CD8+ stem-like T cells, from tumor-draining lymph nodes into the TIME. The MATCH trial showed a confirmed ORR of 87.5% (95% CI, 75.9-94.8). The median PFS was 6.9 months (95% CI, 5.4-9.3). CONCLUSIONS: These findings verified that LDRT plus chemoimmunotherapy was safe, feasible, and effective for ES-SCLC, warranting further investigation. FUNDING: This research was funded by West China Hospital (no. ZYJC21003), the National Natural Science Foundation of China (no. 82073336), and the MATCH trial was fully funded by Roche (China) Holding Ltd. (RCHL) and Shanghai Roche Pharmaceuticals Ltd. (SRPL).

12.
Anal Chem ; 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39001808

RESUMO

The development of abiotic protein affinity adsorbents remains challenging for the accurate acquisition and analysis of specific protein species. Inspired by bacterial cell walls, a hierarchical hybrid framework is fabricated through the oriented growth of an Fe-based metal organic framework (MOF) on V2C MXene for the efficient separation of lysozyme (Lys). After directed evolution of adsorptive materials, the MXene@MOF composite rich in hydroxyl groups (termed as MX@MOF-DH) is found exerting exceptional affinity for Lys. Benefiting from hydrogen-bonding, coordination, and electrostatic interaction-mediated multimodal and multivalent affinity, MX@MOF-DH reveals rapid adsorption rate (5 min), superb enrichment factor (83.1), and favorable binding capacity (609.7 mg g-1), which outperforms other latest adsorbents. Moreover, femtomolar sensitivity is achieved even in the presence of high-abundant interfering proteins, as confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometer analysis. This work not only provides an efficient approach for selective enrichment of lysozyme but also paves an avenue to construct the protein affinity reagents for specific biological medicine and analysis applications.

13.
Artigo em Inglês | MEDLINE | ID: mdl-39001887

RESUMO

PURPOSE: Negative life events are essential proximal factors that may induce suicidal behavior in adolescents, but the mechanisms connecting this link remain to further explored. The present study aimed to investigate the relationship between negative life events (NLEs) and adolescents' suicidal behavior, and the roles of core self-evaluation, depression and gender playing between them. METHODS: Using the whole-group sampling approach, 5296 Chinese adolescents (51.5% males, Meanage = 12.93) took part in this cross-sectional study in September 2021 and completed a battery of surveys including NLEs, suicidal behavior, CSE (core self-evaluation) and depression. Logistic regression and latent structural equation models were used to test the direct and indirect effects between NLEs and suicide behavior with multi-group path analysis, gender differences in this serial mediating effect were also tested. RESULTS: After controlling for age and gender, NLEs were directly associated with adolescents' suicidal behavior. CSE and depression played significant serial mediating effects in this relationship. Moreover, significant gender differences were obtained in these serial mediating pathways, with stronger effects in girls. CONCLUSION: Integrating the environmental, individual cognitive and emotional factors, our findings would be helpful in understanding the mechanism of these antecedents on adolescents' suicide behavior, which has specific practical significance for preventing and reducing suicidal behavior.

14.
Ecotoxicol Environ Saf ; 282: 116689, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39002379

RESUMO

The recent acceleration of industrialization and urbanization has brought significant attention to N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6-PPDQ), an emerging environmental pollutant from tire wear, due to its long-term effects on the environment and organisms. Recent studies suggest that 6-PPDQ can disrupt neurotransmitter synthesis and release, impact receptor function, and alter signaling pathways, potentially causing oxidative stress, inflammation, and apoptosis. This review investigates the potential neurotoxic effects of prolonged 6-PPDQ exposure, the mechanisms underlying its cytotoxicity, and the associated health risks. We emphasize the need for future research, including precise exposure assessments, identification of individual differences, and development of risk assessments and intervention strategies. This article provides a comprehensive overview of 6-PPDQ's behavior, impact, and neurotoxicity in the environment, highlighting key areas and challenges for future research.

15.
J Crohns Colitis ; 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39001689

RESUMO

BACKGROUND AND AIMS: Exosome-based therapies are gaining increasing attention, with growing evidence suggesting a link between alterations in mesentery adipose tissue (MAT) and intestinal disease in Crohn's disease (CD). However, the specific mechanism by which mesenchymal stem cells (MSCs)-Exos may alleviate colitis through targeting MAT remains not fully understood. METHODS: Human umbilical cord MSCs (HucMSCs) were cultured to isolate the corresponding exosomes (HucMSCs-Exos), which were confirmed by their morphology, size distribution, and expression of markers. In vivo, 2,4,6-trinitrobenzenesulfonic acid solution (TNBS) and dextran sodium sulfate (DSS) -induced mouse colitis models were used to detect the therapeutic effects of HucMSCs-Exos. ELISA, qRT-PCR, western blotting, and immunofluorescence determined the expression of key molecules. Luciferase reporter assay was used to confirm the relationship between miR-21-5p and SPRY2. RESULTS: Exosomes treatment through mesenteric injection demonstrated therapeutic effects on mesenteric inflammation and colitis. These therapeutic benefits were contingent on macrophages, significantly facilitating the M2 polarization of mesenteric macrophages. The expression data from GSE159814 and GSE211008 revealed that exosomal miR-21-5p was enriched in HucMSCs-Exos and could be delivered to macrophages. Additionally, the results indicated that miR-21-5p could directly target the 3'UTR of SPRY2 and activate the phosphorylation of ERK to modify macrophage phenotypes. Mechanistically, exosomal miR-21-5p derived from HucMSCs could promote macrophage M2 polarization via the SPRY2/ERK axis. CONCLUSION: Mesenteric injection of HucMSCs-Exos significantly alleviates mesenteric inflammation and colitis by promoting mesenteric macrophage M2 polarization, making it a promising approach to treat colitis and suggesting therapeutic potential role of exosomal miR-21-5p in CD.

16.
J Gastrointest Oncol ; 15(3): 1035-1049, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38989423

RESUMO

Background: B7-H3 (or CD276) represents an important costimulatory molecule expressed in many malignant solid tumors, including colorectal cancer (CRC). The receptor of B7-H3 is not known, and the intracellular function of B7-H3 remains obscure. Herein, we report that B7-H3 upregulated the epidermal growth factor heparin-binding epidermal growth factor (HB-EGF), likely by regulating hypoxia-inducible factor 1α (HIF-1α) and thereby promoting the progression of CRC. Methods: Lentiviral transfection was performed on CRC cells to establish stable low-B7-H3 expression cells. A mechanistic analysis with an Agilent human gene expression profiling chip was conducted on them. Clinical data and specimens were collected to detect the connection between B7-H3 and HB-EGF in CRC. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to detect the messenger RNA (mRNA) level of B7-H3, HB-EGF, and HIF-1α. Chromatin immunoprecipitation (ChIP) quantitative real-time PCR was conducted. The protein level of HIF-1α and the phosphatidylinositide 3-kinases (PI3K)-protein kinase B (AKT) pathway were detected by western blot. HIF-1α was recovered by lentiviral transfection, and the HB-EGF mRNA levels, proliferation, invasion, and angiogenesis ability were detected. Results: B7-H3 promoted tumor progression through HB-EGF and the PI3K-AKT pathway. As B7-H3 was downregulated, HB-EGF levels were significantly reduced simultaneously, a growth trend that was shown by both CRC cell lines and cancer tissues. In addition, B7-H3 and HB-EGF had significant associations with tumor-node-metastasis (TNM) stage and lymph node metastasis in 50 CRC patients. The binding ability of HIF-1α to the HB-EGF promoter region was significantly decreased in the shB7-H3 RKO group. Western blot revealed that PI3K, AKT, and mammalian target of rapamycin (mTOR) protein amounts and p-AKT and p-mTOR phosphorylation were also downregulated in shB7-H3 RKO cells, suggesting that B7-H3 may regulate HIF-1α via PI3K-AKT signaling. After recovery of the HIF-1α level by lentiviral transfection, the HB-EGF mRNA levels, proliferation, invasion, and angiogenesis in CRC cells recovered as well. Conclusions: B7-H3 may transmit intracellular signals through PI3K-AKT-mTOR-HIF-1α signaling, upregulating HB-EGF. As the final transcription factor of the pathway, HIF-1α regulates the transcription of the HB-EGF gene, thereby promoting HB-EGF expression, which eventually mediates cell proliferation, invasion, and angiogenesis and promotes the progression of CRC.

17.
J Asian Nat Prod Res ; : 1-9, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963070

RESUMO

Five new glycosides, namely methyl 3-methoxybenzoate-4,5-di-O-ß-D-glucopyranoside (1), (1aS,3aS,3R)-3-(4'-O-ß-D-glucopyranosyl-3'-methoxyphenyl)-5,6-dioxa-bicyclo[3.3.0]octane-1-one (2), quinolin-4(1H)-one-3-O-ß-D-glucopyranoside (3), 3-methoxy-propiophenone 4-O-(6'-ß-D-xylopyranosyl)-ß-D-glucopyranoside (4), methyl 3-methoxybenzoate 4-O-(6'-ß-D-xylopyranosyl)-ß-D-glucopyranoside (5), and one known compound, bambulignan B (6) were isolated from the culms of Phyllostachys nigra var. henonis. Their structures were determined using spectroscopic analysis. All compounds were evaluated for their DPPH radical scavenging activity. Compound 6 exhibited antioxidant activity with IC50 value of 59.5 µM (positive control, L-ascorbic acid, IC50 = 12.4 µM; 2,6-ditertbutyl-4-methyl phenol, IC50 = 11.8 µM).

18.
Mol Neurobiol ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958889

RESUMO

As a risk factor for Alzheimer's disease (AD), studies have demonstrated that long-term high-fat diet (HFD) could accelerate the deposition of amyloid beta (Aß) in the brain. The glymphatic system plays a critical role in Aß clearance from the brain. However, studies investigating the effects of long-term HFD on glymphatic function have reported paradoxical outcomes, and whether glymphatic dysfunction is involved in the disturbance of Aß clearance in long-term HFD-fed mice has not been determined. In the present study, we injected fluorescently labeled Aß into the hippocampus and found that Aß clearance was decreased in HFD-fed mice. We found that long-term HFD-fed mice had decreased glymphatic function by injecting fluorescent tracers into the cisterna magna and corpus striatum. In long-term HFD-fed mice, aquaporin-4 (AQP4) polarization in the cortex was disrupted, and glymphatic clearance activity was positively correlated with the AQP4 polarization index. In HFD-fed mice, the disturbance of Aß clearance from the hippocampus was exacerbated by TGN-020, a specific inhibitor of AQP4, whereas TGN-073, an enhancer of AQP4, ameliorated it. These findings suggest that long-term HFD disrupts Aß clearance by inhibiting AQP4-mediated glymphatic function. The underlying mechanism may involve the disruption of AQP4 polarization.

19.
J Affect Disord ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39019221

RESUMO

BACKGROUND: According to the healthy context paradox, the negative effects of peer victimization on core self-evaluation and depressive symptoms may vary in different levels of classroom-level victimization. However, previous studies have not investigated this issue using a longitudinal study design. OBJECTIVE: The present study used a longitudinal design to examine why and under what conditions peer victimization was associated with adolescents' depressive symptoms. METHOD: A large number of Chinese adolescents (Time 1: N = 4164, 50.3 % girls, Mage = 12.89, SDage = 0.77; Time 2: N = 4001, 50.4 % girls, Mage = 14.39, SDage = 0.75) were followed for one and a half years. RESULTS: Results showed that adolescents who were victimized in healthy contexts were more depressed and were at an increased risk of reporting more negative core self-evaluation than those victimized in unhealthy contexts. Moreover, core self-evaluation served as a mediator between peer victimization and depressive symptoms. LIMITATIONS: This study included two waves of data, which limited the exploration of dynamic relationships between peer victimization and depressive symptoms. In addition, the self-reported data weakened the objectivity of the results. Finally, this study neglected the effects of different dimensions of peer victimization on depressive symptoms. CONCLUSIONS: The healthy context paradox of peer victimization is identified in China, highlighting that future interventions of peer victimization should pay more attention to specific remaining victimized and self-devaluing individuals in healthy contexts.

20.
Nature ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39020168

RESUMO

Reducing carbon dioxide (CO2) emissions urgently requires the large-scale deployment of carbon-capture technologies. These technologies must separate CO2 from various sources and deliver it to different sinks1,2. The quest for optimal solutions for specific source-sink pairs is a complex, multi-objective challenge involving multiple stakeholders and depends on social, economic and regional contexts. Currently, research follows a sequential approach: chemists focus on materials design3 and engineers on optimizing processes4,5, which are then operated at a scale that impacts the economy and the environment. Assessing these impacts, such as the greenhouse gas emissions over the plant's lifetime, is typically one of the final steps6. Here we introduce the PrISMa (Process-Informed design of tailor-made Sorbent Materials) platform, which integrates materials, process design, techno-economics and life-cycle assessment. We compare more than 60 case studies capturing CO2 from various sources in 5 global regions using different technologies. The platform simultaneously informs various stakeholders about the cost-effectiveness of technologies, process configurations and locations, reveals the molecular characteristics of the top-performing sorbents, and provides insights on environmental impacts, co-benefits and trade-offs. By uniting stakeholders at an early research stage, PrISMa accelerates carbon-capture technology development during this critical period as we aim for a net-zero world.

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