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1.
Huan Jing Ke Xue ; 45(5): 3119-3128, 2024 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-38629572

RESUMO

To accurately predict the life-cycle carbon reduction benefits of replacing a diesel heavy-duty truck with an electric one, taking a single heavy-duty truck as the object, the variation trend in electric and diesel carbon emission factors from 2023 to 2050 were predicted; coupled with the life spans and life-cycle mileage of the two types of heavy-duty trucks, a dynamic carbon emission model for the heavy-duty trucks was constructed in stages. The carbon footprints of the trucks under the "Net Zero Emissions by 2050 Scenario (NZE)", "Announced Pledges Scenario (APS)", and "Stated Policies Scenario (STEPS)" were analyzed. In addition, the carbon reduction and carbon reduction rate were calculated. The results showed that battery manufacturing and battery recycling were the main factors to impair the improvement of carbon reduction in the production and recycling stages of electric heavy-duty trucks, respectively. For every 1 g·(kW·h)-1 reduction in the electricity carbon emission factor (CO2), an electric heavy-duty truck could reduce 1.74 t of carbon emissions over its life cycle. Under the three scenarios, the carbon emissions during the operation stage of both types of heavy trucks accounted for more than 90% of the total life-cycle carbon emissions. Carbon reduction benefits from the highest to the lowest were NZE, APS, and STEPS, and their corresponding life-cycle carbon emission reductions were 1054.68, 1021.78, and 1007.97 t, with carbon reduction rates of 54.38%, 52.68%, and 51.97%, respectively.

2.
BMJ Open Qual ; 13(2)2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38631818

RESUMO

BACKGROUND: In medical research, the effectiveness of machine learning algorithms depends heavily on the accuracy of labeled data. This study aimed to assess inter-rater reliability (IRR) in a retrospective electronic medical chart review to create high quality labeled data on comorbidities and adverse events (AEs). METHODS: Six registered nurses with diverse clinical backgrounds reviewed patient charts, extracted data on 20 predefined comorbidities and 18 AEs. All reviewers underwent four iterative rounds of training aimed to enhance accuracy and foster consensus. Periodic monitoring was conducted at the beginning, middle, and end of the testing phase to ensure data quality. Weighted Kappa coefficients were calculated with their associated 95% confidence intervals (CIs). RESULTS: Seventy patient charts were reviewed. The overall agreement, measured by Conger's Kappa, was 0.80 (95% CI: 0.78-0.82). IRR scores remained consistently high (ranging from 0.70 to 0.87) throughout each phase. CONCLUSION: Our study suggests the detailed manual for chart review and structured training regimen resulted in a consistently high level of agreement among our reviewers during the chart review process. This establishes a robust foundation for generating high-quality labeled data, thereby enhancing the potential for developing accurate machine learning algorithms.

3.
Epilepsia ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38606600

RESUMO

OBJECTIVE: This study was undertaken to determine whether hippocampal T2 hyperintensity predicts sequelae of febrile status epilepticus, including hippocampal atrophy, sclerosis, and mesial temporal lobe epilepsy. METHODS: Acute magnetic resonance imaging (MRI) was obtained within a mean of 4.4 (SD = 5.5, median = 2.0) days after febrile status on >200 infants with follow-up MRI at approximately 1, 5, and 10 years. Hippocampal size, morphology, and T2 signal intensity were scored visually by neuroradiologists blinded to clinical details. Hippocampal volumetry provided quantitative measurement. Upon the occurrence of two or more unprovoked seizures, subjects were reassessed for epilepsy. Hippocampal volumes were normalized using total brain volumes. RESULTS: Fourteen of 22 subjects with acute hippocampal T2 hyperintensity returned for follow-up MRI, and 10 developed definite hippocampal sclerosis, which persisted through the 10-year follow-up. Hippocampi appearing normal initially remained normal on visual inspection. However, in subjects with normal-appearing hippocampi, volumetrics indicated that male, but not female, hippocampi were smaller than controls, but increasing hippocampal asymmetry was not seen following febrile status. Forty-four subjects developed epilepsy; six developed mesial temporal lobe epilepsy and, of the six, two had definite, two had equivocal, and two had no hippocampal sclerosis. Only one subject developed mesial temporal epilepsy without initial hyperintensity, and that subject had hippocampal malrotation. Ten-year cumulative incidence of all types of epilepsy, including mesial temporal epilepsy, was highest in subjects with initial T2 hyperintensity and lowest in those with normal signal and no other brain abnormalities. SIGNIFICANCE: Hippocampal T2 hyperintensity following febrile status epilepticus predicted hippocampal sclerosis and significant likelihood of mesial temporal lobe epilepsy. Normal hippocampal appearance in the acute postictal MRI was followed by maintained normal appearance, symmetric growth, and lower risk of epilepsy. Volumetric measurement detected mildly decreased hippocampal volume in males with febrile status.

4.
Sci Rep ; 14(1): 8580, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38615124

RESUMO

Underwater explosions (UNDEX) generate shock waves that interact with the air-water interface and structures, leading to the occurrence of rarefaction waves and inducing cavitation phenomena. In deep-water explosions, complex coupling relationships exist between shock wave propagation, bubble motion, and cavitation evolution. The shock wave initiates the formation of cavitation, and their growth and collapse are influenced by the pressure field. The collapsing bubbles generate additional shock waves and fluid motion, affecting subsequent shock wave propagation and bubble behavior. This intricate interaction significantly impacts the hydrodynamic characteristics of deep-water explosions, including pressure distribution, density, and phase changes in the surrounding fluid. In this paper, we utilize a two-fluid phase transition model to capture the evolution of cavitation in deep-water explosions. Our numerical results demonstrate that the introduction of a two-phase vapor-liquid phase change model is necessary to accurately capture scenarios involving prominent evaporation or condensation phenomena. Furthermore, we find that the cavitation produced by the same charge under different explosion depths exhibits significant differences, as does the peak value of cavitation collapse pressure. Similarly, the cavitation produced by different charge quantities under the same explosion depth varies, and the relationship between cavitation volume and charge quantity is not a simple linear increase. The research methods and results presented in this paper provide an important reference for studying the dynamic characteristics of deep-water explosions.

5.
World J Psychiatry ; 14(3): 388-397, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38617983

RESUMO

BACKGROUND: Major depressive disorder is a common mental illness among adolescents and is the largest disease burden in this age group. Most adolescent patients with depression have suicidal ideation (SI); however, few studies have focused on the factors related to SI, and effective predictive models are lacking. AIM: To construct a risk prediction model for SI in adolescent depression and provide a reference assessment tool for prevention. METHODS: The data of 150 adolescent patients with depression at the First People's Hospital of Lianyungang from June 2020 to December 2022 were retrospectively analyzed. Based on whether or not they had SI, they were divided into a SI group (n = 91) and a non-SI group (n = 59). The general data and laboratory indices of the two groups were compared. Logistic regression was used to analyze the factors influencing SI in adolescent patients with depression, a nomogram prediction model was constructed based on the analysis results, and internal evaluation was performed. Receiver operating characteristic and calibration curves were used to evaluate the model's efficacy, and the clinical application value was evaluated using decision curve analysis (DCA). RESULTS: There were differences in trauma history, triggers, serum ferritin levels (SF), high-sensitivity C-reactive protein levels (hs-CRP), and high-density lipoprotein (HDL-C) levels between the two groups (P < 0.05). Logistic regression analysis showed that trauma history, predisposing factors, SF, hs-CRP, and HDL-C were factors influencing SI in adolescent patients with depression. The area under the curve of the nomogram prediction model was 0.831 (95%CI: 0.763-0.899), sensitivity was 0.912, and specificity was 0.678. The higher net benefit of the DCA and the average absolute error of the calibration curve were 0.043, indicating that the model had a good fit. CONCLUSION: The nomogram prediction model based on trauma history, triggers, ferritin, serum hs-CRP, and HDL-C levels can effectively predict the risk of SI in adolescent patients with depression.

6.
Inorg Chem ; 63(15): 6692-6700, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38573894

RESUMO

The fabrication of molecular crystalline materials with fast, multistimuli-responsive behavior and the construction of the corresponding structure-activity relationship are of extraordinary significance for the development of smart materials. In this context, three multistimuli-responsive functional metal-organic polyhedra (MOP), {[Dy2(bcbp)3(NO3)1.5(H2O)7]·Cl4.2·(NO3)0.3·H2O}n (1), {[Dy2(bcbp)4(H2O)8]Cl6}n (2), and {[Eu2(bcbp)4(H2O)10]Cl6·H2O}n (3; bcbp = 1,1'-bis(4-carboxyphenyl)-4,4'-bipyridinium), were successfully prepared and characterized. All of the compounds exhibit rapid and reversible photochromic and electrochromic dual-responsive behaviors. Furthermore, benefiting from the well-defined crystal structure and different responsive behaviors, the photoinduced electron transfer (PIET) process and structure-activity relationship were explored. In addition, considering the excellent photochromic performance, function filter paper and smart organic glass were successfully prepared and used for ink-free printing and UV light detection.

7.
New Phytol ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38567702

RESUMO

CO2 release in the light (RL) and its presumed source, oxidative pentose phosphate pathways, were found to be insensitive to CO2 concentration. The oxidative pentose phosphate pathways form glucose 6-phosphate (G6P) shunts that bypass the nonoxidative pentose phosphate reactions of the Calvin-Benson cycle. Using adenosine diphosphate glucose and uridine diphosphate glucose as proxies for labeling of G6P in the stroma and cytosol respectively, it was found that only the cytosolic shunt was active. Uridine diphosphate glucose, a proxy for cytosolic G6P, and 6-phosphogluconate (6PG) were significantly less labeled than Calvin-Benson cycle intermediates in the light. But ADP glucose, a proxy for stromal G6P, is labeled to the same degree as Calvin-Benson cycle intermediates and much greater than 6PG. A metabolically inert pool of sedoheptulose bisphosphate can slowly equilibrate keeping the label in sedoheptulose lower than in other stromal metabolites. Finally, phosphorylation of fructose 6-phosphate (F6P) in the cytosol can allow some unlabeled carbon in cytosolic F6P to dilute label in phosphenolpyruvate. The results clearly show that there is oxidative pentose phosphate pathway activity in the cytosol that provides a shunt around the nonoxidative pentose phosphate pathway reactions of the Calvin-Benson cycle and is not strongly CO2-sensitive.

8.
BMJ Open ; 14(4): e077090, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38582540

RESUMO

OBJECTIVE: The CAPSTONE-1 trial demonstrated that adebrelimab-based immunotherapy yielded a favourable survival benefit compared with chemotherapy for patients with extensive-stage small cell lung cancer (ES-SCLC). This study aims to evaluate the cost-effectiveness of this immunotherapy in the treatment of ES-SCLC from a healthcare system perspective in China. DESIGN: The TreeAge Pro software was used to establish a three-state partitioned survival model. Survival data came from the CAPSTONE-1 trial (NCT03711305), and only direct medical costs were included. Utility values were obtained from the published literature. Sensitivity analysis was performed to explore the robustness of the model. The cost-effectiveness of immunotherapy was investigated through scenario and exploratory analyses in various settings. OUTCOME MEASURES: Total costs, incremental costs, life years, quality-adjusted life-years (QALYs), incremental QALYs and incremental cost-effectiveness ratio (ICER). RESULTS: The basic analysis revealed that the adebrelimab group achieved a total of 1.1 QALYs at a cost of US$65 385, while the placebo group attained 0.78 QALYs at a cost of US$12 741. ICER was US$163 893/QALY. Sensitivity analysis confirmed that the model was robust. Results from scenario and exploratory analyses indicated that the combination of adebrelimab and chemotherapy did not demonstrate cost-effectiveness in any scenario. CONCLUSIONS: From the perspective of the Chinese healthcare system, adebrelimab in combination with chemotherapy for the treatment of ES-SCLC was not economical compared with chemotherapy.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Análise de Custo-Efetividade , Análise Custo-Benefício , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Anticorpos Monoclonais/uso terapêutico
9.
Sci Rep ; 14(1): 8127, 2024 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-38584156

RESUMO

The traditional lecture-based learning (LBL) method is facing great challenges due to its low efficiency and single proceeding form. We designed a PRI-E learning mode that combined and modified problem-based, case-based, and evidence-based learning with a step-by-step approach. We evaluated the practical learning outcomes of using the PRI-E mode by comparing it with traditional lecture-based learning in oral and maxillofacial oncology education. "PRI-E" consists of the first letters of the English words Passion, Research, Innovation, and Education, and it means "the best Education". This prospective randomized controlled trial included 40 participants. We evenly divided the participants into the PRI-E (n = 20) and LBL group (n = 20) based on the entrance test scores. The same staff group designed and then taught the learning content with different group measures. The evaluation included the final test scores and questionnaire assessments. Without affecting the examination results, the PRI-E teaching method was more satisfactory and popular with participants in terms of ability development and classroom participation. Enacting the PRI-E teaching method required more time, but this did not affect its popularity among the participants. Compared with the LBL learning mode, the PRI-E learning mode was more organized and efficient in oral and maxillofacial oncology education without affecting academic performance. This model has a high degree of satisfaction, which is conducive to training students' comprehensive ability.


Assuntos
Aprendizagem , Aprendizagem Baseada em Problemas , Humanos , Aprendizagem Baseada em Problemas/métodos , Estudos Prospectivos , Estudantes , Avaliação Educacional
10.
ACS Pharmacol Transl Sci ; 7(3): 797-808, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38481693

RESUMO

Chronic pain is a common condition that causes negative emotions as the disease progresses. The anterior cingulate cortex (ACC) is a key region in the integration of nociceptive perception and emotional response in chronic pain. Linderane (LDR) is an active ingredient from Linderae radix, a traditional Chinese medicine with anti-inflammatory, analgesic, and antibacterial properties. In this study, the analgesic and antianxiety effects of LDR were evaluated using a complete Freund's adjuvant (CFA)-induced inflammatory pain model in C57BL/6 male mice. Mechanical and thermal pain sensitivity were measured through plantar mechanical analgesia and hot plate apparatus, and anxiety-like behavior was evaluated by open field and elevated plus maze tests. The results showed that LDR-alleviated CFA-induced pain and anxiety, reduced the release of inflammatory cytokines, and inhibited ACC microglial activation. Target prediction, molecular docking, and cellular thermal shift assay demonstrated that LDR could bind to the cannabinoid 2 receptor (CB2R), a key component of the endocannabinoid system with an important role in regulating pain and related emotions. Moreover, both the analgesic effect of LDR and its regulation of microglia polarization were reversed by a CB2R antagonist (SR144528) treatment. Therefore, our results suggested that LDR exerted analgesic effects by regulating microglial polarization in ACC via CB2R activation.

11.
JAMA Netw Open ; 7(3): e242082, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38477918

RESUMO

Importance: Few oncology studies have assessed the effectiveness of adjuvant ovarian function suppression (OFS) in observational settings for premenopausal hormone receptor-positive breast cancer. Target trial emulation is increasingly used for estimating treatment outcomes in observational cohorts. Objectives: To describe hormone therapy and OFS treatment patterns (aim 1), examine the association between adding OFS to tamoxifen (TAM) or aromatase inhibitor (AI) and survival (aim 2), and examine the association between duration of hormone treatment (TAM or AI) plus OFS (H-OFS) and survival (aim 3). Design, Setting, and Participants: This population-based cohort study included all premenopausal, early-stage breast cancer diagnoses between 2010 and 2020 in Alberta, Canada. Target trial emulation was conducted. Eligibility criteria were directly modeled after the Suppression of Ovarian Function Trial (SOFT) and Tamoxifen and Exemestane Trial (TEXT). Participants were followed up for a maximum of 5 years. Data were analyzed from July 2022 through March 2023. Exposures: For aim 2, exposures were receiving the following baseline treatments for 2 years: AI + OFS (AI-OFS), TAM + OFS (T-OFS), and TAM alone. For aim 3, exposures were a 2-year or greater and a less than 2-year duration of H-OFS. Main Outcomes and Measures: Recurrence-free survival was the primary outcome of interest. Marginal structural Cox models with inverse probability treatment and censoring weights were used to estimate hazard ratios (HRs), adjusted for baseline and time-varying confounding variables. Results: Among 3434 female patients with premenopausal, early-stage breast cancer diagnoses (median [IQR] age, 45 [40-48] years), 2647 individuals satisfied SOFT and TEXT eligibility criteria. There were 2260 patients who initiated TAM, 232 patients who initiated T-OFS, and 155 patients who initiated AI-OFS; 192 patients received H-OFS for 2 or more years, and 195 patients received H-OFS for less than 2 years. The 5-year recurrence risks were not significantly lower in AI-OFS vs TAM (HR, 0.76; 95% CI, 0.38-1.33) or T-OFS vs TAM (HR, 0.87; 95% CI, 0.50-1.45) groups. Patients receiving H-OFS for 2 or more years had significantly better 5-year recurrence-free survival compared with those receiving H-OFS for less than 2 years (HR, 0.69; 95% CI, 0.54-0.90). Conclusions and Relevance: This study found no significant reductions in recurrence risk for AI-OFS and T-OFS compared with TAM alone. H-OFS duration for at least 2 years was associated with significantly improved recurrence-free survival.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Pessoa de Meia-Idade , Estudos de Coortes , Adjuvantes Imunológicos , Tamoxifeno , Alberta , Inibidores da Aromatase , Hormônios
12.
J Am Chem Soc ; 146(11): 7400-7407, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38456799

RESUMO

Peptidoglycan (PG), an essential exoskeletal polymer in bacteria, is a well-known antibiotic target. PG polymerization requires the action of bacterial transglycosylases (TGases), which couple the incoming glycosyl acceptor to the donor. Interfering with the TGase activity can interrupt the PG assembly. Existing TGase inhibitors like moenomycin and Lipid II analogues always occupy the TGase active sites; other strategies to interfere with proper PG elongation have not been widely exploited. Inspired by the natural 1,6-anhydro-MurNAc termini that mark the ends of PG strands in bacteria, we hypothesized that the incorporation of an anhydromuramyl-containing glycosyl acceptor by TGase into the growing PG may effectively inhibit PG elongation. To explore this possibility, we synthesized 4-O-(N-acetyl-ß-d-glucosaminyl)-1,6-anhydro-N-acetyl-ß-d-muramyl-l-Ala-γ-d-Glu-l-Lys-d-Ala-d-Ala, 1, within 15 steps, and demonstrated that this anhydromuropeptide and its analogue lacking the peptide, 1-deAA, were both utilized by bacterial TGase as noncanonical anhydro glycosyl acceptors in vitro. The incorporation of an anhydromuramyl moiety into PG strands by TGases afforded efficient termination of glycan chain extension. Moreover, the preliminary in vitro studies of 1-deAA against Staphylococcus aureus showed that 1-deAA served as a reasonable antimicrobial adjunct of vancomycin. These insights imply the potential application of such anhydromuropeptides as novel classes of PG-terminating inhibitors, pointing toward novel strategies in antibacterial agent development.


Assuntos
Antibacterianos , Peptidoglicano , Peptidoglicano/química , Antibacterianos/farmacologia , Bactérias/metabolismo , Glicosiltransferases/metabolismo
13.
J Cancer ; 15(7): 1901-1915, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38434981

RESUMO

Background: Lung adenocarcinoma (LUAD) incidence and mortality take the leading place of most malignancies. Previous studies have revealed the regulator of chromosome condensation 1 (RCC1) family members played an essential role during tumorigenesis. However, its biological functions in LUAD still need further investigation. Methods: Several databases were applied to explore potential effects of RCC1 family members on LUAD, such as Oncomine, GEPIA, and cBioPortal. Real-time PCR and immunohistochemistry were used to verify the expression of RCC2 in stage I LUAD. H1975 and A549 were selected to explore the biological function of RCC2 in cellular malignant phenotype. Results: The expressions of RCC1 and RCC2 showed marked differences in malignant tissue compared to lung tissue. The higher the expression levels of RCC1 or RCC2 in LUAD patients, the shorter their overall survival (OS). In normal lung tissues, RCC1 expression was highly enriched in alveolar cells and endothelial cells. Compare with RCC1, RCC2 expression in normal lung tissue was significantly enriched in macrophages, B cells and granulocytes. Additionally, RCC2 expression level was correlated with multiple immune cell infiltration in LUAD. Moreover, the mutation or different sCNA status of RCC2 exerted influence on multiple immune cell infiltration distribution. We found that the upregulation of RCC1 and RCC2 were obviously related to TP53 mutation. GSEA analysis revealed that RCC2 was involved in the process of DNA replication, nucleotide excision repair and cell cycle, which might affect tumor progression through P53 signaling pathway. We further elucidated that downregulation of RCC2 could dramatically repress the migration and invasion of LUAD cells. Conclusions: The study demonstrated that RCC1 and RCC2 expression were markedly increased in early-stage of LUAD. Patients with high expression of RCC1 or RCC2 had a worse prognosis. Based on our analysis, RCC1 and RCC2 might exert influence on LUAD process through DNA replication, nucleotide excision repair and cell cycle, as well as cells migration and invasion. Different from RCC1, RCC2 also involved in immune infiltration. These analyses provided a novel insight into the identification of diagnostic biomarker.

14.
Ying Yong Sheng Tai Xue Bao ; 35(1): 25-30, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-38511436

RESUMO

We systematically elaborated and compared the spatial scope and landscape changes of Horqin Grassland and Horqin Sand Land from their definitions and ranges. Horqin Grassland is an area with geographical units named after Mongolian tribes, but the boundary is unclear. Horqin Sand Land is also an area that borrows tribal names, but has independent topographic and geomorphic units, and clear boundaries. Horqin Grassland and Horqin Sand Land belong to two spatial regions that are both cross and different. The area and range of Horqin Grassland are larger than that of Horqin Sand Land which has obvious regional characteristics, and is a typical and research object area to study the development and restoration of aeolian desertification. Based on those cognition, we summarized the technologies and example models of comprehensive land management and desertification controlling over the years, and finally sorted out what should be focused on in the future to serve the annihilation war against desertification for Horqin Sand Land.


Assuntos
Conservação dos Recursos Naturais , Areia , Pradaria , China
15.
Br J Haematol ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38513635

RESUMO

This study aimed to identify key proteomic analytes correlated with response to splenectomy in primary immune thrombocytopenia (ITP). Thirty-four patients were retrospectively collected in the training cohort and 26 were prospectively enrolled as validation cohort. Bone marrow biopsy samples of all participants were collected prior to the splenectomy. A total of 12 modules of proteins were identified by weighted gene co-expression network analysis (WGCNA) method in the developed cohort. The tan module positively correlated with megakaryocyte counts before splenectomy (r = 0.38, p = 0.027), and time to peak platelet level after splenectomy (r = 0.47, p = 0.005). The blue module significantly correlated with response to splenectomy (r = 0.37, p = 0.0031). KEGG pathways analysis found that the PI3K-Akt signalling pathway was predominantly enriched in the tan module, while ribosomal and spliceosome pathways were enriched in the blue module. Machine learning algorithm identified the optimal combination of biomarkers from the blue module in the training cohort, and importantly, cofilin-1 (CFL1) was independently confirmed in the validation cohort. The C-index of CFL1 was >0.7 in both cohorts. Our results highlight the use of bone marrow proteomics analysis for deriving key analytes that predict the response to splenectomy, warranting further exploration of plasma proteomics in this patient population.

16.
J Inflamm Res ; 17: 1823-1837, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38523680

RESUMO

Purpose: Acupuncture (ACU) has been demonstrated to alleviate inflammatory pain. Mechanoreceptors are present in acupuncture points. When acupuncture exerts mechanical force, these ion channels open and convert the mechanical signals into biochemical signals. TRPA1 (T ransient receptor potential ankyrin 1) is capable of sensing various physical and chemical stimuli and serves as a sensor for inflammation and pain. This protein is expressed in immune cells and contributes to local defense mechanisms during early tissue damage and inflammation. In this study, we investigated the role of TRPA1 in acupuncture analgesia. Patients and Methods: We injected complete Freund's adjuvant (CFA) into the mouse plantars to establish a hyperalgesia model. Immunohistochemistry and immunofluorescence analyses were performed to determine the effect of acupuncture on the TRPA1 expression in the Zusanli (ST36). We used TRPA1-/- mouse and pharmacological methods to antagonize TRPA1 to observe the effect on acupuncture analgesia. On this basis, collagenase was used to destroy collagen fibers at ST36 to observe the effect on TRPA1. Results: We found that the ACU group vs the CFA group, the number of TRPA1-positive mast cells, macrophages, and fibroblasts at the ST36 increased significantly. In CFA- inflammatory pain models, the TRPA1-/- ACU vs TRPA1+/+ ACU groups, the paw withdrawal latency (PWL) and paw withdrawal threshold (PWT) downregulated significantly. In the ACU + high-, ACU + medium-, ACU + low-dose HC-030031 vs ACU groups, the PWL and PWT were downregulated, and in carrageenan-induced inflammatory pain models were consistent with these results. We further found the ACU + collagenase vs ACU groups, the numbers of TRPA1-positive mast cells, macrophages, and fibroblasts at the ST36 were downregulated. Conclusion: These findings together imply that TRPA1 plays a significant role in the analgesic effects produced via acupuncture at the ST36. This provides new evidence for acupuncture treatment of painful diseases.

17.
Cell Rep ; 43(4): 113980, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38520693

RESUMO

In the brain, the role of matrilin-3, an extracellular matrix component in cartilage, is unknown. Here, we identify that matrilin-3 decreased in reactive astrocytes but was unchanged in neurons after ischemic stroke in animals. Importantly, it declined in serum of patients with acute ischemic stroke. Genetic or pharmacological inhibition or supplementation of matrilin-3 aggravates or reduces brain injury, astrocytic cell death, and glial scar, respectively, but has no direct effect on neuronal cell death. RNA sequencing demonstrates that Matn3-/- mice display an increased inflammatory response profile in the ischemic brain, including the nuclear factor κB (NF-κB) signaling pathway. Both endogenous and exogenous matrilin-3 reduce inflammatory mediators. Mechanistically, extracellular matrilin-3 enters astrocytes via caveolin-1-mediated endocytosis. Cytoplasmic matrilin-3 translocates into the nucleus by binding to NF-κB p65, suppressing inflammatory cytokine transcription. Extracellular matrilin-3 binds to BMP-2, blocking the BMP-2/Smads pathway. Thus, matrilin-3 is required for astrocytes to exert neuroprotection, at least partially, by suppressing astrocyte-mediated neuroinflammation.

18.
J Affect Disord ; 355: 505-512, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38548198

RESUMO

BACKGROUND: Rates of hospitalizations and emergency department (ED) visits due to self-harm are important indicators for understanding the impact of the COVID-19 pandemic on mental health. The objective of this study was to assess changes in self-harm hospitalizations and ED visits in Canada during the first two years of the pandemic. METHODS: Rates of self-harm hospitalizations and ED visits during the pandemic were predicted based on regression analyses that modeled trends over a 5-year pre-pandemic period from fiscal year 2015 to 2019. The ratios of observed and model predicted (expected) rates in 2020 and 2021 were estimated separately to assess changes during the pandemic. RESULTS: Overall, rates of self-harm hospitalizations and ED visits were lower than expected during the pandemic, especially in 2020. In 2021, rates for females returned to near-expected levels; but they remained lower than expected for males. Females aged 10-14 years had higher than expected rates. The rate ratio of observed rate over expected rate was 1.2 in 2020 but further increased to 1.8 in 2021 for both hospitalizations and ED visits. Higher than expected rates were also observed among females aged 15-19 years in 2021 only. LIMITATIONS: Suicide attempts and non-suicidal self-harm cases could not be distinguished. CONCLUSIONS: We observed lower than or close to expected rates of self-harm hospitalizations and ED visits during the pandemic for most population groups. The increased rates for young females highlights the importance of continued surveillance post-pandemic and targeted mental health services and suicide prevention programs.

19.
Mikrochim Acta ; 191(4): 203, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38492084

RESUMO

Chiral covalent organic frameworks (CCOFs) possess a superior chiral recognition environment, abundant pore configuration, and favorable physicochemical stability. In the post-synthetic chiral modification of COFs, research usually focused on increasing the density of chiral sites as much as possible, and little attention has been paid to the influence of the density of chiral sites on the spatial structure and chiral separation performance of CCOFs. In this article, 1,3,5-tris(4-aminophenyl) benzene (TPB), 2,5-dihydroxyterephthalaldehyde (DHTP), and 2,5-dimethoxyterephthalaldehyde (DMTP) served as the platform molecules to directly establish hydroxyl-controlled COFs through Schiff base condensation reactions. Then the novel chiral selectors 6-deoxy-6-[1-(2-aminoethyl)-3-(4-(4-isocyanatobenzyl)phenyl)urea]-ß-cyclodextrin (UB-ß-CD) were pended into the micropore structures of COFs via covalent bond for further construction the [UB-ß-CD]x-TPB-DMTP COFs (x represents the density of chiral sites). The chiral sites density on [UB-ß-CD]x-TPB-DMTP COFs was regulated by changing the construction proportion of DHTP to obtain a satisfactory CCOFs and significantly improve the ability of chiral separation. [UB-ß-CD]x-TPB-DMTP COFs were coated on the inner wall of a capillary via a covalently bonding strategy. The prepared open tubular capillary exhibited strong and broad enantioselectivity toward a variety of chiral analytes, including sixteen racemic amino acids and six model chiral drugs. By comparing the outcomes of chromatographic separation, we observed that the density of chiral sites in CCOFs was not positively correlated with their enantiomeric separation performance. The mechanism of chiral recognition [UB-ß-CD]x-TPB-DMTP COFs were further demonstrated by molecular docking simulation. This study not only introduces a new high-efficiency member of the COFs-based CSPs family but also demonstrates the enantioseparation potential of CCOFs constructed with traditional post-synthetic modification (PSM) strategy by utilizing the inherent characteristics of porous organic frameworks.

20.
J Ethnopharmacol ; 328: 118124, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38556138

RESUMO

ETHNOPHAMACOLOGICAL RELEVANCE: Morinda officinalis oligosaccharides (MOs) is a mixture of oligosaccharides extracted from the roots of Morinda officinalis (MO). It is approved by Chinese Food and Drug Administration (CFDA) for depression treatment. MOs could improve the antidepressant efficacy of escitalopram in clinic. AIM OF THE STUDY: We aim to explore the antidepressant activity and potential mechanism of the combination usage of MOs and escitalopram on animal model of depression. MATERIALS AND METHODS: Depressive animal model was induced by chronic mild stress (CMS). Behavioral tests were conducted to evaluate the antidepressant efficacy of MOs and escitalopram. Serum neurotransmitter levels were detected by High-performance liquid chromatography (HPLC). Quantitative real-time PCR and Western blotting were applied to assay the hippocampus neurotrophic factors' mRNA and protein levels. Peripheral cytokines levels were measured through Enzyme-Linked Immunosorbent Assay (ELISA). Micorglia polization phenotype was assayed by immunofluorescence and flow cytometry. RESULTS: MOs and escitalopram obviously attenuated depression-like behaviors of CMS mice. Importantly, MOs plus escitalopram exhibited better antidepressant activity on CMS mice than monotherapy. At the same time, MOs combined escitalopram treatment significantly increased hippocampus neurotransmitters and neurotrophic factor levels, stimulated hippocampus neurogenesis and relieved central nervous system (CNS) microglia over-activation of CMS mice. The combination therapy had greater effect on neuroprotection and inflammation attenuation of CMS mice than monotherapy. CONCLUSION: Our results indicates MOs combined escitalopram might produce antidepressant activity through protecting neuron activity, relieving inflammation and modulating microglia polarization process.


Assuntos
Escitalopram , Morinda , Camundongos , Animais , Depressão/tratamento farmacológico , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Oligossacarídeos/farmacologia , Oligossacarídeos/uso terapêutico , Inflamação/tratamento farmacológico , Estresse Psicológico/tratamento farmacológico , Modelos Animais de Doenças
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