Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 225
Filtrar
1.
Front Public Health ; 12: 1366838, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38947357

RESUMO

Background: In recent years, the prevalence of obesity has continued to increase as a global health concern. Numerous epidemiological studies have confirmed the long-term effects of exposure to ambient air pollutant particulate matter 2.5 (PM2.5) on obesity, but their relationship remains ambiguous. Methods: Utilizing large-scale publicly available genome-wide association studies (GWAS), we conducted univariate and multivariate Mendelian randomization (MR) analyses to assess the causal effect of PM2.5 exposure on obesity and its related indicators. The primary outcome given for both univariate MR (UVMR) and multivariate MR (MVMR) is the estimation utilizing the inverse variance weighted (IVW) method. The weighted median, MR-Egger, and maximum likelihood techniques were employed for UVMR, while the MVMR-Lasso method was applied for MVMR in the supplementary analyses. In addition, we conducted a series of thorough sensitivity studies to determine the accuracy of our MR findings. Results: The UVMR analysis demonstrated a significant association between PM2.5 exposure and an increased risk of obesity, as indicated by the IVW model (odds ratio [OR]: 6.427; 95% confidence interval [CI]: 1.881-21.968; P FDR = 0.005). Additionally, PM2.5 concentrations were positively associated with fat distribution metrics, including visceral adipose tissue (VAT) (OR: 1.861; 95% CI: 1.244-2.776; P FDR = 0.004), particularly pancreatic fat (OR: 3.499; 95% CI: 2.092-5.855; PFDR =1.28E-05), and abdominal subcutaneous adipose tissue (ASAT) volume (OR: 1.773; 95% CI: 1.106-2.841; P FDR = 0.019). Furthermore, PM2.5 exposure correlated positively with markers of glucose and lipid metabolism, specifically triglycerides (TG) (OR: 19.959; 95% CI: 1.269-3.022; P FDR = 0.004) and glycated hemoglobin (HbA1c) (OR: 2.462; 95% CI: 1.34-4.649; P FDR = 0.007). Finally, a significant negative association was observed between PM2.5 concentrations and levels of the novel obesity-related biomarker fibroblast growth factor 21 (FGF-21) (OR: 0.148; 95% CI: 0.025-0.89; P FDR = 0.037). After adjusting for confounding factors, including external smoke exposure, physical activity, educational attainment (EA), participation in sports clubs or gym leisure activities, and Townsend deprivation index at recruitment (TDI), the MVMR analysis revealed that PM2.5 levels maintained significant associations with pancreatic fat, HbA1c, and FGF-21. Conclusion: Our MR study demonstrates conclusively that higher PM2.5 concentrations are associated with an increased risk of obesity-related indicators such as pancreatic fat content, HbA1c, and FGF-21. The potential mechanisms require additional investigation.


Assuntos
Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Obesidade , Material Particulado , População Branca , Humanos , Obesidade/genética , População Branca/genética , Poluentes Atmosféricos/efeitos adversos , Exposição Ambiental/efeitos adversos , Poluição do Ar/efeitos adversos
2.
MedComm (2020) ; 5(7): e650, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38988496

RESUMO

The pharmacological activation of peroxisome proliferator-activated receptor gamma (PPARγ) is a convenient and promising strategy for promoting beige adipocyte biogenesis to combat obesity-related metabolic disorders. However, thiazolidinediones (TZDs), the full agonists of PPARγ exhibit severe side effects in animal models and in clinical settings. Therefore, the development of efficient and safe PPARγ modulators for the treatment of metabolic diseases is emerging. In this study, using comprehensive methods, we report a previously unidentified ligand-binding pocket (LBP) in PPARγ and link it to beige adipocyte differentiation. Further virtual screening of 4097 natural compounds based on this novel LBP revealed that saikosaponin A (NJT-2), a terpenoid compound, can bind to PPARγ to induce coactivator recruitment and effectively activate PPARγ-mediated transcription of the beige adipocyte program. In a mouse model, NJT-2 administration efficiently promoted beige adipocyte biogenesis and improved obesity-associated metabolic dysfunction, with significantly fewer adverse effects than those observed with TZD. Our results not only provide an advanced molecular insight into the structural ligand-binding details in PPARγ, but also develop a linked selective and safe agonist for obesity treatment.

3.
J Colloid Interface Sci ; 674: 437-444, 2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38941936

RESUMO

Self-assembly of nanoclusters (NCs) is an effective synthetic method for preparing functionalized nanomaterials. However, the assembly process and mechanisms in solutions still remain ambiguous owing to the limited strategies to monitor intermediate assembled states. Herein, the self-assembly process of amphiphilic molecule 4POSS-DL-POM (consisting of four polyhedral oligomeric silsesquioxanes, a dendritic linker, and one polyoxometalate) by evaporation of acetone in a mixed acetone/n-decane solution is monitored by time-resolved synchrotron small-angle X-ray scattering (SAXS). Scattering data assessments, including Kratky analysis, pair distance distribution function, and model fitting, track the self-assembly process of 4POSS-DL-POM from a fractal network to compact NCs, then to core-shell NCs, and finally to superlattice structure. The calculated average aggregation number of a core-shell NC is 11 according to the parameters obtained from core-shell model fitting, in agreement with electron microscopy. The fundamental understanding of the self-assembly dynamics from heterocluster into NCs provides principles to control building block shape and guide target aggregation, which can further promote the design and construction of highly ordered cluster-assembled functional nanomaterials.

4.
Fish Shellfish Immunol ; 151: 109717, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38914179

RESUMO

Aquaculture is one of the fastest growing sectors in global food production, recognized as a significant contributor to poverty alleviation, food security, and income generation. However, the frequent occurrence of diseases caused by pathogen infections result in reduced yields and economic losses, posing a substantial constraint to the sustainable development of aquaculture. Here, our study identified that four catechol compounds, quercetin, luteolin, caffeic acid, and chlorogenic acid, exhibited potent antiparasitic effects against Ichthyophthirius multifiliis in both, in vitro and in vivo. The parasite is recognized as one of the most pathogenic to fish worldwide. Using a combination of in silico methods, the dipeptidyl peptidase (DPP) was identified as a critical target for catechol compounds. The two hydroxyl radicals of the catechol group were essential for its binding to and interacting with the DPP protein. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that catechol compounds disrupt pathways associated with the metabolism and growth of I. multifiliis, thereby exerting antiparasitic effects. Furthermore, these compounds attenuated the expression of proinflammatory cytokines in vivo in fish and promoted macrophage polarization toward M2 phenotype by inhibiting the STAT1 signaling pathway. The dual activity of catechol compounds, acting as both direct antiparasitic and anti-inflammatory agents in fish, offers a promising therapeutic approach for combating I. multifiliis infections in aquaculture.

5.
Clinics (Sao Paulo) ; 79: 100403, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38878321

RESUMO

OBJECTIVES: This study aims to elucidate the role of circUSP9X (Circular RNA Ubiquitin Specific Peptidase 9 X-Linked) in the development of venous thrombosis in the lower extremities. METHODS: An animal model of Deep Vein Thrombosis (DVT) and a hypoxic model of Human Umbilical Vein Endothelial Cells (HUVECs) treated with Cobalt (II) Chloride (CoCl2) were developed. The expression levels of circUSP9X, microRNA-148b-3p (miR-148b-3p), and SRC Kinase Signaling Inhibitor 1 (SRCIN1) were quantified using quantitative reverse transcription Polymerase Chain Reaction and Western blot analysis. Cell cytotoxicity, viability, apoptosis, and inflammation in HUVECs were assessed via Lactate Dehydrogenase (LDH) assay, MTT assay, flow cytometry, Enzyme-Linked Immunosorbent Assay, and Western blot, respectively. Hematoxylin and Eosin staining were employed for histopathological examination of the venous tissues in the animal model. The interaction between circUSP9X, miR-148b-3p, and SRCIN1 was further explored through dual-luciferase reporter assays and RNA Immunoprecipitation experiments. RESULTS: The present findings reveal a significant upregulation of circUSP9X and SRCIN1 and a concurrent downregulation of miR-148b-3p in DVT cases. Knockdown of circUSP9X or overexpression of miR-148b-3p ameliorated CoCl2-induced apoptosis in HUVECs, reduced LDH release, enhanced cellular viability, and mitigated inflammation. Conversely, overexpression of circUSP9X intensified CoCl2's cytotoxic effects. The effects of manipulating circUSP9X expression were counteracted by the corresponding modulation of miR-148b-3p and SRCIN1 levels. Additionally, circUSP9X knockdown effectively inhibited the formation of DVT in the mouse model. A competitive binding mechanism of circUSP9X for miR-148b-3p, modulating SRCIN1 expression, was identified. CONCLUSION: circUSP9X promotes the formation of DVT through the regulation of the miR-148b-3p/SRCIN1 axis.


Assuntos
Modelos Animais de Doenças , Células Endoteliais da Veia Umbilical Humana , MicroRNAs , Regulação para Cima , Trombose Venosa , Animais , Humanos , Masculino , Camundongos , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Apoptose/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , MicroRNAs/metabolismo , RNA Circular/genética , Regulação para Cima/efeitos dos fármacos
6.
BMC Womens Health ; 24(1): 351, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890689

RESUMO

BACKGROUND: Observational data indicates a connection between emotional discomfort, such as anxiety and depression, and uterine fibroids (UFs). However, additional investigation is required to establish the causal relationship between them. Hence, we assessed the reciprocal causality between four psychological disorders and UFs utilizing two-sample Mendelian randomization (MR). METHODS: To evaluate the causal relationship between four types of psychological distress (depressive symptoms, severe depression, anxiety or panic attacks, mood swings) and UFs, bidirectional two-sample MR was employed, utilizing single nucleotide polymorphisms (SNPs) associated with these conditions. Both univariate MR (UVMR) and multivariate MR (MVMR) primarily applied inverse variance weighted (IVW) as the method for estimating potential causal effects. Complementary approaches such as MR Egger, weighted median, simple mode, and weighted mode were utilized to validate the findings. To assess the robustness of our MR results, we conducted sensitivity analyses using Cochran's Q-test and the MR Egger intercept test. RESULTS: The results of our UVMR analysis suggest that genetic predispositions to depressive symptoms (Odds Ratio [OR] = 1.563, 95% Confidence Interval [CI] = 1.209-2.021, P = 0.001) and major depressive disorder (MDD) (OR = 1.176, 95% CI = 1.044-1.324, P = 0.007) are associated with an increased risk of UFs. Moreover, the IVW model showed a nominally significant positive correlation between mood swings (OR: 1.578; 95% CI: 1.062-2.345; P = 0.024) and UFs risk. However, our analysis did not establish a causal relationship between UFs and the four types of psychological distress. Even after adjusting for confounders like body mass index (BMI), smoking, alcohol consumption, and number of live births in the MVMR, the causal link between MDD and UFs remained significant (OR = 1.217, 95% CI = 1.039-1.425, P = 0.015). CONCLUSIONS: Our study presents evidence supporting the causal relationship between genetic susceptibility to MDD and the incidence of UFs. These findings highlight the significance of addressing psychological health issues, particularly depression, in both the prevention and treatment of UFs.


Assuntos
Depressão , Leiomioma , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Humanos , Análise da Randomização Mendeliana/métodos , Feminino , Leiomioma/genética , Leiomioma/psicologia , Depressão/epidemiologia , Depressão/genética , Depressão/psicologia , Angústia Psicológica , Predisposição Genética para Doença/psicologia , Ansiedade/epidemiologia , Ansiedade/psicologia , Neoplasias Uterinas/genética , Neoplasias Uterinas/psicologia , Causalidade , Transtorno de Pânico/genética , Transtorno de Pânico/psicologia , Transtorno de Pânico/epidemiologia
7.
Materials (Basel) ; 17(9)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38730815

RESUMO

The synergistic effects of boron (B) and rare earth (RE) elements on the microstructure and stress rupture properties were investigated in a Ni-based superalloy. The stress rupture lifetime at 650 °C/873 MPa significantly increased with the addition of B as a single element. Furthermore, the stress rupture lifetime reached its peak (303 h), with a certain amount of B and RE added together in test alloys. Although the grain size and morphology of the γ' phase varied a little with the change in B and RE addition, they were not considered to be the main reasons for stress rupture performance. The enhancement in stress rupture lifetime was mostly attributed to the segregation of the B and RE elements, which increased the binding force of the grain boundary and improved its strength and plasticity. In addition, the enrichment of B and RE inhabited the precipitation of carbides along grain boundaries. Furthermore, nano-scale RE precipitates containing sulfur (S) and phosphorus (P) were observed to be distributed along the grain boundaries. The purification of grain boundaries by B and RE elements was favorable to further improve the stress rupture properties.

8.
Angew Chem Int Ed Engl ; : e202403023, 2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38763905

RESUMO

The efficient electrosynthesis of hydrogen peroxide (H2O2) via two-electron oxygen reduction reaction (2e- ORR) in neutral media is undoubtedly a practical route, but the limited comprehension of electrocatalysts has hindered the system advancement. Herein, we present the design of model catalysts comprising mesoporous carbon spheres-supported Pd nanoparticles for H2O2 electrosynthesis at near-zero overpotential with approximately 95 % selectivity in a neutral electrolyte. Impressively, the optimized Pd/MCS-8 electrocatalyst in a flow cell device achieves an exceptional H2O2 yield of 15.77 mol gcatalyst -1 h-1, generating a neutral H2O2 solution with an accumulated concentration of 6.43 wt %, a level sufficiently high for medical disinfection. Finite element simulation and experimental results suggest that mesoporous carbon carriers promote O2 enrichment and localized pH elevation, establishing a favorable microenvironment for 2e- ORR in neutral media. Density functional theory calculations reveal that the robust interaction between Pd nanoparticles and the carbon carriers optimized the adsorption of OOH* at the carbon edge, ensuring high active 2e- process. These findings offer new insights into carbon-loaded electrocatalysts for efficient 2e- ORR in neutral media, emphasizing the role of carrier engineering in constructing favorable microenvironments and synergizing active sites.

9.
Ultrasonics ; 141: 107334, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38733864

RESUMO

Grain size is one of the key microstructural factors affecting the mechanical properties of polycrystalline metal materials. In this study, a novel method for grain size evaluation using ultrasonic coda waves is proposed. Different from conventional bulk wave methods that require a point-by-point scanning of the structure, the proposed method allows for a rapid evaluation of the average grain size of the whole part from a single inspection location using one-pass testing data. A piecewise energy attenuation function dealing with different attenuation mechanisms is proposed to obtain the effective attenuation coefficient of coda waves. A power-law model is constructed to correlate the effective attenuation coefficient with the average grain size. Ultrasonic testing on nickel-based superalloy plate specimens with different average grain sizes is performed for model calibration and method verification. The applicability and robustness of the proposed method are further validated using a realistic turbine disk specimen with an irregular shape and non-uniform grain sizes. Results show that the proposed method yields a reliable and accurate estimation of the average grain size with a maximum relative error less than 20 %.

10.
J Med Chem ; 67(7): 5866-5882, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38556760

RESUMO

MERTK and AXL are members of the TAM (TYRO3, AXL, MERTK) family of receptor tyrosine kinases that are aberrantly expressed and have been implicated as therapeutic targets in a wide variety of human tumors. Dual MERTK and AXL inhibition could provide antitumor action mediated by both direct tumor cell killing and modulation of the innate immune response in some tumors such as nonsmall cell lung cancer. We utilized our knowledge of MERTK inhibitors and a structure-based drug design approach to discover a novel class of macrocyclic dual MERTK/AXL inhibitors. The lead compound 43 had low-nanomolar activity against both MERTK and AXL and good selectivity over TYRO3 and FLT3. Its target engagement and selectivity were also confirmed by NanoBRET and cell-based MERTK and AXL phosphorylation assays. Compound 43 had excellent pharmacokinetic properties (large AUC and long half-life) and mediated antitumor activity against lung cancer cell lines, indicating its potential as a therapeutic agent.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , c-Mer Tirosina Quinase/metabolismo , Receptor Tirosina Quinase Axl , Proteínas Proto-Oncogênicas/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Linhagem Celular Tumoral
11.
Adv Sci (Weinh) ; 11(17): e2309020, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38368272

RESUMO

The requirement for cryogenic supramolecular self-assembly of amphiphiles in subzero environments is a challenging topic. Here, the self-assembly of lamellar lyotropic liquid crystals (LLCs) are presented to a subzero temperature of -70 °C. These lamellar nanostructures are assembled from specifically tailored ultra-long-chain surfactant stearyl diethanolamine (SDA) in water/glycerol binary solvent. As the temperature falls below zero, LLCs with a liquid-crystalline Lα phase, a tilted Lß phase, and a new folded configuration are obtained consecutively. A comprehensive experimental and computational study is performed to uncover the precise microstructure and formation mechanism. Both the ultra-long alkyl chain and head group of SDA play a crucial role in the formation of lamellar nanostructures. SDA head group is prone to forming hydrogen bonds with water, rather than glycerol. Glycerol cannot penetrate the lipid layer, which mixes with water arranging outside of the lipid bilayer, providing an ideal anti-freezing environment for SDA self-assembly. Based on these nanostructures and the ultra-low freezing point of the system, a series of novel cryogenic materials are created with potential applications in extremely cold environments. These findings would contribute to enriching the theory and research methodology of supramolecular self-assembly in extreme conditions and to developing novel anti-freezing materials.

12.
Mol Biol Rep ; 51(1): 365, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38409611

RESUMO

A low-frequency variant of sushi, von Willebrand factor type A, EGF, and pentraxin domain-containing protein 1 (SVEP1) is associated with the risk of coronary artery disease, as determined by a genome-wide association study. SVEP1 induces vascular smooth muscle cell proliferation and an inflammatory phenotype to promote atherosclerosis. In the present study, qRT‒PCR demonstrated that the mRNA expression of SVEP1 was significantly increased in atherosclerotic plaques compared to normal tissues. Bioinformatics revealed that EGR1 was a transcription factor for SVEP1. The results of the luciferase reporter assay, siRNA interference or overexpression assay, mutational analysis and ChIP confirmed that EGR1 positively regulated the transcriptional activity of SVEP1 by directly binding to its promoter. EGR1 promoted human coronary artery smooth muscle cell (HCASMC) proliferation and migration via SVEP1 in response to oxidized low-density lipoprotein (ox-LDL) treatment. Moreover, the expression level of EGR1 was increased in atherosclerotic plaques and showed a strong linear correlation with the expression of SVEP1. Our findings indicated that EGR1 binding to the promoter region drive SVEP1 transcription to promote HCASMC proliferation and migration.


Assuntos
MicroRNAs , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/metabolismo , Vasos Coronários/metabolismo , Estudo de Associação Genômica Ampla , Movimento Celular , Lipoproteínas LDL/farmacologia , Células Cultivadas , Proliferação de Células/genética , Miócitos de Músculo Liso/metabolismo , MicroRNAs/genética , Proteína 1 de Resposta de Crescimento Precoce/genética , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Moléculas de Adesão Celular/genética
13.
Gels ; 10(2)2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38391463

RESUMO

Mesoporous materials containing heteroelements have a huge potential for use as catalysts, exchangers, and adsorbents due to their tunable nanometer-sized pores and exceptionally large internal surfaces accessible to bulky organic molecules. In the present work, ordered mesoporous silica containing Ni atoms as active sites was synthesized by a new low-temperature method of condensation of silica precursors on a micellar template from aqueous solutions in the presence of nickel salt. The homogeneity of the resulting product was achieved by introducing ammonia and ammonium salt as a buffer to maintain a constant pH value. The obtained materials were characterized by nitrogen sorption, X-ray and neutron diffraction, scanning electron microscopy, infrared spectroscopy, and thermal analysis. Their morphology consists of polydisperse spherical particles 50-300 nm in size, with a hexagonally ordered channel structure, high specific surface area (ABET = 900-1200 m2/g), large pore volume (Vp = 0.70-0.90 cm3/g), average mesopore diameter of about 3 nm, and narrow pore size distribution. Adsorption tests for methylene blue show sorption capacities reaching 39-42 mg/g at alkaline pH. The advantages of producing nickel silicates by this method, in contrast to precipitation from silicon alkoxides, are the low cost of reagents, fire safety, room-temperature processing, and the absence of specific problems associated with the use of ethanol as a solvent, as well as the absence of the inevitable capture of organic matter in the precipitation process.

14.
Nat Commun ; 15(1): 983, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302469

RESUMO

The nanoreactor holds great promise as it emulates the natural processes of living organisms to facilitate chemical reactions, offering immense potential in catalytic energy conversion owing to its unique structural functionality. Here, we propose the utilization of precisely engineered carbon spheres as building blocks, integrating micromechanics and controllable synthesis to explore their catalytic functionalities in two-electron oxygen reduction reactions. After conducting rigorous experiments and simulations, we present compelling evidence for the enhanced mass transfer and microenvironment modulation effects offered by these mesoporous hollow carbon spheres, particularly when possessing a suitably sized hollow architecture. Impressively, the pivotal achievement lies in the successful screening of a potent, selective, and durable two-electron oxygen reduction reaction catalyst for the direct synthesis of medical-grade hydrogen peroxide disinfectant. Serving as an exemplary demonstration of nanoreactor engineering in catalyst screening, this work highlights the immense potential of various well-designed carbon-based nanoreactors in extensive applications.

15.
Plants (Basel) ; 13(3)2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38337916

RESUMO

Melatonin plays a vital role in plant growth and development. In this study, we treated hydroponically grown tomato roots with various concentrations of exogenous melatonin (0, 10, 30, and 50 µmol·L-1). We utilized root scanning and microscopy to examine alterations in root morphology and cell differentiation and elucidated the mechanism by which melatonin regulates these changes through the interplay with endogenous hormones and relevant genes. The results showed that for melatonin at concentrations ranging between 10 and 30 µmol·L-1, the development of lateral roots were significantly stimulated, the root hair growth was enhanced, and biomass accumulation and root activity were increased. Furthermore, we elucidated that melatonin acts as a mediator for the expression of genes, such as SlCDKA1, SlCYCA3;1, SlARF2, SlF3H, and SlKT1, which are involved in the regulation of root morphology changes. Additionally, we observed that melatonin influences the levels of endogenous hormones, including ZT, GA3, IAA, ABA, and BR, which subsequently impact the root morphology development of tomato roots. In summary, this study shows that tomato root morphology can be promoted by the optimal concentration of exogenous melatonin (10-30 µmol·L-1).

16.
Nat Med ; 30(3): 749-761, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38287168

RESUMO

Adjuvant chemotherapy benefits patients with resected pancreatic ductal adenocarcinoma (PDAC), but the compromised physical state of post-operative patients can hinder compliance. Biomarkers that identify candidates for prompt adjuvant therapy are needed. In this prospective observational study, 1,171 patients with PDAC who underwent pancreatectomy were enrolled and extensively followed-up. Proteomic profiling of 191 patient samples unveiled clinically relevant functional protein modules. A proteomics-level prognostic risk model was established for PDAC, with its utility further validated using a publicly available external cohort. More importantly, through an interaction effect regression analysis leveraging both clinical and proteomic datasets, we discovered two biomarkers (NDUFB8 and CEMIP2), indicative of the overall sensitivity of patients with PDAC to adjuvant chemotherapy. The biomarkers were validated through immunohistochemistry on an internal cohort of 386 patients. Rigorous validation extended to two external multicentic cohorts-a French multicentric cohort (230 patients) and a cohort from two grade-A tertiary hospitals in China (466 patients)-enhancing the robustness and generalizability of our findings. Moreover, experimental validation through functional assays was conducted on PDAC cell lines and patient-derived organoids. In summary, our cohort-scale integration of clinical and proteomic data demonstrates the potential of proteomics-guided prognosis and biomarker-aided adjuvant chemotherapy for PDAC.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Proteômica , Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Estudos Prospectivos
17.
Sci Rep ; 14(1): 312, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172122

RESUMO

This study aims to improve the performance of automotive battery thermal management systems (BTMS) to achieve more efficient heat dissipation and thus reduce hazards during driving. Firstly, the research parameters and properties of composite thermally conductive silicone materials are introduced. Secondly, the heating principle of the power battery, the structure and working principle of the new energy vehicle battery, and the related thermal management scheme are discussed. Finally, the research results are presented from the experimental test and controller design. In addition, to achieve the research goal, the composite thermally conductive silica gel plate (CSGP) material is studied in detail and parametrically analyzed, and the heating mechanism of the power battery is discussed in depth. The temperature characteristics after adding CSGP are experimentally tested, and the controller of the BTMS of the new energy vehicle is designed, including hardware circuits and software modules. The findings show that the temperature characteristics of the battery module have obvious limitations without CSGP. When the battery module operates at a 4C magnification, the temperature exceeds the safety threshold by 38.4%, with particular potential safety risks. Then, the maximum temperature of the battery module with CSGP can be controlled within 50 °C, and the temperature characteristics are prominently improved. Lastly, the controller of the BTMS is tested, and the results reveal that it has remarkable voltage recovery ability. According to the research results, the performance of automotive BTMS can be significantly improved, and better heat dissipation can be effectively achieved by adding CSGP. This helps reduce the hazards of driving. Moreover, the designed controller performs well in voltage recovery, providing solid theoretical support for further developing the CSGP battery management system.

18.
BMC Musculoskelet Disord ; 25(1): 32, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38178051

RESUMO

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is the most common developmental spine disorder among children. It is characterized by a lateral deviation of the spine that gives rise to the distinctive "S" or "C" shaped bending of the spine. The Lin School of Lingnan Region (LSLR), one of the prominent schools for bare-handed orthopaedic manipulation in southern China, provides preliminary evidences that the orthopaedic manipulation techniques help to correct deviations of the spine. Previous research found that Orthopaedic Manipulation Techniques of LSLR (OMT-LSLR) could reduce the Cobb's angles in patients with AIS. Therefore, the current study aims to investigate the effectiveness and safety of the OMT-LSLR in treating teenagers with AIS. METHODS: In this participant-and-assessor-blinded randomized controlled clinical trial, 50 participants identified AIS without surgical indications will be recruited and randomized into two groups to receive physiotherapy scoliosis-specific exercises training with either orthopaedic manipulation or sham manipulation treatment for 16 weeks, followed by post-treatment visits at week 24. Primary outcome measure is the change of Scoliosis Research Society-22 (SRS-22) questionnaire score. Secondary outcome measures include Traditional Chinese version of Spinal Appearance Questionnaire (TC-SAQ) score, Italian Spine Youth Quality of Life (ISYQOL) score, the change of Cobb's angle measured by Xray, and the change of Cobb's angle, spinal rotation and muscle volume measured by three-dimensional (3D) ultrasound. The trial will be conducted at the Chinese University of Hong Kong Chinese Medicine Specialty Clinic cum Clinical Teaching and Research Centre in Hong Kong (CUHK-CMSCTRC). DISCUSSION: The results of this study will establish comprehensive clinical evidence about the efficacy and safety of the Orthopaedic Manipulation Techniques of the Lin School of Lingnan Region in the Treatment of Adolescent Idiopathic Scoliosis. One of the characteristics of this trial is that it is a participant-and-assessor-blinded randomized controlled clinical trial with sham manipulation. The study would also apply three-dimensional (3D) ultrasound technology to investigate the relationship between the change of the muscle volume and the spinal curve. TRIAL REGISTRATION: The trial is registered on ClinicalTrials.gov (Identifier: NCT05639023 ) on December 6, 2022.


Assuntos
Escoliose , Criança , Humanos , Adolescente , Escoliose/terapia , Escoliose/cirurgia , Manipulação Ortopédica , Qualidade de Vida , Coluna Vertebral , Terapia por Exercício/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Nano Lett ; 24(5): 1650-1659, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38265360

RESUMO

Precision nanoengineering of porous two-dimensional structures has emerged as a promising avenue for finely tuning catalytic reactions. However, understanding the pore-structure-dependent catalytic performance remains challenging, given the lack of comprehensive guidelines, appropriate material models, and precise synthesis strategies. Here, we propose the optimization of two-dimensional carbon materials through the utilization of mesopores with 5-10 nm diameter to facilitate fluid acceleration, guided by finite element simulations. As proof of concept, the optimized mesoporous carbon nanosheet sample exhibited exceptional electrocatalytic performance, demonstrating high selectivity (>95%) and a notable diffusion-limiting disk current density of -3.1 mA cm-2 for H2O2 production. Impressively, the electrolysis process in the flow cell achieved a production rate of 14.39 mol gcatalyst-1 h-1 to yield a medical-grade disinfectant-worthy H2O2 solution. Our pore engineering research focuses on modulating oxygen reduction reaction activity and selectivity by affecting local fluid transport behavior, providing insights into the mesoscale catalytic mechanism.

20.
J Biomech ; 162: 111893, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38064998

RESUMO

The potential use of gait analysis for quantitative preoperative planning in total hip arthroplasty (THA) has previously been demonstrated. However, the joint kinematic data measured through this process tend to be unreliable for surgical planning due to distortions caused by soft tissue artifacts (STAs). In this study, we developed a novel motion capture framework by combining computed tomography (CT)-based postural calibration and subject-specific multibody dynamics modeling to prevent the effect of STAs in measuring hip kinematics. Three subjects with femoroacetabular impingement syndrome were recruited, and CT data for each patient were collected by attaching marker clusters near the hip. A subject-specific multibody hip joint model was developed based on reconstructed CT data. Spring-dashpot network calculations were performed to minimize the distance between the anatomical landmark and its corresponding infrared reflective marker. The STAs of the thigh was described as six degrees of freedom viscoelastic bushing elements, and their parameter values were identified via smooth orthogonal decomposition. Least squares optimization was used to modify the pelvic rotations to compensate for the rigid components of STAs. The results showed that CT-assisted motion tracking enabled the successful identification of STA influences in gait and squat positions. Furthermore, STA effects were found to alter maximal pelvis tilt and hip rotations during a squat. Compared to other techniques, such as dual fluoroscopic imaging, the adopted framework does not require additional medical imaging for patients undergoing robot-assisted THA surgery and is thus a practical way of evaluating hip joint kinematics for preoperative surgical planning.


Assuntos
Artroplastia de Quadril , Artefatos , Humanos , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/cirurgia , Marcha , Tomografia Computadorizada por Raios X , Fenômenos Biomecânicos , Amplitude de Movimento Articular
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...