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1.
Materials (Basel) ; 17(13)2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38998181

RESUMO

This paper explores the impact of steel-PVA hybrid fibers (S-PVA HF) on the flexural performance of panel concrete via three-point bending tests. Crack development in the concrete is analyzed through Digital Image Correlation (DIC) and Scanning Electron Microscope (SEM) experiments, unveiling the underlying mechanisms. The evolution of cracks in concrete is quantitatively analyzed based on fractal theory, and a predictive model for flexural strength (PMFS) is established. The results show that the S-PVA HF exhibits a synergistic effect in enhancing and toughening the concrete at multi-scale. The crack area of steel-PVA hybrid fiber concrete (S-PVA HFRC) is linearly correlated with deflection (δ), and it further reduces the crack development rate and crack area compared to steel fiber-reinforced concrete (SFRC). The S-PVA HF improves the proportional ultimate strength (fL) and residual flexural strength (fR,j) of concrete, and the optimal flexural performance of concrete is achieved when the steel fiber dosage is 1.0% and the PVA fiber dosage is 0.2%. The established PMFS of hybrid fiber-reinforced concrete (HFRC) can effectively predict the flexural strength of concrete.

2.
Materials (Basel) ; 17(13)2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38998182

RESUMO

This paper investigates the effects of steel fiber and PVA fiber hybrid blending on the compressive strength (fcc), splitting tensile strength (fts), compression energy (W1.0), and shrinkage properties of concrete. It also establishes a multi-factor crack resistance index evaluation model based on the Analytic Hierarchy Process (AHP) to comprehensively evaluate the crack resistance of concrete. The results show that the steel-PVA hybrid fiber (S-PVA HF) further enhances fcc, fts, the compression energy, and the shrinkage suppression properties of the concrete. The crack resistance of the steel-PVA hybrid fiber concrete (S-PVA HFRC) is the best when the proportion of steel fiber is 1.0% and that of the PVA fiber is 0.2%, and it increases up to 143% compared to the baseline concrete. The established concrete crack resistance evaluation model has a certain reliability.

3.
Biochim Biophys Acta Mol Basis Dis ; : 167354, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39004378

RESUMO

Acute lung injury (ALI) is a serious disorder characterized by the release of pro-inflammatory cytokines and cascade activation of macrophages. Ferroptosis, a form of iron-dependent cell death triggered by intracellular phospholipid peroxidation, has been implicated as an internal mechanism underlying ALI. In this study, we investigated the effects of m6A demethylase fat mass and obesity-associated protein (FTO) on the inhibition of macrophage ferroptosis in ALI. Using a mouse model of lipopolysaccharide (LPS)-induced ALI, we observed the induction of ferroptosis and its co-localization with the macrophage marker F4/80, suggesting that ferroptosis might be induced in macrophages. Ferroptosis was promoted during LPS-induced inflammation in macrophages in vitro, and the inflammation was counteracted by the ferroptosis inhibitor ferrostatin-1 (fer-1). Given that FTO showed lower expression levels in the lung tissue of mice with ALI and inflammatory macrophages, we further dissected the regulatory capacity of FTO in ferroptosis. The results demonstrated that FTO alleviated macrophage inflammation by inhibiting ferroptosis. Mechanistically, FTO decreased the stability of ACSL4 mRNA via YTHDF1, subsequently inhibiting ferroptosis and inflammation by interrupting polyunsaturated fatty acid consumption. Moreover, FTO downregulated the synthesis and secretion of prostaglandin E2, thereby reducing ferroptosis and inflammation. In vivo, the FTO inhibitor FB23-2 aggravated lung injury, the inflammatory response, and ferroptosis in mice with ALI; however, fer-1 therapy mitigated these effects. Overall, our findings revealed that FTO may function as an inhibitor of the inflammatory response driven by ferroptosis, emphasizing its potential as a target for ALI treatment.

4.
Biomater Adv ; 163: 213950, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38972278

RESUMO

Traditional tendon engineering using cell-loaded scaffold has limited application potential due to the need of autologous cells. We hypothesize that potent mechanical loading can efficiently induce in situ Achilles tendon regeneration in a rabbit model by using a cell-free porous composite scaffold. In this study, melt-spinning was used to fabricate PGA (polyglycolic acid) and PLA (polylactic acid) filament fibers as well as non-woven PGA fibers. The PLA/PGA (4:2) filament fibers were further braided into a hybrid yarn,which was knitted into a PLA/PGA tubular mesh with potent mechanical property for sustaining natural tendon strain. The results showed that a complete cross-section of Achilles tendon created a model of full mechanical loading on the bridging scaffold, which could efficiently induce in situ tendon regeneration by promoting host cell infiltration, matrix production and tissue remodeling. Histologically, mechanical loading assisted in forming parallel aligned collagen fibers and tenocytes in a fashion similar to those of native tendon. Transmission electron microscope further demonstrated that mechanical strain induced collagen fibril development by increasing fibril diameter and forming bipolar structure, which resulted in enhanced mechanical properties. Interestingly, the synergistic effect between mechanical loading and hyaluronic acid modification was also observed on the induced tenogenic differentiation of infiltrated host fibroblasts. In conclusion, potent mechanical loading is the key inductive microenvironment for in situ tendon regeneration for this polymer-based composite scaffold with proper matrix modification, which may serve as a universal scaffold product for tendon regeneration.

5.
BMC Med Inform Decis Mak ; 24(1): 192, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982465

RESUMO

BACKGROUND: As global aging intensifies, the prevalence of ocular fundus diseases continues to rise. In China, the tense doctor-patient ratio poses numerous challenges for the early diagnosis and treatment of ocular fundus diseases. To reduce the high risk of missed or misdiagnosed cases, avoid irreversible visual impairment for patients, and ensure good visual prognosis for patients with ocular fundus diseases, it is particularly important to enhance the growth and diagnostic capabilities of junior doctors. This study aims to leverage the value of electronic medical record data to developing a diagnostic intelligent decision support platform. This platform aims to assist junior doctors in diagnosing ocular fundus diseases quickly and accurately, expedite their professional growth, and prevent delays in patient treatment. An empirical evaluation will assess the platform's effectiveness in enhancing doctors' diagnostic efficiency and accuracy. METHODS: In this study, eight Chinese Named Entity Recognition (NER) models were compared, and the SoftLexicon-Glove-Word2vec model, achieving a high F1 score of 93.02%, was selected as the optimal recognition tool. This model was then used to extract key information from electronic medical records (EMRs) and generate feature variables based on diagnostic rule templates. Subsequently, an XGBoost algorithm was employed to construct an intelligent decision support platform for diagnosing ocular fundus diseases. The effectiveness of the platform in improving diagnostic efficiency and accuracy was evaluated through a controlled experiment comparing experienced and junior doctors. RESULTS: The use of the diagnostic intelligent decision support platform resulted in significant improvements in both diagnostic efficiency and accuracy for both experienced and junior doctors (P < 0.05). Notably, the gap in diagnostic speed and precision between junior doctors and experienced doctors narrowed considerably when the platform was used. Although the platform also provided some benefits to experienced doctors, the improvement was less pronounced compared to junior doctors. CONCLUSION: The diagnostic intelligent decision support platform established in this study, based on the XGBoost algorithm and NER, effectively enhances the diagnostic efficiency and accuracy of junior doctors in ocular fundus diseases. This has significant implications for optimizing clinical diagnosis and treatment.


Assuntos
Oftalmologistas , Humanos , Tomada de Decisão Clínica , Registros Eletrônicos de Saúde/normas , Inteligência Artificial , China , Sistemas de Apoio a Decisões Clínicas
6.
Pract Lab Med ; 40: e00413, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38974938

RESUMO

Background: D-dimer at a low level is important evidence for excluding the onset and progression of thrombosis. It is readily detectable and yields rapid results, although significant variability exists among different detection systems. Our study aims to enhance the consistency across various detection systems. Methods: Twelve detection systems were included in our study. We sought to address this inconsistency by using various calibrators (two supplied by manufacturers and two comprising pooled human plasma diluted with different diluents) to standardize D-dimer measurements. We categorized the data into three groups according to D-dimer concentration levels: low (≤0.5 mg/L), medium (>0.5 mg/L - <3 mg/L), and high (≥3 mg/L). We then analyzed the data focusing on range, consistency, comparability, negative coincidence rate, and false negative rate. Results: Calibrating with pooled human plasma led to narrower result ranges in the low and medium groups (P < 0.05). In the low group, consistency improved from weak to strong (ICC 0.4-0.7, P﹤0.05), while it remained excellent in the other groups and overall (ICCï¹¥0.75, P﹤0.05). The percentage of pairwise comparability increased in both the low and high groups. Additionally, there was an increase in the negative coincidence rate. Conclusion: These findings demonstrate that uniform calibration of D-dimer can significantly enhance the consistency of results across different detection systems.

7.
J Pharm Biomed Anal ; 248: 116338, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38971092

RESUMO

Tetrahydroxy stilbene glucoside (TSG) is a water-soluble natural product that has shown potential in treating atherosclerosis (AS). However, its underlying mechanisms remain unclear. Here, we demonstrate that an 8-week TSG treatment (100 mg/kg/d) significantly reduces atherosclerotic lesions and alleviates dyslipidemia symptoms in ApoE-/- mice. 1H nuclear magnetic resonance metabolomic analysis reveals differences in both lipid components and water-soluble metabolites in the livers of AS mice compared to control groups, and TSG treatment shifts the metabolic profiles of AS mice towards a normal state. At the transcriptional level, TSG significantly restores the expression of fatty acid metabolism-related genes (Srepb-1c, Fasn, Scd1, Gpat1, Dgat1, Pparα and Cpt1α), and regulates the expression levels of disturbed cholesterol metabolism-related genes (Srebp2, Hmgcr, Ldlr, Acat1, Acat2 and Cyp7a1) associated with lipid metabolism. Furthermore, at the cellular level, TSG remarkably polarizes aortic macrophages to their M2 phenotype. Our data demonstrate that TSG alleviates arthrosclerosis by dual-targeting to hepatic lipid metabolism and aortic M2 macrophage polarization in ApoE-/- mice, with significant implications for translational medicine and the treatment of AS using natural products.

8.
Photodiagnosis Photodyn Ther ; 48: 104228, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38866070

RESUMO

BACKGROUND: Diabetic foot ulcer (DFU) is a chronic and challenging condition, addressed through various treatments including photodynamic therapy (PDT) and standard of care (SOC), yet lacking consensus on the optimal approach. This study presents a comprehensive meta-analysis of randomized controlled trials to evaluate the efficacy and safety of PDT versus SOC in managing DFU. METHODS: An extensive literature search was conducted across PubMed, Embase, and the Cochrane Library databases to identify RCTs that compared the effectiveness of PDT with SOC in treating DFU. The primary metrics evaluated included changes in ulcer area, wound healing indices, and pain levels experienced by the patients. RESULTS: This meta-analysis incorporated data from 6 RCTs, encompassing 458 patients with 467 DFUs. The analysis indicated that while PDT led to a faster reduction in ulcer size compared to SOC, the difference was not statistically significant [mean difference (MD): 2.73cm², 95 % Confidence Interval (CI) -2.98 to 8.44; p > 0.05]. However, a notable improvement was observed in the wound healing rate in the PDT group [MD: 29.26 %, 95 % CI 7.24 to 51.28; p = 0.01]. Based on the Visual Analog Scale (VAS), pain assessment revealed no significant difference between the two treatment groups [MD: 2.35, 95 % CI -2.36 to 7.06; p = 0.33]. CONCLUSION: The study suggests that PDT might offer an enhanced healing rate for DFUs compared to SOC alone, potentially leading to improved patient outcomes. Importantly, our findings highlight the superiority of photodynamic therapy in accelerating ulcer healing without an associated increase in complications. PROSPERO: 2023 CRD42023493930.

9.
Biomed Mater ; 19(4)2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38838692

RESUMO

At present, wound dressings in clinical applications are primarily used for superficial skin wounds. However, these dressings have significant limitations, including poor biocompatibility and limited ability to promote wound healing. To address the issue, this study used aldehyde polyethylene glycol as the cross-linking agent to design a carboxymethyl chitosan-methacrylic acid gelatin hydrogel with enhanced biocompatibility, which can promote wound healing and angiogenesis. The CSDG hydrogel exhibits acid sensitivity, with a swelling ratio of up to 300%. Additionally, it exhibited excellent resistance to external stress, withstanding pressures of up to 160 kPa and self-deformation of 80%. Compared to commercially available chitosan wound gels, the CSDG hydrogel demonstrates excellent biocompatibility, antibacterial properties, and hemostatic ability. Bothin vitroandin vivoresults showed that the CSDG hydrogel accelerated blood vessel regeneration by upregulating the expression of CD31, IL-6, FGF, and VEGF, thereby promoting rapid healing of wounds. In conclusion, this study successfully prepared the CSDG hydrogel wound dressings, providing a new approach and method for the development of hydrogel dressings based on natural macromolecules.


Assuntos
Materiais Biocompatíveis , Quitosana , Gelatina , Hidrogéis , Metacrilatos , Cicatrização , Quitosana/química , Quitosana/análogos & derivados , Cicatrização/efeitos dos fármacos , Gelatina/química , Hidrogéis/química , Animais , Metacrilatos/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Camundongos , Humanos , Polietilenoglicóis/química , Antibacterianos/química , Antibacterianos/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Bandagens , Masculino , Reagentes de Ligações Cruzadas/química , Regeneração/efeitos dos fármacos , Hemostáticos/química , Hemostáticos/farmacologia , Teste de Materiais , Ratos
10.
J Econ Entomol ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38935064

RESUMO

Pyriproxyfen (PPF) has been shown to affect the pupal stage and ecdysone levels in holometabolous insects, such as silkworms and mealworms. It remains unknown whether it affects hemimetabolous insects with their hormone levels in insects lacking a pupal stage. In this laboratory study, bioassays were conducted to investigate the effects of varying doses of PPF on Aphis craccivora Koch (Hemiptera: Aphididae). Ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to determine the types and titers of juvenile hormone (JH) and 20-hydroxyecdysone (20E). Additionally, the effects of PPF on A. craccivora reproduction and molting, as well as its influence on relevant gene expression, were examined. The results revealed LC50 and LC90 values of 3.84 and 7.49 mg/l for PPF, respectively, after 48 h of exposure. The results demonstrated a significant reduction in the titer of JH III and a significant increase in the titer of 20E following treatment with PPF. However, there was no significant decrease observed in the titer of JH III skipped bisepoxide (JH SB3). A sublethal concentration of PPF was found to inhibit Krüppel homolog 1 (kr-h1) gene expression and reduce aphid reproduction, but it did not significantly impact ecdysone receptor expression and aphid molting. The results of this study demonstrate that PPF exhibits a lethal effect on aphids, thereby providing an effective means of control. Additionally, sublethal concentrations of PPF have been found to inhibit the JH in aphids, resulting in a decline in their reproductive ability and achieving the desired control objectives.

11.
Cell Death Dis ; 15(6): 444, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914552

RESUMO

Endocrine resistance poses a significant clinical challenge for patients with hormone receptor-positive and human epithelial growth factor receptor 2-negative (HR + HER2-) breast cancer. Dysregulation of estrogen receptor (ER) and ERBB signaling pathways is implicated in resistance development; however, the integration of these pathways remains unclear. While SMAD4 is known to play diverse roles in tumorigenesis, its involvement in endocrine resistance is poorly understood. Here, we investigate the role of SMAD4 in acquired endocrine resistance in HR + HER2- breast cancer. Genome-wide CRISPR screening identifies SMAD4 as a regulator of 4-hydroxytamoxifen (OHT) sensitivity in T47D cells. Clinical data analysis reveals downregulated SMAD4 expression in breast cancer tissues, correlating with poor prognosis. Following endocrine therapy, SMAD4 expression is further suppressed. Functional studies demonstrate that SMAD4 depletion induces endocrine resistance in vitro and in vivo by enhancing ER and ERBB signaling. Concomitant inhibition of ER and ERBB signaling leads to aberrant autophagy activation. Simultaneous inhibition of ER, ERBB, and autophagy pathways synergistically impacts SMAD4-depleted cells. Our findings unveil a mechanism whereby endocrine therapy-induced SMAD4 downregulation drives acquired resistance by integrating ER and ERBB signaling and suggest a rational treatment strategy for endocrine-resistant HR + HER2- breast cancer patients.


Assuntos
Neoplasias da Mama , Resistencia a Medicamentos Antineoplásicos , Receptor ErbB-2 , Receptores de Estrogênio , Transdução de Sinais , Proteína Smad4 , Humanos , Proteína Smad4/metabolismo , Proteína Smad4/genética , Feminino , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Receptores de Estrogênio/metabolismo , Linhagem Celular Tumoral , Animais , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico , Tamoxifeno/análogos & derivados , Camundongos , Antineoplásicos Hormonais/farmacologia , Antineoplásicos Hormonais/uso terapêutico , Camundongos Nus , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Receptores ErbB/metabolismo , Receptores ErbB/genética
12.
Int Immunopharmacol ; 137: 112537, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-38909493

RESUMO

Colorectal cancer (CRC) has been one of the most common malignancies worldwide. Despite the advances in current therapies, the mortality rate of CRC remains high. Among them, immunotherapy has achieved satisfactory results in some CRC patients, however, how to expand the use of immunotherapy in CRC patients remains an urgent challenge. Surprisingly, the intratumoral microbiota has been found in multiple tumor tissues, including CRC. It has been demonstrated that the intratumoral microbiota is associated with the progression and treatment of CRC, and is able to enhance or decrease anti-tumor immune responses via different mechanisms as well as influence the immunotherapy efficacy, providing new potential therapeutic targets for CRC immunotherapy. In this review, we focus on the characteristics of the intratumoral microbiota, its roles in the genesis and development of CRC, its modulation of anti-tumor immune responses and immunotherapy, and propose potential applications of the intratumoral microbiota in CRC immunotherapy. Additionally, we propose possible directions for future research on the intratumoral microbiota related to CRC immunotherapy.


Assuntos
Neoplasias Colorretais , Imunoterapia , Humanos , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/terapia , Neoplasias Colorretais/microbiologia , Imunoterapia/métodos , Animais , Microbiota/imunologia , Microambiente Tumoral/imunologia , Microbioma Gastrointestinal/imunologia
13.
Int J Biol Sci ; 20(8): 2994-3007, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38904008

RESUMO

Osteoarthritis (OA) is a challenging degenerative joint disease to manage. Previous research has indicated that cell-free fat extract (CEFFE) may hold potential for OA treatment. This study investigated the role of Annexin A5 (AnxA5) within CEFFE in regulating macrophage polarization and protecting chondrocytes. In vitro experiments demonstrated that AnxA5 effectively inhibited M1 macrophage polarization by facilitating toll-like receptor (TLR) 4 internalization and lysosomal degradation through calcium-dependent endocytosis. This process decreased TLR4 expression, suppressed pro-inflammatory mediator release, and reduced the production of reactive oxygen species. Furthermore, AnxA5 displayed protective effects against chondrocyte necrosis and apoptosis. In vivo, studies revealed that intra-articular administration of AnxA5 ameliorated pain symptoms in a monosodium iodoacetate-induced osteoarthritis rat model. Histological analyses indicated a decrease in synovial inflammation and mitigation of cartilage damage following AnxA5 treatment. These results underscored the potential of AnxA5 as a therapeutic option for OA due to its capacity to regulate macrophage polarization and maintain chondrocyte viability. Further investigation into the specific mechanisms and clinical applications of AnxA5 may help improve the management of OA.


Assuntos
Anexina A5 , Condrócitos , Macrófagos , Osteoartrite , Ratos Sprague-Dawley , Animais , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Osteoartrite/induzido quimicamente , Ratos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Anexina A5/metabolismo , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Masculino , Receptor 4 Toll-Like/metabolismo , Camundongos , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Apoptose/efeitos dos fármacos
14.
Math Biosci Eng ; 21(4): 5092-5117, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38872528

RESUMO

Glaucoma is a chronic neurodegenerative disease that can result in irreversible vision loss if not treated in its early stages. The cup-to-disc ratio is a key criterion for glaucoma screening and diagnosis, and it is determined by dividing the area of the optic cup (OC) by that of the optic disc (OD) in fundus images. Consequently, the automatic and accurate segmentation of the OC and OD is a pivotal step in glaucoma detection. In recent years, numerous methods have resulted in great success on this task. However, most existing methods either have unsatisfactory segmentation accuracy or high time costs. In this paper, we propose a lightweight deep-learning architecture for the simultaneous segmentation of the OC and OD, where we have adopted fuzzy learning and a multi-layer perceptron to simplify the learning complexity and improve segmentation accuracy. Experimental results demonstrate the superiority of our proposed method as compared to most state-of-the-art approaches in terms of both training time and segmentation accuracy.


Assuntos
Algoritmos , Aprendizado Profundo , Lógica Fuzzy , Glaucoma , Disco Óptico , Humanos , Disco Óptico/diagnóstico por imagem , Glaucoma/diagnóstico por imagem , Redes Neurais de Computação , Processamento de Imagem Assistida por Computador/métodos , Reprodutibilidade dos Testes , Interpretação de Imagem Assistida por Computador/métodos , Fundo de Olho
15.
Cell Rep Med ; : 101615, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38897205

RESUMO

The clinical efficacy of neoadjuvant immunotherapy plus chemotherapy remains elusive in localized epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Here, we report interim results of a Simon's two-stage design, phase 2 trial using neoadjuvant sintilimab with carboplatin and nab-paclitaxel in resectable EGFR-mutant NSCLC. All 18 patients undergo radical surgery, with one patient experiencing surgery delay. Fourteen patients exhibit confirmed radiological response, with 44% achieving major pathological response (MPR) and no pathological complete response (pCR). Similar genomic alterations are observed before and after treatment without influencing the efficacy of subsequent EGFR-tyrosine kinase inhibitors (TKIs) in vitro. Infiltration and T cell receptor (TCR) clonal expansion of CCR8+ regulatory T (Treg)hi/CXCL13+ exhausted T (Tex)lo cells define a subtype of EGFR-mutant NSCLC highly resistant to immunotherapy, with the phenotype potentially serving as a promising signature to predict immunotherapy efficacy. Informed circulating tumor DNA (ctDNA) detection in EGFR-mutant NSCLC could help identify patients nonresponsive to neoadjuvant immunochemotherapy. These findings provide supportive data for the utilization of neoadjuvant immunochemotherapy and insight into immune resistance in EGFR-mutant NSCLC.

16.
Nat Commun ; 15(1): 4851, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844818

RESUMO

The manipulation of spin textures by spin currents is of fundamental and technological interest. A particularly interesting system is the 2D van der Waals ferromagnet Fe3GeTe2, in which Néel-type skyrmions have recently been observed. The origin of these chiral spin textures is of considerable interest. Recently, it was proposed that these derive from defects in the structure that lower the symmetry and allow for a bulk vector Dzyaloshinsky-Moriya interaction. Here, we demonstrate current-induced domain wall motion in Fe3GeTe2 flakes, in which the maximum domain wall velocity is an order of magnitude higher than those reported in previous studies. In heterostructures with Pt or W layers on top of the Fe3GeTe2 flakes, domain walls can be moved via a combination of spin transfer and spin-orbit torques. The competition between these torques leads to a change in the direction of domain wall motion with increasing magnitude of the injected current.

17.
Neuromolecular Med ; 26(1): 27, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38935278

RESUMO

Glioma is the most common primary intracranial tumor with high mortality and poor prognosis. The purpose of this study was to investigate how single-nucleotide polymorphisms (SNPs) of the NID2 gene affect glioma risk and prognosis. Four candidate SNPs of NID2 in 529 glioma patients and 478 healthy controls were successfully genotyped by Agena MassARRAY mass spectrometer. Logistic regression was utilized to assess the associations between NID2 SNPs and glioma risk under different genetic models. Furthermore, the relationship between risk-related SNPs in NID2 and the prognosis of glioma patients was explored through Kaplan-Meier (KM) survival curve and Cox proportional hazard regression analysis. The results showed that rs11846847 (OR 1.24, p = 0.017) and rs1874569 (OR 1.22, p = 0.026) were significantly associated with an increased risk of glioma, and rs11846847 also had a risk-increasing effect on glioma in participants ≤ 40 years old. The interaction model of rs11846847 and rs1874569 could be more suitable for forecasting glioma risk. We also discovered a significant association between rs1874569 and poor prognosis in glioma patients (HR 1.32, p = 0.039) and especially CC genotype was relevant to shorter overall survival (OS) and progression-free survival (PFS) in patients with high-grade glioma. Additionally, the study demonstrated that gross total resection or chemotherapy improve glioma prognosis in the Chinese Han population. This study is the first to provide evidence for the association of NID2 SNPs with glioma risk and prognosis, suggesting that NID2 variants might be potential factors for glioma.


Assuntos
Povo Asiático , Neoplasias Encefálicas , Proteínas de Ligação ao Cálcio , Predisposição Genética para Doença , Glioma , Polimorfismo de Nucleotídeo Único , Humanos , Glioma/genética , Glioma/mortalidade , Feminino , Masculino , Neoplasias Encefálicas/genética , Prognóstico , Adulto , Pessoa de Meia-Idade , Povo Asiático/genética , Proteínas de Ligação ao Cálcio/genética , China/epidemiologia , Estudos de Casos e Controles , Estimativa de Kaplan-Meier , Genótipo , Modelos de Riscos Proporcionais , Fatores de Risco , População do Leste Asiático , Moléculas de Adesão Celular
18.
J Nanobiotechnology ; 22(1): 365, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918839

RESUMO

Bacteriophages (phages) represent a unique category of viruses with a remarkable ability to selectively infect host bacteria, characterized by their assembly from proteins and nucleic acids. Leveraging their exceptional biological properties and modifiable characteristics, phages emerge as innovative, safe, and efficient delivery vectors. The potential drawbacks associated with conventional nanocarriers in the realms of drug and gene delivery include a lack of cell-specific targeting, cytotoxicity, and diminished in vivo transfection efficiency. In contrast, engineered phages, when employed as cargo delivery vectors, hold the promise to surmount these limitations and attain enhanced delivery efficacy. This review comprehensively outlines current strategies for the engineering of phages, delineates the principal types of phages utilized as nanocarriers in drug and gene delivery, and explores the application of phage-based delivery systems in disease therapy. Additionally, an incisive analysis is provided, critically examining the challenges confronted by phage-based delivery systems within the domain of nanotechnology. The primary objective of this article is to furnish a theoretical reference that contributes to the reasoned design and development of potent phage-based delivery systems.


Assuntos
Bacteriófagos , Sistemas de Liberação de Medicamentos , Nanomedicina , Bacteriófagos/genética , Humanos , Nanomedicina/métodos , Sistemas de Liberação de Medicamentos/métodos , Animais , Técnicas de Transferência de Genes , Portadores de Fármacos/química , Nanopartículas/química , Nanotecnologia/métodos
19.
Rev Sci Instrum ; 95(6)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38836718

RESUMO

In light of the limitations of the current piezoelectric energy harvesters and the demand for self-power supply in wireless sensor nodes, a novel positive feedback piezoelectric energy harvester based on nonlinear magnetic coupling is proposed. The operational characteristics of this energy harvester are investigated from three perspectives: theory, simulation, and experiment. First, a nonlinear electromechanical coupling mathematical model that describes the dynamic response of the energy harvester system is established by combining the Hamilton variational principle with the piezoelectric theory. This provides a theoretical foundation for subsequent research. Second, finite element method simulations are employed to optimize the structural parameters of the energy harvester and study the impact of nonlinear magnetic force on its output performance. Finally, an experimental prototype is fabricated and an experimental test system is constructed to validate the designed positive feedback piezoelectric energy harvester. The results demonstrate that changes in the longitudinal beam angle have minimal effect on energy capture efficiency. By appropriately increasing the bending surface length, reducing initial magnetic moment, and augmenting mass block weight, wider working frequency bands and higher power generation capacity can be achieved when vibrating in low-energy orbits. The experimental findings align closely with theoretical design values and contribute to advancing broadband multi-directional piezoelectric energy harvesting technology in order to provide high-performance vibration-based power solutions for wireless applications.

20.
Zhen Ci Yan Jiu ; 49(5): 480-486, 2024 May 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38764119

RESUMO

OBJECTIVES: To observe the activation state and neuronal types of somatosensory cortex and the primary motor cortex induced by electroacupuncture (EA) stimulation of "Sibai" (ST2) and "Quanliao" (SI18) acupoints in mice. METHODS: Male C57BL/6J mice were randomly divided into blank control and EA groups, with 6 mice in each group. Rats of the EA group received EA stimulation (2 Hz, 0.6 mA) at ST2 and SI18 for 30 minutes. Samples were collected after EA intervention, and immunofluorescence staining was performed to quantify the expression of the c-Fos gene (proportion of c-Fos positive cells) in the somatosensory cortex and primary motor cortex. The co-labelled cells of calcium/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) and gamma-aminobutyric acid (GABA) in the somatosensory cortex and primary motor cortex were observed and counted by using microscope after immunofluorescence staining. Another 10 mice were used to detect the calcium activity of excitatory neurons in the somatosensory cortex and primary motor cortex by fiber photometry. RESULTS: In comparison with the blank control group, the number of c-Fos positive cells, and the proportion of c-Fos and CaMKⅡ co-labelled cells in both the somatosensory cortex and primary motor cortex were significantly increased after EA stimulation (P<0.05). No significant changes were found in the proportion of c-Fos and GABA co-labeled cells in both the somatosensory cortex and primary motor cortex after EA. Results of fiber optic calcium imaging technology showed that the spontaneous calcium activity of excitatory neurons in both somatosensory cortex and primary motor cortex were obviously increased during EA compared with that before EA (P<0.01), and strikingly reduced after cessation of EA compared with that during EA (P<0.05). CONCLUSIONS: Under physiological conditions, EA of ST2 and SI18 can effectively activate excitatory neurons in the somatosensory cortex and primary motor cortex.


Assuntos
Pontos de Acupuntura , Eletroacupuntura , Camundongos Endogâmicos C57BL , Neurônios , Animais , Masculino , Camundongos , Neurônios/metabolismo , Córtex Sensório-Motor/metabolismo , Humanos , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , Córtex Motor/metabolismo , Córtex Somatossensorial/metabolismo
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