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BACKGROUND: The long-term impact of drug-coated balloon (DCB) angioplasty for the treatment of patients with de novo coronary artery lesions remains uncertain. We aimed to assess the non-inferiority of DCB angioplasty with rescue stenting to intended drug-eluting stent (DES) deployment for patients with de novo, non-complex coronary artery lesions. METHODS: REC-CAGEFREE I was an open-label, randomised, non-inferiority trial conducted at 43 sites in China. After successful lesion pre-dilatation, patients aged 18 years or older with de novo, non-complex coronary artery disease (irrespective of target vessel diameter) and an indication for percutaneous coronary intervention were randomly assigned (1:1), via a web-based centralised system with block randomisation (block size of two, four, or six) and stratified by site, to paclitaxel-coated balloon angioplasty with the option of rescue stenting due to an unsatisfactory result (DCB group) or intended deployment of second-generation thin-strut sirolimus-eluting stents (DES group). The primary outcome was the device-oriented composite endpoint (DoCE; including cardiovascular death, target vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularisation) assessed at 24 months in the intention-to-treat (ITT) population (ie, all participants randomly assigned to treatment). Non-inferiority was established if the upper limit of the one-sided 95% CI for the absolute risk difference was smaller than 2·68%. Safety was assessed in the ITT population. This study is registered with ClinicalTrials.gov, NCT04561739. It is closed to accrual and extended follow-up is ongoing. FINDINGS: Between Feb 5, 2021, and May 1, 2022, 2272 patients were randomly assigned to the DCB group (1133 [50%]) or the DES group (1139 [50%]). Median age at the time of randomisation was 62 years (IQR 54-69), 1574 (69·3%) of 2272 were male, 698 (30·7%) were female, and all patients were of Chinese ethnicity. 106 (9·4%) of 1133 patients in the DCB group received rescue DES after unsatisfactory DCB angioplasty. As of data cutoff (May 1, 2024), median follow-up was 734 days (IQR 731-739). At 24 months, the DoCE occurred in 72 (6·4%) of 1133 patients in the DCB group and 38 (3·4%) of 1139 in the DES group, with a risk difference of 3·04% in the cumulative event rate (upper boundary of the one-sided 95% CI 4·52; pnon-inferiority=0·65; two-sided 95% CI 1·27-4·81; p=0·0008); the criterion for non-inferiority was not met. During intervention, no acute vessel closures occurred in the DCB group and one (0·1%) of 1139 patients in the DES group had acute vessel closure. Periprocedural myocardial infarction occurred in ten (0·9%) of 1133 patients in the DCB group and nine (0·8%) in the DES group. INTERPRETATION: In patients with de novo, non-complex coronary artery disease, irrespective of vessel diameter, a strategy of DCB angioplasty with rescue stenting did not achieve non-inferiority compared with the intended DES implantation in terms of the DoCE at 2 years, which indicates that DES should remain the preferred treatment for this patient population. FUNDING: Xijing Hospital and Shenqi Medical. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Asunto(s)

Angioplastia Coronaria con Balón , Enfermedad de la Arteria Coronaria , Stents Liberadores de Fármacos , Paclitaxel , Humanos , Masculino , Femenino , Persona de Mediana Edad , Angioplastia Coronaria con Balón/métodos , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Enfermedad de la Arteria Coronaria/terapia , Anciano , Sirolimus/uso terapéutico , Sirolimus/administración & dosificación , Resultado del Tratamiento , Materiales Biocompatibles Revestidos , China/epidemiología , Intervención Coronaria Percutánea/métodos

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Flexible, wearable pressure sensors offer numerous benefits, including superior sensing capabilities, a lightweight and compact design, and exceptional conformal properties, making them highly sought after in various applications including medical monitoring, human-computer interactions, and electronic skins. Because of their excellent characteristics, such as simple fabrication, low power consumption, and short response time, capacitive pressure sensors have received widespread attention. As a flexible polymer material, polydimethylsiloxane (PDMS) is widely used in the preparation of dielectric layers for capacitive pressure sensors. The Young's modulus of the flexible polymer can be effectively decreased through the synergistic application of sacrificial template and laser ablation techniques, thereby improving the functionality of capacitive pressure sensors. In this study, a novel sensor was introduced. Its dielectric layer was developed through a series of processes, including the use of a sacrificial template method using NaCl microparticles and subsequent CO2 laser ablation. This porous PDMS dielectric layer, featuring an array of holes, was then sandwiched between two flexible electrodes to create a capacitive pressure sensor. The sensor demonstrates a sensitivity of 0.694 kPa-1 within the pressure range of 0-1 kPa and can effectively detect pressures ranging from 3 Pa to 200 kPa. The sensor demonstrates stability for up to 500 cycles, with a rapid response time of 96 ms and a recovery time of 118 ms, coupled with a low hysteresis of 6.8%. Furthermore, our testing indicates that the sensor possesses limitless potential for use in detecting human physiological activities and delivering signals.

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Docosahexaenoic acid (DHA) is a potential regulatory substance for flesh quality of fish, while the related evaluation is still barely. In this study, the effects of DHA-enriched diets on the flesh quality of freshwater fish (Megalobrama amblycephala) were investigated systematically. The sub-adult M. amblycephala were randomly fed with control diet (CON), 0.2% DHA diet (DL) or 0.8% DHA diet (DH). After 12-week feeding trial, the DH group flesh had higher concentrations of essential amino acids and polyunsaturated fatty acids compared to the CON group. Meanwhile, the hardness, springiness, shear force and moisture-holding capacity, as well as the values of umami, richness and sweetness were also improved by DH. The non-targeted metabolomics analysis revealed the key metabolites that may have significantly positive influence on flavor. Collectively, the diet supplementation with 0.8% DHA could achieve the improvement of the flesh quality in terms of nutritional value, texture and flavor in freshwater fish.

Asunto(s)

Alimentación Animal , Cyprinidae , Ácidos Docosahexaenoicos , Valor Nutritivo , Gusto , Animales , Ácidos Docosahexaenoicos/análisis , Ácidos Docosahexaenoicos/metabolismo , Ácidos Docosahexaenoicos/administración & dosificación , Cyprinidae/metabolismo , Alimentación Animal/análisis , Alimentos Marinos/análisis , Suplementos Dietéticos/análisis , Agua Dulce/química , Aromatizantes/química , Aromatizantes/metabolismo

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Background: Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is a rare autosomal dominant disorder with a low incidence in Asia. The most frequent clinical manifestations include fever, rash, myalgia, joint pain and abdominal pain. Misdiagnosis rates are high because of the clinical and genetic variability of the disease. The pathogenesis of TRAPS is complex and yet to be fully defined. Early genetic diagnosis is the key to precise treatment. Methods: In this study, a Chinese family with suspected TRAPS were analyzed by genome-wide SNP genotyping, linkage analysis and targeted sequencing for identification of mutations in causative genes. To study the pathogenicity of the identified gene mutation, we performed a conservation analysis of the mutation site and protein structure analysis. Flow cytometry was used to detect TNFRSF1A shedding and quantitative real-time PCR were used to assess the activation of unfolded protein response (UPR) in the mutation carriers and healthy individuals. Results: A typical TRAPS family history, with a pattern of autosomal dominant inheritance, led to the identification of a rare mutation in the TNFRSF1A gene (c.G374A [p.Cys125Tyr]) with unknown significance. The patient responded well to corticosteroids, and long-term therapy with colchicine effectively reduced the inflammatory attacks. No amyloid complications occurred during the 6-year follow-up. In silico protein analysis showed that the mutation site is highly conversed and the mutation prevents the formation of intrachain disulfide bonds in the protein. Despite a normal shedding of the TNFRSF1A protein from stimulated monocytes in the TRAPS patients with p.C125Y mutation, the expression of CHOP and the splicing of XBP1 was significantly higher than healthy controls, suggesting the presence of an activation UPR. Conclusion: This is the first report of a Chinese family with the rare p.C125Y mutation in TNFRSF1A. The p.C125Y mutation does not result in aberrant receptor shedding, but instead is associated with an activated UPR in these TRAPS patients, which may provide new insights into the pathogenesis of this rare mutation in TRAPS.

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OBJECTIVES: To develop and validate a deep learning (DL) model for automated segmentation of hepatic and portal veins, and apply the model in blood-free future liver remnant (FLR) assessments via CT before major hepatectomy. METHODS: 3-dimensional 3D U-Net models were developed for the automatic segmentation of hepatic veins and portal veins on contrast-enhanced CT images. A total of 170 patients treated from January 2018 to March 2019 were included. 3D U-Net models were trained and tested under various liver conditions. The Dice similarity coefficient (DSC) and volumetric similarity (VS) were used to evaluate the segmentation accuracy. The use of quantitative volumetry for evaluating resection was compared between blood-filled and blood-free settings and between manual and automated segmentation. RESULTS: The DSC values in the test dataset for hepatic veins and portal veins were 0.66 ± 0.08 (95% CI: (0.65, 0.68)) and 0.67 ± 0.07 (95% CI: (0.66, 0.69)), the VS values were 0.80 ± 0.10 (95% CI: (0.79, 0.84)) and 0.74 ± 0.08 (95% CI: (0.73, 0.76)), respectively No significant differences in FLR, FLR% assessments, or the percentage of major hepatectomy patients were noted between the blood-filled and blood-free settings (p = 0.67, 0.59 and 0.99 for manual methods, p = 0.66, 0.99 and 0.99 for automated methods, respectively) according to the use of manual and automated segmentation methods. CONCLUSION: Fully automated segmentation of hepatic veins and portal veins and FLR assessment via blood-free CT before major hepatectomy are accurate and applicable in clinical cases involving the use of DL. CRITICAL RELEVANCE STATEMENT: Our fully automatic models could segment hepatic veins, portal veins, and future liver remnant in blood-free setting on CT images before major hepatectomy with reliable outcomes. KEY POINTS: Fully automatic segmentation of hepatic veins and portal veins was feasible in clinical practice. Fully automatic volumetry of future liver remnant (FLR)% in a blood-free setting was robust. No significant differences in FLR% assessments were noted between the blood-filled and blood-free settings.

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Circular RNAs (circRNAs) play a critical role in pathological mechanisms of Mycobacterium tuberculosis (Mtb) and can be used as a new biomarker for active tuberculosis (ATB) diagnosis. Therefore, we identified significantly dysregulated circRNAs in ATB patients and healthy controls (HC) and explored their molecular mechanism. We found that hsa_circ_0002371 was significantly up-regulated in PBMCs of ATB patients and Mycobacterium tuberculosis H37Rv- or Mycobacterium bovis bacillus Calmette Guerin (BCG)-infected THP-1 cells. Functional experiments demonstrated that hsa_circ_0002371 inhibited autophagy in BCG-infected THP-1 cells and promoted intracellular BCG survival rate. In terms of mechanism, hsa_circ_0002371 facilitated the expression of hsa-miR-502-5p, as shown by bioinformatics and dual-luciferase reporter gene analysis, respectively. Notably, hsa-miR-502-5p inhibited autophagy via suppressing autophagy related 16 like 1 (ATG16L1) in BCG-infected macrophages and thus promoting intracellular BCG growth. In summation, hsa_circ_0002371 increased the suppression of hsa-miR-502-5p on ATG16L1 and inhibited autophagy to promote Mtb growth in macrophages. In Conclusion, our data suggested that hsa_circ_0002371 was significantly up-regulated in the PBMCs of ATB patients compared with HC. The hsa_circ_0002371/hsa-miR-502-5p/ATG16L1 axis promoted the survival of intracellular Mtb and inhibited autophagy in macrophages. Our findings suggested hsa_circ_0002371 could act as a potential diagnostic biomarker and therapeutic target.

Asunto(s)

Proteínas Relacionadas con la Autofagia , Autofagia , Macrófagos , MicroARNs , Mycobacterium tuberculosis , ARN Circular , Humanos , MicroARNs/metabolismo , MicroARNs/genética , ARN Circular/genética , ARN Circular/metabolismo , Proteínas Relacionadas con la Autofagia/metabolismo , Proteínas Relacionadas con la Autofagia/genética , Macrófagos/metabolismo , Macrófagos/microbiología , Células THP-1 , Tuberculosis/metabolismo , Tuberculosis/microbiología , Tuberculosis/genética , Tuberculosis/patología , Mycobacterium bovis , Masculino , Femenino

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RHOH, an atypical small GTPase predominantly expressed in hematopoietic cells, plays a vital role in immune function. A deficiency in RHOH has been linked to epidermodysplasia verruciformis, lung disease, Burkitt lymphoma and T cell defects. Here, we report a novel germline homozygous RHOH c.245G > A (p.Cys82Tyr) variant in a 21-year-old male suffering from recurrent, invasive, opportunistic infections affecting the lungs, eyes, and brain. His sister also succumbed to a lung infection during early adulthood. The patient exhibited a persistent decrease in CD4+ T, B, and NK cell counts, and hypoimmunoglobulinemia. The patient's T cell showed impaired activation upon in vitro TCR stimulation. In Jurkat T cells transduced with RHOHC82Y, a similar reduction in activation marker CD69 up-regulation was observed. Furthermore, the C82Y variant showed reduced RHOH protein expression and impaired interaction with the TCR signaling molecule ZAP70. Together, these data suggest that the newly identified autosomal-recessive RHOH variant is associated with T cell dysfunction and recurrent opportunistic infections, functioning as a hypomorph by disrupting ZAP70-mediated TCR signaling.

Asunto(s)

Homocigoto , Infecciones Oportunistas , Humanos , Masculino , Adulto Joven , Células Jurkat , Activación de Linfocitos/genética , Infecciones Oportunistas/genética , Infecciones Oportunistas/inmunología , Linaje , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/metabolismo , Recurrencia , Linfocitos T/inmunología , Proteína Tirosina Quinasa ZAP-70/genética , Proteína Tirosina Quinasa ZAP-70/metabolismo

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Uncoordinated (Unc) 51-like kinase (ulk1) and ulk2 are closely involved in autophagy activation, but little is known about their roles in regulating glucose homeostasis. In this study, the genes of ulk1a, ulk1b and ulk2 were cloned and characterized in fish Megalobrama amblycephala. All the three genes shared the approximate N-terminal kinase domain and the C-terminal Atg1-like_tMIT domain structure, while the amino acid sequence identity of them are different between M. amblycephala and other vertebrates. Their transcripts were widely observed in various tissues (brain, muscle, gill, heart, spleen, eye, liver, intestine, abdominal adipose and kidney), but differed in tissue expression patterns. During the glucose tolerance test and the insulin tolerance test, the up-regulated transcriptions of ulk1a, ulk1b and ulk2 were all found despite some differences in the temporal patterns. At the same time, the activities of glycolytic enzymes like hexokinase and phosphofructokinase both showed parallel increases. Furthermore, the feeding of a high-carbohydrate diet decreased the transcriptions of ulk1a, ulk1b and ulk2. Collectively, this study demonstrated that ulk1a, ulk1b and ulk2 in M. amblycephala had similar molecular characterizations, but with different conservation and tissue expression patterns. In addition, ulk1/2 might play important roles in maintaining the glucose homeostasis in fish through regulating the glycolytic pathway.

Asunto(s)

Cyprinidae , Cipriniformes , Animales , Cipriniformes/genética , Secuencia de Aminoácidos , Clonación Molecular , Glucosa/metabolismo , Cyprinidae/genética , Cyprinidae/metabolismo , Proteínas de Peces/genética , Proteínas de Peces/metabolismo , Filogenia

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Recent years have witnessed substantial progress in cancer immunotherapy, specifically T cell-based therapies. However, the application of T cell therapies has been primarily limited to hematologic malignancies, with limited success in the treatment of solid tumors. The main challenge in treating solid tumor is immune escape, which is characterized by reduced antigenicity, diminished immunogenicity, and the development of suppressive tumor immune microenvironments. To address these obstacles and restore T cell-mediated anti-tumor responses, a novel nanoparticle formulation known as PRA@Oxa-c16 is developed. This innovative approach combines retinoic acid and Pt(IV) to specifically target and overcome immune escape. Notably, the therapeutic efficacy of PRA@Oxa-c16 primarily relies on its ability to induce anti-tumor T cell responses, in contrast to the cytotoxicity associated with conventional chemotherapeutic agents. When combined with an immune checkpoint blockade, anti-programmed death-ligand 1 antibody, PRA@Oxa-c16 effectively eliminates solid tumors and induces immune memory responses, which prevent tumor metastasis and recurrence. This promising approach holds great potential for enhancing the treatment of solid tumors with T cell-based immunotherapy.

Asunto(s)

Antígeno B7-H1 , Linfocitos T CD8-positivos , Inmunoterapia , Nanomedicina , Profármacos , Profármacos/química , Profármacos/uso terapéutico , Profármacos/farmacología , Inmunoterapia/métodos , Linfocitos T CD8-positivos/inmunología , Animales , Nanomedicina/métodos , Ratones , Línea Celular Tumoral , Antígeno B7-H1/inmunología , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/metabolismo , Nanopartículas/química , Neoplasias/terapia , Neoplasias/inmunología , Humanos , Platino (Metal)/química , Tretinoina/química , Tretinoina/farmacología , Tretinoina/uso terapéutico , Microambiente Tumoral/efectos de los fármacos , Activación de Linfocitos/efectos de los fármacos , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología

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Endovascular stenting is a safer alternative to open surgery for use in treating cerebral arterial stenosis and significantly reduces the recurrence of ischemic stroke, but the widely used bare-metal stents (BMSs) often result in in-stent restenosis (ISR). Although evidence suggests that drug-eluting stents are superior to BMSs in the short term, their long-term performances remain unknown. Herein, we propose a potential vascular stent modified by immobilizing clickable chemerin 15 (C15) peptides on the stent surface to suppress coagulation and restenosis. Various characterization techniques and an animal model were used to evaluate the surface properties of the modified stents and their effects on endothelial injury, platelet adhesion, and inflammation. The C15-immobilized stent could prevent restenosis by minimizing endothelial injury, promoting physiological healing, restraining the platelet-leukocyte-related inflammatory response, and inhibiting vascular smooth muscle cell proliferation and migration. Furthermore, in vivo studies demonstrated that the C15-immobilized stent mitigated inflammation, suppressed neointimal hyperplasia, and accelerated endothelial restoration. The use of surface-modified, anti-inflammatory, endothelium-friendly stents may be of benefit to patients with arterial stenosis. STATEMENT OF SIGNIFICANCE: Endovascular stenting is increasingly used for cerebral arterial stenosis treatment, aiming to prevent and treat ischemic stroke. But an important accompanying complication is in-stent restenosis (ISR). Persistent inflammation has been established as a hallmark of ISR and anti-inflammation strategies in stent modification proved effective. Chemerin 15, an inflammatory resolution mediator with 15-aa peptide, was active at picomolar through cell surface receptor, no need to permeate cell membrane and involved in resolution of inflammation by inhibiting inflammatory cells adhesion, modulating macrophage polarization into protective phenotype, and reducing inflammatory factors release. The implications of this study are that C15 immobilized stent favors inflammation resolution and rapid re-endothelialization, and exhibits an inhibitory role of restenosis. As such, it helps the decreased incidence of ISR.

Asunto(s)

Quimiocinas , Hiperplasia , Neointima , Stents , Animales , Quimiocinas/metabolismo , Humanos , Neointima/patología , Masculino , Antiinflamatorios/farmacología , Antiinflamatorios/química , Péptidos y Proteínas de Señalización Intercelular/farmacología , Péptidos/farmacología , Péptidos/química , Ratones , Proliferación Celular/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos , Proteínas Inmovilizadas/farmacología , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos

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BACKGROUND: Surgical methods for patients with osteoporotic fracture vertebral collapse complicated with neurological dysfunction are still a topic of debate. We designed an improved osteotomy for the treatment of osteoporotic compression fracture patients with neurological dysfunction. Compared with traditional osteotomy methods such as pedicle subtraction osteotomy (PSO) and bone-disc-bone osteotomy (BDBO), the osteotomy range is reduced. Therefore, we use a finite element method to analyze the biomechanical conditions of these three osteotomy methods and provide a mechanical theoretical basis for the surgical treatment of these three osteotomy methods. METHODS: Based on the CT scan of a patient with L1 osteoporotic fracture vertebral collapse and neurological dysfunction, the finite element model was constructed by importing Mimics software, and three different osteotomy models were established. The forces and displacements of internal fixation device, T1-L5 whole segment, T10 vertebral body, and T10/11 intervertebral disc were recorded under different working conditions. RESULTS: The displacement levels of internal fixation device, T1-L5 spine, T10 vertebral body, and T10/11 intervertebral disc in the modified osteotomy group were between BDBO group and PSO group. The stress in BDBO group was concentrated in titanium mesh and its maximum stress was much higher than that in PSO group and modified osteotomy group. The mechanical distribution of T10/11 intervertebral disc showed that the maximum stress distribution of the three osteotomy methods was similar. CONCLUSION: The relatively simple modified osteotomy has certain advantages in stress and displacement. In contrast, the stability of BDBO group was poor, especially in the lumbar intervertebral disc and lumbar body. For this type of osteotomy patients, it is recommended to avoid postoperative flexion so as not to increase the load.

Asunto(s)

Fracturas por Compresión , Fracturas Osteoporóticas , Fracturas de la Columna Vertebral , Humanos , Fracturas Osteoporóticas/complicaciones , Fracturas Osteoporóticas/cirugía , Fracturas por Compresión/complicaciones , Fracturas por Compresión/cirugía , Análisis de Elementos Finitos , Vértebras Lumbares/lesiones , Vértebras Torácicas/lesiones , Fracturas de la Columna Vertebral/complicaciones , Fracturas de la Columna Vertebral/cirugía , Osteotomía/métodos , Fenómenos Biomecánicos

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This study aims to overcome the drawbacks associated with hydroxyapatite (HAP) dense structures after sintering, which often result in undesirable features such as large grain size, reduced porosity, high crystallinity, and low specific surface area. These characteristics hinder osseointegration and limit the clinical applicability of the material. To address these issues, a new method involving the preparation of hollow hydroxyapatite (hHAP) microspheres has been proposed. These microspheres exhibit distinctive traits including weak crystallization, high specific surface area, and increased porosity. The weak crystallization aligns more closely with early mineralization products found in the human body and animals. Moreover, the microspheres' high specific surface area and porosity offer advantages for protein loading and facilitating osteoblast attachment. This innovative approach not only mitigates the limitations of conventional HAP structures but also holds the potential for improving the effectiveness of hydroxyapatite in biomedical applications, particularly in enhancing osseointegration. Three-dimensional printed hHAP/chitosan (CS) scaffolds with different hHAP concentration gradients were manufactured, and the physical and biological properties of each group were systematically evaluated. In vitro and in vivo experiments show that the hHAP/CS scaffold has excellent performance in bone remodeling. Furthermore, in-scaffold components, hHAP and CS were cocultured with bone marrow mesenchymal stem cells to explore the regulatory role of hHAP and CS in the process of bone healing and to reveal the cell-level specific regulatory network activated by hHAP. Enrichment analysis showed that hHAP can promote bone regeneration and reconstruction by recruiting calcium ions and regulating inflammatory reactions.

Asunto(s)

Quitosano , Durapatita , Animales , Humanos , Durapatita/farmacología , Durapatita/química , Andamios del Tejido/química , Calcio , Osteogénesis , Regeneración Ósea/fisiología , Quitosano/química , Impresión Tridimensional , Porosidad , Iones

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The immune microenvironment plays a pivotal role in osteoanagenesis. Biomaterials can modulate osteogenic efficacy by inducing specific local immune reactions. As 3D-printing technology advances, digital light projection printing has emerged as a promising method for creating large scale, high-precision biomaterial scaffolds. By adjusting the solid content and the sintering conditions during printing, the pore size of biomaterials can be meticulously controlled. Yet, the systematic influence of pore size on the immune microenvironment remains uncharted. We fabricated 3D-printed hydroxyapatite bioceramic scaffolds with three distinct pore sizes: 400 µm, 600 µm, and 800 µm. Our study revealed that scaffolds with a pore size of 600 µm promote macrophage M2 polarization, which is achieved by upregulating interferon-beta and HIF-1α production. When these materials were implanted subcutaneously in rats and within rabbit skulls, we observed that the 600 µm scaffolds notably improved the long-term inflammatory response, fostered vascular proliferation, and augmented new bone growth. This research paves the way for innovative therapeutic strategies for treating large segmental bone defects in clinical settings.

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As an essential component of flexible electronics, superelastic conductive fibers with good mechanical and electrical properties have drawn significant attention, especially in their preparation. In this study, we prepared a superelastic conductive fiber composed of eutectic gallium-indium (EGaIn) and thermoplastic polyurethane (TPU) by simple wet spinning. The composite conductive fiber with a liquid metal (LM) content of 85 wt % achieved a maximum strain at a break of 659.2%, and after the conductive pathway in the porous structure of the composite fibers was fully activated, high conductivity (1.2 × 105 S/m) was achieved with 95 wt % LM by mechanical sintering and training processes. The prepared conductive fibers exhibited a stable resistive response as the fibers were strained and could be sewn into fabrics and used as wearable strain sensors to monitor various human motions. These conductive fibers can be molded into helical by heating, and they have excellent electrical properties at a maximum mechanical strain of 3400% (resistance change <0.27%) with a helical index of 11. Moreover, the conductive fibers can be welded to various two or three-dimensional conductors. In summary, with a scalable manufacturing process, weldability, superelasticity, and high electrical conductivity, EGaIn/TPU composite fibers fabricated by wet spinning have considerable potential for flexible electronics.

RESUMEN

BACKGROUND: The role of the basal metabolic rate (BMR) in osteoarthritis (OA) remains unclear, as previous retrospective studies have produced inconsistent results. Therefore, we performed a Mendelian randomization (MR) study to systematically investigate the causal relationship between the BMR and OA. METHODS: Single-nucleotide polymorphism (SNP) data related to BMR and OA were collected in a genome-wide association study. Using OA as the outcome variable and BMR as the exposure factor, SNPs with strong correlation with the BMR as the tool variable were screened. The correlation between the BMR and OA risk was evaluated using the inverse-variance weighted method, and heterogeneity and pleiotropy were evaluated using a sensitivity analysis. RESULTS: There was a potential causal relationship between the BMR and OA risk (odds ratio [OR], 1.014; 95% confidence interval [CI], 1.008-1.020; P = 2.29e - 6). A causal relationship was also revealed between the BMR and knee OA (OR, 1.876; 95% CI, 1.677-2.098; P = 2.98e - 28) and hip OA (OR, 1.475; 95% CI, 1.290-1.686; P = 1.26e - 8). Sensitivity analysis confirmed the robustness of these results. CONCLUSION: Here, we identified a latent causal relationship between the BMR and the risk of OA. These results suggest that the risk of OA in the hip or knee joint may be reduced by controlling the BMR.

Asunto(s)

Osteoartritis de la Cadera , Osteoartritis de la Rodilla , Humanos , Metabolismo Basal , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Osteoartritis de la Rodilla/genética , Polimorfismo de Nucleótido Simple

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The significant potential of flexible sensors in various fields such as human health, soft robotics, human-machine interaction, and electronic skin has garnered considerable attention. Capacitive pressure sensor is popular given their mechanical flexibility, high sensitivity, and signal stability. Enhancing the performance of capacitive sensors can be achieved through the utilization of gradient structures and high dielectric constant media. This study introduced a novel dielectric layer, employing the BaTiO3-PDMS material with a gradient micro-cones architecture (GMCA). The capacitive sensor was constructed by incorporating a dielectric layer GMCA, which was fabricated using laser engraved acrylic (PMMA) molds and flexible copper-foil/polyimide-tape electrodes. To examine its functionality, the prepared sensor was subjected to a pressure range of 0-50 KPa. Consequently, this sensor exhibited a remarkable sensitivity of up to 1.69 KPa-1 within the pressure range of 0-50 KPa, while maintaining high pressure-resolution across the entire pressure spectrum. Additionally, the pressure sensor demonstrated a rapid response time of 50 ms, low hysteresis of 0.81%, recovery time of 160 ms, and excellent cycling stability over 1000 cycles. The findings indicated that the GMCA pressure sensor, which utilized a gradient structure and BaTiO3-PDMS material, exhibited notable sensitivity and a broad linear pressure range. These results underscore the adaptability and viability of this technology, thereby facilitating enhanced flexibility in pressure sensors and fostering advancements in laser manufacturing and flexible devices for a wider array of potential applications.

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BACKGROUND AND HYPOTHESIS: Schizophrenia is a multidimensional disease. This study proposes a new research framework that combines multimodal meta-analysis and genetic/molecular architecture to solve the consistency in neuroimaging biomarkers of schizophrenia and whether these link to molecular genetics. STUDY DESIGN: We systematically searched Web of Science, PubMed, and BrainMap for the amplitude of low-frequency fluctuations (ALFF) or fractional ALFF, regional homogeneity, regional cerebral blood flow, and voxel-based morphometry analysis studies investigating schizophrenia. The pooled-modality, single-modality, and illness duration-dependent meta-analyses were performed using the activation likelihood estimation algorithm. Subsequently, Spearman correlation and partial least squares regression analyses were conducted to assess the relationship between identified reliable convergent patterns of multimodality and neurotransmitter/transcriptome, using prior molecular imaging and brain-wide gene expression. STUDY RESULTS: In total, 203 experiments comprising 10 613 patients and 10 461 healthy controls were included. Multimodal meta-analysis showed that brain regions of significant convergence in schizophrenia were mainly distributed in the frontotemporal cortex, anterior cingulate cortex, insula, thalamus, striatum, and hippocampus. Interestingly, the analyses of illness-duration subgroups identified aberrant functional and structural evolutionary patterns: Lines from the striatum to the cortical core networks to extensive cortical and subcortical regions. Subsequently, we found that these robust multimodal neuroimaging abnormalities were associated with multiple neurobiological abnormalities, such as dopaminergic, glutamatergic, serotonergic, and GABAergic systems. CONCLUSIONS: This work links transcriptome/neurotransmitters with reliable structural and functional signatures of brain abnormalities underlying disease effects in schizophrenia, which provides novel insight into the understanding of schizophrenia pathophysiology and targeted treatments.

Asunto(s)

Esquizofrenia , Humanos , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/genética , Imagen por Resonancia Magnética/métodos , Transcriptoma , Encéfalo , Neuroimagen

RESUMEN

BACKGROUND: Structural maintenance of chromosomes protein 1 A (SMC1A) is a crucial subunit of the cohesion protein complex and plays a vital role in cell cycle regulation, genomic stability maintenance, chromosome dynamics. Recent studies demonstrated that SMC1A participates in tumorigenesis. This reseach aims to explore the role and the underlying mechanisms of SMC1A in gastric cancer (GC). MATERIALS AND METHODS: RT-qPCR and western blot were used to examine the expression levels of SMC1A in GC tissues and cell lines. The role of SMC1A on GC cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) were analyzed. Furthermore,the mechanism of SMC1A action was investigated. RESULTS: SMC1A was highly expressed in GC tissues and cell lines. The high expression of SMC1A indicated the poor overall survival of GC patients from Kaplan-Meier Plotter. Enhancing the expression of SMC1A in AGS cells remarkably promoted cell proliferation in vitro and in vivo, migration and invasion, Conversely, knockdown of SMC1A in HGC27 cells inhibited cell proliferation, migration and invasion. Moreover, it's observed that SMC1A promoted EMT and malignant cell behaviors via regulating SNAIL. CONCLUSION: Our study revealed that SMC1A promotes EMT process by upregulating SNAIL, which contributes to gastric cancer cell proliferation, migration and invasion. Therefore, targeting SMC1A may be a potential strategy to improve GC therapy.

Asunto(s)

Proteínas Cromosómicas no Histona , Transición Epitelial-Mesenquimal , Neoplasias Gástricas , Humanos , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Invasividad Neoplásica , Neoplasias Gástricas/patología , Proteínas Cromosómicas no Histona/genética

RESUMEN

Introduction: Bone tissue engineering is a promising method to treat bone defects. However, the current methods of preparing composite materials that mimic the complex structure and biological activity of natural bone are challenging for recruitment of bone marrow mesenchymal stem cells (BMSCs), which affects the application of these materials in situ bone regeneration. Hollow hydroxyapatite microspheres (HHMs) possess a natural porous bone structure, good adsorption, and slow release of chemokines, but have low ability to recruit BMSCs and induce osteogenesis. In this study, The HHM/chitosan (CS) and recombinant human C-X-C motif chemokine ligand 13 (rhCXCL13)-HHM/CS biomimetic scaffolds that optimize bone regeneration and investigated their mechanism of BMSC recruitment and osteogenesis through cell and animal experiments and transcriptomic sequencing. Methods: Evaluate the physical characteristics of the HHM/CS and rhCXCL13-HHM/CS biomimetic scaffolds through Scanning Electron Microscopy (SEM), X-Ray Diffraction (XRD), and the cumulative release curve of rhCXCL13. Transwell migration experiments and co-culture with BMSCs were conducted to study the recruitment ability and osteogenic differentiation of the scaffolds. Transcriptomic sequencing was performed to analyze the osteogenic differentiation mechanism. The osteogenesis and bone healing performance were evaluated using a rabbit radial defect model. Results: SEM demonstrated that the rhCXCL13-HHM/CS scaffold comprised hydroxyapatite microspheres in a porous three-dimensional network. The rhCXCL13 showed excellent sustained release capability. The rhCXCL13-HHM/CS scaffold could recruit BMSCs and induce bone regeneration. Transcriptome sequencing and experimental results showed that the osteogenesis mechanism of rhCXCL13-HHM/CS was through the PI3K-AKT pathway. In vivo, the rhCXCL13-HHM/CS scaffold significantly promoted osteogenesis and angiogenesis at 12 weeks after surgery. Conclusion: The rhCXCL13-HHM/CS scaffold demonstrates excellent potential for BMSC recruitment, osteogenesis, vascularized tissue-engineered bone reconstruction, and drug delivery, providing a theoretical basis for material osteogenesis mechanism study and promising clinical applications for treating large bone defects.

Asunto(s)

Quitosano , Osteogénesis , Animales , Humanos , Conejos , Durapatita/farmacología , Durapatita/química , Andamios del Tejido/química , Microesferas , Ligandos , Fosfatidilinositol 3-Quinasas , Regeneración Ósea , Ingeniería de Tejidos/métodos , Diferenciación Celular

RESUMEN

BACKGROUND: Schizophrenia is characterized by complex psychiatric symptoms and unclear pathological mechanisms. Most previous studies have focused on the morphological changes that occur over the development of the disease; however, the corresponding functional trajectories remain unclear. In the present study, we aimed to explore the progressive trajectories of patterns of dysfunction after diagnosis. METHODS: Eighty-six patients with schizophrenia and 120 healthy controls were recruited as the discovery dataset. Based on multiple functional indicators of resting-state brain functional magnetic resonance imaging, we conducted a duration-sliding dynamic analysis framework to investigate trajectories in association with disease progression. Neuroimaging findings were associated with clinical symptoms and gene expression data from the Allen Human Brain Atlas database. A replication cohort of patients with schizophrenia from the University of California, Los Angeles, was used as the replication dataset for the validation analysis. RESULTS: Five stage-specific phenotypes were identified. A symptom trajectory was characterized by positive-dominated, negative ascendant, negative-dominated, positive ascendant, and negative surpassed stages. Dysfunctional trajectories from primary and subcortical regions to higher-order cortices were recognized; these are associated with abnormal external sensory gating and a disrupted internal excitation-inhibition equilibrium. From stage 1 to stage 5, the importance of neuroimaging features associated with behaviors gradually shifted from primary to higher-order cortices and subcortical regions. Genetic enrichment analysis identified that neurodevelopmental and neurodegenerative factors may be relevant as schizophrenia progresses and highlighted multiple synaptic systems. CONCLUSIONS: Our convergent results indicate that progressive symptoms and functional neuroimaging phenotypes are associated with genetic factors in schizophrenia. Furthermore, the identification of functional trajectories complements previous findings of structural abnormalities and provides potential targets for drug and non-drug interventions in different stages of schizophrenia.

Asunto(s)

Imagen por Resonancia Magnética , Esquizofrenia , Humanos , Imagen por Resonancia Magnética/métodos , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/genética , Encéfalo/patología , Progresión de la Enfermedad