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We recently expanded the viral genomic surveillance program in Minnesota, USA, to include human respiratory syncytial virus. We performed whole-genome sequencing of 575 specimens collected at Minnesota healthcare facilities during July 2023-February 2024. Subgroups A and B differed in their genomic landscapes, and we identified 23 clusters of genetically identical genomes.
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Genoma Viral , Filogenia , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Secuenciación Completa del Genoma , Humanos , Minnesota/epidemiología , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones por Virus Sincitial Respiratorio/virología , Virus Sincitial Respiratorio Humano/genética , Virus Sincitial Respiratorio Humano/aislamiento & purificación , Lactante , Genómica/métodos , Preescolar , Niño , Epidemiología Molecular , Historia del Siglo XXIRESUMEN
Introduction: Varicocele is a dilatation of the internal spermatic vein and it is generally recognized as one cause of male infertility. This study aimed to analyze the roles of activating transcription factor 6 (ATF-6) in experimental varicocele-induced epididymal epithelial cells. Methods: Experimental left varicocele was established in rats through partial left renal vein ligation. At 8 weeks after surgery, the left epididymal damage was observed using H&E and TUNEL staining. The expressions of neutral α-glucosidase (NAG), ATF-6, tumor necrosis factor (TNF)-α, and phospho-nuclear factor (p-NF)-κB p65 (S536) in the left epididymis were measured by immunohistochemistry. ATF-6 silence in rat epididymal epithelial cells was established by ATF-6 siRNA transfection. The cells were treated with hypoxia for 24 h, and cell viability was measured by CCK-8, levels of NAG, TNF-α, and interleukin (IL)-8 in cells were measured by ELISA, levels of p-NF-κB p65 (S536)/NF-κB p65 protein in cells were measured by Western blotting. Results: The results showed that the experimental left varicocele induced hypertrophy and apoptosis of epididymal epithelial cells (p<0.05), and decreased the expressions of NAG in the epididymal epithelial cells compared with the sham-operated control rats (p<0.01). Meanwhile, the expressions of ATF-6, TNF-α, and p-NF-κB p65 (S536) were increased in the epididymal epithelial cells after the experimental left varicocele compared with the sham-operated control rats (p<0.05). In the hypoxia-treated cells, ATF-6 silence increased the cell viability and decreased the levels of TNF-α, IL-8, and p-NF-κB p65 (S536) compared with the control cells (p<0.05). Discussion: The ATF-6 pathway was activated in a rat's left varicocele-induced epididymal damage. Inhibition of the ATF-6 pathway might be a possible novel therapeutic approach for left varicocele-induced epididymal damage.
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Osteoporosis is a chronic metabolic disease that increases bone fragility and, leads to severe osteoporotic fractures. In recent years, the use of high-throughput omics to explore physiological and pathological biomarkers related to bone metabolism has gained popularity. In this review, we first briefly review the technical approaches of proteomics. Additionally, we summarize the relevant literature in the last decade to provide a comprehensive overview of advances in human proteomics related to osteoporosis. We describe the specific roles of various proteins related to human bone metabolism, highlighting their potential as biomarkers for risk assessment, early diagnosis and disease course monitoring in osteoporosis. Finally, we outline the main challenges currently faced by human proteomics in the field of osteoporosis and offer suggestions to address these challenges, to inspire the search for novel osteoporosis biomarkers and a foundation for their clinical translation. In conclusion, proteomics is a powerful tool for discovering osteoporosis-related biomarkers, which can not only provide risk assessment, early diagnosis and disease course monitoring, but also reveal the underlying mechanisms of disease and provide key information for personalized treatment. The translational potential of this article: This review provides an insightful summary of recent human-based studies on osteoporosis-associated proteomics, which can aid the search for novel osteoporosis biomarkers based on human proteomics and the clinical translation of research results.
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OBJECTIVE: Ginsenoside Rh1 (G-Rh1) has been confirmed to inhibit the growth of breast cancer and colon cancer, but its therapeutic effect on hepatocellular carcinoma (HCC) is unclear. This study investigates the therapeutic effect of G-Rh1 on HCC as well as the underlying mechanism. METHODS: Bioinformatics methods were used to analyze glucocorticoid receptor (GR) expression and the tumor microenvironment in HCC tissues from HCC patients. The effect of G-Rh1 on HCC cells was investigated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. The therapeutic effect of G-Rh1 was investigated in vivo using subcutaneous transplantation models in C57BL/6J and nude mice. Additionally, the proportion of infiltrating immune cells in tumors was analyzed using flow cytometry, the GR and major histocompatibility complex class-I (MHC-I) expression of HCC cells after G-Rh1 treatment was analyzed using Western blotting, and G-Rh1-treated Hepa1-6 cells were cocultured with bone marrow-derived dendritic cells and B3Z T cells to further analyze the ability of G-Rh1 to induce dendritic cell (DC) maturation and CD8+ T cell activation. RESULTS: GR expression was upregulated in HCC tissues, and high GR expression was associated with a worsened immune microenvironment. In vitro studies showed that G-Rh1 had no significant effect on the proliferation of HCC cells, while in vivo studies showed that G-Rh1 exerted antitumor effects in C57BL/6J mice but not in nude mice. Further research revealed that G-Rh1 ameliorated the immunosuppressive tumor microenvironment, thereby enhancing the antitumor effects of lenvatinib by increasing the infiltration of CD8+ T cells, mature DCs, and MHC-I-positive cells. MHC-I was upregulated by G-Rh1 via GR suppression. Moreover, overexpression of GR abolished the G-Rh1-mediated promotion of MHC-I expression in Huh7 cells, as well as the maturation of DCs and the activation of CD8+ T cells. CONCLUSION: G-Rh1 can regulate the immune microenvironment of HCC by targeting GR, thus increasing the antitumor effect of lenvatinib. Please cite this article as: Wang XH, Fu YL, Xu YN, Zhang PC, Zheng TX, Ling CQ, Feng YL. Ginsenoside Rh1 regulates the immune microenvironment of hepatocellular carcinoma via the glucocorticoid receptor. J Integr Med. 2024; Epub ahead of print.
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Fragile X syndrome (FXS), the leading genetic cause of intellectual disability, arises from FMR1 gene silencing and loss of the FMRP protein. N6-methyladenosine (m 6 A) is a prevalent mRNA modification essential for post-transcriptional regulation. FMRP is known to bind to and regulate the stability of m 6 A-containing transcripts. However, how loss of FMRP impacts on transcriptome-wide m 6 A modifications in FXS patients remains unknown. To answer this question, we generated cortical neurons differentiated from induced pluripotent stem cells (iPSC) derived from healthy subjects and FXS patients. In electrophysiology recordings, we validated that synaptic and neuronal network defects in iPSC-derived FXS neurons corresponded to the clinical EEG data of the patients from which the corresponding iPSC line was derived. In analysis of transcriptome-wide methylation, we show that FMRP deficiency led to increased translation of m 6 A writers, resulting in hypermethylation that primarily affecting synapse-associated transcripts and increased mRNA decay. Conversely, in the presence of an m 6 A writer inhibitor, synaptic defects in FXS neurons were rescued. Taken together, our findings uncover that an FMRP-dependent epi-transcriptomic mechanism contributes to FXS pathogenesis by disrupting m 6 A modifications in FXS, suggesting a promising avenue for m 6 A-targeted therapies.
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Introduction: The aim of this research was to clarify the mechanism through which baicalin exerts its inhibitory effects on Aeromonas hydrophila infection. Methods: The antibacterial efficacy of baicalin was assessed by determining its minimum inhibitory concentration (MIC) against A. hydrophila. Various parameters, including the growth curve, cell wall integrity, biofilm formation, AKP content, and morphological alterations of A. hydrophila, were analyzed. In vivo experiments involved the administration of A. hydrophila 4 h postintraperitoneal injection of varying doses of baicalin to induce infection, with subsequent monitoring of mortality rates. After a 3 d period, liver, spleen, and intestinal tissues were harvested to evaluate organ indices, antioxidant and immune parameters, as well as intestinal microbial composition. Results: The findings indicated that baicalin treatment resulted in the disruption of the cell wall of A. hydrophila, leading to the loss of its normal structural integrity. Furthermore, baicalin significantly inhibited biofilm formation and facilitated the release of intracellular proteins (P < 0.05). In vivo, baicalin enhanced the survival rates of yellow catfish infected with A. hydrophila. Compared to the control group, the liver index of yellow catfish was elevated, while the spleen and intestinal indices were reduced in the baicalin-treated group (P < 0.05). Additionally, baicalin at an appropriate dosage was found to increase levels of SOD, GSH, CAT, ACP, and AKP in yellow catfish (P < 0.05), while simultaneously decreasing MDA accumulation and the mRNA expression of inflammatory markers such as Keap1, IL1, IFN-γ, and TNF-α, (P < 0.05). Moreover, baicalin significantly enhanced the operational taxonomic unit (OTU) count in A. hydrophila-infected yellow catfish (P < 0.05), restoring the abundance of Barnesiellaceae, Enterobacteriaceae, Plesiomonas, and UBA1819 (P < 0.05). Discussion: In summary, baicalin demonstrates the potential to improve the survival rate of yellow catfish subjected to A. hydrophila infection, augment antioxidant and immune responses, mitigate inflammation, and enhance intestinal microbial diversity.
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In the macro context of global climate change, given the profound challenges that the intensifying greenhouse effect poses to global ecological balance and sustainable economic and social development, the role of foreign direct investment (FDI) is increasingly acknowledged, particularly regarding its dual impact on the environment: while serving as a catalyst for economic growth, it might also exacerbate carbon emissions in host countries. This paper focuses on the panel data of 11 provinces and cities in the western region (excluding Xizang) from 2006 to 2021, calculates the implied carbon of foreign-invested enterprises in the western region, and explores the relationship between the implied carbon of foreign-invested enterprises in the western region and the economic development of the western region. The results indicate that from 2006 to 2021, the implied net carbon value of import and export trade of foreign-invested enterprises in the western region was greater than zero and roughly exhibited an upward trend year by year. FDI has an environmental deficit in terms of carbon emissions in the western region; FDI in the western region has a significant positive effect on the implied carbon emissions in import and export trade; The GDP of the western region has a significant positive effect on the implied carbon emissions of import and export trade. Therefore, this article puts forward corresponding suggestions from five aspects: policy incentives and regulatory constraints, technology research and innovation drive, clean energy development and resource recycling, international cooperation and regional linkage, and public awareness enhancement and cultural advocacy.
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Phosphotungstic acid (HPW) can retain water in proton exchange membranes to increase proton conductivity; however, its water-soluble nature limits further application. In this work, we combined HPW and graphitic carbon nitride (g-C3N4) via sintering to prepare water-insoluble hybrids (HWN), where HPW was chemically linked to g-C3N4 to fix HPW. Then, HWN fillers were added to a sulfonated polyether ether ketone (SPEEK) matrix to prepare composite membranes. The conductivity of the composite membrane with 10 wt% HWN is up to 0.066 S cm-1 at room temperature, which is 53% higher than that of the SPEEK control membrane (0.043 S cm-1). The composite membrane also showed stable proton conductivity after being immersed in water for 2000 h. Therefore, our study demonstrates that preparing water-insoluble nanofillers containing HPW components through sintering is a promising approach.
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Dynamic wetting in confined spaces is pivotal for the functional efficiency of biological organisms and offers significant potential for optimizing microdevices. The fluids encountered in such scenarios often exhibit shear-thinning behavior, which gives rise to complex interfacial phenomena. Here, we present an intriguing wetting phenomenon for shear-thinning fluids in confined capillary spaces. The employed shear-thinning fluids, carboxymethyl cellulose aqueous solutions with mass fractions of 0.5, 1.0, and 1.5 wt %, exhibit an intermediate state between ideal viscoelastic liquids, viscoelastic solids, and gel-like properties. We elucidate the geometric effect on its capillary wetting behavior, demonstrating that distortion of the moving contact line alters flow dynamics near the front corner, modifying the viscous resistance. This intricate interplay between the modified viscous resistance and the driving force results in a novel dynamic equilibrium distinct from that in Newtonian fluids. We further reveal that the viscous resistance in confined capillaries is controlled by both the morphology of the moving contact line and the shear-thinning exponent, particularly within the range of 0.7 to 1. This novel mechanism provides a pathway for manipulating the wetting dynamics of complex fluids in confined spaces.
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The Dung Beetle Optimization (DBO) algorithm, a well-established swarm intelligence technique, has shown considerable promise in solving complex engineering design challenges. However, it is hampered by limitations such as suboptimal population initialization, sluggish search speeds, and restricted global exploration capabilities. To overcome these shortcomings, we propose an enhanced version termed Adaptive Spiral Strategy Dung Beetle Optimization (ADBO). Key enhancements include the application of the Gaussian Chaos strategy for a more effective population initialization, the integration of the Whale Spiral Search Strategy inspired by the Whale Optimization Algorithm, and the introduction of an adaptive weight factor to improve search efficiency and enhance global exploration capabilities. These improvements collectively elevate the performance of the DBO algorithm, significantly enhancing its ability to address intricate real-world problems. We evaluate the ADBO algorithm against a suite of benchmark algorithms using the CEC2017 test functions, demonstrating its superiority. Furthermore, we validate its effectiveness through applications in diverse engineering domains such as robot manipulator design, triangular linkage problems, and unmanned aerial vehicle (UAV) path planning, highlighting its impact on improving UAV safety and energy efficiency.
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OBJECTIVE: Hip fracture (HF) has been described as the "last fracture of life" in the elderly, so the assessment of HF risk is extremely important. Currently, few studies have examined the relationship between imaging data from chest computed tomography (CT) and HF. This study demonstrated that pectoral muscle index (PMI) and vertebral body attenuation values could predict HF, aiming to opportunistically assess the risk of HF in patients without bone mineral density (BMD) based on chest CT for other diseases. METHODS: In the retrospective study, 800 participants who had both BMD and chest CT were enrolled from January 2021 to January 2024. After exclusion, 472 patients were finally enrolled, divided into the healthy control (HC) group and the HF group. Clinical data were collected, and differences between the two groups were compared. A predictive model was constructed based on the PMI and CT value of the fourth thoracic vertebra (T4HU) by logistic regression analysis, and the predictive effect of the model was analyzed by using the receiver operating characteristic (ROC) curve. Finally, the clinical utility of the model was analyzed using decision curve analysis (DCA) and clinical impact curves. RESULTS: Both PMI and T4HU were lower in the HF group than in the HC group (p < 0.05); low PMI and low T4HU were risk factors for HF. The predictive model incorporating PMI and T4HU on the basis of age and BMI had excellent diagnostic efficacy with an area under the curve (AUC) of 0.865 (95% confidence interval [CI]: 0.830-0.894, p < 0.01), sensitivity and specificity of 0.820 and 0.754, respectively. The clinical utility of the model was validated using calibration curves and DCA. The AUC of the predictive model incorporating BMD based on age and BMI was 0.865 (95% CI: 0.831-0.895, p < 0.01), with sensitivity and specificity of 0.698 and 0.711, respectively. There was no significant difference in diagnostic efficacy between the two models (p = 0.967). CONCLUSIONS: PMI and T4HU are predictors of HF in patients. In the absence of dual-energy x-ray absorptiometry (DXA), the risk of HF can be assessed by measuring the PMI and T4HU on chest CT examination due to other diseases, and further treatment can be provided in time to reduce the incidence of HF.
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Considering the dilemma of obtaining economic and high-performance composites based on non-polar and main-chain-saturated ethylene propylene diene monomer rubber (EPDM), we proposed an effective and universal filler modification and nanocomposite preparation method. Specifically, the montmorillonite (MMT) surface was coated with polydopamine (PDA) to obtain DMMT, which was confirmed by XRD, XPS, FTIR, and TGA. After compounding DMMT gel with the solid EPDM via the gel compounding method, a silane coupling agent, vinyltrimethoxysilane, was introduced to construct covalent interactions between rubber and filler. Compared with the unmodified MMT filler EPDM, the EPDM/DMMT nanocomposite showed much fewer filler aggregates in the matrix. The highest tensile strength of the composites reached 6.5 MPa with 10 phr DMMT, almost 200% higher than that of pure EPDM.
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OBJECTIVE: To evaluate the long-term outcomes of subtotal hemispherotomy (SH) in treating drug-resistant epilepsy caused by unilateral hemispheric lesions and try to give the prognostic factors for these outcomes. METHODS: We retrospectively reviewed the clinical data of 19 patients who underwent SH in Sanbo Brain Hospital, Capital Medical University, Beijing, China, from May 2008 to April 2021. All clinical data and factors related to surgical and functional outcomes, including motor, neuropsychiatric, and language function, were collected and analyzed. RESULTS: The surgical outcomes showed 13 (68â¯%) patients were seizure-free at the last follow-up (2-14 years, mean: 5.6±2.9). No changes were found in motor outcomes in 12 (63â¯%) patients; seven (37â¯%) patients had new permanent motor deficits (NPMD). Improvement in the full-scale intelligence quotient (FIQ) (p = 0.009) was observed. Univariate analysis found that patients who did not achieve seizure freedom had a significantly older age at surgery (p = 0.017) and acute post-operative seizures (APOS) (p = 0.046). Kaplan-Meier analysis also identified significant differences in seizure outcomes between the children and adult subgroups (p = 0.0017). Multivariate Cox analysis showed that older age at surgery (HR=1.055, p = 0.034) was associated with shorter time-to-seizure-recurrence. Resection of the central operculum and insula (OR= 80.433, p =0.031) and higher monthly seizure frequency (OR= 1.073, p = 0.040) were also poor prognostic factors for motor function outcomes. CONCLUSION: SH is an effective treatment procedure in treating patients with drug-resistant epilepsy caused by hemispheric lesions with satisfied seizure outcomes, limited impairment of motor function, and preserving neuropsychiatric outcomes.
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Epilepsia Refractaria , Hemisferectomía , Humanos , Epilepsia Refractaria/cirugía , Masculino , Femenino , Hemisferectomía/métodos , Estudios Retrospectivos , Niño , Adolescente , Resultado del Tratamiento , Adulto , Preescolar , Adulto Joven , Estudios de Cohortes , Estudios de SeguimientoRESUMEN
AIM: Pancreatic ductal adenocarcinoma (PAAD) is recognized as an exceptionally aggressive cancer that both highly lethal and unfavorable prognosis. The mitochondrial metabolism pathway is intimately involved in oncogenesis and tumor progression, however, much remains unknown in this area. In this study, the bioinformatic tools have been used to construct a prognostic model with mitochondrial metabolism-related genes (MMRGs) to evaluate the survival, immune status, mutation profile, and drug sensitivity of PAAD patients. METHOD: Univariate Cox regression and LASSO regression were used to screen the differentially expressed genes (DEGs), and multivariate Cox regression was used to develop the risk model. Kaplan-Meier estimator was employed to identify MMRGs signatures associated with overall survival (OS). ROC curves were utilized to evaluate the model's performance. Maftools, immunedeconv and CIBERSORT R packages were applied to analyze the gene mutation profiles and immune status. The corresponding sensitivity to pharmaceutical agents was assessed using oncoPredict R packages. RESULTS: A prognostic model with five MMRGs was developed, which defined the patients as high-risk showed lower survival rates. There was good consistency among individuals categorized as high-risk, showing elevated rates of genetic alterations, particularly in the TP53 and KRAS genes. Furthermore, these patients exhibited increased levels of immunosuppression, characterized by an increased presence of macrophages, neutrophils, Th2 cells, and regulatory T cells. Additionally, high-risk patients showed increased sensitivity to Sabutoclax and Venetoclax. CONCLUSION: By utilizing a gene signature associated with mitochondrial metabolism, a prognostic model has been established which could be a highly efficient method for predicting the outcomes of PAAD patients.
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Objective: This study aims to systematically evaluate the efficacy of bone marrow mesenchymal stem cell-derived exosomes (BMSCs-Exo) in improving spinal cord injury (SCI) to mitigate the risk of translational discrepancies from animal experiments to clinical applications. Methods: We conducted a comprehensive literature search up to March 2024 using PubMed, Embase, Web of Science, and Scopus databases. Two researchers independently screened the literature, extracted data, and assessed the quality of the studies. Data analysis was performed using STATA16 software. Results: A total of 30 studies were included. The results indicated that BMSCs-Exo significantly improved the BBB score in SCI rats (WMD = 3.47, 95% CI [3.31, 3.63]), inhibited the expression of the pro-inflammatory cytokine TNF-α (SMD = -3.12, 95% CI [-3.57, -2.67]), and promoted the expression of anti-inflammatory cytokines IL-10 (SMD = 2.76, 95% CI [1.88, 3.63]) and TGF-ß (SMD = 3.89, 95% CI [3.02, 4.76]). Additionally, BMSCs-Exo significantly reduced apoptosis levels (SMD = -4.52, 95% CI [-5.14, -3.89]), promoted the expression of axonal regeneration markers NeuN cells/field (SMD = 3.54, 95% CI [2.65, 4.42]), NF200 (SMD = 4.88, 95% CI [3.70, 6.05]), and the number of Nissl bodies (SMD = 1.89, 95% CI [1.13, 2.65]), and decreased the expression of astrogliosis marker GFAP (SMD = -5.15, 95% CI [-6.47, -3.82]). The heterogeneity among studies was primarily due to variations in BMSCs-Exo transplantation doses, with efficacy increasing with higher doses. Conclusion: BMSCs-Exo significantly improved motor function in SCI rats by modulating inflammatory responses, reducing apoptosis, inhibiting astrogliosis, and promoting axonal regeneration. However, the presence of selection, performance, and detection biases in current animal experiments may undermine the quality of evidence in this study.
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The predatory gall midge, Aphidoletes aphidimyza (Rondani), and tobacco aphid cocoon wasp, Aphidius gifuensis Ashmead, are important natural enemies of Myzus persicae (Sulzer) (Hemiptera: Aphididae). Predation by A. aphidimyza and A. gifuensis can regulate M. persicae; however, how interspecific interference competition affects their foraging efficiency is unknown. Here, we investigated the consumption and parasitization abilities of A. aphidimyza 3rd instar larva and A. gifuensis adults under various conditions. Consumption of parasitized aphids by A. aphidimyza 3rd instar larvae was significantly lower than that of nonparasitized controls, with a substantial increase in handling time. The presence of A. gifuensis adults did not significantly affect the predation capacity of A. aphidimyza larvae. Relative to controls, A. aphidimyza larvae predation trace (PT) and imago activity significantly decreased A. gifuensis parasitism rates at different aphid densities. Further, A. aphidimyza larvae PT increased the A. gifuensis handling time of M. persicae, whereas the presence of A. aphidimyza adults had the opposite effect. Coexistence with heterospecific natural enemies reduced the parasitic capacity of A. gifuensis, whereas A. aphidimyza larvae predation capability was influenced to a lesser extent. Our results demonstrate that intraguild interactions strongly influence the predatory and parasitic efficacy of A. aphidimyza and A. gifuensis, although the effect on A. gifuensis was more pronounced. For effective biological control of M. persicae using A. aphidimyza and A. gifuensis, we recommend releasing A. aphidimyza first to mitigate intraguild predation and enhance the overall success of the pest control program.
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Áfidos , Dípteros , Larva , Control Biológico de Vectores , Conducta Predatoria , Avispas , Animales , Avispas/fisiología , Larva/fisiología , Larva/crecimiento & desarrollo , Áfidos/fisiología , Áfidos/parasitología , Dípteros/fisiología , Cadena Alimentaria , Especificidad de la EspecieRESUMEN
Natural rubber (NR) composites have been widely applied in damping products to reduce harmful vibrations, while rubber with only a single composition barely meets performance requirements. In this study, rubber blend composites including various ratios of NR and styrene butadiene rubber (SBR) were prepared via the conventional mechanical blending method. The effects of the rubber components on the compression set, compression fatigue temperature rising and the thermal oxidative aging properties of the NR/SBR blend composites were investigated. Meanwhile, the dynamic mechanical thermal analyzer and rubber processing analyzer were used to characterize the dynamic viscoelasticity of the NR/SBR blend composites. It was shown that, with the increase in the SBR ratio, the vulcanization rate of the composites increased significantly, while the compression fatigue temperature rising of the composites decreased gradually from 47 °C (0% SBR ratio) to 31 °C (50% SBR ratio). The compression set of the composites remained at ~33% when the SBR ratio was no more than 20%, and increased gradually when the SBR ratio was more than 20%.
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Poly(l-lactic acid) (PLLA) is a widely used U.S. Food and Drug Administration-approved implantable biomaterial that also possesses strong piezoelectricity. However, the intrinsically low stability of its high-energy piezoelectric ß phase and random domain orientations associated with current synthesis approaches remain a critical roadblock to practical applications. Here, we report an interfacial anchoring strategy for fabricating core/shell PLLA/glycine (Gly) nanofibers (NFs) by electrospinning, which show a high ratio of piezoelectric ß phase and excellent orientation alignment. The self-assembled core/shell structure offers strong intermolecular interactions between the -OH groups on Gly and C=O groups on PLLA, which promotes the crystallization of oriented PLLA polymer chains and stabilizes the ß phase structure. As-received core/shell NFs exhibit substantially enhanced piezoelectric performance and excellent stability. An all NF-based nonwoven fabric is fabricated and assembled as a flexible nanogenerator. The device offers excellent conformality to heavily wrinkled surfaces and thus can precisely detect complex physiological motions often found from biological organs.
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Materiales Biocompatibles , Nanofibras , Poliésteres , Nanofibras/química , Materiales Biocompatibles/química , Poliésteres/química , Prótesis e Implantes , Textiles , Glicina/químicaRESUMEN
OBJECTIVE: To summarize the surgical outcomes of genetically refractory epilepsy and identify prognostic factors for these outcomes. METHODS: A literature search of the PubMed, Web of Science, and Embase databases for relevant studies, published between January 1, 2002 and December 31, 2023, was performed using specific search terms. All studies addressing surgical outcomes and follow-up of genetically refractory epilepsy were included. All statistical analyses were performed using STATA software (StataCorp LLC, College Station, TX, USA). This review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, 2020 (i.e., "PRISMA") reporting guidelines. RESULTS: Of the 3833 studies retrieved, 55 fulfilled the inclusion criteria. Eight studies were eligible for meta-analysis at the study level. Pooled outcomes revealed that 74 % of patients who underwent resective surgery (95 % confidence interval [CI] 0.55-0.89; z = 9.47, p < 0.05) achieved Engel I status at the last follow-up. In the study level analysis, pooled outcomes revealed that 9 % of patients who underwent vagus nerve stimulation achieved seizure-free status (95 % CI 0.00-0.31; z = 1.74, p < 0.05), and 61 % (95 % CI 0.55-0.89; z = 11.96, p < 0.05) achieved a 50 % reduction in seizure frequency at the last follow-up. Fifty-three studies comprising 249 patients were included in an individual-level analysis. Among patients who underwent lesion resection or lobectomy/multilobar resection, 65 % (100/153) achieved Engel I status at the last follow-up. Univariate analysis indicated that female sex, somatic mutations, and presenting with focal seizure symptoms were associated with better prognosis (p < 0.05). Additionally, 75 % (21/28) of patients who underwent hemispherectomy/hemispherotomy achieved Engel I status at the last follow-up. In the individual-level analysis, among patients treated with vagus nerve stimulation, 21 % (10/47) were seizure-free and 64 % (30/47) experienced >50 % reduction in seizure frequency compared with baseline. CONCLUSION: Meticulous presurgical evaluation and selection of appropriate surgical procedures can, to a certain extent, effectively control seizures. Therefore, various surgical procedures should be considered when treating patients with genetically refractory epilepsy.
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Epilepsia Refractaria , Humanos , Epilepsia Refractaria/cirugía , Epilepsia Refractaria/genética , Resultado del Tratamiento , Procedimientos Neuroquirúrgicos , Estimulación del Nervio VagoRESUMEN
Objective: Curcumin, a phenolic compound extracted from turmeric rhizomes, exhibits antitumour effects in preclinical models of tumours. However, its mechanism of action in prostate cancer remains unclear. Exploring the molecular mechanisms of curcumin in prostate cancer based on network pharmacology and molecular docking provides a new theoretical basis for prostate cancer treatment. Method: Using tools such as PharmMapper, SuperPred, TargetNet, and SwissTargetPrediction, we obtained information on curcumin-related targets. We comprehensively collected prostate cancer-related targets from several databases, including GeneCards, CTD, DisGeNET, OMIM, and PharmGKB. Cross-cutting drug-disease targets were then derived by screening using the Venny 2.1.0 tool. Subsequently, we used the DAVID platform to perform in-depth GO and KEGG enrichment analyses of the drug-disease-shared targets. To construct a PPI network map of the cross-targets and screen the 10 core targets, we combined the STRING database and Cytoscape 3.7.2. Molecular docking experiments were performed using AutoDockTools 1.5.7 software. Finally, we used several databases such as GEPIA, HPA, cBioPortal, and TIMER to further analyse the screened core targets in detail. Result: We identified 307 key targets of curcumin in cancer treatment. After GO functional enrichment analysis, we obtained 1119 relevant entries, including 782 biological progression (BP) entries, 112 cellular component (CC) entries, and 225 molecular function (MF) entries. In addition, KEGG pathway enrichment analysis revealed 126 signalling pathways, which were mainly involved in the cancer pathway, such as lipid and atherosclerosis pathway, PI3K-Akt signal pathway, MAPK signal pathway, Ras signal pathways, and chemical carcinogenesis-reactive oxygen species. By applying Cytoscape 3.7.2 software, we identified SRC, PIK3R1, STAT3, AKT1, HSP90AA1, ESR1, EGFR, HSP90AB1, MAPK8, and MAPK1 as core targets. Molecular docking experiments showed that the binding energies of curcumin to these core targets were all below -1.85 kJ mol-1, which fully demonstrated that curcumin could spontaneously bind to these core targets. Finally, these results were validated at multiple levels, including mRNA expression, protein expression, and immune infiltration. Conclusion: Through in-depth network pharmacology and molecular docking studies, we have found that curcumin may have anticancer potential by upregulating the expression of PIK3R1 and STAT3, and downregulating the binding ability of molecules such as SRC, AKT1, HSP90AA1, ESR1, EGFR, HSP90AB1, MAPK8, and MAPK1. In addition, curcumin may interfere with the cyclic process of prostate cancer cells by inhibiting key signalling pathways such as the PI3K-Akt signalling pathway, MAPK signalling pathway, and Ras, thereby inhibiting their growth. This study not only reveals the potential molecular mechanism of curcumin in the treatment of prostate cancer but also provides an important theoretical basis for subsequent research.