The role of PD-L1 in patients with non-small cell lung cancer receiving neoadjuvant immune checkpoint inhibitor plus chemotherapy: a meta-analysis.

BACKGROUND: The use of immune checkpoint inhibitors (ICIs) as neoadjuvant therapy is a promising novel approach in resectable non-small-cell lung cancer (NSCLC). This study aimed to investigate the prognostic value of PD-L1 in patients with NSCLC receiving neoadjuvant immune checkpoint inhibitor plus chemotherapy (CT). MATERIALS AND METHODS: Several databases (PubMed, Embase, and cochrane central register of controlled trials [CENTRAL]) were systematically searched. Randomized controlled trials (RCTs) investigating pathological and survival outcomes with neoadjuvant ICI + CT versus CT alone in NSCLC were analyzed. RESULTS: Overall, eight RCTs (n = 3,404) were included. The analyses showed neoadjuvant ICI + CT significantly improved complete pathological response (pCR) and event-free survival (EFS) in either tumor PD-L1 < 1%, ≥ 1%, 1-49%, or ≥ 50% population (both p < 0.0001) compared with neoadjuvant CT alone. The overall survival (OS) data are not yet mature among all included RCTs, and only three RCTs presented OS data by PD-L1 status of patients. The pooled OS favored neoadjuvant ICI + CT in the PD-L1 ≥ 1% population (hazard ratio [HR], 0.45; 95% CI, 0.31-0.65; p < 0.0001), but not in the PD-L1 < 1% population (HR, 0.89; 95% CI, 0.66-1.19; p = 0.43). CONCLUSIONS: Compared with neoadjuvant CT alone, neoadjuvant ICI + CT significantly enhanced pCR and EFS for patients with resectable NSCLC regardless of the expression of PD-L1. It seems that only patients with PD-L1 positive tumors may achieve a better OS, but it's currently inconclusive due to immature data, so future research with long-term follow-up is still needed.

Comprehensive management of degloving soft tissue injuries of the extremity: A 12-year retrospective study.

BACKGROUND: Degloving soft tissue injuries (DSTIs) of the extremities, which are often underestimated in terms of their severity, present significant challenges to reconstructive surgeons. We propose a comprehensive management protocol to standardize the reconstructive approach, aiming for successful treatment of these devastating injuries. METHODS: We retrospectively analyzed data from consecutive patients with extremity DSTIs over a 12-year period. Patients were categorized into three age groups (0-17, 18-65, and >65 years) to highlight the different treatment options based on age. Various surgical techniques were employed depending on the injury pattern. Treatment strategies for each patient were individualized based on age, underlying conditions, and injury type. Wound healing, complications, and functional outcomes were recorded. RESULTS: Of the hospitalized patients, 20 were lost to follow-up, and 105 were included in the analysis. The mean age at the time of injury was 40 ± 44.9 years, with a mean follow-up of 30.1 ± 12.7 months. Furthermore, 19 % of patients were aged 0-17 years, 61 % were aged 18-65 years, and 20 % were aged >65 years. Treatment plans were personalized based on injury characteristics, with numerous patients being treated with a combination of multiple surgical techniques. Older patients had significantly longer wound healing times and delayed return to activities of daily living compared to the other age groups. Overall, patients were generally satisfied with their outcomes. The total complication rate was 46.7 %, with 79.5 % being categorized as major complications. Each complication was addressed with a tailored treatment plan. CONCLUSION: The management of DSTIs should be individualized, taking into account the specific characteristics of each injury. Age and medical fitness play crucial roles in determining both the surgical approach and prognosis. An accurate initial evaluation and thorough debridement are essential for optimal outcomes.

Design, Synthesis and Biological ActivitiesEvaluation of Novel Pterostilbene-urea DerivativesasPotential Anti-inflammatory Agents.

To remove the toxicity of 10-Pterostilbene methylamine hydrochloride derivatives (PMDS ． HCl) and develop novel anti-inflammatory agents, twenty-five Pterostilbene-urea derivatives (PUDs, Q1-Q25) derived from PMDs were designed, synthesized, characterized by spectroscopic techniques and their anti-inflammatory activity in vitro were evaluated. Results exhibited that compounds (Q1-Q25) were low toxic or non-toxic toward RAW264.7 and L02 cell lines at 20 µM/L. Eight bioactive agents (Q4-Q10, Q20) displayed obvious inhibition ability against LPS-induced NO release, with IC50(NO) values ranged from 9.96 to 33.89 µM/L. Meanwhile, they were potential COX-2 inhibitors with IC50(COX-2) values ranging from 39.42 to 179.84 nM/L. A roughly positive correlation were observed between the inhibitory abilities on LPS-induced NO release and those on COX-2. Q7 , Q10and Q20 manifested stronger COX-2 inhibitory abilities than Celecoxib . The strongest anti-inflammatory agent, Q20 (IC50 (NO) = 9.96 µM/L, IC50(COX-2) = 39.42 nM/L) effectively inhibited the secretion of pro-inflammatory factors such as IL-1ß (IC50 = 12.30 µM/L) and TNF-α (IC50 = 9.07 µM/L) in a dose-dependent manner. Western Blot analysis indicated that at low micromolar concentrations, Q20 obviously down-regulated the expression of COX-2, iNOS as well as TLR4 protein, and suppressed the activation of NLRP3 inflammasome and NF-κB signal pathway.

Sea cucumbers and their symbiotic microbiome have evolved to feed on seabed sediments.

Sea cucumbers are predominant deposit feeders in benthic ecosystems, providing protective benefits to coral reefs by reducing disease prevalence. However, how they receive sufficient nutrition from seabed sediments remains poorly understood. Here, we investigate Holothuria leucospilota, an ecologically significant tropical sea cucumber, to elucidate digestive mechanisms underlying marine deposit-feeding. Genomic analysis reveals intriguing evolutionary adaptation characterized by an expansion of digestive carbohydrase genes and a contraction of digestive protease genes, suggesting specialization in digesting microalgae. Developmentally, two pivotal dietary shifts, namely, from endogenous nutrition to planktonic feeding, and from planktonic feeding to deposit feeding, induce changes in digestive tract enzyme profiles, with adults mainly expressing carbohydrases and lipases. A nuanced symbiotic relationship exists between gut microbiota and the host, namely, specific resident bacteria supply crucial enzymes for food digestion, while other bacteria are digested and provide assimilable nutrients. Our study further identifies Holothuroidea lineage-specific lysozymes that are restrictedly expressed in the intestines to support bacterial digestion. Overall, this work advances our knowledge of the evolutionary innovations in the sea cucumber digestive system which enable them to efficiently utilize nutrients from seabed sediments and promote food recycling within marine ecosystems.

Multi-stage mechanisms of tumor metastasis and therapeutic strategies.

The cascade of metastasis in tumor cells, exhibiting organ-specific tendencies, may occur at numerous phases of the disease and progress under intense evolutionary pressures. Organ-specific metastasis relies on the formation of pre-metastatic niche (PMN), with diverse cell types and complex cell interactions contributing to this concept, adding a new dimension to the traditional metastasis cascade. Prior to metastatic dissemination, as orchestrators of PMN formation, primary tumor-derived extracellular vesicles prepare a fertile microenvironment for the settlement and colonization of circulating tumor cells at distant secondary sites, significantly impacting cancer progression and outcomes. Obviously, solely intervening in cancer metastatic sites passively after macrometastasis is often insufficient. Early prediction of metastasis and holistic, macro-level control represent the future directions in cancer therapy. This review emphasizes the dynamic and intricate systematic alterations that occur as cancer progresses, illustrates the immunological landscape of organ-specific PMN creation, and deepens understanding of treatment modalities pertinent to metastasis, thereby identifying some prognostic and predictive biomarkers favorable to early predict the occurrence of metastasis and design appropriate treatment combinations.

Intestinal microbiota dysbiosis contributes to the liver damage in subchronic arsenic-exposed mice.

There is an extensive amount of evidence that links changes in the intestinal microbiota structure to the progression and pathophysiology of many liver diseases. However, comprehensive analysis of gut flora dysbiosis in arsenic-induced hepatotoxicity is lacking. Herein, C57BL/6 mice are exposed to arsenic (1, 2, or 4 mg/kg) for 12 weeks, after which fecal microbiota transplantation (FMT) study is conducted to confirm the roles of the intestinal microbiome in pathology. Treatment with arsenic results in pathological and histological changes in the liver, such as inflammatory cell infiltration and decreased levels of TP and CHE but increased levels of ALP, GGT, TBA, AST, and ALT. Arsenic causes an increase in the relative abundance of Escherichia-Shigella, Klebsiella and Blautia, but a decrease in the relative abundance of Muribaculum and Lactobacillus. In arsenic-exposed mice, protein expressions of Occludin, ZO-1, and MUC2 are significantly decreased, but the level of FITC in serum is increased, and FITC fluorescence is extensively dispersed in the intestinal tract. Importantly, FMT experiments show that mice gavaged with stool from arsenic-treated mice exhibit severe inflammatory cell infiltration in liver tissues. Arsenic-manipulated gut microbiota transplantation markedly facilitates gut flora dysbiosis in the recipient mice, including an up-regulation in Escherichia-Shigella and Bacteroides, and a down-regulation in Lactobacillus and Desulfovibrio. In parallel with the intestinal microbiota wreck, protein expressions of Occludin, ZO-1, and MUC2 are decreased. Our findings suggest that subchronic exposure to arsenic can affect the homeostasis of the intestinal microbiota, induce intestinal barrier dysfunction, increase intestinal permeability, and cause damage to liver tissues in mice.

Morphology Control and Spectral Study of the 2D and Hierarchical Nanostructures Self-Assembled by the Chiral Alanine-Decorated Perylene Bisimides.

Tailoring the morphologies and optical properties of the 2D and hierarchical nanostructures self-assembled by the π-conjugated molecules is both interesting and challenging. Herein, a series of 2D ribbon-like nanostructures with single or multiple H-aggregated perylene bisimides (PBI) monolayer and hierarchical nanostructures (including straw-like, dumbbell-shaped, and rod-like nanostructures) are fabricated by solution self-assembly of three chiral alanine-decorated PBI. The influence of the solvent's dissolving capacity, the chirality of alanine, and the preparation methods on the morphologies and optical properties of the nanostructures were extensively studied. It was observed that the hierarchical nanostructures are formed by the reorganization of the 2D ribbon-like nanostructures. The size of the 2D ribbon-like nanostructures and the amount of the hierarchical nanostructures increase with the decrease in the solvent's dissolving capacity. The small chiral alanine moiety is unable to induce chirality in the nanostructures, owing to its low steric hindrance and the dominant strong π-π stacking interaction of the PBI skeleton. A weaker π-π stacking interaction and better H-aggregated arrangement of the PBI skeleton could reduce the low-wavelength fluorescence intensity. The process of heating, cooling, and aging promotes the formation of H-aggregation in the PBI skeleton. The region of spectral overlap of the PBI solutions increases with the decrease in the dissolving capacity of the solvent and the steric hindrance of the chiral alanine. This study supplies a view to tailor the morphologies and optical properties of the nanostructures, which could be used as sensors and photocatalysts.

Effect of Extracting Solvent on the Quality of Lentinula edodes Oil Based on Chemical Composition, in vitro Antioxidant Activity and Correlation Analysis.

In this study, effects of 4 solvents (petroleum-ether, n-hexane, ethyl-acetate, and chloroform) on the chemical characterizations and in vitro antioxidant capacities of oil were assessed to determine the optimal extraction solvent for L. edodes oil. Three data analysis techniques including principal component analysis, hierarchical cluster analysis, and multiple linear regression, were applied to determine the relationship between the nutrient and antioxidant capacity. The results showed that chloroform extracted L. edodes oil exhibited the largest amount of α-tocopherol, flavones, and unsaponifiable matter, chloroform was thus confirmed desirable for extracting L. edodes oil rich in nutrition. While based on the best DPPH and ABTS, the ethyl-acetate extracted oil show the strongest antioxidant property. More than that, the results also showed that different extraction solvents could induce large variations in minor components and free radical scavenging activity among the test oils, and the total phenol content was found positively correlated to the antioxidant capacity of L. edodes oil, which could be well predicted by all MLR models. These findings revealed the influence of solvent on the chemical characterization and in vitro antioxidant capacity of L. edodes oil, providing a theoretical foundation for future applications of L. edodes oil.

Vertebral marrow fat fraction is associated with circulating RANKL in postmenopausal females.

Objective: To investigate the relationship between circulating receptor activator of nuclear factor-kappa B ligand (RANKL) levels and marrow adipose tissue in postmenopausal females. Methods: A total of 164 postmenopausal females were included in the study. Serum levels of osteoprotegerin (OPG) and RANKL were measured using ELISA kits. Body composition and bone mineral density (BMD) were assessed using dual-energy X-ray absorptiometry. Complex-based chemical shift imaging-based MRI was employed to evaluate the vertebral marrow proton density fat fraction (PDFF). A multivariate linear regression model was utilized to analyze the predictive effects of PDFF and BMD on circulating levels of OPG and RANKL. Results: Simple regression analysis showed significant associations among the marrow PDFF, BMD at either site, serum RANKL, and the RANKL/OPG ratio. In multivariate linear regression models, marrow PDFF was found to have a positive correlation (ß = 3.15, 95% CI 2.60 to 3.70) and BMD had negative correlations (ß = -0.200, 95% CI -0.348 to -0.051 for vertebral BMD; ß = -0.383, 95% CI -0.589 to -0.177 for total hip BMD; and ß =-0.393, 95% CI -0.598 to -0.188 for femoral neck BMD, all p < 0.01) with circulating soluble RANKL levels after adjusting for age, body mass index, physical activity, total fat mass, android/gynoid ratio, and lean mass. Similar results were observed for the RANKL/OPG ratio. Additionally, multivariate linear regression analyses revealed that marrow PDFF was a significant independent contributor of circulating soluble RANKL (ß = 1.34, 95% CI 1.10 to 1.58, p < 0.001) after further controlling for BMD. However, marrow PDFF or BMD had no associations with circulating levels of OPG after adjusting for all potential confounders mentioned above. Conclusions: Vertebral marrow fat fraction is independently associated with circulating soluble RANKL levels in postmenopausal females.

Targeting capabilities of engineered extracellular vesicles for the treatment of neurological diseases.

ABSTRACT: Recent advances in research on extracellular vesicles have significantly enhanced their potential as therapeutic agents for neurological diseases. Owing to their therapeutic properties and ability to cross the blood-brain barrier, extracellular vesicles are recognized as promising drug delivery vehicles for various neurological conditions, including ischemic stroke, traumatic brain injury, neurodegenerative diseases, glioma, and psychosis.However, the clinical application of natural extracellular vesicles is hindered by their limited targeting ability and short clearance from the body. To address these limitations, multiple engineering strategies have been developed to enhance the targeting capabilities of extracellular vesicles, thereby enabling the delivery of therapeutic contents to specific tissues or cells. Therefore, this review aims to highlight the latest advancements in natural and targeting-engineered extracellular vesicles, exploring their applications in treating traumatic brain injury, ischemic stroke, Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, glioma, and psychosis. Additionally, we summarized recent clinical trials involving extracellular vesicles and discussed the challenges and future prospects of using targeting-engineered extracellular vesicles for drug delivery in treating neurological diseases. This review offers new insights for developing highly targeted therapies in this field.

CTPAD: an interactive web application for comprehensive transcriptomic profiling in allergic diseases.

BACKGROUND: Allergic diseases are systemic chronic inflammatory diseases associated with multiorgan damage and complex pathogenesis. Several studies have revealed the association of gene expression abnormalities with the development of allergic diseases, but the biomedical field still lacks a public platform for comprehensive analysis and visualization of transcriptomic data of allergic diseases. OBJECTIVE: The aim of the study is to provide a comprehensive web tool for multiple analysis in allergic diseases. METHODS: We retrieved and downloaded human and mouse gene expression profile data associated with allergic diseases from the Gene Expression Omnibus (GEO) database and standardized the data uniformly. We used gene sets obtained from the MSigDB database for pathway enrichment analysis and multiple immune infiltration algorithms for the estimation of immune cell proportion. The basic construction of the web pages was based on the Shiny framework. Additionally, more convenient features were added to the server to improve the efficiency of the web pages, such as jQuery plugins and a comment box to collect user feedback. RESULTS: We developed CTPAD, an interactive R Shiny application that integrates public databases and multiple algorithms to explore allergic disease-related datasets and implement rich transcriptomic visualization capabilities, including gene expression analysis, pathway enrichment analysis, immune infiltration analysis, correlation analysis, and single-cell RNA sequencing analysis. All functional modules offer customization options and can be downloaded in PDF format with high-resolution images. CONCLUSIONS: CTPAD largely facilitates the work of researchers without bioinformatics background to enable them to better explore the transcriptomic features associated with allergic diseases. CTPAD is available at https://smuonco.shinyapps.io/CTPAD/ .

Recover then aggregate: unified cross-modal deep clustering with global structural information for single-cell data.

Single-cell cross-modal joint clustering has been extensively utilized to investigate the tumor microenvironment. Although numerous approaches have been suggested, accurate clustering remains the main challenge. First, the gene expression matrix frequently contains numerous missing values due to measurement limitations. The majority of existing clustering methods treat it as a typical multi-modal dataset without further processing. Few methods conduct recovery before clustering and do not sufficiently engage with the underlying research, leading to suboptimal outcomes. Additionally, the existing cross-modal information fusion strategy does not ensure consistency of representations across different modes, potentially leading to the integration of conflicting information, which could degrade performance. To address these challenges, we propose the 'Recover then Aggregate' strategy and introduce the Unified Cross-Modal Deep Clustering model. Specifically, we have developed a data augmentation technique based on neighborhood similarity, iteratively imposing rank constraints on the Laplacian matrix, thus updating the similarity matrix and recovering dropout events. Concurrently, we integrate cross-modal features and employ contrastive learning to align modality-specific representations with consistent ones, enhancing the effective integration of diverse modal information. Comprehensive experiments on five real-world multi-modal datasets have demonstrated this method's superior effectiveness in single-cell clustering tasks.

Rational Strategies for Preparing Highly Efficient Tin-, Bismuth- or Indium Based Electrocatalysts for Electrochemical CO2 Reduction to Formic acid.

Electrochemical carbon dioxide reduction reaction (CO2RR) is an environmentally friendly and economically viable approach to convert greenhouse gas CO2 into valuable chemical fuels and feedstocks. Among various products of CO2RR, formic acid/formate (HCOOH/HCOO-) is considered the most attractive one with its high energy density and ease of storage, thereby enabling widespread commercial applications in chemical, medicine, and energy-related industries. Nowadays, the development of efficient and financially feasible electrocatalysts with excellent selectivity and activity towards HCOOH/HCOO- is paramount for the industrial application of CO2RR technology, in which Tin (Sn), Bismuth (Bi), and Indium (In)-based electrocatalysts have drawn significant attention due to their high efficiency and various regulation strategies have been explored to design diverse advanced electrocatalysts. Herein, we comprehensively review the rational strategies to enhance electrocatalytic performances of these electrocatalysts for CO2RR to HCOOH/HCOO-. Specifically, the internal mechanism between the physicochemical properties of engineering materials and electrocatalytic performance is analyzed and discussed in details. Besides, the current challenges and future opportunities are proposed to provide inspiration for the development of more efficient electrocatalysts in this field.

A Multi-Omics Prognostic Model Capturing Tumor Stemness and the Immune Microenvironment in Clear Cell Renal Cell Carcinoma.

Background: Cancer stem-like cells (CSCs), a distinct subset recognized for their stem cell-like abilities, are intimately linked to the resistance to radiotherapy, metastatic behaviors, and self-renewal capacities in tumors. Despite their relevance, the definitive traits and importance of CSCs in the realm of oncology are still not fully comprehended, particularly in the context of clear cell renal cell carcinoma (ccRCC). A comprehensive understanding of these CSCs' properties in relation to stemness, and their impact on the efficacy of treatment and resistance to medication, is of paramount importance. Methods: In a meticulous research effort, we have identified new molecular categories designated as CRCS1 and CRCS2 through the application of an unsupervised clustering algorithm. The analysis of these subtypes included a comprehensive examination of the tumor immune environment, patterns of metabolic activity, progression of the disease, and its response to immunotherapy. In addition, we have delved into understanding these subtypes' distinctive clinical presentations, the landscape of their genomic alterations, and the likelihood of their response to various pharmacological interventions. Proceeding from these insights, prognostic models were developed that could potentially forecast the outcomes for patients with ccRCC, as well as inform strategies for the surveillance of recurrence after treatment and the handling of drug-resistant scenarios. Results: Compared with CRCS1, CRCS2 patients had a lower clinical stage/grading and a better prognosis. The CRCS2 subtype was in a hypoxic state and was characterized by suppression and exclusion of immune function, which was sensitive to gefitinib, erlotinib, and saracatinib. The constructed prognostic risk model performed well in both training and validation cohorts, helping to identify patients who may benefit from specific treatments or who are at risk of recurrence and drug resistance. A novel therapeutic target, SAA2, regulating neutrophil and fibroblast infiltration, and, thus promoting ccRCC progression, was identified. Conclusions: Our findings highlight the key role of CSCs in shaping the ccRCC tumor microenvironment, crucial for therapy research and clinical guidance. Recognizing tumor stemness helps to predict treatment efficacy, recurrence, and drug resistance, informing treatment strategies and enhancing ccRCC patient outcomes.

Ambient Ozone Exposure, Semen Plasma Metabolites, and Sperm Quality Decline among Adult Men in Wuhan China.

Ambient ozone (O3) exposure may be associated with a reduction of semen quality, yet the potential biological mechanisms remain unclear. We investigated the effects of certain seminal plasma metabolites on mediating the links between O3 exposure and the deterioration of semen quality. The untargeted metabolomics analysis was performed on semen samples of 200 Chinese adult men to determine candidate metabolites associated with characteristics of semen quality. Mediation analysis was adopted to examine whether these metabolites modulated the links between O3 exposure and semen quality. We found a significant reduction in sperm concentration by -28.1% (95% CI: -41.7%, -11.3%), and sperm count by -29.2% (95% CI: -43.7%, -11.0%) associated with each 10 µg/m3 increase in ambient O3 concentration during the period of sperm development. We delineated 7 metabolites in seminal fluid that substantially mediated the links between O3 exposure and declined semen quality, including myristoleic acid, aspartyl-isoleucine, phenylethyl primeveroside, ACar (18:2), ACar (18:1), FAHFA (22:6/22:3), and LPS (22:5). Among these, myristoleic acid exhibited the most pronounced mediation effects, with its indirect effect of which accounts for 46.4% of the overall association. Our findings suggested that exposure to ozone decreased sperm quality by disrupting fatty acid metabolism, particularly myristoleic acid.

Targeting immunosenescence for improved tumor immunotherapy.

Tumor immunotherapy has significantly transformed the field of oncology over the past decade. An optimal tumor immunotherapy would ideally elicit robust innate and adaptive immune responses within tumor immune microenvironment (TIME). Unfortunately, immune system experiences functional decline with chronological age, a process termed "immunosenescence," which contributes to impaired immune responses against pathogens, suboptimal vaccination outcomes, and heightened vulnerability to various diseases, including cancer. In this context, we will elucidate hallmarks and molecular mechanisms underlying immunosenescence, detailing alterations in immunosenescence at molecular, cellular, organ, and disease levels. The role of immunosenescence in tumorigenesis and senescence-related extracellular matrix (ECM) has also been addressed. Recognizing that immunosenescence is a dynamic process influenced by various factors, we will evaluate treatment strategies targeting hallmarks and molecular mechanisms, as well as methods for immune cell, organ restoration, and present emerging approaches in immunosenescence for tumor immunotherapy. The overarching goal of immunosenescence research is to prevent tumor development, recurrence, and metastasis, ultimately improving patient prognosis. Our review aims to reveal latest advancements and prospective directions in the field of immunosenescence research, offering a theoretical basis for development of practical anti-immunosenescence and anti-tumor strategies.

Efficient and secure service function chain deployment method for delay optimization in air traffic information network.

The air traffic information network is fundamental for ensuring the efficient and safe operation of flights. However, with the increasing demands of air traffic services, the rigidity of the traditional air traffic information network has become increasingly pronounced. Network function virtualization (NFV) technology presents an effective solution to address this issue. Within the NFV environment, the deployment of service function chains (SFC) forms the basis for achieving end-to-end air traffic services. This paper addresses the low delay and high security requirements inherent in air traffic services and proposes an efficient and secure SFC deployment for delay optimization (ESSFCD-DO) method. Primarily, the paper conducts a theoretical analysis of SFC deployment, and derives four key principles related to SFC delay, security, and resource cost. Subsequently, based on these principles, the ESSFCD-DO method is developed, which encompasses the virtual network function (VNF) aggregation algorithm for security and resources cost optimization (VNFAA-SRCO), the VNF deployment algorithm based on topology aware (VNFD-TA), and the algorithm for deploying virtual links based on k-shortest path. Experimental results demonstrate that, in comparison to other SFC deployment methods within this domain, ESSFCD-DO achieves significant optimizations in terms of end-to-end delay of SFC and long-term revenue-cost ratio, while ensuring security and service request acceptance rate.

Aberrant overexpression of myosin 1b in glioblastoma promotes angiogenesis via VEGF-myc-myosin 1b-Piezo1 axis.

Glioblastoma (GBM) is the most aggressive intracranial malignancy with poor prognosis. Enhanced angiogenesis is an essential hallmark of GBM, which demonstrates extensive microvascular proliferation and abnormal vasculature. Here, we uncovered the key role of myosin 1b in angiogenesis and vascular abnormality in GBM. Myosin 1b is upregulated in GBM endothelial cells (ECs) compared to the paired nonmalignant brain tissue. In our study, we found that myosin 1b promotes migration, proliferation, and angiogenesis of human/mouse brain ECs. We also found that myosin 1b expression in ECs can be regulated by vascular endothelial growth factor (VEGF) signaling through myc. Moreover, myosin 1b promotes angiogenesis via Piezo1 by enhancing Ca2+ influx, in which process VEGF can be the trigger. In conclusion, our results identified myosin 1b as a key mediator in promoting angiogenesis via mechanosensitive ion channel component 1 (Piezo1) and suggested that VEGF/myc signaling pathway could be responsible for driving the changes of myosin 1b overexpression in GBM ECs.