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Objectives: To study the relationship between the ablation range and applied energy of laser ablation (LA) and microwave ablation (MWA) in papillary thyroid microcarcinoma (PTMC). Methods: A total of 201 PTMC patients were treated with LA (n = 102) or MWA (n = 99) with single-applicator fixed ablation. The ablation range was determined by contrast-enhanced ultrasound. The ratios of ablation volume, longitudinal diameter, and orthogonal diameter to ablation energy (RAV/E, RAL/E, RAO/E) were analyzed and compared between MWA and LA. The effects of PTMC characteristics and Hashimoto's thyroiditis (HT) on ablation efficiency were evaluated by linear regression. Results: The RAV/E was 0.72 (0.65–0.84) mm3/J for MWA and 0.48 (0.39–0.54) mm3/J for LA. HT was significantly correlated with RAV/E of LA (coefficient = − 0.367, p < 0.0001). RAL/E did not differ significantly between MWA and LA (MWA 0.026 mm/J, LA 0.025 mm/J; p = 0.957). However, MWA had a greater RAO/E than LA (MWA 0.014 mm/J, LA 0.012 mm/J; p < 0.0001). The plateau values of MWA and LA on the ablation orthogonal diameter were 10.7 mm and 8.69 mm, respectively. Conclusions: MWA showed a higher RAV/E than LA. More intuitively, MWA had a better ablation performance than LA on the orthogonal axis rather than the longitudinal axis. Theoretically, MWA and LA could achieve complete ablation of ≤ 6.70 mm and ≤ 4.69 mm PTMC separately by single-applicator fixed ablation considering a unilateral 2-mm safe margin. HT had a negative effect on LA but not on MWA. Clinical relevance statement: This study establishes strong connections between ablation energy and ablation range in papillary thyroid microcarcinoma (PTMC) in vivo, possibly contributing to the supplementation of the PTMC Ablation Consensus or Guidelines and providing a scientific basis for choosing clinical ablation parameters in PTMC. Key Points: • Both microwave ablation (MWA) and laser ablation (LA) have excellent performance on the ablation longitudinal axis (easily exceeding 10 mm) for papillary thyroid microcarcinoma (PTMC). • MWA performed much better than LA on the ablation orthogonal axis. • MWA and LA are expected to achieve complete ablation of ≤ 6.70 mm and ≤ 4.69 mm PTMC separately by single-applicator fixed ablation considering a unilateral 2-mm safe margin. [ABSTRACT FROM AUTHOR]

As an acute respiratory disease, scarlet fever has great harm to public health. Some evidence indicates that the time distribution pattern of heavy PM2.5 pollution occurrence may have an impact on health risks. This study aims to reveal the relation between scaling features in high-concentrations PM2.5 (HC-PM2.5) evolution and scarlet fever incidence (SFI). Based on the data of Hong Kong from 2012 to 2019, fractal box-counting dimension (D) is introduced to capture the scaling features of HC-PM2.5. It has been found that index D can quantify the time distribution of HC-PM2.5, and lower D values indicate more cluster distribution of HC-PM2.5. Moreover, scale-invariance in HC-PM2.5 at different time scales has been discovered, which indicates that HC-PM2.5 occurrence is not random but follows a typical power-law distribution. Next, the exposure–response relationship between SFI and scale-invariance in HC-PM2.5 is explored by Distributed lag non-linear model, in conjunction with meteorological factors. It has been discovered that scale-invariance in HC-PM2.5 has a nonlinear effect on SFI. Low and moderate D values of HC-PM2.5 are identified as risk factors for SFI at small time-scale. Moreover, relative risk shows a decreasing trend with the increase of exposure time. These results suggest that exposure to short-term clustered HC-PM2.5 makes individual more prone to SFI than exposure to long-term uniform HC-PM2.5. This means that individuals in slightly-polluted regions may face a greater risk of SFI, once the PM2.5 concentration keeps rising. In the future, it is expected that the relative risk of scarlet fever for a specific region can be estimated based on the quantitative analysis of scaling features in high-concentrations PM2.5 evolution. [ABSTRACT FROM AUTHOR]

Background: Plants can retain atmospheric particulate matter (PM) through their unique foliar microstructures, which has a profound impact on the phyllosphere microbial communities. Yet, the underlying mechanisms linking atmospheric particulate matter (PM) retention by foliar microstructures to variations in the phyllosphere microbial communities remain a mystery. In this study, we conducted a field experiment with ten Ulmus lines. A series of analytical techniques, including scanning electron microscopy, atomic force microscopy, and high-throughput amplicon sequencing, were applied to examine the relationship between foliar surface microstructures, PM retention, and phyllosphere microbial diversity of Ulmus L. Results: We characterized the leaf microstructures across the ten Ulmus lines. Chun exhibited a highly undulated abaxial surface and dense stomatal distribution. Langya and Xingshan possessed dense abaxial trichomes, while Lieye, Zuiweng, and Daguo had sparsely distributed, short abaxial trichomes. Duomai, Qingyun, and Lang were characterized by sparse stomata and flat abaxial surfaces, whereas Jinye had sparsely distributed but extensive stomata. The mean leaf retention values for total suspended particulate (TSP), PM2.5, PM2.5-10, PM10-100, and PM> 100 were 135.76, 6.60, 20.10, 90.98, and 13.08 µg·cm− 2, respectively. Trichomes substantially contributed to PM2.5 retention, while larger undulations enhanced PM2.5-10 retention, as evidenced by positive correlations between PM2.5 and abaxial trichome density and between PM2.5-10 and the adaxial raw microroughness values. Phyllosphere microbial diversity patterns varied among lines, with bacteria dominated by Sediminibacterium and fungi by Mycosphaerella, Alternaria, and Cladosporium. Redundancy analysis confirmed that dense leaf trichomes facilitated the capture of PM2.5-associated fungi, while bacteria were less impacted by PM and struggled to adhere to leaf microstructures. Long and dense trichomes provided ideal microhabitats for retaining PM-borne microbes, as evidenced by positive feedback loops between PM2.5, trichome characteristics, and the relative abundances of microorganisms like Trichoderma and Aspergillus. Conclusions: Based on our findings, a three-factor network profile was constructed, which provides a foundation for further exploration into how different plants retain PM through foliar microstructures, thereby impacting phyllosphere microbial communities. [ABSTRACT FROM AUTHOR]

In recent years, there has been a growing interest in the study of RNA modifications, with some researchers focusing specifically on the connection between these modifications and viruses, as well as the impact they have on viral mRNA and its functionality. The most common type of RNA chemical modification is m6A, which involves the addition of a methyl group covalently to the N6 position of adenosine. It is a widely observed and evolutionarily conserved RNA modification. The regulation of m6A modification primarily involves methyltransferases (writers) and demethylases (erasers) and is mediated by m6A-binding proteins (readers). In HIV-1, m6A sites are predominantly located in the 5′ untranslated region (5′UTR) and 3′ untranslated region (3′UTR). Additionally, m6A modifications are also present in the RRE RNA of HIV-1. This review provides a detailed account of the effects of these m6A modifications on HIV-1 functionality. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to explore the interactions between microbubbles and microwave ablation (MWA). Methods: The study employed custom‐made phantoms (in vitro) and white New Zealand rabbits (in vivo). MWA was performed with or without microbubbles in the phantoms (2 × 105 particles mL−1) and rabbit livers (intravenous injection of 0.05 mL/kg SonoVue). During the MWA, K‐type thermocouple probes were used to monitor the MWA‐induced temperature increase. Contrast‐enhanced ultrasound imaging (CEUS) was used to monitor and analyze the microbubbles signal intensity. After MWA, the ablation‐zone volumes were evaluated and compared between the groups with and without microbubbles. Results: In both the phantom models and rabbits, microbubbles showed no significant influence on MWA, including the ablation range and MWA‐induced temperature increase. In phantoms and rabbit livers filled with microbubbles, MWA caused the formation of a gradually expanding microbubble‐defect region over the ablation time. An increase in the temperature caused microbubble destruction. Conclusions: Microbubbles had no significant influence on MWA. However, MWA induced the destruction of microbubbles in a temperature‐dependent manner. Thus, the poor thermotolerance of microbubbles is a non‐negligible barrier when using CEUS to monitor the ablation range during MWA in real‐time. [ABSTRACT FROM AUTHOR]

To make full use of plant shell fibers (rice husk, walnut shell, chestnut shell), three kinds of wood-plastic composites of plant shell fibers and polyvinyl chloride (PVC) were prepared. X-ray diffraction analysis was carried out on three kinds of plant shell fibers to test their crystallinity. The aging process of the composites was conducted under 2 different conditions. One was artificial seawater immersion and xenon lamp irradiation, and the other one was deionized water spray and xenon lamp irradiation. The mechanical properties (tensile strength, flexural strength, impact strength), changes in color, water absorption, Fourier transform infrared spectroscopy (FTIR), and microstructures of the composites before and after the two aging experiments were analyzed. The results showed that the chestnut shell had the highest crystallinity, which was 42%. The chestnut shell/PVC composites had the strongest interface bonding, the least internal defects, and the best general mechanical properties among the three composites. Its tensile strength, bending strength and impact strength were 23.81 MPa, 34.12 MPa, and 4.32 KJ·m, respectively. Comparing the two aging conditions, artificial seawater immersion and xenon lamp irradiation destroyed the quality of the combination of plant shell fibers and PVC, making the internal defects of the composites increase. This made the water absorption ability and changes in the color of the composites more obvious and led to a great decrease in the mechanical properties. The general mechanical properties of the chestnut shell/PVC composites were the best, but their water absorption ability changed more obviously. [ABSTRACT FROM AUTHOR]

In order to improve the effect of injection–production coupling development to improve crude oil recovery in complex fault-block reservoirs, we carried out a physical simulation experiment based on a sandpack model of transforming water-driven development into injection–production coupling development and quantitatively evaluated the influence of rounds of injection pressure coupling on the crude oil mobilization in reservoirs with different permeability levels and on oil recovery. Meanwhile, the characteristics of residual oil were studied via a numerical simulation method. The mechanism of increased oil production via injection–production coupling development was revealed by analyzing the water and oil contents, formation pressure, and streamline fields through the establishment of mechanism models. The results of the physical experiment show that injection–production coupling can improve the recovery effect of medium- and low-permeability reservoirs by 55.66%. With an increase in the injection pressure, the oil recovery percentage of the low-permeability sandpack model at 20 MPa is 100%, and this study finds that injection–production coupling is the main way to develop the recoverable oil in a low-permeability reservoir. The numerical simulation results show that among the four remaining oil distribution types (interwell-enriched, low-permeability zone-enriched, well network imperfection, and mismatch between injection and production), the interwell-enriched type of the remaining oil reserves accounts for the highest proportion (48.52%). The simulation results of the mechanism model show that water-driven development easily leads to streamline solidification, resulting in ineffective circulation of the injected water. Compared with conventional water-driven development, the pressure propagation range is significantly increased in injection–production coupling development. The reservoir streamline distribution is more continuous and uniform, and the flooding wave is wider in volume and range. This research provides a theoretical basis for the injection–production coupling technology policy in complex fault-block reservoirs. [ABSTRACT FROM AUTHOR]

The distribution of second phase particles in the microstructure of composite ceramics affects the mechanical properties, and the intragranular structures often result in better properties compared to the intergranular structures. However, it is difficult to obtain composite ceramics with intragranular structure by conventional route. To produce composite ceramics with an intragranular structure in a simpler route. In this work, starting powders with different phase compositions were obtained by the co-precipitation method, and zirconia toughened alumina (ZTA) composite ceramics were prepared with these starting powders by spark plasma sintering (SPS). The results show that it is easier to fabricate ZTA composite ceramics with an intragranular structure by using composite powders containing amorphous or transition phase Al2O3 as starting materials. The phase composition of the powder prepared by the co-precipitation method after calcination at 1100 °C is θ-Al2O3 and t-ZrO2, and the average grain size after sintering at 1500 °C is 1.04 ± 0.28 µm, and the maximum Vickers hardness and fracture toughness of the specimens reach 19.37 ± 0.43 GPa and 6.18 ± 0.06 MPa·m1/2, respectively. The ZrO2 particles were the core of crystallization and grow together with the Al2O3 matrix, forming the intragranular structure of ZTA ceramics. This work may provide a new idea for preparing composite ceramics with intragranular structure. [ABSTRACT FROM AUTHOR]

Generalized pustular psoriasis (GPP) is considered to be a distinct clinical entity from psoriasis vulgaris (PV), with different clinical and histological manifestations. The pathogenesis of GPP has not been thoroughly elucidated, especially in those patients lacking interleukin (IL)36RN. In present study, we performed RNA sequence analysis on skin lesions from 10 GPP patients (4 with and 6 without IL36RN mutation) and 10 PV patients without IL36RN mutation. Compared with PV, significantly overexpressed genes in GPP patients were enriched in IL‐17 signalling pathway (MMP1, MMP3, DEFB4A and DEFB4B, etc.) and associated with neutrophil infiltration (MMP1, MMP3, ANXA and SERPINB, etc.). GPP with IL36RN mutations evidenced WNT11 upregulation and IL36RN downregulation in comparison to those GPP without IL36RN mutations. The expression of IL‐17A/IL‐36 in skin or serum and the origin of IL‐17A in skin were also investigated. IL‐17A expression in skin was significantly higher in GPP than PV patients, whereas, there were no differences in skin IL‐36α/IL‐36γ/IL‐36RA or serum IL‐17A/IL‐36α/IL‐36γ between GPP than PV. Besides, double immunofluorescence staining of MPO/IL‐17A or CD3/IL‐17A further confirmed that the majority of IL‐17A in GPP skin was derived from neutrophils, but not T cells. These data emphasized the role of neutrophil‐derived IL‐17A in the pathogenesis of GPP with or without IL36RN mutations. Targeting neutrophil‐derived IL‐17A might be a promising treatment for GPP. [ABSTRACT FROM AUTHOR]

The "Shock and Kill" method is being considered as a potential treatment for eradicating HIV-1 and achieving a functional cure for acquired immunodeficiency syndrome (AIDS). This approach involves using latency-reversing agents (LRAs) to activate human immunodeficiency virus (HIV-1) transcription in latent cells, followed by treatment with antiviral drugs to kill these cells. Although LRAs have shown promise in HIV-1 patient research, their widespread clinical use is hindered by side effects and limitations. In this review, we categorize and explain the mechanisms of these agonists in activating HIV-1 in vivo and discuss their advantages and disadvantages. In the future, combining different HIV-1 LRAs may overcome their respective shortcomings and facilitate a functional cure for HIV-1. [ABSTRACT FROM AUTHOR]

Understanding the dynamic structural and chemical evolutions at the catalyst–electrolyte interfaces is crucial for the development of active and stable electrocatalysts. In this work, β-Li2IrO3 is employed as a model catalyst for the oxygen evolution reaction (OER). Its elastic three-dimensional Ir-O framework enables us to investigate the Li+ cation dissolution-induced structure evolutions and the formation mechanism of amorphous IrOx species. Electrochemical measurements by rotating ring disk electrode (RRDE) reveal that up to 60% of the measured OER current can be ascribed to catalyst degradation. A series of in-situ X-ray diffraction spectroscopy (XRD), X-ray absorption spectroscopy (XAS), and Raman spectroscopy are conducted. Structure vibration is observed with oxidation states of Ir being reduced abnormally during OER at high potentials. It's hypothesized that the reversible proton intercalations are responsible for the Ir turn-over mechanism. Results of this work demonstrate a stable and elastic iridate structure and reveal the initial catalyst degradation behaviors during OER in acid media. [ABSTRACT FROM AUTHOR]

Zirconia toughened alumina (ZTA) ceramics are commonly used in various industries. Adding suitable additives is an effective way to improve the performance of ZTA ceramics. However, the common reinforcement in ZTA, chromia (Cr2O3), tends to volatilize at high temperature in the presence of oxygen, limiting ceramic densification. Consequently, additional amounts of Cr2O3 are typically limited to below 1 wt%. In this study, spark plasma sintering was utilized to inhibit the volatilization of Cr2O3. Dense ZTA ceramics with high Cr2O3 content (from 1 to 10 wt%) were prepared at 1350 °C. The impact of the solid solution on the structure and properties of the ceramics was investigated. The findings demonstrate that the high Cr2O3 solution can regulate the grain size in the matrix, leading to an enhancement in both hardness and fracture toughness. The optimum performance of the sample was obtained with a 5 wt% dosage of Cr2O3, where the maximum values of Vickers hardness and fracture toughness were 20.66 GPa and 6.37 MPa m1/2, respectively. [ABSTRACT FROM AUTHOR]

Papillary thyroid carcinoma (PTC) is the most common pathological type of thyroid cancer. PTC patients with extrathyroidal extension (ETE) are associated with poor prognoses. The preoperative accurate prediction of ETE is crucial for helping the surgeon decide on the surgical plan. This study aimed to establish a novel clinical-radiomics nomogram based on B-mode ultrasound (BMUS) and contrast-enhanced ultrasound (CEUS) for the prediction of ETE in PTC. A total of 216 patients with PTC between January 2018 and June 2020 were collected and divided into the training set (n = 152) and the validation set (n = 64). The least absolute shrinkage and selection operator (LASSO) algorithm was applied for radiomics feature selection. Univariate analysis was performed to find clinical risk factors for predicting ETE. The BMUS Radscore, CEUS Radscore, clinical model, and clinical-radiomics model were established using multivariate backward stepwise logistic regression (LR) based on BMUS radiomics features, CEUS radiomics features, clinical risk factors, and the combination of those features, respectively. The diagnostic efficacy of the models was assessed using receiver operating characteristic (ROC) curves and the DeLong test. The model with the best performance was then selected to develop a nomogram. The results show that the clinical-radiomics model, which is constructed by age, CEUS-reported ETE, BMUS Radscore, and CEUS Radscore, showed the best diagnostic efficiency in both the training set (AUC = 0.843) and validation set (AUC = 0.792). Moreover, a clinical-radiomics nomogram was established for easier clinical practices. The Hosmer–Lemeshow test and the calibration curves demonstrated satisfactory calibration. The decision curve analysis (DCA) showed that the clinical-radiomics nomogram had substantial clinical benefits. The clinical-radiomics nomogram constructed from the dual-modal ultrasound can be exploited as a promising tool for the pre-operative prediction of ETE in PTC. [ABSTRACT FROM AUTHOR]

BACKGROUND: Tilapia skin collagen hydrolysates (TSCHs) are the product of enzymatic hydrolysis of collagen, which is mainly extracted from tilapia skin. The components of TSCHs have recently been reported to play a preventive role in dextran sulfate sodium (DSS)‐induced ulcerative colitis (UC). However, it has not been illustrated whether TSCHs can prevent against DSS‐induced UC via the gut microbiota and its derived metabolites. RESULTS: TSCHs are mainly composed of amino acids, which have similar characteristics to collagen, with most having a molecular weight below 5 kDa. In a mouse model of UC, TSCHs had no toxic effect at a dose of 60 g kg−1 and could reduce body weight changes, colon length, histopathological changes and score, and the level of the serum inflammatory cytokine interleukin (IL)‐6. Concurrently, 16 S rRNA sequencing showed that TSCHs significantly reduced the abundance of Bacteroidetes and Proteobacteria at the phylum level and norank_f__Muribaculaceae and Escherichia‐Shigella at the genus level, while they increased the abundance of Firmicutes at the phylum level and Lachnoclostridium, Allobaculum, Enterorhabdus, and unclassified__f__Ruminococcaceae at the genus level. Target metabolomic analysis showed that TSCHs elevated the concentration of total acid, acetic acid, propanoic acid, and butanoic acid, but reduced isovaleric acid concentrations. Moreover, Pearson correlation analysis revealed that Allobaculum, unclassified_Ruminococcaceae, and Enterorhabdus were positively correlated with acetic acid and butyric acid, but not Escherichia‐Shigella. CONCLUSION: These findings suggest that TSCHs can prevent UC by modulating gut microbial and microbiota‐derived metabolites. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is to blame for about 60% of dementia cases worldwide. The blood–brain barrier (BBB) prevents many medications for AD from having clinical therapeutic effects that can be used to treat the affected area. Many researchers have turned their attention to cell membrane biomimetic nanoparticles (NPs) to solve this situation. Among them, NPs can extend the half-life of drugs in the body as the "core" of the wrapped drug, and the cell membrane acts as the "shell" of the wrapped NPs to functionalize the NPs, which can further improve the delivery efficiency of nano-drug delivery systems. Researchers are learning that cell membrane biomimetic NPs can circumvent the BBB's restriction, prevent harm to the body's immune system, extend the period that NPs spend in circulation, and have good biocompatibility and cytotoxicity, which increases efficacy of drug release. This review summarized the detailed production process and features of core NPs and further introduced the extraction methods of cell membrane and fusion methods of cell membrane biomimetic NPs. In addition, the targeting peptides for modifying biomimetic NPs to target the BBB to demonstrate the broad prospects of cell membrane biomimetic NPs drug delivery systems were summarized. [ABSTRACT FROM AUTHOR]

Because of the blood–brain barrier, only a limited fraction of drugs can penetrate the brain. As a result, there is a need to take larger doses of the drug, which may result in numerous undesirable side effects. Over the past few decades, a plethora of research has been conducted to address this issue. In recent years, the field of nanomedicine research has reported promising findings. Currently, numerous types of polylactic-co-glycolic acid-based drug-delivery systems are being studied, and great progress has been made in the modification of their surfaces with a variety of ligands. In this review, the authors highlight the preparation of polylactic-co-glycolic acid-based nanoparticles and single- and dual-targeted peptide modifications for site-specific drug delivery into the brain. The blood–brain barrier prevents many drugs used to treat brain diseases from having clinical effects. To solve this issue, some promising findings have been reported in the field of nanomedicine research, which will be introduced in this article as possible effective methods for the treatment of brain diseases. This review will focus on the nature of the polylactic-co-glycolic acid polymers involved in the preparation of desired targeted nanocarriers, the synthesis methods for achieving the drug loaded system and the choice and preparation of the targeting agents. This review comprehensively highlights the current research progress of modified polylactic-co-glycolic acid-based nanoparticles for brain-targeted drug delivery and concludes with a discussion on current challenges faced and future perspective. [ABSTRACT FROM AUTHOR]

In this paper, without converting the second-order inertial neural networks (INNs) into a first-order differential system by introducing variable substitution, the problem of passivity-based bipartite synchronization in a signed network composed by an array of coupled INNs with time-varying delay is investigated via quantized pinning control. By choosing an appropriate Lyapunov–Krasovskii functional (LKF), applying Jensen inequality and reciprocally convex inequality to estimate the derivative of the LKF, several sufficient conditions, which guarantee the bipartite leader-following synchronization for the coupled INNs with time-varying delay, are newly obtained in terms of linear matrix inequalities (LMIs). When the quantization is not considered in the pinning controller, the criterion of bipartite leader-following synchronization in terms of low-dimensional LMIs is established by using the properties of M-matrices. And the criterion of bipartite leaderless synchronization in terms of low-dimensional LMIs is also proposed by a matrix U. A numerical example is provided to demonstrate the effectiveness of the derived theoretical results. [ABSTRACT FROM AUTHOR]

Research has proven that light treatment, specifically red light radiation, can provide more clinical benefits to human health. Our investigation was firstly conducted to characterize the tissue morphology of mouse breast post 660 nm laser radiation with low power and long-term exposure. RNA sequencing results revealed that light exposure with a higher intervention dosage could cause a number of differentially expressed genes compared with a low intervention dosage. Gene ontology analysis, protein–protein interaction network analysis, and gene set enrichment analysis results suggested that 660 nm light exposure can activate more transcription-related pathways in HC11 breast epithelial cells, and these pathways may involve modulating critical gene expression. To consider the critical role of the Wnt/T-catenin pathway in light-induced modulation, we hypothesized that this pathway might play a major role in response to 660 nm light exposure. To validate our hypothesis, we conducted qRT-PCR, immunofluorescence staining, and Western blot assays, and relative results corroborated that laser radiation could promote expression levels of β-catenin and relative phosphorylation. Significant changes in metabolites and pathway analysis revealed that 660 nm laser could affect nucleotide metabolism by regulating purine metabolism. These findings suggest that the Wnt/β-catenin pathway may be the major sensor for 660 nm laser radiation, and it may be helpful to rescue drawbacks or side effects of 660 nm light exposure through relative interventional agents. [ABSTRACT FROM AUTHOR]

Cerebrovascular disease is the leading cause of disability and death, and ischemic stroke accounts for most stroke cases. However, few effective drugs are available for the treatment of ischemic stroke; thus, there is an urgent need to develop effective drugs to treat ischemic stroke. DL-3-n-butylphthalide (NBP) is clinically approved as an anti-ischemic drug in China, but its potential hepatotoxicity limits its use. G-3702 (a structural analogue of NBP) is synthesized with the boron hydroxyl group replacing carbonyl group. G-3702 significantly enhanced the survival of middle cerebral artery occlusion (MCAO) rats, decreased neurobehavioral deficit scores and cerebral infarct volume, comparable with NBP, which was also supported by tissue damage assessment, immunohistochemistry staining, biochemical parameters and ELISA assay. G-3702 showed better anti-stroke activity than NBP according to 1H NMR spectroscopy-based metabolomics analysis, demonstrating the feasibility of metabolomics approach to assess drug efficacy. G-3702 markedly ameliorated energy metabolism, attenuated oxidative and inflammatory stress during ischemia/reperfusion (I/R). G-3702 exhibited good neuroprotective effects against I/R induced injury and favorable little possibility of hepatotoxicity, which made it a promising anti-stroke drug and better NBP alternative. [ABSTRACT FROM AUTHOR]

Research on the implications of ferroptosis in tumors has increased rapidly in the last decades. There are evidences that ferroptosis is involved in several aspects of cancer biology, including tumor progression, metastasis, immunomodulation, and therapeutic response. Nonetheless, the interaction between ferroptosis-related lncRNAs (FRLs) and the osteosarcoma immune microenvironment is poorly understood. In this study, a risk model composed of FRLs was developed using univariate and LASSO Cox regression analyses. On the basis of this model, FRL scores were calculated to systematically explore the role of the model in predicting the prognosis and immune characteristics of osteosarcoma patients. Survival analysis showed that osteosarcoma samples with lower FRL-score had better overall survival. After predicting the abundance of immune cells in osteosarcoma microenvironment by single-sample gene-set enrichment analysis (ssGSEA) and ESTIMATE analysis, we found that the FRL-score could distinguish immune function, immune score, stromal score, tumor purity, and tumor infiltration of immune cells in different osteosarcoma patients. In addition, FRL-score was also associated with immune checkpoint gene expression and half-maximal inhibitory concentration of chemotherapeutic agents. Finally, we confirmed that knockdown of RPARP-AS1 suppressed the malignant activity of osteosarcoma cells in vitro experiments. In general, the FRL-based prognostic signature could promote our understanding of the immune microenvironment characteristics of osteosarcoma and guide more effective treatment regimens. [ABSTRACT FROM AUTHOR]

Osteosarcoma is a common malignant bone tumor with a propensity for drug resistance, recurrence, and metastasis. A growing number of studies have elucidated the dual role of pyroptosis in the development of cancer, which is a gasdermin-regulated novel inflammatory programmed cell death. However, the interaction between pyroptosis and the overall survival (OS) of osteosarcoma patients is poorly understood. This study aimed to construct a prognostic model based on pyroptosis-related genes to provide new insights into the prognosis of osteosarcoma patients. We identified 46 differentially expressed pyroptosis-associated genes between osteosarcoma tissues and normal control tissues. A total of six risk genes affecting the prognosis of osteosarcoma patients were screened to form a pyroptosis-related signature by univariate and LASSO regression analysis and verified using GSE21257 as a validation cohort. Combined with other clinical characteristics, including age, gender, and metastatic status, we found that the pyroptosis-related signature score, which we named "PRS-score," was an independent prognostic factor for patients with osteosarcoma and that a low PRS-score indicated better OS and a lower risk of metastasis. The result of ssGSEA and ESTIMATE algorithms showed that a lower PRS-score indicated higher immune scores, higher levels of tumor infiltration by immune cells, more active immune function, and lower tumor purity. In summary, we developed and validated a pyroptosis-related signature for predicting the prognosis of osteosarcoma, which may contribute to early diagnosis and immunotherapy of osteosarcoma. [ABSTRACT FROM AUTHOR]

To investigate the antitumor efficacy of microwave ablation combined with dendritic cell-derived exosomes (Dex) or dendritic cells (DC) in treating hepatocellular carcinoma using a tumor-bearing mouse model. We used a bilateral tumor-bearing mouse model treated with MWA, MWA + DC (DC-combined group) or MWA + Dex (Dex-combined group). Following tumor ablation on one side, the tumor volume on the contralateral side was monitored. The proportions of CD8+ (cytotoxic) T cells and regulatory T (Treg) cells in the spleen were analyzed by flow cytometry, and the number of CD8+ T cells and Treg cells in tumor sites was detected by immunohistochemistry. The concentration of interleukin-10 and interferon-γ in plasma was identified using enzyme-linked immunosorbent assay. The combination therapy significantly inhibited tumor growth compared with MWA monotherapy. In addition, the tumor immune microenvironment was significantly improved in HCC mice in the combination therapy groups compared to MWA group demonstrated by an increased number of CD8+ T cells and a decreased number of Treg cells in tumor sites. A lower proportion of Treg cells were observed in the spleen in the combination therapy groups compared to MWA group. Moreover, the concentration of plasma IFN-γ increased, and the concentration of plasma IL-10 decreased in the combination therapy groups compared to the MWA group. However, there was no statistical difference between the Dex-combined group and the DC-combined group in the comparisons mentioned above. Our results provide evidence that MWA combined with Dex can significantly inhibit tumor growth and improve the immune microenvironment compared to MWA alone. Furthermore, the immune-enhancing effect of Dex and DC was equivalent in our combination therapy strategy. [ABSTRACT FROM AUTHOR]