Search

Abstract Glioblastoma multiforme (GBM) is characterized by pronounced immune escape and resistance to chemotherapy-induced apoptosis. Preliminary investigations revealed a marked overexpression of gasdermin E (GSDME) in GBM. Notably, cisplatin (CDDP) demonstrated a capacity of inducing pyroptosis by activating caspase-3 to cleave GSDME, coupled with the release of proinflammatory factors, indicating the potential as a viable approach of inducing anti-tumor immune activation. For the effective delivery of CDDP, the CDDP-polyphenol nanocomplexes were prepared, and catalase and copper ions were incorporated to fortify structural integrity, enhance glutathione (GSH) responsiveness, and ameliorate tumor hypoxia. Additionally, BV2 microglial cells were engineered to overexpress programmed death-1 (PD-1), and the membrane is employed for nanocomplex coating, effectively blocking the CDDP-induced upregulation of programmed death ligand 1 (PD-L1). Furthermore, the angiopep-2 peptide was modified to efficiently cross the blood brain barrier and specifically target GBM cells. In vitro analyses confirmed potent cytotoxicity and characteristic induction of pyroptosis. In vivo assays corroborated the enhancement of tumor targeting, culminating in an obvious suppression of tumor proliferation. A notable activation of immune cells was observed within tumors and lymph nodes, indicative of a synergistic effect of chemotherapy and immunotherapy, underscoring its potential as a safe and efficacious therapeutic strategy against GBM.

Abstract Chemotherapy is still one of the major approaches in triple-negative breast cancer (TNBC) treatment. The development of new formulations for classic chemotherapeutic drugs remains interests in studies. Camptothecin (CPT) is powerful antitumor agents in TNBC treatment though its clinic applications are limited by its low water solubility and systemic toxicity. To prepare a spatiotemporal controllable CPT nano-formulation, we construct a ROS-responsive self-assembly nanoparticle by combining hydrophobic CPT and hydrophilic 5-floxuridine (FUDR). A ROS-sensitive thioketal (TK) linker is used to prepare CPT-TK-FUDR (CTF). Next, we introduced IR780-based phototherapy to elicit massive ROS regeneration due to the endogenous ROS is not sufficient. IR780 is modified with hyaluronic acid (HA) to prepare HA-modified IR780 (HAIR) for its biocompatibility and tumor targeting ability improvement. CTF and HAIR self-assemble to form an attractive nano-bomb (HAIR/CTF NPs). HA accurately guides the NPs to tumor sites via HA-receptor recognition on tumor cells. After internalization, overexpressed intracellular HAase in tumor cells disassembles the NPs to free the contents. Due to the presence of IR780 molecules, the scheduled irradiation of 808 nm laser induces massive reactive oxygen species (ROS) generation, which further result in the cleavage of TK linker for free drugs release. Additionally, ROS-mediated photodynamic therapy (PDT) and near-infrared laser-mediated photothermal therapy (PTT) synergistically worked to eradicate tumor cells. Then immunogenic cell death (ICD) was evoked by CPT and phototherapy to amplify antitumor immunity, thereby achieving primary and abscopal tumor inhibition. In conclusion, the HAIR/CTF nano-bomb realized spatiotemporal controllable drug release, exciting tumor eradication and attractive anti-metastasis efficacy via combination chemo/photo/immunotherapy, offering a valuable reference for the re-development of classic drug in future clinical practice. Graphical Abstract

BackgroundVirtual reality (VR) technology has shown significant potential in improving the social skills of children and adolescents with autism spectrum disorder (ASD). ObjectiveThis study aimed to systematically review the evidence supporting the effectiveness of VR technology in improving the social skills of children and adolescents with ASD. MethodsThe search for eligible studies encompassed 4 databases: PubMed, Web of Science, IEEE, and Scopus. Two (XY and JW) researchers independently assessed the extracted studies according to predefined criteria for inclusion and exclusion. These researchers also independently extracted information regarding gathered data on the sources, samples, measurement methods, primary results, and data related to the main results of the studies that met the inclusion criteria. The quality of the studies was further evaluated using the Physiotherapy Evidence Database scale. ResultsThis review analyzed 14 studies on using VR technology interventions to improve social skills in children and adolescents with ASD. Our findings indicate that VR interventions have a positive effect on improving social skills in children and adolescents with ASD. Compared with individuals with low-functioning autism (LFA), those with high-functioning autism (HFA) benefited more from the intervention. The duration and frequency of the intervention may also influence its effectiveness. In addition, immersive VR is more suitable for training complex skills in individuals with HFA. At the same time, nonimmersive VR stands out in terms of lower cost and flexibility, making it more appropriate for basic skill interventions for people with LFA. Finally, while VR technology positively enhances social skills, some studies have reported potential adverse side effects. According to the quality assessment using the Physiotherapy Evidence Database scale, of the 14 studies, 6 (43%) were classified as high quality, 4 (29%) as moderate quality, and 4 (29%) as low quality. ConclusionsThis systematic review found that VR technology interventions positively impact social skills in children and adolescents with ASD, with particularly significant effects on the enhancement of complex social skills in individuals with HFA. For children and adolescents with LFA, progress was mainly observed in basic skills. Immersive VR interventions are more suitable for the development of complex skills. At the same time, nonimmersive VR, due to its lower cost and greater flexibility, also holds potential for application in specific contexts. However, the use of VR technology may lead to side effects such as dizziness, eye fatigue, and sensory overload, particularly in immersive settings. These potential issues should be carefully addressed in intervention designs to ensure user comfort and safety. Future research should focus on optimizing individualized interventions and further exploring the long-term effects of VR interventions. Trial RegistrationInternational Platform of Registered Systematic Review and Meta-analysis Protocols INPLASY202420079U1; https://inplasy.com/inplasy-2024-2-0079/

Gastric cancer remains a malignancy with high incidence, mortality rates, and poor prognosis globally. Osteoclastogenesis-associated transmembrane protein 1 (OSTM1), a transmembrane protein overexpressed in various tumors, has unclear functions in gastric-cancer progression. This study explores OSTM1’s role in gastric-cancer proliferation and metastasis. OSTM1 expression was analyzed in gastric-cancer and adjacent tissues using immunohistochemistry and RT-qPCR. OSTM1 overexpression and knockdown cell lines were established to assess its effects on cancer-cell behavior through in vitro and in vivo experiments. Western blot and RT-qPCR were used to examine OSTM1’s regulation of S100A4 expression. OSTM1 was significantly overexpressed in gastric-cancer tissues, negatively correlating with TNM staging and overall survival. OSTM1 overexpression enhanced cancer-cell proliferation, colony formation, migration, and invasion, while its knockdown showed opposite effects. In vivo studies confirmed increased lung metastatic capability in high OSTM1-expressing cells. Mechanistically, OSTM1 positively regulated S100A4 expression, with S100A4 knockdown reducing OSTM1-enhanced metastasis. Gastric-cancer lung metastases showed higher microvascular density and α-SMA-positive fibroblast infiltration in the OSTM1 high-expression group. OSTM1 promotes gastric-cancer progression by upregulating S100A4 and modifying the tumor microenvironment through enhanced angiogenesis and fibroblast activation. OSTM1 represents a potential diagnostic and prognostic biomarker, with the OSTM1–S100A4 axis offering new therapeutic possibilities for gastric-cancer treatment.

BiFeO3–BaTiO3 (BF–BT) based piezoelectric ceramics are a kind of high-temperature lead-free piezoelectric ceramics with great development prospects due to their high Curie temperature (TC) and excellent electrical properties. However, large leakage current limits their performance improvement and practical applications. In this work, direct current (DC) test, alternating current (AC) impedance, and Hall tests were used to investigate conduction mechanisms of 0.75BiFeO3–0.25BaTiO3 ceramics over a wide temperature range. In the range of room temperature (RT)−150 ℃, ohmic conduction plays a predominant effect, and the main carriers are p-type holes with the activation energy (Ea) of 0.51 eV. When T > 200 ℃, the Ea value calculated from the AC impedance and Hall data is 1.03 eV with oxygen vacancies as a cause of high conductivity. The diffusion behavior of thermally activated oxygen vacancies is affected by crystal symmetry, oxygen vacancy concentration, and distribution, dominating internal conduction mechanism. Deciphering the conduction mechanisms over the three temperature ranges would pave the way for further improving the insulation and electrical properties of BiFeO3–BaTiO3 ceramics.

ObjectiveAnodal transcranial direct current stimulation (a-tDCS) has been used to improve athletic performance in various populations; however, its role in improving performance in elite athletes is unclear. This study aimed to investigate the effects of a-tDCS on athletic performance in elite athletes.MethodsWe used a single-blind, randomized controlled experimental design and recruited 24 national-level freestyle swimmers from China. All athletes were randomly divided into two groups; the experimental group underwent a-tDCS (current 2 mA for 20 min) combined with physical training, and the control group underwent a-tDCS sham stimulation combined with physical training. The physical training program was identical in the experimental and control groups. The intervention period was 6 weeks, with five weekly sessions of 110 min each, consisting of 20 min of a-tDCS and 90 min of physical training. Base strength, explosive strength, aerobic endurance, and anaerobic endurance were measured in the athletes before and after the intervention.ResultsThe results were as follows. 1) Basic strength: There was a significant improvement in 5RM pull-ups in the experimental and control groups before and after the intervention (p < 0.05). 2) Explosive strength: There was a significant improvement in vertical jump and swimming start distance into the water in the experimental and control groups before and after the intervention (p < 0.05). 3) Aerobic endurance: There was no significant improvement in the experimental and control groups before and after the intervention. 4) Anaerobic endurance: There was a significant improvement in 400 m running performance in the experimental and control groups before and after the intervention (p < 0.05).ConclusionCompared to physical training alone, a-tDCS combined with physical training can better improve the athletic performance of high-level swimmers, especially in basic strength, explosive strength, and aerobic endurance.

Objectives: This study examined and compared the effects of functional and running high-intensity interval training (HIIT) on body composition, cardiorespiratory fitness, and muscular fitness of young adults with overweight or obesity.Methods: Forty-five participants (22.1 ± 2.1 years, BMI = 25.2 ± 1.0 kg/m2) were assigned to functional HIIT (HIIT-F; n = 15), running HIIT (HIIT-R; n = 15), or non-training control group (CON; n = 15). Participants in HIIT-F and HIIT-R performed functional exercise based-HIIT (four sets of all-out whole-body exercises including jumping jacks, squats, twist jumps and mountain climbers, et al.) and running HIIT (four sets of running on a treadmill) for 12 weeks, respectively. Body composition, muscular fitness, and cardiorespiratory fitness were assessed pre and post intervention.Results: Both HIIT-F and HIIT-R significantly improved the body composition and cardiorespiratory fitness, with HIIT-F induced greater improvements in lean mass (+1.623 vs. −1.034 kg, p < 0.001), back strength (+6.007 vs. +3.333 kg, p < 0.01), and push-ups (+5.692 vs. 1.923 reps, p < 0.001) than that in HIIT-R. HIIT-R reduced more visceral fat area (VFA) (−11.416 vs. −4.338 cm2, p = 0.052) and induced similar improvement in cardiorespiratory fitness (VO2max, +2.192 vs. +2.885 mL/kg/min, p = 0.792) with HIIT-F.Conclusion: Twelve weeks of HIIT-R or HIIT-F improved physical fitness among young adults with overweight or obesity. Despite the similar impact on cardiorespiratory fitness, HIIT-F generates a better positive effect on muscular fitness relative to HIIT-R, which could be partly explained by the greater increase in lean mass after HIIT-F intervention.

Abstract Background Clinical evidence of immune checkpoint inhibitors combined with antiangiogenic drugs in patients with advanced non‐small cell lung cancer (NSCLC) was limited. Recombinant human endostatin (rh‐endostatin), an antiangiogenic drug, and camrelizumab, an anti‐PD‐1 antibody, have been approved for the treatment of advanced NSCLC in China. This study aimed to investigate the efficacy and safety of rh‐endostatin plus camrelizumab and chemotherapy in the treatment of advanced NSCLC. Methods Eligible patients were enrolled and received camrelizumab (200 mg, day 1) every 3 weeks and continuous intravenous infusion of rh‐endostatin (70 mg/day, days 1–3) and cisplatin combined with pemetrexed (for adenocarcinoma) or paclitaxel (for NSCLC other than adenocarcinoma) every 3 weeks. Primary endpoint was progression‐free survival (PFS). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety profiles. Results Overall, 27 patients were included, and 25 patients were eligible for efficacy evaluation. For these 25 patients, ORR was 48.15% (13/27) and DCR was 85.19% (23/27). With a median follow‐up of 10.37 months, the median PFS was 8.9 (95% CI: 4.23–13.57) months. Median OS was not reached. Overall, 96.3% of patients experienced at least one treatment‐related adverse event, and grade 3 TRAEs occurred in 9 (33.3%) patients. No unexpected AEs were observed. Conclusion Rh‐endostatin plus camrelizumab and chemotherapy showed favorable efficacy and safety profile in patients with advanced NSCLC, representing a promising treatment regimen for these patients.

Immunotherapy has been emerging as a powerful strategy for cancer management. Recently, accumulating evidence has demonstrated that bacteria-based immunotherapy including naive bacteria, bacterial components, and bacterial derivatives, can modulate immune response via various cellular and molecular pathways. The key mechanisms of bacterial antitumor immunity include inducing immune cells to kill tumor cells directly or reverse the immunosuppressive microenvironment. Currently, bacterial antigens synthesized as vaccine candidates by bioengineering technology are novel antitumor immunotherapy. Especially the combination therapy of bacterial vaccine with conventional therapies may further achieve enhanced therapeutic benefits against cancers. However, the clinical translation of bacteria-based immunotherapy is limited for biosafety concerns and non-uniform production standards. In this review, we aim to summarize immunotherapy strategies based on advanced bacterial therapeutics and discuss their potential for cancer management, we will also propose approaches for optimizing bacteria-based immunotherapy for facilitating clinical translation.

ObjectiveMetabolic disorders are common among children and adolescents with obesity and are associated with insulin resistance, hyperlipidemia, hypertension, and other cardiovascular risk factors. High-intensity interval training (HIIT) is a time-efficient method to improve cardiometabolic health. We performed a meta-analysis to determine the effects of HIIT on glycolipid metabolism in children with metabolic disorders.MethodsMeta-analyses were conducted to determine the effect of HIIT on glycolipid metabolism markers. Subgroup analysis with potential moderators was explored [i.e., training intensity standard and work/rest time ratio (WRR)].ResultsEighteen trials involving 538 participants were included. HIIT showed positive effects on glycolipid metabolism, such as triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), blood glucose (BG), blood insulin (BI), and homeostasis model assessment (HOMA)-IR, when compared to the non-training control group (CON); in addition to BG (p = 0.257), the combined results of other indicators have high heterogeneity (p = 0.000). HIIT showed no superior effects when compared to moderate-intensity training (MIT). Subgroup analysis demonstrated that HIIT protocol with a WRR of 1:1 was superior to MIT for reducing TG and LDL-C and used %maximal aerobic speed (MAS) as the exercise intensity was superior to MIT for reducing TG. HIIT protocol used %heart rate (HR) as the exercise intensity was superior to MIT for increasing HDL-C, decreasing BI, and HOMA-IR.ConclusionHIIT improved glycolipid metabolism in children with metabolic disorders. WRR and training intensity can affect the intervention effects of HIIT.Systematic Review Registration[https://www.crd.york.ac.uk/], identifier [CRD42021291473]

In order to solve the problem that the security of traditional internet of vehicles devices is relatively low,which may threaten the privacy of users,a privacy protection scheme based on homomorphic encryption and block chain technology was proposed.This scheme added the authentication service composed of two level nodes to the proposed model to realize the permission control of roles in the model.In order to record the information of the internet of vehicles devices,a new block data structure based on homomorphic encryption (HEBDS) was proposed,which enabled the privacy data to be written into the block after being processed by the Paillier encryption algorithm,and then written into the blockchain network by the gateway node obtaining the accounting right.This scheme realized the data processing in ciphertext state,and made up for the shortage of all data disclosure in blockchain network.Through the analysis of the security of the scheme,it is proved that the scheme has the characteristics of unforgeability and privacy data security.Through homomorphic encryption of privacy data and upload to blockchain network,the scheme can distribute,share and calculate privacy data in ciphertext state,which can protect customer privacy more effectively than traditional internet of vehicles model.

The entrance and exit area of parking facilities has the characteristics of high concentration of urban traffic and prominent traffic intertwining phenomenon, which easily induces rapid congestion of mixed heterogeneous traffic at specific times and local locations and quickly spreads to the entire road section or even a larger area. In order to better understand the congestion distribution characteristics and propagation effects of access section of the parking entrance and exit from the mid and microperspective, a 5 m ∗ lane width pixel grid is used to divide the frontage road research. It also proposes a spatially robust autoregressive model and complex network tools suitable for analysis of local traffic flow to analyze it. The results show that as spatial scale increases, the congestion propagation decreases sharply and spatial adjacency within the fourth order can account for more than 90% of the propagation; the frontage road to the entrance and exit is the place where the congestion first happens, and the congestion gradually attenuates as it propagates to the inner lane and the upstream of the road segments; the lateral congestion propagation attenuates faster, so the area affected by congestion is mainly distributed in the outermost lane. This paper can provide theoretical guidance for alleviating traffic congestion in the entrance and exit areas of parking facilities and has theoretical and empirical significance.