A novel hollow iron nanoparticle system loading PEG-Fe3O4 with C5a receptor antagonist for breast cancer treatment.

Breast cancer is the most diagnosed malignancy and major cause of cancer death among women population in the worldwide. Ferroptosis is a recently discovered iron-dependent regulated cell death involved in tumor progression and therapeutic response. Moreover, increasing studies have implied that ferroptosis is a promising approach to eliminating cancer cells like developing iron nanoparticles as a therapeutic agent. However, resistance to ferroptosis is a vital distinctive hallmark of cancer. Therefore, further investigation of the mechanism of ferroptosis resistance to enhance its tumor sensitivity is essential for ferroptosis-target breast cancer therapy. Our results revealed that the activation of C5a/C5aR pathway can drive resistance to ferroptosis and reshaping breast cancer immune microenvironment. Accordingly, loading PEG-Fe3O4 with C5aRA significantly improved the anti-tumor effect of PEG- Fe3O4 by inhibiting ferroptosis resistance and increasing macrophage polarization toward M1 phenotype. Our findings presented a novel cancer therapy strategy that combined cancer cell metal metabolism regulation and immunotherapy. The study also provided support for further evaluation of PEG- Fe3O4@C5aRA as a novel therapeutic strategy for breast cancer in clinical trials.

Organoids in the oral and maxillofacial region: present and future.

The oral and maxillofacial region comprises a variety of organs made up of multiple soft and hard tissue, which are anatomically vulnerable to the pathogenic factors of trauma, inflammation, and cancer. The studies of this intricate entity have been long-termly challenged by a lack of versatile preclinical models. Recently, the advancements in the organoid industry have provided novel strategies to break through this dilemma. Here, we summarize the existing biological and engineering approaches that were employed to generate oral and maxillofacial organoids. Then, we detail the use of modified co-culture methods, such as cell cluster co-inoculation and air-liquid interface culture technology to reconstitute the vascular network and immune microenvironment in assembled organoids. We further retrospect the existing oral and maxillofacial assembled organoids and their potential to recapitulate the homeostasis in parental tissues such as tooth, salivary gland, and mucosa. Finally, we discuss how the next-generation organoids may benefit to regenerative and precision medicine for treatment of oral-maxillofacial illness.

Towards equal neighborhood evolution? A longitudinal study of soundscape and visual evolution and housing value fluctuations in shenzhen.

The equitable evolution of neighborhood environments is closely linked to housing economics. However, the lack of quantitative and longitudinal evaluation methods makes it challenging to assess residents' neighborhood perceptions and achieve social inclusiveness goals. Using long-time series street view imagery, we quantified Shenzhen residents' multidimensional neighborhood perceptions before and after micro-renovations, including visual and soundscape dimensions, and revealed the association between perceptual evolution and the housing value. We identified inequitable results during neighborhood renewal: Neighborhoods with high soundscape scores are accompanied by low visual perception scores, and vice versa. The spatial inequality is reflected in the perceptual differentiation prevalent between urban and suburbs. Visual aspects showed a stable but weak relationship with housing value fluctuations, while soundscape aspects had a strong but more dynamic impact. The inequitable spatial evolution is facilitated by changes in residents' perceptions: expectations for positive audio-visual perceptions are increasing, but sensitivity for negative soundscape is decreasing. Meanwhile, residents are increasingly seeking diverse and rich visual neighborhood landscapes and atmospheres filled with human voices. This study provides quantitative support for the equitable evolution of neighborhoods and the economics of neighborhood landscapes. It offers a novel method for measuring multidimensional perceptions that can be applied to settlements worldwide.

Carnitine is a friend in HFpEF and foe in HFrEF.

Heart failure (HF) is a global concern, particularly HF with preserved ejection fraction (HFpEF), lacking effective treatments. Understanding the differences of metabolic profiles between HFpEF and HFrEF (heart failure with reduced ejection fraction) patients is crucial for therapeutic advancements. In this study, pseudotargeted metabolomics was employed to analyze for disparities of plasma metabolic profiles between HFpEF and HFrEF in two cohorts: discovery (n = 514) and validation (n = 3368). Plasma-free carnitine levels were significant changed in HF patients. A non-linear and U-shaped (for HFpEF) or J-shaped (for HFrEF) association between circulating free carnitine levels and the composite risk of cardiac events were observed. Interestingly, HFpEF patients with low free carnitine (≤40.18 µmol/L) displayed a poorer survival, contrasting with HFrEF where higher levels (≥35.67 µmol/L) were linked to poorer outcomes, indicating distinct metabolism pathways. In conclusion, these findings offer insights into HFpEF metabolic profiles, suggesting potential therapeutic targets.

Infrared radiation for cancer hyperthermia: the light to brighten up oncology.

INTRODUCTION: Cancer constitutes the greatest public health threat to humans, as its incidence and mortality rates continue to increase worldwide. With the development of medical physics, more practitioners focus on the direct and indirect anti-tumor effects of physical factors. Infrared radiation (INR) is currently the most rapidly developing physical therapy method for tumors and has become a favored target for many oncologists and researchers owing to its advantages of high efficiency, low toxicity, and strong feasibility. AREAS COVERED: This work provides a comprehensive collection of the latest information on INR anti-tumor research, drawing from public medical databases (PubMed, Web of Science, Embase, and Clinical Trials) from the last 10 years (2014 to 2024), and encompassing both basic and clinical research in oncology and physics. This article reviews the application of INR in tumor hyperthermia, summarizes and analyzes the practical value of INR for tumor treatment, and discusses future development trends to provide valuable assistance for the subsequent development of oncology. EXPERT OPINION: Currently, INR has continuously accumulated excellent data in the field of tumor hyperthermia, bringing practical survival benefits to patients with cancer, and playing an important role in basic and clinical cancer research.

Dietary Dihydroquercetin Alleviated Colitis via the Short-Chain Fatty Acids/miR-10a-5p/PI3K-Akt Signaling Pathway.

Gut microbiota provides an important insight into clarifying the mechanism of active substances with low bioavailability, but its specific action mechanism varied case by case and remained unclear. Dihydroquercetin (DHQ) is a bioactive flavonoid with low bioavailability, which showed beneficial effects on colitis alleviation and gut microbiota modulation. Herein, we aimed to explore the microbiota-dependent anticolitis mechanism of DHQ in sight of gut microbiota metabolites and their interactions with microRNAs (miRNAs). Dietary supplementation of DHQ alleviated dextran sulfate sodium-induced colitis phenotypes and improved gut microbiota dysbiosis. Fecal microbiota transplantation further revealed that the anticolitis activity of DHQ was mediated by gut microbiota. To clarify how the modulated gut microbiota alleviated colitis in mice, the tandem analyses of the microbiome and targeted metabolome were performed, and altered profiles of metabolite short-chain fatty acids (SCFAs) and bile acids and their producers were observed in DHQ-treated mice. In addition, SCFA treatment showed anticolitis activity compared to that of bile acids, along with the specific inhibition on the phosphoinositide-3-kinase (PI3K)-protein kinase B (Akt) pathway. Subsequently, the colonic miRNA profile of mice receiving SCFA treatment was sequenced, and a differentially expressed miR-10a-5p was identified. Both prediction analysis and dual-luciferase reporter assay indicated that miR-10a-5p directly bind to the 3'-untranslated regions of gene pik3ca, inhibit the PI3K-Akt pathway activation, and lead to colitis alleviation. Together, we proposed that gut microbiota mediated the anticolitis activity of DHQ through the SCFAs/miR-10a-5p/PI3K-Akt axis, and it provided a novel insight into clarifying the microbiota-dependent mechanism via the interaction between metabolites and miRNAs.

Salidroside prevents cadmium chloride-induced DNA damage in human fetal lung fibroblasts.

BACKGROUND: Cadmium (Cd) is an environmental pollutant and a heavy metal known for its genotoxic effects, which can lead to cancer and other related diseases. Preventing Cd-induced genotoxicity is crucial; however, there is limited research on this topic. Salidroside (SAL), a phenylpropanoid glycoside isolated from Rhodiola rosea L., is a popular medicinal compound with several health benefits. Nevertheless, its therapeutic effect on Cd-induced genotoxicity remains unexplored. METHODS: Human fetal lung fibroblasts were treated with 20 µM Cd2+ (CdCl2) for 12 h and 5-20 µM SAL was used to test the anti-DNA damage effect. DNA damage was evaluated using γH2AX expression and the alkaline comet assay. Intracellular reactive oxygen species (ROS) levels were measured using flow cytometry. RESULTS: Exposure to 20 µM Cd2+ for 12 h induced significant DNA damage in human fetal lung fibroblasts, and this effect was notably attenuated by SAL treatment. SAL treatment did not decrease ROS levels in cells treated with Cd2+. CONCLUSION: SAL effectively prevented Cd2+-induced DNA damage in human fetal lung fibroblasts. However, the underlying mechanism requires further investigation.

Do Regional Nerve Blocks During Bimaxillary Surgery Decrease Postoperative Pain and Vomiting Compared With Patient-Controlled Analgesia?

BACKGROUND: Postoperative pain after orthognathic surgery is commonly managed with opioids, which can cause nausea and vomiting. PURPOSE: The purpose of this study was to determine whether regional nerve blocks during bimaxillary surgery reduced postoperative pain and vomiting compared with patient-controlled analgesia (PCA). STUDY DESIGN, SETTING, AND SAMPLE: This retrospective cohort study recruited patients who underwent bimaxillary surgery between August 2018 and September 2020 at the Fourth Military Medical University Hospital. Participants whose procedures involved the cheekbone, temporomandibular joint, mandibular angle, or an autogenous iliac bone graft and those who were admitted to the intensive care unit after surgery were excluded. PREDICTOR VARIABLES: The primary predictor variables were postoperative analgesia management, regional maxillary and inferior alveolar nerve blocks, and PCA. OUTCOME VARIABLES: The primary outcome variables were moderate-to-severe postoperative pain and postoperative vomiting (POV) during the first 24 hours. Moderate-to-severe pain was defined as pain numerical rating scale ≥4, POV was defined as vomiting of gastrointestinal contents. COVARIATES: The study covariates included demographic, surgical, and anesthesia characteristics. ANALYSES: Statistical analyses were conducted using an unpaired t-test, χ2 test, or Fisher's exact test for the bivariate analysis. A multivariate logistic regression analysis was performed to assess the associations between the primary predictor variables and outcomes. Statistical significance was set at P < .05. RESULTS: 354 participants were included in the study (262 in the nerve block group, mean age 22.5 ± 4.0 years; 92 in the PCA group, mean age 22.6 ± 4.4 years; P = .81). There was no significant difference in sex between the groups (63.4 and 55.4% females in nerve block and PCA groups, respectively, P = .18). The multivariate regression analyses demonstrated that nerve blocks did not decrease moderate-to-severe postoperative pain (7.6 vs 10.9%, adjusted odds ratio = 0.67, 95% confidence interval: 0.22-2.01, P = .48), although they were associated with decreased POV (38.5 vs 65.2%, adjusted odds ratio = 0.34, 95% confidence interval: 0.18-0.65, P = .001). CONCLUSION AND RELEVANCE: For bimaxillary surgery, regional nerve blocks as opioid-free postoperative analgesia were not significantly associated with decreased postoperative pain but were associated with a lower POV risk.

Exploring Multiple Perspectives on Psychological Health of Adolescents in Relation to Gender and School Grade - Jiangsu Province, China, 2022.

What is already known about this topic?: Mental health issues in Chinese children and adolescents have emerged as a substantial public health concern, causing distress and strain among families and society. What is added by this report?: This study examines the effects of gender and school grade on mental health symptoms and risky behaviors among Chinese children and adolescents, with a particular focus on the role of family and school environments. What are the implications for public health practice?: Caregivers and educators should enhance their awareness and skills in supporting the mental health of children. These findings offer critical insights for the early detection and intervention of mental health issues in Chinese children and adolescents.

Simple aneuploidy evades p53 surveillance and promotes niche factor-independent growth in human intestinal organoids.

Aneuploidy is nearly ubiquitous in tumor genomes, but the role of aneuploidy in the early stages of cancer evolution remains unclear. Here, by inducing heterogeneous aneuploidy in non-transformed human colon organoids (colonoids), we investigated how the effects of aneuploidy on cell growth and differentiation may promote malignant transformation. Previous work implicated p53 activation as a downstream response to aneuploidy induction. We found that simple aneuploidy, characterized by 1-3 gained or lost chromosomes, resulted in little or modest p53 activation and cell cycle arrest when compared with more complex aneuploid cells. Single-cell RNA sequencing analysis revealed that the degree of p53 activation was strongly correlated with karyotype complexity. Single-cell tracking showed that cells could continue to divide despite the observation of one to a few lagging chromosomes. Unexpectedly, colonoids with simple aneuploidy exhibited impaired differentiation after niche factor withdrawal. These findings demonstrate that simple aneuploid cells can escape p53 surveillance and may contribute to niche factor-independent growth of cancer-initiating colon stem cells.

Bedtime music therapy for college students with insomnia: A randomized assessor-blinded controlled trial.

BACKGROUND: Insomnia, a prevalent sleep disorder in contemporary society, frequently coexists with other mental health conditions such as depression, schizophrenia, and obsessive-compulsive disorder. Sleep disorders can compromise daytime functioning and overall quality of life. While music has been explored as an adjunct therapy for insomnia, its efficacy in improving insomnia among students remains unclear. METHODS: Seventy-five students, aged between 18 and 30 years with an average age of 20.97 years (SD: 1.92), presenting sleep issues were randomly allocated to one of three groups: the classical music group, the jazz music group, and the control group, each with 25 participants. Participants in the classical and jazz music group were instructed to listen to classical or jazz music for a minimum of 30 min preceding bedtime. This was paired with deep breathing and relaxation techniques, practiced two consecutive nights per week from 23:00 to 01:00 over a five-week intervention period. Conversely, participants in the control group were only directed to follow the deep breathing and relaxation techniques before sleep on two consecutive nights weekly. Insomnia severity with the Insomnia Severity Index (ISI), sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), depressive symptoms with the Beck Depression Inventory-II (BDI- II), and anxiety symptoms with the Self-rating Anxiety Scale (SAS). Measurements were taken at baseline, after the second week of intervention, at the intervention's conclusion (five weeks), and two months post-intervention (follow-up). RESULTS: 1. The music groups showed a significant difference in insomnia severity compared with the control group after five weeks of intervention(p < .05). 2. music groups exhibited significant enhancements in sleep quality relative to the control group after a five-week intervention (p < .05). 3. Regarding mood enhancement, music groups showed significant improvements in depression and anxiety symptoms compared to the baseline after the five-week intervention. Notably, the control group also displayed improvements in these symptoms post-intervention. CONCLUSION: 1. Integrating music into a consistent bedtime routine ameliorates sleep quality and insomnia severity. However, no specific genre of music emerged as the superior choice for pre-sleep listening. 2. While music can considerably enhance mood indicators like depression and anxiety, techniques such as deep breathing and mindfulness also contribute positively. 3. Incorporating music before sleep tangibly elevates overall quality of life and daytime functioning. TRIAL REGISTRATION: ChiCTR2300073953.

Water-filtered infrared A radiation hyperthermia combined with immunotherapy for advanced gastrointestinal tumours.

This study pioneered the use of WIRA whole-body infrared hyperthermia combined with ICI therapy to treat GIT and verified the feasibility and safety of HIT. The final results showed a DCR of 55.6%, with a median PFS of 53.5 days, median OS of 134 days, and an irAE incidence of 22.2%. Therefore, we believe that HIT can exert multiple synergistic sensitisation effects, thereby providing clinical benefits to patients with advanced GITs, increasing overall safety, and improving patients' QOL.

INTRODUCTION: This study aimed to validate the effectiveness, safety and feasibility of water­filtered infrared A radiation (WIRA) whole­body hyperthermia combined with immune checkpoint inhibitor (ICI) therapy (HIT) and evaluate the real­world clinical application prospects. METHODS: This open­label single­arm phase 2 clinical trial (NCT06022692) aimed to enrol advanced gastrointestinal tumour (GIT) patients with the MSS/pMMR phenotype. The patients were treated with whole­body hyperthermia on Days 1 and 8 of each HIT cycle along with administration of tislelizumab on Day 2. RESULTS: Between 1 June 2020 and 31 May 2022, 18 patients were enrolled in the study, including those with gastric cancer (n = 6), colon cancer (n = 7), rectal cancer (n = 3) and appendiceal cancer (n = 2). As of 19 May 2023, 17 of the 18 patients had died, including 14 deaths caused by tumour progression and three deaths caused by diseases other than cancer, while one patient was still undergoing follow­up. In terms of efficacy, the median DCR was 55.6%, while the median PFS and OS were 53.5 days and 134 days, respectively. Four patients (22.2%) experienced immune­related adverse events, and none of the patients reported grade 3 or higher irAEs. Hyperthermia was followed by an increase in the number of tumour immune­activated cells. CONCLUSIONS: HIT can provide survival benefits in patients with GITs by activating antitumour immune function and shows good safety and feasibility.

Cell-Driven Fluid Dynamics: A Physical Model of Active Systemic Circulation.

Active fluid circulation and transport are key functions of living organisms, which drive efficient delivery of oxygen and nutrients to various physiological compartments. Because fluid circulation occurs in a network, the systemic flux and pressure are not simple outcomes of any given component. Rather, they are emergent properties of network elements and network topology. Moreover, consistent pressure and osmolarity gradients across compartments such as the kidney, interstitium, and vessels are known. How these gradients and network properties are established and maintained is an unanswered question in systems physiology. Previous studies have shown that epithelial cells are fluid pumps that actively generate pressure and osmolarity gradients. Polarization and activity of ion exchangers that drive fluid flux in epithelial cells are affected by pressure and osmolarity gradients. Therefore, there is an unexplored coupling between the pressure and osmolarity in the circulating network. Here we develop a mathematical theory that integrates the influence of pressure and osmolarity on solute transport and explores both cell fluid transport and systemic circulation. This model naturally generates pressure and osmolarity gradients across physiological compartments, and demonstrates how systemic transport properties can depend on cell properties, and how the cell state can depend on systemic properties. When epithelial and endothelial pumps are considered together, we predict how pressures at various points in the network depend on the overall osmolarity of the system. The model can be improved by including physiological geometries and expanding solute species, and highlights the interplay of fluid properties with cell function in living organisms.

Pentacyclic triterpenoids as potential ACL inhibitors from the rare medicinal plant Semiliquidambar cathayensis.

An extensive phytochemical investigation on the rare medicinal plant Semiliquidambar cathayensis (family: Hamamelidaceae) led to the isolation of four new (1-4, named semiliquidacids A-D, respectively) and 25 related known pentacyclic triterpenoids. The new structures with absolute configurations were elucidated by spectroscopic methods, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. Compound 1 represents the first naturally occurring ursane-type triterpenoid featuring an uncommon C-25 formyl group. Compound 4 and oleanolic acid (13) exhibited remarkable inhibitory effects against the ATP-citrate lyase (ACL, an emerging drug target for hyperlipidemia and related metabolic disorders) with IC50 values of 6.5 and 11.9 µM, respectively. The molecular interaction and binding mode between the bioactive triterpenoids and ACL were elaborated by conducting a molecular docking study. Meanwhile, the chemotaxonomic significance of the isolated triterpenoids has been briefly discussed.

Using deep learning-based artificial intelligence electronic images in improving middle school teachers' literacy.

With the rapid development of societal information, electronic educational resources have become an indispensable component of modern education. In response to the increasingly formidable challenges faced by secondary school teachers, this study endeavors to analyze and explore the application of artificial intelligence (AI) methods to enhance their cognitive literacy. Initially, this discourse delves into the application of AI-generated electronic images in the training and instruction of middle school educators, subjecting it to thorough analysis. Emphasis is placed on elucidating the pivotal role played by AI electronic images in elevating the proficiency of middle school teachers. Subsequently, an integrated intelligent device serves as the foundation for establishing a model that applies intelligent classification and algorithms based on the Structure of the Observed Learning Outcome (SOLO). This model is designed to assess the cognitive literacy and teaching efficacy of middle school educators, and its performance is juxtaposed with classification algorithms such as support vector machine (SVM) and decision trees. The findings reveal that, following 600 iterations of the model, the SVM algorithm achieves a 77% accuracy rate in recognizing teacher literacy, whereas the SOLO algorithm attains 80%. Concurrently, the spatial complexities of the SVM-based and SOLO-based intelligent literacy improvement models are determined to be 45 and 22, respectively. Notably, it is discerned that, with escalating iterations, the SOLO algorithm exhibits higher accuracy and reduced spatial complexity in evaluating teachers' pedagogical literacy. Consequently, the utilization of AI methodologies proves highly efficacious in advancing electronic imaging technology and enhancing the efficacy of image recognition in educational instruction.

Microwave hyperthermia enhances radiosensitization by decreasing DNA repair efficiency and inducing oxidative stress in PC3 prostatic adenocarcinoma cells.

PURPOSE: Radiotherapy (RT) is the primary treatment for prostate cancer (PCa); however, the emergence of castration-resistant prostate cancer (CRPC) often leads to treatment failure and cancer-related deaths. In this study, we aimed to explore the use of microwave hyperthermia (MW-HT) to sensitize PCa to RT and investigate the underlying molecular mechanisms. METHODS: We developed a dedicated MW-HT heating setup, created an in vitro and in vivo MW-HT + RT treatment model for CRPC. We evaluated PC3 cell proliferation using CCK-8, colony experiments, DAPI staining, comet assay and ROS detection method. We also monitored nude mouse models of PCa during treatment, measured tumor weight, and calculated the tumor inhibition rate. Western blotting was used to detect DNA damage repair protein expression in PC3 cells and transplanted tumors. RESULTS: Compared to control, PC3 cell survival and clone formation rates decreased in RT + MW-HT group, demonstrating significant increase in apoptosis, ROS levels, and DNA damage. Lower tumor volumes and weights were observed in treatment groups. Ki-67 expression level was reduced in all treatment groups, with significant decrease in RT + MW-HT groups. The most significant apoptosis induction was confirmed in RT + MW-HT group by TUNEL staining. Protein expression levels of DNA-PKcs, ATM, ATR, and P53/P21 signaling pathways significantly decreased in RT + MW-HT groups. CONCLUSION: MW-HT + RT treatment significantly inhibited DNA damage repair by downregulating DNA-PKcs, ATM, ATR, and P53/P21 signaling pathways, leading to increased ROS levels, aggravate DNA damage, apoptosis, and necrosis in PC3 cells, a well-established model of CRPC.

BAP31 Promotes Angiogenesis via Galectin-3 Upregulation in Neuroblastoma.

Neuroblastoma (NB) is one of the highly vascularized childhood solid tumors, and understanding the molecular mechanisms underlying angiogenesis in NB is crucial for developing effective therapeutic strategies. B-cell receptor-associated protein 31 (BAP31) has been implicated in tumor progression, but its role in angiogenesis remains unexplored. This study investigated BAP31 modulation of pro-angiogenic factors in SH-SY5Y NB cells. Through protein overexpression, knockdown, antibody blocking, and quantification experiments, we demonstrated that overexpression of BAP31 led to increased levels of vascular endothelial growth factor A (VEGFA) and Galectin-3 (GAL-3), which are known to promote angiogenesis. Conditioned medium derived from BAP31-overexpressing neuroblastoma cells stimulated migration and tube formation in endothelial cells, indicating its pro-angiogenic properties. Also, we demonstrated that BAP31 enhances capillary tube formation by regulating hypoxia-inducible factor 1 alpha (HIF-1α) and its downstream target, GAL-3. Furthermore, GAL-3 downstream proteins, Jagged 1 and VEGF receptor 2 (VEGFR2), were up-regulated, and blocking GAL-3 partially inhibited the BAP31-induced tube formation. These findings suggest that BAP31 promotes angiogenesis in NB by modulating GAL-3 and VEGF signaling, thereby shaping the tumor microenvironment. This study provides novel insights into the pro-angiogenic role of BAP31 in NB.

SiRNA-HIF-1α delivered by attenuated Salmonella enhances the efficacy of Lenvatinib against hepatocellular carcinoma.

The treatment of hepatocellular carcinoma (HCC) remains a major challenge in the medical field. Lenvatinib, a multi-target tyrosine kinase inhibitor, has demonstrated anti-HCC effects by targeting and inhibiting pathways such as vascular endothelial growth factor receptor 1-3 (VEGFR1-3). However, the therapeutic efficacy of Lenvatinib is subject to various influences, with the hypoxic microenvironment of the tumor being a pivotal factor. Consequently, altering the hypoxic milieu of the tumor emerges as a viable strategy to augment the efficacy of Lenvatinib. Hypoxia-inducible factor-1α (HIF-1α), synthesized by tumor cells in response to oxygen-deprived conditions, regulates the expression of resistance genes, promotes tumor angiogenesis and cell proliferation, enhances tumor cell invasion, and confers resistance to radiotherapy and chemotherapy. Thus, we constructed a self-designed siRNA targeting HIF-1α to suppress its expression and improve the efficacy of Lenvatinib in treating HCC. The therapeutic efficacy of siRNA-HIF-1α in combination with Lenvatinib on HCC were evaluated through in vivo and in vitro experiments. The results showed that the recombinant Salmonella delivering siRNA-HIF-1α in combination with Lenvatinib effectively inhibited tumor growth and prolonged the survival of tumor-bearing mice. This treatment approach reduced cell proliferation and angiogenesis in HCC tissues while promoting tumor cell apoptosis. Additionally, this combined therapy significantly increased the infiltration of T lymphocytes and M1 macrophages within the tumor microenvironment, as well as elevated the proportion of immune cells in the spleen, thereby potentiating the host's immune response against the tumor.

The use of deep learning integrating image recognition in language analysis technology in secondary school education.

This work aims to investigate the application of advanced deep learning algorithms and image recognition technologies to enhance language analysis tools in secondary education, with the goal of providing educators with more effective resources and support. Based on artificial intelligence, this work integrates data mining techniques related to deep learning to analyze and study language behavior in secondary school education. Initially, a framework for analyzing language behavior in secondary school education is constructed. This involves evaluating the current state of language behavior, establishing a framework based on evaluation comments, and defining indicators for analyzing language behavior in online secondary school education. Subsequently, data mining technology and image and character recognition technology are employed to conduct data mining for online courses in secondary schools, encompassing the processing of teaching video images and character recognition. Finally, an experiment is designed to validate the proposed framework for analyzing language behavior in secondary school education. The results indicate specific differences among the grouped evaluation scores for each analysis indicator. The significance p values for the online classroom discourse's speaking rate, speech intelligibility, average sentence length, and content similarity are -0.56, -0.71, -0.71, and -0.74, respectively. The aim is to identify the most effective teaching behaviors for learners and enhance the support for online course instruction.

A Novel Signature Based on m6A Regulator-Mediated Genes Along Glycolytic Pathway Predicts Prognosis and Immunotherapy Responses of Gastric Cancer Patients.

N6-methyladenosine (m6A) modification is involved in many aspects of gastric cancer (GC). Moreover, m6A and glycolysis-related genes (GRGs) play important roles in immunotherapeutic and prognostic implication of GC. However, GRGs involved in m6A regulation have never been analyzed comprehensively in GC. Herein, the study aims to identify and validate a novel signature based on m6A-related GRGs in GC patients. Therefore, a m6A-related GRGs signature is established, which can predict the survival of patients with GC and remain an independent prognostic factor in multivariate analyses. Clinical significance of the model is well validated in internal cohort and independent validation cohort. In addition, the expression levels of risk model-related GRGs in clinical samples are validated. Consistent with the database results, all model genes are up-regulated in expression except DCN. After regrouping the patients based on this risk model, the study can effectively distinguish between them in respect to immune-cell infiltration microenvironment and immunotherapeutic response. Additionally, candidate drugs targeting risk model-related GRGs are confirmed. Finally, a nomogram combining risk scores and clinical parameters is created, and calibration plots show that the nomogram can accurately predict survival. This risk model can serve as a reliable assessment tool for predicting prognosis and immunotherapeutic responses in GC patients.