Microglia lactylation in relation to central nervous system diseases.

The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis. Microglia, as innate immune cells, play important roles in the maintenance of central nervous system homeostasis, injury response, and neurodegenerative diseases. Lactate has been considered a metabolic waste product, but recent studies are revealing ever more of the physiological functions of lactate. Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions, macrophage polarization, neuromodulation, and angiogenesis and has also been implicated in the development of various diseases. This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation, histone versus non-histone lactylation, and therapeutic approaches targeting lactate. Finally, we summarize the current research on microglia lactylation in central nervous system diseases. A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.

A novel gelatin composite film with melt extrusion for walnut oil packaging.

Gelatin have excellent film-forming and barrier properties, but its lack of biological activity limits its application in packaging. In this study, fish gelatin incorporated with apple polyphenol/cumin essential oil composite films were successfully prepared by melt extrusion. The cross-linking existed in gelatin and apple polyphenol improved the thermal stability and oxidation resistance of the film. The synergistic effect of apple polyphenols and cumin essential oil decreased the sensitivity of the film to water, especially the water solubility decreased from 41.60 % to 26.07 %. The plasticization of essential oil nearly doubled the elongation at break while maintaining the tensile strength of the film (11.45 MPa). Furthermore, the FG-CEO-AP film can inhibit peroxide value to extend the shelf life about 20 days in the walnut oil preservation. In summary, the apple polyphenol/cumin essential oil of FG film exhibits excellent comprehensive properties and high preparation efficiency for utilization as an active packaging material.

[Protective effect and mechanism of Zuogui Jiangtang Jieyu Formula on damage to hippocampal synaptic microenvironment in rats with diabetes-related depression based on microglia-neuron crosstalk signal CD300f/TLR4].

This study aims to reveal the protective effect and mechanism of Zuogui Jiangtang Jieyu Formula on the damage to hippo-campal synaptic microenvironment in rats with diabetes-related depression(DD) via regulating microglia immune receptor molecule-like family member f(CD300f)/Toll-like receptor 4(TLR4) signal. Firstly, the model of DD rats was established by a two-week high-fat diet+STZ injection+chronic mild and unpredictable stress plus isolation for 28 days. The rats were randomly divided into normal group, model group, CD300f blocker(CLM1, 2 µg·kg~(-1)) group, CD300f agonist(Fcγ, 5 µg·kg~(-1)) group, positive drug(0.18 g·kg~(-1) metformin+1.8 mg·kg~(-1) fluoxetine) group, and high-dose and low-dose(20.52 and 10.26 g·kg~(-1)) Zuogui Jiangtang Jieyu Formula groups. Depression-like behavior of rats was evaluated by open field and forced swimming experiments. The levels of blood glucose and insulin were detected by biochemical analysis. The levels of tumor necrosis factor α(TNF-α), interleukin-1ß(IL-1ß), indoleamine 2, 3-dioxygenase(IDO), 5-hydroxytryptamine(5-HT), and dopamine(DA) in the hippocampus were detected by enzyme-linked immunosorbent assay. The changes in the synaptic ultrastructure in hippocampal neurons of rats were observed by transmission electron microscopy. The protein expressions of CD300f, TLR4, synaptophysin(SYN), and postsynaptic density protein 95(PSD-95) in microglial cells of the hippocampus were detected by immunofluorescence and Western blot. The results indicated that compared with that in the normal group, the total movement distance in open field experiments was reduced in the model group, and the immobility time in forced swimming experiments increased, with an elevated insulin level in serum, as well as TNF-α, IL-1ß, and IDO levels in the hippocampus. The 5-HT and DA levels in the hippocampus were reduced. In addition, the CD300f expression was down-regulated in microglial cells of the hippocampus, and the TLR4 expression was up-regulated. Moreover, the expression of synapse-related proteins SYN and PSD-95 in hippocampal neurons decreased, and the synaptic ultrastructure of hippocampal neurons was significantly damaged. Compared with the model group, the CD300f blocker and agonist aggravated and alleviated the above abnormal changes, respectively. High-dose and low-dose Zuogui Jiangtang Jieyu Formula could significantly improve the above depression-like beha-vior in rats, inhibit the abnormal increase of TNF-α, IL-1ß, and IDO and the decrease of 5-HT and DA, effectively increase the expression of CD300f in microglial cells, and decrease the expression of TLR4. They could up-regulate the protein expression of presyna-ptic membrane SYN and postsynaptic membrane PSD-95 in hippocampal neurons and finally improve the damage to the hippocampal synaptic microenvironment. In conclusion, this research confirmed that Zuogui Jiangtang Jieyu Formula effectively alleviated the depression-like behavior and inhibited inflammatory activation of microglial cells in the hippocampus of rats with DD, and the mechanism might be related to the regulation of CD300f/TLR4 signal to alleviate the damage to hippocampal synaptic microenvironment.

[Research progress in prevention and treatment of vascular calcification with traditional Chinese medicine].

Vascular calcification is a pathological stage involved in the occurrence and development of cardiovascular diseases, seriously threatening human life and health. At present, few drugs can completely reverse or cure vascular calcification in clinical practice. The pathogenesis of vascular calcification mainly involves the disturbance of calcium and phosphorus homeostasis, autophagy dysfunction, loss of endogenous calcium inhibition, and the apoptosis, cytokine storm, cell osteoblastic transdifferentiation, and stromal vesicle release induced by endoplasmic reticulum stress. Following the therapeutic concepts of warming channels and dredging vessels, activating blood and resolving stasis, tonifying kidney and invigorating spleen, and removing dampness and eliminating turbid, a large number of traditional Chinese medicine(TCM) active compounds/extracts and TCM prescriptions/Chinese patent medicines have shown satisfactory performance in treating vascular calcification, while the specific mechanisms remain unclear and awaits further investigations. This article systematically summarized the pathogenesis of vascular calcification and the latest research progress of TCM in the prevention and treatment of vascular calcification, providing theoretical support for the clinical application of TCM in the prevention and treatment of vascular calcification.

Applying Deep Learning with Convolutional Neural Networks to Laryngoscopic Imaging for Automated Segmentation and Classification of Vocal Cord Leukoplakia.

Objectives: Vocal cord leukoplakia is clinically described as a white plaque or patch on the vocal cords observed during macroscopic examination, which does not take into account histological features or prognosis. A clinical challenge in managing vocal cord leukoplakia is to assess the potential malignant transformation of the lesion. This study aims to investigate the potential of deep learning (DL) for the simultaneous segmentation and classification of vocal cord leukoplakia using narrow band imaging (NBI) and white light imaging (WLI). The primary objective is to assess the model's accuracy in detecting and classifying lesions, comparing its performance in WLI and NBI. Methods: We applied DL to segment and classify NBI and WLI of vocal cord leukoplakia, and used pathological diagnosis as the gold standard. Results: The DL model autonomously detected lesions with an average intersection-over-union (IoU) >70%. In classification tasks, the model differentiated between lesions in the surgical group with a sensitivity of 93% and a specificity of 94% for WLI, and a sensitivity of 99% and a specificity of 97% for NBI. In addition, the model achieved a mean average precision of 81% in WLI and 92% in NBI, with an IoU threshold >0.5. Conclusions: The model proposed by us is helpful in assisting in accurate diagnosis of vocal cord leukoplakia from NBI and WLI.

Deciphering the influence of AP1M2 in modulating hepatocellular carcinoma growth and Mobility through JNK/ErK signaling pathway control.

BACKGROUND: Hepatocellular Carcinoma (HCC) is the most common digestive system malignancy, with unclear pathogenesis and low survival rates. AP1M2 is associated with tumor progression, but its role and molecular mechanisms in HCC remain poorly understood and require further investigation. METHODS: We utilized the Gene Expression Omnibus (GEO) and Expression Analysis Interactive Hub (XENA) databases to assess AP1M2 mRNA expression levels in HCC patients. Additionally, we employed the Cancer Genome Atlas (TCGA) database to identify pathways associated with both AP1M2 and HCC development. To evaluate the effect of AP1M2 on HCC cell proliferation and migration, we employed various techniques including EdU, CCK-8, Colony formation assay, and Transwell assays. Furthermore, Western blot analysis was conducted to examine the signaling pathways influenced by AP1M2. RESULTS: AP1M2 expression was significantly increased at the mRNA level in HCC tissues(P<0.001). Importantly, overall survival (OS) analysis confirmed the association between higher AP1M2 expression and a poorer prognosis in HCC patients compared to those with lower AP1M2 expression (P<0.019).Multivariate Cox regression analysis showed that AP1M2 was an independent prognostic factor and a valid predictor for HCC patients. Furthermore, GSEA results indicated differential enrichment of lipid, metal metabolism, and coagulation processes in HCC samples demonstrating a high AP1M2 expression phenotype. In vitro experiments supported these findings by demonstrating that AP1M2 promotes HCC cell proliferation and migration, while activating the JNK/ERK pathway. CONCLUSION: Our findings indicate that AP1M2 expression may serve as a potential molecular marker indicating a poor prognosis for HCC patients. Furthermore, we have demonstrated that AP1M2 significantly influences HCC cell proliferation and migration, with the JNK/ERK signaling pathway playing a key role in AP1M2-mediated regulation in the context of HCC.

Deciphering the complex mechanics of atherosclerotic plaques: a hybrid hierarchical theory-microrheology approach.

Understanding the viscoelastic properties of atherosclerotic plaques at rupture-prone scales is crucial for assessing their vulnerability. Here, we develop a Hybrid Hierarchical theory-Microrheology (HHM) approach, enabling the analysis of multiscale mechanical variations and distribution changes in regional tissue viscoelasticity within plaques across different spatial scales. We disclose a universal two-stage power-law rheology in plaques, characterized by distinct power-law exponents (αshort and αlong), which serve as mechanical indexes for plaque components and assessing mechanical gradients. We further propose a self-similar hierarchical theory that effectively delineates plaque heterogeneity from the cytoplasm, cell, to tissue levels. Moreover, our proposed multi-layer perceptron model addresses the viscoelastic heterogeneity and gradients within plaques, offering a promising diagnostic strategy for identifying unstable plaques. These findings not only advance our understanding of plaque mechanics but also pave the way for innovative diagnostic approaches in cardiovascular disease management. STATEMENT OF SIGNIFICANCE: Our study pioneers a Hybrid Hierarchical theory-Microrheology (HHM) approach to dissect the intricate viscoelasticity of atherosclerotic plaques, focusing on distinct components including cap fibrosis, lipid pools, and intimal fibrosis. We unveil a universal two-stage power-law rheology capturing mechanical variations across plaque structures. The proposed hierarchical model adeptly captures viscoelasticity changes from cytoplasm, cell to tissue levels. Based on the newly proposed markers, we further develop a machine learning (ML) diagnostic model that sets precise criteria for evaluating plaque components and heterogeneity. This work not only reveals the comprehensive mechanical heterogeneity within plaques but also introduces a mechanical marker-based ML strategy for assessing plaque conditions, offering a significant leap towards understanding and diagnosing atherosclerotic risks.

Terminal sequence consistency verification method for small diameter abreast optical fibers based on computer vision.

In a kind of precision industrial equipment, small diameter abreast optical fibers are used for high-speed communication among functional nodes. The arrangement order at both terminals of the abreast optical fibers need to comply with communication protocols. In this paper, we propose an automatic terminal sequence consistency verification method based on computer vision. The Hue Saturation Value (HSV) color space is used for improving the image feature extraction capability. An abreast optical fiber sequence dictionary which converts the protocol logic into an input-output mapping table is provided to follow protocol confidentiality and improve inspecting speed. A light control baffle position adaptive algorithm is designed for improving the accuracy of optical fiber incident light control. The experimental results show that the method can achieve the conductivity inspection of 1 optical fiber every 50 seconds, and the inspection accuracy is over 96.5%, which generally improves the inspection efficiency by 45% compared with manual inspection.

Association of Methylenetetrahydrofolate Reductase rs1801133 Polymorphism with osteoporosis and fracture risk in Taiwan.

Introduction: Osteoporosis is a prevalent skeletal disorder influenced by age, hormonal changes, medication use, nutrition, and genetics. The relationship between MTHFR and osteoporosis remains unclear, especially in Asians. The aim of our study was to elucidate the impact of MTHFR on osteoporosis and fracture risk. Materials and Methods: Participants were recruited from the Taiwan Precision Medicine Initiative at Taichung Veterans General Hospital. A total of 3,503 subjects with available bone mineral density measurements were selected. Using the Axiom Genome-Wide TWB 2.0 Array, we identified the MTHFR rs1801133 variant. Among these subjects, 1,624 patients carrying the variant were included in the case group, while the remaining 1,879 patients without the variant served as the control group. Results: Overall, individuals carrying the MTHFR rs1801133 variant exhibited a significantly elevated risk of developing osteoporosis. Stratified analysis by different genotypes, the results revealed a statistically significant association between the heterozygous genotype of MTHFR rs1801133 and osteoporosis. However, there was no significant correlation between MTHFR genotypes and fracture risk. Furthermore, subgroup analysis of female patients revealed age, a known risk factor, was associated with both osteoporosis and fractures. Interestingly, the presence of the MTHFR rs1801133 variant did not confer an increased risk of osteoporosis or fractures in females. Conclusion: Our study revealed a notable increase in the prevalence of osteoporosis among individuals carrying the MTHFR rs1801133 variant. Nevertheless, these individuals did not exhibit a heightened risk of major or hip fractures compared to non-carriers. Our findings could be of value in raising awareness of the increased risk of osteoporosis among individuals with this genetic variant.

Clinicopathological and prognostic features of colorectal mucinous adenocarcinomas: a systematic review and meta-analysis.

BACKGROUND: Many studies have explored the clinicopathological features and prognosis between colorectal mucinous adenocarcinoma (MAC) and adenocarcinoma (AC) and have given different results. This meta-analysis summarizes previous evidence and evaluates the clinicopathological and prognostic features of MAC relative to AC in colorectal cancers (CRCs). METHODS: The meta-analysis was conducted by searching the databases of PubMed, China National Knowledge Infrastructure (CNKI), WANFANG data, Embase, and Web of Science. Pooled odds ratios (ORs) and hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were calculated to assess the clinicopathological and prognostic differences between MAC and AC. RESULTS: Fifty-six studies involving 803157 patients met the inclusion criteria and were included in this meta-analysis. The clinicopathological features of MAC were greatly different from AC, except for lymphatic invasion (OR = 1.07, 95% CI: 0.99-1.15, P = 0.09) and perineural invasion (OR = 0.92, 95% CI: 0.79-1.06, P = 0.09). Further investigation found that MAC predicted poor OS (HR = 1.04, 95% CI: 1.03-1.04, P < 0.01), but not DFS in CRCs (HR = 1.01,95% CI: 0.88- 1.17, P = 0.85). Subgroup analysis found that MAC was obviously correlated with OS in patients with different recruitment time, with tumor located in rectum, from different regions, with different sample sizes and with TNM stage in II, and calculated by different data types(P < 0.01). CONCLUSIONS: This study shows that MAC displays obviously different clinicopathological features compared with AC. And MAC has a poor OS relative to AC but the DFS was comparable.

The effects of simvastatin on the bone microstructure and mechanics of ovariectomized mice: a micro-CT and micro-finite element analysis study.

BACKGROUND: Osteoporosis is a major health concern for postmenopausal women, and the effect of simvastatin (Sim) on bone metabolism is controversial. This study aimed to investigate the effect of simvastatin on the bone microstructure and bone mechanical properties in ovariectomized (OVX) mice. METHODS: 24 female C57BL/6J mice (8-week-old) were randomly allocated into three groups including the OVX + Sim group, the OVX group and the control group. At 8 weeks after operation, the L4 vertebral bones were dissected completely for micro-Computed Tomography (micro-CT) scanning and micro-finite element analysis (µFEA). The differences between three groups were compared using ANOVA with a LSD correction, and the relationship between bone microstructure and mechanical properties was analyzed using linear regression. RESULTS: Bone volume fraction, trabecular number, connectivity density and trabecular tissue mineral density in the OVX + Sim group were significantly higher than those in the OVX group (P < 0.05). For the mechanical properties detected via µFEA, the OVX + Sim group had lower total deformation, equivalent elastic strain and equivalent stress compared to the OVX group (P < 0.05). In the three groups, the mechanical parameters were significantly correlated with bone volume fraction and trabecular bone mineral density. CONCLUSIONS: The findings suggested that simvastatin had a potential role in the treatment of osteoporosis. The results of this study could guide future research on simvastatin and support the development of simvastatin-based treatments to improve bone health.

Application of advanced surface modification techniques in titanium-based implants: latest strategies for enhanced antibacterial properties and osseointegration.

Titanium-based implants, renowned for their excellent mechanical properties, corrosion resistance, and biocompatibility, have found widespread application as premier implant materials in the medical field. However, as bioinert materials, they often face challenges such as implant failure caused by bacterial infections and inadequate osseointegration post-implantation. Thus, to address these issues, researchers have developed various surface modification techniques to enhance the surface properties and bioactivity of titanium-based implants. This review aims to outline several key surface modification methods for titanium-based implants, including acid etching, sol-gel method, chemical vapor deposition, electrochemical techniques, layer-by-layer self-assembly, and chemical grafting. It briefly summarizes the advantages, limitations, and potential applications of these technologies, presenting readers with a comprehensive perspective on the latest advances and trends in the surface modification of titanium-based implants.

High-risks drug adverse events associated with Cetirizine and Loratadine for the treatment of allergic diseases: A retrospective pharmacovigilance study based on the FDA adverse event reporting system database.

BACKGROUND: Cetirizine and Loratadine are the two best-selling second-generation antihistamines for allergic diseases. This study aims to provide a comparative analysis of the differences in adverse drug events (ADEs) between these two medications, which can assist clinicians in making appropriate treatment decisions. METHODS: ADE reports related to Cetirizine and Loratadine obtained from the FDA adverse event reporting system (FAERS) database were analyzed using disproportionality analysis and Bayesian analysis to evaluate and compare the ADE signals of both drugs. RESULTS: A total of 28,051 and 28,073 ADE reports were retrieved from the FAERS database related to Cetirizine and Loratadine, respectively, with both drugs showing a predominance of middle-aged females. Specifically, Loratadine was associated with respiratory symptoms, mainly nasal symptoms such as rhinorrhea (n = 326, ROR 6.75), sneezing (n = 251, ROR 15.24), and nasal congestion (n = 185, ROR 4.25), while Cetirizine did not show this association. Notably, both drugs exhibited strong signals for somnolence in the nervous and psychiatric systems, especially Cetirizine (Cetirizine, n = 2556, ROR 10.52 vs. Loratadine, n = 1200, ROR 7.76). Additionally, Cetirizine itself showed strong signals for attention disturbance (n = 233, ROR 3.3), while Loratadine was associated with nervousness (n = 145, ROR 3.3). Further exploration revealed more severe adverse reactions closely associated with Cetirizine, including hallucinations, aggression, and abnormal behavior. Importantly, Cetirizine was significantly associated with the occurrence of pericarditis (n = 138, ROR 8.13), potentially leading to serious adverse consequences. CONCLUSION: Compared to Loratadine, Cetirizine poses a greater potential risk in the nervous and psychiatric systems. Additionally, this study reveals previously underestimated potential cardiac toxicity of Cetirizine; albeit at a relatively low incidence rate, the high signal intensity warrants further attention and exploration. These findings highlight the need for enhanced patient monitoring and therapy optimization when prescribing these medications, ensuring better management of allergic diseases while minimizing risks.

Ginsenoside Rh2 Alleviates LPS-Induced Inflammatory Responses by Binding to TLR4/MD-2 and Blocking TLR4 Dimerization.

Lipopolysaccharide (LPS) triggers a severe systemic inflammatory reaction in mammals, with the dimerization of TLR4/MD-2 upon LPS stimulation serving as the pivotal mechanism in the transmission of inflammatory signals. Ginsenoside Rh2 (G-Rh2), one of the active constituents of red ginseng, exerts potent anti-inflammatory activity. However, whether G-Rh2 can block the TLR4 dimerization to exert anti-inflammatory effects remains unclear. Here, we first investigated the non-cytotoxic concentration of G-Rh2 on RAW 264.7 cells, and detected the releases of pro-inflammatory cytokines in LPS-treated RAW 264.7 cells, and then uncovered the mechanisms involved in the anti-inflammatory activity of G-Rh2 through flow cytometry, fluorescent membrane localization, Western blotting, co-immunoprecipitation (Co-IP), molecular docking and surface plasmon resonance (SPR) analysis in LPS-stimulated macrophages. Our results show that G-Rh2 stimulation markedly inhibited the secretion of LPS-induced interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and nitric oxide (NO). Additionally, G-Rh2 blocked the binding of LPS with the membrane of RAW 264.7 cells through direct interaction with TLR4 and MD-2 proteins, leading to the disruption of the dimerization of TLR4 and MD-2, followed by suppression of the TLR4/NF-κB signaling pathway. Our results suggest that G-Rh2 acts as a new inhibitor of TLR4 dimerization and may serve as a promising therapeutic agent against inflammation.

Enhancing mental well-being of undergraduates: establishing cut-off values and analyzing substitutive effects of physical activity on depression regulation.

Objective: This study aimed to analyze the effects of physical activity (PA), sleep quality, and sedentary behavior on subthreshold depression (StD) among undergraduates. Methods: This study included 834 undergraduates and assessed the impact of PA time, sleep quality, and sedentary behavior on depression. The receiver operating characteristic (ROC) analysis was performed to determine cut-off values for StD risk, while the isochronous substitution analysis was performed to evaluate the effects of different activities on depression regulation. Results: Gender, age, and academic grade had no significant influence on depression levels among undergraduates (p > 0.05). However, students engaging in sedentary behavior for more than 12.1 h per day or with a Pittsburgh Sleep Quality Index score above 3.5 were at an increased risk of subclinical depression. Additionally, the isochronous substitution of light-intensity physical activity for other activities (sleep, sedentary behavior, moderate and vigorous intensity physical activity) showed statistically significant effects (p < 0.05) in both 5-min and 10-min substitution models, demonstrating a positive effect on alleviating depression. Conclusion: The findings indicate that specific lifestyle factors, particularly high levels of sedentary behavior and poor sleep quality, are crucial determinants of subclinical depression among undergraduates, independent of demographic variables such as gender, age, and academic grade. Notably, light-intensity PA plays a key role in StD regulation, as substituting it with more intense physical activities or improving sleep quality substantially reduces depression scores. Furthermore, the benefits such substitution became more pronounced with the increase in duration of the activity.

TNFSF14+ natural killer cells prevent spontaneous abortion by restricting leucine-mediated decidual stromal cell senescence.

In preparation for a potential pregnancy, the endometrium of the uterus changes into a temporary structure called the decidua. Senescent decidual stromal cells (DSCs) are enriched in the decidua during decidualization, but the underlying mechanisms of this process remain unclear. Here, we performed single-cell RNA transcriptomics on ESCs and DSCs and found that cell senescence during decidualization is accompanied by increased levels of the branched-chain amino acid (BCAA) transporter SLC3A2. Depletion of leucine, one of the branched-chain amino acids, from cultured media decreased senescence, while high leucine diet resulted in increased senescence and high rates of embryo loss in mice. BCAAs induced senescence in DSCs via the p38 MAPK pathway. In contrast, TNFSF14+ decidual natural killer (dNK) cells were found to inhibit DSC senescence by interacting with its ligand TNFRSF14. As in mice fed high-leucine diets, both mice with NK cell depletion and Tnfrsf14-deficient mice with excessive uterine senescence experienced adverse pregnancy outcomes. Further, we found excessive uterine senescence, SLC3A2-mediated BCAA intake, and insufficient TNFRSF14 expression in the decidua of patients with recurrent spontaneous abortion. In summary, this study suggests that dNK cells maintain senescence homeostasis of DSCs via TNFSF14/TNFRSF14, providing a potential therapeutic strategy to prevent DSC senescence-associated spontaneous abortion.

Open-Source Throttling of CD8+ T Cells in Brain with Low-Intensity Focused Ultrasound-Guided Sequential Delivery of CXCL10, IL-2, and aPD-L1 for Glioblastoma Immunotherapy.

Improving clinical immunotherapy for glioblastoma (GBM) relies on addressing the immunosuppressive tumor microenvironment (TME). Enhancing CD8+ T cell infiltration and preventing its exhaustion holds promise for effective GBM immunotherapy. Here, a low-intensity focused ultrasound (LIFU)-guided sequential delivery strategy is developed to enhance CD8+ T cells infiltration and activity in the GBM region. The sequential delivery of CXC chemokine ligand 10 (CXCL10) to recruit CD8+ T cells and interleukin-2 (IL-2) to reduce their exhaustion is termed an "open-source throttling" strategy. Consequently, up to 3.39-fold of CD8+ T cells are observed with LIFU-guided sequential delivery of CXCL10, IL-2, and anti-programmed cell death 1 ligand 1 (aPD-L1), compared to the free aPD-L1 group. The immune checkpoint inhibitors (ICIs) therapeutic efficacy is substantially enhanced by the reversed immunosuppressive TME due to the expansion of CD8+ T cells, resulting in the elimination of tumor, prolonged survival time, and long-term immune memory establishment in orthotopic GBM mice. Overall, LIFU-guided sequential cytokine and ICIs delivery offers an "open-source throttling" strategy of CD8+ T cells, which may present a promising strategy for brain-tumor immunotherapy.

Molecular Regulation of Shoot Architecture in Soybean.

Soybean (Glycine max [L.] Merr.) serves as a major source of protein and oil for humans and animals. Shoot architecture, the spatial arrangement of a plant's above-ground organs, strongly affects crop yield and is therefore a critical agronomic trait. Unlike wheat and rice crops that have greatly benefitted from the Green Revolution, soybean yield has not changed significantly in the past six decades owing to its unique shoot architecture. Soybean is a pod-bearing crop with pods adhered to the nodes, and variation in shoot architecture traits, such as plant height, node number, branch number and number of seeds per pod, directly affects the number of pods and seeds per plant, thereby determining yield. In this review, we summarize the relationship between soybean yield and these major components of shoot architecture. We also describe the latest advances in identifying the genes and molecular mechanisms underlying soybean shoot architecture and discuss possible directions and approaches for breeding new soybean varieties with ideal shoot architecture and improved yield.

EtROP38 suppresses apoptosis of host cells infected with Eimeria tenella by inhibition of the p38MAPK pathway.

Coccidiosis is an important parasitic disease that has serious adverse effects on the global poultry industry. The mechanism by which the pathogenic factors of Eimeria tenella damage host cells is unknown. Some kinases from the rhoptry compartment can regulate apoptosis of host cells. This study focused on revealing the role and critical nodes of E. tenella rhoptry protein (EtROP) 38 in controlling the apoptosis of host cells via the P38 mitogen-activated protein kinase (MAPK) signaling pathway. The cells were treated with EtROP38 protein, siRNA p38MAPK, or both. The rate of infection, apoptosis, and the dynamic changes in the expression and activation of key factor genes of the P38MAPK signaling pathway in host cells infected with E. tenella were measured. The results showed that the addition of EtROP38 and/or knockdown of the host cells p38 gene reduced the apoptosis rate of cecal epithelial cells (CECS), decreased the mRNA expressions of p38, p53, c-myc, c-fos, and c-jun and increased the expression of p65, decreased the protein expressions of c-myc, c-fos, and c-jun, decreased the p38 protein phosphorylation level, and increased the p65 protein phosphorylation level in CECS. When E. tenella was inoculated for 4-96 h, the addition of Et ROP38 and/or host cell p38 knockdown both increased the infection rate of host cells, and this effect was more pronounced with the addition of EtROP38 with the host cell p38 knockdown. These observations indicate that E. tenella can inhibits the activation of the p38MAPK signaling pathway in host cells via EtROP38, which suppresses apoptosis in host cells.