Molecular evolution and functional diversification of metal tolerance protein families in cereals plants and function of maize MTP protein.

Plants employ metal tolerance proteins (MTPs) to confer tolerance by sequestering excess ions into vacuoles. MTPs belong to the cation diffusion facilitator (CDF) family, which facilitates the transport of divalent transition metal cations. In this study, we conducted a comprehensive analysis of the MTP gene families across 21 plant species, including maize (Zea mays). A total of 247 MTP genes were identified within these plant genomes and categorized into distinct subgroups, namely Zn-CDF, Mn-CDF, and Fe/Zn-CDF, based on phylogenetic analyses. This investigation encompassed the characterization of genomic distribution, gene structures, cis-regulatory elements, collinearity relationships, and gene ontology functions associated with MTPs. Transcriptomic analyses unveiled stress-specific expression patterns of MTP genes under various abiotic stresses. Moreover, quantitative RT-PCR assays were employed to assess maize MTP gene responses to diverse heavy metal stress conditions. Functional validation of metal tolerance roles was achieved through heterologous expression in yeast. This integrated evolutionary scrutiny of MTP families in cereals furnishes a valuable framework for the elucidation of MTP functions in subsequent studies. Notably, the prioritized MTP gene ZmMTP6 emerged as a positive regulator of plant Cd tolerance, thereby offering a pivotal genetic asset for the development of Cd-tolerant crops, particularly maize cultivars.

Human Amniotic Epithelial Stem Cells Alleviate Autoimmune Premature Ovarian Insufficiency in Mice by Targeting Granulosa Cells via AKT/ERK Pathways.

Autoimmune factors play an important role in premature ovarian insufficiency (POI). Human amniotic epithelial stem cells (hAESCs) have recently shown promising treatment effects on chemotherapy-induced POI. However, the therapeutic efficacy and underlying mechanisms of hAESCs in autoimmune POI remain to be investigated. In this study, we showed for the first time that intravenous transplantation of hAESCs could reside in the ovary of zona pellucida 3 peptide (pZP3) induced autoimmune POI mice model for at least 4 weeks. hAESCs could improve ovarian function and fertility, alleviate inflammation and reduce apoptosis of granulosa cells (GCs) in autoimmune POI mice. The transcriptome analysis of mice ovaries and in vitro co-cultivation experiments suggest that activation of the AKT and ERK pathways may be the key mechanism in the therapeutic effect of hAESCs. Our work provides the theoretical and experimental foundation for optimizing the administration of hAESCs, as well as the clinical application of hAESCs in autoimmune POI patients.

Identification and Validation of SLC9A2 as A Potential Tumor Suppressor in Colorectal Cancer: Integrating Bioinformatics Analysis with Experimental Confirmation.

OBJECTIVE: To uncover the mechanisms underlying the development of colorectal cancer (CRC), we applied bioinformatic analyses to identify key genes and experimentally validated their possible roles in CRC onset and progression. METHODS: We performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis on differentially expressed genes (DEGs), constructed a protein-protein interaction (PPI) network to find the top 10 hub genes, and analyzed their expression in colon adenocarcinoma (COAD) and rectum adenocarcinoma (READ). We also studied the correlation between these genes and immune cell infiltration and prognosis and validated the expression of SLC9A2 in CRC tissues and cell lines using qRT-PCR and Western blotting. Functional experiments were conducted in vitro to investigate the effects of SLC9A2 on tumor growth and metastasis. RESULTS: We found 130 DEGs, with 45 up-regulated and 85 down-regulated in CRC. GO analysis indicated that these DEGs were primarily enriched in functions related to the regulation of cellular pH, zymogen granules, and transmembrane transporter activity. KEGG pathway analysis revealed that the DEGs played pivotal roles in pancreatic secretion, rheumatoid arthritis, and the IL-17 signaling pathway. We identified 10 hub genes: CXCL1, SLC26A3, CXCL2, MMP7, MMP1, SLC9A2, SLC4A4, CLCA1, CLCA4, and ZG16. GO enrichment analysis showed that these hub genes were predominantly involved in the positive regulation of transcription. Gene expression analysis revealed that CXCL1, CXCL2, MMP1, and MMP7 were highly expressed in CRC, whereas CLCA1, CLCA4, SLC4A4, SLC9A2, SLC26A3, and ZG16 were expressed at lower levels. Survival analysis revealed that 5 key genes were significantly associated with the prognosis of CRC. Both mRNA and protein expression levels of SLC9A2 were markedly reduced in CRC tissues and cell lines. Importantly, SLC9A2 overexpression in SW480 cells led to a notable inhibition of cell proliferation, migration, and invasion. Western blotting analysis revealed that the expression levels of phosphorylated ERK (p-ERK) and phosphorylated JNK (p-JNK) proteins were significantly increased, whereas there were no significant changes in the expression levels of ERK and JNK following SLC9A2 overexpression. Correlation analysis indicated a potential link between SLC9A2 expression and the MAPK signaling pathway. CONCLUSION: Our study suggests that SLC9A2 acts as a tumor suppressor through the MAPK pathway and could be a potential target for CRC diagnosis and therapy.

Zeolite-Templated Carbons Supported Rh and Ru Electrocatalysts for Highly Active Hydrogen Evolution Reaction.

Here, we report the systematical synthesis of zeolite-templated carbon (ZTC) supported Ru and Rh mono- or bi-metallic electrocatalysts towards hydrogen evolution reaction (HER). The zeolite A or ZSM-5 derived ZTC supports and metal sites were adjusted, and all electrocatalysts outperformed the commercial Pt/C electrocatalyst for HER performance. In particular, the RhRu/(ZTC/ZSM5) sample exhibited superior catalytic performance with the overpotential of 24.8 mV@10 mA ⋅ cm-2, and outstanding stability with 1 mV drop after 20000 cyclic voltammetry circles. This work offers a simple impregnation method for the synthesis of highly performed HER electrocatalysts supported on porous zeolite-templated carbon.

AMPA receptor potentiation alleviates NLRP3 knockout-induced fear generalization in mice.

Genetic knockout and pharmaceutical inhibition of the NLRP3 inflammasome enhances the extinction of contextual fear memory, which is attributed to its role in neuronal and synaptic dysregulation, concurrent with neurotransmitter function disturbances. This study aimed to determine whether NLRP3 plays a role in generalizing fear via the inflammatory axis. We established the NLRP3 KO mice model, followed by behavioral and biochemical analyses. The NLRP3 KO mice displayed impaired fear generalization, lower neuroinflammation levels, and dysregulated neurotransmitter function. Additionally, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, but not the inhibition of NMDA or 5-HT2C receptors, resulted in fear generalization in NLRP3 KO mice because TAT-GluA2 3Y, but not SB242084 and D-cycloserine, treated blocked NLRP3 deprivation effects on fear generalization. Thus, global knockout of NLRP3 is associated with aberrant fear generalization, possibly through AMPA receptor signaling.

Amphiphilic hydroxyethyl starch-based nanoparticles carrying linoleic acid modified berberine inhibit the expression of krasv12 oncogene in zebrafish.

Cancer is one of the most lethal diseases all over the world. Despite that many drugs have been developed for cancer therapy, they still suffer from various limitations including poor treating efficacy, toxicity to normal human cells, and the emergence of multidrug resistance. In this study, the amphiphilic LHES polymers were prepared using hydroxyethyl starch (HES) and linoleic acid as starting materials. The content and substitution degree of linoleic acid groups in LHES polymers were analyzed. The LHES polymers were used for fabricating LHES-B nanoparticles carrying a linoleic acid modified berberine derivative (L-BBR). The LHES-B nanoparticles showed high drug loading efficiency (29%) and could quickly release L-BBR under acidic pH condition (pH = 4.5). Biological investigations revealed that LHES-B nanoparticles significantly inhibited the proliferation of HepG2 cells and exhibited higher cytotoxicity than L-BBR. In a transgenic Tg(fabp10:rtTA2s-M2; TRE2:EGFP-krasv12) zebrafish model, LHES-B nanoparticles obviously inhibited the expression of krasv12 oncogene. These results indicated that LHES carriers could improve the anticancer activity of L-BBR, and the synthesized LHES-B nanoparticles showed great potential as anticancer drug.

Precise capture of circulating endometrial cells in endometriosis.

BACKGROUND: Endometriosis (EM) is a complex benign gynecological disease, but it has malignant biological behavior and can invade any part of the body. Clinical manifestations include pelvic pain, dysmenorrhea, infertility, pelvic nodules, and masses. Our previous study successfully detected circulating endometrial cells (CECs) in the peripheral blood of patients with EM. The purpose of this study is to overcome the limitation of cell size in the previous microfluidic chip method, to further accurately capture CECs, understand the characteristics of these cells, and explore the relationship between CECs and the clinical course characteristics of patients with EM. METHODS: Human peripheral venous blood used to detect CECs and circulating vascular endothelial cells (CVECs) was taken from EM patients (n = 34) hospitalized in the Peking University People's Hospital. We use the subtraction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) method to exclude the interference of red blood cells, white blood cells, and CVECs, so as to accurately capture the CECs in the peripheral blood of patients with EM. Then we clarify the size and ploidy number of chromosome 8 of CECs, and a second grouping of patients was performed based on clinical characteristics to determine the relationship between CECs and clinical course characteristics. RESULTS: The peripheral blood of 34 EM patients and 12 non-EM patients was evaluated by SE-iFISH. Overall, 34 eligible EM patients were enrolled. The results showed that the detection rates of CECs were 58.8% in EM patients and 16.7% in the control group. However, after classification according to clinical characteristics, more CECs could be detected in the peripheral blood of patients with rapidly progressive EM, with a detection rate of 94.4% (17/18). In total, 63.5% (40/63) of these cells were small cells with diameters below 5 µm, and 44.4% (28/63) were aneuploid cells. No significant association was found between the number of CECs and EM stage. CONCLUSION: The number and characteristics of CECs are related to the clinical course characteristics of patients with EM, such as pain and changes in lesion size, and may be used as biomarkers for personalized treatment and management of EM in the future.

Gamma oscillations induced by 40-Hz visual-auditory stimulation for the treatment of acute-phase limb motor rehabilitation after stroke: study protocol for a prospective randomized controlled trial.

BACKGROUND: The incidence of hemiparetic limb dysfunction reaches 85% in stroke patients, emerging as a critical factor influencing their daily lives. However, the effectiveness of current rehabilitation treatments is considerably limited, particularly in patients with upper extremity impairment. This study aims to conduct a prospective clinical trial to validate the safety and effectiveness of gamma oscillations induced by 40-Hz visual-auditory stimulation in treating post-stroke upper limb dysfunction and to explore the relevant mechanisms. METHODS: This trial is a prospective, randomized controlled, double-blind study. All enrolled patients were randomly assigned to two groups. The experimental group received intervention through 40-Hz visual-auditory stimulation, while the control group underwent intervention with randomly matched visual-auditory stimulation frequencies. The primary efficacy endpoint is the change in motor function. Secondary efficacy endpoints include motor-evoked potentials, cerebral hemodynamic changes, neural network connectivity, and alterations in synaptic-related genes. Safety evaluation included major adverse events, all-cause mortality, and photosensitive epilepsy. Assessments will be conducted at baseline, after a 14-day treatment period, and during subsequent follow-up visits (at 3 and 6 months) post-treatment. The differences between the two groups will be compared. DISCUSSION: This study will evaluate the safety and efficacy of gamma oscillations induced by 40-Hz visual-auditory stimulation in treating patients with upper extremity dysfunction after an acute cerebral stroke. Concurrently, we will explore potential mechanisms, including changes in synaptic-related genes and neural network connectivity. This trial is expected to provide evidence for the effectiveness of this new technique in treating upper extremity dysfunction after a stroke and improving patients' quality of life. TRIAL REGISTRATION: The study protocol has been registered with the Chinese Clinical Trial Registry (ChiCTR) under registration number ChiCTR2300076579 on October 12, 2023.

Retracted: Expression of TP53, BCL-2, and VEGFA Genes in Esophagus Carcinoma and its Biological Significance.

The Editors of Medical Science Monitor wish to inform you that the above manuscript has been retracted from publication due to concerns with the credibility and originality of the study, the manuscript content, and the Figure images. Reference: Wei Wei, Yanqin Wang, Xiaoming Yu, Lan Ye, Yuhua Jiang, Yufeng Cheng. Expression of TP53, BCL-2, and VEGFA Genes in Esophagus Carcinoma and its Biological Significance. Med Sci Monit, 2015; 21: 3016-3022. DOI: 10.12659/MSM.894640.

Conventional dendritic cells 2, the targeted antigen-presenting-cell, induces enhanced type 1 immune responses in mice immunized with CVC1302 in oil formulation.

Multifunctional CD4+ T helper 1 (Th1) cells, producing IFN-γ, TNF-α and IL-2, define a correlate of vaccine-mediated protection against intracellular infection. In our previous study, we found that CVC1302 in oil formulation promoted the differentiation of IFN-γ+/TNF-α+/IL-2+Th1 cells. In order to extend the application of CVC1302 in oil formulation, this study aimed to elucidate the mechanism of action in improving the Th1 immune response. Considering the signals required for the differentiation of CD4+ T cells to Th1 cells, we detected the distribution of innate immune cells and the model antigen OVA-FITC in lymph node (LN), as well as the quantity of cytokines produced by the innate immune cells. The results of these experiments show that, cDC2 and OVA-FITC localized to interfollicular region (IFR) of the draining lymph nodes, inflammatory monocytes localized to both IFR and T cell zone, which mainly infiltrate from the blood. In this inflammatory niche within LN, CD4+ T cells were attracted into IFR by CXCL10, secreted by inflammatory monocytes, then activated by cDC2, secreting IL-12. Above all, CVC1302 in oil formulation, on the one hand, targeted antigen and inflammatory monocytes into the LN IFR in order to attract CD4+ T cells, on the other hand, targeted cDC2 to produce IL-12 in order to promote optimal Th1 differentiation. The new finding will provide a blueprint for application of immunopotentiators in optimal formulations.

Ceftriaxone averts neuroinflammation and relieves depressive-like behaviors via GLT-1/TrkB signaling.

The beneficial effect of a beta-lactam antibiotic, Ceftriaxone (CEF), to improve depressive-like symptoms has been documented previously, attributed to its modulation of glutamate neurotransmission. Here, we aimed to determine whether CEF could improve LPS-altered glutamatergic signaling associated with neuroinflammation-allied depression. To assess our goals, we established a neuroinflammation-allied depression mice model by injecting lipopolysaccharides (LPS), followed by behavioral and biochemical analysis. LPS-treated mice displayed depressive symptoms, neuroinflammation, dysregulated glutamate and its transporter (GLT-1) expression, altered expression of astrocyte reactive markers (GFAP, cxcl10, steap4, GBP2, and SRGN), and dysregulated BDNF/TrkB signaling. However, these changes were rescued by CEF treatment, as we found decreased neuroinflammation, relief of depression symptoms, and improved GLT-1 and BDNF/TrkB signaling upon CEF treatment. Moreover, GLT-1 and BDNF/TrkB regulation role of CEF was validated by K252a and DHK treatment. In summary, the anti-depressive effects of glutamate modulators, like CEF, are closely related to their anti-inflammatory role.

Dipole Field-Driven Organic-Inorganic Heterojunction for Highly Sensitive Ultraviolet Photodetector.

Developing high-performance organic-inorganic ultraviolet (UV) photodetectors (PDs) has attracted considerable attention. However, this development has been hindered due to poor directional charge-transfer ratios in transport layers, excessive costs, and an ambiguous underlying mechanism. To tackle these challenges, we constructed a heterojunction of economic Mg-doped ZnO (MgZnO) nanorods and poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) [PEDOT:PSS (P:P)] that utilizes dipole field-driven spontaneous polarization to enhance photogenerated charge kinetics. As a result, the proposed heterojunction has an improved noise equivalent power of 3.16 × 10-11 W Hz-1/2), a normalized detection rate (D*) of 8.96 × 109 jones, and external quantum efficiency comparable to other ZnO-based devices. Notably, the prepared PDs showed a photocurrent of 4.8 × 10-3 µA under a faint UV light having an intensity of 1 × 10-5 W cm-2, exceeding the performance of the most state-of-the-art ZnO-based UV sensors. The introduction of Mg into ZnO is responsible for the high performance, as it causes a lattice mismatch and distortion of the Mg-doped ZnO unit cell. It results in improved dipole movement and the creation of a dipole field, accelerating the directional electron-transfer process. Using a dipole field to manipulate the migration and transport of photogenerated carriers represents a promising approach for achieving outstanding performance in UV PDs.

A contactless monitoring system for accurately predicting energy expenditure during treadmill walking based on an ensemble neural network.

The monitoring of treadmill walking energy expenditure (EE) plays an important role in health evaluations and management, particularly in older individuals and those with chronic diseases. However, universal and highly accurate prediction methods for walking EE are still lacking. In this paper, we propose an ensemble neural network (ENN) model that predicts the treadmill walking EE of younger and older adults and stroke survivors with high precision based on easy-to-obtain features. Compared with previous studies, the proposed model reduced the estimation error by 13.95% and 66.20% for stroke survivors and younger adults, respectively. Furthermore, a contactless monitoring system was developed based on Kinect, mm-wave radar, and ENN algorithms, and the treadmill walking EE was monitored in real time. This ENN model and monitoring system can be combined with smart devices and treadmill, making them suitable for evaluating, monitoring, and tracking changes in health during exercise and in rehabilitation environments.

Analyzing the molecular mechanism of xuefuzhuyu decoction in the treatment of pulmonary hypertension with network pharmacology and bioinformatics and verifying molecular docking.

BACKGROUND: XueFuZhuYu (XFZY), a typical Chinese herbal formula, has remarkable clinical effects for treating Pulmonary Hypertension (PH) with unclear mechanisms. Our research involved the utilization of network pharmacology to explore the traditional Chinese herbal monomers and their related targets within XFZY for PH treatment. Furthermore, molecular docking verification was performed. METHODS: The XFZY's primary active compounds, along with their corresponding targets, were both obtained from the TCMSP, ChEMBL, and UniProt databases. The target proteins relevant to PH were sifted through OMIM, GeneCards and TTD databases. The common "XFZY-PH" targets were evaluated with Disease Ontology (DO), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses with the assistance of R software. The Protein-Protein Interaction (PPI) network and compound-target-pathway network were constructed and a systematic analysis of network parameters was performed by the powerful software Cytoscape. Molecular docking was employed for assessing and verifying the interactions between the core targets and the top Chinese herbal monomer. RESULTS: The screening included 297 targets of active compounds in XFZY and 8400 PH-related targets. DO analysis of the above common 268 targets indicated that the treatment of the diseases by XFZY is mediated by genes related to Chronic Obstructive Pulmonary Disease (COPD), Obstructive Lung Disease (OLD), ischemia, and myocardial infarction. The findings from molecular docking indicated that the binding energies of 57 ligand-receptor pairs in PH and 20 ligand-receptor pairs in COPD-PH were lower than -7kJ•mol-1. CONCLUSIONS: This study indicates that XFZY is a promising option within traditional Chinese medicine compound preparation for combating PH, particularly in cases associated with COPD. Our demonstration of the specific molecular mechanism of XFZY anti-PH and its effective active ingredients provides a theoretical basis for better clinical application of the compound.

Effectiveness and brain mechanism of multi-target transcranial alternating current stimulation (tACS) on motor learning in stroke patients: study protocol for a randomized controlled trial.

BACKGROUND: Transcranial alternating current stimulation (tACS) has proven to be an effective treatment for improving cognition, a crucial factor in motor learning. However, current studies are predominantly focused on the motor cortex, and the potential brain mechanisms responsible for the therapeutic effects are still unclear. Given the interconnected nature of motor learning within the brain network, we have proposed a novel approach known as multi-target tACS. This study aims to ascertain whether multi-target tACS is more effective than single-target stimulation in stroke patients and to further explore the potential underlying brain mechanisms by using techniques such as transcranial magnetic stimulation (TMS) and magnetic resonance imaging (MRI). METHODS: This study employs a double-blind, sham-controlled, randomized controlled trial design with a 2-week intervention period. Both participants and outcome assessors will remain unaware of treatment allocation throughout the study. Thirty-nine stroke patients will be recruited and randomized into three distinct groups, including the sham tACS group (SS group), the single-target tACS group (ST group), and the multi-target tACS group (MT group), at a 1:1:1 ratio. The primary outcomes are series reaction time tests (SRTTs) combined with electroencephalograms (EEGs). The secondary outcomes include motor evoked potential (MEP), central motor conduction time (CMCT), short interval intracortical inhibition (SICI), intracortical facilitation (ICF), magnetic resonance imaging (MRI), Box and Block Test (BBT), and blood sample RNA sequencing. The tACS interventions for all three groups will be administered over a 2-week period, with outcome assessments conducted at baseline (T0) and 1 day (T1), 7 days (T2), and 14 days (T3) of the intervention phase. DISCUSSION: The study's findings will determine the potential of 40-Hz tACS to improve motor learning in stroke patients. Additionally, it will compare the effectiveness of multi-target and single-target approaches, shedding light on their respective improvement effects. Through the utilization of techniques such as TMS and MRI, the study aims to uncover the underlying brain mechanisms responsible for the therapeutic impact. Furthermore, the intervention has the potential to facilitate motor learning efficiency, thereby contributing to the advancement of future stroke rehabilitation treatment. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300073465. Registered on 11 July 2023.

Analysis of CVC1302-Mediated Enhancement of Monocyte Recruitment in Inducing Immune Responses.

Monocytes (Mos) are believed to play important roles during the generation of immune response. In our previous study, CVC1302, a complex of PRRs agonists, was demonstrated to recruit Mo into lymph nodes (LNs) in order to present antigen and secret chemokines (CXCL9 and CXCL10), which attracted antigen-specific CD4+ T cells. As it is known that Mos in mice are divided into two main Mo subsets (Ly6C+ Mo and Ly6C- Mo), we aimed to clarify the CVC1302-recruiting Mo subset and functions in the establishment of immunity. In this study, we found that CVC1302 attracted both Ly6C+ Mo and Ly6C- Mo into draining LNs, which infiltrated from different origins, injection muscles and high endothelial venule (HEV), respectively. We also found that the numbers of OVA+ Ly6C+ Mo in the draining LNs were significantly higher compared with OVA+ Ly6C- Mo. However, the levels of CXCL9 and CXCL10 produced by Ly6C- Mo were significantly higher than Ly6C+ Mo, which plays important roles in attracting antigen-specific CD4+ T cells. Under the analysis of their functions in initiating immune responses, we found that the ability of the Ly6C+ monocyte was mainly capturing and presenting antigens, otherwise; the ability of the Ly6C- monocyte was mainly secreting CXCL9 and CXCL10, which attracted antigen-specific CD4+ T cells through CXCR3. These results will provide new insights into the development of new immunopotentiators and vaccines.

Electroacupuncture stimulation to modulate neural oscillations in promoting neurological rehabilitation.

Electroacupuncture (EA) stimulation is a modern neuromodulation technique that integrates traditional Chinese acupuncture therapy with contemporary electrical stimulation. It involves the application of electrical currents to specific acupoints on the body following acupuncture. EA has been widely used in the treatment of various neurological disorders, including epilepsy, stroke, Parkinson's disease, and Alzheimer's disease. Recent research suggests that EA stimulation may modulate neural oscillations, correcting abnormal brain electrical activity, therefore promoting brain function and aiding in neurological rehabilitation. This paper conducted a comprehensive search in databases such as PubMed, Web of Science, and CNKI using keywords like "electroacupuncture," "neural oscillations," and "neurorehabilitation", covering the period from year 1980 to 2023. We provide a detailed overview of how electroacupuncture stimulation modulates neural oscillations, including maintaining neural activity homeostasis, influencing neurotransmitter release, improving cerebral hemodynamics, and enhancing specific neural functional networks. The paper also discusses the current state of research, limitations of electroacupuncture-induced neural oscillation techniques, and explores prospects for their combined application, aiming to offer broader insights for both basic and clinical research.

Increases in Cellular Immune Responses Due to Positive Effect of CVC1302-Induced Lysosomal Escape in Mice.

This study found a higher percentage of CD8+ T cells in piglets immunized with a CVC1302-adjuvanted inactivated foot-and-mouth disease virus (FMDV) vaccine. We wondered whether the CVC1302-adjuvanted inactivated FMDV vaccine promoted cellular immunity by promoting the antigen cross-presentation efficiency of ovalbumin (OVA) through dendritic cells (DCs), mainly via cytosolic pathways. This was demonstrated by the enhanced levels of lysosomal escape of OVA in the DCs loaded with OVA and CVC1302. The higher levels of ROS and significantly enhanced elevated lysosomal pH levels in the DCs facilitated the lysosomal escape of OVA. Significantly enhanced CTL activity levels was observed in the mice immunized with OVA-CVC1302. Overall, CVC1302 increased the cross-presentation of exogenous antigens and the cross-priming of CD8+ T cells by alkalizing the lysosomal pH and facilitating the lysosomal escape of antigens. These studies shed new light on the development of immunopotentiators to improve cellular immunity induced by vaccines.

Efficacy and safety of platelet-rich plasma combined with Tai Chi for knee osteoarthritis: study protocol for a placebo-controlled randomized trial.

BACKGROUND: No definitive treatment methods of curative for knee osteoarthritis (KOA). The combined therapies that into account both the biochemical and biomechanical may provide potential opportunities for treat KOA, and previous studies have demonstrated that the platelet-rich plasma of intra-articular injection (IAI-PRP) and exercise treatments afford more benefits than do their corresponding monotherapies. The absence of a specific exercise plan and detailed explanation renders the aforementioned study results questionable. Furthermore, Tai Chi (TC) with moderate-intensity, whole body movements and good adherence may prove to be more effective for treating KOA. However, few studies examined the effectiveness and safety of combined IAI-PRP and TC for KOA. METHODS: This study protocol will be a placebo-controlled, assessor-blinded randomized trial involving 12-week intervention and 1-year follow-up. The stratified randomization will be used to randomly assign the 212 participants to four groups: group A (placebo IAI); group B (PRP IAI); group C (TC and placebo IAI); group D (TC and PRP IAI). Injection will be performed once a week, three consecutive times as a course, after a week of rest to continue the next course, a total of 3 courses (12 week). Additionally, the TC interventions will be carried out 3 days per week for a total of 12 weeks. The primary outcome measures will include the efficacy (Western Ontario and McMaster Universities Osteoarthritis Index), acceptability and safety of these interventions. The secondary outcome measures will include physical function (Timed Up and Go test), walking function (Gait Analysis), inflammatory factor levels (e.g., Interleukin-1 ß, interleukin-6, vascular endothelial growth factor), quality of life (36-Item Short Form Health Survey), volume of patellofemoral cartilage and effusion-synovitis (MRI). Two-way of variance with repeated measures will be applied to examine the main effects of the group and the time factor and group-time interaction effects for all outcome measures. DISCUSSION: This trial will be first one to propose an integrated scheme combing IAI-PRP and TC for treatment of KOA, based on the consideration of the biochemical and biomechanical pathogenesis of KOA. These results of the study will provide evidence with high quality for integrated IAI-PRP and TC to treatment KOA. Trial Registration Chinese Clinical Trial Registry ChiCTR2300067559. Registered on 11 January 2023.

Synergizing the enhanced RIME with fuzzy K-nearest neighbor for diagnose of pulmonary hypertension.

Pulmonary hypertension (PH) is an uncommon yet severe condition characterized by sustained elevation of blood pressure in the pulmonary arteries. The delaying treatment can result in disease progression, right ventricular failure, increased risk of complications, and even death. Early recognition and timely treatment are crucial in halting PH progression, improving cardiac function, and reducing complications. Within this study, we present a highly promising hybrid model, known as bERIME_FKNN, which constitutes a feature selection approach integrating the enhanced rime algorithm (ERIME) and fuzzy K-nearest neighbor (FKNN) technique. The ERIME introduces the triangular game search strategy, which augments the algorithm's capacity for global exploration by judiciously electing distinct search agents across the exploratory domain. This approach fosters both competitive rivalry and collaborative synergy among these agents. Moreover, an random follower search strategy is incorporated to bestow a novel trajectory upon the principal search agent, thereby enriching the spectrum of search directions. Initially, ERIME is meticulously compared to 11 state-of-the-art algorithms using the IEEE CEC2017 benchmark functions across diverse dimensionalities such as 10, 30, 50, and 100, ultimately validating its exceptional optimization capability within the model. Subsequently, employing the color moment and grayscale co-occurrence matrix methodologies, a total of 118 features are extracted from 63 PH patients' and 60 healthy individuals' images, alongside an analysis of 14,514 recordings obtained from these patients utilizing the developed bERIME_FKNN model. The outcomes manifest that the bERIME_FKNN model exhibits a conspicuous prowess in the realm of PH classification, attaining an accuracy and specificity exceeding 99%. This implies that the model serves as a valuable computer-aided tool, delivering an advanced warning system for diagnosis and prognosis evaluation of PH.