Inhibition of EREG/ErbB/ERK by Astragaloside IV reversed taxol-resistance of non-small cell lung cancer through attenuation of stemness via TGFß and Hedgehog signal pathway.

PURPOSE: Taxol is the first-line chemo-drug for advanced non-small cell lung cancer (NSCLC), but it frequently causes acquired resistance, which leads to the failure of treatment. Therefore, it is critical to screen and characterize the mechanism of the taxol-resistance reversal agent that could re-sensitize the resistant cancer cells to chemo-drug. METHOD: The cell viability, sphere-forming and xenografts assay were used to evaluate the ability of ASIV to reverse taxol-resistance. Immunohistochemistry, cytokine application, small-interfering RNA, small molecule inhibitors, and RNA-seq approaches were applied to characterize the molecular mechanism of inhibition of epiregulin (EREG) and downstream signaling by ASIV to reverse taxol-resistance. RESULTS: ASIV reversed taxol resistance through suppression of the stemness-associated genes of spheres in NSCLC. The mechanism exploration revealed that ASIV promoted the K48-linked polyubiquitination of EREG along with degradation. Moreover, EREG could be triggered by chemo-drug treatment. Consequently, EREG bound to the ErbB receptor and activated the ERK signal to regulate the expression of the stemness-associated genes. Inhibition of EREG/ErbB/ERK could reverse the taxol-resistance by inhibiting the stemness-associated genes. Finally, it was observed that TGFß and Hedgehog signaling were downstream of EREG/ErbB/ERK, which could be targeted using inhibitors to reverse the taxol resistance of NSCLC. CONCLUSIONS: These findings revealed that inhibition of EREG by ASIV reversed taxol-resistance through suppression of the stemness of NSCLC via EREG/ErbB/ERK-TGFß, Hedgehog axis.

The dual role of ribosomal protein SA in pathogen infection: the key role of structure and localization.

Ribosomal protein SA (RPSA) plays multiple roles in cells, including ribosomal biogenesis and translation, cellular migration, and cytoskeleton reorganization. RPSA is crucial in the process of pathogen infection. Extensive research has examined RPSA's role in pathogen adhesion and invasion, but its broader functions, particularly its anti-infective capabilities, have garnered increasing attention in recent years. This dual role is closely related to its structural domains, which influence its localization and function. This review summarizes key research findings concerning the functional domains of RPSA and analyzes the relationship between its membrane localization and structural domains. Additionally, the functional implications of RPSA are categorized based on its different localizations during pathogen infection. Specifically, when RPSA is located on the cell surface, it promotes pathogen adhesion and invasion of host cells; conversely, when RPSA is located intracellularly, it exhibits anti-infective properties. Overall, RPSA shows a dual nature, both in facilitating pathogen invasion of the host and in possessing the ability to resist pathogen infection. This review comprehensively examines the dual role of RPSA in pathogen infection by analyzing its structural domains, localization, and interactions with cellular and pathogen molecules. Our aim is to update and deepen researchers' understanding of the various functions of RPSA during pathogen infection.

Relations between dimensions of self-perceptions and academic achievement in Chinese children: A cross-lagged panel analysis.

The goal of the present study was to examine the associations between different dimensions of self-perceptions and academic achievement in Chinese children. Participants were 604 children in Grades 4-7 attending primary and middle schools in mainland China (342 boys, 262 girls; Mage = 11.25 years). Measures of children's self-perceptions and academic achievement were collected via self-reports and school records at two time points over one academic year. Results from cross-lagged panel analysis indicated that after controlling for the effects of gender, grade, and stabilities, Time 1 perceived scholastic competence positively predicted Time 2 academic achievement (ß = .08, p < .05), and Time 1 academic achievement predicted Time 2 perceived scholastic competence (ß = .10, p < .05). Time 1 perceived athletic competence negatively predicted Time 2 academic achievement (ß = -.08, p < .01). The findings provide evidence that self-perceptions have different facets and are differently associated with academic achievement and emphasize the reciprocal predictive relations between perceived scholastic competence and academic achievement and the negative impact of perceived athletic competence self-perception on academic achievement. The implications of these results are discussed in the context of self-development and academic performance within Chinese culture, as well as their educational implications for school practices. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Ultrafast Tailoring Amorphous Zn0.25V2O5 with Precision-Engineered Artificial Atomic-Layer 1T'-MoS2 Cathode Electrolyte Interphase for Advanced Aqueous Zinc-Ion Batteries.

Vanadium (V)-based oxides as cathode materials for aqueous zinc-ion batteries (AZIBs) still encounter challenges such as sluggish Zn2+ diffusion kinetics and V-dissolution, thus leading to severe capacity fading and limited life span. Here, we designed an ultrafast and facile colloidal chemical synthesis strategy based on crystalline Zn0.25V2O5 (c-ZVO) to successfully prepare a-ZVO@MoS2 core@shell heterostructures, where atomic-layer MoS2 uniformly coats on the surface of amorphous a-ZVO. The tailored amorphous structure of a-ZVO provides more isotropic pathways and active sites for Zn2+, thus significantly enhancing the Zn2+ diffusion kinetics during charge-discharge processes. Meanwhile, as an efficient artificial cathode electrolyte interphase, the precision-engineered atomic-layer MoS2 with semi-metallic 1T' phase not only contributes to improved electron transport but also effectively inhibits the V-dissolution of a-ZVO. Therefore, the prepared a-ZVO@MoS2 and conceptually validated a-V2O5@MoS2 derived from commercial c-V2O5 exhibit excellent cycling stability at an ultralow current density (0.05 A g-1) while maintaining good rate capability and capacity retention. This research achievement provides a new effective strategy for various amorphous cathode designs for AZIBs with superior performance.

Single-Particle Imaging Photoinduced Charge Transfer of Ferroelectric Polarized Heterostructures for Photocatalysis.

Piezoelectric-assisted photocatalysis has a huge potential in solving the energy shortage and environmental pollution problems, and imaging their detailed charge-transfer process can provide in-depth understanding for the development of high-active piezo-photocatalysts; however, it is still challenging. Herein, topotactic heterostructures of TiO2@BaTiO3 (TO@BTO-S) were constructed by the epitaxial growth of ferroelectric BaTiO3 mesocrystals on TiO2-{001} facets, resulting in a ferroelectric photocatalyst with a polarization orientation on the surface. Notably, the photoinduced charge transfer in ferroelectric TiO2@BaTiO3 was accurately monitored and directly visualized at the single-particle level by the advanced photoluminescence (PL) imaging microscopy systems. The longer PL lifetime of TO@BTO-S demonstrated the efficient charge separation caused by a built-in electric field, which is constructed by the polarization orientation of BaTiO3 mesocrystals. Therefore, the TO@BTO-S heterostructure exhibits efficient piezoelectric-assisted photocatalytic pure water splitting, which is 290 times higher than photocatalysis. This work revealed time/spatial-resolved photoinduced charge transfer in piezoelectric assistance photocatalysts at the single-particle level and demonstrated the great role of polarization orientation in promoting charge transfer for photocatalysis.

Tailoring Copper Single-Atoms-Stabilized Metastable Transition-Metal-Dichalcogenides for Sustainable Hydrogen Production.

Unconventional 1T' phase transition metal dichalcogenides (TMDs) show great potential for hydrogen evolution reaction (HER). However, they are susceptible to transitioning into the stable 2H phase, which reduces their catalytic activity and stability. Herein, we present a scalable approach for designing thermally stable 1T'-TMDs hollow structures (HSs) by etching Cu1.94S templates from pre-synthesized Cu1.94S@TMDs heterostructures, including 1T'-MoS2, MoSe2, WS2, and WSe2 HSs. Furthermore, taking 1T'-MoS2 HSs as an example, the etched Cu ions can be firmly adsorbed on their surface in the form of single atoms (SAs) through Cu-S bonds, thereby elevating the phase transition temperature from 149 ºC to 373 ºC. Due to the advantages conferred by the 1T' phase, hollow structure, and synergistic effect between Cu SAs and 1T'-MoS2 supports, the fabricated 1T'-MoS2 HSs demonstrate superior HER performance. Notably, their high-phase stability enables continuous operation of designed 1T'-MoS2 HSs for up to 200 hours at an ampere-level current density without significant activity decay. This work provides a universal method for synthesizing highly stable 1T'-TMDs electrocatalysts, with a particular focus on the relationship between their phase and catalytic stability.

Promoting Cathodic Kinetics and Anodic Stability in Practical Room-Temperature Sodium-Sulfur Batteries with Bifunctional Electrolytes.

The development of room-temperature (RT) sodium-sulfur (Na-S) batteries is severely hindered due to the slow kinetics of the S cathode and the instability of the Na-metal anode. To overcome this, we introduced a dual-functional electrolyte cosolvent, trifluoromethanesulfonamide (TFMSA). Short-chain Na2Sx (1 ≤ x ≤ 2) can be effectively dissolved due to the strong H-S bond interaction between TFMSA and sulfides, which changes the S conversion process, thereby effectively enhancing the conversion kinetics of the cathode. Meanwhile, TFMSA can generate a stable solid electrolyte interphase on the Na-metal surface to protect it from soluble polysulfide attack. Therefore, the RT Na-S batteries using the ether electrolyte show a high initial discharge capacity of 896.6 mAh g-1 and a capacity retention rate of 73% after 150 cycles at 0.2C, and the pouch cell also demonstrates its practical performance. This work proposes a dual-functional electrolyte cosolvent selection principle to inspire the practical application of high-performance RT Na-S batteries.

Clinical characteristics and risk factors for acute abdomen in patients with abdominal lymphatic malformations.

OBJECTIVE: The diagnosis of abdominal lymphatic malformations (ALMs) is often overlooked in clinical practice. However, reports in the literature about ALMs are limited to case reports and series with small sample sizes. This study aimed to review our currently available data to describe the clinical characteristics of ALMs and evaluate the risk factors for acute abdomen caused by ALMs. METHODS: We reviewed the records of patients with ALMs who were diagnosed between December 2008 and January 2023 in our institution. The associations between acute abdomen and ALMs were analyzed based on single-factor and multivariate logistic regression analyses. RESULTS: This study included 345 patients with pathologically confirmed ALMs, with a slight female predominance of 1:1.4. Approximately 39.1% (135/345) of patients were asymptomatic, and 24.6% (85/345) presented with acute abdomen. Among the ALMs in the cohort, 42.6% (147/345) were retroperitoneal lymphatic malformations (LMs). The maximal lesion dimensions in patients with acute abdomen and nonacute abdomen were 10.0 cm and 7.8 cm, respectively, with no significant difference based on multivariate analyses. Children were more likely to develop acute abdomen than adults were (P = .002; odds ratio, 5.128; 95% confidence interval, 1.835-14.326). ALMs accompanying acute abdomen were more common for lesions involving the small intestinal mesentery (P = .023; odds ratio, 2.926; 95% confidence interval, 1.157-7.400). CONCLUSIONS: ALMs are rare with an insidious onset, and retroperitoneal LMs are the most common ALMs, followed by jejunal mesenteric LMs. Our retrospective analysis suggested that young age and small intestinal mesenteric lymphatic malformation are independent risk factors for acute abdomen with ALMs.

Lesion-Adaptative Bionic Tracheal Stent with Local Paclitaxel Release for Enhanced Therapy of Tracheal Tumor and Stenosis.

The efficacy of tracheal stents (TSs) in treating malignant tracheal stenosis is often compromised by tumor overgrowth, leading to restenosis and other stent-related complications that conventional chemotherapy and commercial stents fail to adequately address. Drug-loaded tracheal stents have the potential to deliver chemotherapeutics directly to tumors while relieving stenosis, but their effectiveness has yet to be studied in vivo. The design of drug-loaded tracheal stents adapting to lesions to achieve optimal antitumor effects and minimal side effects remains an area worth exploring. In this study, a lesion-adaptive bionic tracheal stent (PTX-TS) designed for the dual purpose of treating tracheal tumors and associated stenosis was developed. This novel PTX-TS was evaluated using an orthotopic rabbit model of malignant tracheal stenosis, newly established in this study. The rabbit lesions were precisely scanned using computed tomography (CT) for 3D reconstruction, enabling the design of a PTX-TS that fit both the tumor and airway dimensions to ensure complete tumor coverage and effective dilation of the stenotic airway. The PTX-TS featured a bilayer structure including a surface layer of PTX/ethylene-vinyl acetate copolymer (EVA) blends for sustained PTX release and an inner layer of polycaprolactone (PCL)/EVA blends for appropriate mechanical performance. The stent was fabricated layer by layer using a custom-built 3D printer, and the drug-loaded surface layer was printed using a novel liquid printing technique developed in our lab, achieving a high drug loading of up to 80%. The dose of the PTX-TS was investigated and set as 7.5 mg/cm2, which leads to maximum tissue permeation. With its bionic cross-sectional C-shaped structure, the PTX-TS demonstrated excellent radial flexibility, allowing successful implantation at the lesion site using a specially designed delivery apparatus, where it self-expanded to relieve stenosis. Additionally, the PTX-TS effectively delivered PTX directly to the tracheal tumor, resulting in superior antitumor efficacy without significant toxicity or complications.

Peptide-based supramolecular hydrogels and their biotherapeutic applications.

In recent years, supramolecular hydrogels have made groundbreaking research progress in biomedical fields such as drug delivery, biosensing, imaging analysis, and tissue engineering. Peptides, with their unique characteristics of facile preparation, low immunogenicity and easy biodegradability, are commonly used as building blocks of supramolecular hydrogels. Peptide-based supramolecular hydrogels loaded with drugs, prepared via physical means or covalent crosslinking, exhibit unique three-dimensional network structures and strong water retention capacities. These properties enhance drug bioavailability and reduce side effects, enabling drug accumulation and responsive release at disease sites, significantly improving the therapeutic efficacy. Here, we review recent advancements in peptide-based supramolecular hydrogels and their biotherapeutic applications, including chemotherapy, photothermal therapy, photodynamic therapy, immunotherapy, gene therapy, antibacterial and anti-inflammatory treatments, and other biological applications. This review aims to provide new inspiration for the development of biomaterials in the therapeutic field and provide more personalized options for disease treatment. Additionally, challenges and limitations in this field are briefly discussed.

Polycyclic polyprenylated acylphloroglucinols from the pericarps of Garcinia multiflora champ. ex Benth. with cytotoxic property.

The phytochemical investigation on the pericarps of Garcinia multiflora resulted in the isolation of 12 previously undescribed polycyclic polyprenylated acylphloroglucinols (PPAPs, 1-12) with a variety of skeletons. Their structures were determined by comprehensive spectroscopic analyses, ECD calculations, and single-crystal X-ray diffraction. Compounds 6-9 possess a rare bicyclo[4.3.1]decane skeleton. Additionally, the anti-tumor activity of the 12 isolates was evaluated. The results indicated that compounds 5, 9, and 12 exhibited significant cytotoxicity in a wide range of cancer cell lines, including the human breast cancer MDA-MB-231 cells, human lung cancer A549 cells, human colon cancer SW480 cells and human ovarian cancer HEY cells. Further studies indicated that compound 5 induced cell cycle arrest and apoptosis, to inhibit the growth of MDA-MB-231 cells. Taken together, these findings expand the chemical diversity of PPAPs and further demonstrate the potential of PPAPs as candidates for cancer treatment.

Effectiveness of repetitive transcranial magnetic stimulation combined with intelligent Gait-Adaptability Training in improving lower limb function and brain symmetry after subacute stroke: a preliminary study.

OBJECTIVES: Persistent lower limb dysfunction is a major challenge in post-stroke recovery. Repetitive transcranial magnetic stimulation is recognized for addressing post-stroke motor deficits. Our study explores the efficacy of combining rTMS with gait-adaptive training to enhance lower limb function and regulatory mechanisms in subacute stroke. MATERIALS AND METHODS: This randomized controlled trial enrolled 27 patients with subacute hemiparesis, dividing them into experimental and control groups. Both groups underwent gait-adaptability training 5 times/week for 4 weeks, with the experimental group receiving daily low-frequency transcranial magnetic stimulation before training. Primary outcomes included the pairwise derived brain symmetry index, lower-extremity Fugl-Meyer Assessment, 10-meter walk test, and Berg Balance Scale. Assessments occurred before and after the four-week intervention. RESULTS: The experimental and control groups showed significant improvements in the Fugl-Meyer Assessment, 10-meter walk test, and Berg Balance Scale after the 4-week intervention compared to baseline (all p<0.05). However, the experimental group demonstrated significantly greater improvements compared to the control group in the Fugl-Meyer Assessment (p=0.024) and the 10-meter walk test (p=0.033). Additionally, the experimental group exhibited a more pronounced decrease in the pairwise derived brain symmetry index (p=0.026) compared to the control group. Within the experimental group, the cortical subgroup's pairwise derived brain symmetry index was significantly lower than that of the control group (p=0.006). CONCLUSIONS: Combining low-frequency transcranial magnetic stimulation with Gait-Adaptive Training effectively enhances lower limb function and Regulatory mechanisms of the cerebral hemisphere in subacute stroke recovery, and it can provide rapid and effective rehabilitation effect compared with gait adaptation training alone.

Study on Active Components and Mechanism of Lettuce Latex Against Spodoptera Litura.

Plant latex is a sticky emulsion exuded from laticifers once the plant is damaged. Latex is an essential component of plant defense against herbivores. Lettuce (Lactuca sativa L.) in the Compositae family has relatively fewer insect herbivores compared with other leaf vegetables. The larvae of a generalist lepidopteran pest Spodoptera litura (Fabricius) avoided feeding on living lettuce plants. However, the larvae rapidly damaged the excised leaves that were unable to produce latex. Six compounds were isolated from lettuce latex. They were identified as 2,5-dihydroxybenzaldehyde (1), 3ß-hydroxy-4,15-dehydrograndolide (2), annuolide D (3), lactucin (4), lactucopicrin (5), and hanphyllin (6). Bioassays showed that the inhibition rate of compound 1 (2,5-dihydroxybenzaldehyde) and 6 (hanphyllin, a sesquiterpene lactone) on the weight gain of S. litura were 52.4 % and 10 %, respectively, at the concentration of 100 µg/g. RNA-seq analyses showed that larval exposure to compound 1 down-regulated the genes associated with heterobiotic metabolism including drug metabolism-cytochrome P450, metabolism of xenobiotics by cytochrome P450, retinol metabolism, glutathione metabolism, and drug metabolism-other enzymes (mainly uridine diphosphate glucuronyltransferase, UGTs). RT-qPCR further confirmed that 33 genes in the family of carboxylesterase (CarE), P450s and UGTs were down-regulated by compound 1. The activities of CarE, P450s and UGTs in the larvae fed on diets containing compound 1 were significantly lower than those fed on control diets, with the inhibition for the three detoxification enzymes being 55.4 %, 53.9 %, and 52.9 %. These findings suggest that secondary metabolites including 2,5-dihydroxybenzaldehyde in the latex play a key role in protecting lettuce from insect herbivory.

Epigenetic Dynamics in Meniscus Cell Migration and its Zonal Dependency in Response to Inflammatory Conditions: Implications for Regeneration Strategies.

Meniscus injuries pose significant challenges in clinical settings, primarily due to the intrinsic heterogeneity of the tissue and the limited efficacy of current treatments. Endogenous cell migration is crucial for the healing process, yet the regulatory mechanisms of meniscus cell migration and its zonal dependency within the meniscus are not fully understood. Thus, this study investigates the role of epigenetic mechanisms in governing meniscus cell migration under inflammatory conditions, with a focus on their implications for injury healing and regeneration. Here, we discovered that a proinflammatory cytokine, TNF-α treatment significantly impedes the migration speed of inner meniscus cells, while outer meniscus cells are unaffected, underscoring a zonal-dependent response within the meniscus. Our analysis identified distinct histone modification patterns and chromatin dynamics between inner and outer meniscus cells during migration, highlighting the necessity to consider these zonal-dependent properties in devising repair strategies. Specifically, we found that TNF-α differentially influences histone modifications, particularly H3K27me3, between the two cell types. Transcriptome analysis further revealed that TNF-α treatment induces substantial gene expression changes, with inner meniscus cells exhibiting more pronounced alterations than outer cells. Gene cluster analysis pointed to distinct responses in chromatin remodeling, extracellular matrix assembly, and wound healing processes between the zonal cell populations. Moreover, we identified potential therapeutic targets by employing existing epigenetic drugs, GSKJ4 (a histone demethylase inhibitor) and C646 (a histone acetyltransferase inhibitor), to successfully restore the migration speed of inner meniscus cells under inflammatory conditions. This highlights their potential utility in treating meniscus tear injuries. Overall, our findings elucidate the intricate interplay between epigenetic mechanisms and meniscus cell migration, along with its meniscus zonal dependency. This study provides insights into potential targets for enhancing meniscus repair and regeneration, which may lead to improved clinical outcomes for patients with meniscus injuries and osteoarthritis.

Inhibition of PLA2G4A attenuated valproic acid- induced lysosomal membrane permeabilization and restored impaired autophagic flux: Implications for hepatotoxicity.

Valproic acid (VPA) has broad efficacy against several seizures but causes liver injury limiting its prolonged clinical use. Some studies have demonstrated that VPA-induced hepatotoxicity is characterized by microvesicular hepatic steatosis. However, novel detailed mechanisms to explain VPA-induced hepatic steatosis and experimentally rigorously validated protective agents are still lacking. In this study, 8-week-old C57BL/6J mice were gavaged with VPA (500 mg/kg/d) for 4 weeks to establish an in vivo model of VPA-induced chronic liver injury. Quantitative proteomic and non-targeted lipidomic analyses were performed to explore the underlying mechanisms of VPA-induced hepatotoxicity. As a result, VPA-induced hepatotoxicity is associated with impaired autophagic flux, which is attributed to lysosomal dysfunction. Further studies revealed that VPA-induced lysosomal membrane permeabilization (LMP), allows soluble lysosomal enzymes to leak into the cytosol, which subsequently led to impaired lysosomal acidification. A lower abundance of glycerophospholipids and an increased abundance of lysophospholipids in liver tissues of mice in the VPA group strongly indicated that VPA-induced LMP may be mediated by the activation of phospholipase PLA2G4A. Metformin (Met) acted as a potential protective agent attenuating VPA-induced liver dysfunction and excessive lipid accumulation. Molecular docking and cellular thermal shift assays demonstrated that Met inhibited the activity of PLA2G4A by directly binding to it, thereby ameliorating VPA-induced LMP and autophagic flux impairment. In conclusion, this study highlights the therapeutic potential of targeting PLA2G4A-mediated lysosomal dysfunction in VPA-induced hepatotoxicity.

Atractylenolide II combined with Interferon-γ synergistically ameliorates colorectal cancer progression in vivo and in vitro by blocking the NF-kB p65/PD-L1 pathway.

Purpose: Atractylodes macrocephala Koidz is a widely used classical traditional Chinese herbal medicine, that has shown remarkable efficacy in cancers. Colorectal cancer (CRC) is the most common malignant tumor globally. Interferon (IFN)-γ, a prominent cytokine involved in anti-tumor immunity that has cytostatic, pro-apoptotic, and immune-stimulatory properties for the detection and removal of transformed cells. Atractylenolides-II (AT-II) belongs to the lactone compound that is derived from Atractylodes macrocephala Koidz with anti-cancer activity. However, whether AT-II combined with IFN-γ modulates CRC progression and the underlying mechanisms remain unclear. The present study aimed to elucidate the efficacy and pharmaceutical mechanism of action of AT-II combined with IFN-γ synergistically against CRC by regulating the NF-kB p65/PD-L1 signaling pathway. Methods: HT29 and HCT15 cells were treated with AT-II and IFN-γ alone or in combination and cell viability, migration, and invasion were then analyzed using Cell Counting Kit-8 (CCK-8) and Transwell assays, respectively. Furthermore, the underlying mechanism was investigated through western blot assay. The role of AT-II combined with IFN-γ on tumor growth and lung metastases was estimated in vivo. Finally, the population of lymphocytes in tumor tissues of lung metastatic C57BL/6 mice and the plasma cytokine levels were confirmed by flow cytometry and enzyme-linked immunosorbent assay (ELISA). Results: AT-II or the combination IFN-γ significantly inhibited the growth and migration abilities of CRC cells in vitro and in vivo. The biological mechanisms behind the beneficial effects of AT-II combined with IFN-γ were also measured and inhibition of p38 MAPK, FAK, Wnt/ß-catenin, Smad, and NF-kB p65/PD-L1 pathways was observed. Moreover, AT-II combined with IFN-γ significantly inhibited HCT15 xenograft tumor growth and lung metastases in C57BL/6 mice, which was accompanied by lymphocyte infiltration into the tumor tissues and inflammatory response inactivation. Conclusions: The results showed that the AT-II in combination with IFN-γ could be used as a potential strategy for tumor immunotherapy in CRC. More importantly, the mechanism by which AT-II suppressed CRC progressions was by inhibiting the NF-kB p65/PD-L1 signal pathway.

Deep Learning-Based State-of-Health Estimation of Proton-Exchange Membrane Fuel Cells under Dynamic Operation Conditions.

Proton-exchange membrane fuel cells (PEMFCs) play a crucial role in the transition to sustainable energy systems. Accurately estimating the state of health (SOH) of PEMFCs under dynamic operating conditions is essential for ensuring their reliability and longevity. This study designed dynamic operating conditions for fuel cells and conducted durability tests using both crack-free fuel cells and fuel cells with uniform cracks. Utilizing deep learning methods, we estimated the SOH of PEMFCs under dynamic operating conditions and investigated the performance of long short-term memory networks (LSTM), gated recurrent units (GRU), temporal convolutional networks (TCN), and transformer models for SOH estimation tasks. We also explored the impact of different sampling intervals and training set proportions on the predictive performance of these models. The results indicated that shorter sampling intervals and higher training set proportions significantly improve prediction accuracy. The study also highlighted the challenges posed by the presence of cracks. Cracks cause more frequent and intense voltage fluctuations, making it more difficult for the models to accurately capture the dynamic behavior of PEMFCs, thereby increasing prediction errors. However, under crack-free conditions, due to more stable voltage output, all models showed improved predictive performance. Finally, this study underscores the effectiveness of deep learning models in estimating the SOH of PEMFCs and provides insights into optimizing sampling and training strategies to enhance prediction accuracy. The findings make a significant contribution to the development of more reliable and efficient PEMFC systems for sustainable energy applications.

Effects of combining rTMs and augmented reality gait adaptive training on walking function of patients with stroke based on three-dimensional gait analysis and sEMG: a randomized controlled trial.

BACKGROUND: Augmented reality gait adaptive training (ARGAT) and repetitive transcranial magnetic stimulation (rTMS) have both demonstrated efficacy in improving lower limb motor function in survivors of stroke. PURPOSE: To investigate the effects of combining rTMS and ARGAT on motor function in survivors of stroke. METHODS: The experimental group received a combination of rTMS and ARGAT, while the control group received ARGAT alone. The interventions comprised a total of 20 sessions, conducted over four weeks with five consecutive daily sessions. Outcome measures included three-dimensional gait analysis (3DGA), surface electromyography (sEMG), Fugl-Meyer assessment for the lower extremity (FMA-LE), and the Berg Balance Scale (BBS). RESULTS: Following the intervention, both groups showed significant improvements in walking speed, symmetry index, affected step length, affected stride length, FMA-LE, and BBS scores (p < .05). Furthermore, the experimental group demonstrated greater improvements in walking speed (F = 4.58, p = .040), cadence (F = 5.67, p = .023), affected step length (F = 5.79, p = .022), affected stride length (F = 4.84, p = .035), FMA-LE (Z = 2.43, p = .019), and BBS (F = 4.76, p = .036) compared to the control group. The experimental group demonstrated a significant improvement in the co-contraction index (CCI) of the knee joint (F = 14.88, p < .001), a change not observed in the control group (F = 2.16, p = .151). However, neither group showed significant alterations in CCI of the ankle joint (F = 1.58, p = .218), step width (F = 0.24, p = .630), unaffected step length (F = 0.22, p = .641), or unaffected stride length (F = 2.99, p = .093). CONCLUSION: The combination of low-frequency rTMS and ARGAT demonstrated superior effects on motor function recovery compared to ARGAT alone in survivors of stroke.

A unified framework to control estimation error in reinforcement learning.

In reinforcement learning, accurate estimation of the Q-value is crucial for acquiring an optimal policy. However, current successful Actor-Critic methods still suffer from underestimation bias. Additionally, there exists a significant estimation bias, regardless of the method used in the critic initialization phase. To address these challenges and reduce estimation errors, we propose CEILING, a simple and compatible framework that can be applied to any model-free Actor-Critic methods. The core idea of CEILING is to evaluate the superiority of different estimation methods by incorporating the true Q-value, calculated using Monte Carlo, during the training process. CEILING consists of two implementations: the Direct Picking Operation and the Exponential Softmax Weighting Operation. The first implementation selects the optimal method at each fixed step and applies it in subsequent interactions until the next selection. The other implementation utilizes a nonlinear weighting function that dynamically assigns larger weights to more accurate methods. Theoretically, we demonstrate that our methods provide a more accurate and stable Q-value estimation. Additionally, we analyze the upper bound of the estimation bias. Based on two implementations, we propose specific algorithms and their variants, and our methods achieve superior performance on several benchmark tasks.