Bioinspired Artificial Intelligent Nociceptive Alarm System Based on Fibrous Biomemristors.

With the advancement of modern medical and brain-computer interface devices, flexible artificial nociceptors with tactile perception hold significant scientific importance and exhibit great potential in the fields of wearable electronic devices and biomimetic robots. Here, a bioinspired artificial intelligent nociceptive alarm system integrating sensing monitoring and transmission functions is constructed using a silk fibroin (SF) fibrous memristor. This memristor demonstrates high stability, low operating power, and the capability to simulate synaptic plasticity. As a result, an artificial pressure nociceptor based on the SF fibrous memristor can detect both fast and chronic pain and provide a timely alarm in the event of a fall or prolonged immobility of the carrier. Further, an array of artificial pressure nociceptors not only monitors the pressure distribution across various parts of the carrier but also provides direct feedback on the extent of long-term pressure to the carrier. This work holds significant implications for medical support in biological carriers or targeted maintenance of electronic carriers.

Bulk/Interfacial Structure Design of Li-Rich Mn-Based Cathodes for All-Solid-State Lithium Batteries.

Li-rich Mn-based cathode materials (LRMO) are promising for enhancing energy density of all-solid-state batteries (ASSBs). Nonetheless, the development of efficient Li+/e- pathways is hindered by the poor electrical conductivity of LRMO cathodes and their incompatible interfaces with solid electrolytes (SEs). Herein, we propose a strategy of in-situ bulk/interfacial structure design to construct fast and stable Li+/e- pathways by introducing Li2WO4, which reduces the energy barrier for Li+ migration and enhances the stability of the surface oxygen structure. The reversibility of oxygen redox was improved, and the voltage decay of the LRMO cathode was addressed significantly. As a result, the bulk structure of the LRMO cathodes and the high-voltage solid-solid interfacial stability are improved. Therefore, the ASSBs achieve a high areal capacity (∼3.15 mAh/cm2) and outstanding cycle stability of ≥1200 cycles with 84.1% capacity retention at 1 C at 25 °C. This study offers new insights into LRMO cathode design strategies for ASSBs, focusing on ultrastable high-voltage interfaces and high-loading composite electrodes.

Characterization of transgenic insect resistant sunflower (Helianthus annuus L.) expressing fusion protein Cry1Ab-Vip3Af2.

Lepidopteran pests frequently cause significant damage to Sunflowers (Helianthus annuus). In this study, the insect resistant fusion gene Cry1Ab-Vip3Af2 was transformed into sunflower by Agrobacterium-mediated transformation. A transgenic event, named MCPN-7, was selected and characterized for its high resistance to both yellow peach moth (Dichocrocis punctiferalis) and cotton bollworm (Helicoverpa armigera), two polyphagous pests feeding on various plants including sunflower. The neonates of both species feeding on MCPN-7 resulted to 100 % mortality within 72 h in laboratory bioassays. No significant damage caused by the two insects was observed in field trials of MCPN-7. ELISA analysis revealed that the fusion protein was predominantly expressed in leaves, seeds and heads. The flanking genomic sequence of the T-DNA of the event MCPN-7 was determined and confirmed by PCR analysis. In conclusion, the transgenic sunflowers obtained in this study is highly resistant to wide spectrum of Lepidopteran insect pests and could potentially be a candidate event for commercial development.

Reliability and validity of patient-reported outcome measures in assessing knee osteoarthritis in the Chinese population: A systematic review.

Objective: Knee osteoarthritis (KOA) is a prevalent condition in China, necessitating effective assessment tools for treatment outcomes. This study systematically reviews and analyzes the reliability, validity, and selection of patient-reported outcome measures (PROMs) for evaluating KOA. Methods: Following PRISMA guidelines, a literature search was conducted across seven databases, including CNKI, PubMed, and Embase, covering publications from December 2012 to December 2022. The methodological quality of the studies was assessed using the COSMIN checklist. Results: Twenty-one studies met the inclusion criteria, involving eight types of KOA PROMs. The Oxford Knee Score (OKS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were the most frequently utilized, appearing in nine and four studies, respectively. OKS achieved a "strong" rating in internal consistency, test-retest reliability, content validity, responsiveness, and measurement error, while WOMAC received a "strong" rating in internal consistency, test-retest reliability, and content validity, with a "moderate" rating in structural validity. Conclusion: Both OKS and WOMAC are effective PROMs for evaluating KOA in China. However, the choice of a specific tool should be based on the study's objectives and the practical context, considering each tool's reliability, validity, and other measurement properties.

Rapid genome-wide profiling of DNA methylation and genetic variation using guide positioning sequencing (GPS).

Whole-genome bisulfite sequencing (WGBS) has been extensively utilized for DNA methylation profiling over the past decade. However, it has shown limitations in terms of high costs and inefficiencies. The productivity and accuracy of DNA methylation detection rely critically on the optimization of methodologies and the continuous refinements of related sequencing platforms. Here, we describe a detailed protocol of guide positioning sequencing (GPS), a bisulfite-based, location-specific sequencing technology designed for comprehensive DNA methylation characterization across the genome. The fundamental principle of GPS lies in the substitution of dCTP with 5-methyl-dCTP (5 mC) at the 3'-end of DNA fragments by T4 DNA polymerase, which protects cytosines from bisulfite conversion to preserve the integrity of the base composition. This alteration allows the 3'-end to independently facilitate genetic variation profiling and guides the 5'-end, enriched with methylation information, to align more rapidly to the reference genome. Hence, GPS enables the concurrent detection of both genetic and epigenetic variations. Additionally, we provide an accessible description of the data processing, specifically involving certain software and scripts. Overall, the entire GPS procedure can be completed within a maximum of 15 days, starting with a low initial DNA input of 100-500 ng, followed by 4-5 days for library construction, 8-10 days for high-throughput sequencing (HTS) and data analysis, which can greatly facilitate the promotion and application of DNA methylation detection, especially for the rapid clinical diagnosis of diverse disease pathologies associated with concurrent genetic and epigenetic variations.

Osteogenic mechanism of deciduous teeth periodontal ligament stem cells in inflammatory environment.

This study aimed to illustrate the biological behavior and changes in cell function during the progression of apical periodontitis in deciduous teeth and to explore the underlying molecular mechanism. Deciduous teeth periodontal ligament stem cells (DePDLSCs) were derived and their identity was confirmed. The viability, inflammation, and osteogenic ability of cells were tested by exposing them to various concentrations of lipopolysaccharide (LPS) (0-100 µg/mL) using the cell counting kit-8 (CCK-8) assay, reverse transcription polymerase chain reaction (real-time PCR), alkaline phosphatase (ALP) staining, and ALP activity assay. In addition, osteogenic-induced cells with and without 10 µg/mL LPS were harvested for high-throughput sequencing. Based on sequencing data, proinflammatory factors and ALP expression were measured after interference with the PI3K-AKT signaling pathway activator, 740Y-P. LPS biphasically affected the proliferation and osteogenesis of DePDLSCs. Low concentrations of LPS showed stimulatory effects, whereas inhibitory effects were observed at high concentrations. Sequencing analysis showed that the PI3K-AKT signaling pathway was significantly downregulated when DePDLSCs were treated with 10 µg/mL LPS. The LPS-induced inflammation and osteogenesis inhibition of DePDLSCs were partially rescued by 740Y-P treatment. In conclusion, LPS affected DePDLSCs proliferation and osteogenesis in a biphasic manner. Moderate activation of PI3K-AKT signaling pathway was beneficial for osteogenic differentiation and anti-inflammatory effect in DePDLSCs. This research may provide etiological probes for apical periodontitis and its treatment.

Neuro-Immune Communication at the Core of Craving-Associated Brain Structural Network Reconfiguration in Methamphetamine Users.

Methamphetamine (MA) use disorder is a chronic neurotoxic brain disease characterized by a high risk of relapse driven by intense cravings. However, the neurobiological signatures of cravings remain unclear, limiting the effectiveness of various treatment methods. Diffusion MRI (dMRI) scans from 62 MA users and 57 healthy controls (HC) were used in this study. The MA users were longitudinally followed up during their period of long-term abstinence (duration of long-term abstinence: 347.52±99.25 days). We systematically quantified the control ability of each brain region for craving-associated state transitions using network control theory from a causal perspective. Craving-associated structural alterations (CSA) were investigated through multivariate group comparisons and biological relevance analysis. The neural mechanisms underlying CSA were elucidated using transcriptomic and neurochemical analyses. We observed that long-term abstinence-induced structural alterations significantly influenced the state transition energy involved in the cognitive control response to external information, which correlated with changes in craving scores (r ∼ 0.35, P <0.01). Our causal network analysis further supported the crucial role of the prefrontal cortex (PFC) in craving mechanisms. Notably, while the PFC is central to the craving, the CSAs were distributed widely across multiple brain regions (PFDR<0.05), with strong alterations in somatomotor regions (PFDR<0.05) and moderate alterations in high-level association networks (PFDR<0.05). Additionally, transcriptomic, chemical compounds, cell-type analyses, and molecular imaging collectively highlight the influence of neuro-immune communication on human craving modulation. Our results offer an integrative, multi-scale perspective on unraveling the neural underpinnings of craving and suggest that neuro-immune signaling may be a promising target for future human addiction therapeutics.

Gold nanoclusters stabilized with dopa-containing ligands: Catalyst-indicator integrated probe for tumor cell screening.

Elevated hydrogen peroxide (H2O2) levels not only inflict cellular damage but also serve as a harbinger for various diseases. Tumor cells, in particular, often exhibit an abundance of H2O2. Hence, the detection of this pivotal molecule assumes paramount importance in monitoring physiological states and expediting cancer diagnosis. To this end, we have ingeniously devised an enzyme-free and monomeric system for intracellular H2O2 detection. Our astute selection of dopa-containing peptidomimetics, replete with ortho-bisphenol and amino acid moieties, has engendered the synthesis of distinctive fluorescent gold nanoclusters (AuNCs). These nanoclusters not only function as a peroxidase-like catalyst, catalyzing the decomposition of H2O2 into hydroxyl radicals (·OH), but also serve as an indicator, with their fluorescence quenched in response to varying H2O2 concentrations. Experimental results evince that our GDpE-AuNCs exhibit remarkable sensitivity, boasting a detection limit of 0.49 µM and a linear range of 5-1000 µM. Moreover, the amalgamation of catalyst and indicator within a single structure, facilitating efficient cellular uptake, engenders intracellular H2O2 detection and discernment of tumor cells. This pioneering approach bequeaths a valuable assay probe for monitoring physiological states and ushering in early disease diagnosis.

Efficacy and Safety of Sacubitril/Allisartan for the Treatment of Primary Hypertension.

Background: The prevalence of hypertension still increases with the very rapidly increasing longevity in some countries, such as China. The control rate remains low. Objectives: This randomized, double-blind, phase 3 study assessed the efficacy and safety of sacubitril/allisartan, compared with olmesartan in Chinese patients with mild-to-moderate hypertension. Methods: Eligible patients aged 18 to 75 years (n = 1,197) with mild-to-moderate hypertension were randomized to receive sacubitril/allisartan 240 mg (n = 399), sacubitril/allisartan 480 mg (n = 399), or olmesartan 20 mg (n = 399) once daily for 12 weeks. Patients who completed the 12-week treatment then received another 12-week extended treatment (n = 1,084) and 28-week prolonged treatment (n = 189). The primary end point was a reduction in clinic mean sitting systolic blood pressure (msSBP) from baseline at 12 weeks. Results: Sacubitril/allisartan 240 mg/d provided a greater reduction in msSBP than olmesartan at 12 weeks (between-group difference: -1.9 mm Hg [95% CI: -4.2 to 0.4 mm Hg]; P = 0.0007, for noninferiority). Sacubitril/allisartan 480 mg/d provided a significantly greater reduction in msSBP than olmesartan at 12 weeks (between-treatment difference: -5.0 mm Hg [95% CI: -7.3 to -2.8 mm Hg]; P < 0.001, for superiority). Greater reductions in 24-hour, and daytime and nighttime systolic and diastolic blood pressure were also observed with both doses of sacubitril/allisartan compared with olmesartan (P ≤ 0.001 for 480 mg/d). The blood pressure reductions tended to be dose-dependent for sacubitril/allisartan. Sacubitril/allisartan was well tolerated, and no cases of angioedema or death were reported. Conclusions: Sacubitril/allisartan is effective for the treatment of hypertension and well tolerated in Chinese patients.

Understanding wrist skin temperature changes to hormone variations across the menstrual cycle.

Consumer devices are increasingly used to monitor peripheral body temperature (PBT) for menstrual cycle tracking, but the link between PBT and hormone variations remains underexplored. This study examines the relationship between these variables with a focus on nightly wrist skin temperature (WST). Fifty participants provided physiological and self-reported data, including WST, daily step counts, glucose levels, hormone levels (E3G, LH), and diary entries. Results show a negative correlation between WST and hormone levels when E3G and LH are below average, and this trend was robust to demographics and self-reported stress. Increased variance between mid-cycle hormonal peaks and WST fluctuations may stem from differences between basal body temperature (BBT) and WST. This research suggests that algorithms reliant on body temperature for tracking hormonal changes or other aspects of the menstrual cycle may need to account for increased variance in WST trends if they are meant to be deployed on wearable devices.

Tumor-associated lymphatic vessel density is a reliable biomarker for prognosis of esophageal cancer after radical resection: a systemic review and meta-analysis.

Purpose: To explore whether tumor-associated lymphatic vessel density (LVD) could be a biomarker for the prognosis of patients with esophageal cancer after radical resection. Methods: A systematic literature search was performed through PubMed, EMBASE, Wanfang Data, and Cochrane Library from the inception of databases until March 19, 2024. The selected studies investigated overall survival (OS) and/or recurrence-free survival (RFS) of patients with esophageal cancer with different levels of LVD after radical resection. The OS and RFS data were pooled as hazard ratios (HR) and 95% confidential interval (CI). Furthermore, the standardized mean differences (SMDs) and 95% CI were aggregated to evaluate the correlation between LVD and clinicopathological features. Results: A total of 10 retrospective studies of 1,201 patients were finally included for the meta-analysis. Patients with esophageal cancer with a high level of LVD exhibited worse OS (HR 1.65, 95% CI 1.18 to 2.31) and RFS (HR 1.57, 95% CI 1.09 to 2.26) than those with a low level of LVD. Subgroup analysis of different pathological subtypes revealed that patients with esophageal adenocarcinoma with a high level of LVD had significantly worse RFS (HR 2.84, 95% CI 1.61 to 5.02) than those with a low level of LVD; while patients with esophageal squamous cell carcinoma with a high level of LVD had similar OS (HR 1.52, 95% CI 0.93 to 2.47) and RFS (HR 1.03, 95% CI 0.72 to 1.48) to those with a low level of LVD. Furthermore, tumors with lymph node metastasis had significantly higher levels of LVD than those without lymph node metastasis (SMD = 1.11, 95% CI 0.54 to 1.67). Tumors at the stages III-IV had significantly higher levels of LVD than those at the stages I-II (SMD = 1.62, 95% CI 0.90 to 2.34). Conclusion: A high level of LVD in tumor was associated with worse survival of patients with esophageal cancer after radical resection, especially in patients with esophageal adenocarcinoma. Tumor-associated LVD is a new parameter that should be measured in postoperative pathology for predicting the prognosis of patients with esophageal cancer. Systematic review registration: https://www.crd.york.ac.uk/prospero/ PROSPERO, identifier CRD42024553766.

Self-assembled micro-patterns in uphill-diffusion solution system.

In this work we present self-organized regular patterns in a solution system through uphill-diffusion. Organic semiconductor solution is sandwiched between a substrate and cover plate with micrometer distance. Self-assembled regular patterns can be observed on the substrate after solvent evaporation. Different micro-patterns and pattern defects were displayed and analyzed. Mechanisms of pattern and defect formation, competitive mode selection process, and pattern sedimentation onto substrate from solution were proposed. Organic thin film transistors were fabricated with the assembled line patterns which demonstrate a promising way to produce patterned micro/nano materials. .

Meso/Microporous Single-Atom Catalysts with Curved Fe-N4 sites Boost the Oxygen Reduction Reaction Activity.

Zeolitic-imidazolate frameworks (ZIFs) are among the most efficient precursors for the synthesis of atomically dispersed Fe-N/C materials, which are promising catalysts for enhancing the performance of Zn-air batteries (ZABs) and proton exchange fuel cells (PEMFCs). However, existing ZIF-derived Fe-N/C electrocatalysts mostly consist of microporous materials, leading to insufficient mass transport and inadequate battery/cell performance. In this study, we synthesize an atomically dispersed meso/microporous Fe-N/C material with curved Fe-N4 active sites, denoted as FeSA-N/TC, through the pyrolysis of hemin-modified ZIF films on ZnO nanorods, obtained from the self-assembly reaction between Zn2+ from ZnO hydrolysis and 2-methylimidazole. Density functional theory calculations demonstrate that the curved Fe-N4 active sites can weaken the intermediate adsorptions, resulting in lower free energy barriers and enhanced performance during oxygen reduction reaction (ORR). Specifically, FeSA-N/TC exhibits exceptional ORR performance with half-wave potentials of 0.925 V in alkaline media and 0.825 V in acidic media. When used as the cathodic catalyst in PEMFCs and ZABs, FeSA-N/TC achieves high peak power densities (H2-O2 PEMFC: 1100 mW cm-2; H2-Air PEMFC: 715 mW cm-2; liquid-state ZAB: 228 mW cm-2; solid-state ZAB: 112 mW cm-2), demonstrating its feasibility and efficiency in practical applications.

Rab8a Is a Key Target That Melatonin Prevents Lipid Disorder from Atrazine.

Atrazine (ATZ), a widely used herbicide, disrupts mitochondrial function and lipid metabolism in the liver. Melatonin (MLT), a naturally synthesized hormone, combats mitochondrial dysfunction and alleviates lipid toxicity. However, the mechanisms behind ATZ-induced lipid metabolism toxicity and the protective effects of MLT remain unexplored. Mice were randomly assigned to four groups: control (Con), 5 mg/kg MLT, 170 mg/kg ATZ, and a cotreatment group receiving 170 mg/kg ATZ with 5 mg/kg MLT (ATZ+MLT). Additionally, we analyzed the effects of MLT and Rab8a on mRNA and proteins related to mitochondrial function and lipid metabolism disrupted by ATZ in AML12 cells. In conclusion, ATZ induced mitochondrial stress and disrupted fatty acid metabolism in mouse hepatocytes and AML12 cells. Exogenous MLT restores Rab8a levels, regulating fatty acid utilization in mitochondria and mitochondrial function. Notably, targeting Rab8a does not significantly affect mitochondrial function but prevents ATZ-induced lipid metabolism disorders in hepatocytes.

Hippocampal dipeptidyl peptidase 9 bidirectionally regulates memory associated with synaptic plasticity.

INTRODUCTION: Subtypes of the dipeptidyl peptidase (DPP) family, such as DPP4, are reportedly associated with memory impairment. DPP9 is widely distributed in cells throughout the body, including the brain. However, whether DPP9 regulates memory has not yet been elucidated. OBJECTIVES: This study aimed to elucidate the role of DPP9 in memory, as well as the underlying molecular mechanism. METHODS: We performed immunofluorescence on mouse brains to explore the distribution of DPP9 in different brain regions and used AAV vectors to construct knockdown and overexpression models. The effects of changing DPP9 expression on memory were demonstrated through behavioral experiments. Finally, we used electrophysiology, proteomics and affinity purification mass spectrometry (AP-MS) to study the molecular mechanism by which DPP9 affects memory. RESULTS: Here, we report that DPP9, which is found almost exclusively in neurons, is expressed and has enzyme activity in many brain regions, especially in the hippocampus. Hippocampal DPP9 expression increases after fear memory formation. Fear memory was impaired by DPP9 knockdown and enhanced by DPP9 protein overexpression in the hippocampus. According to subsequent hippocampal proteomics, multiple pathways, including the peptidase pathway, which can be bidirectionally regulated by DPP9. DPP9 directly interacts with its enzymatic substrate neuropeptide Y (NPY) in neurons. Hippocampal long-term potentiation (LTP) is also bidirectionally regulated by DPP9. Moreover, inhibiting DPP enzyme activity impaired both LTP and memory. In addition, AP-MS revealed that DPP9-interacting proteins are involved in the functions of dendritic spines and axons. By combining AP-MS and proteomics, DPP9 was shown to play a role in regulating actin functions. CONCLUSION: Taken together, our findings reveal that DPP9 affects the CNS not only through enzymatic activity but also through protein-protein interactions. This study provides new insights into the molecular mechanisms of memory and DPP family functions.

A photoinduced electron-transfer strategy for switchable fluorescence and phosphorescence in lanthanide-based coordination polymers.

Smart optical materials with tunable fluorescence and room temperature phosphorescence (RTP) exhibit promising application prospects in the field of intelligent switches, information security, etc. Herein, a tetraimidazole derivative was grafted to one-dimensional lanthanum-diphosphonate through H-bonds, generating a coordination polymer (CP), (H4-TIBP)·[La2Li(H2-HEDP)4(H-HEDP)]·3H2O (termed La; TIBP = 3,3,5,5-tetra(imidazole-1-yl)-1,1-biphenyl; H4-HEDP = 1-hydroxyethylidene-1,1-diphosphonic acid) with a three-dimensional supramolecular structure. La shows dynamic fluorescence from blue to red and switchable monotonous yellowish-green RTP, which can be manipulated by reversible photochromism. It is worth noting that Eu3+/Tb3+-doped CPs exhibit time-resolved (red to yellow) and monotonous green afterglow, respectively, which can be attributed to multiple emissions with different decay rates. The dynamic and multicolor luminescence endows these CPs with potential for application in the domains of optical communications, multi-step encryption, and anti-counterfeiting. This work not only integrates color-adjustable fluorescence, switchable RTP, and photochromism in one material, but also realizes the manipulation of the resultant optical performances via photochromism, paving the pathway for the design and synthesis of smart optical materials.

Mitotic spindle positioning protein serves as prognostic biomarker in patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) ranks among the most aggressive types of cancer globally. Currently, clinical tumor prognostic biomarkers still lack accuracy. Mitotic spindle positioning (MISP) protein connects microtubules to the actin cytoskeleton and adhesive plaques, playing a critical role in spindle positioning, orientation, and the process of cell division. MISP can regulate the malignant biological functions of pancreatic cancer and intrahepatic cholangiocarcinoma and it acts as biomarker for prognosis, but its role in CRC remains unclear. METHODS: This study has collected 37 CRC tissue samples and 37 corresponding adjacent nontumor tissue samples, and 57 additional CRC tissues samples. Clinical data were obtained from the patients with CRC. MISP mRNA and protein expression levels were analyzed in normal control and CRC tissues using the GEPIA and Human Protein Atlas website. MISP protein levels in the collected tissues were analyzed using immunohistochemistry. RESULTS: MISP mRNA and protein expression levels were significantly increased in CRC tissues compared to adjacent nontumor tissues. Higher MISP protein levels were associated with distant metastasis, recurrence, and lower survival rates. Kaplan-Meier analysis showed that high expression levels of MISP protein were associated with recurrence and death in CRC patients. In addition, a high expression level of MISP protein, lymph node metastasis, and distance metastasis were risk factors for recurrence and a poor prognosis in patients with CRC. CONCLUSION: Elevated MISP protein correlated with tumor metastasis, recurrence, and lower survival rates in patients with CRC, and thus, MISP has the potential to become a prognostic marker for CRC.

CD2AP promotes the progression of glioblastoma multiforme via TRIM5-mediated NF-kB signaling.

CD2-associated protein (CD2AP) is a scaffolding/adaptive protein that regulates intercellular adhesion and multiple signaling pathways. Although emerging evidence suggests that CD2AP is associated with several malignant tumors, there is no study investigating the expression and biological significance of CD2AP in glioblastoma multiforme (GBM). Here by studying public datasets, we found that CD2AP expression was significantly elevated in GBM and that glioma patients with increased CD2AP expression had a worse prognosis. We also confirmed the increase of CD2AP expression in clinical GBM samples and GBM cell lines. CD2AP overexpression in GBM cells promoted their proliferation, colony formation, migration, and invasion in vitro and their tumorigenesis in vivo, and reduced cell apoptosis both at basal levels and in response to temozolomide. While CD2AP knockdown had the opposite effects. Mechanistically, we revealed that CD2AP interacted with TRIM5, an NF-κB modulator. CD2AP overexpression and knockdown increased and decreased TRIM5 levels as well as the NF-κB activity, respectively. Moreover, downregulation of TRIM5 reversed elevated NF-κB activity in GBM cells with CD2AP overexpression; and inhibition of the NF-κB activity attenuated malignant features of GBM cells with CD2AP overexpression. Our findings demonstrate that CD2AP promotes GBM progression through activating TRIM5-mediated NF-κB signaling and that downregulation of CD2AP can attenuate GBM malignancy, suggesting that CD2AP may become a biomarker and the CD2AP-TRIM5-NF-κB axis may become a therapeutic target for GBM.

Challenges and resilience of Taiwan's oral health care system after Covid-19 pandemic.

This paper examines the resilience of Taiwan's oral healthcare system in response to COVID-19, focusing on pre-pandemic conditions, pandemic impacts, and policy recommendations for future resilience. In Taiwan, oral diseases were prevalent, with 80.48% of adults affected by periodontitis in 2016, and 65.43% of 5-year-old children experiencing dental caries. Taiwan's National Health Insurance (NHI) covers over 99% of the population, providing comprehensive dental care. The global budget (GB) payment system, implemented in 1998, ensured financial stability. During the pandemic, dental visits in Taiwan decreased by 5.1% in 2021 compared to 2019. Despite reduced visits, the GB system maintained financial stability, mitigating financial impacts on healthcare institutions. The pandemic generally negatively affected healthcare workers' well-being, increasing resignation intentions. However, the number of practicing dentists in Taiwan remained stable from 2016 to 2022, with slight increases. Urban-rural disparities persisted, and workplace transitions increased, indicating greater mobility among dental professionals. To enhance resilience, the following recommendations are proposed: 1. Strengthen hierarchy of oral healthcare system: Balance dental resources across regions, and improve referrals between hospital and clinics; 2. Provide integrated patient-centered care: Integrate oral health into disease prevention and offer comprehensive services across all stages of life; 3. Integrate digital technology: Promote teledentistry and leverage Taiwan's strengths in information and communication technology (ICT).