Effects of Connectivity Isomerization on Electron Transport Through Thiophene Heterocyclic Molecular Junction.

Connectivity isomerization of the same aromatic molecular core with different substitution positions profoundly affects electron transport pathways and single-molecule conductance. Herein, we designed and synthesized all connectivity isomers of a thiophene (TP) aromatic ring substituted by two dihydrobenzo[b]thiophene (BT) groups with ethynyl spacers (m,n-TP-BT, (m,n = 2,3; 2,4; 2,5; 3,4)), to systematically probe how connectivity contributes to single-molecule conductance. Single-molecule conductance measurements using a scanning tunneling microscopy break junction (STM-BJ) technique show ∼12-fold change in conductance values, which follow an order of 10-4.83 G0 (2,4-TP-BT) < 10-4.78 G0 (3,4-TP-BT) < 10-4.06 G0 (2,3-TP-BT) < 10-3.75 G0 (2,5-TP-BT). Electronic structure analysis and theoretical simulations show that the connectivity isomerization significantly changes electron delocalization and HOMO-LUMO energy gaps. Moreover, the connectivity-dependent molecular structures lead to different quantum interference (QI) effects in electron transport, e.g., a strong destructive QI near E = EF leads the smallest conductance value for 2,4-TP-BT. This work proves a clear relationship between the connectivity isomerization and single-molecule conductance of thiophene heterocyclic molecular junctions for the future design of molecular devices.

Images with harder-to-reconstruct visual representations leave stronger memory traces.

Much of what we remember is not because of intentional selection, but simply a by-product of perceiving. This raises a foundational question about the architecture of the mind: how does perception interface with and influence memory? Here, inspired by a classic proposal relating perceptual processing to memory durability, the level-of-processing theory, we present a sparse coding model for compressing feature embeddings of images, and show that the reconstruction residuals from this model predict how well images are encoded into memory. In an open memorability dataset of scene images, we show that reconstruction error not only explains memory accuracy, but also response latencies during retrieval, subsuming, in the latter case, all of the variance explained by powerful vision-only models. We also confirm a prediction of this account with 'model-driven psychophysics'. This work establishes reconstruction error as an important signal interfacing perception and memory, possibly through adaptive modulation of perceptual processing.

Clinical Effect of Dermatologic Trephination Combined With Radiotherapy in the Treatment of Keloids.

BACKGROUND: Keloids are excessive formations of scar tissue that develop at the site of a skin injury. Due to their invasive nature, they have a negative impact on the skin's appearance and are prone to recurrence, making them a challenging condition to treat in terms of skin aesthetics. OBJECTIVES: The objective of this article is to compare the long-term effects of dermatologic trephination with non-surgical treatments in scar repair and evaluate their clinical value. METHODS: A retrospective analysis was conducted on 48 patients who received keloids treatment in the Department of Dermatology and Thoracic Surgery of our hospital from January 2021 to October 2023, of which 24 patients received dermatologic trephination and 24 patients received non-surgical treatment. Outcome measures included scar appearance, scar healing time, pain and itching levels, and patient satisfaction. RESULTS: In the comparison of scar healing time, the healing time of patients using dermatologic trephination was significantly shorter than that of patients in the non-surgical group. In the evaluation of the degree of itching, the degree of itching in patients undergoing dermatologic trephination was significantly lower than that of patients in the non-surgical group. In the evaluation of satisfaction, the satisfaction of patients using dermatologic trephination was significantly higher than that of patients in the non-surgical group. CONCLUSIONS: This study demonstrates that trephination achieves more significant long-term results in keloid revision, including improved keloid appearance, itching and patient satisfaction.

Essential role of N-terminal SAM regions in STIM1 multimerization and function.

The single-pass transmembrane protein Stromal Interaction Molecule 1 (STIM1), located in the endoplasmic reticulum (ER) membrane, possesses two main functions: It senses the ER-Ca2+ concentration and directly binds to the store-operated Ca2+ channel Orai1 for its activation when Ca2+ recedes. At high resting ER-Ca2+ concentration, the ER-luminal STIM1 domain is kept monomeric but undergoes di/multimerization once stores are depleted. Luminal STIM1 multimerization is essential to unleash the STIM C-terminal binding site for Orai1 channels. However, structural basis of the luminal association sites has so far been elusive. Here, we employed molecular dynamics (MD) simulations and identified two essential di/multimerization segments, the α7 and the adjacent region near the α9-helix in the sterile alpha motif (SAM) domain. Based on MD results, we targeted the two STIM1 SAM domains by engineering point mutations. These mutations interfered with higher-order multimerization of ER-luminal fragments in biochemical assays and puncta formation in live-cell experiments upon Ca2+ store depletion. The STIM1 multimerization impeded mutants significantly reduced Ca2+ entry via Orai1, decreasing the Ca2+ oscillation frequency as well as store-operated Ca2+ entry. Combination of the ER-luminal STIM1 multimerization mutations with gain of function mutations and coexpression of Orai1 partially ameliorated functional defects. Our data point to a hydrophobicity-driven binding within the ER-luminal STIM1 multimer that needs to switch between resting monomeric and activated multimeric state. Altogether, these data reveal that interactions between SAM domains of STIM1 monomers are critical for multimerization and activation of the protein.

Deep learning based digital pathology for predicting treatment response to first-line PD-1 blockade in advanced gastric cancer.

BACKGROUND: Advanced unresectable gastric cancer (GC) patients were previously treated with chemotherapy alone as the first-line therapy. However, with the Food and Drug Administration's (FDA) 2022 approval of programmed cell death protein 1 (PD-1) inhibitor combined with chemotherapy as the first-li ne treatment for advanced unresectable GC, patients have significantly benefited. However, the significant costs and potential adverse effects necessitate precise patient selection. In recent years, the advent of deep learning (DL) has revolutionized the medical field, particularly in predicting tumor treatment responses. Our study utilizes DL to analyze pathological images, aiming to predict first-line PD-1 combined chemotherapy response for advanced-stage GC. METHODS: In this multicenter retrospective analysis, Hematoxylin and Eosin (H&E)-stained slides were collected from advanced GC patients across four medical centers. Treatment response was evaluated according to iRECIST 1.1 criteria after a comprehensive first-line PD-1 immunotherapy combined with chemotherapy. Three DL models were employed in an ensemble approach to create the immune checkpoint inhibitors Response Score (ICIsRS) as a novel histopathological biomarker derived from Whole Slide Images (WSIs). RESULTS: Analyzing 148,181 patches from 313 WSIs of 264 advanced GC patients, the ensemble model exhibited superior predictive accuracy, leading to the creation of ICIsNet. The model demonstrated robust performance across four testing datasets, achieving AUC values of 0.92, 0.95, 0.96, and 1 respectively. The boxplot, constructed from the ICIsRS, reveals statistically significant disparities between the well response and poor response (all p-values < = 0.001). CONCLUSION: ICIsRS, a DL-derived biomarker from WSIs, effectively predicts advanced GC patients' responses to PD-1 combined chemotherapy, offering a novel approach for personalized treatment planning and allowing for more individualized and potentially effective treatment strategies based on a patient's unique response situations.

Fractionated radiation therapy alters energy metabolism and induces cellular quiescence exit in patient-derived orthotopic xenograft models of high-grade glioma.

Radiation is one of the standard therapies for pediatric high-grade glioma (pHGG), of which the prognosis remains poor. To gain an in-depth understanding of biological consequences beyond the classic DNA damage, we treated 9 patient-derived orthotopic xenograft (PDOX) models, including one with DNA mismatch repair (MMR) deficiency, with fractionated radiations (2 Gy/day x 5 days). Extension of survival time was noted in 5 PDOX models (P < 0.05) accompanied by γH2AX positivity in >95 % tumor cells in tumor core and >85 % in the invasive foci as well as ∼30 % apoptotic and mitotic catastrophic cell death. The model with DNA MMR (IC-1406HGG) was the most responsive to radiation with a reduction of Ki-67(+) cells. Altered metabolism, including mitochondria number elevation, COX IV activation and reactive oxygen species accumulation, were detected together with the enrichment of CD133+ tumor cells. The latter was caused by the entry of quiescent G0 cells into cell cycle and the activation of self-renewal (SOX2 and BMI1) and epithelial mesenchymal transition (fibronectin) genes. These novel insights about the cellular and molecular mechanisms of fractionated radiation in vivo should support the development of new radio-sensitizing therapies.

Purification of inorganic nitrogen from the mariculture tail water by anaerobic/anoxic/oxic (A2O) process.

This study aims to address the suboptimal performance of conventional denitrifying strains in treating mariculture tail water (MTW) containing inorganic nitrogen (IN). The concentration of inorganic nitrogen in the mariculture tail water is about 5-20 mg·L-1. A biofilm treatment process was developed and evaluated using an anoxic-anoxic-aerobic biofilter composite system inoculated with the denitrifying strain Meyerozyma guilliermondii Y8. The removal effect of total nitrogen (TN), IN, and Chemical Oxygen Demand (CODMn) from MTW was investigated. The results indicate that the A2O composite biological filter has excellent pollutant removal efficiency within 25 days of operation, after the acclimation of the denitrifying microorganisms. The initial concentrations of TN, IN, and CODMn ranged between 10.24 and 12.89 mg·L-1, 7.84-10.49 mg·L-1, and 9.44-11.52 mg·L-1, respectively, and the removal rates of these indexes reached 38-68 %, 45-70 %, and 55-70 %, respectively. The experiments with different hydraulic retention times (HRT = 6 h, 8 h, 10 h) demonstrated that longer HRT was more conducive to the removal of inorganic nitrogen. Moreover, scanning electron microscopy observations revealed that the target strain successfully grew and attached to the filler in large quantities. The findings of this study provide practical guidance for the development of efficient biofilm processes for the treatment of MTW.

Insights into growth stages and genotypes in airborne Pb accumulation in Oryza sativa L. grains: Utilizing isotope fingerprinting alongside a model study.

Atmospheric exposure is an important pathway of accumulation of lead (Pb) in Oryza sativa L. grains. In this study, source contributions of soil, early atmospheric exposure, and late atmospheric exposure, along with their bioaccumulation ratios were examined both in the pot and field experiments using stable Pb isotope fingerprinting technology combined with a three-compartment accumulation model. Furthermore, genotype differences in airborne Pb accumulation among four field-grown rice cultivars were investigated using the partial least squares path model (PLS-PM) linking rice Pb accumulation to agronomic traits. The findings revealed that during the late growth period, the air-foliar-grain transfer of Pb was crucial for rice Pb accumulation. Approximately 69-82% of the Pb found in polished rice was contributed by atmospheric source, with more than 80% accumulating during the late growth stage. The air accumulation ratios of rice grains were genotype-specific and estimated to be 0.364-1.062 m3/g during the late growth. Notably, grain size exhibited the highest standardized total effects on the airborne Pb concentrations in the polished rice, followed by leaf Pb and the upward translocation efficiency of Pb. The present study indicates that mitigating the health risks associated with Pb in rice can be achieved by controlling atmospheric Pb levels during the late growth stage and choosing Japonica inbred varieties characterized by large grain size.

Relationship Between Mindfulness and Affiliate Stigma in Parents of Children with Autism Spectrum Disorder in China: The Mediating Role of Coping Styles.

PURPOSE: This study aims to investigate the current status of affiliate stigma among parents of autistic children, analyze the influencing factors, explore the relationship among mindfulness, coping styles, and affiliate stigma, and verify the mediating role of coping styles between mindfulness and affiliate stigma in parents of children with autism in China. METHOD: Between February and April 2023, the Child Development Behaviour Centre of a public hospital in China recruited 345 parents of children with autism. These parents completed the general information questionnaire, the Mindful Attention Awareness Scale, the Affiliate Stigma Scale, and the Simple Coping Style Questionnaire. We then adapted the Hayes Process Macro and Bootstrap methods to examine the mediating effects of coping styles between mindfulness and affiliate stigma. RESULTS: (1) The total affiliate stigma score of parents of children with autism was 48.53 (standard deviation:: 10.74). Parents' age, monthly family income, duration of care, mindfulness, and coping styles were the influencing factors of parental affiliate stigma. (2) Mindfulness was positively correlated with positive coping style (r = 0.33, p < .01) and negatively correlated with negative coping style, affiliate stigma (r = -0.38, -0.39, p < .01), whereas affiliate stigma was negatively correlated with positive coping style (r = -0.34, p < .01) and positively correlated with negative coping style (r = 0.41, p < .01). (3) Positive coping style and negative coping style play a parallel mediating role between mindfulness and affiliate stigma of parents of autistic children. CONCLUSIONS: Parents of children with autism experience significant levels of affiliate stigma. Mindfulness has a direct impact on associated stigma in parents of children with autism and also indirectly predicts associated stigma through the intermediary influence of positive and negative coping styles. Healthcare professionals could perform mindfulness interventions from an optimistic psychology viewpoint to boost parents' mindfulness and coping abilities, thereby accomplishing the objective of mitigating affiliate stigma.

Rethinking the effects of adjuvant beam radiation therapy on overall survival in atypical meningioma patients: age considerations.

Background: This study aimed to investigate the effects of adjuvant beam radiation therapy (ABRT) on overall survival (OS) in patients with primary single intracranial atypical meningioma (AM), with a focus on age-related outcomes. Methods: We conducted a retrospective study using data from SEER database. Our cohort consisted of patients diagnosed with a primary single intracranial AM tumor and had undergone surgery. The primary endpoint was OS. For survival analysis, univariable and multivariable Cox regression analysis were performed. A multivariable additive Cox model was used to assess the functional relationship between age and OS in patients with or without ABRT. Results: Of the 2,759 patients included, 1,650 underwent gross total resection and 833 received ABRT. Multivariable Cox analysis indicated that ABRT did not significantly influence OS across the entire cohort. According to the multivariable generalized additive Cox model, the relative risk of all-cause mortality increased with advancing age in both ABRT-yes and ABRT-no group. ABRT-yes had a lower relative risk than ABRT-no when age ≤ 55 years old while a higher relative risk when age > 55 years old. Subsequent multivariable Cox analysis showed that ABRT was associated with a significant lower risk for all-cause mortality in patients with age ≤ 55 years old while a significant higher risk in patients with age > 55 years old. Conclusion: Our study found that ABRT enhanced OS in younger primary single intracranial AM patients. But we also revealed a negative correlation between OS and ABRT in older patients.

Unveiling the impact of cryptic plasmids curing on Escherichia coli Nissle 1917: massive increase in Ag43c expression.

Escherichia coli Nissle 1917 (EcN) is an important chassis strain widely used for the development of live biotherapeutic products (LBPs). EcN strain naturally harbors two cryptic plasmids with unknown function. During the development of LBPs using EcN strain, the cryptic plasmids were cured usually to avoid plasmid incompatibility or alleviate metabolic burdens associated with these cryptic plasmids. While the cryptic plasmids curing in EcN may appear to be a routine procedure, the comprehensive impact of cryptic plasmids curing on the EcN strain remains incompletely understood. In the present study, the effects of cryptic plasmids curing on EcN were investigated using transcriptome sequencing. The results revealed that only a small number of genes showed significant changes in mRNA levels after cryptic plasmid curing (4 upregulated and 6 downregulated genes), primarily involved in amino acid metabolism. Furthermore, the flu gene showed the most significant different expression, encoding Antigen 43 (Ag43) protein, a Cah family adhesin. Mass spectrometry analysis further confirmed the significant increase in Ag43 expression. Ag43 is commonly present in Escherichia coli and mediates the bacterial autoaggregation. However, despite the upregulation of Ag43 expression, no Ag43-mediated cell self-sedimentation was observed in the cured EcN strain. These findings contribute to making informed decisions regarding the curing of the cryptic plasmids when Escherichia coli Nissle 1917 is used as the chassis strain.

Co-Assembled Nanoparticles toward Multi-Target Combinational Therapy of Alzheimer's Disease by Making Full Use of Molecular Recognition and Self-Assembly.

The complex pathologies in Alzheimer's disease (AD) severely limit the effectiveness of single-target pharmic interventions, thus necessitating multi-pronged therapeutic strategies. While flexibility is essentially demanded in constructing such multi-target systems, for achieving optimal synergies and also accommodating the inherent heterogeneity within AD. Utilizing the dynamic reversibility of supramolecular strategy for conferring sufficient tunability in component substitution and proportion adjustment, amphiphilic calixarenes are poised to be a privileged molecular tool for facilely achieving function integration. Herein, taking ß-amyloid (Aß) fibrillation and oxidative stress as model combination pattern, a supramolecular multifunctional integration is proposed by co-assembling guanidinium-modified calixarene with ascorbyl palmitate and loading dipotassium phytate within calixarene cavity. Serial pivotal events can be simultaneously addressed by this versatile system, including 1) inhibition of Aß production and aggregation, 2) disintegration of Aß fibrils, 3) acceleration of Aß metabolic clearance, and 4) regulation of oxidative stress, which is verified to significantly ameliorate the cognitive impairment of 5×FAD mice, with reduced Aß plaque content, neuroinflammation, and neuronal apoptosis. Confronted with the extremely intricate clinical realities of AD, the strategy presented here exhibits ample adaptability for necessary alterations on combinations, thereby may immensely expedite the advancement of AD combinational therapy through providing an exceptionally convenient platform.

In Situ Reduction of Silver Nanoparticles/Urushiol-Based Polybenzoxazine Composite Coatings with Enhanced Antimicrobial and Antifouling Performances.

Marine anti-fouling coatings represent an efficient approach to prevent and control the marine biofouling. However, a significant amount of antifouling agent is added to improve the static antifouling performance of the coatings, which leads to an issue whereby static antifouling performance conflicts with eco-friendly traits. Herein, this work reports an in situ reduction synthesis of silver nanoparticles (AgNPs) within polymers to produce composite coatings, aiming to solve the aforementioned issue. Firstly, urushiol-based benzoxazine monomers were synthesized by the Mannich reaction, using an eco-friendly natural product urushiol and n-octylamine and paraformaldehyde as the reactants. Additionally, AgNPs were obtained through the employment of free radicals formed by phenolic hydroxyl groups in the urushiol-based benzoxazine monomers, achieved by the in situ reduction of silver nitrate in benzoxazine. Then, the urushiol-based benzoxazine/AgNPs composite coatings were prepared by the thermosetting method. AgNPs exhibit broad-spectrum and highly efficient antimicrobial properties, with a low risk to human health and a minimal environmental impact. The composite coating containing a small amount of AgNPs (≤1 wt%) exhibits effective inhibition against various types of bacteria and marine microalgae in static immersion, thereby displaying outstanding antifouling properties. This organic polymer and inorganic nanoparticle composite marine antifouling coating, with its simple preparation method and eco-friendliness, presents an effective solution to the conflict between static antifouling effectiveness and environmental sustainability in marine antifouling coatings.

Flat-band Friedrich-Wintgen bound states in the continuum based on borophene metamaterials.

Many applications involve the phenomenon of a material absorbing electromagnetic radiation. By exploiting wave interference, the efficiency of absorption can be significantly enhanced. Here, we propose Friedrich-Wintgen bound states in the continuum (F-W BICs) based on borophene metamaterials to realize coherent perfect absorption with a dual-band absorption peak in commercially important communication bands. Metamaterials consist of borophene gratings and a borophene sheet that can simultaneously support a Fabry-Perot plasmon resonance and a guided plasmon mode. The formation and dynamic modulation of the F-W BIC can be achieved by adjusting the width or carrier density of the borophene grating, while the strong coupling leads to the anti-crossover behavior of the absorption spectrum. Due to the weak angular dispersion originating from the intrinsic flat-band characteristic of the deep sub-wavelength periodic structure, the proposed plasmonic system exhibits almost no change in wavelength and absorption at large incident angles (within 70 degrees). In addition, we employ the temporal coupled-mode theory including near- and far-field coupling to obtain strong critical coupling, successfully achieve coherent perfect absorption, and can realize the absorption switch by changing the phase difference between the two coherent beams. Our findings can offer theoretical support for absorber design and all-optical tuning.

Transient social-ecological dynamics reveal signals of decoupling in a highly disturbed Anthropocene landscape.

Understanding the transient dynamics of interlinked social-ecological systems (SES) is imperative for assessing sustainability in the Anthropocene. However, how to identify critical transitions in real-world SES remains a formidable challenge. In this study, we present an evolutionary framework to characterize these dynamics over an extended historical timeline. Our approach leverages multidecadal rates of change in socioeconomic data, paleoenvironmental, and cutting-edge sedimentary ancient DNA records from China's Yangtze River Delta, one of the most densely populated and intensively modified landscapes on Earth. Our analysis reveals two significant social-ecological transitions characterized by contrasting interactions and feedback spanning several centuries. Initially, the regional SES exhibited a loosely connected and ecologically sustainable regime. Nevertheless, starting in the 1950s, an increasingly interconnected regime emerged, ultimately resulting in the crossing of tipping points and an unprecedented acceleration in soil erosion, water eutrophication, and ecosystem degradation. Remarkably, the second transition occurring around the 2000s, featured a notable decoupling of socioeconomic development from ecoenvironmental degradation. This decoupling phenomenon signifies a more desirable reconfiguration of the regional SES, furnishing essential insights not only for the Yangtze River Basin but also for regions worldwide grappling with similar sustainability challenges. Our extensive multidecadal empirical investigation underscores the value of coevolutionary approaches in understanding and addressing social-ecological system dynamics.

Multi-modality deep learning model reaches high prediction accuracy in the diagnosis of ovarian cancer.

We evaluated the diagnostic performance of a multimodal deep-learning (DL) model for ovarian mass differential diagnosis. This single-center retrospective study included 1,054 ultrasound (US)-detected ovarian tumors (699 benign and 355 malignant). Patients were randomly divided into training (n = 675), validation (n = 169), and testing (n = 210) sets. The model was developed using ResNet-50. Three DL-based models were proposed for benign-malignant classification of these lesions: single-modality model that only utilized US images; dual-modality model that used US images and menopausal status as inputs; and multi-modality model that integrated US images, menopausal status, and serum indicators. After 5-fold cross-validation, 210 lesions were tested. We evaluated the three models using the area under the curve (AUC), accuracy, sensitivity, and specificity. The multimodal model outperformed the single- and dual-modality models with 93.80% accuracy and 0.983 AUC. The Multimodal ResNet-50 DL model outperformed the single- and dual-modality models in identifying benign and malignant ovarian tumors.

Evaluating Prognosis of Gastrointestinal Metastatic Neuroendocrine Tumors: Constructing a Novel Prognostic Nomogram Based on NETPET Score and Metabolic Parameters from PET/CT Imaging.

INTRODUCTION: The goal of this study is to compare the prognostic performance of NETPET scores, based on gallium-68 DOTANOC (68Ga-DOTANOC) and fluorine-18 fluorodeoxyglucose (18F-FDG) Positron Emission Tomography-Computed Tomography (PET-CT), and PET-CT metabolic parameters in metastatic gastrointestinal neuroendocrine tumors (GI-NET), while constructing and validating a nomogram derived from dual-scan PET-CT. METHODS: In this retrospective study, G1-G3 GI-NET patients who underwent 68Ga-DOTANOC and 18F-FDG PET scans were enrolled and divided into training and internal validation cohorts. Three grading systems were constructed based on NETPET scores and standardized uptake value maximum (SUVmax). LASSO regression selected variables for a multivariable Cox model, and nomograms predicting progression-free survival (PFS) and overall survival (OS) were created. The prognostic performance of these systems was assessed using time-dependent receiver-operating characteristic (ROC) curves, concordance index (C-index), and other methods. Nomogram evaluation involved calibration curves, decision curve analysis (DCA), and the aforementioned methods in both cohorts. RESULTS: In this study, 223 patients (130 males; mean age ± SD: 52.6 ± 12 years) were divided into training (148) and internal validation (75) cohorts. Dual scans were classified based on NETPET scores (D1-D3). Single 68Ga-DOTANOC and 18F-FDG PET-CT scans were stratified into S1-S3 and F1-F3 based on SUVmax. The NETPET score-based grading system demonstrated the best OS and PFS prediction (C-index, 0.763 vs. 0.727 vs. 0.566). Nomograms for OS and PFS exhibited superior prognostic performance in both cohorts (all AUCs > 0.8). CONCLUSIONS: New classification based on NETPET score predicts patient OS/PFS best. PET-CT-based nomograms show accurate OS/PFS forecasts.

Hippocampal HDAC6 promotes POCD by regulating NLRP3-induced microglia pyroptosis via HSP90/HSP70 in aged mice.

BACKGROUND: Postoperative Cognitive Dysfunction (POCD) has attracted increased attention, but its precise mechanism remains to be explored. This study aimed to figure out whether HDAC6 could regulate NLRP3-induced pyroptosis by modulating the functions of HSP70 and HSP90 in microglia to participate in postoperative cognitive dysfunction in aged mice. METHODS: Animal models of postoperative cognitive dysfunction in aged mice were established by splenectomy under sevoflurane anesthesia. Morris water maze was used to examine the cognitive function and motor ability. Sixteen-months-old C57BL/6 male mice were randomly divided into six groups: control group (C group), sham surgery group (SA group), splenectomy group (S group), splenectomy + HDAC6 inhibitor ACY-1215 group (ACY group), splenectomy + HDAC6 inhibitor ACY-1215 + HSP70 inhibitor Apoptozole group (AP group), splenectomy + solvent control group (SC group). The serum and hippocampus of mice were taken after mice were executed. The protein levels of HDAC6, HSP90, HSP70, NLRP3, GSDMD-N, cleaved-Caspase-1 (P20), IL-1ß were detected by western blotting. Serum IL-1ß, IL-6 and S100ß were measured using ELISA assay, and cell localization of HDAC6 was detected by immunofluorescence. In vitro experiments, BV2 cells were used to validate whether this mechanism worked in microglia. The protein levels of HDAC6, HSP90, HSP70, NLRP3, GSDMD-N, P20, IL-1ß were detected by western blotting and the content of IL-1ß in the supernatant was measured using ELISA assay. The degree of acetylation of HSP90, the interaction of HSP70, HSP90 and NLRP3 were analyzed by coimmunoprecipitation assay. RESULTS: Splenectomy under sevoflurane anesthesia in aged mice could prolong the escape latency, reduce the number of crossing platforms, increase the expression of HDAC6 and activate the NLRP3 inflammasome to induce pyroptosis in hippocampus microglia. Using ACY-1215 could reduce the activation of NLRP3 inflammasome, the pyroptosis of microglia and the degree of spatial memory impairment. Apoptozole could inhibit the binding of HSP70 to NLRP3, reduce the degradation of NLRP3 and reverse the protective effect of HDAC6 inhibitors. The results acquired in vitro experiments closely resembled those in vivo, LPS stimulation led to the pyroptosis of BV2 microglia cells and the release of IL-1ß due to the activation of the NLRP3 inflammasome, ACY-1215 showed the anti-inflammatory effect and Apoptozole exerted the opposite effect. CONCLUSIONS: Our findings suggest that hippocampal HDAC6 promotes POCD by regulating NLRP3-induced microglia pyroptosis via HSP90/HSP70 in aged mice.

Construction methods and biomedical applications of PVA-based hydrogels.

Polyvinyl alcohol (PVA) hydrogel is favored by researchers due to its good biocompatibility, high mechanical strength, low friction coefficient, and suitable water content. The widely distributed hydroxyl side chains on the PVA molecule allow the hydrogels to be branched with various functional groups. By improving the synthesis method and changing the hydrogel structure, PVA-based hydrogels can obtain excellent cytocompatibility, flexibility, electrical conductivity, viscoelasticity, and antimicrobial properties, representing a good candidate for articular cartilage restoration, electronic skin, wound dressing, and other fields. This review introduces various preparation methods of PVA-based hydrogels and their wide applications in the biomedical field.

S100A8 is a prognostic signature and associated with immune response in diffuse large B-cell lymphoma.

Background: S100A8, a calcium-binding protein belonging to the S100 family, is involved in immune responses and multiple tumor pathogens. Diffuse large B-cell lymphoma (DLBCL) is one of the most common types of B-cell lymphoma and remains incurable in 40% of patients. However, the role of S100A8 and its regulation of the immune response in DLBCL remain unclear. Methods: The differential expression of S100A8 was identified via the GEO and TCGA databases. The prognostic role of S100A8 in DLBCL was calculated using the Kaplan-Meier curve. The function enrichment of differentially expressed genes (DEGs) was explored through GO, KEGG, GSEA, and PPI analysis. In our cohort, the expression of S100A8 was verified. Meanwhile, the biological function of S100A8 was applied after the inhibition of S100A8 in an in vitro experiment. The association between S100A8 and immune cell infiltration and treatment response in DLBCL was analyzed. Results: S100A8 was significantly overexpressed and related to a poor prognosis in DLBCL patients. Function enrichment analysis revealed that DEGs were mainly enriched in the IL-17 signaling pathway. Our cohort also verified this point. In vitro experiments suggested that inhibition of S100A8 should promote cell apoptosis and suppress tumor growth. Single-cell RNA sequence analysis indicated that S100A8 might be associated with features of the tumor microenvironment (TME), and immune infiltration analyses discovered that S100A8 expression was involved in TME. In terms of drug screening, we predicted that many drugs were associated with preferable sensitivity. Conclusion: Elevated S100A8 expression is associated with a poor prognosis and immune infiltration in DLBCL. Inhibition of S100A8 could promote cell apoptosis and suppress tumor growth. Meanwhile, S100A8 has the potential to be a promising immunotherapeutic target for patients with DLBCL.