Acute Kidney Injury Following Acute Cholangitis: A Risk Multiplier for Adverse Outcomes and Healthcare Utilization.

BACKGROUND: Acute kidney injury (AKI) is a common, fatal complication of acute cholangitis (AC). The link between AC and AKI is poorly understood. AIMS: To delineate the incidence trends, clinical outcomes and healthcare utilization of inpatients with AKI following AC and to explore the risk factors for AKI following AC. METHODS: This population-based retrospective study used the National Inpatient Sample database from 2010 to 2018 to compare the demographics, complications, in-hospital mortality and healthcare utilization between AC patients with and without AKI. Predictors of AKI and the prognostic impact of AKI on in-hospital outcomes were defined using multivariate logistic regression. RESULTS: The overall incidence of AKI was 24.06% among AC patients. Its trend generally increased annually. AKI was associated with more complications, greater invasive therapy requirements, longer hospital stays, costlier total hospital charges, and higher in-hospital mortality. The risk factors for AKI following AC were advanced age, black race, multiple comorbidities, large hospitals, teaching hospitals, urban hospitals, hospitals in the southern and western USA, choledocholithiasis/cholelithiasis, surgery, percutaneous transhepatic biliary drainage, deficiency anemia, congestive heart failure, coagulopathy, diabetes, hypertension, chronic liver disease, obesity, chronic kidney disease excluding end-stage renal disease, weight loss, acute pancreatitis, and severe sepsis. Female sex, private insurance, elective admission, and endoscopic retrograde cholangiopancreatography were protective factors against AKI in AC patients. CONCLUSION: AKI often follows AC and is strongly associated with poor prognosis and increased healthcare utilization. Healthcare professionals should make more efforts to identify patients with AC at risk of AKI and start management promptly to limit adverse outcomes.

Metabolome and Transcriptome Unveil the Correlated Metabolites and Transcripts with 2-acetyl-1-pyrroline in Fragrant Rice.

Fragrance is a valuable trait in rice varieties, with its aroma significantly influencing consumer preference. In this study, we conducted comprehensive metabolome and transcriptome analyses to elucidate the genetic and biochemical basis of fragrance in the Shangsixiangnuo (SSXN) variety, a fragrant indica rice cultivated in Guangxi, China. Through sensory evaluation and genetic analysis, we confirmed SSXN as strongly fragrant, with an 806 bp deletion in the BADH2 gene associated with fragrance production. In the metabolome analysis, a total of 238, 233, 105 and 60 metabolic compounds exhibited significant changes at the seedling (S), reproductive (R), filling (F), and maturation (M) stages, respectively. We identified four compounds that exhibited significant changes in SSXN across all four development stages. Our analyses revealed a significant upregulation of 2-acetyl-1-pyrroline (2AP), the well-studied aromatic compound, in SSXN compared to the non-fragrant variety. Additionally, correlation analysis identified several metabolites strongly associated with 2AP, including ethanone, 1-(1H-pyrrol-2-yl)-, 1H-pyrrole, and pyrrole. Furthermore, Weighted Gene Co-expression Network Analysis (WGCNA) analysis highlighted the magenta and yellow modules as particularly enriched in aroma-related metabolites, providing insights into the complex aromatic compounds underlying the fragrance of rice. In the transcriptome analysis, a total of 5582, 5506, 4965, and 4599 differential expressed genes (DEGs) were identified across the four developmental stages, with a notable enrichment of the common pathway amino sugar and nucleotide sugar metabolism in all stages. In our correlation analysis between metabolome and transcriptome data, the top three connected metabolites, phenol-, 3-amino-, and 2AP, along with ethanone, 1-(1H-pyrrol-2-yl)-, exhibited strong associations with transcripts, highlighting their potential roles in fragrance biosynthesis. Additionally, the downregulated expression of the P4H4 gene, encoding a procollagen-proline dioxygenase that specifically targets proline, in SSXN suggests its involvement in proline metabolism and potentially in aroma formation pathways. Overall, our study provides comprehensive insights into the genetic and biochemical mechanisms underlying fragrance production in rice, laying the foundation for further research aimed at enhancing fragrance quality in rice breeding programs.

Examination of the masseter muscle in patients with hemifacial microsomia using high-frequency ultrasound and shear wave elastography.

BACKGROUND: This study aimed to prospectively investigate the reference values for masseter muscle thickness and hardness using ultrasonography and shear wave elastography, respectively, in patients with hemifacial microsomia (HFM). METHODS: We enrolled 51 patients, aged 5-20 years, with HFM including 31 males and 20 females. The upper-lower, left-right, and anterior-posterior diameters of 102 masseter muscles and stiffness of 98 masseter muscles were determined by examining the unaffected and affected sides of each participant's face. RESULTS: The upper-lower, left-right, and anterior-posterior diameters of the masseter muscle were significantly smaller at rest (4.26 ± 0.83, 2.94 ± 0.75, and- 0.80 ± 0.25 cm, respectively) and during contraction (3.95 ± 0.78, 2.71 ± 0.78, and 0.87 ± 0.29 cm, respectively) in the affected side than those in the healthy side (5.45 ± 0.66, 3.87 ± 0.49, and 0.97 ± 0.20 cm, respectively, at rest and 4.99 ± 0.45, 3.49 ± 0.53, and 1.07 ± 0.23 cm, respectively, during contraction, p < 0.05). In the resting state, the hardness of the masseter muscle on the affected side (0.77 ± 0.66 m/s) was significantly greater than that on the healthy side (0.42 ± 0.41 m/s; p < 0.05). The magnitude of changes in the upper-lower, left-right, and anterior-posterior diameters of the biting muscle in the occlusal state were significantly smaller on the affected side (-0.30 ± 0.27, -0.23 ± 0.17, and 0.08 ± 0.08 cm, respectively) than those in the healthy side (-0.47 ± 0.38, -0.37 ± 0.25, and 0.10 ± 0.12 cm, respectively, p < 0.05). CONCLUSIONS: The knowledge of these values allows for better understanding of the disease characteristics of HFM, which may be used for its diagnosis, treatment, and prognosis. Patients experiencing different severity levels exhibited significant differences in the morphology and function of the masseter muscle on the affected-side (p < 0.05). EVIDENCE LEVEL: Level III.

Anti-HBc mirrors the activation of HBV-specific CD8+ T cell immune response and exhibits a direct effect on HBV control.

BACKGROUND: Hepatitis B core antibody (anti-HBc) is commonly present in patients with chronic hepatitis B virus (HBV) infection and serves as a marker of humoral immunity. Herein, we aim to investigate the correlation between anti-HBc and antiviral immune response and its putative role in HBV control. METHODS: Quantitative anti-HBc and levels of anti-HBc subtypes were measured in chronic hepatitis B (CHB) patients. The effects of anti-HBc on immune cells and HBV replication were evaluated using the HBV mouse models and human hepatoma cell lines. RESULTS: Baseline levels of IgG1 and IgG3 anti-HBc were elevated in CHB patients with favorable treatment response, and correlated with the virological response observed at week 52. Additionally, increased levels of IgM and IgG1 anti-HBc were observed exclusively in CHB patients with liver inflammation. Notably, significant correlations were identified between quantitative levels of anti-HBc and the frequencies of HBcAg-specific CD8+ T cells. Intriguingly, HBcAg efficiently activates T cells aided by B cells in vitro experiments. Moreover, anti-HBc inhibits HBV replication either by a direct effect or through complement-mediated cytotoxicity in HBV-producing cell lines. CONCLUSIONS: Anti-HBc reflects the activation of an HBV-specific CD8+ T cell immune response and may have anti-HBV activity.

Ultrafast Sintered Composite Cathode Incorporating a Negative Thermal Expansion Material for High-Performance Protonic Ceramic Fuel Cells.

Protonic ceramic fuel cells (PCFCs) offer a promising, clean, and efficient energy conversion solution. However, thermal mismatch between cathodes and electrolytes remains a critical obstacle, leading to interfacial damage such as cracking and delamination. Incorporating negative thermal expansion (NTE) materials into the cathode can mitigate this issue. The challenge lies in integrating NTE materials without compromising electrochemical performance or causing unwanted reactions during sintering. This study introduces a novel BaFe0.9Zr0.1O3-δ (BFZ)-NdMnO3-δ composite cathode fabricated using an ultrafast high-temperature sintering (UHS) process. This approach mitigates thermal expansion while boosting the cathode's catalytic activity compared to a single-phase BFZ cathode. The resulting fuel cell achieves a high peak power density of ∼550 mW cm-2 at 600 °C and demonstrates excellent stability during a 100 h test at 550 °C. These findings highlight the potential of UHS for developing high-performance, thermally compatible cathode materials that advance the field of PCFCs.

Robust gesture recognition based on attention-deep fast convolutional neural network and surface electromyographic signals.

The surface electromyographic (sEMG) signals reflect human motor intention and can be utilized for human-machine interfaces (HMI). Comparing to the sparse multi-channel (SMC) electrodes, the high-density (HD) electrodes have a large number of electrodes and compact space between electrodes, which can achieve more sEMG information and have the potential to achieve higher performance in myocontrol. However, when the HD electrodes grid shift or damage, it will affect gesture recognition and reduce recognition accuracy. To minimize the impact resulting from the electrodes shift and damage, we proposed an attention deep fast convolutional neural network (attention-DFCNN) model by utilizing the temporary and spatial characteristics of high-density surface electromyography (HD-sEMG) signals. Contrary to the previous methods, which are mostly base on sEMG temporal features, the attention-DFCNN model can improve the robustness and stability by combining the spatial and temporary features. The performance of the proposed model was compared with other classical method and deep learning methods. We used the dataset provided by The University Medical Center Göttingen. Seven able-bodied subjects and one amputee involved in this work. Each subject executed nine gestures under the electrodes shift (10 mm) and damage (6 channels). As for the electrodes shift 10 mm in four directions (inwards; onwards; upwards; downwards) on seven able-bodied subjects, without any pre-training, the average accuracy of attention-DFCNN (0.942 ± 0.04) is significantly higher than LSDA (0.910 ± 0.04, p < 0.01), CNN (0.920 ± 0.05, p < 0.01), TCN (0.840 ± 0.07, p < 0.01), LSTM (0.864 ± 0.08, p < 0.01), attention-BiLSTM (0.852 ± 0.07, p < 0.01), Transformer (0.903 ± 0.07, p < 0.01) and Swin-Transformer (0.908 ± 0.09, p < 0.01). The proposed attention-DFCNN algorithm and the way of combining the spatial and temporary features of sEMG signals can significantly improve the recognition rate when the HD electrodes grid shift or damage during wear.

Hofmeister Effect-Assisted Facile Fabrication of Self-Assembled Poly(Vinyl Alcohol)/Graphite Composite Sponge-Like Hydrogel for Solar Steam Generation.

The use of hydrogel-based interfacial solar evaporators for desalination is a green, sustainable, and extremely concerned freshwater acquisition strategy. However, developing evaporators that are easy to manufacture, cheap, and have excellent porous structures still remains a considerable challenge. This work proposes a novel strategy for preparing a self-assembling sponge-like poly(vinyl alcohol)/graphite composite hydrogel based on the Hofmeister effect for the first time. The sponge-like hydrogel interfacial solar evaporator (PGCNG) is successfully obtained after combining with graphite. The whole process is environmental-friendly and of low-carbon free of freezing process. The PGCNG can be conventionally dried and stored. PGCNG shows impressive water storage performance and water transmission capacity, excellent steam generation performance and salt resistance. PGCNG has a high evaporation rate of 3.5 kg m-2 h-1 under 1 kW m-2 h-1 solar irradiation and PGCNG demonstrates stable evaporation performance over both 10 h of continuous brine evaporation and 30 cycles of brine evaporation. Its excellent performance and simple, scalable preparation strategy make it a valuable material for practical interface solar seawater desalination devices.

Synbiotic therapy with Clostridium sporogenes and xylan promotes gut-derived indole-3-propionic acid and improves cognitive impairments in an Alzheimer's disease mouse model.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized primarily by cognitive impairment. Recent investigations have highlighted the potential of nutritional interventions that target the gut-brain axis, such as probiotics and prebiotics, in forestalling the onset of AD. In this study, whole-genome sequencing was employed to identify xylan as the optimal carbon source for the tryptophan metabolism regulating probiotic Clostridium sporogenes (C. sporogenes). Subsequent in vivo studies demonstrated that administration of a synbiotic formulation comprising C. sporogenes (1 × 1010 CFU per day) and xylan (1%, w/w) over a duration of 30 days markedly enhanced cognitive performance and spatial memory faculties in the 5xFAD transgenic AD mouse model. The synbiotic treatment significantly reduced amyloid-ß (Aß) accumulation in the cortex and hippocampus of the brain. Importantly, synbiotic therapy substantially restored the synaptic ultrastructure in AD mice and suppressed neuroinflammatory responses. Moreover, the intervention escalated levels of the microbial metabolite indole-3-propionic acid (IPA) and augmented the relative prevalence of IPA-synthesizing bacteria, Lachnospira and Clostridium, while reducing the dominant bacteria in AD, such as Aquabacterium, Corynebacterium, and Romboutsia. Notably, synbiotic treatment also prevented the disruption of gut barrier integrity. Correlation analysis indicated a strong positive association between gut microbiota-generated IPA levels and behavioral changes. In conclusion, this study demonstrates that synbiotic supplementation significantly improves cognitive and intellectual deficits in 5xFAD mice, which could be partly attributed to enhanced IPA production by gut microbiota. These findings provide a theoretical basis for considering synbiotic therapy as a novel microbiota-targeted approach for the treatment of metabolic and neurodegenerative diseases.

Programmable Lanthanide Metal-Organic Framework for Ultra-Efficient Nucleic Acids Extraction and Interaction Analysis.

Efficient, mild, and reversible adsorption of nucleic acids onto nanomaterials represents a promising analytical approach for medical diagnosis. However, there is a scarcity of efficient and reversible nucleic acid adsorption nanomaterials. Additionally, the lack of comprehension of the molecular mechanisms governing their interactions poses significant challenges. These issues hinder the rational design and analytical applications of the nanomaterials. Herein, we propose an ultra-efficient nucleic acid affinity nanomaterial based on programmable lanthanide metal-organic frameworks (Ln-MOFs). Through experiments and density functional theory calculations, a rational design guideline for nucleic acid affinity of Ln-MOF was proposed, and a modular and flexible preparation scheme was provided. Then, Er-TPA (terephthalic acid) MOF emerged as the optimal candidate due to its pore size-independent adsorption and desorption capabilities for nucleic acids, enabling ultra-efficient adsorption (about 150% mass ratio) within 1 min. Furthermore, we elucidate the molecular-level mechanisms underlying the Ln-MOF adsorption of single- and double-stranded DNA and G4 structures. The affinity nanomaterial based on Ln-MOF exhibits robust nucleic acid extraction capability (4-fold higher than commercial reagent kits) and enables mild and reversible CRISPR/Cas9 functional regulation. This method holds significant promise for broad application in DNA/RNA liquid biopsy and gene editing, facilitating breakthroughs in analytical chemistry, pharmacy, and medical research.

Nickel-Catalyzed Enantioconvergent Allenylic Amination of Allenols Activated by Hydrogen-Bonding Interaction with Methanol.

The ubiquitous nature of amines in drug compounds, bioactive molecules and natural products has fueled intense interest in their synthesis. Herein, we introduce a nickel-catalyzed enantioconvergent allenylic amination of methanol-activated allenols. This protocol affords a diverse array of functionalized allenylic amines in high yields and with excellent enantioselectivities. The synthetic potential of this method is demonstrated by employing bioactive amines as nucleophiles and conducting gram-scale reactions. Furthermore, mechanistic investigations and DFT calculations elucidate the role of methanol as an activator in the nickel-catalyzed reaction, facilitating the oxidative addition of the C-O bond of allenols through hydrogen-bonding interactions. The remarkable outcomes arise from a rapid racemization of allenols enabled by the nickel catalyst and from highly enantioselective dynamic kinetic asymmetric transformation of η3-alkadienylnickel intermediates.

Mitigating radiation-induced brain injury via NLRP3/NLRC4/Caspase-1 pyroptosis pathway: Efficacy of memantine and hydrogen-rich water.

Radiation-induced brain injury (RIBI) is a significant challenge in radiotherapy for head and neck tumors, impacting patients' quality of life. In exploring potential treatments, this study focuses on memantine hydrochloride and hydrogen-rich water, hypothesized to mitigate RIBI through inhibiting the NLRP3/NLRC4/Caspase-1 pathway. In a controlled study involving 40 Sprague-Dawley rats, divided into five groups including a control and various treatment groups, we assessed the effects of these treatments on RIBI. Post-irradiation, all irradiated groups displayed symptoms like weight loss and salivation, with notable variations among different treatment approaches. Particularly, hydrogen-rich water showed a promising reduction in these symptoms. Histopathological analysis indicated substantial hippocampal damage in the radiation-only group, while the groups receiving memantine and/or hydrogen-rich water exhibited significant mitigation of such damage. Molecular studies, revealed a decrease in oxidative stress markers and an attenuated inflammatory response in the treatment groups. Immunohistochemistry further confirmed these molecular changes, suggesting the effectiveness of these agents. Echoing recent scientific inquiries into the protective roles of specific compounds against radiation-induced damages, our study adds to the growing body of evidence on the potential of memantine and hydrogen-rich water as novel therapeutic strategies for RIBI.

Overactivation of XBP1 in plasma cells implies worse survival through innate immunity in esophageal squamous cell carcinoma.

To maintain protein homeostasis, X-box binding protein 1 (XBP1) undergoes splicing following the activation of the unfolded protein response (UPR) in response to endoplasmic reticulum (ER) stress. Although targeting ER stress represents a promising therapeutic strategy, a comprehensive understanding of XBP1 at the cellular level and the link between XBP1 and the innate nervous system is lacking. Here, TCGA pancancer datasets from 33 cancer types, scRNA pancancer datasets from 454 patients and bulk RNA-seq datasets from 155 paired esophageal squamous cell carcinoma (ESCC) patients were analyzed. To cope with ER stress, plasma cells tend to activate XBP1 after undergoing bacterial infection and inflammatory signaling from the innate immune system. Patients with high XBP1 expression in their plasma cells have a higher tumor grade and worse survival. However, activation of the innate immune system with increased XBP1 expression in plasma cells correlates with an increased lymphocyte ratio, indicative of a more robust immune response. Moreover, XBP1 activation appears to initiate leukocyte migration at the transcriptional level. Our study revealed that the XBP1-induced UPR could mediate the crosstalk between optimal acquired humoral immune responses and innate immunity in ESCC.

Enhancing mitochondrial proteolysis alleviates alpha-synuclein-mediated cellular toxicity.

Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by mitochondrial dysfunction and accumulation of alpha-synuclein (α-Syn)-containing protein aggregates known as Lewy bodies (LB). Here, we investigated the entry of α-Syn into mitochondria to cause mitochondrial dysfunction and loss of cellular fitness in vivo. We show that α-Syn expressed in yeast and human cells is constitutively imported into mitochondria. In a transgenic mouse model, the level of endogenous α-Syn accumulation in mitochondria of dopaminergic neurons and microglia increases with age. The imported α-Syn is degraded by conserved mitochondrial proteases, most notably NLN and PITRM1 (Prd1 and Cym1 in yeast, respectively). α-Syn in the mitochondrial matrix that is not degraded interacts with respiratory chain complexes, leading to loss of mitochondrial DNA (mtDNA), mitochondrial membrane potential and cellular fitness decline. Importantly, enhancing mitochondrial proteolysis by increasing levels of specific proteases alleviated these defects in yeast, human cells, and a PD model of mouse primary neurons. Together, our results provide a direct link between α-synuclein-mediated cellular toxicity and its import into mitochondria and reveal potential therapeutic targets for the treatment of α-synucleinopathies.

Gate-tunable subband degeneracy in semiconductor nanowires.

Degeneracy and symmetry have a profound relation in quantum systems. Here, we report gate-tunable subband degeneracy in PbTe nanowires with a nearly symmetric cross-sectional shape. The degeneracy is revealed in electron transport by the absence of a quantized plateau. Utilizing a dual gate design, we can apply an electric field to lift the degeneracy, reflected as emergence of the plateau. This degeneracy and its tunable lifting were challenging to observe in previous nanowire experiments, possibly due to disorder. Numerical simulations can qualitatively capture our observation, shedding light on device parameters for future applications.

Isolation of potentially novel species expands the genomic and functional diversity of Lachnospiraceae.

The Lachnospiraceae family holds promise as a source of next-generation probiotics, yet a comprehensive delineation of its diversity is lacking, hampering the identification of suitable strains for future applications. To address this knowledge gap, we conducted an in-depth genomic and functional analysis of 1868 high-quality genomes, combining data from public databases with our new isolates. This data set represented 387 colonization-selective species-level clusters, of which eight genera represented multilineage clusters. Pan-genome analysis, single-nucleotide polymorphism (SNP) identification, and probiotic functional predictions revealed that species taxonomy, habitats, and geography together shape the functional diversity of Lachnospiraceae. Moreover, analyses of associations with atherosclerotic cardiovascular disease (ACVD) and inflammatory bowel disease (IBD) indicated that several strains of potentially novel Lachnospiraceae species possess the capacity to reduce the abundance of opportunistic pathogens, thereby imparting potential health benefits. Our findings shed light on the untapped potential of novel species enabling knowledge-based selection of strains for the development of next-generation probiotics holding promise for improving human health and disease management.

Metagenomic next-generation sequencing identified a brain abscess caused by mixed oral anaerobe infection: A case report.

Fusobacterium vincentii brain abscesses are relatively rare. Here, we report our treatment of an anaerobic brain abscess caused by a mixed infection of Parvimonas micra, Streptococcus constellatus, Fusobacterium vincentii, and Bacteroides heparinolyticus diagnosed by metagenomic next-generation sequencing (mNGS). This is the first reported case of Fusobacterium vincentii in a brain abscess. This case highlights the possibility that oral anaerobic microbes can cause a brain abscess and demonstrates that mNGS has the potential to be deployed to provide rapid infection diagnosis and rationalize antimicrobial therapy for brain abscesses.

Metabolic regulation of misfolded protein import into mitochondria.

Mitochondria are the cellular energy hub and central target of metabolic regulation. Mitochondria also facilitate proteostasis through pathways such as the 'mitochondria as guardian in cytosol' (MAGIC) whereby cytosolic misfolded proteins (MPs) are imported into and degraded inside mitochondria. In this study, a genome-wide screen in Saccharomyces cerevisiae uncovered that Snf1, the yeast AMP-activated protein kinase (AMPK), inhibits the import of MPs into mitochondria while promoting mitochondrial biogenesis under glucose starvation. We show that this inhibition requires a downstream transcription factor regulating mitochondrial gene expression and is likely to be conferred through substrate competition and mitochondrial import channel selectivity. We further show that Snf1/AMPK activation protects mitochondrial fitness in yeast and human cells under stress induced by MPs such as those associated with neurodegenerative diseases.

Enhancing transmission type frame structures: A BBO algorithm-based integrated design approach.

The stable and site-specific operation of transmission lines is a crucial safeguard for grid functionality. This study introduces a comprehensive optimization design method for transmission line crossing frame structures based on the Biogeography-Based Optimization (BBO) algorithm, which integrates size, shape, and topology optimization. By utilizing the BBO algorithm to optimize the truss structure's design variables, the method ensures the structure's economic and practical viability while enhancing its performance. The optimization process is validated through finite element analysis, confirming the optimized structure's compliance with strength, stiffness, and stability requirements. The results demonstrate that the integrated design of size, shape, and topology optimization, as opposed to individual optimizations of size or shape and topology, yields the lightest structure mass and a maximum stress of 151.4 MPa under construction conditions. These findings also satisfy the criteria for strength, stiffness, and stability, verifying the method's feasibility, effectiveness, and practicality. This approach surpasses traditional optimization methods, offering a more effective solution for complex structural optimization challenges, thereby enhancing the sustainable utilization of structures.

Proteogenomic analysis identifies neoantigens and bacterial peptides as immunotherapy targets in colorectal cancer.

Considerable progress has recently been made in cancer immunotherapy, including immune checkpoint blockade, cancer vaccine, and adoptive T cell methods. The lack of effective targets is a major cause of the low immunotherapy response rate in colorectal cancer (CRC). Here, we used a proteogenomic strategy comprising immunopeptidomics, whole exome sequencing, and 16 S ribosomal DNA sequencing analyses of 8 patients with CRC to identify neoantigens and bacterial peptides that can serve as antitumor targets. This study directly identified several personalized neoantigens and bacterial immunopeptides. Immunoassays showed that all neoantigens and 5 of 8 bacterial immunopeptides could be recognized by autologous T cells. Additionally, T cell receptor (TCR) αß sequencing revealed the TCR repertoire of epitope-reactive CD8+ T cells. Functional studies showed that T cell receptor-T (TCR-T) could be activated by epitope pulsed lymphoblastoid cells. Overall, this study comprehensively profiled the CRC immunopeptidome, revealing several neoantigens and bacterial peptides with potential to serve as immunotherapy targets in CRC.

C8-ceramide modulates microglia BDNF expression to alleviate postoperative cognition dysfunction via PKCδ/NF-κB signaling pathway.

Postoperative cognitive dysfunction (POCD) is a kind of serious postoperative complication in surgery with general anesthesia and it may affect patients' normal lives. Activated microglia are thought to be one of the key factors in the regulation of POCD process. Once activated, resident microglia change their phenotype and secrete kinds of cytokines to regulate inflammatory response in tissues. Among these secretory factors, brain-derived neurotrophic factor (BDNF) is considered to be able to inhibit inflammation response and protect nervous system. Therefore, the enhancement of BDNF expression derived from resident microglia is suggested to be potential treatment for POCD. In our study, we focused on the role of C8-ceramide (a kind of interventional drug) and assessed its regulatory effect on improving the expression of BDNF secreted from microglia to treat POCD. According to the results of our study, we observed that C8-ceramide stimulated primary microglia to up-regulate the expression of BDNF mRNA after being treated with lipopolysaccharide (LPS) in vitro. We proved that C8-ceramide had ability to effectively improve POCD of mice after being accepted carotid artery exposure and their abnormal behavior recovered better than that of mice from the surgery group. Furthermore, we also demonstrated that C8-ceramide enhanced the cognitive function of mice via the PKCδ/NF-κB signaling pathway. In general, our study has confirmed a potential molecular mechanism that led to the occurrence of POCD caused by surgery and provided a new clinical strategy to treat POCD.