Development and application of a WebGIS-based prediction system for multi-criteria decision analysis of porcine pasteurellosis.

Porcine pasteurellosis is an infectious disease caused by Pasteurella multocida (P. multocida), which seriously endangers the healthy development of pig breeding industry. Early detection of disease transmission in animals is a crucial early warning for humans. Therefore, predicting risk areas for disease is essential for public health authorities to adopt preventive measures and control strategies against diseases. In this study, we developed a predictive model based on multi-criteria decision analysis (MCDA) and assessed risk areas for porcine pasteurellosis in the Chinese mainland. By using principal component analysis, the weights of seven spatial risk factors were determined. Fuzzy membership function was used to standardize all risk factors, and weight linear combination was used to create a risk map. The sensitivity of the risk map was analyzed by calculating the mean of absolute change rates of risk factors, as well as calculating an uncertainty map. The results showed that risk areas for porcine pasteurellosis were predicted to be locate in the south-central of the Chinese mainland, including Sichuan, Chongqing, Guangdong, and Guangxi. The maximum standard deviation of the uncertain map was less than 0.01and the ROC results showed that the prediction model has moderate predictive performance with the area under the curve (AUC) value of 0.80 (95% CI 0.75-0.84). Based on the above process, MCDA was combined with WebGIS technology to construct a system for predicting risk areas of porcine pasteurellosis. Risk factor data was directly linked to the developed model, providing decision support for disease prevention and control through monthly updates.

ST-GEARS: Advancing 3D downstream research through accurate spatial information recovery.

Three-dimensional Spatial Transcriptomics has revolutionized our understanding of tissue regionalization, organogenesis, and development. However, existing approaches overlook either spatial information or experiment-induced distortions, leading to significant discrepancies between reconstruction results and in vivo cell locations, causing unreliable downstream analysis. To address these challenges, we propose ST-GEARS (Spatial Transcriptomics GEospatial profile recovery system through AnchoRS). By employing innovative Distributive Constraints into the Optimization scheme, ST-GEARS retrieves anchors with exceeding precision that connect closest spots across sections in vivo. Guided by the anchors, it first rigidly aligns sections, next solves and denoises Elastic Fields to counteract distortions. Through mathematically proved Bi-sectional Fields Application, it eventually recovers the original spatial profile. Studying ST-GEARS across number of sections, sectional distances and sequencing platforms, we observed its outstanding performance on tissue, cell, and gene levels. ST-GEARS provides precise and well-explainable 'gears' between in vivo situations and in vitro analysis, powerfully fueling potential of biological discoveries.

Evidence of longitudinal differences in spring migration strategies of an Arctic-nesting goose.

During spring, migratory birds are required to optimally balance energetic costs of migration across heterogeneous landscapes and weather conditions to survive and reproduce successfully. Therefore, an individual's migratory performance may influence reproductive outcomes. Given large-scale changes in land use, climate, and potential carry-over effects, understanding how individuals migrate in relation to breeding outcomes is critical to predicting how future scenarios may affect populations. We used GPS tracking devices on 56 Greater White-fronted Geese (Anser albifrons) during four spring migrations to examine whether migration characteristics influenced breeding propensity and breeding outcome. We found a strong longitudinal difference in arrival to the breeding areas (18 days earlier), pre-nesting duration (90.9% longer), and incubation initiation dates (9 days earlier) between western- and eastern-Arctic breeding regions, with contrasting effects on breeding outcomes, but no migration characteristic strongly influenced breeding outcome. We found that breeding region influenced whether an individual likely pursued a capital or income breeding strategy. Where individuals fell along the capital-income breeding continuum was influenced by longitude, revealing geographic effects of life-history strategy among conspecifics. Factors that govern breeding outcomes likely occur primarily upon arrival to breeding areas or are related to individual quality and previous breeding outcome, and may not be directly tied to migratory decision-making across broad scales.

The MYC2 and MYB43 transcription factors cooperate to repress HMA2 and HMA4 expression, altering cadmium tolerance in Arabidopsis thaliana.

Cadmium (Cd) represents a hazardous heavy metal, prevalent in agricultural soil due to industrial and agricultural expansion. Its propensity for being absorbed by edible plants, even at minimal concentrations, and subsequently transferred along the food chain poses significant risks to human health. Accordingly, it is imperative to investigate novel genes and mechanisms that govern Cd tolerance and detoxification in plants. Here, we discovered that the transcription factor MYC2 directly binds to the promoters of HMA2 and HMA4 to repress their expression, thereby altering the distribution of Cd in plant tissues and negatively regulating Cd stress tolerance. Additionally, molecular, biochemical, and genetic analyses revealed that MYC2 interacts and cooperates with MYB43 to negatively regulate the expression of HMA2 and HMA4 and Cd stress tolerance. Notably, under Cd stress conditions, MYC2 undergoes degradation, thereby alleviating its inhibitory effect on HMA2 and HMA4 expression and plant tolerance to Cd stress. Thus, our study highlights the dynamic regulatory role of MYC2, in concert with MYB43, in regulating the expression of HMA2 and HMA4 under both normal and Cd stress conditions. These findings present MYC2 as a promising target for directed breeding efforts aimed at mitigating Cd accumulation in edible plant roots.

The Use of Identified Hypoxia-related Genes to Generate Models for Predicting the Prognosis of Cerebral Ischemia‒reperfusion Injury and Developing Treatment Strategies.

Cerebral ischemia‒reperfusion injury (CIRI) is a type of secondary brain damage caused by reperfusion after ischemic stroke due to vascular obstruction. In this study, a CIRI diagnostic model was established by identifying hypoxia-related differentially expressed genes (HRDEGs) in patients with CIRI. The ischemia‒reperfusion injury (IRI)-related datasets were downloaded from the Gene Expression Omnibus (GEO) database ( http://www.ncbi.nlm.nih.gov/geo ), and hypoxia-related genes in the Gene Cards database were identified. After the datasets were combined, hypoxia-related differentially expressed genes (HRDEGs) expressed in CIRI patients were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the HRDEGs were performed using online tools. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were performed with the combined gene dataset. CIRI diagnostic models based on HRDEGs were constructed via least absolute shrinkage and selection operator (LASSO) regression analysis and a support vector machine (SVM) algorithm. The efficacy of the 9 identified hub genes for CIRI diagnosis was evaluated via mRNA‒microRNA (miRNA) interaction, mRNA-RNA-binding protein (RBP) network interaction, immune cell infiltration, and receiver operating characteristic (ROC) curve analyses. We then performed logistic regression analysis and constructed logistic regression models based on the expression of the 9 HRDEGs. We next established a nomogram and calibrated the prediction data. Finally, the clinical utility of the constructed logistic regression model was evaluated via decision curve analysis (DCA). This study revealed 9 critical genes with high diagnostic value, offering new insights into the diagnosis and selection of therapeutic targets for patients with CIRI. : Not applicable.

Improved therapeutic index of the liposomal docetaxel-glutathione prepared by active click loading.

The clinical usage of docetaxel (DTX) is severely hindered by the dose-limiting neutropenia and peripheral neurotoxicity of polysorbate 80-solubilized DTX injection, and there are no alternative formulations until now. In this study, we developed a new liposomal formulation of DTX to reduce its toxicities, accompanying with the greatly improved antitumor activity. The DTX was encapsulated into liposomes in the form of hydrophilic glutathione (GSH)-conjugated prodrugs using a click drug loading method, which achieved a high encapsulation efficiency (∼95 %) and loading capacity (∼30 % wt). The resulting liposomal DTX-GSH provided a sustained and efficient DTX release (∼50 % within 48 h) in plasma, resulting in a greatly improved antitumor activities as compared with that of polysorbate 80-solubilized DTX injection in the subcutaneous and orthotopic 4 T1 breast tumor bearing mice. Even large tumors > 500 mm3 could be effectively inhibited and shrunk after the administration of liposomal DTX-GSH. More importantly, the liposomal DTX-GSH significantly decreased the neutropenia and peripheral neurotoxicity as compared with that of polysorbate 80-solubilized DTX injection at the equivalent dose. These data suggested that the liposomal DTX-GSH might become a superior alternative formulation to the commercial DTX injection.

Retrospective Analysis of Risk Factors for Urinary Tract Infection after Ureteral Calculi Surgery.

BACKGROUND: Ureteral calculi are a common diagnosis in the field of urology worldwide, and they represent a prevalent subtype of urolithiasis. Ureteroscopic stone surgery is the cornerstone treatment, but postoperative urinary tract infection (UTI) remains a clinical concern. Our study aims to analyse specific risk factors associated with postoperative UTIs following ureteroscopic stone surgery. METHODS: We conducted a case-control study and collected clinical data from 145 patients who underwent ureteroscopic lithotripsy at our hospital from January 2021 to January 2023. Binary logistic regression analysis was used to investigate risk factors for postoperative UTI. Receiver operating characteristic curves were plotted, and area under the curve (AUC) was calculated to evaluate the predictive value of each factor. RESULTS: Forty patients developed UTI after ureteroscopic stone surgery. Compared with the control group, the case group showed significant differences in stone size, history of diabetes mellitus and preoperative urine culture results (p < 0.05). Multivariable binary logistic regression analysis revealed that stone size (Odds Ratio (OR) = 1.952, p = 0.010), history of diabetes mellitus (OR = 2.438, p = 0.038) and preoperative urine culture (OR = 2.914, p = 0.009) were independent risk factors for postoperative UTI. The AUC values of stone size, history of diabetes mellitus and preoperative urine culture were 0.680, 0.627 and 0.630, respectively. The AUC of the combined prediction was 0.756. CONCLUSIONS: This study identified risk factors for postoperative UTI following ureteroscopic stone surgery and emphasised the importance of stone size, history of diabetes mellitus and preoperative urine culture in the diagnosis.

A lightweight Color-changing melon ripeness detection algorithm based on model pruning and knowledge distillation: leveraging dilated residual and multi-screening path aggregation.

Color-changing melons are a kind of cucurbit plant that combines ornamental and food. With the aim of increasing the efficiency of harvesting Color-changing melon fruits while reducing the deployment cost of detection models on agricultural equipment, this study presents an improved YOLOv8s network approach that uses model pruning and knowledge distillation techniques. The method first merges Dilated Wise Residual (DWR) and Dilated Reparam Block (DRB) to reconstruct the C2f module in the Backbone for better feature fusion. Next, we designed a multilevel scale fusion feature pyramid network (HS-PAN) to enrich semantic information and strengthen localization information to enhance the detection of Color-changing melon fruits with different maturity levels. Finally, we used Layer-Adaptive Sparsity Pruning and Block-Correlation Knowledge Distillation to simplify the model and recover its accuracy. In the Color-changing melon images dataset, the mAP0.5 of the improved model reaches 96.1%, the detection speed is 9.1% faster than YOLOv8s, the number of Params is reduced from 6.47M to 1.14M, the number of computed FLOPs is reduced from 22.8GFLOPs to 7.5GFLOPs. The model's size has also decreased from 12.64MB to 2.47MB, and the performance of the improved YOLOv8 is significantly more outstanding than other lightweight networks. The experimental results verify the effectiveness of the proposed method in complex scenarios, which provides a reference basis and technical support for the subsequent automatic picking of Color-changing melons.

H2O2 oxidation - CaO precipitation pretreatment combining forward osmosis for electroless nickel spent tank liquid (ENSTL) reduction.

The electroless nickel spent tank liquid (ENSTL), as a typical hazardous waste, contains a variety of refractory organic substances as well as heavy metals and inorganic salts. Generally, ENSTL is delegated for disposing by qualified hazardous waste disposal departments in China. However, the temporary storage, transportation, and higher entrusted disposal expenses increase the burden on enterprises producing the hazardous ENSTL. This paper explored an oxidation/precipitation pretreatment and forward osmosis (FO) combined process for ENSTL reduction. 400 mmol/L Hydrogen peroxide and 5.0 wt% calcium oxide were selected as the optimal pretreatment in order to minimize the osmotic pressure of ENSTL, by which the conductivity was significantly reduced from 50.8 mS/cm to 26.8 mS/cm. As a result, the concentrating factor (N) could be dramatically increased from 2.45 by the direct FO to 8.71 by the combined system. Accordingly, the average water flux during the 24 h concentrating cycle increased from 2.47 L/(m2·h) to 4.56 L/(m2·h). TOC rejection rate decreased from 90.23% to 84.39% due to the transformation of organic matter forms by the chemical oxidation during the pretreatment. Meanwhile, TP, Ni and NH4+ rejection rates decreased to a certain extent, which may related to the mitigation of membrane fouling by the pretreatment.

Suicide among patients with oral cancer: A population-based study.

BACKGROUND: Patients with oral cancer usually experience disfigurement and dysfunction which are shared risk factors of suicide. The aim of the study was to comprehensively assess the characteristics of suicide and risk factors for suicide in patients with oral cancer. METHODS: Surveillance, Epidemiology, and End Results database was used to acquire information of patients with common malignant tumors including oral cancer from 1975 to 2020. The aim was to explore the incidence of suicide, and timing of suicide among patients with oral cancer. A Fine-Gray competing risks regression model was employed to analyze risk factors associated with suicide among patients with various demographic and tumor characteristics. RESULTS: Totally, 7685 patients with different malignant tumors committed suicide. Among them, 203 patients with oral cancer died due to suicide, presenting a suicide rate of 54.5/100,000 person-years, which was almost 3.5 times that of the US general population and 1.5 times that of the overall US patients with cancer in our study. Approximately 18 %, 40 %, and 55 % of suicides occurred in first year, first 3 years, and first 5 years after diagnosis. Being male, White race, and having a single primary tumor might be regarded as the risk factors for suicide. CONCLUSION: As oral cavity is closely associated with appearance, pronunciation and ingestion, patients with oral cancer have a significant high risk of suicide. Tremendous attention needs to be paid to patients with oral cancer particularly those exhibiting characteristics associated with a high risk of suicide.

Deciphering deep-sea chemosynthetic symbiosis by single-nucleus RNA-sequencing.

Bathymodioline mussels dominate deep-sea methane seep and hydrothermal vent habitats and obtain nutrients and energy primarily through chemosynthetic endosymbiotic bacteria in the bacteriocytes of their gill. However, the molecular mechanisms that orchestrate mussel host-symbiont interactions remain unclear. Here, we constructed a comprehensive cell atlas of the gill in the mussel Gigantidas platifrons from the South China Sea methane seeps (1100 m depth) using single-nucleus RNA-sequencing (snRNA-seq) and whole-mount in situ hybridisation. We identified 13 types of cells, including three previously unknown ones, and uncovered unknown tissue heterogeneity. Every cell type has a designated function in supporting the gill's structure and function, creating an optimal environment for chemosynthesis, and effectively acquiring nutrients from the endosymbiotic bacteria. Analysis of snRNA-seq of in situ transplanted mussels clearly showed the shifts in cell state in response to environmental oscillations. Our findings provide insight into the principles of host-symbiont interaction and the bivalves' environmental adaption mechanisms.

Long non-coding RNA TPT1-AS1 inhibits ferroptosis in ovarian cancer by regulating GPX4 via CREB1 regulation.

BACKGROUND: Long non-coding RNAs (lncRNAs) play crucial roles in cellular processes, with dysregulation implicated in various diseases, including cancers. The lncRNA TPT1-AS1 (TPT1 Antisense RNA 1) promotes tumor progression in several cancers, including ovarian cancer (OC), but its influence on ferroptosis and interaction with other proteins remains underexplored. METHODS: In this study, we employed a multi-faceted approach to investigate the functional significance of TPT1-AS1 in OC. We assessed TPT1-AS1 expression in OC specimens and cell lines using RT-qPCR, in situ hybridization (ISH), and fluorescence in situ hybridization (FISH) assays. Functional assays included evaluating the impact of TPT1-AS1 knockdown on OC cell proliferation, migration, invasiveness, and cell cycle progression. Further, we explored and validated the interaction of TPT1-AS1 with other proteins using bioinformatics. Finally, we investigated TPT1-AS1 involvement in erastin-induced ferroptosis using Iron Assay, Malondialdehyde (MDA) assay, and reactive oxygen species (ROS) detection. RESULTS: Our findings revealed that TPT1-AS1 overexpression in OC correlated with an unfavorable prognosis. TPT1-AS1 knockdown suppressed cell proliferation, migration, and invasiveness. Additionally, TPT1-AS1 inhibited erastin-induced ferroptosis, and in vivo experiments confirmed its oncogenic impact on tumor development. Mechanistically, TPT1-AS1 was found to regulate Glutathione Peroxidase 4 (GPX4) transcription via CREB1 (cAMP response element-binding protein 1) and interact with RNA-binding protein (RBP) KHDRBS3 (KH RNA Binding Domain Containing, Signal Transduction Associated 3) to regulate CREB1. CONCLUSION: TPT1-AS1 promotes OC progression by inhibiting ferroptosis and upregulating CREB1, forming a regulatory axis with KHDRBS3. These findings highlight the regulatory network involving lncRNAs, RBPs, and transcription factors in cancer progression.

Tumor microenvironment-responsive macrophage-mediated immunotherapeutic drug delivery.

Immunotherapy, as a promising treatment strategy for cancer, has been widely employed in clinics, while its efficiency is limited by the immunosuppression of tumor microenvironment (TME). Tumor-associate macrophages (TAMs) are the most abundant immune cells infiltrating the TME and play a crucial role in immune regulation. Herein, a M0-type macrophage-mediated drug delivery system (PR-M) was designed for carrying Toll-like receptors (TLRs) agonist-loaded nanoparticles. When TLR agonist R848 was released by responding to the TME, the PR-Ms were polarized from M0-type to M1-type and TAMs were also stimulated from M2-type to M1-type, which eventually reversed the immunosuppressive states of TME. By synergizing with the released R848 agonists, the PR-M significantly activated CD4+ and CD8+ T cells in the TME and turned the 'cold' tumor into 'hot' tumor by regulating the secretion of cytokines including IFN-γ, TNF-α, IL-10, and IL-12, thus ultimately promoting the activation of antitumor immunity. In a colorectal cancer mouse model, the PR-M treatment effectively accumulated at the tumor site, with a 5.47-fold increase in M1-type and a 65.08 % decrease in M2-type, resulting in an 85.25 % inhibition of tumor growth and a 87.55 % reduction of tumor volume compared with the non-treatment group. Our work suggests that immune cell-mediated drug delivery systems can effectively increase drug accumulation at the tumor site and reduce toxic side effects, resulting in a strong immune system for tumor immunotherapy. STATEMENT OF SIGNIFICANCE: The formation of TME and the activation of TAMs create an immunosuppressive network that allows tumor to escape the immune system and promotes its growth and spread. In this study, we designed an M0-type macrophage-mediated drug delivery system (PR-M). It leverages the synergistic effect of macrophages and agonists to improve the tumor immunosuppressive micro-environment by increasing M1-type macrophages and decreasing M2-type macrophages. As part of the treatment, the drug-loaded macrophages endowed the system with excellent tumor targeting. Furthermore, loading R848 into TME-responsive nanoparticles could protect macrophages and reduce the potential toxicity of agonists. Further investigations demonstrated that the designed PR-M could be a feasible strategy with high efficacy in tumor targeting, drug loading, autoimmunity activation, and lower side effects.

Triborane (B3H7)-mediated regioselective substitution reactions of pyridine derivatives.

There exists an interplay between borane and a Lewis base in their adducts. However, studies on these adducts so far have mainly focused on the different reactions of B-H bonds with limited attention given to the influence of borane on the chemistry of the Lewis base, except for BF3 and BAr3. Herein, we have synthesized novel borane adducts with pyridine derivatives, Py·B3H7, in which the coordination of B3H7 efficiently achieved the intra-molecular charge transfer. The strong B-N bond in these adducts resulted in the formation of stable dearomatic intermediates of pyridine derivatives, confirmed by 1H and 11B NMR spectroscopy, from which different reactions have transpired to realize C(sp3)-H and C(sp2)-H functionalization under mild conditions. The B3H7 pyridine derivatives are stable and do not dissociate or decompose during the reaction process. The high stability of the B-N bond makes this method a good option for boron-containing drugs with potential for use in boron neutron capture therapy (BNCT).

Transcriptomic responses and evolutionary insights of deep-sea and shallow-water mussels under high hydrostatic pressure condition.

Marine mussels inhabit a wide range of ocean depths, necessitating unique adaptations to cope with varying hydrostatic pressures. This study investigates the transcriptomic responses and evolutionary adaptations of the deep-sea mussel Gigantidas platifrons and the shallow-water mussel Mytilus galloprovincialis to high hydrostatic pressure (HHP) conditions. By exposing atmospheric pressure (AP) acclimated G. platifrons and M. galloprovincialis to HHP, we aim to simulate extreme environmental challenges and assess their adaptive mechanisms. Through comparative transcriptomic analysis, we identified both conserved and species-specific mechanisms of adaptation, with a notable change in gene expression associated with immune system, substance transport, protein ubiquitination, apoptosis, lipid metabolism and antioxidant processes in both species. G. platifrons demonstrated an augmented lipid metabolism, whereas M. galloprovincialis exhibited a dampened immune function. Additionally, the expressed pattern of deep-sea mussel G. platifrons were more consistent than shallow-water mussel M. galloprovincialis under hydrostatic pressures changed conditions which corresponding the long-term living stable deep-sea environment. Moreover, evolutionary analysis pinpointed positively selected genes in G. platifrons that are linked to transmembrane transporters, DNA repair and replication, apoptosis, ubiquitination which are important to cell structural integrity, substances transport, and cellular growth regulation. This indicates a specialized adaptation strategy in G. platifrons to cope with the persistent HHP conditions of the deep sea. These results offer significant insights into the molecular underpinnings of mussel adaptation to varied hydrostatic conditions and enhance our comprehension of the evolutionary forces driving their depth-specific adaptations.

Effects of chronic naltrexone treatment on relapse-related behavior and neural responses to fentanyl in awake nonhuman primates.

Naltrexone, an opioid antagonist that blocks the reinforcing properties of opioid agonists, is often prescribed to preclude relapse to opioid use disorder (OUD) following detoxification. However, few laboratory studies have directly investigated the ability of naltrexone to alter relapse-inducing effects of opioid agonists, including their priming strength in reinstatement studies and their impact in brain regions known to be involved in drug-induced reinforcement in MRI studies. Here we directly address this issue by investigating the effects of continuous exposure to naltrexone on 1) fentanyl-induced reinstatement of drug-seeking behavior, 2) fentanyl-induced patterns of blood oxygenation level dependent (BOLD) activation in the nucleus accumbens (NAcc), and 3) fentanyl-induced changes in NAcc functional connectivity (FC) in awake non-human primates that are engaged in ongoing opioid self-administration studies. We found that naltrexone antagonizes the priming strength of fentanyl as shown by a rightward shift in its reinstatement dose-effect curve and that naltrexone surmountably antagonizes the BOLD response induced by fentanyl. However, while naltrexone also countered fentanyl's effects on NAcc FC, the effects were not surmounted by a higher dose of fentanyl. Together, these data suggest that, in contrast to naltrexone's modulation of fentanyl's effects on behavior and BOLD responses, their interactive effects on FC between multiple brain regions do not reflect their receptor-mediated activity. Additionally, we demonstrated opposing effects in the absence and presence of naltrexone on NAcc FC at baseline (i.e., in the absence of any fentanyl prime) suggesting that naltrexone alters FC at baseline, even though naltrexone appears behaviorally silent in the absence of an agonist prime. Together these data provide additional insight into ways in which naltrexone interacts with opioid agonists, both behaviorally and in the brain. Further understanding the effects of opioid agonists on patterns of FC could help elucidate our understanding of the neural processes that contribute to the initiation of and relapse to opioid-seeking behavior in OUD.

Intranasal administration of insulin on the incidence of postoperative delirium in middle-aged patients undergoing elective on-pump cardiac surgery (INIPOD-MOPS): a prospective double-blinded randomized control study protocol.

BACKGROUND: Delirium, marked by acute cognitive decline, poses a life-threatening issue among older individuals, especially after cardiac surgery, with prevalence ranging from 15 to 80%. Postoperative delirium is linked to increased morbidity and mortality. Although clinical trials suggest preventability, there is limited research on intranasal insulin (INI) for cardiac surgery-related delirium. INI has shown promise in managing cognitive disorders. It rapidly elevates brain hormone levels, enhancing memory even in non-impaired individuals. While effective in preventing delirium in gastrointestinal surgery, its impact after cardiac surgery remains understudied, especially for middle-aged patients. METHOD: This is a prospective randomized, double-blind, single-center controlled trial. A total of 76 eligible participants scheduled for elective on-pump cardiac surgery will be enrolled and randomly assigned in a 1:1 ratio to either receive Intranasally administered insulin (INI) or intranasally administered normal saline. The primary outcome of our study is the incidence of postoperative delirium (POD). Secondary outcomes include duration of ICU, postoperative hospital length of stay, all in-hospital mortality, the change in MMSE scores pre- and post-operation, and incidence of postoperative cognitive dysfunction at 1 month, 3 months, and 6 months after operation. Moreover, we will subjectively and objectively evaluate perioperative sleep quality to investigate the potential impact of nasal insulin on the development of delirium by influencing sleep regulation. DISCUSSION: Our study will aim to assess the impact of intranasal administration of insulin on the incidence of postoperative delirium in middle-aged patients undergoing on-pump elective cardiac surgery. If intranasal insulin proves to be more effective, it may be considered as a viable alternative for preventing postoperative delirium. TRIAL REGISTRATION: ChiCTR ChiCTR2400081444. Registered on March 1, 2024.

Capecitabine mitigates cardiac allograft rejection via inhibition of TYMS-Mediated Th1 differentiation in mice.

OBJECTIVES: Previous studies elucidated that capecitabine (CAP) works as an anti-tumor agent with putative immunosuppressive effects. However, the intricate mechanisms underpinning these effects remain to be elucidated. In this study, we aimed to unravel the molecular pathways by which CAP exerts its immunosuppressive effects to reduce allograft rejection. METHODS: Hearts were transplanted from male BALB/c donors to male C57BL/6 recipients and treated with CAP for seven days. The rejection of these heart transplants was assessed using a range of techniques, including H&E staining, immunohistochemistry, RNA sequencing, LS-MS/MS, and flow cytometry. In vitro, naïve CD4+ T cells were isolated and cultured under Th1 condition medium with varying treatments, flow cytometry, LS-MS/MS were employed to delineate the role of thymidine synthase (TYMS) during Th1 differentiation. RESULTS: CAP treatment significantly mitigated acute allograft rejection and enhanced graft survival by reducing graft damage, T cell infiltration, and levels of circulating pro-inflammatory cytokines. Additionally, it curtailed CD4+ T cell proliferation and the presence of Th1 cells in the spleen. RNA-seq showed that TYMS, the target of CAP, was robustly increased post-transplantation in splenocytes. In vitro, TYMS and its metabolic product dTMP were differentially expressed in Th0 and Th1, and were required after activation of CD4+ T cell and Th1 differentiation. TYMS-specific inhibitor, raltitrexed, and the metabolite of capecitabine, 5-fluorouracil, could inhibit the proliferation and differentiation of Th1. Finally, the combined use of CAP and the commonly used immunosuppressant rapamycin can induce long-term survival of allograft. CONCLUSION: CAP undergoes metabolism conversion to interfere pyrimidine metabolism, which targets TYMS-mediated differentiation of Th1, thereby playing a significant role in mitigating acute cardiac allograft rejection in murine models.

Prediction of early remission after infliximab in Crohn's disease using baseline microbiome and metabolomics.

To characterize the microbiome and metabolic profile in Crohn's disease (CD) patients with different outcome after infliximab (IFX) treatment. The clinical data of a cohort of 35 patients with moderate-to-severe CD admitted at Jinling hospital between Oct 2022 and Dec 2023 were collected. Stool samples at baseline were collected to perform 16SrRNA and ITS2 sequencing and LC-MS untargeted metabolomics. Of these, seven discontinued IFX and underwent surgery during the induction period, and 28 received IFX at weeks 0, 2, and 6, each administered intravenously. Clinical remission was assessed based on the clinical symptoms and HBI at baseline and week 14. Baseline microbial richness and evenness was not significantly different between remission and non-remission group. The taxonomic community analysis identified decrease of Ruminococcus, Lachnoclostridium, Akkermansia in bacterial community and decrease of Asterotremella and Wallemia in fungal community in the non-remission group. LC-MS analysis showed that histamine, creatinine and L-proline significantly increased in remission group, while androsterone, berberine and episterol significantly decreased. The combined prediction model of histamine, androsterone, and episterol demonstrated a high predictive value of remission in patients after IFX treatment (AUC=0.898, p<0.001). Together, these data might facilitate a priori determination of optimal therapeutics for CD patients.

Novel analysis of functional relationship linking moyamoya disease to moyamoya syndrome.

Objective: The aim of this study was to elucidate the genetic pathways associated with Moyamoya disease (MMD) and Moyamoya syndrome (MMS), compare the functional activities, and validate relevant related genes in an independent dataset. Methods: We conducted a comprehensive search for genetic studies on MMD and MMS across multiple databases and identified related genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments analyses were performed for these genes. Commonly shared genes were selected for further validation in the independent dataset, GSE189993. The Sangerbox platform was used to perform statistical analysis and visualize the results. P＜0.05 indicated a statistically significant result. Results: We included 52 MMD and 51 MMS-related publications and identified 126 and 51 relevant genes, respectively. GO analysis for MMD showed significant enrichment in cytokine activity, cell membrane receptors, enzyme binding, and immune activity. A broader range of terms was enriched for MMS. KEGG pathway analysis for MMD highlighted immune and cellular activities and pathways related to MMS prominently featured inflammation and metabolic disorders. Notably, nine overlapping genes were identified and validated. The expressions of RNF213, PTPN11, and MTHFR demonstrated significant differences in GSE189993. A combined receiver operating characteristic curve showed high diagnostic accuracy (AUC = 0.918). Conclusions: The findings indicate a close relationship of MMD with immune activity and MMS with inflammation, metabolic processes and other environmental factors in a given genetic background. Differentiating between MMD and MMS can enhance the understanding of their pathophysiology and inform the strategies for their diagnoses and treatment.