The Effect of Ambient Temperature on Lipid Metabolism in Children: from a Prospective Cohort Study.

BACKGROUND: Dyslipidemia is increasingly recognized as an essential risk factor for cardiovascular diseases. However, few studies illustrated the effects of ambient temperature exposure (TE) on lipid levels in children. The study aimed to examine the association between ambient TE and lipid levels in children. METHODS: Based on a prospective cohort, a total of 2,423 children (with 4,466 lipids measure person-time) were collected from 2014 to 2019. The meteorological observation data and adjusted variables were collected. Mixed-effect models and generalized additive mixed model (GAMM) were applied to investigate the association between ambient TE and lipid levels. RESULTS: A significant negative association was observed between TE and low-density lipoprotein cholesterol (LDL-C) or total cholesterol (TC) levels both in all children [LDL-C, ß(95%CI)= -0.350(-0.434,-0.265), P<0.001; TC, ß(95%CI)= -0.274(-0.389,-0.160), P<0.001] and by different sex group. However, no significant association was found in low-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) levels. The estimated optimal ambient TEs for LDL-C were 18.273 °C and 18.024 °C for girls and boys, respectively. For TC, the optimal ambient TEs were 17.949 °C and 18.024 °C, respectively. With ambient TE decreased, the risk of dyslipidemia increased for both boys [OR=0.032(0.006,0.179), P<0.001] and girls [OR=0.582(0.576,0.587), P<0.001]. CONCLUSION: This study provided a comprehensive illustration about the associations between ambient TE and lipid levels in different sex and ages from a prospective cohort study. The findings will provide evidence for the government to prevent dyslipidemia in vulnerable children through regulating TE.

Exploring the prognostic value and biological pathways of transcriptomics and radiomics patterns in glioblastoma multiforme.

Objectives: To develop a multi-omics prognostic model integrating transcriptomics and radiomics for predicting overall survival in patients with glioblastoma multiforme (GBM), and investigate the biological pathways of radiomics patterns. Materials and methods: Transcription profiles of GBM patients and normal controls were used to obtain differentially expressed mRNAs and long non-coding RNAs (lncRNAs). Radiomics features were extracted from magnetic resonance imaging (MRI). Least absolute shrinkage and selection operator (LASSO) Cox regression was employed to select survival-associated features for the construction of transcriptomics and radiomics signatures. Genes associated with GBM prognosis were identified through the analysis of lncRNA-mRNA co-expression networks and Weighted Gene Co-expression Network Analysis (WGCNA), and their biological pathways were investigated using Genomes enrichment analysis. Transcriptomics, radiomics, and clinical data were integrated to evaluate the multi-omics prognostic model's performance. Results: LASSO Cox regression yielded 21 survival-related features, including 19 transcriptomics features and 2 radiomics features. Based on transcriptomics and radiomics signature, GBM patients were classified as high-risk or low-risk. The genes obtained from the co-expression network screen were associated with microtubule binding, while those from the WGCNA screen were associated with growth factor receptor binding. In the training set, the AUC values for the multi-omics model and clinical model were 0.964 and 0.830, respectively, while in the validation set, they were 0.907 and 0.787. The multi-omics prognostic model outperformed the clinical prognostic model. Conclusions: The co-expression network and WGCNA methods revealed genes associated with multiple biological pathways in GBM. The multi-omics prognostic model demonstrated excellent performance and indicated significant potential for clinical application.

Predictive Value of Multiple Scoring Systems in the Prognosis of Septic Patients with Different Infection Sites: Analysis of the Medical Information Mart for the Intensive Care IV Database.

The heterogeneity nature of sepsis is significantly impacted by the site of infection. This study aims to explore the predictive value of multiple scoring systems in assessing the prognosis of septic patients across different infection sites. Data for this retrospective cohort study were extracted from the Medical Information Mart for Intensive Care IV database (MIMIC-IV) (v2.2). Adult patients meeting the criteria for sepsis 3.0 and admitted to the intensive care unit (ICU) were enrolled. Infection sites included were pneumonia, urinary tract infection (UTI), cellulitis, abdominal infection, and bacteremia. The primary outcome assessed was 28-day mortality. The sequential Organ Failure Assessment (SOFA) score, Oxford Acute Severity of Illness Score (OASIS), and Logistic Organ Dysfunction System (LODS) score were compared. Binomial logistic regression analysis was conducted to evaluate the association between these variables and mortality. Additionally, differences in the area under the curve (AUC) of receiver operating characteristic (ROC) among the scoring systems were analyzed. A total of 4721 patients were included in the analysis. The average 28-day mortality rate was 9.4%. Significant differences were observed in LODS, OASIS, and SOFA scores between the 28-day survival and non-survival groups across different infection sites (p < 0.01). In the pneumonia group and abdominal infection group, both the LODS and OASIS scoring systems emerged as independent risk factors for mortality in septic patients (odds ratio [OR]: 1.165, 95% confidence interval [CI]: 1.109-1.224, p < 0.001; OR: 1.047, 95% CI: 1.028-1.065, p < 0.001) (OR: 1.200, 95% CI: 1.091-1.319, p < 0.001; OR: 1.060, 95% CI: 1.025-1.095, p < 0.001). For patients with UTI, the LODS, OASIS, and SOFA scoring systems were identified as independent risk factors for mortality (OR: 1.142, 95% CI: 1.068-1.220, p < 0.001; OR: 1.062, 95% CI: 1.037-1.087, p < 0.001; OR: 1.146, 95% CI: 1.046-1.255, p = 0.004), with the AUC of LODS score and OASIS significantly higher than that of the SOFA score (p = 0.006). Among patients with cellulitis, the OASIS and SOFA scoring systems were identified as independent risk factors for mortality (OR: 1.055, 95% CI: 1.007-1.106, p = 0.025; OR: 1.187, 95% CI: 1.005-1.403, p = 0.044), with no significant difference in prognosis prediction observed (p = 0.243). In the bacteremia group, the LODS scoring system was identified as an independent risk factor for mortality (OR: 1.165, 95% CI: 1.109-1.224, p < 0.001). The findings suggest that LODS scores offer better prognostic accuracy for predicting the mortality risk in septic patients with pneumonia, abdominal infections, bacteremia, and UTI compared to SOFA scores.

Association of social determinants, lifestyle, and metabolic factors with mortality in Chinese adults: A nationwide 10-year prospective cohort study.

Nationwide estimates of the impact of common modifiable risk factors on mortality remain crucial. We aim to assess the influence of social determinants, lifestyle, and metabolic factors on mortality in 174,004 adults aged ≥40 years from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. We reveal that 17 modifiable factors are independently associated with mortality, accounting for 64.8% of all-cause mortality, 77.4% of cardiovascular mortality, and 44.8% of cancer mortality. Low education emerges as the leading factor for both all-cause and cancer mortality, while hypertension is predominant for cardiovascular mortality. Moreover, low gross domestic product per capita and high ambient particulate matter with a diameter of <2.5 µm (PM2.5) air pollution account for 7.8% and 4.3% for all-cause mortality, respectively, using a different method. Gender-specific analyses reveal distinct patterns, with women's mortality primarily associated with social determinants and men exhibiting stronger associations with lifestyle factors. Targeted health interventions are essential to mitigate mortality risks effectively in China.

Icariin alleviates cisplatin-induced premature ovarian failure by inhibiting ferroptosis through activation of the Nrf2/ARE pathway.

Cisplatin is a widely used chemotherapeutic drug that can induce ovarian damage. Icariin (ICA), a natural antioxidant derived from Epimedium brevicornum Maxim., has been found to protect against organ injury. The aim of the present study was to investigate whether ICA can exert an ovarian-protective effect on cisplatin induced premature ovarian failure (POF) and the underlying mechanism involved. The preventive effect of ICA was evaluated using body weight, the oestrous cycle, ovarian histological analysis, and follicle counting. ICA treatment increased body weight, ovarian weight, and the number of follicles and improved the oestrous cycle in POF mice. ICA reduced cisplatin-induced oxidative damage and upregulated the protein expression levels of Nrf2, GPX4 and HO-1. Moreover, ICA reduced the expression levels of Bax and γH2AX and inhibited ovarian apoptosis. In addition, ICA activated the Nrf2 pathway in vitro and reversed changes in the viability of cisplatin-induced KGN cells, reactive oxygen species (ROS) levels, lipid peroxidation, and apoptosis, and these effects were abrogated when Nrf2 was knocked down or inhibited. Molecular docking confirmed that ICA promotes the release of Nrf2 by competing with Nrf2 for binding to Keap1. The inhibitory effects of ICA on cisplatin-induced oxidative stress, ferroptosis, and apoptosis may be mediated by its modulatory effects on the Nrf2 pathway, providing a novel perspective on the potential mechanisms by which ICA prevents POF.

Integrative analyses identified gap junction beta-2 as a prognostic biomarker and therapeutic target for breast cancer.

Background: Increasing evidence has shown that connexins are involved in the regulation of tumor development, immune escape, and drug resistance. This study investigated the gene expression patterns, prognostic values, and potential mechanisms of connexins in breast cancer. Methods: We conducted a comprehensive analysis of connexins using public gene and protein expression databases and clinical samples from our institution. Connexin mRNA expressions in breast cancer and matched normal tissues were compared, and multiomics studies were performed. Results: Gap junction beta-2 mRNA was overexpressed in breast cancers of different pathological types and molecular subtypes, and its high expression was associated with poor prognosis. The tumor membrane of the gap junction beta-2 mutated group was positive, and the corresponding protein was expressed. Somatic mutation and copy number variation of gap junction beta-2 are rare in breast cancer. The gap junction beta-2 transcription level in the p110α subunit of the phosphoinositide 3-kinase mutant subgroup was higher than that in the wild-type subgroup. Gap junction beta-2 was associated with the phosphoinositide 3-kinase-Akt signaling pathway, extracellular matrix-receptor interaction, focal adhesion, and proteoglycans in cancer. Furthermore, gap junction beta-2 overexpression may be associated with phosphoinositide 3-kinase and histone deacetylase inhibitor resistance, and its expression level correlated with infiltrating CD8+ T cells, macrophages, neutrophils, and dendritic cells. Conclusions: Gap junction beta-2 may be a promising therapeutic target for targeted therapy and immunotherapy and may be used to predict breast cancer prognosis.

Application-based big data development framework for health sciences libraries.

The study is a part of a student research project on performance-based evaluation of big data application in health sciences libraries. It presents a theoretical framework of the performance-based evaluation system for health institutes' libraries in the digital environment. The health sciences libraries' systematic approach was judged based on the five main components (data culture, organisational infrastructure, responsibilities, skills and technology competence) of big data analytics (BDA). A comprehensive literature review of the published studies was undertaken related to BDA, including the diffusion of innovation theory, and the theoretical background of the technology acceptance model to produce an application-based big data development framework for the health sciences libraries. The application-based evaluation model integrates BDA in health sciences libraries for improving library services and performance. The study proposed a need for skilled professionals with the knowledge and experience both professionally and technically. Finally, the study proposed a model that will help to measure the organisation's ability to analyse vast amounts of data to empirically validate the association concerning big data analysis and analytical practices in health libraries.

Mid-term clinical effect of resecting posterior longitudinal ligament in anterior approach for cervical spondylosis with sympathetic symptoms: retrospective cohort analysis.

STUDY DESIGN: Retrospective cohort analysis. OBJECTIVE: The purpose of this study is to investigate whether the removal of the posterior longitudinal ligament (PLL) affects the mid-term outcome of anterior cervical fusion for cervical spondylosis with sympathetic symptoms(CSSS). METHODS: From January 2012 to July 2013, 66 patients who were diagnosed with CSSS with ≥ 10-year follow-up at our institution were assessed. All patients were divided into two groups: Group A (36 cases) in which patients underwent anterior cervical fusion with PLL resection and Group B (30 cases) in which patients underwent anterior cervical fusion without PLL resection. The sympathetic symptom 20-point system was used to evaluate the sympathetic symptoms, such as tinnitus, headache and vertigo, etc. And the neurological status was assessed by the Japanese Orthopedic Association (JOA) scores. Clinical and radiologic data were evaluated preoperatively, 9 days, 3 months, 6 months, 12 months, 24 months, 60 months, and 120 months postoperatively. Data collected included all perioperative complications as morbidities that occurred during the period of follow-up. RESULTS: The postoperative JOA scores and 20-point score can be significantly improved compared with preoperative whether the PLL is removed in both groups. However, the postoperative 20-point score of patients in group A was significantly different from that in group B. No loosening and displacement of prosthesis occurred. CONCLUSION: A better clinical effect could be attained when resecting the PLL in the operation. The PLL may play an important role in CSSS. The mid-term outcomes of anterior cervical fusion with PLL resection were satisfied in treating CSSS.

Tendon Decellularized Matrix Modified Fibrous Scaffolds with Porous and Crimped Microstructure for Tendon Regeneration.

Current engineered synthetic scaffolds fail to functionally repair and regenerate ruptured native tendon tissues, partly because they cannot satisfy both the unique biological and biomechanical properties of these tissues. Ideal scaffolds for tendon repair and regeneration need to provide porous topographic structures and biological cues necessary for the efficient infiltration and tenogenic differentiation of embedded stem cells. To obtain crimped and porous scaffolds, highly aligned poly(l-lactide) fibers were prepared by electrospinning followed by postprocessing. Through a mild and controlled hydrogen gas foaming technique, we successfully transformed the crimped fibrous mats into three-dimensional porous scaffolds without sacrificing the crimped microstructure. Porcine derived decellularized tendon matrix was then grafted onto this porous scaffold through fiber surface modification and carbodiimide chemistry. These biofunctionalized, crimped, and porous scaffolds supported the proliferation, migration, and tenogenic induction of tendon derived stem/progenitor cells, while enabling adhesion to native tendons. Together, our data suggest that these biofunctionalized scaffolds can be exploited as promising engineered scaffolds for the treatment of acute tendon rupture.

A Clinical-radiomic Nomogram for the Non-invasive Evaluation of Glomerular Status in Diabetic Kidney Disease.

OBJECTIVE: Utilizing ultrasound radiomics, we developed a machine learning (ML) model to construct a nomogram for the non-invasive evaluation of glomerular status in diabetic kidney disease (DKD). MATERIALS AND METHODS: Patients with DKD who underwent renal biopsy were retrospectively enrolled between February 2017 and February 2023. The patients were classified into mild or moderate-severe glomerular severity based on pathological findings. All patients were randomly divided into a training (n =79) or testing cohort (n = 35). Radiomic features were extracted from ultrasound images, and a logistic regression ML algorithm was applied to construct an ultrasound radiomic model after selecting the most significant features using univariate analysis and the least absolute shrinkage and selection operator algorithm (LASSO). A clinical model was created following univariate and multivariate logistic regression analyses of the patient's clinical characteristics. Then, the clinical-radiomic model was constructed by combining rad scores and independent clinical characteristics and plotting the nomogram. The receiver operating characteristic curve (ROC) and decision curve analysis (DCA), respectively, were used to evaluate the prediction abilities of the clinical model, ultrasound-radiomics model, and clinical-radiomics model. RESULTS: A total of 114 DKD patients were included in the study, including 43 with mild glomerulopathy and 71 with moderate-severe glomerulopathy. The area under the curve (AUC) for the clinical model based on clinical features and the radiomic model based on 2D ultrasound images in the testing cohort was 0.729 and 0.761, respectively. Further, the AUC for the clinical-radiomic nomogram was constructed by combining clinical features, and the rad score was 0.850 in the testing cohort. The outcomes were better than those of both the radiomic and clinical single-model approaches. CONCLUSION: The nomogram constructed by combining ultrasound radiomics and clinical features has good performance in assessing the glomerular status of patients with DKD and will help clinicians monitor the progression of DKD.

Emotional dispositions and intracerebral hemorrhage: a Mendelian Randomization insight.

Background: Intracerebral hemorrhage (ICH) is a severe form of stroke with high mortality and limited treatment options. While traditional risk factors like hypertension have been well-studied, the role of emotional states as acute triggers for ICH remains unclear. This study employs Mendelian Randomization (MR) to investigate the causal relationship between emotional traits of worry and anxiety and the incidence of ICH. Methods: We used a two-sample MR approach, leveraging summary-level data from genome-wide association studies (GWAS) for emotional traits and ICH. The primary analysis was conducted using the Inverse-Variance Weighted (IVW) method, supplemented by multiple sensitivity analyses including Maximum Likelihood and MR PRESSO methods. Results: Our MR analysis revealed a robust and significant causal relationship between the emotional trait "Worrier/anxious feelings" and ICH, supported by 195 instrumental variables (SNPs). The odds ratio (OR) was 2.98 (95% CI: 1.16, 7.61) with a p-value of 0.0229. Sensitivity analyses corroborated these findings, enhancing the reliability of our results. In contrast, other emotional traits such as "Nervous feelings" and "Sensitivity/hurt feelings" did not show significant associations, reinforcing the specificity of our primary finding. Conclusion: Our study provides compelling evidence for a causal relationship between the emotional traits of worry and anxiety and the incidence of ICH, offering a new dimension in our understanding of this devastating condition and paving the way for more nuanced risk stratification and preventive strategies.

Targeting RNA N6-methyladenosine modification-- a novel therapeutic target for HER2- positive gastric cancer.

Gastric cancer is one of the most common cancers and is considered the 5th most frequent occurring cancer worldwide. It has gained great attention from the clinicians and researchers because of high mortality rate. It is generally treated with chemotherapy, radiotherapy, and surgery. Recently, additional treatment options including immunotherapy and targeted therapy and immunotherapy have been developed. However, poor prognosis, limited survival rate of patients, and drug resistance to treatment remain critical problems. To improve treatment options or to overcome the bottleneck of treatment, identification of diagnostic and prognostic markers, determining the most effective therapeutic options, and uncovering the molecular regulations associated with treatment strategies are required. In this regard n6-methyladenosine (m6A) regulation is considered important. This reversible modification plays a crucial role in progression, development and treatment of HER2-positive gastric cancer. Here, we discuss the role of m6A modification in HER2-positive gastric cancer progression through collecting related studies at present. We further discuss the association of m6A modification with therapeutic efficacy in HER2-positive gastric cancer and list some examples. We conclude that modification of m6A can be a new strategy for improving the prognosis and survival rate of HER2-positive gastric cancer patients.

Anthropogenic activity shapes the assemble and co-occurrence pattern of microbial communities in fishing harbors around the Bohai Economic Circle.

This study aimed to elucidate the effects of coastal environmental stress on the composition of sediment bacterial communities and their cooccurrence patterns in fishing harbors around the Bohai Economic Circle, China. Compared with the natural sea area, fishing harbors contained higher levels of organic pollution (organic pollution index = 0.12±0.026) and considerably reduced bacterial richness and evenness. The distributions of sediment microbial communities clustered along the pollutant concentration gradients across fishing harbors. Betaproteobacteria dominated (76%) organically polluted fishing harbors, which were mostly disturbed by anthropogenic activities. However, the harbors also revealed the absence of numerous pathogenic (Coxiella and Legionella) and photosynthetic (Synechococcus and Leptolyngbya) bacteria. Abundant genera, including Thiobacillus and Arenimonas, exhibited a positive correlation with total phosphorus and a negative correlation with total nitrogen in sediments. Meanwhile, Sulfurovum, Psychrobacter, and Woeseia showed the opposite trend. Pollutant accumulation and anthropogenic activities caused the decrease in the sediment microbial diversity and dispersal ability and promoted convergent evolution. Severely polluted harbors with simplified cooccurrence networks revealed the presence of destabilized microbial communities. In addition, the modularity of bacterial networks decreased with organic pollution. Our results provide important insights into the adjustment mechanism of microbial communities to community organization and functions under environmental pollution stress. Overall, this study enhanced our understanding of how microbial communities in coastal sediments adapted and survived amidst anthropogenic activities like oily effluent discharges from large ships, wash water, domestic sewage, garbage, and fisheries wastes. It also examined their resilience to future contamination.

Impact of Heating Conventional Cigarettes with a Novel Device on Health-related Biomarkers and Cigarette Use Patterns among Chinese Adult Smokers Unwilling to Quit: A Pilot Randomized Controlled Trial.

INTRODUCTION: We evaluated the impact of heating conventional cigarettes with a novel heated tobacco product (HTP) device on biomarkers and cigarette use patterns in Chinese adult smokers unwilling to quit smoking. METHODS: In this pilot randomized controlled trial, 50 eligible participants were allocated to either Control group (smoking conventional cigarettes) or HTP device group (switching to using heated conventional cigarettes by the HTP device). Participants in the HTP device group went through a 2-day run-in period then used heated conventional cigarettes exclusively for 5 days, followed by flexible use for 14 days. Five biomarkers of exposure (BoEs) were measured at baseline and on Day 7. Thirteen biomarkers of biological effect (BoBEs) were measured at baseline and on Day 21. Safety, daily cigarette consumption, craving, withdrawal symptoms, and device acceptability, were assessed. RESULTS: BoE levels decreased by 26.4 % to 71.4% from baseline in the HTP device group, while BoBE levels did not significantly change in either group. In the HTP group, 56% exclusively used heated conventional cigarettes during the flexible use period, experiencing reduced cravings and withdrawal symptoms, while dual users consumed more cigarettes. Mild to moderate device-related reactions were reported in 36% of users. Satisfaction, taste, and harm reduction belief scores averaged 7.4, 6.6, and 8.7 (out of 10), respectively. CONCLUSIONS: Switching to heated cigarettes with the HTP device may reduce short-term exposure to smoke toxicants. However, it can lead to increased tobacco use among dual users. Further investigation is needed to confirm these preliminary findings. IMPLICATIONS: This study is the first to evaluate the impact of heating conventional cigarettes with a novel heated tobacco product (HTP) device on health-related biomarkers and cigarette use patterns among Chinese adult smokers. This novel HTP device can directly heat conventional cigarettes without the necessity for specifically designed tobacco products, avoiding potential additive risks of traditional HTPs. If the results of this study could be further verified by randomized controlled clinical trials with larger sample sizes, this novel HTP device could serve as a short-term harm reduction alternative for smokers unwilling to quit.

AhR ligands from LGG metabolites promote piglet intestinal ILC3 activation and IL-22 secretion to inhibit PEDV infection.

In maintaining organismal homeostasis, gut immunity plays a crucial role. The coordination between the microbiota and the immune system through bidirectional interactions regulates the impact of microorganisms on the host. Our research focused on understanding the relationships between substantial changes in jejunal intestinal flora and metabolites and intestinal immunity during porcine epidemic diarrhea virus (PEDV) infection in piglets. We discovered that Lactobacillus rhamnosus GG (LGG) could effectively prevent PEDV infection in piglets. Further investigation revealed that LGG metabolites interact with type 3 innate lymphoid cells (ILC3s) in the jejunum of piglets through the aryl hydrocarbon receptor (AhR). This interaction promotes the activation of ILC3s and the production of interleukin-22 (IL-22). Subsequently, IL-22 facilitates the proliferation of IPEC-J2 cells and activates the STAT3 signaling pathway, thereby preventing PEDV infection. Moreover, the AhR receptor influences various cell types within organoids, including intestinal stem cells (ISCs), Paneth cells, and enterocytes, to promote their growth and development, suggesting that AhR has a broad impact on intestinal health. In conclusion, our study demonstrated the ability of LGG to modulate intestinal immunity and effectively prevent PEDV infection in piglets. These findings highlight the potential application of LGG as a preventive measure against viral infections in livestock.IMPORTANCEWe observed high expression of the AhR receptor on pig and human ILC3s, although its expression was negligible in mouse ILC3s. ILC3s are closely related to the gut microbiota, particularly the secretion of IL-22 stimulated by microbial signals, which plays a crucial regulatory role in intestinal immunity. In our study, we found that metabolites produced by beneficial gut bacteria interact with ILC3s through AhR, thereby maintaining intestinal immune homeostasis in pigs. Moreover, LGG feeding can enhance the activation of ILC3s and promote IL-22 secretion in the intestines of piglets, ultimately preventing PEDV infection.

Analysis and Research on the Relationship between Oral Microorganisms and Alzheimer's Disease.

Background: The common neurodegenerative disease among the elderly is Alzheimer's disease, which in severe cases can affect the quality of life of patients and their families. It has been reported that oral microorganisms are involved in the progression of Alzheimer's disease. Objective: To analyze the relationship between oral microorganisms and Alzheimer's disease. Methods: The oral microbial population, a comprehensive analysis of relevant literature was conducted. Immunofluorescence was adopted to assess albumin deposition in the cerebral cortex of mice. Western blot was used to detect expression level of CYP46 in mouse brain. Results: It can be concluded that the population of oral microorganisms includes bacteria, viruses, fungi, and spirochetes, which can cause various oral diseases. They can enter the human brain through the blood and surrounding nerves, leading to permeability increase of the blood-brain barrier and neuroimmune related inflammation. They will participate in and worsen the pathological process of Alzheimer's disease, leading to damage to neurons and cerebral blood vessels. The intervention methods for oral microbiota population include vaccination and phage therapy. Vaccines provide suitable treatment methods for periodontal disease, and phage therapy is a new method for controlling oral infections. At the same time, postoperative patients with oral diseases can use gel containing ethanol extract of Brazilian green propolis to ensure oral hygiene. In the rat blood-brain barrier model, porphyromonas gingivalis bacteremia enhanced barrier permeability, and immunofluorescence showed an increase in albumin deposition in the rat cerebral cortex. The expression of cytochrome P450 46A1 (CYP46A1) enzyme in the brain of Alzheimer's disease mice aged 24-56 weeks after long-term administration of SLAB51 increased. Conclusion: The elderly population should develop good living habits, maintain a clean mouth, and adjust the oral environment through methods such as oral and Alzheimer's disease promotion, combined with medication treatment.

Lysine L-lactylation is the dominant lactylation isomer induced by glycolysis.

Lysine L-lactylation (Kl-la) is a novel protein posttranslational modification (PTM) driven by L-lactate. This PTM has three isomers: Kl-la, N-ε-(carboxyethyl)-lysine (Kce) and D-lactyl-lysine (Kd-la), which are often confused in the context of the Warburg effect and nuclear presence. Here we introduce two methods to differentiate these isomers: a chemical derivatization and high-performance liquid chromatography analysis for efficient separation, and isomer-specific antibodies for high-selectivity identification. We demonstrated that Kl-la is the primary lactylation isomer on histones and dynamically regulated by glycolysis, not Kd-la or Kce, which are observed when the glyoxalase system was incomplete. The study also reveals that lactyl-coenzyme A, a precursor in L-lactylation, correlates positively with Kl-la levels. This work not only provides a methodology for distinguishing other PTM isomers, but also highlights Kl-la as the primary responder to glycolysis and the Warburg effect.

Intraoperative application of low-dose dexmedetomidine or lidocaine for postoperative analgesia in pediatric patients following craniotomy: a randomized double-blind placebo-controlled trial.

Background: Postoperative pain is a common occurrence in pediatric patients following craniotomy, often leading to negative outcomes. Intravenous dexmedetomidine and lidocaine are commonly used adjuvant medicines in general anesthesia to reduce perioperative opioid consumption and relieve postoperative pain in adults. While they show promise for use in pediatrics, the evidence of their application in pediatric craniotomy patients is limited. Therefore, we aimed to compare the effects of dexmedetomidine and lidocaine on postoperative pain in pediatric patients following craniotomy. Methods: We conducted a randomized, double-blind, single-center trial on children scheduled for craniotomy. The 255 recruited participants aged 1-12 years were randomly assigned to intraoperatively receive a loading intravenous dose of either dexmedetomidine 1 µg·kg-1 or lidocaine 2 mg·kg-1 or normal saline for 15 min followed by dexmedetomidine 0.5 µg·kg-1·h-1 or lidocaine 1 mg·kg-1·h-1 or normal saline until the sutures of endocranium were completed. The primary outcome was the cumulative sufentanil consumption within 24 h post-surgery. Results: A total of 241 patients were included in the statistical analysis. The primary outcome did not show any significant differences among the three groups (median (IQR) lidocaine group: 3.36 (1.32-5.64) µg vs. dexmedetomidine group: 3.12 (1.36-6.39) µg vs. control group 3.46 (1.77-7.62) µg, p = 0.485). Among the secondary outcomes, there was a statistically significant but small reduction in sufentanil consumption within 2 h, postoperative FLACC/WBFS/NRS pain scores within 4 h after surgery and postoperative Ramsay sedation scores in dexmedetomidine group (p < 0.05). Regarding postoperative complications, the incidence of electrolyte disturbance within 24 and 48 h after surgery was significantly higher in control group compared to the other two groups. There were no significant differences in intraoperative opioid consumption, postoperative frequency of remedy medication, or length of hospitalization among the three groups. No adverse events related to lidocaine or dexmedetomidine were observed. Conclusions: There were no significant differences in the primary outcome among the three groups. Although dexmedetomidine showed some benefits in reducing postoperative opioid consumption within the first 2 h and pain intensity within the first 4 h post-surgery, these findings should be interpreted with caution. Further research is required to comprehensively assess the outcomes and determine the optimal administration strategy. Clinical Trial Registration: [http://www.chictr.org.cn/index.aspx], identifier [ChiCTR1800019411].

Quercetin-loaded melanin nanoparticle mediated konjac glucomannan/polycaprolactone bilayer film with dual-mode synergistic bactericidal activity for food packaging.

It is still difficult for a single antibacterial modality to realize satisfactory management of bacterial breeding in food preservation. To solve this problem, we developed a photothermal-derived dual-mode synergistic bactericidal konjac glucomannan (KGM)/polycaprolactone (PCL) bilayer film incorporated with quercetin-loaded melanin-like nanoparticles (Q@MNPs). The results showed that the mechanical properties (TS: 29.8 MPa, EAB: 43.1 %), UV shielding properties, and water resistance (WCA: 124.1°, WVP: 3.92 g mm/m2 day kPa) of KGM-Q@MNPs/PCL bilayer films were significantly improved. More importantly, KGM-Q@MNPs/PCL bilayer film presented outstanding photothermal inversion and controlled release behavior of Q triggered by near infrared (NIR) radiation, thus contributing to excellent dual-mode synergistic antibacterial properties against E. coli and S. aureus. Meanwhile, the KGM-Q@MNPs/PCL bilayer film possessed good biocompatibility and low toxicity. As a proof-of-concept application, we further verified the significant value of film for the preservation of cherry tomatoes. Since KGM-Q@MNPs/PCL bilayer film showed excellent biodegradability, this work will aid the development of sustainable antibacterial food packaging materials.