Identification of blood metabolites associated with risk of Alzheimer's disease by integrating genomics and metabolomics data.

Specific metabolites have been reported to be potentially associated with Alzheimer's disease (AD) risk. However, the comprehensive understanding of roles of metabolite biomarkers in AD etiology remains elusive. We performed a large AD metabolome-wide association study (MWAS) by developing blood metabolite genetic prediction models. We evaluated associations between genetically predicted levels of metabolites and AD risk in 39,106 clinically diagnosed AD cases, 46,828 proxy AD and related dementia (proxy-ADD) cases, and 401,577 controls. We further conducted analyses to determine microbiome features associated with the detected metabolites and characterize associations between predicted microbiome feature levels and AD risk. We identified fourteen metabolites showing an association with AD risk. Five microbiome features were further identified to be potentially related to associations of five of the metabolites. Our study provides new insights into the etiology of AD that involves blood metabolites and gut microbiome, which warrants further investigation.

A novel subpopulation of monocytes with a strong interferon signature indicated by SIGLEC-1 is present in patients with in recent-onset type 1 diabetes.

AIMS/HYPOTHESIS: Type 1 diabetes is a T cell-mediated autoimmune disease characterised by pancreatic beta cell destruction. In this study, we explored the pathogenic immune responses in initiation of type 1 diabetes and new immunological targets for type 1 diabetes prevention and treatment. METHODS: We obtained peripheral blood samples from four individuals with newly diagnosed latent autoimmune diabetes in adults (LADA) and from four healthy control participants. Single-cell RNA-sequencing (scRNA-seq) was performed on peripheral blood mononuclear cells to uncover transcriptomic profiles of early LADA. Validation was performed through flow cytometry in a cohort comprising 54 LADA, 17 adult-onset type 2 diabetes, and 26 healthy adults, matched using propensity score matching (PSM) based on age and sex. A similar PSM method matched 15 paediatric type 1 diabetes patients with 15 healthy children. Further flow cytometry analysis was performed in both peripheral blood and pancreatic tissues of non-obese diabetic (NOD) mice. Additionally, cell adoptive transfer and clearance assays were performed in NOD mice to explore the role of this monocyte subset in islet inflammation and onset of type 1 diabetes. RESULTS: The scRNA-seq data showed that upregulated genes in peripheral T cells and monocytes from early-onset LADA patients were primarily enriched in the IFN signalling pathway. A new cluster of classical monocytes (cluster 4) was identified, and the proportion of this cluster was significantly increased in individuals with LADA compared with healthy control individuals (11.93% vs 5.93%, p=0.017) and that exhibited a strong IFN signature marked by SIGLEC-1 (encoding sialoadhesin). These SIGLEC-1+ monocytes expressed high levels of genes encoding C-C chemokine receptors 1 or 2, as well as genes for chemoattractants for T cells and natural killer cells. They also showed relatively low levels of genes for co-stimulatory and HLA molecules. Flow cytometry analysis verified the elevated levels of SIGLEC-1+ monocytes in the peripheral blood of participants with LADA and paediatric type 1 diabetes compared with healthy control participants and those with type 2 diabetes. Interestingly, the proportion of SIGLEC-1+ monocytes positively correlated with disease activity and negatively with disease duration in the LADA patients. In NOD mice, the proportion of SIGLEC-1+ monocytes in the peripheral blood was highest at the age of 6 weeks (16.88%), while the peak occurred at 12 weeks in pancreatic tissues (23.65%). Adoptive transfer experiments revealed a significant acceleration in diabetes onset in the SIGLEC-1+ group compared with the SIGLEC-1- or saline control group. CONCLUSIONS/INTERPRETATION: Our study identified a novel group of SIGLEC-1+ monocytes that may serve as an important indicator for early diagnosis, activity assessment and monitoring of therapeutic efficacy in type 1 diabetes, and may also be a novel target for preventing and treating type 1 diabetes. DATA AVAILABILITY: RNA-seq data have been deposited in the GSA human database ( https://ngdc.cncb.ac.cn/gsa-human/ ) under accession number HRA003649.

Unveiling the oncogenic role of LZTS1 in colorectal cancer.

Although leucine zipper tumour suppressor 1 (LZTS1) has been considered a potential tumour suppressor, accumulating evidence suggests that LZTS1 is highly expressed in many cancer types. To unravel the exact role of LZTS1 in colorectal carcinogenesis, we performed the bioinformatic analysis of LZTS1, including expression differences, correlations between expression levels and survival, methylation status of LZTS1 promoter and related cellular pathways based on TCGA dataset, GEO databases and our own CRC patient cohort. Furthermore, we confirmed the oncogenic function of LZTS1 in human mammalian cells by employing a series of assays including tissue microarray, immunoblotting, cell proliferation and migration assay. We found that the expression of LZTS1 is higher in tumour samples compared to paired normal tissue in CRC cancer and its different clinical subtypes, which is, at least in part, due to the low methylation status of LZTS1 promoter in CRC tumour samples. Functional analysis identified the close relationship between high expression of LZTS1 and PI3K-AKT pathway and the epithelial-mesenchymal transition (EMT) process. Consistently, we found that the expression of LZTS1 positively correlated with the expression PIK3CD, N-cadherin in CRC tumour samples, while the expression of LZTS1 negatively correlated with the expression of E-cadherin and PTEN in CRC tumour samples. Experimental data further confirmed that overexpression of LZTS1 upregulated activity of AKT and promoted EMT process. Furthermore, depletion of LZTS1 repressed the proliferation and migration rate of CRC cells. Thus, this study indicates that LZTS1 plays an oncogenic role in colorectal carcinogenesis.

Trade-off in the partitioning of recent photosynthate carbon under global change.

There may be trade-offs in the allocation patterns of recent photosynthetic carbon (RPC) allocation in response to environmental changes, with a greater proportion of RPC being directed towards compartments experiencing limited resource availability. Alternatively, the allocation of RPC could shift from sources to sinks as plants processing excess photosynthates. It prompts the question: Does the pattern of RPC allocation vary under global changes? If so, is this variation driven by optimal or by residual C allocation strategies? We conducted a meta-analysis by complicating 273 pairwise observations from 55 articles with 13 C or 14 C pulse or continuous labeling to assess the partitioning of RPC in biomass (leaf, stem, shoot, and root), soil pools (soil organic C, rhizosphere, and microbial biomass C) and CO2 fluxes under elevated CO2 (eCO2 ), warming, drought and nitrogen (N) addition. We propose that the increased allocation of RPC to belowground under sufficient CO2 results from the excretion of excess photosynthates. Warming led to a significant reduction in the percentage of RPC allocated to shoots, alongside an increase in roots allocation, although this was not statistically significant. This pattern is due to the reduced water availability resulting from warming. In conditions of drought, there was a notable increase in the partitioning of RPC to stems (+7.25%) and roots (+36.38%), indicative of a greater investment of RPC in roots for accessing water from deeper soil. Additionally, N addition led to a heightened allocation of RPC in leaves (+10.18%) and shoots (+5.78%), while reducing its partitioning in soil organic C (-8.92%). Contrary to the residual C partitioning observed under eCO2 , the alterations in RPC partitioning in response to warming, drought, and N supplementation are more comprehensively explained through the lens of optimal partitioning theory, showing a trade-off in the partitioning of RPC under global change.

Body Fat Depletion: the Yin Paradigm for Treating Type 2 Diabetes.

PURPOSE OF REVIEW: To highlight that body fat depletion (the Yin paradigm) with glucose-lowering treatments (the Yang paradigm) are associated with metabolic benefits for patients with type 2 diabetes mellitus (T2DM). RECENT FINDINGS: The sodium-glucose cotransporter-2 inhibitor-mediated sodium/glucose deprivation can directly improve glycemic control and kidney outcome in patients with T2DM. The glucose deprivation might also promote systemic fatty acid ß-oxidation to deplete ectopic/visceral fat and thereby contribute to the prevention of cardiovascular diseases. As with metabolic surgery, bioengineered incretin-based medications with potent anorexigenic and insulinotropic efficacy can significantly reduce blood glucose as well as body weight (especially in the ectopic/visceral fat depots). The latter effects could be a key contributor to their cardiovascular-renal protective effects. In addition to a healthy diet, the newer glucose-lowering medications, with body fat reduction effects, should be prioritized when treating patients with T2DM, especially for those with established cardiovascular/renal risks or diseases.

Long-term changes in frailty and incident type 2 diabetes: A prospective cohort study based on the UK Biobank.

AIMS: To estimate the association between long-term changes in frailty and the risk of incident type 2 diabetes (T2DM) and to evaluate the effect of preventing the worsening of frailty on the risk of T2DM. METHODS: We included 348 205 participants free of baseline T2DM and with frailty phenotype (FP) data from the UK Biobank; among them, 36 175 had at least one follow-up assessment. According to their FP score, participants were grouped into nonfrailty, prefrailty and frailty groups. Frailty assessed at baseline and at follow-up was used to derive the trajectory of frailty (ΔFP). Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Compared with those in the nonfrailty group at baseline, the HRs of T2DM for the prefrailty and frailty groups were 1.38 (95% CI 1.33-1.43) and 1.69 (95% CI 1.59-1.79), respectively (both p < 0.001), in the multivariable-adjusted model. During a median follow-up of 5.4 years after the final assessment, data for 472 T2DM patients were recorded. A 1-point increase in the final FP was associated with a 25% (95% CI 1.14-1.38; p < 0.001) increased risk of T2DM. For the trajectory of frailty, each 0.5-point/year increase in ΔFP was associated with a 52% (95% CI 1.18-1.97; p < 0.001) greater risk of T2DM, independent of the FP score at baseline. Compared with those that remained in the nonfrailty group, the greatest risk of T2DM over time was prefrailty aggravation (HR 3.03, 95% CI 2.00-4.58; p < 0.001). Using the frailty index did not materially change the results. CONCLUSIONS: Long-term changes in frailty were associated with the risk of incident T2DM, irrespective of baseline frailty status. Preventing the worsening of frailty may reduce T2DM risk.

Optimization of Flavonoid Extraction from Eucommia ulmoides pollen using Respond Surface Methodology and its biological activities.

Flavonoids, known for their abundance in Eucommia ulmoides pollen, possess diverse biological functions, including antioxidants, antibacterial agents, and anti-tumor properties. This study aims to establish effective parameters for flavonoid extraction from Eucommia ulmoides pollen using a microwave-assisted method, characterize the flavonoid composition of the extracted material, and explore its biological activities. Building upon the initial results from single-factor experiments, response surface methodology was employed to optimize the extraction parameters. The inhibitory effect of human breast cancer cells (MCF-7) was evaluated by CCK assay and Live/dead staining. Simultaneously, the extract's scavenging ability against DPPH free radicals and its antibacterial properties against Escherichia coli and Staphylococcus aureus were investigated. The results demonstrated that the flavonoid yield reached 3.28 g per 100 g of pollen, closely aligning with the predicted value. The IC50 for flavonoid-mediated DPPH radical scavenging was 0.04 mg/mL. The extract exhibited a robust inhibitory effect on both Escherichia coli and Staphylococcus aureus. Concurrently, the extract displayed a significant inhibitory effect on the growth and proliferation of MCF-7 cells in a dose-dependent and time-dependent manner. In addition, six kinds of flavonoids have been identified by UPLC-TOF-MS/MS technology, providing further support to the study on the anti-oxidation and anti-tumor mechanism of Eucommia ulmoides pollen extracts.

The Facial Artery Perforator Flap for Reconstruction of Facial Defects: Surgical Pearls and Clinical Series.

BACKGROUND: Based on the knowledge of facial vascularity, facial artery perforator flaps could be used as potent tools for facial defect reconstruction. However, lack of experience and misconception of this technique limits the broad application in the clinical background. Here, we discussed surgical techniques based on our previous experience with facial artery perforator (FAP)-based facial defect reconstruction. METHODS: A retrospective review of 12 patients undergoing facial defect reconstruction using an FAP flap was performed, including 8 defects in the mid-facial part and 4 defects in the nasal area generally resulted from basal cell carcinoma (8 patients), squamous cell carcinoma (3 patients), and actinic keratosis (one patient). RESULTS: All patients received one-stage FAP flap reconstruction. The overall follow-up period was 6 to 12 months. All reconstructions were successful with satisfactory patient-reported outcome and no local recurrence. No significant complications were observed in most cases, except for one instance of partial flap loss. CONCLUSIONS: Overall, taking advantage of FAP flaps will contribute to a good functional and esthetic outcome of facial defect reconstructions.

Selecting Flap Transfer Methods to Repair Helix Soft Tissue Defect Based on the Direction of Long Axis.

BACKGROUND: The posterior auricular flap has long been favored for repairing skin defects on the ear's surface. However, achieving optimal esthetic outcomes in ear reconstruction requires a flexible approach to flap transfer methods. While bipedicle advancement flaps are commonly used for body wound coverage, they are rarely used in auricular defect repair. OBJECTIVE: To propose a modified flap transfer approach based on the orientation of the auricular defect's long axis and assess the postoperative esthetic outcomes. METHODS: The authors reported 12 patients treated using 2 distinct flap transfer techniques. Mild to moderate helix soft tissue defects remained after excision of the masses. A direct island flap was created for patients with longitudinal defects to cover the defect. For patients with transverse defects, a combination of bipedicle and island flaps was used for repair. Scar quality and esthetic outcomes were assessed at least 6 months postsurgery using the Scar Cosmesis Assessment and Rating scale. RESULTS: All patients experienced no serious complications and achieved excellent cosmetic results. Patients undergoing combined flap transfer exhibited relatively more favorable esthetic outcomes. CONCLUSION: The authors propose a novel concept for repairing helix soft tissue defects by designing local flaps based on the direction of the defect's long axis. For repairing helix soft tissue defects with a long axis parallel to the auricular edge, the combined utilization of bipedicle advancement flap and island rotation flap transfer should be consideration more.

[Comparison on anti-inflammatory activity of Gynostemma pentaphyllum processed with different methods].

The aim of this study is to investigate the effects of Gynostemma pentaphyllum dried with two different methods(air drying and heating) on inflammation in acute lung injury(ALI) mice in vivo and in vitro. Lipopolysaccharide(LPS) was sprayed into the airway of wild type C57BL/6J male mice to establish the model, and the drug was injected into the tail vein 24 h after modeling. Lung function, lung tissue wet/dry weight(W/D) ratio, the total protein concentration, interleukin 6(IL-6), IL-1ß, and tumor necrosis factor-α(TNF-α) in the bronchoalveolar lavage fluid(BALF), and pathological changes of the lung tissue were used to evaluate the effects of different gypenosides on ALI mice. The results showed that total gypenosides(YGGPs) and the gypenosides substituted with one or two glycosyl(GPs_(1-2)) in the air-dried sample improved the lung function, significantly lowered the levels of IL-1ß and TNF-α in BALF, and alleviated the lung inflammation of ALI mice. Moreover, GPs_(1-2) had a more significant effect on inhibiting NO release in RAW264.7 cells. This study showed that different drying methods affected the anti-inflammatory activity of G. pentaphyllum, and the rare saponins in the air-dried sample without heating had better anti-inflammatory activity.

Mothers' Perceived Co-Parenting and Preschooler's Problem Behaviors: The Mediating Role of Maternal Parenting Stress and the Moderating Role of Family Resilience.

Introduction: Problem behaviors in preschoolers signals social adjustment challenges. This study investigates the mediating role of parenting stress in the relationship between co-parenting and these behaviors, and examines how family resilience impacts this dynamic. Methods: A detailed survey was conducted with 1279 mothers of 3-6-year-olds in Shanghai, China, focusing on co-parenting, family resilience, parenting stress, and children's behaviors. We employed SPSS 26 for initial tests and the Hayes PROCESS macro in SPSS 23.0 for advanced analysis, using bootstrap methods to assess mediation and moderation effects. Results: The analysis revealed that maternal parenting stress mediates the relationship between co-parenting and children's problem behaviors. Specifically, unsupportive co-parenting or low levels of supportive co-parenting heightened maternal stress, which in turn increased children's problem behaviors. Family resilience was found to moderate this relationship, buffering the impact of unsupportive co-parenting on maternal stress. High family resilience levels were associated with lower parenting stress, regardless of co-parenting quality. Conclusion: These findings highlight the importance of enhancing family resilience and supportive co-parenting to mitigate parenting stress and reduce problem behaviors in children. It has practical implications for developing family-centred interventions and policies to strengthen family resilience and co-parenting skills.

Relations between maternal parenting styles and callous-unemotional behavior in Chinese children: A longitudinal study.

BACKGROUND: Previous studies on maternal parenting styles and children's callous-unemotional behavior (CU behavior) have focused on the West, and few studies have examined the longitudinal relationship between maternal parenting styles and CU behavior using Chinese preschoolers as subjects. OBJECTIVE: Through a 1.5-year longitudinal lens, this study probed the relations between maternal parenting styles and CU behavior in the Chinese cultural setting. PARTICIPANTS: Participants were N = 492 Chinese young children (Mage = 52.44 months, SD = 5.00, 48 % girls). METHODS: At Time 1 (T1), mothers reported their use of authoritative parenting styles (i.e., warmth, reasoning, and autonomy), authoritarian parenting styles (i.e., physical coercion, verbal hostility, and nonreasoning) and children's CU behavior. At Time 2 (T2; approximately 1.5 years later), mothers again reported the above variables. RESULTS: Cross-lagged models indicated that maternal warmth, reasoning, autonomy, and nonreasoning at T1 predicted CU behavior at T2. However, not only did maternal physical coercion and verbal hostility at T1 predict CU behavior at T2, but CU behavior at T1 also predicted maternal physical coercion and verbal hostility at T2. Additionally, there were no gender differences in the relationship between dimensions of maternal parenting styles and CU behavior. CONCLUSIONS: It underscores the influence of authoritative parenting in potentially mitigating CU behavior, while authoritarian approaches may exacerbate CU behavior. The absence of gender differences suggests these dynamics are broadly applicable across genders. These findings have significant implications for parenting strategies aimed at addressing CU behavior in children, emphasizing the need for warmth, reasoning, and autonomy in parenting practices.

Callous-unemotional behaviors and conduct problems in Chinese preschoolers: the moderating roles of surgency and gender.

Introduction: Conduct problems in children are related to callous-unemotional (CU) behaviors. However, results of the relationships between CU behaviors and conduct problems among preschoolers mainly focused on Western countries, no studies have examined whether CU behaviors predict conduct problem in Chinese preschoolers. The primary objective of the current study therefore was to examine the associations between CU behaviors and conduct problems as well as the moderating effects of surgency and child gender in Chinese preschool children. Methods: The present study randomly selected 2,154 children (1,043 boys, Mage = 56 months, SD = 10.47) from six kindergartens in Shanghai, People's Republic of China. Mothers rated children's surgency and teachers reported children's CU behaviors and conduct problems. Results: Results demonstrated that CU behaviors were positively associated with conduct problems. Surgency and child gender significantly moderated these associations. Specifically, CU behaviors were positively associated with conduct problems, with a stronger effect found for high levels of surgency. CU behaviors had a positive association with conduct problems, with a stronger effect found for boys. Discussion: This study indicate that temperament and gender characteristics influence conduct problems in preschoolers who exhibit high levels of CU behaviors. As well, the findings emphasize the significance of considering the meaning and implication of CU behaviors in Chinese culture.

Unsociability and social adjustment in Chinese preschool migrant children: the moderating role of receptive vocabulary.

Peer relationships play an indispensable role in the social, emotional, and cognitive development of children. However, children exhibiting social withdrawal, such as unsociability, may face challenges in social adjustment. In collectivistic cultures like China, unsociability may be perceived negatively, aligning poorly with collective norms. The objective of the present investigation was to examine the associations between unsociability, receptive vocabulary, and indicators of social adjustment in a cohort of young migrant children residing in urban regions of mainland China. The study mainly aimed to investigate the potential moderating influence of receptive language on these associations. The study involved 148 young children (82 boys, 66 girls, Mage = 62.32 months, SD = 6.76) enrolled in preschools or kindergartens in Shanghai, People's Republic of China. Multiple sources of assessment were utilized, encompassing evaluations from mothers (about child unsociability), teacher (assessing social adjustment), and standardized tests (measuring receptive vocabulary). The results indicated that the relations between unsociability and peer exclusion were more positive among children with lower levels of receptive vocabulary but not significant for children with higher levels of receptive vocabulary. Similarly, the relations between unsociability and peer exclusion were more negative among children with lower levels of receptive vocabulary but not significant for children with higher levels of receptive vocabulary. Thus, this study informs us about how receptive vocabulary is jointly associated with unsociable children's development. As well, the findings highlight the importance of considering the meaning and implication of unsociability in Chinese culture.

Neoantigen identification: Technological advances and challenges.

Neoantigens have emerged as promising targets for cutting-edge immunotherapies, such as cancer vaccines and adoptive cell therapy. These neoantigens are unique to tumors and arise exclusively from somatic mutations or non-genomic aberrations in tumor proteins. They encompass a wide range of alterations, including genomic mutations, post-transcriptomic variants, and viral oncoproteins. With the advancements in technology, the identification of immunogenic neoantigens has seen rapid progress, raising new opportunities for enhancing their clinical significance. Prediction of neoantigens necessitates the acquisition of high-quality samples and sequencing data, followed by mutation calling. Subsequently, the pipeline involves integrating various tools that can predict the expression, processing, binding, and recognition potential of neoantigens. However, the continuous improvement of computational tools is constrained by the availability of datasets which contain validated immunogenic neoantigens. This review article aims to provide a comprehensive summary of the current knowledge as well as limitations in neoantigen prediction and validation. Additionally, it delves into the origin and biological role of neoantigens, offering a deeper understanding of their significance in the field of cancer immunotherapy. This article thus seeks to contribute to the ongoing efforts to harness neoantigens as powerful weapons in the fight against cancer.

Comparison of Batroxobin Versus the Combination of Batroxobin and Intratympanic Dexamethasone Injection in the Treatment of Sudden Sensorineural Hearing Loss.

Introduction: Sudden sensorineural hearing loss (SSNHL) manifests as an abrupt decline in hearing by at least 30 dB within a 3 day period. Intratympanic dexamethasone injection (ITDI) has gained recognition as a potential treatment for SSNHL. This study aims to investigate the efficacy of combining batroxobin with ITDI (Bat and ITDI) in treating SSNHL patients and its influence on peripheral blood inflammatory indicators. Methods: SSNHL patients were retrospectively categorized into the control group (treated with Bat) and the observation group (treated with Bat and ITDI). The study involved analyzing clinical baseline data, evaluating clinical efficacy, and comparing the total effective rates among SSNHL patients with different audiometric curve types in the observation group. Routine blood tests were performed on peripheral blood samples to calculate the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), and to determine C-reactive protein (CRP) levels. Adverse reactions and complications were closely monitored. Results: Following treatment, both groups displayed improvements in hearing, with the observation group exhibiting a significantly higher total effective rate (75.90%) than the control group (59.78%). For patients with 3 distinct types of sudden hearing loss (high-frequency, flat-frequency, total deafness), Bat and ITDI treatment demonstrated increased total effective rate for patients with different sudden hearing loss types (high-frequency, flat-frequency, and total deafness). Both groups experienced reduced peripheral blood CRP levels and the NLR/PLR values, with the observation group demonstrating lower values. Additionally, across the 4 audio metric subtypes, the levels of peripheral blood CRP, NLR, and PLR decreased in SSNHL patients, and the observation group had a lower incidence of adverse reactions compared to the control group. Conclusions: Bat and ITDI emerge as notably more effective for SSNHL patients, displaying potential for reducing peripheral blood inflammatory indicator levels and mitigating the incidence of adverse reactions or complications, thereby enhancing safety.

MicroRNA-375-3p Alleviates Salicylate-Induced Neuronal Injury by Targeting ELAVL4 in Tinnitus.

Purpose Tinnitus is a phantom perception of sound in the absence of acoustic source. Previous evidence has indicated that miR-375-3p is downregulated in rats with tinnitus in comparison to the controls. Nevertheless, its molecular mechanism underlying tinnitus pathogenesis is unclarified. Methods SH-SY5Y cells were differentiated into neuronlike cells and stimulated with salicylate to mimic tinnitus in vitro. Immunofluorescence staining was utilized for measuring expression of NR2B (glutamate ionotropic receptor NMDA type subunit 2B). Intracellular reactive oxygen species (ROS) level was determined using DCFH-DA assay kit. Real-time quantitative polymerase chain reaction as well as western blotting was utilized for examining RNA and protein levels. Luciferase reporter assay was implemented for verifying the interaction between miR-375-3p and ELAVL4 (ELAV-like RNA-binding protein 4). Results Salicylate treatment enhanced levels of NR2B and the early immediate gene ARC as well as ROS production. miR-375-3p was downregulated in salicylate-treated group. Overexpressing miR-375-3p attenuated the effects induced by salicylate in SH-SY5Y cells. miR-375-3p targeted ELAVL4 and upregulating ELAVL4 reversed miR-375-3p upregulation-triggered effects on SH-SY5Y cells under salicylate treatment. Conclusion miR-375-3p mitigates salicylate-triggered neuronal injury in SH-SY5Y cells by regulating ELAVL4 expression.

Association of systemic immune-inflammation index with insulin resistance and prediabetes: a cross-sectional study.

Background and Objective: Previous research suggested a relationship between the Systemic Immune-Inflammation Index (SII) and multiple adverse health conditions. However, the role of SII in prediabetes and insulin resistance (IR) remains poorly understood. Therefore, this study aims to explore the potential relationship between SII and prediabetes and IR, providing data support for effective diabetes prevention by reducing systemic inflammation. Methods: Linear regression models were used to assess the correlation between continuous SII and risk markers for type 2 diabetes (T2D). Subsequently, multivariate logistic regression models and subgroup analyses were employed to evaluate the association between SII tertiles and prediabetes and IR, controlling for various confounding factors. Finally, restricted cubic spline graphs were used to analyze the nonlinear relationship between SII and IR and prediabetes. Results: After controlling for multiple potential confounders, SII was positively correlated with fasting blood glucose (FBG) (ß: 0.100; 95% CI: 0.040 to 0.160), fasting serum insulin (FSI) (ß: 1.042; 95% CI: 0.200 to 1.885), and homeostasis model assessment of insulin resistance (HOMA-IR) (ß: 0.273; 95% CI: 0.022 to 0.523). Compared to participants with lower SII, those in the highest tertile had increased odds of prediabetes (OR: 1.17; 95% CI: 1.02-1.34; p for trend < 0.05) and IR (OR: 1.35; 95% CI: 1.18 to 1.51; p for trend<0.001). Conclusions: Our study results demonstrate an elevated association between SII levels and both IR and prediabetes, indicating SII as a straightforward and cost-effective method identifying individuals with IR and prediabetes.

Business decision-making of power generators in competitive electricity market.

This paper presents a theoretical framework for the business decision-making process of the power generators as price takers when considering the participation of energy storage. The framework assesses rational valuation, optimal sales strategies, and hedging options for power plants with and without a gross sales constraint. The valuation and optimal sales strategy problems are analyzed using a risk-neutral pricing approach, dynamic programming principles, and the trinomial tree model suitable for the regime switching model. The formulation of a price risk hedging scheme flexible and widely used over-the-counter electricity derivative, the electricity contract for difference, as a tool for hedging electricity spot price risk. The minimum variance hedge ratio and its corresponding hedging efficiency formula are derived. In the section of numerical simulations, we first use the EM algorithm to calibrate the electricity spot model based on electricity spot price data of Nord Pool. Numerical simulations are then conducted on the operational decision-making of power generators under three different forms of energy storage. The results of the simulations provide a basis for power generators to evaluate the real-time value of power plants, to select optimal real-time power sales, and to determine the optimal timing of power plant transfer and storage methods.