Frailty index and risk of delirium in hospitalized patients: a two-sample Mendelian randomization study.

Objective: Observational studies suggest that the frailty index (FI) is closely related to delirium, but the relationship between them is still uncertain due to the influence of various confounding factors. Therefore, two-sample Mendelian randomization (MR) was used to explore the causal relationship between the FI and delirium risk. Methods: This study obtained pooled statistics for the FI and delirium from two of the most extensive genome-wide association studies. To make the results more robust and reliable, supplementary analyses were performed using several robust analytical methods (inverse-variance weighting, MR-Egger regression, and weighted median). In addition, this study used the MR-Egger intercept test, Cochran's Q test, funnel plots and the leave-one-out method to evaluate the pleiotropy and heterogeneity among the abovementioned genetic variation instrumental variables. Results: Frailty might increase the relative risk of delirium, as shown by IVW (OR = 1.849, 95% CI 0.027∼2.067, P = 0.044), weighted median (OR = 1.726, 95% CI -0.178∼2.664, P = 0.083), MR-Egger regression (OR = 1.768, 95% CI -3.08∼6.171, P = 0.525) and leave-one-out sensitivity analysis (P = 0.058). Although the WME method and MR-Egger regression analysis showed no statistically significant causal relationship between the FI and the risk of delirium, the direction of the causal effect was consistent with the IVW method. Conclusion: There is a notable correlation between a higher FI and an elevated risk of delirium. This indicates that healthcare providers should take proactive measures to prevent delirium in hospitalized patients with a higher FI.

Discovery of a novel BTK inhibitor S-016 and identification of a new strategy for the treatment of lymphomas including BTK inhibitor-resistant lymphomas.

Bruton's tyrosine kinase (BTK) has emerged as a therapeutic target for B-cell malignancies, which is substantiated by the efficacy of various irreversible or reversible BTK inhibitors. However, on-target BTK mutations facilitating evasion from BTK inhibition lead to resistance that limits the therapeutic efficacy of BTK inhibitors. In this study we employed structure-based drug design strategies based on established BTK inhibitors and yielded a series of BTK targeting compounds. Among them, compound S-016 bearing a unique tricyclic structure exhibited potent BTK kinase inhibitory activity with an IC50 value of 0.5 nM, comparable to a commercially available BTK inhibitor ibrutinib (IC50 = 0.4 nM). S-016, as a novel irreversible BTK inhibitor, displayed superior kinase selectivity compared to ibrutinib and significant therapeutic effects against B-cell lymphoma both in vitro and in vivo. Furthermore, we generated BTK inhibitor-resistant lymphoma cells harboring BTK C481F or A428D to explore strategies for overcoming resistance. Co-culture of these DLBCL cells with M0 macrophages led to the polarization of M0 macrophages toward the M2 phenotype, a process known to support tumor progression. Intriguingly, we demonstrated that SYHA1813, a compound targeting both VEGFR and CSF1R, effectively reshaped the tumor microenvironment (TME) and significantly overcame the acquired resistance to BTK inhibitors in both BTK-mutated and wild-type BTK DLBCL models by inhibiting angiogenesis and modulating macrophage polarization. Overall, this study not only promotes the development of new BTK inhibitors but also offers innovative treatment strategies for B-cell lymphomas, including those with BTK mutations.

LncRNA GABPB1-IT1 is upregulated in ischemia-induced acute kidney injury and downregulates miR-204-5p to promote hypoxia-induced human renal proximal tubular epithelial cell apoptosis.

INTRODUCTION: The present study investigated the role of long non-coding RNA (lncRNA) GABPB1-IT1 in ischemia-induced acute kidney injury (AKI). METHODS: The expression of GABPB1-IT1 in plasma of patients with ischemia-induced AKI and healthy controls was detected by RT-qPCR. GABPB1-IT1 and miR-204-5p were overexpressed in human renal proximal tubular epithelial cells (HRPTEpCs), followed by RT-qPCR to assess the overexpression effect and the regulatory relationship between GABPB1-IT1 and miR-204-5p. Methylation-specific PCR (MSP) was performed to assess the promoter methylation status of miR-204-5p. Additionally, cell apoptosis assay was carried out to evaluate the correlation between miR-204-5p and GABPB1-IT1 in the context of hypoxia-induced apoptosis of HRPTEpCs. RESULTS: GABPB1-IT1 was upregulated in plasma of patients with ischemia-induced AKI. In HRPTEpCs, hypoxia upregulated the expression of GABPB1-IT1. MiR-204-5p was downregulated in ischemia-induced AKI, and the expression of miR-204-5p was inversely correlated with GABPB1-IT1. In HRPTEpCs, overexpression of GABPB1-IT1 decreased the expression levels of miR-204-5p and increased miR-204-5p gene methylation. In addition, overexpression of GABPB1-IT1 reduced the inhibitory effects of miR-204-5p on the apoptosis of HRPTEpC induced by hypoxia. Furthermore, overexpression of GABPB1-IT1 promoted kidney injury, renal tissue injury scores, and the level of serum creatinine. However, miR-204-5p had the opposite effect. CONCLUSION: GABPB1-IT1 was upregulated in ischemia-induced AKI and may induce hypoxia-induced apoptosis of HRPTEpC by methylation of miR-204-5p.

Causal relationship between gut microbiota and differentiated thyroid cancer: a two-sample Mendelian randomization study.

Background: The gut microbiota has been significantly associated with differentiated thyroid cancer (DTC). However, the causal relationship between the gut microbiota and DTC remains unexplored. Methods: Genome-wide association study (GWAS) summary databases were utilized to select exposures and outcomes. The Mendelian randomization (MR) method was employed to investigate the causal relationship between the gut microbiota and DTC. A sensitivity analysis was performed to assess the reliability of the findings. Results: Four bacterial traits were associated with the risk of DTC: Class Mollicutes [odds ratio (OR) = 10.953, 95% confidence interval (95% CI): 2.333-51.428, p = 0.002], Phylum Tenericutes (OR = 10.953, 95% CI: 2.333-51.428, p = 0.002), Genus Eggerthella (OR = 3.219, 95% CI: 1.033-10.024, p = 0.044), and Order Rhodospirillales (OR = 2.829, 95% CI: 1.096-7.299, p = 0.032). The large 95% CI range for the Class Mollicutes and the Phylum Tenericutes may be attributed to the small sample size. Additionally, four other bacterial traits were negatively associated with DTC: Genus Eubacterium fissicatena group (OR = 0.381, 95% CI: 0.148-0.979, p = 0.045), Genus Lachnospiraceae UCG008 (OR = 0.317, 95% CI: 0.125-0.801, p = 0.015), Genus Christensenellaceae R-7 group (OR = 0.134, 95% CI: 0.020-0.886, p = 0.037), and Genus Escherichia Shigella (OR = 0.170, 95% CI: 0.037-0.769, p = 0.021). Conclusion: These findings contribute to our understanding of the pathological mechanisms underlying DTC and provide novel insights for the clinical treatment of DTC.

Photoperiod-Dependent Nutrient Accumulation in Rice Cultivated in Plant Factories: A Comparative Metabolomic Analysis.

Plant factories offer a promising solution to some of the challenges facing traditional agriculture, allowing for year-round rapid production of plant-derived foods. However, the effects of conditions in plant factories on metabolic nutrients remain to be explored. In this study, we used three rice accessions (KongYu131, HuangHuaZhan, and Kam Sweet Rice) as objectives, which were planted in a plant factory with strict photoperiods that are long-day (12 h light/12 h dark) or short-day (8 h light/16 h dark). A total of 438 metabolites were detected in the harvested rice grains. The difference in photoperiod leads to a different accumulation of metabolites in rice grains. Most metabolites accumulated significantly higher levels under the short-day condition than the long-day condition. Differentially accumulated metabolites were enriched in the amino acids and vitamin B6 pathway. Asparagine, pyridoxamine, and pyridoxine are key metabolites that accumulate at higher levels in rice grains harvested from the short-day photoperiod. This study reveals the photoperiod-dependent metabolomic differences in rice cultivated in plant factories, especially the metabolic profiling of taste- and nutrition-related compounds.

AM-DMF-SCP: Integrated Single-Cell Proteomics Analysis on an Active Matrix Digital Microfluidic Chip.

Single-cell proteomics offers unparalleled insights into cellular diversity and molecular mechanisms, enabling a deeper understanding of complex biological processes at the individual cell level. Here, we develop an integrated sample processing on an active-matrix digital microfluidic chip for single-cell proteomics (AM-DMF-SCP). Employing the AM-DMF-SCP approach and data-independent acquisition (DIA), we identify an average of 2258 protein groups in single HeLa cells within 15 min of the liquid chromatography gradient. We performed comparative analyses of three tumor cell lines: HeLa, A549, and HepG2, and machine learning was utilized to identify the unique features of these cell lines. Applying the AM-DMF-SCP to characterize the proteomes of a third-generation EGFR inhibitor, ASK120067-resistant cells (67R) and their parental NCI-H1975 cells, we observed a potential correlation between elevated VIM expression and 67R resistance, which is consistent with the findings from bulk sample analyses. These results suggest that AM-DMF-SCP is an automated, robust, and sensitive platform for single-cell proteomics and demonstrate the potential for providing valuable insights into cellular mechanisms.

Ginsenoside Rg3, enriched in red ginseng extract, improves lipopolysaccharides-induced suppression of brown and beige adipose thermogenesis with mitochondrial activation.

Brown adipose tissue (BAT) which is a critical regulator of energy homeostasis, and its activity is inhibited by obesity and low-grade chronic inflammation. Ginsenoside Rg3, the primary constituent of Korean red ginseng (steamed Panax ginseng CA Meyer), has shown therapeutic potential in combating inflammatory and metabolic diseases. However, it remains unclear whether Rg3 can protect against the suppression of browning or activation of BAT induced by inflammation. In this study, we conducted a screening of ginsenoside composition in red ginseng extract (RGE) and explored the anti-adipogenic effects of both RGE and Rg3. We observed that RGE (exist 0.25 mg/mL of Rg3) exhibited significant lipid-lowering effects in adipocytes during adipogenesis. Moreover, treatment with Rg3 (60 µM) led to the inhibition of triglyceride accumulation, subsequently promoting enhanced fatty acid oxidation, as evidenced by the conversion of radiolabeled 3H-fatty acids into 3H-H2O with mitochondrial activation. Rg3 alleviated the attenuation of browning in lipopolysaccharide (LPS)-treated beige adipocytes and primary brown adipocytes by recovered by uncoupling protein 1 (UCP1) and the oxygen consumption rate compared to the LPS-treated group. These protective effects of Rg3 on inflammation-induced inhibition of beige and BAT-derived thermogenesis were confirmed in vivo by treating with CL316,243 (a beta-adrenergic receptor agonist) and LPS to induce browning and inflammation, respectively. Consistent with the in vitro data, treatment with Rg3 (2.5 mg/kg, 8 weeks) effectively reversed the LPS-induced inhibition of brown adipocyte features in C57BL/6 mice. Our findings confirm that Rg3-rich foods are potential browning agents that counteract chronic inflammation and metabolic complications.

Mendelian randomization study shows no causal relationship between psychiatric disorders and glaucoma in European and East Asian populations.

Background: Glaucoma is a leading cause of blindness strongly associated with psychiatric disorders, but the causal association between glaucoma and psychiatric disorders remains uncertain because of the susceptibility of observational studies to confounding and reverse causation. This study aims to explore the potential causal association between glaucoma and three highly related psychiatric disorders (Depression, Insomnia, and Schizophrenia) in the European and East Asian populations using a two-sample Mendelian randomization analysis. Methods: Instrumental variables (IVs) of depression, insomnia, and schizophrenia in the European population were obtained after strict filtering. Summary-level data for glaucoma and glaucoma subtypes (primary open-angle glaucoma and primary closed-angle glaucoma) were obtained as outcomes. The inverse variance weighting (IVW) method was used as the primary method. Additionally, the causal effect was evaluated in the East Asian population using the same methods to validate analysis results. The robustness of these results was confirmed using heterogeneity, pleiotropy, and Steiger directionality test. Results: The primary MR results indicated that genetically driven psychiatric disorders were not causally associated with glaucoma (Depression: odds ratio (OR): 1.15, 95% confidence interval (CI): 0.93-1.42, p = 0.20; Insomnia: OR: 1.14, 95% CI: 0.63-2.05, p = 0.66; Schizophrenia: OR: 1.00, 95% CI: 0.93-1.08, p = 0.95), either with the risk of glaucoma subtypes in the European population. Meanwhile, results in the East Asian population were consistent with the results among the European population (Depression: OR = 1.38, CI 0.75-2.53, p = 0.30; Insomnia: OR = 0.99, CI 0.83-1.18, p = 0.93; Schizophrenia: OR = 1.06, CI 0.94-1.20, p = 0.34) with similar causal estimates in direction. Consistency was obtained by corroborating with other supporting methods. Besides, the robustness of the results was proved and the directionality test confirmed our estimation of potential causal direction (p < 0.001). Conclusion: This study found a non-causal association between psychiatric disorders and the risk of glaucoma in the European and East Asian populations, which contradicts many existing observational reports, indicating that increased psychiatric disorders in glaucoma patients were more likely modifiable rather not inheritable.

Untargeted urine metabolomics and machine learning provide potential metabolic signatures in children with autism spectrum disorder.

Background: Complementary to traditional biostatistics, the integration of untargeted urine metabolomic profiling with Machine Learning (ML) has the potential to unveil metabolic profiles crucial for understanding diseases. However, the application of this approach in autism remains underexplored. Our objective was to delve into the metabolic profiles of autism utilizing a comprehensive untargeted metabolomics platform coupled with ML. Methods: Untargeted metabolomics quantification (UHPLC/Q-TOF-MS) was performed for urine analysis. Feature selection was conducted using Lasso regression, and logistic regression, support vector machine, random forest, and extreme gradient boosting were utilized for significance stratification. Pathway enrichment analysis was performed to identify metabolic pathways associated with autism. Results: A total of 52 autistic children and 40 typically developing children were enrolled. Lasso regression identified ninety-two urinary metabolites that significantly differed between the two groups. Distinct metabolites, such as prostaglandin E2, phosphonic acid, lysine, threonine, and phenylalanine, were revealed to be associated with autism through the application of four different ML methods (p<0.05). The alterations observed in the phosphatidylinositol and inositol phosphate metabolism pathways were linked to the pathophysiology of autism (p<0.05). Conclusion: Significant urinary metabolites, including prostaglandin E2, phosphonic acid, lysine, threonine, and phenylalanine, exhibit associations with autism. Additionally, the involvement of the phosphatidylinositol and inositol phosphate pathways suggests their potential role in the pathophysiology of autism.

Electroacupuncture on Baihui (DU20) and Xuehai (SP10) acupoints alleviates psoriatic inflammation by regulating neurotransmitter substance P- Neurokinin-1 receptor signaling.

Background: At present, acupuncture-related practices have been widely used to treat psoriasis. In our study, we investigated the effect and explored the mechanism of electroacupuncture (EA) on acupoints Baihui (DU20) and Xuehai (SP10) for the treatment of psoriasis. Methods: Imiquimod-induced psoriasis-like mouse model was used in this study. Mice were treated with electroacupuncture at DU20 and SP10 (depth of 2-3 mm, frequency of 2/15 Hz, intensity of 0.5-1.0 mA, 10 min/day). The severity of psoriasis-like lesions for each group was assessed. In addition, histological analysis of the lesions were performed. The levels of inflammatory cytokines were determined using Elisa. The expression levels of Substance P (SP) and NK1R were measured using Western blotting. In addition, NK1R inhibitor was administrated to evaluate the target of electroacupuncture in our mouse model. Results: Electroacupuncture significantly alleviated IMQ-induced skin lesions and epidermal thickness, accompanied with reduced keratinocyte proliferation, CD3+, CD4+, and CD8+ T cells infiltration. The reduced levels of inflammatory cytokines was observed after electroacupuncture treatment. In addition, electroacupuncture inhibited the expression levels of SP and NK1R. NK1R inhibitor could ameliorate lesional symptoms and suppress epidermal thickening and CD3+, CD4+, and CD8 + T cell infiltration. Conclusions: Electroacupuncture relieved psoriasis-like inflammation and T cell infiltration. This therapeutic action was likely mediated by the modulation of Substance P and its receptor NK1R.

Clinical features and demographic characteristics of gestational trophoblastic neoplasia: Single center experience and the SEER database.

The aim of this study was to analyze the clinical features and demographic characteristics of gestational trophoblastic neoplasia (GTN) patients, specifically choriocarcinoma (CC), placental site trophoblastic tumour (PSTT), and epithelioid trophoblastic tumor (ETT). We utilized data from a local hospital and the SEER database, as well as survival outcomes of CC in SEER database. Additionally, we used multiple risk factors to create a prognostic nomogram model for CC patients. The study included GTN patients from the SEER database between 1975 and 2016 as well as those from the First Affiliated Hospital of Xi 'an Jiaotong University between January 2005 and May 2022. Related factors of patients were compared using the chi-square (χ2) or Fisher's exact test. For assessing overall survival we employed the Kaplan-Meier method and log-rank test. To construct the nomogram, we used Cox regression. Statistically significant differences were found between CC and PSTT/ETT patients in terms of surgery in local hospital, as well as age and year of diagnosis in the SEER database. Moreover, significant differences were observed between low and high (HR) /ultra-high risk (UHR) groups regarding FIGO stage, surgery and chief complaint at the local hospital, and FIGO stage, surgery and unemployment in the SEER database. The Cox regression analysis confirmed that age, race, surgery, marital status, FIGO stage, and unemployment were correlated with CC prognosis. Furthermore, the analysis showed that patients aged 40 years or older and those with FIGO Ⅲ/Ⅳ were independent prognostic factors of CC. The study indicates that atypical symptoms or signs may be the main reasons for HR /UHR patients to seek medical treatment. Therefore, providing multidisciplinary care is recommended for CC patients experiencing psychological distress due to unfavorable marital status or unemployment.

Effects of 2-dodecyl-6-methoxycyclohexa-2,5-diene-l ,4-dione on resisting hepatic fibrosis induced by CC14 in rats and its mechanisms via TGF-pi/Smads signaling pathway / 中国药理学通报

Aim To investigate the effects of 2-dode-cyl-6-methoxycyclohexa-2 , 5-diene-l, 4-dione ( DM-DD) on resisting hepatic fibrosis induced by carbon tetrachloride ( CC14 ) in rats and the underlying mechanisms , with a specific focus on the TGF-pi/Smads signaling pathway. Methods The hepatic fibrosis model was replicated using 50% CC14. Various parameters, including levels of aspartate transferase ( AST) , ala-nine transferase ( ALT ) , albumin/globulin ( A/G ) , total protein (TP) , total bilirubin (T-BIL) , hyaluron-ic acid ( HA ) , laminin ( LN ) , collagen type Ж ( Col Ж) , and collagen type IV(ColIV) in the blood, were measured. Liver tissue lesions and fiber formation were observed using HE and Masson staining. The expression levels of a smooth muscle actin (a-SMA) , collagen type I ( Col I ) , transformed growth factor (TGF-pi), Smad2, and Smad7 proteins were assessed using immunohistochemistry. a-SMA, Coll, TGF-pi, and Smad7 mRNA levels in liver tissue were measured by RT-PCR. Additionally, the expression levels of TGF-pi, Smad4, and Smad7 proteins in liver tissue were determined by Western blot. Results In comparison to the normal control group, the model group exhibited significantly elevated levels of AST, ALT, TP, T-BIL, HA, LN, Col Ш and Col IV in serum. But A/G level notably decreased. Successful modeling was confirmed by the presence of extensive fiber formations observed through HE and Massonstaining in liver tissue. The DMDD administration group demonstrated a notable decrease levels of AST, ALT, TP, T-BIL, HA, LN, Col III, and CollV, but A/G was significantly elevated when compared to the model group. Furthermore, a-SMA, Coll, TGF-f31, Smad2 and Smad4 mRNA and protein levels in the DMDD administration group were significantly reduced, while Smad7 significantly declined. HE and Masson staining results reflected a marked reduction in fibrous hyper-plasia. Conclusion DMDD exhibits a protective effect against CCl4-induced hepatic fibrosis, and its mechanism appears to be associated with the TGF-fJl/ Smads signaling pathway.

Preclinical and early clinical studies of a novel compound SYHA1813 that efficiently crosses the blood-brain barrier and exhibits potent activity against glioblastoma.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults and is poorly controlled. Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression, and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment. Therefore, this study developed a novel and selective inhibitor of CSF1R and VEGFR, SYHA1813, possessing potent antitumor activity against GBM. SYHA1813 inhibited VEGFR and CSF1R kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo. SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models, including temozolomide (TMZ) insensitive tumors. Notably, SYHA1813 could penetrate the blood-brain barrier (BBB) and prolong the survival time of mice bearing intracranial GBM xenografts. Moreover, SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody. As a clinical proof of concept, SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial. The data of this study support the rationale for an ongoing phase I clinical study (ChiCTR2100045380).

Electrochemiluminescent bioassay based on Ru@Zr-BTC-MOFs nanoparticles for determination of let-7a miRNA using the hybridization chain reaction.

Carboxyl-rich tris(4,4'-dicarboxylic acid-2,2'-bipyridyl) ruthenium(II) ([Ru(dcbpy)3]2+) and 1,3,5-phenyl tricarboxylic acid (H3BTC) were used as the organic ligand to synthesize the metal-organic frameworks by a simple one-pot hydrothermal method with ZrCl4 as metal ion source. Subsequently, the excellent electrochemiluminescence (ECL) luminophore (denoted as Ru@Zr-BTC-MOFs) was obtained. The Ru@Zr-BTC-MOFs displayed outstanding ECL properties, and a sensitive ECL bioassay based on Ru@Zr-BTC-MOFs was designed for the detection of let-7a microRNA (miRNA) using hybrid chain reaction (HCR). Under the optimal experimental conditions, the proposed bioassay exhibited a good linear relationship in the range from 50.0 fM to 5.00 × 102 pM with a detection limit of 3.71 fM. Besides, the proposed sensor exhibited satisfactory performance in real samples. The recovery was 91 ~ 108%, and the relative standard deviation was less than 5.6%. It might have potential clinical applications for detecting miRNA in biomedical research and clinical diagnosis. The schematic diagram of the preparation of Ru@Zr-BTC-MOFs (a) and ECL sensor for detecting let -7a (b).

Factors contributing to emotional distress when caring for children with imperforate anus: a multisite cross-sectional study in China.

Background: Imperforate anus (IA) has a life-long impact on patients and their families. The caregivers of children with IA (CoCIA) might experience distress, which could be detrimental to them physically and mentally. However, there are limitations in the related studies. This study aimed to investigate the prevalence of IA and the associated factors contributing to the distress experienced by CoCIA. Methods: A cross-sectional study was conducted in three tertiary children's hospitals from November 2018 to February 2019. Distress was assessed using the Chinese version of the Kessler Psychological Distress Scale, and possible determinants were assessed by the Caregiver Reaction Assessment, the Parent Stigma Scale, the Parent Perception of Uncertainty Scale, and the Social Support Scale. Demographic and clinical information was also collected. Multiple regression analysis was performed to explore the association between variables. Results: Out of 229 CoCIA, 52.9% reported experiencing a high level of distress or above. The data analysis revealed that health problems associated with caregiving, stigma, uncertainty, social support, and children who underwent anal reconstruction surgery 1 year before or earlier could significantly predicate caregivers' distress, and these factors could explain 50.1% of the variance. Conclusions: The majority of the caregivers of children with IA experience high levels of distress, particularly when their children undergo anal reconstruction surgery 1 year before or earlier. Additionally, health problems related to caregiving, stigma, uncertainty, and low social support could significantly predicate caregivers' distress. It is important for clinical staff to be aware of the prevalent situation of caregivers' distress and to make targeted interventions focused on addressing modifiable factors that should be carried out in family-based care.

[Research progress of metabolomics in acute kidney injury].

Acute kidney injury (AKI) is caused by a variety of diseases, which leads to acute renal function decline, azotemia, water and electrolyte disorders and acid-base balance disorders. Metabolomics is a research method that can quantitatively analyze all metabolites in an organism and find the relative relationship between metabolites and physiological and pathological changes. In recent years, several metabolites screened based on metabolomics have been proposed as potential biomarkers to assess the early development and prognosis of AKI and for the discovery of unknown potential therapeutic targets. Based on metabolomics, this paper reviews the risk prediction, early diagnosis, disease monitoring, prognosis assessment and the application of corresponding drugs for AKI, so as to provide reference for precision medicine.

Resveratrol Ameliorates Imiquimod-Induced Psoriasis-Like Mouse Model via Reducing Macrophage Infiltration and Inhibiting Glycolysis.

Purpose: Resveratrol (Res) is a natural polyphenol with anti-inflammatory and immunomodulatory effects. Alterations in metabolic pathways have been studied in psoriasis. This study is aimed to further explore the potential molecular mechanism of psoriasis improvement by Res. Patients and Methods: Imiquimod (IMQ)-induced psoriasis-like mouse model was established to observe the effects of Res. NanoString nCounter Metabolic Pathways Panel was used to analyze the changed mRNA and qRT-PCR was used for validation. Flow cytometry was used to analyze immune cell subsets in skin lesions. In vitro, we observed the effects of Res on R848-stimulated macrophages glycolysis and inflammation. Results: Res reduced the proliferation of keratinocytes and the secretion of inflammatory cytokines in IMQ-induced psoriasis-like mouse model. Psoriasis model skin lesions were in a state of hypoxia, with upregulated glycolysis and downregulated AMPK activity. Res inhibited the levels of hypoxia-related genes (hif1α, hif3α) and glycolysis-related genes (hk1, ldha), meanwhile increased the levels of AMPK genes (prkaa1, prkaa2). Flow cytometry analysis revealed that Res decreased the infiltration of macrophages in psoriasis-like lesions. In addition, Res decreased the secretion of macrophage-associated pro-inflammatory cytokines (IL-23, TNF-α, IL-1ß). In vitro, Res diminished the secretion of IL-23, TNF-α, IL-1ß, and lactate by R848-stimulated macrophages and activated AMPK. Conclusion: This study suggested that Res diminished psoriasis symptoms by inhibiting macrophages infiltration and inhibiting glycolysis, which providing novel insights into the underlying mechanisms of therapeutic action of Res in the treatment of psoriasis.

[Association between maternal gestational diabetes mellitus and the risk of autism spectrum disorder in offspring]. / æ¯äº²å¦Šå¨ ç³–å°¿ç— ä¸Žå­ä»£å­¤ç‹¬ç—‡è°±ç³»éšœç¢å‘ç”Ÿé£Žé™©çš„å ³è”åˆ†æž.

OBJECTIVES: To explore the association between maternal gestational diabetes mellitus (GDM) exposure and the development of autism spectrum disorder (ASD) in offspring. METHODS: A case-control study was conducted, recruiting 221 children with ASD and 400 healthy children as controls. Questionnaires and interviews were used to collect information on general characteristics of the children, socio-economic characteristics of the family, maternal pregnancy history, and maternal disease exposure during pregnancy. Multivariate logistic regression analysis was used to investigate the association between maternal GDM exposure and the development of ASD in offspring. The potential interaction between offspring gender and maternal GDM exposure on the development of ASD in offspring was explored. RESULTS: The proportion of maternal GDM was significantly higher in the ASD group compared to the control group (16.3% vs 9.4%, P=0.014). After adjusting for variables such as gender, gestational age, mode of delivery, parity, and maternal education level, maternal GDM exposure was a risk factor for ASD in offspring (OR=2.18, 95%CI: 1.04-4.54, P=0.038). On the basis of adjusting the above variables, after further adjusting the variables including prenatal intake of multivitamins, folic acid intake in the first three months of pregnancy, and assisted reproduction the result trend did not change, but no statistical significance was observed (OR=1.94, 95%CI: 0.74-5.11, P=0.183). There was an interaction between maternal GDM exposure and offspring gender on the development of ASD in offspring (P<0.001). Gender stratified analysis showed that only in male offspring of mothers with GDM, the risk of ASD was significantly increased (OR=3.67, 95%CI: 1.16-11.65, P=0.027). CONCLUSIONS: Maternal GDM exposure might increase the risk of ASD in offspring. There is an interaction between GDM exposure and offspring gender in the development of ASD in offspring.

Antibacterial oxygenated ergostane-type steroids produced by the marine sponge-derived fungus Aspergillus sp.

Two oxygenated ergostane-type steroids including one new compound, 3ß-hydroxy-5α,6ß-methoxyergosta-7,22-dien-15-one (1) along with a known analogue ergosta-6,22-dien-3ß,5α,8α-triol (2) were isolated from the crude extracts of the marine sponge-derived fungus Aspergillus sp. Their structures were elucidated on the basis of combined NMR and MS spectroscopic methods. Compound 1 was a marine ergostane-type steroid with two methoxy groups at C-5 and C-6, respectively. These oxygenated ergostane-type steroids were evaluated for their antibacterial activities against human or aquatic pathogens. Among them, compound 1 exhibited antibacterial activity against Staphylococcus aureus.