Prenatal LPS leads to increases in RAS expression within the PVN and overactivation of sympathetic outflow in offspring rats.

The renin-angiotensin system (RAS) and the sympathetic nervous system (SNS) are two major blood pressure-regulating systems. The link between the renal and cerebral RAS axes was provided by reflex activation of renal afferents and efferent sympathetic nerves. There is a self-sustaining enhancement of the brain and the intrarenal RAS. In this study, prenatal exposure to lipopolysaccharide (LPS) led to increased RAS activity in the paraventricular nucleus (PVN) and overactivation of sympathetic outflow, accompanied by increased production of reactive oxygen species (ROS) and disturbances between inhibitory and excitatory neurons in PVN. The AT1 receptor blocker losartan and α2 adrenergic receptor agonist clonidine in the PVN significantly decreased renal sympathetic nerve activity (RSNA) and synchronously reduced systolic blood pressure. Prenatal LPS stimulation caused H3 acetylation at H3K9 and H3K14 in the PVN, which suggested that epigenetic changes are involved in transmitting the prenatal adverse stimulative information to the next generation. Additionally, melatonin treatment during pregnancy reduced RAS activity and ROS levels in the PVN; balanced the activity of inhibitory and excitatory neurons in the PVN; increased urine sodium secretion; reduced RSNA and blood pressure. In conclusion, prenatal LPS leads to increased RAS expression within the PVN and overactivation of the sympathetic outflow, thereby contributing to hypertension in offspring rats. Melatonin is expected to be a promising agent for preventing prenatal LPS exposure-induced hypertension.

SERS and electrochemical dual-mode detection of miRNA-141 by using single Au@Ag nanowire as a new platform.

As biomarkers of cancer, the accurate and sensitive detection of microRNAs is of great significance. Therefore, we proposed a surface-enhanced Raman scattering (SERS)/electrochemical (EC) dual-mode nanosensor for sensitively detecting miRNA-141. The nanosensor uses Au@Ag nanowires as a novel SERS/EC sensing platform, which has the advantages of good biocompatibility, fast response, and high sensitivity. The dual-mode nanosensor can not only effectively overcome the problem of insufficient reliability of single signal, but also realize the amplification and stable output of the detection signal, to ensure the reliability and repeatability of miRNA detection. With this sensing strategy, the target miRNA-141 can be detected over a wide linear range (100 fM to 50 nM) (LOD of 18.4 fM for SERS and 16.0 fM for electrochemical methods). In addition, the process shows good selectivity and can distinguish miRNA-141 from other interfering miRNAs. The actual analysis of human serum samples also proves that our strategy has good reliability, repeatability, and has broad application prospects in the field of analysis and detection.

Lipidomic Profiling of Flammulina velutipes (Curtis) Singer (Agaricomycetes) through Ultra-Performance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Mass Spectrometry: Examining Lipid Dynamics Changes during Fruiting Body Formation and Development.

Flammulina velutipes (enokitake) is widely recognized for its nutritional and medicinal properties. Understanding the biochemical processes, such as lipid metabolism during fruiting body formation, is essential for enhancing mushroom cultivation and utilization. This study aimed at elucidating the dynamic lipidomic changes during seven growth stages of F. velutipes using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Our results revealed significant increases in ceramides along with the growth and a sharp decline in phosphatidylinositols from mycelial to primordial stages. Fatty acid esters of hydroxy fatty acids, recently discovered for their bioactivities, showed high intensities in the mycelial and primordial stages but decreased rapidly thereafter. These findings provide profound insights into the lipid profiles associated with mushroom morphology and development. This lipidomics study establishes a foundational understanding for future research in agricultural and food chemistry applications, potentially improving industrial production and quality control of F. velutipes.

Three Polyhedron-Based Metal-Organic Frameworks Exhibiting Excellent Acetylene Selective Adsorption.

The separation of acetylene (C2H2) from ethylene (C2H4) and ethane (C2H6) is crucial for the production of high-purity C2H2 and the recovery of other gases. Polyhedron-based metal-organic frameworks (PMOFs) are characterized by their spacious cavities, which facilitate gas trapping, and cage windows with varying sizes that enable gas screening. In this study, we carefully selected a class of PMOFs based on V-type tetracarboxylic acid linker (JLU-Liu22 containing benzene ring, JLU-Liu46 containing urea group and recombinant reconstructed In/Cu CBDA on the basis of JLU-Liu46) to study the relationship between pore environment and C2 adsorption and separation performance. Among the three compounds, JLU-Liu46 exhibits superior selectivity toward C2H2/C2H4 (2.06) as well as C2H2/C2H6 (2.43). Comparative structural analysis reveals that the exceptional adsorbed-C2H2 performance of JLU-Liu46 can be attributed to the synergistic effects arising from coordinatively unsaturated Cu sites combined with an optimal pore environment (matched pore size and polarity, urea functional group), resulting in a strong affinity between the framework and C2H2 molecules. Furthermore, transient breakthrough simulations of JLU-Liu46 confirmed its potential for separating C2H2 in ternary C2 gas.

A Blood Hepatocellular Carcinoma Signature Recognizes Very Small Tumor Nodules with Metastatic Traits.

Background and Aims: Hepatocellular carcinoma (HCC) cases with small nodules are commonly treated with radiofrequency ablation (RFA), but the recurrence rate remains high. This study aimed to establish a blood signature for identifying HCC with metastatic traits pre-RFA. Methods: Data from HCC patients treated between 2010 and 2017 were retrospectively collected. A blood signature for metastatic HCC was established based on blood levels of alpha-fetoprotein and des-γ-carboxy-prothrombin, cell-free DNA (cfDNA) mutations, and methylation changes in target genes in frozen-stored plasma samples that were collected before RFA performance. The HCC blood signature was validated in patients prospectively enrolled in 2021. Results: Of 251 HCC patients in the retrospective study, 33.9% experienced recurrence within 1 year post-RFA. The HCC blood signature identified from these patients included des-γ-carboxy-prothrombin ≥40 mAU/mL with cfDNA mutation score, where cfDNA mutations occurred in the genes of TP53, CTNNB1, and TERT promoter. This signature effectively predicted 1-year post-RFA recurrence of HCC with 92% specificity and 91% sensitivity in the retrospective dataset, and with 87% specificity and 76% sensitivity in the prospective dataset (n=32 patients). Among 14 cases in the prospective study with biopsy tissues available, positivity for the HCC blood signature was associated with a higher HCC tissue score and shorter distance between HCC cells and microvasculature. Conclusions: This study established an HCC blood signature in pre-RFA blood that potentially reflects HCC with metastatic traits and may be valuable for predicting the disease's early recurrence post-RFA.

Anti-CRMP2 antibody induces anxiety-like behavior and increases pyramidal neuron excitability in mice.

BACKGROUND: We have previously identified auto-antibody (Ab) to collapsin response mediator protein 2 (CRMP2) in patients with encephalitis. The present study aims to evaluate the pathogenic effects of anti-CRMP2 Ab. METHODS: Recombinant CRMP2 protein was injected subcutaneously into mice to establish an active immune mouse model with anti-CRMP2 Ab. Behavioral assessments, histopathological staining, and electrophysiological testing were performed to identify any pathogenic changes. RESULTS: The mice exhibited signs of impaired motor coordination four weeks post-immunization of CRMP2 protein. Moreover, CRMP2 immunized mice for eight weeks showed anxiety-like behaviors indicating by tests of open field and the elevated plus maze. After incubating the CA1 region of hippocampal brain section with the sera from CRMP2 immunized mice, the whole-cell path-clamp recordings showed increased excitability of pyramidal neurons. However, no obvious inflammation and infiltration of immune cells were observed by histopathological analysis. Western blot showed that the phosphorylation levels of CRMP2-Thr514 and -Ser522 were not affected. CONCLUSION: In an active immunization model with CRMP2 protein, impaired coordination and anxiety-like behaviors were observed. Also, anti-CRMP2 Abs containing sera heightened the excitability of hippocampal pyramidal neurons in vitro, which imply the pathogenic effects of anti-CRMP2 Ab.

Research perspective in the clinical management of Kawasaki disease.

This study examines research perspective in the clinical diagnosis, treatment, and prevention of cardiovascular complications in Kawasaki Disease (KD). Starting with an overview of the disease, it introduces KD's clinical manifestations, etiology, epidemiological features, and its impact on the cardiovascular system. Subsequently, the study discusses in detail the diagnostic methods, pathological mechanisms, and treatment strategies for KD, including foundational and emerging approaches such as high-dose intravenous immunoglobulin and aspirin therapy, biologic therapy, and corticosteroid pulse therapy. Additionally, it outlines strategies for preventing cardiovascular complications, including early risk assessment and long-term management. The study also explores the intersection of the COVID-19 pandemic with an increase in KD-like symptoms, emphasizing the need for further studies on the association between SARS-CoV-2 and KD. Lastly, it explores future research directions to enhance understanding of KD and improve patient outcomes and quality of life. This study provides valuable insights into the comprehensive treatment and management of KD and highlights avenues for future research.

Maternal high fat diet induces circadian clock-independent endocrine alterations impacting the metabolism of the offspring.

Maternal obesity has long-term effects on offspring metabolic health. Among the potential mechanisms, prior research has indicated potential disruptions in circadian rhythms and gut microbiota in the offspring. To challenge this hypothesis, we implemented a maternal high fat diet regimen before and during pregnancy, followed by a standard diet after birth. Our findings confirm that maternal obesity impacts offspring birth weight and glucose and lipid metabolisms. However, we found minimal impact on circadian rhythms and microbiota that are predominantly driven by the feeding/fasting cycle. Notably, maternal obesity altered rhythmic liver gene expression, affecting mitochondrial function and inflammatory response without disrupting the hepatic circadian clock. These changes could be explained by a masculinization of liver gene expression similar to the changes observed in polycystic ovarian syndrome. Intriguingly, such alterations seem to provide the first-generation offspring with a degree of protection against obesity when exposed to a high fat diet.

Effects of a semi-interpenetrating network hydrogel loaded with oridonin and DNase-I on the healing of chemoradiotherapy-induced oral mucositis.

The aim of this study was to develop a semi-interpenetrating network (IPN) hydrogel system suitable for the oral environment, capable of controlled release of DNase-I and oridonin (ORI), to exert antimicrobial, anti-inflammatory, and reparative effects on chemoradiotherapy-induced oral mucositis (OM). This IPN was based on the combination of ε-polylysine (PLL) and hetastarch (HES), loaded with DNase-I and ORI (ORI/DNase-I/IPN) for OM treatment. In vitro studies were conducted to evaluate degradation, adhesion, release analysis, and bioactivity including cell proliferation and wound healing assays using epidermal keratinocyte and fibroblast cell lines. Furthermore, the therapeutic effects of ORI/DNase-I/IPN were investigated in vivo using Sprague-Dawley (SD) rats with chemoradiotherapy-induced OM. The results demonstrated that the IPN exhibited excellent adhesion to wet mucous membranes, and the two drugs co-encapsulated in the hydrogel were released in a controlled manner, exerting inhibitory effects on bacteria and degrading NETs in wound tissues. The in vivo wound repair effect, microbiological assays, H&E and Masson staining supported the non-toxicity of ORI/DNase-I/IPN, as well as its ability to accelerate the healing of oral ulcers and reduce inflammation. Overall, ORI/DNase-I/IPN demonstrated a therapeutic effect on OM in rats by significantly accelerating the healing process. These findings provide new insights into possible therapies for OM.

Predicting biomarkers related to idiopathic pulmonary fibrosis: Robust ranking aggregation analysis and animal experiment verification.

Idiopathic pulmonary fibrosis (IPF) is a progressive and incurable lung disease characterized by unknown etiology. This study employs robust ranking aggregation to identify consistent differential genes across multiple datasets, aiming to enhance prognostic evaluation and facilitate the development of more effective immunotherapy strategies for IPF. Using the GSE10667, GSE110147, and GSE24206 datasets, the analysis identifies 92 robust differentially expressed genes (DEGs), including SPP1, IGF1, ASPN, and KLHL13, highlighted as potential biomarkers through machine learning and experimental validation. Additionally, significant differences in immune cell types between IPF samples and controls, such as Plasma cells, Macrophages M0, Mast cells resting, T cells CD8, and NK cells resting, inform the construction of diagnostic and survival prediction models, demonstrating good applicability. These findings provide insights into IPF pathophysiology and suggest potential therapeutic targets.

Information disclosure, multifaceted collaborative governance, and carbon total factor productivity---an evaluation of the effects of the 'environmental information disclosure pilot' policy based on double machine learning.

As an environmental institutional arrangement related to the information factor of the diversified participation of the government, enterprises, the media and the public, the environmental information disclosure pilot policy, can and how to affect the carbon emission efficiency through multiple collaborative governance? This study uses the Environmental Information Disclosure Pilot Policy implemented in China in 2007 as a quasi-natural experiment. It examines 284 prefecture-level cities from 2004 to 2021 and A-share listed companies from 2004 to 2021, constructing an evolutionary game dynamic model involving government, public, enterprises, and media. Through mathematical derivation and assignment analysis, it explores how environmental information impacts carbon emission efficiency under multifaceted collaborative governance, assessing the strategic choices and evolutionary paths of stakeholders before and after policy implementation, using methods like double machine learning for empirical testing. The study highlights several key findings: First, the implementation of the Environmental Information Disclosure Pilot Policy significantly enhanced carbon total factor productivity in pilot cities, as revealed through Double Machine Learning (DML) policy effect evaluation. Second, adjustments for potential estimation biases using Doubly Debiased LASSO (DDL) regression indicated that environmental information disclosure impacts carbon productivity via a governance mechanism involving government, public, media, and enterprises. Third, a causal pathway analysis suggested a sequential logic in governance effectiveness, starting from governmental environmental focus to corporate environmental responsibility. Lastly, integrating DML with a moderation effect model revealed a regulatory role for environmental legislation construction, offering new insights for achieving dual carbon goals and enriching empirical evidence on information's impact on carbon emission efficiency.

Sex- and age-specific associations of serum essential elements with diabetes among the Chinese adults: a community-based cross-sectional study.

BACKGROUND: Although several studies have found the relationship between essential elements and diabetes, the studies about the association of essential elements with diabetes diagnosed according to an oral glucose tolerance test (OGTT) and glycated hemoglobin (HbA1c) in a sex- and age-specific manner were limited. To investigate the linear and nonlinear relationship of five essential elements including iron (Fe), copper (Cu), Zinc (Zn), magnesium (Mg), and calcium (Ca) with diabetes, fasting plasma glucose (FPG), 2-h postprandial plasma glucose (PPG), and HbA1c and to evaluate the sex- and age-specific heterogeneities in these relationships. METHODS: A total of 8392 community-dwelling adults were recruited to complete a questionnaire and undergo checkups of anthropometric parameters and serum levels of five metals (Fe, Cu, Zn, Mg, and Ca). The multivariable logistic and linear regression, the restricted cubic spline (RCS) analysis, and subgroup analysis were applied to find the associations between the essential elements and the prevalence of diabetes as well as FPG, PPG, and HbA1c. RESULTS: In the multivariable logistic regression and multivariable linear regression, serum Cu was positively associated with FPG, PPG, and HbA1c while serum Mg was significantly inversely correlated with FPG, PPG, HbA1c, and diabetes (all P < 0.001). In the RCS analysis, the non-linear relationship of Cu and diabetes (P < 0.001) was found. In the subgroup analysis, stronger positive associations of Cu with diabetes (P for interaction = 0.027) and PPG (P for interaction = 0.002) were found in younger women. CONCLUSIONS: These findings may lead to more appropriate approaches to essential elements supplementation in people with diabetes of different ages and sexes. However, more prospective cohort and experimental studies are needed to probe the possible mechanism of sex- and age-specific associations between serum essential elements and diabetes.

Circulating exosomal circRNA-miRNA-mRNA network in a familial partial lipodystrophy type 3 family with a novel PPARG frameshift mutation c.418dup.

Familial Partial Lipodystrophy 3 (FPLD3) is a rare genetic disorder caused by loss-of-function mutations in the PPARG gene, characterized by a selective absence of subcutaneous fat and associated metabolic complications. However, the molecular mechanisms of FPLD3 remain unclear. In this study, we recruited a 17-year-old Chinese female with FPLD3 and her family, identifying a novel PPARG frameshift mutation (exon 4: c.418dup: p.R140Kfs*7) that truncates the PPARγ protein at the 7th amino acid, significantly expanding the genetic landscape of FPLD3. By performing next generation sequencing of circular RNAs (circRNAs), microRNAs (miRNAs), and mRNAs in plasma exosomes, we discovered 59 circRNAs, 57 miRNAs, and 299 mRNAs were significantly altered in the mutation carriers in the comparison of healthy controls. Integration analysis highlighted that the circ_0001597-miR-671-5p pair and 18 mRNAs might be incorporated into the metabolic regulatory networks of the FPLD3 induced by the novel PPARG mutation. Functional annotation suggested that these genes were significantly enriched in glucose and lipid metabolism related pathways. Among the circRNA-miRNA-mRNA network, we identified two critical regulators, EGR1, a key transcription factor known for its role in insulin signaling pathways and lipid metabolism, and AGPAT3, which gets involved in the biosynthesis of triglycerides and lipolysis. Circ_0001597 regulates the expression of these genes through miR-671-5p, potentially contributing to the pathophysiology of FPLD3. Overall, this study clarified a circulating exosomal circRNA-miRNA-mRNA network in a FPLD3 family with a novel PPARG mutation, providing evidence for exploring promising biomarkers and developing novel therapeutic strategies for this rare genetic disorder.

RHOF activation of AKT/ß-catenin signaling pathway drives acute myeloid leukemia progression and chemotherapy resistance.

Acute myeloid leukemia (AML) is a clonal malignancy originating from leukemia stem cells, characterized by a poor prognosis, underscoring the necessity for novel therapeutic targets and treatment methodologies. This study focuses on Ras homolog family member F, filopodia associated (RHOF), a Rho guanosine triphosphatase (GTPase) family member. We found that RHOF is overexpressed in AML, correlating with an adverse prognosis. Our gain- and loss-of-function experiments revealed that RHOF overexpression enhances proliferation and impedes apoptosis in AML cells in vitro. Conversely, genetic suppression of RHOF markedly reduced the leukemia burden in a human AML xenograft mouse model. Furthermore, we investigated the synergistic effect of RHOF downregulation and chemotherapy, demonstrating significant therapeutic efficacy in vivo. Mechanistically, RHOF activates the AKT/ß-catenin signaling pathway, thereby accelerating the progression of AML. Our findings elucidate the pivotal role of RHOF in AML pathogenesis and propose RHOF inhibition as a promising therapeutic approach for AML management.

ZbMYB111 Expression Positively Regulates ZbUFGT-Mediated Anthocyanin Biosynthesis in Zanthoxylum bungeanum with the Involvement of ZbbHLH2.

Anthocyanin (ACN)-derived pigmentation in the red Zanthoxylum bungeanum peel is an essential commercial trait. Therefore, exploring the metabolic regulatory networks involved in peel ACN levels in this species is crucial for improving its quality. However, its underlying transcriptional regulatory mechanisms are still unknown. This transcriptomic and bioinformatics study not only discovered a new TF (ZbMYB111) as a potential regulator for ACN biosynthesis in Z. bungeanum peel, but also deciphered the underlying molecular mechanisms of ACN biosynthesis. Overexpression of ZbMYB111 and flavonoid 3-O-glucosyltransferase (ZbUFGT) induced ACN accumulation in both Z. bungeanum peels and callus along with Arabidopsis thaliana and tobacco flowers, whereas their silencing impaired ACN biosynthesis. Therefore, the dual-luciferase reporter, yeast-one-hybrid, and electrophoretic mobility shift assays showed that ZbMYB111 directly interacted with the ZbUFGT promoter to activate its expression. This diverted the secondary metabolism toward the ACN pathway, thereby promoting ACN accumulation.

Three new flavonoids from the roots of Sophora tonkinensis.

Three new flavonoids including two isoflavanones sophortones A and B (1 and 2), and one chalcone sophortone C (3) were isolated from the roots of Sophora tonkinensis. Their structures were established by UV, IR, HRESIMS, and NMR data. The absolute configurations of 1 and 2 were determined by electronic circular dichroism (ECD) calculations.

Ginkgo biloba for Tardive Dyskinesia and Plasma MnSOD Activity: Association with MnSOD Ala-9Val Variant.

BACKGROUND: Excessive free radicals are implicated in the pathophysiology of tardive dyskinesia (TD), and Ginkgo biloba extract (EGb761) scavenges free radicals, thereby enhancing antioxidant enzymes such as mitochondrial manganese superoxide dismutase (MnSOD). This study examined whether EGb761 treatment would improve TD symptoms and increase MnSOD activity, particularly in TD patients with specific MnSOD Val-9Ala genotype. METHODS: An EGb761 (240 mg/day) 12-week double-blind clinical trial with 157 TD patients was randomized. The severity of TD was measured by the Abnormal Involuntary Movement Scale (AIMS) and plasma MnSOD activity was assayed before and after 12 weeks of treatment. Further, in an expanded sample, we compared MnSOD activity in 159 TD, 227 non-TD and 280 healthy controls, as well as the allele frequencies and genotypes for the MnSOD Ala-9Val polymorphism in 352 TD, 486 non-TD and 1150 healthy controls. RESULTS: EGb761 significantly reduced TD symptoms and increased MnSOD activity in TD patients compared to placebo (both p < 0.01). Moreover, we found an interaction between genotype and treatment response (p < 0.001). Furthermore, in the EGb761 group, patients carrying the Ala allele displayed a significantly lower AIMS total score than patients with the Val/Val genotype. In addition, MnSOD activity was significantly lower at baseline in TD patients compared with healthy controls or non-TD patients. CONCLUSION: EGb761 treatment enhanced low MnSOD activity in TD patients and produced greater improvement in TD symptoms in patients with the Ala allele of the MnSOD Ala-9Val polymorphism.

APOE expression in papillary thyroid carcinoma: Influencing tumor progression and macrophage polarization.

BACKGROUND: As metastatic papillary thyroid carcinoma becomes increasingly challenging to treat, immunotherapy has emerged as a new research direction. Tumor-associated macrophages (TAMs) influence the occurrence, invasion, and metastasis of tumors. Apolipoprotein E (APOE) can regulate the polarization changes of macrophages and participate in the remodeling of the tumor microenvironment. However, the role of APOE in regulating the polarization and biological functions of TAMs in papillary thyroid carcinoma (PTC) remains unclear, as it acts as a dual biomarker. METHODS: We probed APOE expression in PTC tissues using immunohistochemical staining. A cell co-culture model was established where different APOE-expressing K1 cells were co-cultured with THP-1-derived M0 macrophages. An in-depth analysis of macrophage polarization behavior was performed using real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and western blotting. Subsequently, the impact of APOE-regulated macrophages on tumor cell behavior, especially proliferation, migration, and invasion, was evaluated utilizing IncuCyte ZOOM system, flow cytometry, colony formation, and scratch experiments. Finally, we used a xenograft model to confirm the effects of APOE on PTC tumorigenesis. RESULTS: Tumor dimensions, stage, and lymphatic metastases were significantly associated with increased APOE expression in PTC tissues. K1 cells were markedly limited in their proliferation, migration, and invasion abilities when APOE expression was silenced, a process mediated by the PI3K/Akt/NF-κB signaling axis. Moreover, APOE is a key facilitator of the enhancement of the anti-inflammatory cytokines IL-10 and TGF-ß1. In PTC cellular models, APOE contributed to the phenotypic shift of THP-1 derived macrophages towards an M2 phenotypic polarization, predominantly through the modulation of IL-10. Furthermore, in vivo studies involving athymic nude mice have demonstrated pivotal role of APOE in tumor progression and the induction of M2-like TAM polarization. CONCLUSION: Our results elucidated that APOE could promote the shift of TAMs from M0-type to M2-type polarization by regulating inflammatory factors expressions in K1 cell through the PI3K/Akt/NF-κB pathway. These findings are crucial for understanding the molecular mechanisms underlying PTC pathogenesis and for developing immunological drugs to treat this disease.