Ferroptosis-Related Gene Signatures in Epilepsy: Diagnostic and Immune Insights.

Epilepsy is characterized by a multifaceted aetiology. Ferroptosis has recently been implicated in seizure pathophysiology, although its mechanistic role in epilepsy remains obscure. We examined the roles of ferroptosis-related genes (FRGs) in epilepsy cohorts from the GSE143272 dataset. We investigated the associations between gene expression and the immune response by performing CIBERSORT and MCP-counter analyses. By employing unsupervised consensus clustering and weighted gene coexpression network analysis (WGCNA), we delineated robust gene clusters across cohorts. Single-cell RNA sequencing data from the GSE201048 dataset provided insights into the interactions between pivotal ferroptosis-related genes and immune cells. Additionally, we employed qRT‒PCR technology to measure the levels of these central genes in the tissues of epileptic patients and mice. Our findings revealed seven pivotal genes (TFRC, POR, PTGS2, RELA, PGD, TRIM21, and QSOX1) at the forefront in epilepsy specimens. A diagnostic model harnessing these genes exhibited substantial efficacy (AUC = 0.913). Similarly, the qRT‒PCR analysis of samples from epileptic patients and mouse epileptic brain tissues substantiated these findings. Stratification of 91 patients with epilepsy via WGCNA, based on gene expression, revealed distinct immunological profiles. The scRNA-seq data further indicated increased expression of central genes in macrophages and microglia. Notably, these cells and those with elevated ferroptosis scores were significantly enriched in inflammation-related pathways. These findings support the strong involvement of FRGs in the pathogenesis of epilepsy, particularly neuroinflammation. These central genes hold promise as novel diagnostic biomarkers for epilepsy.

Cinnamaldehyde: Pharmacokinetics, anticancer properties and therapeutic potential (Review).

Cancer incidence is increasing globally, presenting a growing public health challenge. While anticancer drugs are crucial in treatment, their limitations, including poor targeting ability and high toxicity, hinder effectiveness and patient safety, requiring relentless scientific research and technological advancements to develop safer and more effective therapeutics. Cinnamaldehyde (CA), an active compound derived from the natural plant cinnamon, has garnered attention in pharmacological research due to its diverse therapeutic applications. CA has potential in treating a wide array of conditions, including cardiovascular diseases, diabetes, inflammatory disorders and various forms of cancer. The present review comprehensively summarizes the physicochemical and pharmacokinetic profiles of CA, and delves into the latest advancements in elucidating its potential mechanisms and targets across various cancer types. CA and its derivatives have antitumor effects, which encompass inhibiting cell proliferation, arresting the cell cycle, inducing apoptosis, limiting cell migration and invasion, and suppressing angiogenesis. Additionally, the present review explores targeted formulations of CA, laying a scientific foundation for further exploration of its implications in cancer prevention and treatment strategies.

Cryogenic Photoelectron Spectroscopic and Theoretical Study of the Electronic and Geometric Structures of Undercoordinated Osmium Chloride Anions OsCln- (n = 3-5).

A series of anionic transition metal halides, OsCln- (n = 3-5), have been investigated using a newly developed, home-constructed, cryogenic anion cluster photoelectron spectroscopy. The target anionic species are generated through collision-induced dissociation in a two-stage ion funnel. The measured vertical detachment energies (VDEs) are 3.48, 4.54, and 4.81 eV for n = 3, 4, and 5, respectively. Density functional theory calculations at the B3LYP-D3(BJ)//aug-cc-pVTZ(-pp) level predict the lowest energy structures of the atomic form of OsCln- (n = 3-5) to be a quintet triangle, quartet square, and quintet square-based pyramid, respectively. The CCSD(T)-calculated VDEs and corresponding adiabatic detachment energies agree well with our experimental measurements. Analysis of the corresponding frontier molecular orbitals and charge density differences suggests that the d-orbitals of the transition metal Os play a primary role in the single-photon detachment processes, and the detached electrons originating from different molecular orbitals are distinguishable.

Relationship of weight-adjusted waist index and developmental disabilities in children 6 to 17 years of age: a cross-sectional study.

Purpose: The development of multiple system diseases is increased by obesity. However, the connection between obesity and developmental disabilities (DDs) in children is unclear. As an obesity index, the weight-adjusted waist index (WWI) assessed fat distribution and muscle mass. In this study, we examined the correlation between WWI and DDs among children 6 to 17 years of age. Methods: This study used data from the National Health and Nutrition Examination Survey database (NHANES) covering 2003 to 2018, which included the data of 17,899 participants between 6 and 17 years of age. Data regarding their waist circumference, weight, and DDs were collected via physical examinations and questionnaire, respectively. A person's WWI is calculated by dividing their waist circumference by their weight squared. The correlation between WWI and DDs was studied using weighted multiple logistic regression models. Additionally, a sensitivity analysis was conducted utilizing a generalized additive model and smooth curve fitting. Results: After adjusting for all covariates, WWI was positively related to DDs in children ages 6-17. Based on the sensitivity analysis, the correlation between the WWI and prevalence of DDs remained consistent across subgroups. Additionally, there was a J-shaped correlation between the WWI and the prevalence of DDs in children ages 6 through 11. Conclusion: Children 6-17 years of age with a high WWI were at greater risk for DDs; however, the causal relationships and potential mechanisms require further exploration.

Tumor suppressor FRMD3 controls mammary epithelial cell fate determination via notch signaling pathway.

The luminal-to-basal transition in mammary epithelial cells (MECs) is accompanied by changes in epithelial cell lineage plasticity; however, the underlying mechanism remains elusive. Here, we report that deficiency of Frmd3 inhibits mammary gland lineage development and induces stemness of MECs, subsequently leading to the occurrence of triple-negative breast cancer. Loss of Frmd3 in PyMT mice results in a luminal-to-basal transition phenotype. Single-cell RNA sequencing of MECs indicated that knockout of Frmd3 inhibits the Notch signaling pathway. Mechanistically, FERM domain-containing protein 3 (FRMD3) promotes the degradation of Disheveled-2 by disrupting its interaction with deubiquitinase USP9x. FRMD3 also interrupts the interaction of Disheveled-2 with CK1, FOXK1/2, and NICD and decreases Disheveled-2 phosphorylation and nuclear localization, thereby impairing Notch-dependent luminal epithelial lineage plasticity in MECs. A low level of FRMD3 predicts poor outcomes for breast cancer patients. Together, we demonstrated that FRMD3 is a tumor suppressor that functions as an endogenous activator of the Notch signaling pathway, facilitating the basal-to-luminal transformation in MECs.

Molecular characteristics and evaluation of the phenotypic detection of carbapenemases among Enterobacterales and Pseudomonas via whole genome sequencing.

Background/purposes: The continuously increasing carbapenem resistance within Enterobacterales and Pseudomonas poses a threat to public health, nevertheless, the molecular characteristics of which in southern China still remain limited. And carbapenemase identification is a key factor in effective early therapy of carbapenem-resistant bacteria infections. We aimed to determine the molecular characteristics of these pathogens and compare commercial combined disc tests (CDTs) with the modified carbapenem inactivation method (mCIM) and EDTA-CIM (eCIM) in detecting and distinguishing carbapenemases using whole genome sequencing (WGS). Methods: A total of 78 Enterobacterales, 30 Pseudomonas were obtained from two tertiary hospitals in southern China. Susceptibility tests were conducted using an automated VITEK2 compact system with confirmation via the Kirby-Bauer method. The WGS was conducted on all clinical isolates and the molecular characteristics were analyzed by screening the whole genome sequences. CDTs with or without cloxacillin, mCIM, and eCIM, were performed and compared by taking WGS results as the benchmark. Results: A total of 103 carbapenem non-susceptible and 5 carbapenem susceptible bacteria were determined, with Klebsiella pneumoniae (42.7%), Pseudomonas aeruginosa (23.3%) and Escherichia coli (18.4%) being most prevalent. Carbapenemase genes were detected in 58 (56.3%) of the 103 carbapenem-non-susceptible clinical isolates, including 46 NDM, 6 KPC, 3 IMP, 1 IPM+VIM,1NDM+KPC, and 1 OXA-181. Carbapenemase-producing isolates were detected more frequently in Enterobacterales (76.3%). Among K. pneumoniae, the major sequence types were st307 and st11, while among E. coli and P. aeruginosa, the most prevalent ones were st410 and st242 respectively. For carbapenemase detection in Enterobacterales, the mCIM method achieved 100.00% (95% CI, 92.13-100.00%) sensitivity and 94.44% (70.63-99.71%) specificity (kappa, 0.96); for Pseudomonas, detection sensitivity was 100% (5.46-100.00%), and 100% (84.50-100.00%) specificity (kappa, 0.65). Commercial CDT carbapenemase detection sensitivity for Enterobacterales was 96.49% (86.84-99.39%), and 95.24% (74.13-99.75%) specificity (kappa, 0.90); for Pseudomonas, carbapenemase detection sensitivity was 100.00% (5.46-100.00%) and 37.93% (21.30-57.64%) specificity (kappa, 0.04). When cloxacillin testing was added, CDT specificity reached 84.61% (64.27-94.95%). Conclusion: The molecular epidemiology of carbapenem-non-susceptible isolates from pediatric patients in Southern China exhibited distinctive characteristics. Both the mCIM-eCIM combination and CDT methods effectively detected and differentiated carbapenemases among Enterobacterales isolates, and the former performed better than CDT among Pseudomonas.

Effect of Metagenomic Next-Generation Sequencing on Clinical Outcomes of Patients with Severe Community-Acquired Pneumonia in ICU: A Multicenter Randomized Controlled Trial.

BACKGROUND: Metagenomic next-generation sequencing (mNGS) was previously established as a method that can increase the pathogen identification rate in patients with severe community-acquired pneumonia (SCAP). RESEARCH QUESTION: What is the impact on clinical outcomes of mNGS of BALF in ICU patients with SCAP? STUDY DESIGN AND METHODS: A multicenter, randomized, open-label clinical trial was conducted in 10 ICUs. Patients were randomized in a 1:1 ratio to undergo BALF with the conventional microbiological tests (CMTs) only (CMT group) or both BALF with mNGS and CMTs (mNGS group). The primary outcome was the time to clinical improvement, defined as the time from randomization to either an improvement of two points on a six-category ordinal scale or discharge from the ICU, whichever occurred first. RESULTS: A total of 349 patients were randomized between January 1, 2021, to November 18, 2022, of whom 170 were assigned to the CMT group and 179 to the mNGS group. In the intention-to-treat analysis, the time to clinical improvement was better in the mNGS group than that in the CMT group (10 d vs. 13 d, difference: -2.0 [95% CI = -3.0 to 0.0]). Similar results were obtained in the per-protocol analysis. The proportion of patients with clinical improvement within 14 d was significantly higher in the mNGS group (62.0%) than that in the CMT group (46.5%). There was no significant difference in other secondary outcomes. CONCLUSION: MNGS combined with CMTs reduced the time to clinical improvement for patients with SCAP, compared to the use of CMTs alone.

Antioxidation Activity Enhancement by Intramolecular Hydrogen Bond and Non-Browning Mechanism of Active Ingredients in Rosemary: Carnosic Acid and Carnosol.

Rosemary is one of the most promising, versatile, and studied natural preservatives. Carnosic acid (CA) and carnosol (CARN), as the primary active ingredients of rosemary extracts, have little difference in structure, but their antioxidant activities vary significantly, depending on the system studied. The underlying molecular mechanisms remain unclear. By means of optical spectroscopies, stopped-flow, laser photolysis, and density functional theory (DFT) calculations, we have compared CA and CARN between their reaction dynamics of radical scavenging, metal ion chelation, and oxidation inhibition in lipid emulsion and beef, as well as between their interactions with ß-carotene (ß-Car). For reference, 3-isopropyl catechol (IC), which is structurally similar to the active groups of CA and CARN, was studied in parallel. It is found for CA that the intramolecular hydrogen bond can boost the acidity of its phenol hydroxyl and that the synergistic effect with ß-Car can substantially enhance its antioxidation activity in the model systems of lipid and meat via the CA-to-ß-Car electron transfer reaction. The substitution of A and B rings on the catechol group in both CA and CARN limits browning caused by their formation of oxidative products as antioxidants.

Exploring genetic codon expansion for unnatural amino acid incorporation in filamentous fungus Aspergillus nidulans.

Genetic code expansion technology allows the incorporation of unnatural amino acids (UAAs) into proteins, which is useful in protein engineering, synthetic biology, and gene therapy. Despite its potential applications in various species, filamentous fungi remain unexplored. This study aims to address this gap by developing these techniques in Aspergillus nidulans. We introduced an amber stop codon into a specific sequence within the reporter gene expressed in A. nidulans and replaced the anticodon of the fungal tRNATyr with CUA. This resulted in the synthesis of the target protein, confirming the occurrence of amber suppression in the fungus. When exogenous E. coli tRNATyrCUA (Ec. tRNATyrCUA) and E. coli tyrosyl-tRNA (Ec.TyrRS) were introduced into A. nidulans, they successfully synthesized the target protein via amber suppression and were shown to be orthogonal to the fungal translation system. By replacing the wild-type Ec.TyrRS with a mutant with a higher affinity for the UAA O-methyl-L-tyrosine, the fungal system was able to initiate the synthesis of the UAA-labeled protein (UAA-protein). We further increased the expression level of the UAA-protein through several rational modifications. The successful development of a genetic code expansion technique for A. nidulans has introduced a potentially valuable approach to the study of fungal protein structure and function.

HMGA2 promotes resistance against paclitaxel by targeting the p53 signaling pathway in colorectal cancer cells.

Colorectal cancer is one of the most common malignancies and ranks second in terms of cancer-related mortality worldwide due to its metastasis, drug resistance, and reoccurrence. High-mobility gene group A2 (HMGA2) is overexpressed in colorectal cancer, contributing to the aggressiveness of tumor malignance, and promotes drug resistance in many types of cancer. However, the underlying molecular mechanism of HMGA2 is yet to be elucidated. In this study, we showed that HMGA2 is overexpressed in colorectal cancer tissue, and knockdown of HMGA2 significantly inhibited colorectal cancer cell growth and migratory capability. HMGA2 regulates the cancer cell response to a widely used anti-cancer drug, paclitaxel (PTX). HMGA2 knockdown increased cell death, whereas HMGA2 overexpression decreased cell death after PTX treatment. Furthermore, lower reactive oxygen species (ROS) levels and mitochondrial potential were detected in HMGA2 overexpression cells after PTX treatment. However, HMGA2 knockdown produced the opposite effect. RNA sequencing showed a p53 signaling pathway-dependent regulation in HMGA2 knockdown cells. Combined with p53 inhibitors and HMGA2 knockdown, a synergetic effect of more cell death was observed in colorectal cancer cells after PTX treatment. Thus, we showed that HMGA2 can activate p53 signaling to regulate colorectal cancer cell death after PTX treatment. Altogether, our results reveal novel insights into the molecular mechanisms underlying HMGA2-mediated cancer cell resistance against PTX and highlight the potential of targeting HMGA2 and p53 signaling for the therapeutic investigation of colorectal cancer.

Disrupted Dynamic Network Attribution Associated with Gait Disorder in Cerebral Small Vessel Disease.

Background and Aims: Previous research has focused on static functional connectivity in gait disorders caused by cerebral small vessel disease (CSVD), neglecting dynamic functional connections and network attribution. This study aims to investigate alterations in dynamic functional network connectivity (dFNC) and topological organization variance in CSVD-related gait disorders. Methods: A total of 85 patients with CSVD, including 41 patients with CSVD and gait disorders (CSVD-GD), 44 patients with CSVD and non-gait disorders (CSVD-NGD), and 32 healthy controls (HC), were enrolled in this study. Five networks composed of 10 independent components were selected using independent component analysis. Sliding time window and k-means clustering methods were used for dFNC analysis. The relationship between alterations in the dFNC properties and gait metrics was further assessed. Results: Three reproducible dFNC states were determined (State 1: sparsely connected, State 2: intermediate pattern, and State 3: strongly connected). CSVD-GD showed significantly higher fractional windows (FW) and mean dwell time (MDT) in State 1 compared with CSVD-NGD. Higher local efficiency variance was observed in the CSVD-GD group compared with HC, but no differences were found in the global efficiency comparison. Both the FW and MDT in State 1 were negatively correlated with gait speed and step length, and the relationship between MDT of State 1 and gait speed was mediated by overall cognition, information processing speed, and executive function. Conclusions: Our study uncovered abnormal dFNC indicators and variations in topological organization in CSVD-GD, offering potential early prediction indicators and freshening insights into the underlying pathogenesis of gait disturbances in CSVD.

The Role of Bacteria in Central Nervous System Tumors: Opportunities and Challenges.

Tumors of the central nervous system (CNS) are severe and refractory diseases with poor prognosis, especially for patients with malignant glioblastoma and brain metastases. Currently, numerous studies have explored the potential role of bacteria and intestinal flora in tumor development and treatment. Bacteria can penetrate the blood-brain barrier (BBB), targeting the hypoxic microenvironment at the core of tumors, thereby eliminating tumors and activating both the innate and adaptive immune responses, rendering them promising therapeutic agents for CNS tumors. In addition, engineered bacteria and derivatives, such as bacterial membrane proteins and bacterial spores, can also be used as good candidate carriers for targeted drug delivery. Moreover, the intestinal flora can regulate CNS tumor metabolism and influence the immune microenvironment through the "gut-brain axis". Therefore, bacterial anti-tumor therapy, engineered bacterial targeted drug delivery, and intervention of the intestinal flora provide therapeutic modalities for the treatment of CNS tumors. In this paper, we performed a comprehensive review of the mechanisms and therapeutic practices of bacterial therapy for CNS tumors and discussed potential future research directions in this field.

Rapid response of fly populations to gene dosage across development and generations.

Although the effects of genetic and environmental perturbations on multicellular organisms are rarely restricted to single phenotypic layers, our current understanding of how developmental programs react to these challenges remains limited. Here, we have examined the phenotypic consequences of disturbing the bicoid regulatory network in early Drosophila embryos. We generated flies with two extra copies of bicoid, which causes a posterior shift of the network's regulatory outputs and a decrease in fitness. We subjected these flies to EMS mutagenesis, followed by experimental evolution. After only 8-15 generations, experimental populations have normalized patterns of gene expression and increased survival. Using a phenomics approach, we find that populations were normalized through rapid increases in embryo size driven by maternal changes in metabolism and ovariole development. We extend our results to additional populations of flies, demonstrating predictability. Together, our results necessitate a broader view of regulatory network evolution at the systems level.

Tea Polysaccharide Ameliorates High-Fat Diet-Induced Renal Tubular Ectopic Lipid Deposition via Regulating the Dynamic Balance of Lipogenesis and Lipolysis.

Renal tubular ectopic lipid deposition (ELD) plays a significant role in the development of chronic kidney disease, posing a great threat to human health. The present work aimed to explore the intervention effect and potential molecular mechanism of a purified tea polysaccharide (TPS3A) on renal tubular ELD. The results demonstrated that TPS3A effectively improved kidney function and slowed the progression of tubulointerstitial fibrosis in high-fat-diet (HFD)-exposed ApoE-/- mice. Additionally, TPS3A notably suppressed lipogenesis and enhanced lipolysis, as shown by the downregulation of lipogenesis markers (SREBP-1 and FAS) and the upregulation of lipolysis markers (HSL and ATGL), thereby reducing renal tubular ELD in HFD-fed ApoE-/- mice and palmitic-acid-stimulated HK-2 cells. The AMPK-SIRT1-FoxO1 axis is a core signal pathway in regulating lipid deposition. Consistently, TPS3A significantly increased the levels of phosphorylated-AMPK, SIRT1, and deacetylation of Ac-FoxO1. However, these effects of TPS3A on lipogenesis and lipolysis were abolished by AMPK siRNA, SIRT1 siRNA, and FoxO1 inhibitor, resulting in exacerbated lipid deposition. Taken together, TPS3A shows promise in ameliorating renal tubular ELD by inhibiting lipogenesis and promoting lipolysis through the AMPK-SIRT1-FoxO1 signaling pathway.

HER2-targeting CAR-T cells show highly efficient anti-tumor activity against glioblastoma both in vitro and in vivo.

Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults. Current treatment options for GBM include surgical resection, radiation, and chemotherapy, which predominantly slow cancer growth and reduce symptoms, resulting in a 5-year survival rate of no more than 10%. Chimeric antigen receptor (CAR) T-cell therapy is a new class of cellular immunotherapy that has made great progress in treating malignant tumors. Human epidermal growth factor receptor 2 (HER2) is overexpressed in GBM and may provide a potential therapeutic target for GBM treatment. In this study, we constructed third-generation CAR-T cells targeting the HER2 antigen in GBM. HER2-CAR-T cells showed effective anti-tumor activity both in vitro and in vivo. Furthermore, HER2-specific CAR-T cells exhibited strong cytotoxicity and cytokine-secreting abilities against GBM cells in vitro. Anti-HER2 CAR-T cells also exhibited increased cytotoxicity with increasing effector-to-target ratios. Anti-HER2 CAR-T cells delivered via peritumoral injection successfully stunted tumor progression in vivo. Moreover, peritumoral intravenous administration of anti-HER2 CAR-T cells resulted in therapeutic improvement against GBM cells compared with intravenous administration. In conclusion, our study shows that HER2 CAR-T cells represent an emerging immunotherapy for treating GBM.

Effects of Phloroglucinol on Embryo Transfer: A Systematic Review and Meta-Analysis.

INTRODUCTION: Phloroglucinol may be able to improve embryo transfer outcomes. We aimed to systematically evaluate the effects of phloroglucinol on embryo transfer outcomes. METHODS: The databases searched were PubMed, Ovid MEDLINE, Web of Science, Wanfang, CQVIP, China National Knowledge Infrastructure, and ClinicalTrials.gov. The last search was on February 7, 2023. The included studies were written in English or Chinese. Randomized controlled trials and cohort studies aiming to assess the effect of phloroglucinol on embryo transfer outcomes were included. The studies reported at least one of the primary outcomes (biochemical pregnancy rate, clinical pregnancy rate, and live birth rate). The odds ratio (OR) and 95% confidence interval (CI) were calculated. A random-effects or fixed model was used where applicable to estimate the results. RESULTS: Seventeen articles reporting 5,953 cycles were included. Biochemical pregnancy rate (OR = 1.58, 95% CI = 1.20-2.08, I2 = 71%), clinical pregnancy rate (OR = 1.69, 95% CI = 1.35-2.10, I2 = 64%), and live birth rate (OR = 1.45, 95% CI = 1.23-1.71, I2 = 36%) were improved by phloroglucinol. Less miscarriage (OR = 0.46, 95% CI = 0.35-0.60, I2 = 0%), less ectopic pregnancy (OR = 0.45, 95% CI = 0.28-0.72, I2 = 0%), higher implantation rate (OR = 1.45, 95% CI = 1.24-1.71, I2 = 62%) but more multiple pregnancy rate (OR = 1.48, 95% CI = 1.13-1.94, I2 = 0%) were induced by phloroglucinol. Endometrial peristaltic waves were improved by phloroglucinol (OR = 22.87, 95% CI = 5.52-94.74, I2 = 72%). CONCLUSION: Phloroglucinol may improve the outcomes of embryo transfer, including biochemical pregnancy, clinical pregnancy, and live birth rates. Further studies are warranted.

Two swords combination: Smartphone-assisted ratiometric fluorescent and paper sensors for dual-mode detection of glyphosate in edible malt.

The long-term and excessive use of glyphosate (GLY) in diverse matrices has caused serious hazard to the human and environment. However, the ultrasensitive detection of GLY still remains challenging. In this study, the smartphone-assisted dual-signal mode ratiometric fluorescent and paper sensors based on the red-emissive gold nanoclusters (R-AuNCs) and blue-emissive carbon dots (B-CDs) were ingeniously designed accurate and sensitive detection of GLY. Upon the presence of GLY, it would quench the fluorescence of B-CDs through dynamic quenching effect, and strengthen the fluorescence response of R-AuNCs due to aggregation-induced enhancement effect. Through calculating the GLY-induced fluorescence intensity ratio of B-CDs to R-AuNCs by using a fluorescence spectrophotometer, low to 0.218 µg/mL of GLY could be detected in lab in a wide concentration range of 0.3-12 µg/mL with high recovery of 94.7-103.1% in the spiked malt samples. The smartphone-assisted ratiometric fluorescent sensor achieved in the 96-well plate could monitor 0-11 µg/mL of GLY with satisfactory recovery of 94.1-107.0% in real edible malt matrices for high-throughput analysis. In addition, a portable smartphone-assisted ratiometric paper sensor established through directly depositing the combined B-CDs/R-AuNCs probes on the test strip could realize on-site measurement of 2-8 µg/mL of GLY with good linear relationship. This study provides new insights into developing the dual-signal ratiometric sensing platforms for the in-lab sensitive detection, high-throughput analysis, and on-site portable measurement of more trace contaminants in foods, clinical and environmental samples.

Establishment of a Dual-Signal Enhanced Fluorescent Aptasensor for Highly Sensitive Detection of Ochratoxin A.

A robust and versatile dual-signal enhanced fluorescent aptasensor was developed for ochratoxin A (OTA) detection based on fluorescence resonance energy transfer between 5-carboxyfluorescein (FAM) and Super Green I (SG) fluorophores as the donor and graphene oxide (GO) nanosheet as the acceptor. Abundant SG probes were adsorbed into the FAM-complementary DNA (cDNA)-aptamer double-stranded structure to achieve remarkably enhanced fluorescence responses. Without OTA, the FAM-cDNA-SG conjugates coexisted with GO nanosheets, exhibiting strong fluorescence signals. In the presence of OTA, it was captured by the aptamers to release cDNA-FAM and SG probes, which were adsorbed by GO, leading to OTA-dependent fluorescence quenching. The changed fluorescence intensity was measured for accurate quantitation of OTA. Under optimum conditions, the dual-signal enhanced fluorescent aptasensor realized fascinating sensitivity with a limit of detection of 0.005 ng/mL and a wide concentration range of 0.02-20 ng/mL, as well as high selectivity for OTA over other interfering substances, excellent accuracy with average recoveries of 91.37-116.83% in the fortified malt matrices, and superior reliability and practicability in actual samples. This FAM-cDNA-aptamer-SG/GO nanosheet-based aptasensing platform could be extended to monitor other contaminants or trace molecules in food, environmental, and diagnostic fields by altering the corresponding aptamers.

Multiple functions of HMGB1 in cancer.

High mobility group box 1 (HMGB1) is a nuclear DNA-binding protein with a dual role in cancer, acting as an oncogene and a tumor suppressor. This protein regulates nucleosomal structure, DNA damage repair, and genomic stability within the cell, while also playing a role in immune cell functions. This review comprehensively evaluates the biological and clinical significance of HMGB1 in cancer, including its involvement in cell death and survival, its potential as a therapeutic target and cancer biomarker, and as a prosurvival signal for the remaining cells after exposure to cytotoxic anticancer treatments. We highlight the need for a better understanding of the cellular markers and mechanisms involved in the involvement of HMGB1in cancer, and aim to provide a deeper understanding of its role in cancer progression.

Causal relationship between circulating cytokines and follicular lymphoma: a two-sample Mendelian randomization study.

Follicular lymphoma (FL), derived from germinal centre (GC) B cells, is a kind of systemic neoplasm. Even though FL is indolent, it remains an incurable haematology Neoplasm. Accumulating evidence has suggested that the circulating cytokine is associated with the development of FL, yet the causal relationship between FL and circulating cytokines remains undetermined. Therefore, we conducted a two-sample Mendelian randomization (MR) to confirm the causal link between FL and levels of circulating cytokines with the use of summary data on circulating cytokines and FL. All these data from genome-wide association study were derived from the Genome-wide pQTL mapping which contains 14,824 individuals. FL data were acquired exclusively from FinnGen, where 218,792 individuals (522 cases vs. 218,270 controls) were involved. Various statistical methods, including the inverse variance weighted method (IVW), weighted median (WME), simple model, weighted model (WM) and MR-Egger, were used to evaluate the potential causal connection between circulating cytokines and FL. Sensitivity analysis, which involves the examination of the heterogeneity, pleiotropy, and leave-one-out method, was also performed to ensure more trustworthy results. A bidirectional MR test was performed to evaluate the direction of causal association between circulating cytokines and FL. Combining all the steps of MR analysis, we revealed four causal cytokines: C-X-C motif chemokine ligand 5 (CXCL5), interleukin-15 receptor A (IL15RA), interleukin-20 (IL20), and neurotrophin-3 (NT-3). The risk of FL may be inversely linked to CXCL5 (OR=0.73, CI: 0.545-0.979, P=0.036), IL-15RA (OR=0.669, CI: 0.451-0.993, P=0.046), and IL-20 (OR=0.565, CI: 0.325-0.981, P=0.043) but positively linked to NT-3 (OR=1.872, CI: 1.063-3.297, P=0.03). In addition, in our study, no causal effect of FL on cytokines was demonstrated and no significant heterogeneity and pleiotropy were found. Our research revealed the causal relationship between cytokines and FL, along with both the anti-protective effect of CXCL5, IL-15RA, and IL-20 and the protective effect of neurotrophin-3 on FL. These findings aim to provide new clues regarding the pathogenesis of FL and to extend the potential of circulating cytokines to therapeutic interventions.