Circadian rhythm and epilepsy: a nationally representative cross-sectional study based on actigraphy data.

Objective: The study aims to assess the relationship between epilepsy and circadian rhythms.

Method: This study included a cohort of 7,410 participants sourced from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) database. The investigation focused on the comparative analysis of seven nonparametric indices associated with circadian rhythms (Interdaily Stability (IS), Intradaily Variability (IV), Relative Amplitude (RA), L5, M10, L5 start time, and M10 start time) between the overall population and patients with epilepsy.

Alternate-day fasting delays pubertal development in normal-weight mice but prevents high-fat diet-induced obesity and precocious puberty.

Background/objectives: Childhood obesity, particularly in girls, is linked to early puberty onset, heightening risks for adult-onset diseases. Addressing childhood obesity and precocious puberty is vital to mitigate societal burdens. Despite existing costly and invasive medical interventions, introducing lifestyle-based alternatives is essential.

Oncolytic Peptide-Nanoplatform Drives Oncoimmune Response and Reverses Adenosine-Induced Immunosuppressive Tumor Microenvironment.

The application of oncolytic peptides has become a powerful approach to induce complete and long-lasting remission in multiple types of carcinomas, as affirmed by the appearance of tumor-associated antigens and adenosine triphosphate (ATP) in large quantities, which jumpstarts the cancer-immunity cycle. However, the ATP breakdown product adenosine is a significant contributor to forming the immunosuppressive tumor microenvironment, which substantially weakens peptide-driven oncolytic immunotherapy. In this study, a lipid-coated micelle (CA@TLM) loaded with a stapled oncolytic peptide (PalAno) and an adenosine 2A receptor (A2AR) inhibitor (CPI-444) is devised to enact tumor-targeted oncolytic immunotherapy and to overcome adenosine-mediated immune suppression simultaneously.

Saturated fatty acids stimulate cytokine production in tanycytes via the PP2Ac-dependent signaling pathway.

The hypothalamic tanycytes are crucial for free fatty acids (FFAs) detection, storage, and transport within the central nervous system. They have been shown to effectively respond to fluctuations in circulating FFAs, thereby regulating energy homeostasis. However, the precise molecular mechanisms by which tanycytes modulate lipid utilization remain unclear.

Perinatal metabolic inflammation in the hypothalamus impairs the development of homeostatic feeding circuitry.

Over the past few decades, there has been a global increase in childhood obesity. This rise in childhood obesity contributes to the susceptibility of impaired metabolism during both childhood and adulthood. The hypothalamus, specifically the arcuate nucleus (ARC), houses crucial neurons involved in regulating homeostatic feeding.

A Novel Metabolic Score for Predicting the Acute Exacerbation in Patients with Chronic Obstructive Pulmonary Disease.

Background: Chronic obstructive pulmonary disease (COPD) has higher mortality when developing to acute exacerbation (AECOPD); hence, the early intervention of COPD is critical for preventing AECOPD. Exploring the serum metabolites associated with acute exacerbation in patients with COPD will contribute to the early intervention of COPD.

Methods: In the study, a non-targeted metabolomics strategy combined with multivariate statistical methods was performed to explore the metabolic profiling of COPD developing acute exacerbation, to screen the potential metabolites associated with AECOPD and to analyze the potential value of these metabolites in predicting the development of COPD.

Breast cancer cells that preferentially metastasize to lung or bone are more glycolytic, synthesize serine at greater rates, and consume less ATP and NADPH than parent MDA-MB-231 cells.

Gene expression signatures associated with breast cancer metastases suggest that metabolic re-wiring is important for metastatic growth in lungs, bones, and other organs. However, since pathway fluxes depend on additional factors such as ATP demand, allosteric effects, and post-translational modification, flux analysis is necessary to conclusively establish phenotypes. In this study, the metabolic phenotypes of breast cancer cell lines with low (T47D) or high (MDA-MB-231) metastatic potential, as well as lung (LM)- and bone (BoM)-homing lines derived from MDA-MB-231 cells, were assessed by C metabolite labeling from [1,2-C] glucose or [5-C] glutamine and the rates of nutrient and oxygen consumption and lactate production.

Crizotinib-based proteolysis targeting chimera suppresses gastric cancer by promoting MET degradation.

As one of the common malignant cancer types, gastric cancer (GC) is known for late-stage diagnosis and poor prognosis. Overexpression of the receptor tyrosine kinase MET is associated with poor prognosis among patients with advanced stage GC. However, no MET inhibitor has been used for GC treatment.

Baseline Pydiflumetofen Sensitivity of Isolates Collected from Henan, China, and Potential Resistance Mechanisms.

Fusarium crown rot (FCR), caused by , is one of the most important diseases impacting wheat production in the Huanghuai region, the most important wheat-growing region of China. The current study found that the SDHI fungicide pydiflumetofen, which was recently developed by Syngenta Crop Protection, provided effective control of 67 wild-type isolates in potato dextrose agar, with an average EC value of 0.060 ± 0.

Small-molecule PROTAC mediates targeted protein degradation to treat STAT3-dependent epithelial cancer.

The aberrant activation of STAT3 is associated with the etiology and progression in a variety of malignant epithelial-derived tumors, including head and neck squamous cell carcinoma (HNSCC) and colorectal cancer (CRC). Due to the lack of an enzymatic catalytic site or a ligand-binding pocket, there are no small-molecule inhibitors directly targeting STAT3 that have been approved for clinical translation. Emerging proteolysis targeting chimeric (PROTAC) technology-based approach represents a potential strategy to overcome the limitations of conventional inhibitors and inhibit activation of STAT3 and downstream genes.

CD47: Beyond an immune checkpoint in cancer treatment.

The transmembrane protein, CD47, is recognized as an important innate immune checkpoint, and CD47-targeted drugs have been in development with the aim of inhibiting the interaction between CD47 and the regulatory glycoprotein SIRPα, for antitumor immunotherapy. Further, CD47 mediates other essential functions such as cell proliferation, caspase-independent cell death (CICD), angiogenesis and other integrin-activation-dependent cell phenotypic responses when bound to thrombospondin-1 (TSP-1) or other ligands. Mounting strategies that target CD47 have been developed in pre-clinical and clinical trials, including antibodies, small molecules, siRNAs, and peptides, and some of them have shown great promise in cancer treatment.

Diet-induced inflammation in the anterior paraventricular thalamus induces compulsive sucrose-seeking.

Overconsumption of palatable food may initiate neuroadaptive responses in brain reward circuitry that may contribute to eating disorders. Here we report that high-fat diet (HFD) consumption impedes threat-cue-induced suppression of sucrose-seeking in mice. This compulsive sucrose-seeking was due to enhanced cue-triggered neuronal activity in the anterior paraventricular thalamus (aPVT) resulting from HFD-induced microglia activation.

Reduced astrocytic mGluR5 in the hippocampus is associated with stress-induced depressive-like behaviors in mice.

Major depressive disorder (MDD) is one of the most common and disabling mental disorders that characterized by profound disturbances in emotional regulation, motivation, cognition, and the physiology of affected individuals. Although MDD was initially thought to be primarily triggered through neuronal dysfunction, the pathological alterations in astrocytic function have been previously reported in MDD. We report that chronic restraint stress (CRS) induces astrocyte activation and decreases expression of astrocytic mGluR5 in the hippocampal CA1 of susceptible mice exhibited depressive-like behaviors.

Baseline Sensitivity and Potential Resistance Mechanisms for to Fludioxonil.

Fusarium crown rot (FCR), which is caused by , is one of the most important diseases affecting wheat production in the Huanghuai wheat-growing region of China. Although the phenylpyrrole fungicide fludioxonil is known to have a broad-spectrum activity against a wide range of plant pathogens, including , it has not yet been registered for the control of FCR in China, and further research is needed to assess the biological characteristics and molecular mechanisms associated with fludioxonil resistance, and especially the potential for highly resistant isolates to emerge. The current study demonstrated that the baseline fludioxonil sensitivity of 61 isolates collected from the Henan province of China during the summers of 2019 to 2021 conformed to a unimodal distribution with a mean effective concentration for 50% inhibition (EC) value of 0.

Increasing astrogenesis in the developing hippocampus induces autistic-like behavior in mice via enhancing inhibitory synaptic transmission.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized primarily by impaired social communication and rigid, repetitive, and stereotyped behaviors. Many studies implicate abnormal synapse development and the resultant abnormalities in synaptic excitatory-inhibitory (E/I) balance may underlie many features of the disease, suggesting aberrant neuronal connections and networks are prone to occur in the developing autistic brain. Astrocytes are crucial for synaptic formation and function, and defects in astrocytic activation and function during a critical developmental period may also contribute to the pathogenesis of ASD.

Mechanistic insight into high-fat diet-induced metabolic inflammation in the arcuate nucleus of the hypothalamus.

A high-fat diet (HFD) is linked with cytokines production by non-neuronal cells within the hypothalamus, which mediates metabolic inflammation. These cytokines then activate different inflammatory mediators in the arcuate nucleus of the hypothalamus (ARC), a primary hypothalamic area accommodating proopiomelanocortin (POMC) and agouti-related peptide (AGRP) neurons, first-order neurons that sense and integrate peripheral metabolic signals and then respond accordingly. These mediators, such as inhibitor of κB kinase-β (IKKβ), suppression of cytokine signaling 3 (SOCS3), c-Jun N-terminal kinases (JNKs), protein kinase C (PKC), etc.

Application of omics- and multi-omics-based techniques for natural product target discovery.

Natural products continue to be an unparalleled source of pharmacologically active lead compounds because of their unprecedented structures and unique biological activities. Natural product target discovery is a vital component of natural product-based medicine translation and development and is required to understand and potentially reduce mechanisms that may be associated with off-target side effects and toxicity. Omics-based techniques, including genomics, transcriptomics, proteomics, metabolomics, and bioinformatics, have become recognized as effective tools needed to construct innovative strategies to discover natural product targets.

EZH2 regulates the malignancy of human glioblastoma cells via modulation of Twist mRNA stability.

Glioblastoma multiforme (GBM) is a lethal primary brain tumor with poor survival lifespan and dismal outcome. However, the effects and mechanisms of epigenetic factors on the development of GBM were still not well illustrated. We found that expression of enhancer of zeste homolog 2 (EZH2), which can catalyze histone H3K27me3 to modulate gene expression, was increased in GBM cells.

Targeting CTGF in Cancer: An Emerging Therapeutic Opportunity.

Despite the dramatic advances in cancer research over the decades, effective therapeutic strategies are still urgently needed. Increasing evidence indicates that connective tissue growth factor (CTGF), a multifunctional signaling modulator, promotes cancer initiation, progression, and metastasis by regulating cell proliferation, migration, invasion, drug resistance, and epithelial-mesenchymal transition (EMT). CTGF is also involved in the tumor microenvironment in most of the nodes, including angiogenesis, inflammation, and cancer-associated fibroblast (CAF) activation.

Restoration of Cingulate Long-Term Depression by Enhancing Non-apoptotic Caspase 3 Alleviates Peripheral Pain Hypersensitivity.

Nerve injury in somatosensory pathways may lead to neuropathic pain, which affects the life quality of ∼8% of people. Long-term enhancement of excitatory synaptic transmission along somatosensory pathways contributes to neuropathic pain. Caspase 3 (Casp3) plays a non-apoptotic role in the hippocampus and regulates internalization of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits.

Coix Seed Oil Exerts an Anti-Triple-Negative Breast Cancer Effect by Disrupting miR-205/S1PR1 Axis.

Coix Seed Oil (CSO) possesses a wide range of pharmacological activities. Kanglaite Injection, a commercial product of CSO, has been used clinically as an anticancer drug in China for decades. However, its molecular mechanisms on triple-negative breast cancer (TNBC) remains to be elucidated.

Blocking CTGF-Mediated Tumor-Stroma Interplay in Pancreatic Cancer.

As the major feature of pancreatic ductal adenocarcinoma (PDAC), desmoplastic stroma poses a significant obstacle for treatment. Recent studies revealed that connective tissue growth factor (CTGF) aggravates the fibrotic environment and drives cancer initiation and progression, thus suggesting CTGF as a novel target for PDAC treatment.

Maternal immune activation alters visual acuity and retinogeniculate axon pruning in offspring mice.

Individuals with autism spectrum disorder (ASD) have been found to have a variety of sensory processing deficits. Here we report that maternal immune activation, a known factor for ASD, alters visual acuity in the offspring mice. By intraperitoneally injecting polyinosinic-polycytidylic acid (polyI:C) to induce maternal immune activation during embryonic days 10 to 14, we found that polyI:C treatment impairs visual acuity in young adult offspring mice as examined by their optomotor responses.