Neurologic impairment and brain microstructural-functional alterations in infantile spasms: A multimodal magnetic resonance imaging study.

Objective: Infantile spasms (IS) are associated with significant neurodevelopmental impairments, yet the underlying brain microstructural and functional alterations remain poorly understood. This study aimed to investigate gray and white matter abnormalities in IS patients and their correlations with neurological dysfunction using advanced neuroimaging techniques.

Methods: Thirty-four IS patients (21 males, age = 2.

Proteomics and single cell profiling identify keratin driven preexisting immunity influences lung squamous carcinoma neoadjuvant therapy.

Lung squamous cell carcinoma (LUSC) demonstrates heterogeneous responses to neoadjuvant immune checkpoint blockade, necessitating biomarkers for outcome prediction. Here, we identify tumor keratinization as a key determinant of therapeutic resistance. In 470 LUSC patients, elevated serum CYFRA 21-1 correlated with non-complete pathological response (non-CPR), while CK5/6 immunohistochemistry revealed strong association between keratinization and residual tumor burden.

Identification of Indoquinazoline Derivatives as Novel NR4A1 Agonists by Suppressing Adipocyte Lipogenesis for Treatment of Obesity.

Developing safe and effective antiobesity therapies through lipid metabolism regulation remains challenging. Our previous research identified the indolequinazoline-based compound as a promising lead with significant lipid-lowering activity in a 3T3-L1 cell model, but its direct molecular target was unknown. In this study, we demonstrate that is a novel agonist of the nuclear receptor subfamily 4 group A member 1 (NR4A1) by activity-based protein profiling (ABPP) as well as the validation of targets and pharmacological effects both intracellularly and extracellularly.

Targeting Cystine Metabolism in the Lung Cancer Environment Enhances the Efficacy of Immune Checkpoint Inhibition.

Immunotherapy with Immune Checkpoint Inhibitors (ICIs) has shown promising therapeutic effects in the treatment of lung cancer, the overall efficacy of PD-1/PD-L1 inhibitors is only 20%-30%. Thus, more effective combination therapies are needed. This study finds that cystine and cysteine levels in tumor tissues of lung cancer patients are significantly higher than adjacent non-tumor tissues.

The effect and mechanism of areca nut in ovarian cancer were investigated based on network pharmacology, molecular docking, and in vitro experiments.

Background: Ovarian cancer ranks as the leading cause of death among gynecological malignancies[1, 2]. Areca nut has demonstrated notable antitumor activity, yet its underlying mechanism remains incompletely understood.

Objective: To explore the potential of areca nut - derived active ingredients in regulating ovarian cancer progression via the PTEN/AKT1 signaling axis.

Engineered interaction elements enable enhanced multi-enzyme assembly and cascade biocatalysis for indigo synthesis.

Efficient interacting peptides or protein scaffolds can be used to achieve multi-enzymatic cascade reactions to trigger substrate channeling effect, prevent intermediate diffusion, and control the flux of metabolites. However, the limited availability of existing interactive elements hinders the broad application of the multi-enzyme assembly strategy. Here, a peptide-peptide pair (PB1C/PB2N) and a protein-peptide pair (importin/PB2C) were fused to the target protein to induce protein assembly for the first time.

Cross-population tongue image features and tongue coating microbiome changes in the evolution of colorectal cancer.

Introduction: Tongue diagnosis, a cornerstone of Traditional Chinese Medicine (TCM), relies significantly on the assessment of tongue coating, which is used to evaluate Zang-fu organ functions, qi and blood dynamics, and the influence of pathogenic factors. This diagnostic method is integral to disease diagnosis and treatment in TCM. Recent research suggests a strong correlation between the characteristics of tongue coating and its microbial composition.

KLF2 controls the apoptosis of neutrophils and is associated with disease activity of systemic lupus erythematosus.

Background: Neutropenia is more common in patients with systemic lupus erythematosus (SLE) and is a major cause of life-threatening infections. The increased apoptosis of neutrophils is likely to be an essential cause of neutropenia in SLE. However, the detailed mechanisms of increased neutrophil apoptosis in SLE remain unknown.

Synergistic anticancer activity of HSP70 and HSF1 inhibitors in colorectal cancer cells: A new strategy for combination therapy.

Background: The heat shock response (HSR) is a highly conserved mechanism that maintains intracellular homeostasis in response to various environmental and physiological stresses. Heat shock proteins (HSPs), particularly HSP70, play a pivotal role in this process as molecular chaperones. Although HSP70 inhibitors have demonstrated anti-cancer activity, their therapeutic potential has been limited by the negative feedback mechanism between HSP70 and heat shock factor 1 (HSF1).

L-aspartate ameliorates diet-induced obesity by increasing adipocyte energy expenditure.

Aims: Obesity always leads to profound perturbation of metabolome. Metabolome studies enrich the knowledge on associations between endogenous metabolites and obesity, potentially providing innovative strategies for the development of novel anti-obesity pharmacotherapy. This study aims to identify an endogenous metabolite that regulates energy expenditure and to explore its application for obesity treatment.

Corrigendum: Mechanism of LncRNA Gm2044 in germ cell development.

[This corrects the article DOI: 10.3389/fcell.2024.

Mechanism of LncRNA Gm2044 in germ cell development.

Germ cell development in mammals is a complex physiological process that involves the proliferation of primordial germ cells, meiosis, and the formation of male and female gametes. Long non-coding RNA (lncRNA) is a type of RNA with more than 200 nucleotides that does not code for proteins. A small number of lncRNAs have been shown to participate in spermatogenesis in the testes and in follicular development in the ovaries, but the role of the vast majority of lncRNAs and their molecular mechanisms still need further study.

Development of Novel -Acylhydrazone Derivatives with High Anti-obesity Activity and Improved Safety by Exploring the Pharmaceutical Properties of Aldehyde Group.

The discovery of effective and safe antiobesity agents remains a challenging yet promising field. Our previous studies identified Bouchardatine derivatives as potential antiobesity agents. However, the 8a-aldehyde moiety rendered them unsuitable for drug development.

Clinical evaluation of droplet digital PCR in the early identification of suspected sepsis patients in the emergency department: a prospective observational study.

Background: Rapid and accurate diagnosis of the causative agents is essential for clinical management of bloodstream infections (BSIs) that might induce sepsis/septic shock. A considerable number of suspected sepsis patients initially enter the health-care system through an emergency department (ED), hence it is vital to establish an early strategy to recognize sepsis and initiate prompt care in ED. This study aimed to evaluate the diagnostic performance and clinical value of droplet digital PCR (ddPCR) assay in suspected sepsis patients in the ED.

AZIN2 is associated with apoptosis of germ cells in undescended testis.

Undescended testis (UDT), known as cryptorchidism (CRY), is a common congenital disorder in which one or both testicles do not descend normally into the scrotum. A unilateral UDT model was established by inducing UDT in mice through surgery. The results showed that the testis in the UDT model group was abnormal; the lumen of the seminiferous tubule was atrophic; apoptosis, necrosis and shedding were observed in many of the germ cells; the level of sex hormones was abnormal; and mature sperm was reduced.

Integrated analysis reveals critical cisplatin-resistance regulators E2F7 contributed to tumor progression and metastasis in lung adenocarcinoma.

Background: Drug resistance poses a significant challenge in cancer treatment, particularly as a leading cause of therapy failure. Cisplatin, the primary drug for lung adenocarcinoma (LUAD) chemotherapy, shows effective treatment outcomes. However, the development of resistance against cisplatin is a major obstacle.

Near-infrared Light-Triggered Size-Shrinkable theranostic nanomicelles for effective tumor targeting and regression.

Most nanomedicines with suitable sizes (normally 100-200 nm) exhibit favorable accumulation in the periphery of tumors but hardly penetrate into deep tumors. Effective penetration of nanomedicines requires smaller sizes (less than 30 nm) to overcome the elevated tumor interstitial fluid pressure. Moreover, integrating an efficient diagnostic agent in the nanomedicines is in high demand for precision theranostics of tumors.

Unveiling the role of PD-L1 in vascular endothelial dysfunction: Insights into the mtros/NLRP3/caspase-1 mediated pyroptotic pathway.

Background: Programmed death ligand-1(PD-L1) has been postulated to play a crucial role in the regulation of barrier functions of the vascular endothelium, yet how this novel molecule mediates dysfunction in endothelial cells (ECs) during acute lung injury (ALI) remains largely unknown.

Methods: PD-L1 siRNA and plasmids were synthesized and applied respectively to down- or up-regulate PD-L1 expression in human lung microvascular endothelial cells (HMVECs). RNA sequencing was used to explore the differentially expressed genes following PD-L1 overexpression.

Discovery of Novel Coumarin-quinolinium Derivatives as Pan-KRAS Translation Inhibitors by Targeting 5'-UTR RNA G-Quadruplexes.

Hyperactivated KRAS mutations fuel tumorigenesis and represent attractive targets for cancer treatment. While covalent inhibitors have shown clinical benefits against the KRAS mutant, advancements for non-G12C mutants remain limited, highlighting the urgent demand for pan-KRAS inhibitors. RNA G-quadruplexes (rG4s) in the 5'-untranslated region of mRNA can regulate KRAS translation, making them promising targets for pan-KRAS inhibitor development.

Bisphenol A triggers apoptosis in mouse pre-antral follicle granulosa cells via oxidative stress.

Background: Bisphenol A (BPA), an endocrine disrupting chemical with weak estrogenic and anti-androgenic activity, is widely present in various environmental media and organisms. It has certain reproductive toxicity and can cause a variety of female reproductive system diseases. Although BPA-stimulated apoptosis of granulosa cells has been widely elaborated, the effect of BPA on mouse pre-antral follicle granulosa cells (mpGCs) has not been well elucidated.

The link between neutrophils, NETs, and NLRP3 inflammasomes: The dual effect of CD177 and its therapeutic potential in acute respiratory distress syndrome/acute lung injury.

Neutrophils are important inflammatory effector cells that protect against foreign invasion but also cause self-harm. Numerous neutrophils infiltrate the lungs in acute respiratory distress syndrome/acute lung injury (ARDS/ALI) patients. However, the exact impact of neutrophil infiltration on ARDS's onset and progression remains unclear.

Enhancing surgical precision: unveiling the impact of preoperative colonoscopy in anal fistula patients.

Background: Anal fistula is a common benign anorectal disease that often requires surgical intervention for effective treatment. In recent years, preoperative colonoscopy as a diagnostic tool in patients with anal fistula has garnered increasing attention due to its potential clinical application value. By investigating underlying inflammatory bowel disease (IBD), polyps, and other abnormalities, preoperative colonoscopy can offer insights to refine surgical strategies and improve patient outcomes.

A novel MRI feature, the cut green pepper sign, can help differentiate a suprasellar pilocytic astrocytoma from an adamantinomatous craniopharyngioma.

Objective: There are no specific magnetic resonance imaging (MRI) features that distinguish pilocytic astrocytoma (PA) from adamantinomatous craniopharyngioma (ACP). In this study we compared the frequency of a novel enhancement characteristic on MRI (called the cut green pepper sign) in PA and ACP.

Methods: Consecutive patients with PA (n = 24) and ACP (n = 36) in the suprasellar region were included in the analysis.