LTA4H improves the tumor microenvironment and prevents HCC progression via targeting the HNRNPA1/LTBP1/TGF-β axis.

Leukotriene A4 hydrolase (LTA4H), an inflammatory mediator, has garnered attention for its role in the development of chronic lung diseases and various cancers. Our study highlights the protective role of LTA4H in hepatocellular carcinoma (HCC) occurrence and progression. LTA4H is downregulated in clinical and mouse HCC tumors.

LINE-1 ORF1p expression occurs in clear cell ovarian carcinoma precursors and is a candidate blood biomarker.

Long interspersed element 1 (LINE-1) retrotransposons are repetitive sequences that can move within the genome by an autonomous mechanism. To limit their mutagenic potential, benign cells restrict LINE-1 expression through molecular mechanisms such as DNA methylation and histone modification, but these mechanisms are usually impaired in cancer. Clear cell ovarian carcinoma (CCOC) represents 5-10% of ovarian cancers and is thought to arise from endometriosis.

Integrated Macrogenomics and Metabolomics Analysis of the Effect of Sea Cucumber Ovum Hydrolysates on Dextran Sodium Sulfate-Induced Colitis.

Inflammatory bowel disease remains a significant challenge in clinical settings. This study investigated the therapeutic potential of sea cucumber ovum hydrolysates (SCH) in a dextran sulfate sodium (DSS)-induced colitis mouse model. SCH, defined by its elevated stability and solubility, with a molecular weight below 1000 Da, significantly alleviated DSS-induced colitis, as evidenced by enhanced splenic index, reduced colonic damage, and diminished serum pro-inflammatory cytokines.

Mesenchymal Stem Cell Exosome and Fibrin Sealant Composite Enhances Rabbit Anterior Cruciate Ligament Repair.

Background: The anterior cruciate ligament (ACL) fails to heal after rupture, leading to joint instability and an increased risk of osteoarthritis. Mesenchymal stem/stromal cell (MSC) exosomes have reported wide-ranging therapeutic efficacy; however, their potential for augmenting ACL repair remains to be investigated.

Purpose: To evaluate the use of MSC exosomes with fibrin sealant on biological augmentation of ACL healing after suture repair and their effects on ACL fibroblast functions.

De-escalating Dual Antiplatelet Therapy to Ticagrelor Monotherapy in Acute Coronary Syndrome : A Systemic Review and Individual Patient Data Meta-Analysis of Randomized Clinical Trials.

Background: The role of transitioning from short dual antiplatelet therapy (DAPT) to potent P2Y12 inhibitor monotherapy in patients with acute coronary syndrome (ACS) undergoing drug-eluting stent (DES) implantation remains inconclusive.

Purpose: To compare the effects of de-escalating DAPT to ticagrelor monotherapy versus standard DAPT from randomized clinical trials in patients with ACS.

Data Sources: PubMed, EMBASE, Scopus, and ClinicalTrials.

Small cell lung cancer and prostate cancer cells with varying neuroendocrine differentiation markers show sensitivity to imipridone ONC201/TIC10.

Objectives: To investigate whether neuroendocrine differentiation (NED) markers, activation of the integrated stress response (ISR), and TRAIL pathway alter neuroendocrine tumor (NET) cell death and ONC201 sensitivity.

Methods: We conducted cell viability assays to determine ONC201 sensitivity. Western blot analysis was performed to evaluate NED, ISR, and TRAIL pathway markers.

Dense, continuous membrane labeling and expansion microscopy visualization of ultrastructure in tissues.

Lipid membranes are key to the nanoscale compartmentalization of biological systems, but fluorescent visualization of them in intact tissues, with nanoscale precision, is challenging to do with high labeling density. Here, we report ultrastructural membrane expansion microscopy (umExM), which combines an innovative membrane label and optimized expansion microscopy protocol, to support dense labeling of membranes in tissues for nanoscale visualization. We validate the high signal-to-background ratio, and uniformity and continuity, of umExM membrane labeling in brain slices, which supports the imaging of membranes and proteins at a resolution of ~60 nm on a confocal microscope.

Dynamics of molecular heterogeneity in high-risk luminal breast cancer-From intrinsic to adaptive subtyping.

We evaluate therapy-induced molecular heterogeneity in longitudinal samples from high-risk, hormone-receptor positive/HER2-negative breast cancer patients with residual tumor after neoadjuvant chemotherapy from the Penelope-B trial (NCT01864746; EudraCT 2013-001040-62). Intrinsic subtypes are prognostic in pre-therapeutic (Tx) samples (n = 629, p < 0.0001) and post-Tx residual tumors (n = 782, p < 0.

Gadoxetic Acid-enhanced MRI Scoring Model to Predict Pathologic Features of Hepatocellular Carcinoma.

Background Prediction of high-risk pathologic features such as microvascular invasion (MVI), poorly differentiated pathologic grade (poor PG), and satellite nodules (SNs) has significant clinical value, as these features are associated with early recurrence and metastasis in hepatocellular carcinoma (HCC). Purpose To develop and validate a preoperative scoring model using gadoxetic acid-enhanced MRI features for noninvasive prediction of HCC high-risk pathologic features and early recurrence. Materials and Methods This retrospective study included consecutive patients with HCC who underwent preoperative gadoxetic acid-enhanced MRI at three centers (one training dataset and two external validation datasets) between January 2014 and January 2021.

Nanopore discrimination of rare earth elements.

Rare earth elements (REEs), including scandium, yttrium and lanthanides, are strategic resources with unique electric, luminescent and magnetic properties. However, owing to their highly similar physiochemical properties, the identification and separation of all REEs are challenging. Here a Mycobacterium smegmatis porin A nanopore is engineered to contain a nitrilotriacetic acid ligand at its pore constriction.

Relationship between gestational weight gain with fetal body composition and organ volumes in the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Dimensional Study: a prospective pregnancy cohort.

Background: Inadequate and excessive gestational weight gain (GWG) are associated with increased risk of newborn small- and large-for-gestational-age, respectively, and future offspring adiposity. However, the relationship between GWG and three-dimensional (3D) measures of fetal body composition and organ volumes, which may provide greater insight into fetal growth via measurement of soft tissue, remains unknown.

Objectives: The objective of this study was to examine the relationship between trimester-specific GWG and 3D fetal body composition and organ volume measurements.

The Alzheimer's Association Global Biomarker Standardization Consortium (GBSC) plasma phospho-tau Round Robin study.

Introduction: The Alzheimer's Association Global Biomarker Standardization Consortium conducted a blinded case-control study to learn which phosphorylated tau (p-tau) assays provide the largest fold-changes in Alzheimer's disease (AD) versus non-AD and show commutability in measuring patient samples and candidate certified reference materials (CRMs).

Methods: Thirty-three different p-tau assays measured paired plasma and cerebrospinal fluid (CSF) from 40 participants (25 with "AD pathology" and 15 with "non-AD pathology" by CSF amyloid beta [Aβ]42/Aβ40 and p-tau181 criteria). Four CRMs were assessed.

MERS-CoV spike vaccine-induced N-terminal domain-specific antibodies are more protective than receptor binding domain-specific antibodies.

The COVID-19 pandemic underscores the need to prepare for future emerging coronavriuses (CoVs) by understanding the principles behind effective CoV vaccine design such as protective immunity and antibody responses. To study which epitopes and subdomains contribute to protection, we utilized the prefusion-stabilized spike protein of MERS-CoV, MERS S-2P, as a vaccine immunogen. Vaccination with MERS S-2P elicited both receptor-binding domain (RBD)- and non-RBD-specific antibodies, including N-terminal domain (NTD)-specific G2-and CDC2-A2-like antibodies.

HMPL-306 in relapsed or refractory IDH1- and/or IDH2-mutated acute myeloid leukemia: A phase 1 study.

Background: HMPL-306 has equally high inhibitory activity against mutated isocitrate dehydrogenases 1 and 2 (mIDH1/2).

Methods: This first-in-human, phase 1 dose-escalation/dose-expansion study (this study was registered at ClinicalTrials.gov: NCT04272957) enrolled patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) harboring mIDH1 and/or mIDH2.

Early fusion intermediate of ACE2-using coronavirus spike acting as an antiviral target.

Coronavirus fusion with and entry into the host cell depends on viral spike, which acts as a crucial component of viral infection. However, the lack of receptor-activated spike intermediate conformation has hindered a comprehensive understanding of spike-induced membrane fusion. Here, we captured an angiotensin-converting enzyme 2 (ACE2)-induced early fusion intermediate conformation (E-FIC) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike in which heptad repeat 1 (HR1) in S2 has ejected while S1 remains attached.

MRI-assessed Dynamic Hyperinflation Induced by Tachypnea in Chronic Obstructive Pulmonary Disease: The SPIROMICS-HF Study.

Purpose To assess the repeatability of real-time cine pulmonary MRI measures of metronome-paced tachypnea (MPT)-induced dynamic hyperinflation and its relationship with chronic obstructive pulmonary disease (COPD) severity. Materials and Methods SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) (ClinicalTrials.gov identifier no.

Structural determinants of peanut-induced anaphylaxis.

Background: Human IgE mAbs recognizing peanut allergens have recently become available, but we lack a detailed understanding of how these IgEs target allergens.

Objective: We sought to determine the molecular details of the antibody-allergen interaction for a panel of clinically important human IgE mAbs and to develop strategies to disrupt disease causing antibody-allergen interactions.

Methods: We identified candidates from a panel of epitope binned human IgE mAbs that recognize 2 important and homologous peanut allergens, Ara h 2 and Ara h 6.

Synergistic combination therapy with ONC201 or ONC206, and enzalutamide or darolutamide in preclinical studies of castration-resistant prostate cancer.

Androgen receptor (AR) signaling is a target in prostate cancer therapy and can be treated with non-steroidal anti-androgens (NSAA) including enzalutamide, and apalutamide for patients with advanced disease. Metastatic castration-resistant prostate cancer (mCPRC) develop resistance becomes refractory to therapy limiting patient overall survival. Darolutamide is a novel next-generation androgen receptor-signaling inhibitor that is FDA approved for non-metastatic castration resistant prostate cancer (nmCRPC).

Xalnesiran with or without an Immunomodulator in Chronic Hepatitis B.

Background: Xalnesiran, a small interfering RNA molecule that targets a conserved region of the hepatitis B virus (HBV) genome and silences multiple HBV transcripts, may have efficacy, with or without an immunomodulator, in patients with chronic HBV infection.

Methods: We conducted a phase 2, multicenter, randomized, controlled, adaptive, open-label platform trial that included the evaluation of 48 weeks of treatment with xalnesiran at a dose of 100 mg (group 1), xalnesiran at a dose of 200 mg (group 2), xalnesiran at a dose of 200 mg plus 150 mg of ruzotolimod (group 3), xalnesiran at a dose of 200 mg plus 180 μg of pegylated interferon alfa-2a (group 4), or a nucleoside or nucleotide analogue (NA) alone (group 5) in participants with chronic HBV infection who had virologic suppression with NA therapy. The primary efficacy end point was hepatitis B surface antigen (HBsAg) loss (HBsAg level, <0.

Endovascular Thrombectomy for Acute Vertebrobasilar Artery Occlusion with Mild Deficits: A Multicenter Registry Study.

Background Endovascular thrombectomy (EVT) is an effective method for vertebrobasilar artery occlusion (VBAO) in patients with moderate to severe deficits but has unclear benefits in patients with low National Institutes of Health Stroke Scale (NIHSS) scores at hospital admission. Purpose To compare the clinical outcomes of best medical management (BMM) alone versus BMM and early EVT (door-to-puncture time [DPT] ≤ 120 minutes) versus BMM and late EVT (DPT > 120 minutes) in patients with VBAO who have NIHSS scores of 10 or less at admission. Materials and Methods This retrospective study evaluated patients with VBAO and admission NIHSS score of 10 or less who were seen at 65 stroke centers in China from December 2015 to June 2022.

Rapidly Manufactured CAR-T with Conserved Cell Stemness and Distinctive Cytokine-Secreting Profile Shows Improved Anti-Tumor Efficacy.

The emergence of chimeric antigen receptor T-cell (CAR-T) immunotherapy holds great promise in treating hematologic malignancies. While advancements in CAR design have enhanced therapeutic efficacy, the time-consuming manufacturing process has not been improved in the commercial production of CAR-T cells. In this study, we developed a "DASH CAR-T" process to manufacture CAR-T cells in 72 h and found the excelling anti-tumor efficacy of DASH CAR-T cells over conventionally manufactured CAR-T cells.

The association between the thickness of the hypoechoic halo of thyroid nodules and thyroid cancer: A retrospective study.

Rationale And Objectives: The association between hypoechoic halos and thyroid cancer in patients with thyroid nodules remains a contentious issue. The objective of this study was to examine the potential correlation between the thickness of hypoechoic halos and the presence of thyroid cancer in individuals with thyroid nodules.

Methods: The study retrospectively analyzed a cohort of 320 patients with thyroid nodules presenting hypoechoic halos from January 2019 to December 2022.

Cardiovascular-Liver-Metabolic Health: Recommendations in Screening, Diagnosis, and Management of Metabolic Dysfunction-Associated Steatotic Liver Disease in Cardiovascular Disease via Modified Delphi Approach.

There is a new awareness of the widespread nature of metabolic dysfunction-associated steatotic liver disease (MASLD) and its connection to cardiovascular disease (CVD). This has catalyzed collaboration between cardiologists, hepatologists, endocrinologists, and the wider multidisciplinary team to address the need for earlier identification of those with MASLD who are at increased risk for CVD. The overlap in the pathophysiologic processes and parallel prevalence of CVD, metabolic syndrome, and MASLD highlight the multisystem consequences of poor cardiovascular-liver-metabolic health.

Predicting upper limb motor recovery in subacute stroke patients via fNIRS-measured cerebral functional responses induced by robotic training.

Background: Neural activation induced by upper extremity robot-assisted training (UE-RAT) helps characterize adaptive changes in the brains of poststroke patients, revealing differences in recovery potential among patients. However, it remains unclear whether these task-related neural activities can effectively predict rehabilitation outcomes. In this study, we utilized functional near-infrared spectroscopy (fNIRS) to measure participants' neural activity profiles during resting and UE-RAT tasks and developed models via machine learning to verify whether task-related functional brain responses can predict the recovery of upper limb motor function.