Spatial covariance reveals isothiocyanate natural products adjust redox stress to restore function in alpha-1-antitrypsin deficiency.

Alpha-1 antitrypsin (AAT) deficiency (AATD) is a monogenic disease caused by misfolding of AAT variants resulting in gain-of-toxic aggregation in the liver and loss of monomer activity in the lung leading to chronic obstructive pulmonary disease (COPD). Using high-throughput screening, we discovered a bioactive natural product, phenethyl isothiocyanate (PEITC), highly enriched in cruciferous vegetables, including watercress and broccoli, which improves the level of monomer secretion and neutrophil elastase (NE) inhibitory activity of AAT-Z through the endoplasmic reticulum (ER) redox sensor protein disulfide isomerase (PDI) A4 (PDIA4). The intracellular polymer burden of AAT-Z can be managed by combination treatment of PEITC and an autophagy activator.

Enabling tumor-specific drug delivery by targeting the Warburg effect of cancer.

Metabolic reprogramming of tumor cells is an emerging hallmark of cancer. Among all the changes in cancer metabolism, increased glucose uptake and the accumulation of lactate under normoxic conditions (the "Warburg effect") is a common feature of cancer cells. In this study, we develop a lactate-responsive drug delivery platform by targeting the Warburg effect.

Reanalysis of Samburupithecus reveals similarities to nyanzapithecines.

Samburupithecus kiptalami is an ape found in Late Miocene deposits (ca. 9.5 Ma) of northern Kenya.

Spaceflight alters protein levels and gene expression associated with stress response and metabolic characteristics in human cardiac spheroids.

Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) possess tremendous advantage for cardiac regeneration. However, cell survival is challenging upon cell transplantation. Since microgravity can profoundly affect cellular properties, we investigated the effect of spaceflight on hiPSC-CMs.

Black/White disparities in low birth weight across maternal trajectories of social mobility in South Carolina.

Persistent racial disparities in low birth weight (LBW) in the United States may be better understood through the adoption of a life course perspective that considers differential exposure and vulnerability of Black and White women to socioeconomic position across generations. Using a multigenerational dataset of singleton birth certificates from South Carolina from 1989 to 2020 linked along the maternal line, we constructed intergenerational social mobility trajectories of grandmaternal and maternal education and compared unadjusted and adjusted associations between trajectories and LBW among Black and White women. We found that White women were more likely to be upwardly mobile, and Black women to be downwardly mobile.

Structural and dynamical investigation of glassforming smectogen by X-ray diffraction and infra-red spectroscopy aided by density functional theory calculations.

Molecular arrangement in the chiral smectic phases of the glassforming (S)-4'-(1-methylheptylcarbonyl)biphenyl-4-yl 4-[7-(2,2,3,3,4,4,4-heptafluorobutoxy) heptyl-1-oxy]benzoate is investigated by X-ray diffraction. An increased correlation length of the positional short-range order in the supercooled state agrees with the previous assumption of the hexatic smectic phase. However, the registered X-ray diffraction patterns are not typical for the hexatic phases.

Assessing the ecological and economic transformation pathways of plastic production system.

Plastic's incredible versatility drives its continuous production growth, contributing to 4.5% of global greenhouse gas (GHG) emissions. With an unsustainable 4% annual production growth rate, plastics' environmental impact is significant.

AI-derived automated quantification of cardiac chambers and myocardium from non-contrast CT: Prediction of major adverse cardiovascular events in asymptomatic subjects.

Background And Aims: The significance of left ventricular mass and chamber volumes from non-contrast computed tomography (CT) for predicting major adverse cardiovascular events (MACE) has not been studied. Our objective was to evaluate the role of artificial intelligence-enabled multi-chamber cardiac volumetry from non-contrast CT for long-term risk stratification in asymptomatic subjects without known coronary artery disease.

Methods: Our study included 2022 asymptomatic individuals (55.

Exploring novel antifungal peptides from peptic hydrolysis of chicken cruor protein via regression-based machine learning approach.

There is a growing interest in natural preservatives driven by consumer demand for clean-label products. In Canada, approximately 48 million liters of blood are produced annually during chicken slaughter, offering an opportunity to valorize cruor, the solid blood component rich in hemoglobin, for use in food preservation. This study investigated the hydrolysis of chicken cruor with pepsin at pH 2, 3, 4, and 5 for 180 min to produce antimicrobial peptides.

Estimating the ovarian cancer CA-125 preclinical detectable phase, in-vivo tumour doubling time, and window for detection in early stage: an exploratory analysis of UKCTOCS.

Background: The ovarian cancer (OC) preclinical detectable phase (PCDP), defined as the interval during which cancer is detectable prior to clinical diagnosis, remains poorly characterised. We report exploratory analyses from the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).

Methods: In UKCTOCS between Apr-2001 and Sep-2005, 101,314 postmenopausal women were randomised to no screening (NS) and 50,625 to annual multimodal screening (MMS) (until Dec-2011) using serum CA-125 interpreted by the Risk of Ovarian Cancer Algorithm (ROCA).

RIPK3 activation of CaMKII triggers mitochondrial apoptosis in NIBV-infected renal tubular epithelial cells.

The purpose of this study was to investigate whether RIPK3-mediated programmed cell death can promote the replication and transmission of renal infectious bronchitis virus in renal tubular epithelial cells. Primary renal tubular epithelial cells were extracted from 1 to 7 day old Hy-Line Brown chicks, cultured in vitro by type I collagenase digestion, and infected with 1MOI SX9 strain. Cell samples were collected at 12 hpi, 24 hpi, 36 hpi and 48 hpi for experimental exploration.

Modeling, synthesis and cell-based evaluation of pyridine-substituted analogs of CD3254 and fluorinated analogs of CBt-PMN as novel therapeutics.

Six pyridine analogs of (E)-3-(3-(1,2,3,4-tetrahydro-1,1,4,4,6-pentamethylnaphthalen-7-yl)-4-hydroxyphenyl)acrylic acid-or CD3254 (11)-in addition to two novel analogs of 1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-1H-benzo[d][1,2,3]triazole-5-carboxylic acid (CBt-PMN or 23) were prepared and evaluated for selective retinoid-X-receptor (RXR) agonism alongside bexarotene (1), an FDA-approved drug for cutaneous T-cell lymphoma (CTCL). Treatment with 1 often elicits side-effects by disrupting or provoking other RXR-dependent nuclear receptors and cellular pathways. All analogs were assessed through modeling for their ability to bind RXR and then evaluated in human colon and kidney cells employing an RXR-RXR mammalian-2-hybrid (M2H) system and in an RXRE-controlled transcriptional assay.

Optimized detection of calcium ion in serum using constant potential coulometry with metastable liquid-liquid contact doping enhanced PEDOT: PSS ink.

Highly stable calcium ion selective electrodes (Ca-ISEs) were developed by drop-casting a layer of poly(3,4-ethylenedioxythiophene): polystyrene sulfonate (PEDOT: PSS) as an ion-to-electron transfer layer onto Au electrode. The conductive PEDOT: PSS ink was prepared using a metastable liquid-liquid contact (MLLC) doping method, which induced phase separation, removed excess PSS, and significantly enhanced charge transfer kinetics and conductivity. The resulting Ca-ISEs exhibited excellent electrochemical performance.

Brodifacoum causes coagulopathy, hemorrhages, and mortality in rainbow trout (Oncorhynchus mykiss) at environmentally relevant hepatic residue concentrations.

Widely used second-generation anticoagulant rodenticides like brodifacoum are classified as persistent, bioaccumulative, and toxic. Widespread exposure of terrestrial and avian non-target species is well-known and recently hepatic anticoagulant rodenticide residues have been detected in wild fish. However, no sufficient data exist to interpret the effects of these findings on fish health.

Attention incorporated network for sharing low-rank, image and k-space information during MR image reconstruction to achieve single breath-hold cardiac Cine imaging.

Cardiac Cine Magnetic Resonance Imaging (MRI) provides an accurate assessment of heart morphology and function in clinical practice. However, MRI requires long acquisition times, with recent deep learning-based methods showing great promise to accelerate imaging and enhance reconstruction quality. Existing networks exhibit some common limitations that constrain further acceleration possibilities, including single-domain learning, reliance on a single regularization term, and equal feature contribution.

The role of intolerance of uncertainty in health anxiety in cancer patients: Exploring demographic and cancer-related variations.

Purpose: Health anxiety (HA) is a critical issue for cancer patients. This study investigates the role of intolerance of uncertainty (IU) in HA among a heterogeneous sample of cancer patients, comparing those with hematological malignancies and solid tumor cancers. It also explores the impact of demographic and cancer-related factors on HA.

Association of non-English as primary language on clinical outcomes for arteriovenous fistula creation within a safety net system.

Approximately 22 ​% of the United States population communicates in a non-English language, potentially impacting healthcare communication and outcomes. Few studies have examined the association between non-English primary language (NEPL) and surgical outcomes and none to our knowledge in patients undergoing arteriovenous fistula creation within a safety net system. In this study, we conducted a retrospective analysis on adults who underwent AVF creation for hemodialysis access between January 1, 2014, and December 31, 2019.

Investigation and elimination of noncovalent artificial aggregates during non-reduced capillary electrophoresis-sodium dodecyl sulfate analysis of a multi-specific antibody.

Capillary electrophoresis-sodium dodecyl sulfate (CE-SDS) is widely used in the biopharmaceutical industry for monitoring purity and analyzing impurities. The accuracy of the method may be compromised by artificial species resulting from sample preparation or electrophoresis separation due to suboptimal conditions. During non-reduced CE-SDS analysis of a multispecific antibody (msAb), named as multispecific antibody C (msAb-C), a cluster of unexpected peaks was observed after the main peak.

Assembly and functional mechanisms of plant NLR resistosomes.

Nucleotide-binding and leucine-rich repeat (NLR) proteins are essential intracellular immune receptors in both animal and plant kingdoms. Sensing of pathogen-derived signals induces oligomerization of NLR proteins, culminating in the formation of higher-order protein complexes known as resistosomes in plants. The NLR resistosomes play a pivotal role in mediating the plant immune response against invading pathogens.

Gender Imbalance in Citation Practices in Communication Sciences and Disorders Before and During the COVID-19 Pandemic.

Purpose: Despite recent advances, gender inequality remains a major concern within the workforce. One manifestation of gender inequality in academia is the undercitation of women-authored compared to men-authored papers that is thought to reflect implicit biases and has important implications for the academic advancement for research-intensive female faculty. These studies largely stem from male-dominant professions.

Downstaging of hepatocellular carcinoma before liver transplantation: Results from a national multi-center prospective cohort study.

Background Aims: Patients with hepatocellular carcinoma (HCC) meeting UNOS-downstaging (DS) criteria have excellent post-liver transplantation (LT) outcomes. Studies on HCC beyond UNOS-DS criteria ("All-comers" (AC)) have been limited by small sample size and short follow-up time, prompting this analysis.

Approach Results: 326 patients meeting UNOS-DS and 190 meeting AC criteria from 9 LT centers across 5 UNOS regions were enrolled from 2015 to 2023 and prospectively followed.

Large clones of Clonal Hematopoiesis affect outcome in Mantle Cell Lymphoma: Results from The FIL MCL0208 Clinical Trial.

Although recent evidence suggests that myeloid clonal hematopoiesis (M-CH) may influence lymphoma clinical outcome, its impact in mantle cell lymphoma (MCL) remains unclear. Here, we report a comprehensive NGS-based analysis of the M-CH mutational landscape at baseline and follow-up in patients enrolled in the Fondazione Italiana Linfomi (FIL) MCL0208 phase 3 trial (NCT02354313), evaluating lenalidomide maintenance versus observation after chemoimmunotherapy and autologous stem cell transplantation (ASCT) in untreated young MCL patients. Overall, 254/300 (85%) enrolled patients (median age 57 years [32-66]) had a baseline sample available for CH analysis.

Characterization of Individuals Achieving Type 2 Diabetes Remission in Real-World Settings: Bridging Clinical Evidence and Patient Experiences.

The objectives of the study were to: 1) Describe characteristics and lifestyle factors of individuals who have achieved type 2 diabetes (T2D) remission (sub-diabetes glucose levels without glucose-lowering medications for ≥3 months) through changes to diet and exercise behaviour in real-world settings; 2) Investigate continuous glucose monitoring (CGM) profiles of these individuals and explore how dietary pattern may influence glucose regulation metrics. This cross-sectional study recruited individuals living with T2D who achieved remission via changes to diet or exercise behaviours. Various questionnaires were used to assess overall health and participants wore a blinded CGM for 14 days to assess glucose profiles and filled out three-day food records.

Antiseizure Medications in Poststroke Seizures: A Systematic Review and Network Meta-Analysis.

Background And Objectives: The most effective antiseizure medications (ASMs) for poststroke seizures (PSSs) remain unclear. We aimed to determine outcomes associated with ASMs in people with PSS.

Methods: We systematically searched electronic databases for studies on patients with PSS on ASMs.