Seafloor geodesy unveils seismogenesis of large subduction earthquakes in Mexico.

Based on measurements of near-trench deformations of the oceanic and overriding plates, in this investigation, we elucidate the tectonic and mechanical processes leading to the 7.0 (moment magnitude of 7.0) Acapulco, Mexico, earthquake in 2021.

Skin-adaptive focused flexible micromachined ultrasound transducers for wearable cardiovascular health monitoring.

Continuous monitoring of cardiovascular vital signs can reduce the incidence and mortality of cardiovascular diseases, yet cannot be implemented by current technologies because of device bulkiness and rigidity. Here, we report self-adhesive and skin-conformal ultrasonic transducer arrays that enable wearable monitoring of multiple hemodynamic parameters without interfering with daily activities. A skin-adaptive focused ultrasound method with rational array design is proposed to implement measurement under wide ranges of skin curvatures and depths with improved sensing performances.

Non-neutralizing antibodies to influenza A matrix-protein-2-ectodomain are broadly effective therapeutics and resistant to viral escape mutations.

Influenza A viruses remain a global health threat, yet no universal antibody therapy exists. Clinical programs have centered on neutralizing mAbs, only to be thwarted by strain specificity and rapid viral escape. We instead engineered three non-neutralizing IgG2a mAbs that target distinct, overlapping epitopes within the conserved N terminus of the M2 ectodomain (M2e).

A plant-specific cytochrome -like protein is essential for phytosterol biosynthesis.

Sterols are essential isoprenoid derivatives that contribute to membrane structure and function. In plants, they also serve as precursors to phytohormones and specialized metabolites important for development, defense, and health. Although the sterol biosynthetic pathway is considered well-characterized, we report the discovery of a plant-specific cytochrome -like protein, CB5LP, as a critical component of phytosterol biosynthesis.

Genomic characterization of normal and aberrant human milk production.

Breastfeeding is essential for reducing infant morbidity and mortality, yet exclusive breastfeeding rates remain low, often because of insufficient milk production. The molecular causes of low milk production are not well understood. Fresh milk samples from 30 lactating individuals, classified by milk production levels across postpartum stages, were analyzed using genomic and microbiome techniques.

Somatic mtDNA mutations at intermediate levels of heteroplasmy are a source of functional heterogeneity among primary leukemic cells.

Somatic mitochondrial DNA (mtDNA) mutations are frequently observed in tumors, yet their role in pediatric cancers remains poorly understood. The heteroplasmic nature of mtDNA-where mutant and wild-type mtDNA coexist-complicates efforts to define its contribution to disease progression. In this study, bulk whole-genome sequencing of 637 matched tumor-normal samples from the Pediatric Cancer Genome Project revealed an enrichment of functionally impactful mtDNA variants in specific pediatric leukemia subtypes.

A soft robotic device for rapid and self-guided intubation.

Endotracheal intubation is a critical medical procedure for protecting a patient's airway. Current intubation technology requires extensive anatomical knowledge, training, technical skill, and a clear view of the glottic opening. However, all of these may be limited during emergency care for trauma and cardiac arrest outside the hospital, where first-pass failure is nearly 35%.

Impaired TIM4-mediated efferocytosis by liver macrophages contributes to fibrosis in metabolic dysfunction-associated steatohepatitis.

Hepatocyte apoptosis is a key feature of metabolic dysfunction-associated steatohepatitis (MASH), but the fate of apoptotic hepatocytes in MASH is poorly understood. Here, we explore the hypotheses that clearance of dead hepatocytes by liver macrophages (efferocytosis) is impaired in MASH because of low expression of the efferocytosis receptor T cell immunoglobulin and mucin domain containing 4 (TIM4; gene ) by MASH liver macrophages, which then drives liver fibrosis in MASH. We show that apoptotic hepatocytes accumulate in human and experimental MASH, using mice fed the fructose-palmitate-cholesterol (FPC) diet or the high-fat, choline-deficient amino acid-defined (HF-CDAA) diet.

Functional, immunogenetic, and structural convergence in influenza immunity between humans and macaques.

Human B cell immunity to the influenza hemagglutinin (HA) stem, a universal vaccine target, is often stereotyped and immunogenetically restricted, posing hurdles to study outside of humans. Here, we show that cynomolgus macaques vaccinated with an HA stem immunogen elicit humanlike public B cell lineages targeting two major conserved sites of vulnerability, the central stem and anchor epitopes. Central stem antibodies were predominantly derived from V1-138, the macaque homolog of human V1-69, a V gene preferentially used in human central stem broadly neutralizing antibodies (bnAbs).

Universal Effective Charges in the sd and fp Shells.

The 247-keV state in ^{54}Sc, populated in the β decay of ^{54}Ca, is reported here as a nanosecond isomer with a half-life of 26.0(22) ns. The state is interpreted as the 1^{+} member of the πf_{7/2}⊗νf_{5/2} spin-coupled multiplet, which decays to the 3^{+},πf_{7/2}⊗νp_{1/2} ground state.

Pro-Fibrotic Immune Cells and Fibro-Adipogenic Progenitors Contribute to Skeletal Muscle Extracellular Matrix Remodeling and Fibrosis in Cancer Cachexia.

Cachexia, the loss of skeletal muscle mass and function with cancer, contributes to reduced life quality and worsened survival. Skeletal muscle fibrosis leads to disproportionate muscle weakness; however, the role of infiltrating immune cells and fibro-adipogenic progenitors (FAPs) in cancer-induced muscle fibrosis is not well understood. Using the C26 model of cancer cachexia, we sought to examine the changes to skeletal muscle immune cells and FAPs which contribute to excessive extracellular matrix (ECM) collagen deposition.

Volunteering With Mild Cognitive Impairment: Implications for Subsequent Cognitive Changes.

Background And Objectives: Volunteering has cognitive benefits in later life and has been theorized to protect against Alzheimer's disease and related dementias (ADRD). A small but growing body of volunteer programs target people with mild cognitive impairment (MCI)-who are presumably at elevated risk for ADRD, but we know surprisingly little about who volunteers with MCI and how volunteering affects their subsequent cognitive changes. The current study sought to address these gaps.

Effect of Aspirin on Grip Strength and Gait Speed in Community-Dwelling Older Adults in the ASPirin in Reducing Events in the Elderly (ASPREE) Study.

Background: Grip strength and gait speed are key markers of physical functional capacity and general health in older people. This study aimed to examine the effect of low-dose aspirin on hand-grip strength and habitual gait speed in relatively healthy older people.

Methods: The ASPREE (ASPirin in Reducing Events in the Elderly) trial randomized 19,114 community-dwelling Australians and U.

Exploring the Unmet Needs of Latino Dementia Caregivers: A Qualitative Study.

Background And Objectives: Over 12% of older Latinos in the United States have Alzheimer's disease and related dementias (ADRD), facing earlier onset of the disease and severe symptoms compared to non-Hispanic Whites. These disparities in ADRD among Latinos can lead to significant caregiver strain and burden in Latino ADRD caregivers. Notably, Latino ADRD caregivers have poor overall health outcomes and face systemic inequities including limited access to quality dementia care resources that impact their well-being significantly.

Utility of GERAADA score for predicting long-term survival following surgical repair of aortic dissection.

Objectives: We aimed to assess the long-term survival following surgical repair because of type A aortic dissection (ATAAD) and the correlation with the preoperative GERAADA-score value.

Methods: We enrolled patients who underwent emergent aortic surgery because of ATAAD from 2010 to 2022 from 9 hospitals. Follow-up information was obtained by matching the clinical patient data with a national administrative database.

Characterization of strontium-rich groundwater in a typical alpine basin on Tibetan Plateau: Implications for sustainable exploitation and development.

This study focuses on mineral groundwater in alpine regions and its sustainable exploitation. The Tongde basin on Tibetan Plateau was investigated to reveal the hydrochemistry and formation of mineral groundwater in alpine basins and its sustainable development under anthropogenic disturbances. The results show that groundwater there is characterized by enriched strontium, with concentrations in the range of 0.

Challenges in the return of molecular tumor profiling results.

Next-generation sequencing (NGS) has transformed cancer care by providing essential insights for diagnosis, prognosis, and treatment. However, variability in testing timing, reporting practices, and interpretation challenges limits its clinical impact. This manuscript highlights key opportunities to optimize somatic reporting, emphasizing the importance of timely testing throughout the cancer care continuum to maximize the diagnostic and therapeutic relevance of findings.

Gaps in care across the cancer screening continuum for cervical, colorectal and lung cancer.

Background: While screening for cervical, colorectal, and lung cancers reduce cancer-specific mortality, the full benefits of screening are only realized when coupled with timely care across the subsequent "screening continuum" steps, including surveillance (results warranting frequent monitoring), diagnostic evaluation (results that require additional testing), and treatment (detected cancers). Our goal was to describe the proportion of individuals receiving timely cervical, colorectal, and lung cancer care at each step in the screening continuum.

Methods: This retrospective cohort study used data from the 10 health care settings that participate in the Population-based Research to Optimize the Screening Process (PROSPR II) consortium and included individuals who were eligible for a step along the cancer screening continuum in 2018.

A Late Bronze Age foreign elite? Investigating mobility patterns at Seddin, Germany.

During the Late Bronze Age (ca. 11th-8th century BCE), far-reaching and extensive trade and exchange networks linked communities across Europe. The area around Seddin in north-western Brandenburg, Germany, has long been considered as at the core of one such networks.

Tarlatamab exposure-efficacy and exposure-safety relationships to inform dose selection in patients with small cell lung cancer (SCLC).

Purpose: Tarlatamab is a first-in-class, half-life extended bispecific T-cell engager (BiTE®) immunotherapy targeting delta-like ligand 3 (DLL3) currently approved for the treatment of adult patients with small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. Here we report tarlatamab exposure-response relationships to inform dose selection in patients with SCLC.

Experimental Design: Pharmacokinetic data were correlated with therapeutic effect [exposure-response (ER) analyses] for efficacy and safety measures using pooled data from DeLLphi-300 and DeLLphi-301 studies.

Dynamic regulation of the oxidative stress response by the E3 ligase TRIP12.

Centered on the transcription factor NRF2 and its E3 ligase CUL3, the oxidative stress response protects cells from damage by reactive oxygen species (ROS). Increasing ROS inhibits CUL3 to stabilize NRF2 and elicit antioxidant gene expression, while cells recovering from stress rapidly turn over NRF2 again to prevent reductive stress and oxeiptosis-dependent death. How cells reinitiate NRF2 degradation after ROS have been cleared remains poorly understood.

Cryo-EM structure of a type VI secretion system-delivered membrane-depolarizing toxin involved in bacterial antagonism.

Many Gram-negative bacteria use type VI secretion systems (T6SSs) to deliver toxic effector proteins into neighboring cells. Proteins in the VasX toxin family form ion-permeable channels in the bacterial cytoplasmic membrane that dissipate the proton motive force, thereby interfering with essential physiological processes. However, the structure of any VasX family effector has remained unknown.

Adsorption modes of cysteine on gold: from neutral molecules to unconventional zwitterions.

The adsorption of amino acids on coinage metal surfaces is of interest for a range of biological applications. Central to advancing these applications is understanding the structure of the adsorbed molecules and the state they are present in. Cysteine, the focus of this work, has been studied extensively, both experimentally and theoretically.

Experimentally enhancing dispersal reveals the outsized importance of transient dynamics in a fluctuating environment.

The size and composition of local species pools are, in part, determined by past dispersal events. Predicting how communities respond to future disturbances, such as fluctuating environmental conditions, requires knowledge of such histories. We assessed the influence of a historical dispersal event on community assembly by simulating various scales of dispersal for 240 serpentine annual plant communities that experienced a large shift from drought to high rainfall conditions over three years.

Sensitization of cancer cells to DNA-damaging agents by expression of the REV1 C-terminal domain: Implications for chemotherapy.

The mutagenic translesion synthesis (TLS) pathway, which is critically dependent on REV1's ability to recruit inserter TLS polymerases and the POLζ extender polymerase, enables cancer cells to bypass DNA lesions while introducing mutations that likely contribute to the development of chemotherapy resistance and secondary malignancies. Targeting this pathway represents a promising therapeutic strategy. Here, we demonstrate that the expression of the C-terminal domain (CTD) of human REV1, a ca.