Browse Articles

IPEC-J2 as a cellular model for studying intestinal mucus

Abstract Mucus in the proximal small intestine serves critical protective and transport functions, regulating nutrient absorption to enterocytes. The porcine jejunal epithelial cell line IPEC-J2 is widely used to study epithelial barrier function, yet its capacity to express mucins remains inconsistently described. This study aimed to investigate the ability of IPEC-J2 cells to express mucins under various culture conditions: 5% or 10% porcine serum (5PS, 10PS), with agitation (5PSAg and 10PSAg) and air-liquid interface (ALI). Mucus production was assessed using functional and structural approaches. Expression of secreted mucin MUC2 and goblet cell marker TFF3 was limited under most conditions but markedly enhanced in ALI and 5PSAg cultures. Immunohistochemistry revealed membrane-associated mucins (MUC3, MUC13) although MUC13 localisation differed between IPEC-J2 and jejunal tissue. Flow cytometry revealed that ~ 8% of IPEC-J2 cells expressed MUC2 in 5PSAg, comparable to the proportion of jejunum’s goblet cells in vivo (~ 5%). This study demonstrated that IPEC-J2 cells can differentiate into mucus-secreting cells under specific culture conditions, and they are a suitable in vitro model for investigating interactions between mucus and food components, providing a valuable tool for nutritional research.

Investigation of nutritional and phytochemical properties of wild medicinal plant species

Integrating extensive functional annotations and multiomics of cattle enhances climate resilience prediction and mapping

To understand the biological function of genomic regions, vast molecular data have been generated to annotate mammalian genomes. However, how to effectively use such extensive information to improve the mapping and prediction of complex traits, including those that respond to climate change, remains unresolved. Here, we apply a Bayesian framework to estimate a Functional-And-Evolutionary Multi-trait Importance (FAEMI) score that combines extensive functional annotations to predict the probability that a variable genomic site causes variation in 16 complex traits of 103 K cattle. The functional annotations include information from the transcriptome, epigenome, and metabolome of cattle as well as genome constraints across species from multiple genome annotation consortia, covering 2.13 million molecular phenotypes from 24 tissues/cell types of 8,446 cattle worldwide. FAEMI analyses quantify the phenotypic importance of functional assays to guide future annotation efforts and reveal significant correlations between molecular functionality and genotype-to-phenotype associations. In new data of 45 K cattle with heat tolerance phenotypes, the FAEMI score demonstrates significant advantages in improving genomic prediction and mapping. The FAEMI score improved genomic prediction accuracy of multiple heat tolerance phenotypes by ~11%. A cellular stress-related locus, stress-associated endoplasmic reticulum protein family member 2 ( SERP2 ), was identified as underlying heat tolerance, with the lead variant (rs383130643) associated with enhancer activity. Additionally, high FAEMI-ranking variants are significantly enriched in variants affecting beef cattle traits. Together, our work provides methods and resources to map informative variants genome-wide, enhancing our understanding of the biology behind thermal tolerance and helping breed resilient cattle in a hotter world.

Explainable machine learning using EMG and accelerometer sensor data quantifies surgical skill and identifies biomarkers of expertise

Low-normal free thyroxine is associated with a higher prevalence of lower extremity arterial disease in euthyroid type 2 diabetes mellitus

Abstract Recent studies suggest that high-normal concentrations of free triiodothyronine (FT3) were associated with a lower prevalence of microangiopathy in adult euthyroid people with type 1 diabetes. This study was performed to identify the association between thyroid hormones and lower extremity arterial disease (LEAD) in euthyroid patients with type 2 diabetes mellitus (T2DM). A total of 1052 euthyroid T2DM patients were enrolled, including 704 patients with LEAD as observation group and 348 patients with T2DM alone as control group. The differences in clinical characteristics, biochemical indexes, thyroid hormone between the two groups were compared. At the same time, the association between the incidence of LEAD and thyroid hormone was analyzed. The data demonstrated that FT4 levels were significantly lower in the LEAD patients than in the without LEAD patients (16.1 vs. 16.5 pmol/L). The logistic regression analysis revealed that free thyroxine (FT4) was significantly associated with the incidence of LEAD in T2DM patients, and the prevalence of LEAD increased gradually from the highest FT4 quartile to the lowest FT4 quartile ( P  < 0.05). In conclusion, patients with low-normal FT4 had a higher prevalence of diabetic LEAD, suggesting that adjusting FT4 levels may better regulate metabolism and thus reduce lower extremity arterial injury.

Unraveling species diversification and niche separation in Phedimus Kamtschaticus and P. aizoon using RAD-seq data and ecological niche modeling

Nicorandil attenuates thioacetamide induced liver fibrosis via AMPK, SIRT1 and HIF1α mediated cellular energy homeostasis

Abstract Liver fibrosis, marked by excessive extracellular matrix deposition and chronic inflammation, is a significant health concern that can progress to cirrhosis and liver failure. Current treatments are limited, highlighting the need for novel therapies. Nicorandil (NIC), a potassium channel opener with nitric oxide-donating properties, has shown cytoprotective and anti-inflammatory effects. This study evaluates the efficacy of NIC in attenuating thioacetamide (TAA)-induced liver fibrosis in rats, focusing on the AMPK/SIRT-1/HIF-1α signaling pathway. Twenty-four adult male albino rats were randomly assigned to four groups: a control group, a TAA-treated group, and two groups treated with NIC at doses of 7.5 mg/kg/day and 15 mg/kg/day, respectively, for six weeks. TAA was administered intraperitoneally for six weeks to induce fibrosis, while NIC was given concurrently at both doses. TAA administration caused marked liver injury and fibrosis, as shown by increased ALT, AST, collagen-1α, and hydroxyproline levels. NIC treatment, particularly at 15 mg, significantly reduced these markers, indicating improved liver function and less fibrosis. NIC also alleviated oxidative stress by increasing SOD and GSH while lowering MDA, NO₂⁻, and iNOS. At the molecular level, NIC upregulated AMPK, SIRT-1, P53, and PGC-1α, and downregulated HIF-1α and STAT3. It further suppressed pro-inflammatory cytokines (IL-6, IL-1β, TNF-α, NF-κB, TGF-β1) while elevating IL-10. Histopathology confirmed improved liver structure with reduced collagen deposition, and immunohistochemistry showed decreased COX-II expression. In conclusion, both NIC doses showed therapeutic potential, with the 15 mg dose demonstrating superior efficacy. These findings highlight NIC’s promise as an effective treatment for liver fibrosis by mediating the AMPK/SIRT-1/HIF-1α pathway and modulating key molecular and cellular processes.

Prebiotic organic compounds in samples of asteroid Bennu indicate heterogeneous aqueous alteration

NASA’s OSIRIS-REx mission characterized the asteroid Bennu and delivered pristine samples of its regolith to Earth. Coordinated analyses of this primitive, carbonaceous material are elucidating the abiotic formation and inventory of prebiotic organic compounds in the early Solar System. Using pyrolysis and wet-chemistry techniques, we analyzed aggregate (unsorted particulate) material and three distinct stones that appear to correspond to different boulder types observed by the spacecraft. Results from the aggregate were consistent with previous work that detected the five canonical nucleobases and 14 of the 20 α-amino acids utilized by life to synthesize proteins. However, our analytical approach tentatively uncovered trace signals of a fifteenth α-amino acid, tryptophan, which has not been detected previously in extraterrestrial materials. Further, we found that the distributions of insoluble and soluble-derived organics differ between distinct stones, suggesting heterogeneous geologic processing within Bennu’s parent body. The distributions of alkylated polycyclic aromatic hydrocarbons resemble those in aqueously altered carbonaceous chondrites and are consistent with an abiotic origin through aqueous reactions. Our findings expand the evidence that prebiotic organic molecules can form within primitive accreting planetary bodies and could have been delivered via impacts to the early Earth and other Solar System bodies, potentially contributing to the origins of life.

Decoding Natufian mortuary practices through the taphonomy of an experimental burial

Treadmill exercise ameliorates atherogenesis and vascular inflammation in ApoE−/− mice via circulating exosome-derived let-7c-5p

Abstract Regular exercise training has been shown to significantly decrease atherosclerosis (AS) related mortality and hospitalization rates. Recent research has identified that circulating exosome-derived microRNAs (miRNAs) are closely related to the progression of AS through intercellular communication. But the role of exosome-derived miRNAs in exercise-mediated protection remains to be explored. This study proposes that exercise may ameliorate vascular dysfunction and plaque formation associated with AS by modulating the expression profile of exosomal miRNAs. In this study, ApoE −/− mice were used and subjected to a ten-week treadmill exercise regimen to elucidate the molecular mechanisms by which exercise influences AS, specifically through alterations in exosomal miRNAs. The results demonstrated that exercise significantly diminished plaque area and enhanced both vascular endothelium-dependent vasodilation and cardiac function in AS mice. However, no significant differences in arterial mechanical stiffness were observed. Isolation and sequencing of serum exosomes revealed a marked decrease in serum let-7c-5p levels in AS mice after exercise. Correspondingly, let-7c-5p expression in arterial vessels was significantly reduced. The negative regulatory relationship between let-7c-5p and its target gene, tissue inhibitor of metalloproteinases-3 (Timp-3), was subsequently validated through dual luciferase assays. Concurrently, an increase in Timp-3 expression in arterial vessels was observed, alongside a significant reduction in the inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and matrix metalloproteinase-9 (MMP-9). Cellular experiments further corroborated the regulatory effect of let-7c-5p on Timp-3. Overall, these results suggest that exercise promotes Timp-3 expression by downregulating let-7c-5p carried by circulating exosomes, thereby mitigating atherogenesis and vascular inflammation in ApoE −/− mice.

Quantum-entangled neuro-symbolic swarm federation for privacy-preserving IoMT-driven multimodal healthcare

A poetic ode to eddies and an earwig’s brush with death

What will be the first AI-designed drug? These disease-fighting antibodies are top contenders

Invisible water in subducted crust: Lawsonite velocity anomalies under mantle conditions

Subduction zones transport significant amounts of water into Earth’s mantle, primarily through hydrous minerals such as lawsonite. However, the seismic detectability of lawsonite-bearing oceanic crust at mantle depths remains uncertain. To address this issue, we measured sound velocities of lawsonite up to 7.4 GPa and 600 °C. Both P- and S-wave velocities exhibited unexpected increases with temperature under high-pressure conditions. Our result suggest that hydrous oceanic crust exhibits higher seismic velocities than the surrounding mantle at depths of 150 to 250 km, resulting in high-velocity anomalies rather than the previously assumed low-velocity anomalies. Furthermore, the seismic velocity difference between hydrous and dry oceanic crust is less than 2%, making it challenging to distinguish between them using seismic velocities. This limitation may hinder the detection of the hydration state in subducted crust. In addition, lawsonite remains stable in 90% of subduction zones, and thus, such “seismically invisible water” may exist in most subducted slabs around the world.

Competition–colonization trade-off can explain any observed abundances and assumed competitive hierarchies

The competition–colonization trade-off is a possible explanation for coexistence of species in a metacommunity context that has been intensively studied for decades. Nonetheless, questions about the ubiquity and generality of the mechanism remain. The outcome of the model, equilibrium species abundances, are relatively easy to measure. However, the input into the basic model, the competitive hierarchy and the colonization rates, are not easy to measure in the field. We propose an approach that starts with an observed equilibrium configuration. We show that for any assumed competitive hierarchy we can find a corresponding set of colonization rates that would produce the observed equilibrium. We also find a simple formula for the colonization rates in terms of the observed abundances. This approach both shows that any observed set of abundances can result from a competition–colonization trade-off, and provides a method for future analyses. Additionally, generalizations of our approach can apply to generalizations of the basic competition–colonization model that avoid any biologically questionable assumptions.

Ace2 safeguards embryonic hematopoietic stem and progenitor cell production by restraining Nlrp3-mediated pyroptosis

During vertebrate embryogenesis, hematopoietic stem and progenitor cells (HSPCs) originate from hemogenic endothelium (HE) in the dorsal aorta through endothelial-to-hematopoietic transition (EHT). While basal inflammation is essential for this process, excessive immune activation disrupts HSPC emergence. Here, we identify angiotensin-converting enzyme 2 (Ace2), a key component of renin–angiotensin system, as a crucial anti-inflammatory regulator of embryonic hematopoiesis in zebrafish and mice. Loss of Ace2 impairs HE specification and reduces nascent HSPC production. Mechanistically, transcriptomic profiling reveals that ace2 deficiency leads to aberrant activation of NLR family pyrin domain containing 3 (Nlrp3) signaling and pyroptosis in vascular endothelial cells. Importantly, pharmacological inhibition of Nlrp3 or Caspase-1 restores HSPC emergence upon ace2 deficiency, consistent with treatment with exogenous angiotensin-(1–7) [Ang-(1–7)], a downstream product of Ace2 enzymatic activity. Moreover, Ace2 knockdown in mouse embryos phenocopies the defects in zebrafish, demonstrating evolutionary conservation of ACE2 in developmental hematopoiesis in mammals. Together, our findings uncover an essential role for ACE2 in maintaining a permissive inflammatory environment for HSPC development and suggest therapeutic potential for targeting the ACE2/Ang-(1–7)/Nlrp3-pyroptosis axis in inflammatory hematopoietic disorders.

Correction for Ucla et al., Quantifying cell traction forces at the single-fiber scale in 3D: An approach based on deformable photopolymerized fiber arrays

Local equations describe unreasonably efficient stochastic algorithms in random K-SAT

Despite significant advances in characterizing the highly nonconvex landscapes of constraint satisfaction problems, the good performance of certain algorithms in solving hard combinatorial optimization tasks remains poorly understood. This gap in understanding stems largely from the lack of theoretical tools for analyzing their out-of-equilibrium dynamics. To address this challenge, we develop a system of approximate master equations that capture the behavior of local search algorithms in constraint satisfaction problems. Our framework shows excellent qualitative agreement with the phase diagrams of two paradigmatic algorithms: Focused Metropolis Search (FMS) and greedy-WalkSAT (G-WalkSAT) for random 3-SAT. The equations not only confirm the numerical observation that G-WalkSAT’s algorithmic threshold is nearly parameter-independent but also successfully predict FMS’s threshold beyond the clustering transition. We also exploit these equations in a decimation scheme, demonstrating that the computed marginals encode valuable information about the local structure of the solution space explored by stochastic algorithms. Notably, our decimation approach achieves a threshold that surpasses the clustering transition, outperforming conventional methods like Belief Propagation-guided decimation. These results challenge the prevailing assumption that long-range correlations are always necessary to describe efficient local search dynamics and open a path to designing efficient algorithms to solve combinatorial optimization problems.

Recovery of infectious recombinant human norovirus using zebrafish embryos

Human norovirus (HuNoV) is the leading cause of gastroenteritis. However, the lack of a reverse genetics system for infectious HuNoV has hindered the development of antivirals and vaccines. Herein, we established a reverse genetics system for infectious HuNoV using a robust HuNoV replication system based on zebrafish embryos. Transfection of a HuNoV cDNA clone into cultured cells, followed by microinjection of the supernatant into zebrafish embryos, produced infectious recombinant HuNoVs. The recombinant HuNoVs can replicate in human intestinal organoids, confirming their infectivity in a physiologically relevant system. Notably, we also recovered recombinant HuNoVs following direct HuNoV cDNA microinjection into zebrafish embryos without the use of cultured cells, which is a simpler and more efficient approach. Using the established systems, we recovered an infectious recombinant HuNoV carrying a reporter tag insertion, enabling rapid antiviral evaluation and virus inactivation assays. Furthermore, we generated recombinant HuNoVs of the GII.17 and GII.4 genotypes, as well as a chimeric virus carrying the GII.4 VP1 gene in a GII.17 backbone, demonstrating the utility of the systems for viral replication studies. These systems will accelerate research on HuNoV replication and enhance efforts to develop vaccines and antivirals.

Measuring the Young’s modulus of individual lithium whiskers

The primary challenge hindering widespread adoption of lithium (Li) anodes is the safety risks of short circuits owing to the penetration of Li whiskers, where their mechanical property plays a crucial role. However, measurement of the overall Young’s modulus of individual Li whiskers with solid electrolyte interphase (SEI) remains elusive. Here, via an in situ electric-field-induced resonance method, the Young’s modulus of individual electrochemically deposited Li whiskers along <211> is measured to be 3.2 ± 0.2 GPa in a transmission electron microscope, lower than that of pure Li metal, suggesting that hard short circuits induced by mechanical penetration are expected to have a low probability of occurrence. Quantitative analysis reveals that a simple linear combination of the Young’s moduli of pure Li metal and the SEI, based on a linear mixed model, fails to account for the reduced Young’s modulus. With the aid of atomic-level imaging and simulations, the lower value is ascribed to intricate interfacial microstructures, including highly-crystalline-Li|poorly-crystalline-Li, Li|Li 2 O, Li|organic, and others.