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Despite continuous expansion of the RNA binding protein (RBP) world, there is a lack of systematic understanding of RBPs in themammalian testis, which harbors one of themost complex tissue transcriptomes. We adapted RNA interactome capture to mouse male germ cells, building an RBP atlas characterized by multiple layers of dynamics along spermatogenesis. Trapping of RNA-cross-linked peptides showed that the glutamic acid-arginine (ER) patch, a residue-coevolved polyampholytic element present in coiled coils, enhances RNA binding of its host RBPs. Deletion of this element in NONO (non-POU domain-containing octamer-binding protein) led to a defective mitosis-to-meiosis transition due to compromised NONO-RNA interactions. Whole-exome sequencing of over 1000 infertile men revealed a prominent role of RBPs in the human genetic architecture of male infertility and identified risk ER patch variants. [ABSTRACT FROM AUTHOR]

Here, we characterize the DNA methylation phenotypes of bone marrow cells from mice with hematopoietic deficiency of Dnmt3a or Dnmt3b (or both enzymes) or expressing the dominant-negative Dnmt3aR878H mutation [R882H in humans; the most common DNMT3A mutation found in acute myeloid leukemia (AML)]. Using these cells as substrates, we defined DNA remethylation after overexpressing wild-type (WT) DNMT3A1, DNMT3B1, DNMT3B3 (an inactive splice isoform of DNMT3B), or DNMT3L (a catalytically inactive "chaperone" for DNMT3A and DNMT3B in early embryogenesis). Overexpression of DNMT3A for 2 weeks reverses the hypomethylation phenotype of Dnmt3a-deficient cells or cells expressing the R878H mutation. Overexpression of DNMT3L (which is minimally expressed in AML cells) also corrects the hypomethylation phenotype of Dnmt3aR878H/+ marrow, probably by augmenting the activity of WT DNMT3A encoded by the residual WT allele. DNMT3L reactivation may represent a previously unidentified approach for restoring DNMT3A activity in hematopoietic cells with reduced DNMT3A function. [ABSTRACT FROM AUTHOR]

The use of bioelectronic devices relies on direct contact with soft biotissues. For transistor-type bioelectronic devices, the semiconductors that need to have direct interfacing with biotissues for effective signal transduction do not adhere well with wet tissues, thereby limiting the stability and conformability at the interface. We report a bioadhesive polymer semiconductor through a double-network structure formed by a bioadhesive brush polymer and a redox-active semiconducting polymer. The resulting semiconducting film can form rapid and strong adhesion with wet tissue surfaces together with high charge-carrier mobility of ~1 square centimeter per volt per second, high stretchability, and good biocompatibility. Further fabrication of a fully bioadhesive transistor sensor enabled us to produce high-quality and stable electrophysiological recordings on an isolated rat heart and in vivo rat muscles. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) that express T cell immunoglobulin domain molecule-4 (TIM4), a cell surface receptor for phosphatidylserine, induce T helper 2 (TH2) cell responses and allergic reactions. We elucidated the role of the transcription factor X-box–binding protein-1 (XBP1) in the induction of the TH2 cell response through its role in generating TIM4+ DCs. We found that XBP1 was required for TIM4 mRNA and protein expression in airway DCs in response to the cytokine interleukin-2 (IL-2) and that this pathway was required for TIM4 expression on DCs in response to the allergens PM2.5 and Derf1. The IL-2–XBP1–TIM4 axis in DCs contributed to Derf1/PM2.5-induced, aberrant TH2 cell responses in vivo. An interaction between the guanine nucleotide exchange factor Son of sevenless-1 (SOS1) and the GTPase RAS promoted XBP1 and TIM4 production in DCs. Targeting the XBP1-TIM4 pathway in DCs prevented or alleviated experimental airway allergy. Together, these data suggest that XBP1 is required for TH2 cell responses by inducing the development of TIM4+ DCs, which depends on the IL-2–XBP1–SOS1 axis. This signaling pathway provides potential therapeutic targets for the treatment of TH2 cell–dependent inflammation or allergic diseases. Editor's summary: T helper 2 (TH2) cells mediate allergic responses, and their development depends on dendritic cells (DCs) expressing the receptor TIM4. Yang et al. found that the transcription factor XBP1 induced expression of the gene encoding TIM4 in DCs. Production of the cytokine IL-2 in the airways of allergen-exposed mice induced expression of XBP1 and then TIM4 in DCs through a pathway involving the GEF Sos1 and the GTPase Ras. Targeting this pathway in DCs reduced the severity of experimentally induced allergic airway responses in mice, suggesting that these factors could be therapeutic targets for treating TH2 cell–dependent inflammatory or allergic diseases. —John F. Foley [ABSTRACT FROM AUTHOR]

A research article is presented by a team of researchers has developed a noninvasive method to measure the stresses inside soft materials, such as living tissue or implantable bioelectronics, without knowing their constitutive parameters. Using acoustoelasticity, the method remotely excites and visualizes shear waves, which are sensitive to mechanical stresses, allowing for accurate measurement of the stresses within a material.

Although the physics of materials at surfaces and edges has been extensively studied, the movement of individual atoms at an isolated edge has not been directly observed in real time. With a transmission electron aberration-corrected microscope capable of simultaneous atomic spatial resolution and 1-second temporal resolution, we produced movies of the dynamics of carbon atoms at the edge of a hole in a suspended, single atomic layer of graphene. The rearrangement of bonds and beam-induced ejection of carbon atoms are recorded as the hole grows. We investigated the mechanism of edge reconstruction and demonstrated the stability of the 'zigzag' edge configuration. This study of an ideal low-dimensional interface, a hole in graphene, exhibits the complex behavior of atoms at a boundary.

The article highlights that Meiosis is a unique cell division process in sexually reproducing organisms where the meiotic cell cycle begins with one round of DNA replication, followed by two successive rounds of cell divisions, thus creating haploid germ cells from diploid progenitors. It also discusses that N6 -methyladenosine is the most abundant internal modification of mRNAs and has emerged as a key posttranscriptional mechanism regulating gene expression.

The article explores the understanding of how active site inhibition of Calcineurin (CN) achieved in a highly specific manner. It discusses that the regulator of calcineurin 1 (RCAN1) as an endogenous inhibitor of the Ser/Thr phosphatase calcineurin and explains excessive inhibition of CN as a critical factor for Down syndrome and Alzheimer's disease.

A nuclear option for acute kidney injury: Acute kidney injury is a life-threatening health problem with many potential causes such as hypoxic injury, toxins, and sepsis. Patients can recover with supportive care, but they may have long-lasting kidney damage that increases the risk of chronic kidney disease, and there is no specific targeted treatment. Yu et al. discovered that nuclear receptor PXR is down-regulated in the setting of acute kidney injury, which contributes to the impairment of mitochondrial function. Conversely, interventions that restored PXR function in mouse models of acute kidney injury were effective at protecting the kidneys, suggesting the potential for a therapeutic approach targeting PXR. Acute kidney injury (AKI) is a worldwide public health problem with no specific and satisfactory therapies in clinic. The nuclear pregnane X receptor (PXR) is involved in the progression of multiple diseases, including metabolic diseases, atherosclerosis, hypertension, liver injury, etc. However, its role in kidney injury remains to be understood. In this study, we have investigated the role of PXR in AKI and underlying mechanism(s) involved in its function. PXR was robustly down-regulated and negatively correlated with renal dysfunction in human and animal kidneys with AKI. Silencing PXR in rats enhanced cisplatin-induced AKI and induced severe mitochondrial abnormalities, whereas activating PXR protected against AKI. Using luciferase reporter assays, genomic manipulation, and proteomics data analysis on the kidneys of PXR−/− rats, we determined that PXR targeted Aldo-keto reductase family 1, member B7 (AKR1B7) to improve mitochondrial function, thereby ameliorating AKI. We confirmed the protective role of PXR against kidney injury using genomic and pharmacologic approaches in an ischemia/reperfusion model of AKI. These findings demonstrate that disabling the PXR/AKR1B7/mitochondrial metabolism axis is an important factor that can contribute to AKI, whereas reestablishing this axis can be useful for treating AKI. [ABSTRACT FROM AUTHOR]

Two early Late Pleistocene (~105,000- to 125,000-year-old) crania from Lingjing, Xuchang, China, exhibit a morphological mosaic with differences from and similarities to their western contemporaries. They share pan–Old World trends in encephalization and in supraorbital, neurocranial vault, and nuchal gracilization. They reflect eastern Eurasian ancestry in having low, sagittally flat, and inferiorly broad neurocrania. They share occipital (suprainiac and nuchal torus) and temporal labyrinthine (semicircular canal) morphology with the Neandertals. This morphological combination reflects Pleistocene human evolutionary patterns in general biology, as well as both regional continuity and interregional population dynamics. [ABSTRACT FROM AUTHOR]

Two-dimensional transition metal dichalcogenides (TMDCs) such as molybdenum sulfide MoS2 and tungsten sulfide WSe2 have potential applications in electronics because they exhibit high on-off current ratios and distinctive electro-optical properties. Spatially connected TMDC lateral heterojunctions are key components for constructing monolayer p-n rectifying diodes, light-emitting diodes, photovoltaic devices, and bipolar junction transistors. However, such structures are not readily prepared via the layer-stacking techniques, and direct growth favors the thermodynamically preferred TMDC alloys. We report the two-step epitaxial growth of lateral WSe2-MoS2 heterojunction, where the edge of WSe2 induces the epitaxial MoS2 growth despite a large lattice mismatch. The epitaxial growth process offers a controllable method to obtain lateral heterojunction with an atomically sharp interface. [ABSTRACT FROM AUTHOR]

Formaldehyde is a ubiquitious environmental pollutant found in many occupational settings and in tobacco smoke, consumer products, and exhaust from gasoline and diesel combustion (1). The compound can also be [...]

Diverse eukaryotic hosts produce virus-derived small interfering RNAs (siRNAs) to direct antiviral immunity by RNA interference (RNAi). However, it remains unknown whether the mammalian RNAi pathway has a natural antiviral function. Here, we show that infection of hamster cells and suckling mice by Nodamura virus (NoV), a mosquito-transmissible RNA virus, requires RNAi suppression by its B2 protein. Loss of B2 expression or its suppressor activity leads to abundant production of viral siRNAs and rapid clearance of the mutant viruses in mice. However, viral small RNAs detected during virulent infection by NoV do not have the properties of canonical siRNAs. These findings have parallels with the induction and suppression of antiviral RNAi by the related Flock house virus in fruit flies and nematodes and reveal a mammalian antiviral immunity mechanism mediated by RNAi. [ABSTRACT FROM AUTHOR]

The article discusses the catabolism of exogenous membrane phospholipid components, specifically the lipid headgroups phosphorylethanolamine (PE) and phosphocholine (PC), by the marine bacterium Phaeobacter sp. MED193. Topics discussed include how Phaeobacter acquires and catabolizes these phospholipid components, with an emphasis on their role as a source of phosphorus.

In metazoans, cells depend on extracellular growth factors for energy homeostasis. We found that glycogen synthase kinase-3 (GSK3), when deinhibited by default in cells deprived of growth factors, activates acetyltransferase TIP60 through phosphorylating TIP60-Ser86, which directly acetylates and stimulates the protein kinase ULK1, which is required for autophagy. Cells engineered to express TIP60S86A that cannot be phosphorylated by GSK3 could not undergo serum deprivation-induced autophagy. An acetylation-defective mutant of ULK1 failed to rescue autophagy in ULK1-/- mouse embryonic fibroblasts. Cells used signaling from GSK3 to TIP60 and ULK1 to regulate autophagy when deprived of serum but not glucose. These findings uncover an activating pathway that integrates protein phosphorylation and acetylation to connect growth factor deprivation to autophagy. [ABSTRACT FROM AUTHOR]

Hydrogels, known for their mechanical and chemical similarity to biological tissues, are widely used in biotechnologies, whereas semiconductors provide advanced electronic and optoelectronic functionalities such as signal amplification, sensing, and photomodulation. Combining semiconducting properties with hydrogel designs can enhance biointeractive functions and intimacy at biointerfaces, but this is challenging owing to the low hydrophilicity of polymer semiconductors. We developed a solvent affinity-induced assembly method that incorporates water-insoluble polymer semiconductors into double-network hydrogels. These semiconductors exhibited tissue-level moduli as soft as 81 kilopascals, stretchability of 150% strain, and charge-carrier mobility up to 1.4 square centimeters per volt per second. When they are interfaced with biological tissues, their tissue-level modulus enables alleviated immune reactions. The hydrogel's high porosity enhances molecular interactions at semiconductor-biofluid interfaces, resulting in photomodulation with higher response and volumetric biosensing with higher sensitivity. [ABSTRACT FROM AUTHOR]

Achilles tendinopathy is often attributed to overuse, but its pathophysiology remains poorly understood. Disruption to the molecular structure of collagen is fundamental for the onset and progression of tendinopathy but has mostly been investigated in vitro. Here, we interrogated the in vivo molecular structure changes of collagen in rat Achilles tendons following treadmill running. Unexpectedly, the tendons' collagen molecules were not mechanically unfolded by running but denatured through proteolysis during physiological post-run remodeling. We further revealed that running induces inflammatory gene expressions in Achilles tendons and that long-term running causes prolonged, elevated collagen degradation, leading to the accumulation of denatured collagen and tendinopathy development. For applications, we demonstrated magnetic resonance imaging of collagenase-induced Achilles tendon injury in vivo using a denatured collagen targeting contrast agent. Our findings may help close the knowledge gaps in the mechanobiology and pathogenesis of Achilles tendinopathy and initiate new strategies for its imaging-based diagnosis. [ABSTRACT FROM AUTHOR]

Vaccination-induced protection against influenza is greatly diminished and increasingly heterogeneous with age. We investigated longitudinally (up to five time points) a cohort of 234 vaccinated >65-year-old vaccinees with adjuvanted vaccine FluAd across two independent seasons. System-level analyses of multiomics datasets measuring six modalities and serological data revealed that poor responders lacked time-dependent changes in response to vaccination as observed in responders, suggestive of systemic dysregulation in poor responders. Multiomics integration revealed key molecules and their likely role in vaccination response. High prevaccination plasma interleukin-15 (IL-15) concentrations negatively associated with antibody production, further supported by experimental validation in mice revealing an IL-15-driven natural killer cell axis explaining the suppressive role in vaccine-induced antibody production as observed in poor responders. We propose a subset of long-chain fatty acids as modulators of persistent inflammation in poor responders. Our findings provide a potential link between low-grade chronic inflammation and poor vaccination response and open avenues for possible pharmacological interventions to enhance vaccine responses. [ABSTRACT FROM AUTHOR]

Climate-sensitive northern cryosphere inland waters emit greenhouse gases (GHGs) into the atmosphere, yet their total emissions remain poorly constrained. We present a data-driven synthesis of GHG emissions from northern cryosphere inland waters considering water body types, cryosphere zones, and seasonality. We find that annual GHG emissions are dominated by carbon dioxide (1149.21307.5 1004.8 teragrams of CO2; medianQ3 Q1) and methane (14.218.5 10.1 teragrams of CH4), while the nitrous oxide emission (5.412.2 -1.4 gigagrams of N2O) is minor. The annual CO2-equivalent (CO2e) GHG emissions from northern cryosphere inland waters total 1.51.8 1.3 or 2.32.8 1.8 petagrams of CO2e using the 100-or 20-year global warming potentials, respectively. Rivers emit 64% more CO2e GHGs than lakes, despite having only one-fifth of their surface area. The continuous permafrost zone contributed half of the inland water GHG emissions. Annual CO2e emissions from northern cryosphere inland waters exceed the region's terrestrial net ecosystem exchange, highlighting the important role of inland waters in the cryospheric land-aquatic continuum under a warming climate. [ABSTRACT FROM AUTHOR]

Magnetite is rare on the Moon. The ubiquitous presence of magnetite in lunar soil has been hypothesized in previous Apollo Mössbauer spectroscopy and electron spin resonance studies, but there is currently no mineralogical evidence to prove it. Here, we report a large number of submicroscopic magnetite particles embedded within iron-sulfide on the surface of Chang'e-5 glass, with a close positive correlation between magnetite content and the TiO2 content of the surrounding glass. The morphology and mineralogy of the iron-sulfide grains suggest that these magnetite particles formed via an impact process between iron-sulfide droplets and silicate glass melt, and ilmenite is necessary for magnetite formation. Magnetite in lunar glass is a potential candidate for the "magnetite-like" phase detected in the Apollo era and suggests that impact-induced submicroscopic magnetite may be ubiquitous in high-Ti regions of the Moon. Moreover, these impact-induced magnetite particles may be crucial for understanding the lunar magnetic anomalies and mineral components of the deep Moon. [ABSTRACT FROM AUTHOR]

The article presents a study that explores about the stretchable and strain-unperturbed pressure sensor for motion interference–free tactile monitoring on skins. It mentions about the capability to provide all the desired characteristics for quantitative pressure sensing on a deformable surface, sensor has been used to realize the accurate sensation of physical interactions on human or soft robotic skin.

Cyclin G1 regulates G2-M arrest in proximal tubular cells, promoting a TASCC-induced secretory phenotype, fibrosis, and kidney disease progression. Taking kidney fibrosis to TASCC: The kidney has an inherent capacity to recover from acute injury; however, severe injury can lead to chronic kidney disease and fibrosis. Canaud et al. studied kidney epithelial cells' maladaptive response to injury. The formation of target of rapamycin–autophagy spatial coupling compartments (TASCCs) in proximal epithelial cells was associated with cell cycle arrest and fibrosis in human chronic kidney disease, whereas knocking out cyclin G1 prevented TASCC formation and fibrosis in mouse models. This study provides mechanistic insight into renal fibrosis and identifies a potential therapeutic target. Fibrosis contributes to the progression of chronic kidney disease (CKD). Severe acute kidney injury can lead to CKD through proximal tubular cell (PTC) cycle arrest in the G2-M phase, with secretion of profibrotic factors. Here, we show that epithelial cells in the G2-M phase form target of rapamycin (TOR)–autophagy spatial coupling compartments (TASCCs), which promote profibrotic secretion similar to the senescence-associated secretory phenotype. Cyclin G1 (CG1), an atypical cyclin, promoted G2-M arrest in PTCs and up-regulated TASCC formation. PTC TASCC formation was also present in humans with CKD. Prevention of TASCC formation in cultured PTCs blocked secretion of profibrotic factors. PTC-specific knockout of a key TASCC component reduced the rate of kidney fibrosis progression in mice with CKD. CG1 induction and TASCC formation also occur in liver fibrosis. Deletion of CG1 reduced G2-M phase cells and TASCC formation in vivo. This study provides mechanistic evidence supporting how profibrotic G2-M arrest is induced in kidney injury and how G2-M–arrested PTCs promote fibrosis, identifying new therapeutic targets to mitigate kidney fibrosis. [ABSTRACT FROM AUTHOR]

Modern synthetic technology generally invokes high temperatures to control the hydration level of ceramics, but even the state-of-the-art technology can still only control the overall hydration content. Magically, natural organisms can produce bioceramics with tailorable hydration profiles and crystallization traits solely from amorphous precursors under physiological conditions. To mimic the biomineralization tactic, here, we report pressure-controlled hydration and crystallization in fabricated ceramics, solely from the amorphous precursors of purely inorganic gels (PIGs) synthesized from biocompatible aqueous solutions with most common ions in organisms (Ca2+, Mg2+, CO3 2-, and PO4 3-). Transparent ceramic tablets are directly produced by compressing the PIGs under mild pressure, while the pressure regulates the hydration characteristics and the subsequent crystallization behaviors of the synthesized ceramics. Among the various hydration species, the moderately bound and ordered water appears to be a key in regulating the crystallization rate. This nature-inspired study offers deeper insights into the magic behind biomineralization. [ABSTRACT FROM AUTHOR]

The article reports on a small-molecule compound CYD19 that forms a high-affinity interaction with the evolutionarily conserved arginine-174 pocket of Snail protein. It mentions that in aggressive cancer cells, CYD19 binds to Snail and thus disrupts Snail's interaction with CREB-binding protein; and also mentions that CYD19 reverses Snail-mediated epithelial-mesenchymal transition (EMT) and impairs EMT-associated tumor invasion and metastasis.

The article studies the potential existence of Archean mantle at a mid-ocean ridge. The study shows the Southwest Indian Ridge (SWIR) abyssal peridotites with protogranular to porphyroclastic textures have variable compositions, the Protea and low-Fo Knorr samples are relatively fertile, Archean lithospheric material consists of ultrarefractory, low-density peridotites, which are relative to the asthenospheric mantle.

The article presents a study that explores the recapitulating hepatitis E virus–host interactions and facilitating antiviral drug discovery in human liver–derived organoids. It mentions that hepatotropic viruses naturally have narrow host and tissue tropisms, challenging the development of robust experimental models.

The article presents RAD51AP2 is required for efficient meiotic recombination between X and Y chromosomes. Topic discussed include Faithful segregation of X and Y chromosomes requires meiotic recombination to form a crossover between them in the pseudo autosomal region (PAR); and double-strand breaks (DSBs) than crossovers, one crossover must be formed from the one or two DSBs in PARs, implying the existence of a sex chromosome–specific recombination mechanism.

The article presents a study that explores the chromatin architecture at susceptible gene loci in cerebellar Purkinje cells characterizes DNA damage–induced neurodegeneration. It mentions about the pathogenic basis of DNA damage in the nervous system and suggest chromatin conformation as a feature in directing genome instability–associated neuropathology.

The article provides information about the utilization of atomic electron tomography to determine the three-dimensional (3D) atomic structures and crystal defects at the interface of a MoS2-WSe2 heterojunction with high precision. This research reveals the existence of point defects, bond distortion, and atomic-scale ripples at the heterointerface and quantifies the 3D strain tensor.

The article presents a study that explores the improved estimates of preindustrial biomass burning reduce the magnitude of aerosol climate forcing in the Southern Hemisphere. It mentions the role of fire in shaping terrestrial ecosystems and the chemical composition of the atmosphere and thus influences Earth's climate.

The article offers information on the oxidation oftrimethylamine to trimethylamine N-oxide facilitates high hydrostatic pressure tolerance in a generalist bacterial lineage. It mentions the improved High hydrostatic pressure (HHP) tolerance in the presence of TMA, implying the universality of this HHP tolerance strategy in marine Bacteroidetes.

The article offers information on Accumulation of collagen molecular unfolding is the mechanism of cyclic fatigue damage and failure in collagenous tissues. It mentions results revealed that triple-helical collagen denaturation accumulates with increasing cycles of fatigue loading, and damage is correlated with creep strain independent of the cyclic strain rate.

The article presents a study deepens understanding of CLC-7/Ostm1 transporter and provides insights into the molecular basis of the disease-related mutations. It mentions that CLC family proteins translocate chloride ions across cell membranes to maintain the membrane potential, regulate the transepithelial Cl− transport, and control the intravesicular pH among different organelles.

The article offers information on in vivo application strategies for 3D-printed macroscale products for surgical implantation. Topics discussed include use of digital near-infrared (NIR) photopolymerization (DNP)–based 3D printing technology for noninvasive in vivo 3D bioprinting of tissue; modulation of near-infrared (NIR) for spatially inducing the polymerization of monomer solutions; and generation of customized living tissue constructs in body without surgery implantation.

The article presents a study of a low-profile membrane-based stretchable ultrasonic transducer using an array of thin and high-performance piezoelectric composites, which conform to and detect nonplanar complex surfaces. The probe shows improved electromechanical coupling, reduced cross-talk and over 50% of stretchability, demonstrated through the reconstruction of defects in three-dimensional (3D) space.

The NLR family apoptosis inhibitory proteins (NAIPs) bind conserved bacterial ligands, such as the bacterial rod protein PrgJ, and recruit NLR family CARD-containing protein 4 (NLRC4) as the inflammasome adapter to activate innate immunity. We found that the PrgJ-NAIP2-NLRC4 inflammasome is assembled into multisubunit disk-like structures through a unidirectional adenosine triphosphatase polymerization, primed with a single PrgJ-activated NAIP2 per disk. Cryo-electron microscopy (cryo-EM) reconstruction at subnanometer resolution revealed a ~90° hinge rotation accompanying NLRC4 activation. Unlike in the related heptameric Apaf-1 apoptosome, in which each subunit needs to be conformationally activated by its ligand before assembly, a single PrgJ-activated NAIP2 initiates NLRC4 polymerization in a domino-like reaction to promote the disk assembly. These insights reveal the mechanism of signal amplification in NAIP-NLRC4 inflammasomes. [ABSTRACT FROM AUTHOR]