Browse Articles

Typical development of the human fetal subplate: Regional heterogeneity, growth, and asymmetry assessed by in vivo T2-weighted MRI

The subplate (SP) is a transient fetal brain compartment supporting neuronal migration, axonal ingrowth, and early cortical activity, yet the dynamics of its regional development remain poorly understood in vivo. Using T2-weighted fetal MRI of 68 typically developing fetuses (22 to 32 wk gestational age, GA), we developed a semiautomated pipeline to quantify regional SP morphology (thickness, surface area, and volume). SP characteristics scaled strongly with GA and residual brain volume and showed marked regional differences. After correcting for geometric confounds, regional variation of SP thickness persisted, with highest values in parietal and perisylvian regions, suggesting that SP thickness may serve as a sensitive marker of intrinsic developmental differences. Between the late 2nd and early 3rd trimesters, mean SP thickness increased by 39.2% with large variation across regions (±11.0 SD), whereas surface area growth was more uniform (64.3% ±0.7 SD). Continuous growth trajectories clustered into distinct spatiotemporal profiles: early-developing regions (e.g., pericentral and medial occipital cortices) contrasted with later-developing regions (prefrontal, temporal, and parietal cortices). These patterns partially recapitulate primary-to-association, medial-to-lateral, and posterior-to-anterior maturational hierarchies, pointing to organized developmental programs. SP development also showed region-specific hemispheric asymmetries, including leftward thickness and volume asymmetry in the superior temporal and precentral gyri. Some asymmetries amplified, others attenuated or reversed with age, suggesting both transient states and potential precursors of postnatal lateralization. Together, these findings provide a framework for regional SP quantification and position SP morphology, particularly thickness, as a promising early biomarker that might link fetal SP changes to subsequent cortical development and neurodevelopmental outcomes.

Serum metabolomics identifies gut-derived uremic toxins and bile acid dysregulation associated with chronic kidney disease severity

Abstract Chronic kidney disease (CKD) affects more than 700 million people worldwide, however conventional biomarkers like creatinine cannot identify early-stage disease or accurately predict progression. In this study, untargeted and targeted metabolomic approaches were combined to identify novel biomarkers relevant for CKD staging and early detection in an underrepresented Egyptian population. Untargeted ultra-high-performance liquid chromatography–mass spectrometry analyses in both ionization modes were performed on serum samples of 50 CKD patients [25 early-stage CKD (eCKD), 25 end-stage kidney disease (ESKD)] and 20 controls. Differential metabolites were determined by univariate and multivariate analyses, coupled with pathway analysis and correlations with estimated glomerular filtration rate (eGFR). Five discriminating metabolites (p-hydroxyphenyllactic acid, indoxyl sulfate, xanthurenic acid, trimethylamine-N-oxide, and glycochenodeoxycholate) were subjected to targeted LC-MS/MS validation in an independent cohort (35 eCKD, 35 ESKD, 15 controls). Gut-derived uremic toxins, bile acid and tryptophan–kynurenine metabolic dysregulation were associated with CKD severity. p-hydroxyphenyllactic acid, xanthurenic acid, glutamyl-valine and indoxyl sulfate showed strong inverse correlations with eGFR ( r = -0.75 to -0.85). A five-metabolite panel (indoxyl sulfate, p-hydroxyphenyllactic acid, trimethylamine-N-oxide, glycochenodeoxycholate, xanthurenic acid), demonstrated superior discriminatory performance compared with creatinine alone for distinguishing ESKD, especially indoxyl sulfate and p-hydroxyphenyllactic acid (AUC 0.847 and 0.828, respectively vs. 0.688). This first comprehensive metabolomics study in Egyptian CKD patients identifies alterations in gut microbiome–derived metabolites and bile acid metabolism associated with CKD severity. The multi-metabolite panel demonstrates potential for non-invasive discrimination between CKD stages and supports future longitudinal metabolomic studies aimed at improving CKD risk stratification and patient management.

Deep learning–enabled scaffolding of spatial arrays of PfCSP epitopes

Malaria is a leading cause of disease in developing countries. The licensed malaria vaccine RTS,S/AS01 confers partial protection in part due to the elicitation of circumsporozoite protein (CSP) antibodies, of which those to the CSP repeat and junctional regions offer the most potent protection. Anti-repeat region antibodies, including the protective antibody L9, frequently develop mutations that promote inter-Fab contacts when bound to CSP in “spiral” quaternary structures. As a first step toward the design of immunogens that elicit L9-like antibodies, we utilized generative deep learning models to design epitope scaffolds that incorporated up to three junctional repeat epitopes with structural conformations and relative spatial orientations matching those of the multivalent complex of CSP bound to three copies of L9. Affinity and structural studies demonstrated accurate scaffolding of two epitopes with the intended relative orientation, and displacement of the third epitope, while maintaining inter-Fab contacts between L9 antibodies. In a mouse model of malaria liver invasion, immunization with nanoparticles displaying these scaffold immunogens inhibited liver invasion as potently as matched nanoparticles displaying a short junctional peptide but less potently than the same nanoparticles displaying longer junctional peptides. This study demonstrates a substantial advance for design of multiepitope scaffolds with predetermined relative epitope spatial positioning. The study also represents an initial step toward development of multiepitope immunogens to elicit antibodies that utilize homotypic interactions to bind pathogens in multivalent clusters.

First-principles study of hydrogen-related defects at the a-SiO2/Si(100) interface

The colors of images preferred by individual voxels can be used to delineate functionally distinct visually responsive brain areas

We exploited co-occurrences between color and other properties of natural scenes to identify and visualize functionally distinct brain regions. For each voxel in the Natural Scenes Dataset (NSD), we computed a scaled response-weighted average of the stimulus images. The colors of “voxel-preferred images” (VPIs) reflect stimulus properties that covary with color in natural scenes: Color serves as a tag for functional distinctions in voxel responses. Mapping VPIs onto cortical surfaces revealed reliable and structured color patterns that segment voxel clusters. Boundaries between clusters of similarly colored VPIs tend to coincide with boundaries defined using other methods, and heterogeneity within regions suggests functional subdivisions. VPIs provide a simple data-driven method for analyzing fMRI responses to natural scenes and visualizing cortical organization.

Visual obstacle avoidance technology of VSLAM indoor intelligent logistics robot combining optical flow and feature extraction

Meiotic prophase I disruption as a strategy for nonhormonal male contraception using small-molecule inhibitor JQ1

Developing safe, reversible, and nonhormonal male contraceptives has been hindered by the lack of defined biological windows that can be transiently interrupted without compromising long-term fertility. Here, we tested whether meiotic prophase I can serve as such a window by pharmacologically inhibiting the testis-specific chromatin reader BRDT using the small-molecule bromodomain inhibitor (+)-JQ1 as proof-of-principle. Short-term JQ1 administration (3 wk) selectively disrupted the pachytene transcriptional program, depleted postmeiotic germ cells, and induced a reversible arrest in spermatogenesis. Upon drug withdrawal, prophase I cytological markers normalized within 6 wk, accompanied by restoration of testis architecture and germ-cell composition. Crossover metrics and transcriptional programs recovered more gradually, reaching full normalization by 30 wk alongside complete restoration of fertility and fecundity. These results demonstrate that meiotic prophase I can be transiently inhibited to suppress spermatogenesis reversibly without inducing lasting genomic or reproductive defects, defining a stage-specific framework for the rational design of nonhormonal male contraceptives.

Enhanced color image denoising using fuzzy metric-like space and peer group

Munc13 serves as a molecular filter for SNARE sorting and assembly in active zone condensates

Neurotransmitter release requires the precise localization and assembly of the SNARE machinery at presynaptic release sites. Although liquid–liquid phase separation of active zone scaffolds is known to organize these sites, the mechanism for the specific enrichment of the SNARE machinery has remained unclear. In this study, we establish that within RIM1/RIM-BP2 biomolecular condensates, Munc13-1 functions as an organizational hub that spatially sorts and concentrates cognate SNAREs, orchestrating their stepwise assembly. In particular, this condensate environment empowers Munc13-1 to cluster Syb2 into nanodomains on the vesicle membrane, dramatically increasing local SNARE density and ensuring efficient complex formation. Consequently, the introduction of RIM1/RIM-BP2 into PC12 cells enhances spatiotemporally precise dense-core vesicle exocytosis in a Munc13-dependent manner. Our findings suggest a model in which phase separation creates a privileged platform that enables Munc13-1 to direct SNARE complex assembly, thereby ensuring the speed and precision of synaptic vesicle exocytosis.

Comparing substrates for mycelium-based composite insulation materials with thermal and environmental assessment

Abstract The construction industry needs to transition toward more sustainable materials to reduce environmental impacts. Insulation materials reduce energy demands of buildings, yet traditional options often have high embodied carbon and rely on finite resources. Mycelium-based composites (MBCs) have emerged as promising bio-based alternatives, formed by the colonisation of fungal mycelium on lignocellulosic feedstocks; the mycelium acts as a natural adhesive and upon drying an inert material is produced. MBCs have demonstrated low thermal conductivity ( $$\lambda$$ ) and sustainability benefits, with substrate choice being a key factor in determining both thermal and environmental performance. This study emphasises the need for a functional unit (FU) that accounts for thermal performance rather than mass-based declared units (DUs) in Life Cycle Assessment (LCA). MBCs were produced using Lentinus tigrinus mycelium and five different substrates: ash-wood chips, bark, beech-wood sawdust, hemp shiv, and wheat straw. Thermal conductivity measurements (ASTM C518) were conducted, revealing that ash-wood chip MBCs exhibited the highest thermal conductivity ( $$\lambda$$ = 0.048 W/m $$\cdot$$ K), while straw-based MBCs had the lowest ( $$\lambda$$ = 0.031 W/m $$\cdot$$ K). Thermal conductivity and density of the material were used to calculate the FU (mass of insulation required to achieve an R-value of 1 m $$^2$$ K/W). A cradle-to-gate LCA (EN 15804) compared environmental impacts per FU for each MBC produced at lab-scale. Ash-wood chip MBCs demonstrated the lowest total global warming potential (GWP) (-9.77 kg CO $$_2$$ eq), while straw-based MBCs had the highest (4.04 kg CO $$_2$$ eq). Further analyses examined whether transport distance, waste designation, and carbon sequestration uncertainty would affect substrate ranking and, consequently, selection. While local sourcing and waste-derived substrates reduced emissions, it did not alter rankings. A Monte Carlo analysis confirmed that even with uncertainty in substrate carbon sequestration, MBCs maintained low GWP values. These findings show that low $$\lambda$$ MBCs can be produced from various substrates. Substrate selection should consider thermal and environmental performance, as carbon sequestration, rather than $$\lambda$$ , is the dominant factor influencing GWP. This underscores the need to consider broader environmental trade-offs when optimising MBC insulation materials.

A regulatory axis for tonotopic MYO7A expression in cochlear hair cells

Myo7a , a gene mutated in Usher syndrome and nonsyndromic deafness, encodes an unconventional myosin essential for hair cell function. Our previous work revealed that cochlear hair cells express distinct Myo7a isoforms with unique spatial and cell type–specific patterns. The canonical isoform ( Myo7a-C ) and an additional isoform ( Myo7a-N ) are co-expressed in outer hair cells (OHCs) but exhibit opposing tonotopic gradients, while inner hair cells primarily express Myo7a-C . These isoforms arise from distinct transcriptional start sites, indicating separate regulatory inputs. Here, we identify an intronic cis- regulatory element, EnhancerA , essential for tonotopically graded Myo7a expression. EnhancerA deletion reduces MYO7A protein levels in a tonotopically varied manner, disrupts hair bundle morphogenesis, alters OHC mechanotransduction, and leads to hair cell degeneration and hearing loss. We further identify SIX2, a tonotopically expressed transcription factor that may interact with EnhancerA to regulate Myo7a-N in OHCs. These findings define a cis–trans regulatory axis critical for isoform-specific Myo7a expression and cochlear function.

Utilizing deep learning from mobile phone photos for early detection of horizontal strabismus: a screening approach

Antagonism by the type VI secretion system of <i>Bacteroides fragilis</i> is controlled by a TetR family regulator and released small molecule

Antagonistic systems of bacteria are often tightly regulated. The human gut Bacteroidales harbor three distinct antagonistic type VI secretion systems (T6SS), one of which is present only in Bacteroides fragilis , known as the GA3 T6SS. Although this is the best studied of the three T6SSs, little is known about how it is regulated. The gene upstream of the GA3 T6SS locus encodes a TetR family transcriptional regulator (TetR GA3 ), which we show represses expression of the GA3 T6SS locus. The gene immediately upstream and divergently transcribed from tetR GA3 , designated here as lgs GA3 , encodes a product of the α-oxoamine synthase family of pyridoxal phosphate-dependent enzymes with structural homology to the CqsA autoinducer synthase of the CAI-1 quorum sensing system of Vibrio spp . When lgs GA3 is deleted, transcription of the GA3 T6SS locus is repressed in a TetR-dependent manner. Strains synthesizing Lgs GA3 produce a molecule released into the supernatant that likely serves as the TetR GA3 ligand, overcoming TetR transcriptional repression of the GA3 T6SS. We show that GA3 T6SS-specific immunity genes present on two acquired immunity defense islands are also regulated by Lgs GA3 coordinating expression of GA3 T6SS antagonism with protection from competitor’s GA3 T6SS toxins. Production and firing of the GA3 T6SS and subsequent antagonism occurs in bacteria deleted for lgs GA3 when growing with bacteria containing this gene or their supernatants or when cocolonizing gnotobiotic mice. These data show that the GA3 T6SS is regulated by a small molecule acting through TetR GA3 allowing the bacteria to coordinate antagonistic and protective systems.

Investigation of optical, structural, and radiation shielding properties of novel polyvinyl alcohol and cesium dichromate Cs2Cr2O7 nanocomposite films

Spatial and semantic memory reorganize a hippocampal long-axis gradient

The hippocampus supports episodic memory by binding spatial and semantic information, yet how this information is simultaneously organized along its long axis remains debated. Gradient accounts propose a continuous shift in representational scale, from coarse coding in anterior to fine coding in posterior regions, whereas modular accounts posit discrete subregions specialized for distinct functions. Using high-resolution fMRI together with eye tracking as a readout of spatial and semantic memory during sequence learning, we directly tested these competing models. During predictable sequences, hippocampal activity continuously varied along the long axis. In contrast, modular organization emerged when sequences mismatched memory. Subregions in the anterior and posterior hippocampus were sensitive to semantic and spatial mismatches, respectively. Notably, the intermediate hippocampus was specifically sensitive to concurrent mismatches in both dimensions, but not to mismatches in either dimension alone. These content-sensitive subregions were embedded within distinct cortical networks that reorganized according to memory demands. Together, our findings reveal a dynamic hippocampal architecture that flexibly combines gradient and modular principles to simultaneously represent the spatial and semantic content that defines episodic memory.

Predictive modelling of Uranium (238U) and Thorium (232Th) in soils of Central India: integrating ICP-MS/MS, spectroscopic, and machine learning models

Shift current anomalous photovoltaics in a double perovskite ferroelectric

Ferroelectric anomalous photovoltaic (APV) effect, as a fascinating physical conceptual phenomenon, holds significant potentials for new optoelectronic device applications. However, due to the lack of knowledge on the origin and underlying mechanism of ferroelectric APV effect, substantial challenges still remain in exploring new APV-active candidate materials. The emerging shift current model, involving the transfer of photogenerated charges through the displacement of wave functions, has attracted considerable attention for its unique insights into the bulk photovoltaic effect. Here, we present strong APV properties in a high-temperature double perovskite ferroelectric (cyclohexylmethylammonium) 2 CsAgBiBr 7 , showing an extremely large above-bandgap photovoltage up to ~40 V. This figure-of-merit is far beyond its bandgap of ~2.3 eV and comparable to the state-of-art molecular ferroelectrics. Strikingly, the shift current model reveals an intrinsic correlation with Cs + cation displacement and provides an explicit explanation for the structural origin of ferroelectric APV activities. Besides, its steady-state APV photocurrent exhibits the unique light-polarization dependence, which endows remarkable polarization-sensitivity with the highest polarization ratios of ~41 among the known 2D single-phase materials. As the feasible exploration of ferroelectric APV characteristics illuminated by the shift current mechanism, this finding paves a pathway to assemble new optoelectronic smart devices.

Uncertainty and unmet needs in older high-risk blunt trauma survivors and their caregivers: a multi-centre mixed methods study

Heat- and PIP2-dependent TRPM4 activity underlies mutually exclusive human diseases

Temperature-sensitive transient receptor potential melastatin subfamily 4 (TRPM4) ion channels convert intracellular calcium increases into membrane depolarization, thereby linking these two powerful cellular signaling pathways in diverse physiological processes. TRPM4 mutations cause severe human hereditary cardiovascular and skin diseases; mysteriously, while these mutations are gain-of-function in nature, they affect the heart and the skin in a mutually exclusive manner. Here, we show that phosphatidylinositol 4,5-bisphosphate (PIP2) lipid is a required cofactor for TRPM4 activity by tightly regulating its calcium sensitivity. We detected two PIP2 binding sites and located the high-affinity site adjacent to the S4-S5 linker. We demonstrated that skin disease–associated TRPM4 mutations relieve the tight control of PIP2, resulting in elevated channel activity but only at the body surface temperature. In contrast, heart diseases are associated with mutations known to boost the number of channels, an effect we found to be annihilated by channel desensitization outside the body core. Indeed, dendritic cells from transgenic mice carrying a skin disease mutant exhibited elevated migration at 25-to-30°C range compared to those from normal mice, but no difference was observed at 37°C. These findings shed light on a molecular mechanism for dynamic regulation of cellular signaling in physiology and diseases.

Multiphase horizontal migration of BTEX in aquifers during in-situ oil shale exploitation