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Wen, Q.

Publications and source records attributed to Wen, Q..

At least 19 recordsLinked to original sources

Physiological Oscillations of Lateral Ventricular Volume Revealed by Fast fMRI: Effects of Aging and Vigilance

Abstract Background: Cyclic ventricular deformation may contribute to CSF displacement. However, the physiological mechanisms underlying ventricular motion remain poorly understood. This study characterized physiological oscillations of lateral ventricular volume (LVV) and examined their associations with aging and vigilance. Methods: We analyzed two fast resting-state fMRI scans from 99 adults aged 35-82 years. The first scan was acquired during eyes-open wakefulness, followed by 30 min of eyes-closed rest and a second scan during eyes-closed drowsiness. LVV was estimated for each image volume using automated ventricular segmentation, yielding time-resolved volume measurements. Temporal variability was quantified using the standard deviation and coefficient of variation, and spectral power was quantified for low-frequency, respiratory, and cardiac oscillations. Age-related associations were assessed using multiple linear regression adjusted for sex. Awake-drowsy differences were assessed using paired t-tests. False discovery rate correction was applied for multiple comparisons in all analyses. Results: After quality-control exclusions, 97 participants were analyzed. LVV exhibited distinct low-frequency, respiratory, and cardiac oscillatory components. Respiratory and cardiac oscillations accounted for 37.7% and 38.4% of total physiological spectral power, respectively, compared with 23.9% for low-frequency oscillations. Mean lateral ventricular volume increased with age (FDR-adjusted p = 0.010), while respiratory and cardiac power also showed positive associations with age, although neither survived FDR correction (both FDR-adjusted p = 0.067). The transition to eyes-closed drowsiness was associated with greater LVV fluctuation magnitude, reflected by increases in standard deviation (FDR-adjusted p < 0.001) and coefficient of variation (FDR-adjusted p = 0.028) and accompanied by increased low-frequency (FDR-adjusted p < 0.001) and respiratory power (FDR-adjusted p = 0.015). Mean LVV and cardiac power did not change significantly between conditions. Conclusions: LVV exhibits prominent respiratory and cardiac oscillations in addition to low-frequency fluctuations, suggesting that ventricular dynamics reflect multiple physiological influences rather than a single dominant physiological driver. Aging was primarily associated with ventricular enlargement, whereas reduced vigilance was accompanied by increased LVV fluctuation magnitude, primarily reflected in increased low-frequency and respiratory power, without a change in mean LVV. Time-resolved LVV provides a complementary approach for investigating the physiological regulation of ventricular dynamics in health and disease. Keywords: Cerebrospinal fluid; Lateral ventricular volume; Fast fMRI; Physiological oscillations; Cardiac pulsation; Respiration; Low-frequency oscillations; Aging; Vigilance

bioengineering↗

Structure and energy transfer of a minimal PSI-LHCI supercomplex with FNR binding from a terrestrial eustigmatophyte

Soil microalgae endure harsh terrestrial stressors, such as intense light. Eustigmatophytes are an independent evolutionary branch within stramenopiles and occupy diverse aquatic and terrestrial environments, but the structural organization of their photosynthetic apparatus remains poorly understood. Here, we determined the cryo-electron microscopy structure of a photosystem I-light-harvesting complex I (PSI-LHCI) supercomplex bound with ferredoxin-NADP+ oxidoreductase (FNR) from the terrestrial eustigmatophyte Vischeria stellata at 2.44 [A] resolution. The supercomplex contains a monomeric PSI core associated with only three LHCI subunits, representing the smallest PSI-LHCI reported among structurally characterized red-lineage PSI complexes composed of violaxanthin-Chl a proteins (VCPs). The three VCPIs with distinct structure features and arrangements form a compact belt along the PsaL-PsaI-PsaM side of PSI. The structure also resolves a 43-residue N-terminal segment of FNR (FNR-N) bound to the PSI stromal surface, which is stabilized by both a eustigmatophyte-conserved insertion in PsaL and the N-terminal region of PsaD. In contrast, the catalytic region of FNR was not resolved, suggesting conformational flexibility. Computational simulations indicate potential excitation-energy-transfer pathways connecting the three VCPI subunits to the PSI core and highlight lineage-specific pigments that maintain energetic connectivity within the exceptionally compact antenna. Our analysis further reveals conservation of FNR tethering despite pronounced diversification of antenna size and organization. These findings uncover a modular evolutionary principle in which PSI acceptor-side organization is retained while the light-harvesting antenna is extensively remodeled, providing a framework for understanding the diversification of photosynthetic energy conversion across ecological transitions.

plant biology↗

Partial epithelial-to-mesenchymal transition mediates profound gap closure through growth and fluidization

Epithelial gap closure is essential for maintaining tissue integrity during development and wound healing. Previous studies have shown that closure of small gaps is driven by actomyosin purse-string contraction and traction forces generated at the gap edge. Here, we show that millimeter-scale circular gap closure in mouse epicardial (MEC1) monolayers is driven primarily by growth-mediated compressive stresses. Compared with MDCK monolayers, MEC1 cells close gaps more rapidly with reduced undulation near gap edge through coordinated tissue-wide extension-contraction. The collective closing dynamics can be modulated by partial epithelial-mesenchymal transition induction and Rho kinase inhibition. By integrating tissue and cell kinematic analyses, traction-force mapping, and a continuum framework that decomposes tissue strain rates into growth-, elastic-, and fluidity-related contributions, we reveal that growth-generated compression drives inward tissue flow, while elastic cell elongation and fluid-like tissue remodeling through cell-cell intercalation act synergistically to accommodate deformation and promote robust collective gap closure.

biophysics↗

A Structural Principle for Macroscopic Neural Dynamics Correlations

A central question in neuroscience is how the brains structural connectivity gives rise to its emergent, correlated dynamics. These large-scale dynamical correlations underlie functional networks that support cognitive functions. Here, we identify coupling correlation--the similarity between the input connectivity profiles of brain regions--as a key structural determinant of macroscopic neural dynamical correlation. Using dynamical mean-field theory (DMFT) and numerical simulations of random neural network models, we demonstrate that coupling correlation quantitatively governs dynamical correlation. The functional form of this structure-function mapping is dictated by the eigenvalue spectrum of the coupling correlation matrix: networks with bulk eigenspectra exhibit an exact linear relationship, whereas biologically plausible long-tailed spectra yield an approximately linear mapping except when the magnitude of coupling correlation approaches unity. Particularly, a long-tailed spectrum is necessary to reproduce the appropriate magnitude and size-invariance of coupling correlations observed in empirical data, thereby sustaining non-vanishing dynamical correlations that may support brain function in large systems. The theoretical prediction of approximate linearity is consistently validated using empirical datasets that include both structural coupling and neural dynamics in humans, mice, and Drosophila. Together, these results provide a mechanistic and quantitative framework linking macroscopic brain network structure to emergent neural dynamics--an essential step toward a theory of structure-function relationship in the brain. Significance StatementHow the brains wiring gives rise to its coordinated activity is a fundamental unsolved problem in neuroscience. Prior work has identified correlations between structural and functional connectivity, but these relationships lacked a mechanistic, first-principles explanation. Here, we derive an analytical framework using Dynamical Mean-Field Theory and random neural network models to show that a single structural statistic--coupling correlation, the similarity between the input connectivity profiles of brain regions--linearly and causally determines the magnitude of correlated neural dynamics. We further show that a long-tailed eigenvalue spectrum in biological structural connectivity is necessary to sustain the strong, size-invariant functional correlations observed across species. Validated in humans, mice, and Drosophila using multiple imaging and connectome modalities, this principle may provide a quantitative bridge between structural connectomics and emergent brain dynamics, with implications extending to a broad class of complex networked systems.

neuroscience↗

Zero-shot design of a de novo metalloenzyme

The de novo design of enzymes remains a central challenge, requiring consideration of catalytic mechanism and optimization across biochemical and biophysical criteria. Here we present dEVA (design by EVolutionary Algorithm), a multi-objective protein design framework built on principles drawn from evolutionary biology. We apply dEVA to the zero-shot, de novo design of metalloenzymes by optimizing the coordination sphere of catalytic metals. We characterize a bizinc metalloenzyme that exhibits promiscuous hydrolytic activity towards both phosphomonoesters and phosphodiesters. This design achieves a rate enhancement ((kcat/KM)/kw) up to 3 x 1013, comparable to characterized natural phosphatases. dEVA offers a general and modular strategy for the programmable design of protein function without dependence on natural templates or evolutionary information.

biochemistry↗

Scaling Multiplex qPCR Primer Design to 1000-plex using the Degenerate Incomplete Multiplex Primer List Extension (DIMPLE) Algorithm

Massively multiplexed qPCR is primarily constrained by increasing primer dimer formation as the number of distinct primers in a single reaction increases. Previous multiplex primer design algorithms either fail to sufficiently suppress primer dimers at 100+ plex, or take exceedingly high amounts of computational resources to complete. Here, we present DIMPLE, a linear-runtime primer design algorithm that effectively generates 10,000+ primers to amplify thousands of potential amplicons in a single qPCR reaction. As one clinical demonstration of this algorithm, we designed an assay to detect 2,302 distinct KMT2A gene fusion subtypes using 204 primers in a single tube. In contrast to FISH and convention NGS approaches with 2% variant allele frequency (VAF) limit of detection, our DIMPLE qPCR assay was able to analytically detect gene fusions down to 0.05% VAF. We also constructed proof-of-concept multiplex qPCR panels for additional oncology gene fusions, multiplex pathogen detection, and DNA methylation markers. The scalability and low computational cost DIMPLE are complementary to new instrument platforms for massively multiplex qPCR readout for enabling rapid, point-of-care nucleic acid testing.

bioengineering↗

Serotonergic modulation of motor subspace dynamics drives a sleep-independent quiescent state

The dorsal raphe nucleus (DRN) serotonergic (5-HT) system has been implicated in regulating sleep and motor control; however, its specific role remains controversial. In this study, we found that optogenetic activation of DRN 5-HT neurons in larval zebrafish induced a quiescent state and a reduced response to acoustic stimuli. Unlike sleep, the induced quiescent state was not accompanied by a loss of postural control, and nighttime activation of DRN 5-HT neurons led to a subsequent sleep rebound. Whole brain light field imaging combined with demixed principal component analysis (dPCA) revealed distinct neural subspaces related to DRN activation, sound responses, and motor activity. DRN 5-HT activation selectively modulated the motor-related subspace while leaving the sound-evoked subspace unaffected. Unlike DRN activation, sleep induced by mepyramine significantly altered sound-evoked neuronal activity patterns. Further analysis demonstrated that serotonin had a graded effect on the motor subspace, wherein downstream neurons responsible for particular bout types were more significantly influenced. Embedding motor population activity in a curved geometric space revealed that the degree of curvature scales with behavioral suppression across animals, providing a quantitative signature of the quiescent state. Together, these results elucidate that serotonergic modulation promotes behavioral quiescence through selective regulation of motor populations.

neuroscience↗

ADAPT-M: A workflow for rapid, quantitative in vitro measurements of enriched protein libraries

Protein-protein interactions underpin most cellular interactions, and engineered binders present powerful tools for probing biology and developing novel therapeutics. One bottleneck in binder generation is the scalable, quantitative characterization of these interactions. We present ADAPT-M (Affinity Determination by Adaptation of ProTein binders for Microfluidics), a streamlined workflow that connects yeast surface display (YSD) with in vitro affinity and kinetic measurements using the high-throughput STAMMPPING microfluidic platform. ADAPT-M quantifies Kds and dissociation kinetic parameters for hundreds of enriched protein variants in under one week without requiring hands-on protein purification. We applied ADAPT-M to a computationally designed library targeting the SARS-CoV-2 Omicron BA.1 receptor binding domain, successfully recovering and measuring Kds for most highly enriched YSD variants. Measurements correlate strongly with biolayer interferometry and yeast titration assays. ADAPT-M further enabled selection of lead candidates for structural and mutational analysis, which revealed designed paratopes were preserved despite binding to off-target epitopes. By bridging YSD screening and in vitro validation, ADAPT-M accelerates protein binder discovery and supports data-driven protein engineering.

biophysics↗

Independent Tuning of Stiffness and Pore Size in 3D Rat Tail Collagen I Matrices

The interplay between extracellular matrix (ECM) mechanics and the tumor microenvironment is increasingly recognized as a key driver of cancer progression. Three-dimensional (3D) collagen I culture systems provide more physiologically relevant environments than traditional 2D cultures, yet seperately controlling the structural and mechanical features of 3D matrices remains challenging due to their inherent interdependence. Here, we present a collagen-based approach to decouple bulk stiffness and pore size by varying collagen concentration and polymerization temperature. Collagen concentration was varied to modulate bulk storage modulus, while polymerization temperature was adjusted to alter pore dimensons at comparable collagen concentrations. Using this approach, we generated 3D Collagen I matrices with bulk storage moduli of approximately 80, 228, and 360 Pa while maintaining a similar median pore sizes near 2.5 m. Conversely, 1.5 mg/mL collagen, median pore size varied from approximately 2.5 to 3.1 m while bulk storage modulus remained near 80 Pa, whereas at 3.5 mg/mL collagen, pore size varied from approximately 2.0 to 2.4 m while bulk storage modulus remained near 350 Pa. We further evaluated the responses of MCF-10A epithelial cells and MDA-MB-231 metastatic breast cancer cells to matrices spanning these sturactual and mechanical conditions. Although the changes in pore size within each stiffness range were modest, they were associated with measurable and statistical differences in cell morphology. These findings demonstrate that even modest changes in collagen network architecture can produce measurable differences in cellular behvarior under comparable bulk mechanical conditions, highlighitng the importance of considering matrix structure in addition to stiffness when investigating cell-matrix interactions.

biophysics↗

TRACC-PHYSIO: Time-domain Resolution-Aligned Cross-Correlation to estimate PHYSIOlogical coupling and time delays in dynamic MRI

Physiological brain pulsations, primarily driven by cardiac and respiratory activity, play a key role in driving neurofluid circulation and waste clearance. Capturing the temporal dynamics of cardiac- and respiratory-driven brain pulsations (0.2-1.5 Hz) requires fast imaging with TRs near 100 ms, which is often unachievable in functional MRI or dynamic diffusion MRI. As a result, valuable physiological information remains hidden in these datasets. Here, we introduce TRACC-PHYSIO, a time-domain analytical framework designed to quantify physiological coupling and pulse time delays in dynamic MRI without requiring a fast acquisition. TRACC-PHYSIO uses cross-correlation to detect co-fluctuations between slowly sampled dynamic MRI data and simultaneously recorded physiological waveforms. It measures two key metrics: the peak Coupling Coefficient (peak CorrCoeff), quantifying the strength of co-fluctuations, and the TimeDelay, reflecting the relative arrival time of the physiological impulse in the brain with millisecond-level temporal resolution. The primary aim of this study is to validate TRACC-PHYSIO through systematic simulations that model realistic dynamic MR signals with mixed physiological components. We comprehensively evaluate TRACC-PHYSIOs performance under a wide range of conditions, including varying cardiac-to-respiratory composition ratios, TRs, and acquisition times. Results demonstrate that TRACC-PHYSIO can robustly assess coupling strengths and time delays for both cardiac (TRACC-Cardiac) and respiratory (TRACC-Respiratory) components, even in datasets with long TRs up to 3 seconds. By enabling a reliable time-domain coupling analysis, TRACC-PHYSIO opens new avenues for revealing brain pulsation mechanisms and elucidating the physiological drivers of neurofluid dynamics in health and disease. This stimulation study provides a valuable reference for interpreting TRACC-PHYSIO results and understanding associated uncertainties in future applications. Highlights- TRACC-PHYSIO is a time-domain method developed to estimate cardiac and respiratory coupling and their pulsation time delays in dynamic MRI without requiring high temporal resolution. - TRACC-PHYSIO was validated through systematic simulations across varying physiological compositions and MR acquisition parameters. - Results demonstrated that TRACC-PHYSIO reliably quantifies cardiac and respiratory components in dynamic MR signals. - The stimulation study provides a useful reference for interpreting TRACC-PHYSIO results and understanding associated uncertainties in future applications.

bioengineering↗

Mesoscopic SCAPE Microscope with a Rescanned, Super-oblique Illumination Plane

Investigating structural and functional dynamics across large spatial scales in living organisms calls for volumetric microscopy that combines a wide field of view (FOV), high spatial resolution, and sufficient temporal resolution. Swept confocally-aligned planar excitation (SCAPE) microscopy offers a compelling balance of optical sectioning, cellular resolution, and high-speed volumetric imaging. However, extending SCAPE to mesoscopic scales has been hindered by the limited tilting angle of the oblique illumination light sheet achievable with commercial low-magnification objectives. Here, we present a mesoscopic SCAPE microscope that overcomes this constraint by implementing a super-oblique light sheet--tilted up to ~60{degrees} relative to the optical axis of a 0.5-NA primary objective--enabled by an air-to-water bridging reflector. In addition, we introduce a single-galvanometer, self-conjugating rescanning strategy that allows arbitrary customization of the optical-to-mechanical angle ratio. This innovation accommodates the reversed and modulated scan displacement of the reflected light sheet and preserves descanned epi-fluorescence detection. Together, these advancements enable our mesoscopic SCAPE microscope to achieve a lateral FOV of 5.0 mm x 2.9 mm, cellular-level spatial resolution (~9.4 m x ~5.9 m lateral, and ~6.0 m axial), and a volumetric imaging rate of 9 volumes per second.

bioengineering↗

Molecular basis of vitamin K-dependent protein γ-glutamyl carboxylation

Gamma-glutamyl carboxylase (GGCX) in human is the sole enzyme responsible for catalyzing the carboxylation of glutamate (Glu) to {gamma}-carboxyglutamate (Gla), a process that relies on the deprotonation of reduced vitamin K. This post-translational modification of vitamin K-dependent proteins (VKDPs) plays a pivotal role in numerous biological processes. Mutations in GGCX are responsible for multiple clinical phenotypes; however, the molecular mechanisms of GGCX activity and its pathology remain poorly understood. In this study, we reported the cryo-electron microscopy (cryo-EM) structures of GGCX bound with the either FIX or FX, two VKDPs and vitamin K, and employed the biochemical and cellular assays as well as molecular dynamics simulations to elucidate its dual-catalytic properties. The enzyme comprises a transmembrane domain that anchors the vitamin K-binding site, along with an ER luminal domain that facilitates binding of coagulation factor IX (FIX) at the exosite. The catalytic center orchestrates the oxidation of vitamin K and the carboxylation of Glu residues through a Cap-H2 coupling mechanism, along where disease-associated mutations in GGCX are predominantly clustered. These findings offer a comprehensive molecular framework for understanding the allosteric regulation of GGCXs dual enzymatic activities and provide valuable insights for developing strategies to monitor and therapeutically target vitamin K metabolism in related diseases.

biochemistry↗

TurboID-based proximity labeling identifies novel germline proteins that maintain E granule integrity and small RNA homeostasis in C. elegans

Germ granules are biomolecular condensates composed of RNA and proteins that play crucial roles in RNA metabolism and posttranscriptional gene regulation. C. elegans germ granules consist of at least seven distinct subcompartments, including P granules, Z granules, Mutator foci, SIMR foci, P-bodies, D granules and E granules. Among these condensates, the E granule, which is nonrandomly positioned within the germ granule, is required for the production of a specialized class of small interfering RNAs (siRNAs). However, the mechanisms underlying E granule formation and its functional significance remain largely unexplored. In this study, via the use of TurboID- based proximity labeling technology combined with an RNAi-based reverse genetic screen, we identified two novel components of the E granule, EGC-2/C27B7.5 and EGC-3/F59G1.8, which initiate E granule assembly. The depletion of EGC-2 or EGC- 3 disrupts the perinuclear localization of the EGO and PICS complexes, both of which are enriched in E granules and are required for E-class siRNA and piRNA biogenesis, respectively. Small RNAomic analyses revealed that both EGC-2 and EGC-3 promote the production of 5 E-class siRNA, whereas prohibiting piRNA maturation. Taken together, our results elucidate the roles of EGC-2 and EGC-3 in maintaining E granule integrity and small RNA homeostasis, and suggest that intracellular condensation may exert distinct regulatory effects on different biological processes. Additionally, the combination of proximity labeling technology and reverse genetic screening provides a robust strategy for studying the assembly of biomolecular condensates.

genetics↗

Dual-timescale motor circuit dynamics underlies fast head exploratory behavior and efficient locomotion

Motor systems must balance flexibility and structure to enable efficient and adaptive movements. Traditional hierarchical descending models struggle to explain the intrinsic dynamism in natural behaviors. Here, we investigate the head exploratory behavior of Caenorhabditis elegans, a minimal system capable of intricate motor patterns. Using variational mode decomposition, we identified two distinct motor dynamics: slow rhythmic bends propagating along the body and fast, phase-specific head casts influencing directional bias. Combinatorial ablations of three types of cholinergic motor neurons, in conjunction with dynamical systems analysis, revealed their distinct and overlapping roles: RMD contributes to head casts, SMD sustains bending states, SMB and SMD enable slow rhythmic bending and head-body coupling. Collectively, these neurons form a central pattern generator (CPG) driving forward locomotion. In addition, RMD subgroups displayed unique calcium dynamics correlated with rapid head movements and slow transitions between behavior states. We propose that dual-proprioceptive feedback underlies these multi-timescale dynamics, with slow feedback coordinating rhythmic bending and fast feedback shaping head casts, thereby optimizing roaming efficiency. These findings highlight how intrinsic dynamics and structured composition emerge from highly interactive low-level circuits.

neuroscience↗

Targeted degradation of endogenous condensation-prone proteins improves crop performance

Effective methods, such as CRISPR and RNA interference, exist for modulating gene expression at DNA and RNA levels, but approaches for directly modifying endogenous proteins remain lacking in plants. Here, we develop a targeted condensation-prone-protein degradation (TCD) strategy to eliminate endogenous proteins, particularly those prone to condensation. We identify an E3 ligase, E3TCD1, that degrades itself but selectively targets other proteins when fused to them. In rice, transgenic E3TCD1 fusions with Teosinte branched 1 and Early flowering 3 (OsELF3) modulate tiller numbers and flowering times, respectively. The TCD system is also controllable. Using the ProTBF1-uORFsTBF1 expression control cassette, we can conditionally degrade the negative defense regulator OsELF3 upon pathogen invasion, enhancing rice resistance without interfering with rice flowering time. This method, unlike animal-targeting strategies, does not rely on small molecules, antibodies, or genetic knock-ins, showing promise as a gene therapeutic avenue for optimizing crop performance and potentially addressing human diseases.

plant biology↗

Investigation of cell mechanics and migration on DDR2-expressing neuroblastoma cell line

Neuroblastoma is a devastating disease accounting for ~15% of all childhood cancer deaths. Collagen content and fiber association within the tumor stroma influence tumor progression and metastasis. High expression levels of collagen receptor kinase, Discoidin domain receptor II (DDR2), are associated with poor survival of neuroblastoma patients. Additionally, cancer cells generate and sustain mechanical forces within their enviroment as a part of their normal physiology. Despite this, whether collagen activated DDR2 signaling dysregulate these migration forces is still elusive. To address these questions, a shRNA DDR2 knockdown neuroblastoma cell line (SH-SY5Y) was engineered to evaluate the consequence of DDR2 on cellular mechanics. Atomic force microscopy and traction force microscopy were utlizing to unveil the biophysical altercations. DDR2 down-regulation was found to significantly reduce proliferation, cell stiffness, and cellular elongation. Aditionally, DDR2 down-regulated cells had decreased traction forces when plated on collagen coated elastic substrates. Together, these results highlight the important role that DDR2 has in reducing migration mechanics in neuroblastoma and might be a promising target for future therapies.

cell biology↗

Robust data-driven segmentation of pulsatile cerebral vessels using functional magnetic resonance imaging

Functional magnetic resonance imaging (fMRI) captures rich physiological and neuronal information that can offer insights into neurofluid dynamics, vascular health, and waste clearance function. The availability of cerebral vessel segmentation could facilitate fluid dynamics research in fMRI. However, without magnetic resonance angiography scans, cerebral vessel segmentation is challenging and time-consuming. This study leverages cardiac-induced pulsatile fMRI signal to develop a data-driven, automatic segmentation of large cerebral arteries and the superior sagittal sinus (SSS). The method was validated in a local dataset by comparing it to ground truth cerebral artery and SSS segmentations. Using the Human Connectome Project (HCP) aging dataset, the methods reproducibility was tested on 422 participants aged 36 to 100 years, each with four repeated fMRI scans. The method demonstrated high reproducibility, with an intraclass correlation coefficient > 0.7 in both cerebral artery and SSS segmentation volumes. This study demonstrates that the large cerebral arteries and SSS can be reproducibly and automatically segmented in fMRI datasets, facilitating the investigation of fluid dynamics in these regions.

bioengineering↗

Follicle stimulating hormone receptor expression in human pancreas and effects on insulin secretion: A translational study

Follicle-stimulating hormone (FSH) is traditionally known for its role in reproduction, but recent studies suggest it may also influence metabolic processes. This study aimed to examine FSH receptor (FSHR) expression in human pancreatic islets and the direct effects of FSH on insulin secretion, as well as explore FSHs metabolic role during puberty, focusing on enhanced insulin secretion during this critical period. FSHR gene and protein expression were detected in isolated human pancreatic islets and co-localized with insulin-producing beta-cells. Additionally, FSH at prepubertal (0.1 IU/L) and pubertal concentrations (10 IU/L) significantly enhanced glucose-stimulated insulin secretion (GSIS) and increased intracellular cAMP concentrations in intact human pancreatic islets. In children with obesity from the Beta-JUDO cohort (n=608), plasma FSH levels were positively associated with several insulin secretion indices, particularly in pubertal children. These findings suggest that FSH has significant metabolic roles beyond reproduction, involving insulin secretion and potentially contributing to puberty-related hyperinsulinemia and insulin resistance.

cell biology↗