Biology subjects

Yan, J.

Publications and source records attributed to Yan, J..

At least 91 records · Page 5Linked to original sources

bioRxiv2026

Surf2Spot: A Surface-Informed Geometry-Aware Model for Predicting Binder and Nanobody Design Hotspots

Protein-protein interactions (PPIs) and nanobody-antigen interactions (NAIs) play essential roles in cellular function, yet accurate hotspot prediction remains challenging. We present Surf2Spot, a deep learning framework that integrates sequence embeddings, structural features, and protein surface properties to predict interaction hotspots. By jointly modeling structural and physicochemical determinants, Surf2Spot achieves superior performance on curated PPI and NAI datasets, improving F1-scores by 45.9-46.9% and AUPRC by 43.2% over existing methods. Case studies on NbPDS1 and VdPDA1 demonstrate that Surf2Spot accurately recovers experimentally validated hotspots clustered within functional domains. When incorporated into binder design pipelines (RFdiffusion and BindCraft), Surf2Spot-guided designs yielded a 4-fold increase in successful design throughput and enhanced binding affinities compared to baseline strategies. These results establish Surf2Spot as a powerful tool for hotspot discovery and rational protein engineering.

bioinformatics↗

bioRxiv2026

An Aggregation Prone Region (APR) in talin controls talin self-interactions to regulate integrin adhesion complex dynamics

The tight regulation of the integrin family of extracellular matrix (ECM) receptors is essential for the coordination of most cellular processes. Talin regulates integrin function by binding to the cytoplasmic tail of the integrin beta subunit. Two integrin-binding sites (IBS) in talin have been reported, one in the talin head domain (IBS1), and a second in the C-terminal rod region of talin (IBS2), mapped to the R11-R12 domains. Whilst the structural details of integrin binding to IBS1 are well understood, IBS2s mode of binding integrin is less clear, and the biochemical details of this site have been elusive. Here we report that talin R11 contains a cryptic high affinity talin-binding site. We show that mechanical unfolding of R11 exposes an Aggregation Prone Region (APR) in Helix50 that oligomerizes with other talin R11s. Our data support a model whereby the process of mechanically unfolding one R11, exposes and maintains the APR in a high affinity conformation that drives unfolding of other R11 domains and oligomerisation. Atomic Force Microscopy confirms that the APR region alone forms micron long amyloid-like fibres, via a beta-sheet amyloid arrangement which can be abolished using a canonical "gatekeeper" point mutation, V2078K, that prevents APR interactions. Introducing this gatekeeper mutant in talin eliminates recruitment of talin IBS2 to integrin adhesion sites. The APR region in talin overlaps with a vinculin-binding site in Helix50, and we show a novel role for vinculin as a mechano-chaperone for talin, able to resolve the talin large species by binding to the VBS in Helix50. In light of this new information, we propose that the ability of R11-R12 to target to integrin adhesion complexes and enhance integrin activation can be better explained by a model where functional aggregation of talin serves to recruit and activate more talin molecules at the adhesion site leading to enhanced integrin activation. Whilst further work is required to fully exclude integrin binding to R11 we suggest that the name IBS2 might be a misnomer and propose the name Aggregation Prone Region 1 (APR1) for this talin oligomerisation motif.

cell biology↗

bioRxiv2026

NORAD orchestrates KLC1-mediated SFPQ transport via liquid-liquid phase separation

Neuronal function requires precise long-distance axonal transport mediated by molecular motors and RNA-binding proteins like SFPQ, though regulatory mechanisms remain poorly defined. We identify long non-coding RNA NORAD as a master regulator of this process through liquid-liquid phase separation (LLPS). While SFPQ and kinesin-1 mediate cargo delivery, the specific RNA coordinating their interaction was unknown. We demonstrate NORAD directly binds kinesin light chain 1 (KLC1) and promotes SFPQ condensation into dynamic LLPS droplets, enabling efficient transport. CRISPR-assisted mapping and functional assays show NORAD depletion disrupts granule dynamics, impairs neuroprotective mRNA localization, and induces axonal degeneration. In vitro reconstitution confirms NORAD-KLC1 synergy enhances SFPQ phase separation, and neuron-specific knockout mice exhibit motor deficits with reduced neuronal density. These findings establish the first evidence of lncRNA NORAD-mediated LLPS in axonal transport, revealing a new paradigm for RNA-guided neuronal maintenance.

molecular biology↗

bioRxiv2025

Discovery of Abundant Nano-scale Lymphatic-like Vessels in Brains

As one of the most metabolically active organs, the brain requires an exceptionally efficient system for waste clearance to sustain its high metabolic demands. However, whether such a system exists--and, if so, what structural features enable its efficiency--remains incompletely understood. More than a decade ago, the "glymphatic system" was proposed to describe neurofluid transport through cerebrospinal fluid (CSF) and perivascular spaces (PVS), in conjunction with dural and meningeal lymphatic pathways. Nevertheless, it remains unresolved whether neurofluid transport is organized as a structured, vessel-like flow network. Moreover, in stark contrast to the dense network of blood capillaries in the brain, only a sparse population of lymphatic vessels has been identified, raising doubts as to whether the currently recognized lymphatic architecture alone can support efficient metabolic waste clearance. By combining expansion microscopy with CRANAD-3, a pan-{beta}-amyloid fluorescent probe, we discovered abundant nanoscale lymphatic-like vessels (NLVs) within the brain parenchyma of both mice and humans. The majority of these structures have diameters below 1,000 nm and exhibit moderate positivity for multiple lymphatic markers, including LYVE-1, Prox-1, PDPN, and VEGFR3. NLVs frequently coil around blood vessels, and putative connections between vascular structures were observed. Notably, some NLVs traverse multiple cortical layers and display distinct orientation patterns that vary across cortical laminae. This discovery reveals a previously "hidden" vascular network in the brain parenchyma and raises the possibility that an abundant, highly organized system of nanoscale tubular structures may provide an efficient conduit for metabolic waste clearance. Such a system could represent a critical, previously unrecognized component supporting the brains extraordinary metabolic demands.

neuroscience↗

bioRxiv2025

Modeling Individualized Adolescent Mental Health through a Multifactorial Causal Framework to Identify Potential Intervention Strategies

Associations between psychopathology, cognition, and personality are well established. However, these associations unfold within a broader developmental context shaped by brain maturation, environmental exposures and pubertal transitions, whose influences remain poorly understood. Here, we characterized how cognition and personality relate to adolescent mental health within this developmental context. Using data from the Adolescent Brain Cognitive Development Study (N = 4501), we simultaneously modeled 16610 brain structural, environmental, and pubertal measures to examine 165 behavioral pairs comprising cognitive and personality traits with mental health symptoms. Using an integrated analytic pipeline combining multifactorial mediation and longitudinal interaction-inclusive models, we evaluated whether developmental changes in cognition and personality relate to mental health at the individual level, and whether these associations vary across brain, environmental, and pubertal profiles. Most behavioral pairs showing significant mediation effects likewise exhibited significant longitudinal effects. These pairs were primarily influenced by neurobiological and environmental measures; cortical frontal and temporal regions relevant for cognitive control and emotional regulation as well as family and lifestyle contexts were most prominently implicated. Finally, after accounting for inter-individual heterogeneity, personality traits emerged as the main behavior associated with mental health. These findings characterize developmental associations linking cognition and personality with adolescent mental health, and show that these associations vary across brain, environmental, and pubertal profiles. The study advances understanding of behavioral development and provides a framework for identifying targets for psychopathology prevention.

neuroscience↗

bioRxiv2025

Genome-scale perturb-seq in primary human CD4+ T cells maps context-specific regulators of T cell programs and human immune traits

Gene regulatory networks encode the fundamental logic of cellular functions, but systematic network mapping remains challenging, especially in cell states relevant to human biology and disease. Here, we perturbed all expressed genes across 22 million primary human CD4+ T cells from four donors and developed a probe-based perturb-seq platform to measure the transcriptome effects in cells at rest and after stimulation. These data allow us to map genes that regulate known and novel pathways, including novel regulators of cytokine production. Importantly, active regulators and the gene programs they control change dramatically across stimulation conditions. Perturbation signatures enabled us to model T cell states observed in population-scale transcriptomic atlases, nominating regulators of Th1 and Th2 polarization and of age-related T cell phenotypes. Finally, we leveraged perturb-seq to implicate context-specific gene regulatory pathways in autoimmune disease risk. Our data provide a foundational resource to decode human immune function and genetic variation and for new approaches to study gene regulatory networks.

genetics↗

bioRxiv2025

GIGEM (Group Isolation Gauge Effect Metrics), A Software Suite for Analyzing Social Isolation-Induced Sleep Loss and Multi-Batch Experiments in Drosophila

We introduce Group Isolation Gauge Effect Metrics (GIGEM), a high-throughput software suite for Drosophila sleep analysis designed to manage large population datasets from multi-batch experiments. In this study, we characterized social isolation-induced sleep phenotypes across 38 Sleep Inbred Panel (SIP) lines after both acute and chronic social isolation. Beyond this specific study, GIGEM is broadly suited for diverse Drosophila sleep research involving large-scale and multi-batch datasets. GIGEM enabled an extensive analysis of sleep parameters and allowed systematic identification of sleep changes in response to social isolation. Following acute social isolation, SIP line animals showed heterogeneous responses, including sleep loss, sleep gain, and no change in sleep. In contrast, chronic social isolation led to significant sleep loss in nearly all lines, though to varying degrees. While most SIP lines were sensitive to chronic social isolation, a select few were resistant to it. These results were obtained across 38 SIP lines and wild-type controls (totaling 5670 animals). Collectively, our results demonstrate that chronic social isolation-induced sleep loss is a robust yet variable trait and establish GIGEM as a powerful, generalizable tool for Drosophila sleep phenotyping in large-scale, multi-batch studies.

animal behavior and cognition↗

bioRxiv2025

Bioinformatic analysis of metastasis-associated metabolic landscape reveals an oncogenic role for the transsulfuration pathway

Cancer metastasis is a leading cause of cancer-related deaths, while its underlying mechanisms remain incompletely understood. To colonize distant organs, cancer cells reprogram their metabolism to adapt to diverse environmental challenges. Therefore, elucidating the metabolic pathways that drive cancer metastasis will uncover novel biomarkers and therapeutic targets. In this study, we integrated published datasets and systematically analyzed metabolites across multiple cancer cell lines. This large-scale bioinformatic analysis revealed distinct metabolites and metabolic pathways associated with organ-specific metastasis, and underscored the crucial role of tissue of origin in shaping the metabolic landscape of metastatic tumors. Notably, the transsulfuration pathway (also known as the cysteine and methionine metabolism) was strongly enriched in cancer cells with high metastatic potential. We validated this finding in pancreatic cancer, where the pathway enzyme cystathionine {beta}-synthase (CBS) and its metabolic products were highly expressed in metastatic cancer cells. Targeting the transsulfuration pathway either by methionine deprivation or pharmacological inhibition of CBS significantly impaired the migration and invasion of metastatic pancreatic cancer cells. Taken together, our study not only provides a global view of the altered metabolic landscape in metastasis, but also identifies the transsulfuration pathway as an oncogenic driver and a therapeutic target for pancreatic cancer metastasis.

cancer biology↗

bioRxiv2025

Near-atomic in-situ architecture and membrane-coupled dynamics of the Vibrio cholerae sheathed flagellum

The sheathed flagellum of Vibrio cholerae is a self-assembling membranous organelle that must coordinate axial assembly, sheath biogenesis, and rapid motor rotation. Here, we determine in-situ near-atomic structures of the sheathed flagellar motor inside intact cells. The motor anchors to the outer membrane through lipidated HL-rings without forming a membrane pore, thereby allowing axial assembly to drive sheath formation. Conserved LP-rings act as slide-rotary bushings that permit high-speed rotation within a dynamic envelope yet can constrict to seal the pore upon stress-induced ejection. We further show that stator activation requires a specific PomB-MotX interaction rather than peptidoglycan engagement. Together, these findings reveal how the distinctive architecture and dynamics of the sheathed flagellum promote V. cholerae motility, environmental survival, and persistent colonization of the human gut.

microbiology↗

bioRxiv2025

ClsDiff-AMP30: Generating Antimicrobial Peptides by a Classifier Guidance Noise Predictor

Antimicrobial peptides (AMPs) represent a promising therapeutic strategy to combat the increasing challenge of multidrug-resistant pathogens, a crisis intensified by the overuse of conventional antibiotics. In addition to their broad-spectrum antimicrobial activity, low toxicity, and reduced propensity for resistance development, AMPs offer significant advantages over traditional antibiotic therapies. However, the discovery of novel AMPs through biological experiments remains constrained by high costs, labor-intensive workflows, and time-consuming procedures, underscoring the urgent need for in silico computational methods to design AMP sequences. Notably, shorter AMPs ([≤] 30 residues) demonstrate superior antimicrobial efficacy, improved structural stability, and minimal cytotoxicity toward human cells. To address these challenges, we present a classifier-guided diffusion framework specialized for generating AMPs shorter than 30 residues (ClsDiff-AMP30). The architecture integrates two interdependent submodels, including a noisy AMP classifier that evaluates AMP likelihood at intermediate denoising steps and a noise predictor guided by classifier-derived probability scores, dynamically adjusted via a self-optimized coefficient to modulate guidance strength. ClsDiff-AMP30 achieves a validation accuracy of 66% across 10,000 synthesized sequences by a self-developed AMP classifier. Furthermore, wet lab experiments demonstrated that all 11 selected sequences exhibited high antimicrobial activity against at least one of the three tested bacterial strains and low hemolytic activity.

bioinformatics↗

bioRxiv2025

Deep learning reveals a microprotein atlas in maize and uncovers novel regulators of seed amino acid metabolism

Microproteins represent a vast and functionally important class of genes that remain largely unexplored in plant genomes. Here, we developed DeepMp, a deep learning framework that integrated multi-omics evidence and built the most comprehensive plant microprotein atlas to date, identifying 18,338 high-confidence candidates in maize. The majority of these appear to have originated de novo from regions previously annotated as noncoding, and they show hallmarks of rapid, lineage-specific evolution and pronounced tissue specificity. These novel microproteins were found integrated into core regulatory networks, particularly in organ development and nutrient storage. Focusing on the maize kernel, population-scale analyses linked microprotein expression to natural variation in amino acid content. We functionally validated three grain-filling-specific candidates originating from noncoding regions by CRISPR-Cas9 knockouts, which confirmed their roles as precise modulators of arginine, aspartate, and methionine levels, without pleiotropic effects on kernel morphology. Our study provides a foundational resource and analytical framework, establishes microproteins as a new and functionally important coding layer in maize, and uncovers a previously untapped source of targets for crop improvement.

genomics↗

bioRxiv2025

Inherited retinal degenerations: PARP regulates calpain activation via TRPM2 channels in rd1 mouse photoreceptors

Inherited retinal degeneration (IRD) refers to untreatable blinding diseases characterized by progressive photoreceptor loss. Photoreceptor degeneration is often associated with an excessive activation of poly (ADP-ribose) polymerase (PARP) and Ca2+-dependent calpain-type proteases. To explore the interplay between PARP and calpain activity, we employed organotypic retinal explant cultures derived from wild-type mice and from the rd1 mouse model for IRD. Retinae were treated with the PARP inhibitors INO1001 or Olaparib, the poly (ADP-ribose) glycohydrolase (PARG) inhibitor JA2131, or the transient receptor potential channel M2 (TRPM2) blocker 8-Br-ADPR. Readouts included the TUNEL assay to detect cell death, in situ activity assays for histone-deacetylases (HDAC), PARP, and calpain, as well as immunostaining for activated calpain-2, and poly (ADP-ribose) (PAR). PARP, PARG, and TRPM2 inhibition reduced calpain activity and calpain-2 activation. PARP activity was decreased by PARP and TRPM2 inhibitors but not by PARG inhibition. Remarkably, the PARP inhibitor INO1001 increased HDAC activity unlike any of the other compounds. When combined with the PARG inhibitor JA2131, INO1001 reduced photoreceptor cell death in a synergistic fashion, although such synergy was not observed for calpain or PARP activity. Moreover, synergistic photoreceptor preservation was not observed when JA2131 was combined with the PARP inhibitor Olaparib. Overall, these results indicate that in rd1 photoreceptors, PARP controls calpain activity via PARG and TRPM2-induced Ca2+ influx. We also characterize INO1001 as potentially more beneficial for IRD treatment than Olaparib. Our study details the complexity of PARP-signalling in photoreceptors and identifies PARG and TRPM2 as new targets for IRD therapy development.

neuroscience↗

bioRxiv2025

PRC2 Restricts Malignant Peripheral Nerve Sheath Tumorigenesis in a Genetically Engineered Mouse Model of MPNST

Polycomb Repressive Complex 2 (PRC2), which normally regulates transcriptional silencing, chromatin compaction, and stem cell biology, has both oncogenic and tumor suppressor roles in cancer development depending on tumor type. Malignant peripheral nerve sheath tumor (MPNST), characterized by NF1, CDKN2A and PRC2 loss, is an aggressive subtype of sarcoma with poor prognosis and no effective therapy. In high-grade human MPNSTs, inactivating mutations in PRC2 core components SUZ12 or EED are prevalent and contributes to oncogenic transformation and progression of MPNST. How PRC2 inactivation contributes to MPNST pathogenesis, however, remains incompletely understood. Here we show that genetic inactivation of Eed in addition to Nf1 and Cdkn2a in the Schwann-progenitor lineage leads to widespread tumorigenesis within the sciatic nerve compartment of mice. In contrast, loss of Nf1 and Cdkn2a is insufficient to drive tumorigenesis in the sciatic nerve but leads to MPNST development in other anatomic locations with a longer latency. Single-nucleus multiome sequencing of the sciatic nerves revealed that PRC2-loss reprograms Nf1/Cdkn2a-deficient Schwann-lineage cells toward a dedifferentiated, neural crest stem cell-like state that resembles the transcriptomic signatures of human PRC2-loss MPNST. Together, these findings suggest a context-dependent tumor suppressive role for PRC2 within the sciatic nerve and establish a novel mouse model that recapitulates human PRC2-loss MPNST. SIGNIFICANCEWe present a novel genetically engineered mouse model that faithfully recapitulates human PRC2-loss MPNST, enabling mechanistic and preclinical studies of malignant transformation in the context of PRC2 loss.

cancer biology↗

bioRxiv2025

PGC-1α and PPARs cooperatively mediate photoreceptor neuroprotection in rd1 mouse inherited retinal degeneration

Retinitis pigmentosa (RP) is a group of inherited diseases characterized by a primary rod photoreceptor dysfunction and progressive rod and cone cell death. Due to their very high energy demand, the degeneration of photoreceptors may be linked to insufficient energy supply or metabolic imbalance. Critical transcription factors that regulate metabolism such as peroxisome proliferator-activated receptors (PPARs) and their co-activator PGC-1 have been found to play important roles in neurodegenerative diseases, but their potential roles in RP have yet not been disclosed. In this study, we used organotypic retinal explant cultures derived from the rd1 mouse model for RP to investigate the effects of PPAR, PPAR{gamma}, PPAR{beta}/{delta} agonists, as well as PGC-1 activation and inhibition. Photoreceptor death in the outer nuclear layer (ONL) of the retina was quantified using the TUNEL assay, while in situ activity assays were used to monitor effects of PPARs and PGC-1 on poly (ADP-ribose) polymerase (PARP) and calpain activity. In addition, we performed immunostainings to evaluate poly (ADP-ribose) (PAR) generation and activation of calpain-1 and calpain-2. We found that PPAR{beta}/{delta} agonists had limited effects, while activation of PPAR, PPAR{gamma}, and PGC-1 significantly reduced photoreceptor death and PARP activity in rd1 retina. Conversely, inhibition of PGC-1 had a strong detrimental effect on photoreceptor viability. Activation of the histone deacetylase sirtuin-1, an upstream agonist of PGC-1, had no effect unless it was combined with simultaneous inhibition of PARP. Furthermore, PPAR{gamma} and PGC-1 effectively suppressed overall calpain activity and overactivation of calpain-2, alleviating photoreceptor degeneration caused by Ca2+ imbalance. In summary, our data supports the concept of a PARP-sirtuin-1-PGC-1-PPAR-PARP feedback control that connects defective energy metabolism to photoreceptor degeneration. Specifically, our findings suggest that PPAR, PPAR{gamma}, and PGC-1 cooperate to preserve photoreceptor viability, highlighting PPAR-signaling as a promising target for future therapeutic interventions.

neuroscience↗

bioRxiv2025

An ultra-long acting insulin enables glucose-synchronised release

Delayed and weak glucose-responsive kinetics, coupled with short plasma exposure and complicated formulation, remain major obstacles to the clinical translation of glucose-responsive insulin formulations. Here we report a rapidly absorbable, ultra-long acting, and glucose-responsive insulin analogue via engineering recombinant human insulin with two phenylboronic acids. The insulin analogue has a long circulating half-life (t1/2{beta} [~]150 h) due to its unique, unprecedented, glucose-responsive binding to blood circulation-associated proteins. This interaction drives the formation of a unique systemic reservoir that allows synchronised dynamic response in insulin levels to glucose fluctuations. In type 1 diabetic mice and minipigs, a single subcutaneous dose can maintain normoglycaemia for over one week (47.5-fold compared to insulin glargine). After the last injection of four consecutive weekly administrations in mice, the glucose-lowering effect can last 800 hours. Administering this glucose-responsive insulin analogue with a fully automated insulin delivery system can leverage dual closed loops and achieve a glucose time in range of over 85% and a coefficient of variation of approximately 30%, better than the recommended targets for human therapy. Importantly, no toxicity was identified in the study.

bioengineering↗

bioRxiv2025

Early developmental characterization of gap-induced prepulse inhibition and habituation in the Fragile X Syndrome mouse model

IntroductionAtypical sensory processing, particularly auditory hypersensitivity, is a common and debilitating phenotype of Fragile X Syndrome (FXS). Electrophysiology studies in FMR1-knockout (KO) mice previously observed hyperexcitability at the auditory cortex (AC), with enhanced neuronal firing to auditory stimuli. Prepulse inhibition (PPI), a behavioral measure of sensorimotor gating, is robustly impaired in FXS individuals. Interestingly, a related paradigm called gap-induced inhibition of the acoustic startle (GPIAS) is mediated by the AC, and a previous study observed decreased GPIAS in mature FMR1-KO mice. Further, habituation is also an important sensory filtering mechanism, which has been reported to be impaired in mature FMR1-KO mice. However, not much is known about GPIAS and habituation in FMR1- KO mice during early development. MethodsWe evaluated GPIAS in male and female FMR1-KO mice at post-natal days 15 (P15), 20 (P20) and 30 (P30). The paradigm consisted of a prepulse stimulus (a gap in a continuous background noise) followed by a startle stimulus, with an inter-stimulus interval of 50 or 100 ms. Habituation was assessed prior to the GPIAS trials, with a series of startle only stimulus. ResultsWe observed a trend for genotype difference in acoustic startle response (ASR) magnitude, particularly in the female mice at P30. No significant genotype differences were noted in GPIAS or latency of ASR. Response duration was significantly increased in the male FMR1-KO mice compared to their WT counterparts during early development. Significant genotype differences were also observed in habituation and sensitization. In terms of development, we observed a significant increase in GPIAS with maturation. Furthermore, we also observed significant changes in the magnitude, response latency and duration of ASR with maturation. Finally, significant sex differences were observed in ASR magnitude and duration. ConclusionOur findings suggest that behavioral responses to auditory stimuli are dynamic during development and differ between females and males, an important consideration for future study design. Additionally, the FMR1-KO mice display habituation deficits during early development, which could be an ideal window for addressing auditory hypersensitivity in FXS.

neuroscience↗

bioRxiv2025

Magnesium isoglycyrrhizinate alleviates alcohol-associated liver disease through targeting HSD11B1

While magnesium isoglycyrrhizinate (MgIG) is a clinically approved therapy for alcohol-associated liver disease (ALD), its precise molecular targets and mechanisms remain uncharacterized. This study aimed to define MgIGs hepatoprotective actions in chronic-binge ALD mouse models and ethanol/palmitic acid-exposed AML-12 hepatocytes. Through an integrated strategy encompassing RNA sequencing, molecular docking, and microscale thermophoresis, we discovered that MgIG directly binds to hydroxysteroid 11-beta dehydrogenase 1 (HSD11B1) at residue 187, a finding corroborated by molecular dynamics simulations. In vivo, MgIG markedly attenuated alcohol-induced liver injury, evidenced by ameliorated histological damage, reduced hepatic steatosis, and normalized liver-to-body weight ratios. In vitro, it effectively reduced lipid accumulation, inflammation, and apoptosis. Mechanistically, RNA sequencing identified isopentenyl diphosphate delta isomerase 1 (IDI1) as a key downstream effector. Hepatocyte-specific genetic manipulations confirmed that MgIG modulates the SREBP2-IDI1 axis, thereby suppressing lipogenesis, inflammatory responses, and apoptotic pathways. We reveal HSD11B1 as a novel direct molecular target of MgIG and elucidate its therapeutic mechanism through the HSD11B1-SREBP2-IDI1 signaling axis, which profoundly impacts ALD pathogenesis. These findings not only validate MgIGs clinical utility but also highlight a promising new therapeutic target for ALD.

pharmacology and toxicology↗

bioRxiv2025

Gravity-Dependent Metabolomic Responses in Starbor Kale Brassica oleracea: Comparisons With Simulated Microgravity Versus Gravity Grown

As science continues to push the frontiers on the length of space flight, we begin to experience an enhanced need for food that is nutritionally dense. Nasa-grants have worked to explore the ability of growing superfoods in space on aircrafts. However, it is paramount to ensure the physiological health of the plants being grown in space flight, perform relatively similar to the plants that grow on earth. An aspect which needs to be further probed is the comparison of microgravity and gravity on the plants seeking to be grown in space flight. Within this NASA-funded research, we grew a superfood vegetable, Kale. The kale was grown in simulated microgravity environments to mimic life in outer space. This simulation was induced by means of a 2-D clinostat. Additionally, kale was grown in gravity conditions as well. We used multivariate statistical tools such as Principal Component Analysis (PCA), together with differential-expression visualizations like volcano plots, to summarize complex data rendered from LC-MS. In this study, we used these approaches to examine how horizontal and vertical orientations both in static and rotating configurations simulate aspects of simulated-microgravity and influence metabolic responses; this combined analysis provided a broad perspective on gravity-related metabolic adaptations and points to potential molecular markers that could guide future research on spaceflight health and countermeasure development.

plant biology↗