Ulcerative colitis (UC) is a prevalent chronic inflammatory bowel disease globally, driven mainly by immune dysregulation and gut microbiota dysbiosis. This study focused on Lactiplantibacillus plantarum BF_15, an infant-derived strain with potential to alleviate UC. Four experimental groups were established, including the control group, DSS group, BF_15 group, and LGG group. Probiotics were administrated at a dosage of 1 × 10[9] CFU/mL and 0.1 mL/10 g body weight (BW) for 21 days. The therapeutic effects and mechanisms of BF_15 against UC were explored based on physiological indicators, gut microbiota, and tandem mass tag (TMT)-based quantitative proteomics. The results showed that BF_15 intervention significantly reduced the disease activity index (DAI) from 3.00 ± 0.50 to 1.16 ± 0.36 (p < 0.05) and mitigated UC-related symptoms including body weight loss and colon shortening, with colon length restored from 4.43 ± 0.32 cm to 5.41 ± 0.26 cm (p < 0.05). Meanwhile, BF_15 downregulated the levels of pro-inflammatory factors such as interleukin IL-6 and IL-17A, and upregulated the levels of IL-10 (from 565.92 ± 79.40 pg/mL to 656.84 ± 66.01 pg/mL) and secretory immunoglobulin A (SIgA, from 9.75 ± 1.29 μg/mL to 12.79 ± 1.77 μg/mL) (p < 0.05), with a therapeutic effect comparable to that of LGG. Further, gut microbiota analysis demonstrated that BF_15 restored the relative abundance of Bacteroidetes (from 28.02% to 30.85%) and regulated gut microbiota homeostasis. Finally, TMT-based proteomic analysis indicated that BF_15 regulated 528 differentially expressed proteins (DEPs) and exhibited a superior regulatory effect on the antigen presentation and processing (APC) pathway compared with LGG. The above findings provide potential novel therapeutic targets and probiotic strain resources for the treatment of UC.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated disorder affecting the peripheral nerves and nerve roots. It typically presents with symmetrical weakness of both proximal and distal muscles. Although cranial nerve involvement is rare, it can occasionally occur before the typical peripheral neuropathy develops. We report an unusual case of a 37-year-old woman in whom cranial neuropathy preceded peripheral demyelinating neuropathy. She initially presented with painful vision loss caused by compressive optic neuropathy due to trigeminal nerve hypertrophy. She later developed lower limb weakness, and characteristic MRI findings of cranial nerve hypertrophy together with persistent demyelinating changes on nerve conduction studies over a 2-year follow-up confirmed the diagnosis of CIDP. This case highlights the importance of considering CIDP in patients with painful ophthalmoplegia and cranial nerve hypertrophy. Early recognition of these atypical presentations may lead to earlier diagnosis, timely treatment, and better outcomes.

Allograft reconstruction is indicated for chronic pectoralis major tears because such tears will have fibrotic changes, retraction, and stiffness that prevent primary repair[1-3]. Various reconstruction techniques have been described, particularly in cases in which the myotendinous unit is degenerated. Autografts (such as hamstring tendons and bone-patellar tendon-bone grafts) and allografts (such as Achilles tendon, fascia lata, and dermal grafts) have both been utilized[4,5]. In the present video article, we describe a technique utilizing a doubled Achilles tendon allograft, which provides sufficient width to replicate the native sternal head insertion. A 3-point fixation construct is utilized to enhance graft-to-muscle interface strength.

Diabetic retinopathy (DR) is a leading cause of preventable visual loss in type 2 diabetes mellitus (T2DM), yet current screening largely detects disease after microvascular damage has occurred. This review synthesizes emerging evidence that three measurable biomarkers - fibroblast growth factor-21 (FGF21), growth differentiation factor-15 (GDF15), and microalbuminuria -capture complementary dimensions of early DR pathobiology. FGF21 reflects hepatometabolic stress and adaptive signaling via the β-Klotho-FGFR1 axis; GDF15 mirrors mitochondrial/integratedstress-response activation with systemic effects through the glial cell-derived neurotrophic factor family receptor-α-like (GFRAL) REarranged during Transfection (RET); and microalbuminuria indicates systemic endothelial dysfunction and increased microvascular permeability. We narratively integrate cross-sectional, cohort, and meta-analytic studies in human T2DM populations (excluding type 1 diabetes and animal experiments) and map these signals onto a unified metabolic-renal-retinal framework. Across studies, higher circulating FGF21 and GDF15 associate with DR presence and severity, while microalbuminuria correlates with DR grade and predicts progression independent of glycemic control. We propose a tri-biomarker model in which chronic lipotoxicity and oxidative stress elevate FGF21/GDF15, drive endothelial injury detectable as microalbuminuria, and together forecast early retinal microangiopathy. Translational implications include risk stratification before funduscopic changes, therapy monitoring for metabolic/mitochondrial targets, and development of multimarker algorithms alongside OCTA imaging. To our knowledge, this is the first review to integrate FGF21, GDF15, and microalbuminuria as a coherent predictive axis for early DR in T2DM, highlighting priorities for longitudinal validation and population-specific cut-offs.

Non-arteritic anterior ischemic optic neuropathy (NAION) is a leading cause of sudden visual loss in older adults, often associated with vascular risk factors. The aim of this study was to investigate the retinal microvascular changes in chronic NAION and their relationship with systemic vascular conditions and obstructive sleep apnea (OSA). This retrospective observational study included 31 patients with chronic NAION (≥6 months from onset) and 17 age-matched healthy controls. Retinal microvascular parameters were assessed using the Dynamic Vessel Analyzer (DVA), including static and dynamic vessel metrics. Data were correlated with systemic vascular risk factors and polysomnographic findings. Arterial dilation amplitude was significantly reduced in eyes affected by chronic NAION compared to both contralateral unaffected eyes and healthy controls (p < .01). Static analysis revealed a significantly lower arteriovenous ratio (AVR) in both affected and unaffected eyes compared to controls. No significant differences were observed in venous parameters. Arterial diameter and dilation amplitude were positively correlated with ganglion cell layer thickness thickness and visual field sensitivity. OSA was diagnosed in 51% of patients, but no significant association was found between OSA and DVA parameters. In chronic NAION, DVA demonstrated impaired retinal arterial function, likely reflecting secondary effects of optic nerve damage. Retinal venous parameters remained unaffected. Cerebrovascular risk appeared more strongly associated with systemic vascular comorbidities than NAION itself. OSA, even in mild form, may contribute to disease severity.

Glaucoma is the leading cause of irreversible blindness worldwide, primarily driven by the progressive loss of retinal ganglion cells (RGCs) under pathological high intraocular pressure (ph-IOP). Despite the established role of ferroptosis in RGC degeneration, specific molecular targets that can be used for clinical intervention still need to be optimized, and the slow onset of conventional gene therapy vectors is incompatible with the acute clinical course of glaucoma. Here, we integrate single-cell RNA sequencing and spatial transcriptomics to profile the dynamic transcriptomic landscape of the rat retina across acute, subacute, and chronic stages of ph-IOP injury. Through ferroptosis-focused screening of an early-activated RGC gene cluster, we identify the lipid metabolism regulator phosphatidylethanolamine-binding protein 1 (PEBP1) as a candidate mediator of RGC ferroptosis. We demonstrate that Pebp1 is specifically upregulated in injured RGCs with a trajectory mirroring ferroptosis pathway activation, and that AAV-mediated Pebp1 knockdown suppresses ferroptosis through the GPX4/ACSL4 signaling axis, thereby preserving RGC survival, retinal structure, and visual function. To overcome the critical time-window bottleneck-the several weeks delay required for AAV-mediated silencing versus the rapid, irreversible RGC loss in acute glaucoma-we engineer Exosomes-siPebp1, a mesenchymal stem cell-derived exosome system loaded with siPebp1, which enables immediate single-dose intervention post-injury. This system exhibits efficient RGC uptake, prolonged intraocular retention, and robust target gene silencing, and, in a head-to-head comparison, significantly outperforms unloaded exosomes, liposomal formulations, and AAV vectors in RGC protection, without detectable acute systemic or local toxicity. Collectively, this study implicates Pebp1 in ph-IOP-associated RGC ferroptosis and supports exosome-mediated siRNA delivery as a rapid, cell-free intervention strategy for acute glaucomatous injury.

Corneal chemical injury, including mustard vesicant injury, remains a clinical challenge with limited therapeutic options. To enable effective mechanistic and therapeutic studies, we developed a mouse model of nitrogen mustard (NM)-induced corneal injury using a 3D-molded, cap-shaped filter paper conforming to the corneal surface to generate reproducible injuries. Multimodal in vivo imaging and histological assessment revealed an injury course characterized by acute epithelial disruption, stromal edema, and inflammation, followed by transient partial recovery and chronic stromal remodeling with persistent endothelial loss. After NM exposure, bromodomain (BD)-containing protein 4 (BRD4) expression and activity were upregulated. Short-term topical BRD4 inhibition with JQ1 reduced acute corneal inflammation (e.g., reducing CD45[+] cells by 86%) and oxidative stress, and conferred long-term preservation of corneal clarity, stromal organization, and endothelial integrity. Selective inhibition of BD1 or BD2 recapitulated JQ1's effects, indicating that blockade of either bromodomain is sufficient. BRD4 inhibition also significantly attenuated NM-induced corneal pathology in a rabbit model, supporting cross-species efficacy and translational relevance. Mechanistically, BRD4 inhibition selectively counteracted key NM-driven pathogenic programs, including inflammation, oxidative stress, and extracellular matrix remodeling. These findings identify BRD4 as a central epigenetic driver of vesicant-induced corneal injury and position BRD4 inhibition as a promising translational therapeutic strategy.

Intron retention, a form of alternative RNA splicing, can occur as part of normal gene regulation or result from disruption of the splicing machinery. Retained introns can potentially form double-stranded RNA, activating innate immune sensors and inflammation. This mechanism has been implicated in cancer but has not been studied in neuropsychiatric diseases like alcohol use disorder. We systematically analysed transcriptome-wide intron retention events in post-mortem brain tissue from 142 individuals (66 with alcohol use disorder and 76 controls), encompassing 320 region-specific samples from the superior frontal cortex, nucleus accumbens, central nucleus and basolateral amygdala. Analyses were adjusted for demographic, technical and biological covariates. Validation was performed in alcohol-preferring (P) rats using long-read sequencing. In complementary experiments, immunofluorescent staining was used to detect double-stranded RNA in rat brain tissue, while single-cell RNA-sequencing was performed to test activation of double-stranded RNA-sensing pathways in human brains. Brains from individuals with alcohol use disorder showed significantly higher total intron retention compared with controls, independent of age, with females showing greater increases than males. A total of 368 introns were positively associated with alcohol use disorder, and these introns were significantly longer and had weaker splice acceptor sites compared with non-associated introns. Genes harbouring these intron retention events were enriched in Purkinje neurons, visual cortex neurons and oligodendrocytes. Computational predictions indicated these long introns could form duplex RNA structures. Increased double-stranded RNA was confirmed experimentally in multiple brain regions of alcohol-consuming rats, where it co-localized primarily with neuronal nuclei and dendrites. In individuals with alcohol use disorder, we found that multiple pathways including double-stranded RNA responses, neuroinflammation, interferon and NF-κB signalling, adaptive immunity and apoptosis were activated. In addition, NeuN-positive neuronal counts significantly decreased in both the prefrontal and visual cortices. Furthermore, single-cell analysis demonstrated upregulation of TICAM1, the target of double-stranded RNA sensor TLR3, in oligodendrocytes, as well as widespread activation of downstream inflammatory pathways across glial and neuronal cell types. These findings provide the first evidence that chronic alcohol consumption promotes an overall increase of intron retention in the brain and is associated with the presence of double-stranded RNA. Furthermore, the double-stranded RNA may contribute to neuronal loss and brain pathology by activating a neuroinflammatory response.

Sleep disorders are increasingly understood as systems-level conditions in which the brain and body reweight sensory evidence from the external world and internal milieu. We systematically reviewed human evidence for sensory and multisensory dysfunction across sleep disorders and experimental sleep loss. Searches identified 25,777 records; after removal of 7235 duplicates, 18,542 records were screened, 4452 full records were assessed for eligibility, and 377 studies met inclusion criteria. Evidence was organised across 31 sensory modalities in seven domains: olfaction, gustation, vision, audition, somatosensation/nociception, vestibular-proprioceptive function, and interoception/autonomic function, with higher-order perceptual outcomes analysed separately. Using a prespecified conservative criterion requiring a non-null direction of effect with at least moderate certainty, 23 of 31 modalities were altered in at least one sleep disorder or experimental sleep-loss category (74.2%). The evidence clustered in specific disorder-domain pairs. Moderate-certainty signals identified clinically meaningful hyposmia in isolated rapid eye movement sleep behaviour disorder and obstructive sleep apnoea, heightened pain sensitivity in chronic insomnia, altered chronoception after experimental sleep loss, and obstructive sleep apnoea-associated hearing-threshold impairment. Central auditory-processing, visual, gustatory, and vestibular-proprioceptive findings were more heterogeneous or lower certainty. Across disorders, the emerging map is consistent with state-dependent disturbances in sensory gain, gating, salience, and interoceptive control. These findings position sensory profiling as a clinically tractable strategy for phenotyping and for prospective evaluation of risk and treatment response in selected sleep disorders. Longitudinal and interventional studies should now test whether sensory measures predict disease course, sleep stability, and clinical outcomes, and whether targeted sensory or interoceptive modulation can improve sleep-related symptoms.