Small extracellular vesicles derived from human induced pluripotent stem cell-differentiated neural progenitor cells mitigate retinal ganglion cell degeneration in a mouse model of optic nerve injury.

JOURNAL/nrgr/04.03/01300535-202502000-00034/figure1/v/2024-05-28T214302Z/r/image-tiff Several studies have found that transplantation of neural progenitor cells (NPCs) promotes the survival of injured neurons. However, a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical application. Small extracellular vesicles (sEVs) contain bioactive molecules for neuronal protection and regeneration. Previous studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye diseases. In this study, we intravitreally transplanted sEVs derived from human induced pluripotent stem cells (hiPSCs) and hiPSCs-differentiated NPCs (hiPSC-NPC) in a mouse model of optic nerve crush. Our results show that these intravitreally injected sEVs were ingested by retinal cells, especially those localized in the ganglion cell layer. Treatment with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration, and regulated the retinal microenvironment by inhibiting excessive activation of microglia. Component analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells, which had protective effects on RGCs after optic nerve injury. These findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.

Integrative Analysis of Hepatopancreas Transcriptome and Proteome in Female Eriocheir sinensis under Thermal Stress.

The Chinese mitten crab (Eriocheir sinensis), an economically important crustacean that is endemic to China, has recently experienced high-temperature stress. The high thermal tolerance of E. sinensis points to its promise in being highly productive in an aquacultural context. However, the mechanisms underlying its high thermal tolerance remain unknown. In this study, female E. sinensis that were heat exposed for 24 h at 38.5 °C and 33 °C were identified as high-temperature-stressed (HS) and normal-temperature-stressed (NS) groups, respectively. The hepatopancreas of E. sinensis from the HS and NS groups were used for transcriptome and proteomic analyses. A total of 2350 upregulated and 1081 downregulated differentially expressed genes (DEGs) were identified between the HS and NS groups. In addition, 126 differentially expressed proteins (DEPs) were upregulated and 35 were downregulated in the two groups. An integrated analysis showed that 2641 identified genes were correlated with their corresponding proteins, including 25 genes that were significantly differentially expressed between the two omics levels. Ten Gene Ontology terms were enriched in the DEGs and DEPs. A functional analysis revealed three common pathways that were significantly enriched in both DEGs and DEPs: fluid shear stress and atherosclerosis, leukocyte transendothelial migration, and thyroid hormone synthesis. Further analysis of the common pathways showed that MGST1, Act5C, HSP90AB1, and mys were overlapping genes at the transcriptome and proteome levels. These results demonstrate the differences between the HS and NS groups at the two omics levels and will be helpful in clarifying the mechanisms underlying the thermal tolerance of E. sinensis.

Comprehensive identification of pathogenic variants in retinoblastoma by long- and short-read sequencing.

Retinoblastoma (RB) is the most common intraocular malignancy in childhood. The causal variants in RB are mostly characterized by previously used short-read sequencing (SRS) analysis, which has technical limitations in identifying structural variants (SVs) and phasing information. Long-read sequencing (LRS) technology has advantages over SRS in detecting SVs, phased genetic variants, and methylation. In this study, we comprehensively characterized the genetic landscape of RB using combinatorial LRS and SRS of 16 RB tumors and 16 matched blood samples. We detected a total of 232 somatic SVs, with an average of 14.5 SVs per sample across the whole genome in our cohort. We identified 20 distinct pathogenic variants disrupting RB1 gene, including three novel small variants and five somatic SVs. We found more somatic SVs were detected from LRS than SRS (140 vs. 122) in RB samples with WGS data, particularly the insertions (18 vs. 1). Furthermore, our analysis shows that, with the exception of one sample who lacked the methylation data, all samples presented biallelic inactivation of RB1 in various forms, including two cases with the biallelic hypermethylated promoter and four cases with compound heterozygous mutations which were missing in SRS analysis. By inferring relative timing of somatic events, we reveal the genetic progression that RB1 disruption early and followed by copy number changes, including amplifications of Chr2p and deletions of Chr16q, during RB tumorigenesis. Altogether, we characterize the comprehensive genetic landscape of RB, providing novel insights into the genetic alterations and mechanisms contributing to RB initiation and development. Our work also establishes a framework to analyze genomic landscape of cancers based on LRS data.

A review of recent advances of piezoelectric poly-L-lactic acid for biomedical applications.

Poly-L-lactic acid (PLLA), recognized as a piezoelectric material, not only demonstrates exceptional piezoelectric properties but also exhibits commendable biocompatibility and biodegradability. These properties render PLLA highly promising for diverse applications, including sensors, wearable devices, biomedical engineering, and related domains. This review offers a comprehensive overview of the distinctive piezoelectric effect of PLLA-based material and delves into the latest advancements in its preparation strategies as a piezoelectric material. It further presents recent research progress in PLLA-based piezoelectric materials, particularly in the realms of health monitoring, skin repair, nerve regeneration, and tissue repair. The discourse extends to providing insights into potential future trajectories for the development of PLLA-based piezoelectric materials.

SiO 2 Induces Iron Overload and Ferroptosis in Cardiomyocytes in a Silicosis Mouse Model.

Objective: The aim of this study was to explore the role and mechanism of ferroptosis in SiO 2-induced cardiac injury using a mouse model. Methods: Male C57BL/6 mice were intratracheally instilled with SiO 2 to create a silicosis model. Ferrostatin-1 (Fer-1) and deferoxamine (DFO) were used to suppress ferroptosis. Serum biomarkers, oxidative stress markers, histopathology, iron content, and the expression of ferroptosis-related proteins were assessed. Results: SiO 2 altered serum cardiac injury biomarkers, oxidative stress, iron accumulation, and ferroptosis markers in myocardial tissue. Fer-1 and DFO reduced lipid peroxidation and iron overload, and alleviated SiO 2-induced mitochondrial damage and myocardial injury. SiO 2 inhibited Nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream antioxidant genes, while Fer-1 more potently reactivated Nrf2 compared to DFO. Conclusion: Iron overload-induced ferroptosis contributes to SiO 2-induced cardiac injury. Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO 2 cardiotoxicity, potentially via modulation of the Nrf2 pathway.

Exploring the Potential of Cyclic Peptidyl Antitumor Agents Derived from Natural Macrocyclic Peptide Phakellistatin 13.

The exploration of novel anticancer compounds based on natural cyclopeptides has emerged as a pivotal paradigm in the contemporary advancement of macrocyclic pharmaceuticals. Phakellistatin 13 is a cycloheptapeptide derived from the brown snubby sponge and exhibits remarkable antitumor activity. In this study, we have designed and synthesized a series of chiral cyclopeptides incorporating the rigid isoindolinone moiety at various sites within the natural cycloheptapeptide Phakellistatin 13, with the aim of investigating conformationally constrained cyclopeptides as potential antitumor agents. Cyclopeptide 3, comprising alternating l-/d-amino acid residues, exhibited promising antihepatocellular carcinoma effects. Detailed biological experiments have revealed that Phakellistatin 13 analogs effectively inhibit the proliferation of tumor cells and induce apoptosis and autophagy, while also causing cell cycle arrest through the modulation of the p53 and mitogen-activated protein kinase (MAPK) signaling pathway. This study not only provides valuable insights into chemical structural modifications but also contributes to a deeper understanding of the biological mechanisms underlying the development of natural cyclopeptide-based drugs.

Goal-directed attention transforms both working and long-term memory representations in the human parietal cortex.

The abundance of distractors in the world poses a major challenge to our brain's limited processing capacity, but little is known about how selective attention modulates stimulus representations in the brain to reduce interference and support durable target memory. Here, we collected functional magnetic resonance imaging (fMRI) data in a selective attention task in which target and distractor pictures of different visual categories were simultaneously presented. Participants were asked to selectively process the target according to the effective cue, either before the encoding period (i.e., perceptual attention) or the maintenance period (i.e., reflective attention). On the next day, participants were asked to perform a memory recognition task in the scanner in which the targets, distractors, and novel items were presented in a pseudorandom order. Behavioral results showed that perceptual attention was better at enhancing target memory and reducing distractor memory than reflective attention, although the overall memory capacity (memory for both target and distractor) was comparable. Using multiple-voxel pattern analysis of the neural data, we found more robust target representation and weaker distractor representation in working memory for perceptual attention than for reflective attention. Interestingly, perceptual attention partially shifted the regions involved in maintaining the target representation from the visual cortex to the parietal cortex. Furthermore, the targets and distractors simultaneously presented in the perceptual attention condition showed reduced pattern similarity in the parietal cortex during retrieval compared to items not presented together. This neural pattern repulsion positively correlated with individuals' recognition of both targets and distractors. These results emphasize the critical role of selective attention in transforming memory representations to reduce interference and improve long-term memory performance.

Depletion of TDP-43 exacerbates tauopathy-dependent brain atrophy by sensitizing vulnerable neurons to caspase 3-mediated endoproteolysis of tau in a mouse model of Multiple Etiology Dementia.

TDP-43 proteinopathy, initially disclosed in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), coexists with tauopathy in a variety of neurodegenerative disorders, termed multiple etiology dementias (MEDs), including Alzheimer's Disease (AD). While such co-pathology of TDP-43 is strongly associated with worsened neurodegeneration and steeper cognitive decline, the pathogenic mechanism underlying the exacerbated neuron loss remains elusive. The loss of TDP-43 splicing repression that occurs in presymptomatic ALS-FTD individuals suggests that such early loss could facilitate the pathological conversion of tau to accelerate neuron loss. Here, we report that the loss of TDP-43 repression of cryptic exons in forebrain neurons (CaMKII-CreER;Tardbp f/f mice) is necessary to exacerbate tauopathy-dependent brain atrophy by sensitizing vulnerable neurons to caspase 3-dependent cleavage of endogenous tau to promote tauopathy. Corroborating this finding within the human context, we demonstrate that loss of TDP-43 function in iPSC-derived cortical neurons promotes early cryptic exon inclusion and subsequent caspase 3-mediated endoproteolysis of tau. Using a genetic approach to seed tauopathy in CaMKII-CreER;Tardbp f/f mice by expressing a four-repeat microtubule binding domain of human tau, we show that the amount of tau seed positively correlates with levels of caspase 3-cleaved tau. Importantly, we found that the vulnerability of hippocampal neurons to TDP-43 depletion is dependent on the amount of caspase 3-cleaved tau: from most vulnerable neurons in the CA2/3, followed by those in the dentate gyrus, to the least in CA1. Taken together, our findings strongly support the view that TDP-43 loss-of-function exacerbates tauopathy-dependent brain atrophy by increasing the sensitivity of vulnerable neurons to caspase 3-mediated endoproteolysis of tau, resulting in a greater degree of neurodegeneration in human disorders with co-pathologies of tau and TDP-43. Our work thus discloses novel mechanistic insights and therapeutic targets for human tauopathies harboring co-pathology of TDP-43 and provides a new MED model for testing therapeutic strategies.

Beyond water and soil: Air emerges as a major reservoir of human pathogens.

Assessing the risk of human pathogens in the environment is crucial for controlling the spread of diseases and safeguarding human health. However, conducting a thorough assessment of low-abundance pathogens in highly complex environmental microbial communities remains challenging. This study compiled a comprehensive catalog of 247 human-pathogenic bacterial taxa from global biosafety agencies and identified more than 78 million genome-specific markers (GSMs) from their 17,470 sequenced genomes. Subsequently, we analyzed these pathogens' types, abundance, and diversity within 474 shotgun metagenomic sequences obtained from diverse environmental sources. The results revealed that among the four habitats studied (air, water, soil, and sediment), the detection rate, diversity, and abundance of detectable pathogens in the air all exceeded those in the other three habitats. Air, sediment, and water environments exhibited identical dominant taxa, indicating that these human pathogens may have unique environmental vectors for their transmission or survival. Furthermore, we observed the impact of human activities on the environmental risk posed by these pathogens, where greater amounts of human activities significantly increased the abundance of human pathogenic bacteria, especially in water and air. These findings have remarkable implications for the environmental risk assessment of human pathogens, providing valuable insights into their presence and distribution across different habitats.

Comprehensive comparison of water quality risk and microbial ecology between new and old cast iron pipe distribution systems.

The effects of cast iron pipe corrosion on water quality risk and microbial ecology in drinking water distribution systems (DWDSs) were investigated. It was found that trihalomethane (THMs) concentration and antibiotic resistance genes (ARGs) increased sharply in the old DWDSs. Under the same residual chlorine concentration conditions, the adenosine triphosphate concentration in the effluent of old DWDSs (Eff-old) was significantly higher than that in the effluent of new DWDSs. Moreover, stronger bioflocculation ability and weaker hydrophobicity coexisted in the extracellular polymeric substances of Eff-old, meanwhile, iron particles could be well inserted into the structure of the biofilms to enhance the mechanical strength and stability of the biofilms, hence enhancing the formation of THMs. Old DWDSs significantly influenced the microbial community of bulk water and triggered stronger microbial antioxidant systems response, resulting in higher ARGs abundance. Corroded cast iron pipes induced a unique interaction system of biofilms, chlorine, and corrosion products. Therefore, as the age of cast iron pipes increases, the fluctuation of water quality and microbial ecology should be paid more attention to maintain the safety of tap water.

A Self-Cascade Oxygen-Generating Nanomedicine for Multimodal Tumor Therapy.

Natural and artificial enzyme oxygen-generating systems for photodynamic therapy (PDT) are developed for tumor treatment, yet they have fallen short of the desired efficacy. Moreover, both the enzymes and photosensitizers usually need carriers for efficient delivery to tumor sites. Here, a self-cascade-enhanced multimodal tumor therapy is developed by ingeniously integrating self-cascade-enhanced PDT with Zn2+-overloading therapy. Manganese-porphyrin (TCPP-Mn) is chosen both as the photosensitizer and catalase (CAT) mimic, which can be encapsulated within glucose oxidase (GOx). Acid-responsive zeolitic imidazolate framework-8 (ZIF-8) is applied as the carrier for TCPP-Mn@GOx (T@G), attaining TCPP-Mn@GOx@ZIF-8 (T@G@Z). T@G@Z demonstrates robust anti-tumor ability as follows: upon the structural degradation of ZIF-8, GOx can mediate the oxidation of glucose and generate hydrogen peroxide (H2O2); TCPP-Mn can catalyze H2O2 into O2 for self-cascade-enhanced PDT; meanwhile, the released Zn2+ can enhance oxidative stress and induce mitochondrial dysfunction by destroying mitochondrial membrane potential; furthermore, immunotherapy can be activated to resist primary tumor and tumor metastasis. The self-cascade-enhanced T@G@Z exhibited its potential application for further tumor management.

Overexpression of CsBRC, an F-box gene from Camellia sinensis, increased the plant branching in tobacco and rice.

Tea plant (Camellia sinensis [L.]) is one of the most important crops in China, and tea branch is an important agronomic trait that determines the yield of tea plant. In previous work focused on GWAS that detecting GWAS signals related to plant architecture through whole genome re-sequencing of ancient tea plants, a gene locus TEA 029928 significantly related to plant type was found. Sequence alignment results showed that this gene belonged to the F-box family. We named it CsBRC. CsBRC-GFP fusion proteins were mainly localized in the plasma membrane. By comparing the phenotypes of CsBRC transgenic tobacco and WT tobacco, it was found that the number of branches of transgenic tobacco was significantly higher than that of wild-type tobacco. Through RNA-seq analysis, it was found that CsBRC affects the branching development of plants by regulating the expression of genes related to brassinosteroid synthesis pathway in plants. In addition, overexpression of CsBRC in rice could increase tiller number, grain length and width, and 1,000-grain weight.

α-Ketoglutarate plays an inflammatory inhibitory role by regulating scavenger receptor class a expression through N6-methyladenine methylation during sepsis.

Sepsis arises from an uncontrolled inflammatory response triggered by infection or stress, accompanied by alteration in cellular energy metabolism, and a strong correlation exists between these factors. Alpha-ketoglutarate (α-KG), an intermediate product of the TCA cycle, has the potential to modulate the inflammatory response and is considered a crucial link between energy metabolism and inflammation. The scavenger receptor (SR-A5), a significant pattern recognition receptor, assumes a vital function in anti-inflammatory reactions. In the current investigation, we have successfully illustrated the ability of α-KG to mitigate inflammatory factors in the serum of septic mice and ameliorate tissue damage. Additionally, α-KG has been shown to modulate metabolic reprogramming and macrophage polarization. Moreover, our findings indicate that the regulatory influence of α-KG on sepsis is mediated through SR-A5. We also elucidated the mechanism by which α-KG regulates SR-A5 expression and found that α-KG reduced the N6-methyladenosine level of macrophages by up-regulating the m6A demethylase ALKBH5. α-KG plays a crucial role in inhibiting inflammation by regulating SR-A5 expression through m6A demethylation during sepsis. The outcomes of this research provide valuable insights into the relationship between energy metabolism and inflammation regulation, as well as the underlying molecular regulatory mechanism.

Screening of active components in Astragalus mongholicus Bunge and Panax notoginseng formula for anti-fibrosis in CKD: nobiletin inhibits Lgals1/PI3K/AKT signaling to improve renal fibrosis.

The Astragalus mongholicus Bunge and Panax notoginseng formula (A&P) has been clinically shown to effectively slow down the progression of chronic kidney disease (CKD) and has demonstrated significant anti-fibrosis effects in experimental CKD model. However, the specific active ingredients and underlying mechanism are still unclear. The active ingredients of A&P were analyzed by Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-HR-MS). A mouse model of CKD was constructed by 5/6 nephrectomy. Renal function was assessed by creatinine and urea nitrogen. Real-time PCR and Western Blot were performed to detect the mRNA and protein changes in kidney and cells. An in vitro fibrotic cell model was constructed by TGF-ß induction in TCMK-1 cells. The results showed that thirteen active ingredients of A&P were identified by UPLC-HR-MS, nine of which were identified by analysis with standards, among which the relative percentage of NOB was high. We found that NOB treatment significantly improved renal function, pathological damage and reduced the expression level of fibrotic factors in CKD mice. The results also demonstrated that Lgals1 was overexpressed in the interstitial kidney of CKD mice, and NOB treatment significantly reduced its expression level, while inhibiting PI3K and AKT phosphorylation. Interestingly, overexpression of Lgals1 significantly increased fibrosis in TCMK1 cells and upregulated the activity of PI3K and AKT, which were strongly inhibited by NOB treatment. NOB is one of the main active components of A&P. The molecular mechanism by which NOB ameliorates renal fibrosis in CKD may be through the inhibition of Lgals1/PI3K/AKT signaling pathway.

Functional and evolutionary comparative analysis of the DIR gene family in Nicotiana tabacum L. and Solanum tuberosum L.

BACKGROUND: The dirigent (DIR) genes encode proteins that act as crucial regulators of plant lignin biosynthesis. In Solanaceae species, members of the DIR gene family are intricately related to plant growth and development, playing a key role in responding to various biotic and abiotic stresses. It will be of great application significance to analyze the DIR gene family and expression profile under various pathogen stresses in Solanaceae species. RESULTS: A total of 57 tobacco NtDIRs and 33 potato StDIRs were identified based on their respective genome sequences. Phylogenetic analysis of DIR genes in tobacco, potato, eggplant and Arabidopsis thaliana revealed three distinct subgroups (DIR-a, DIR-b/d and DIR-e). Gene structure and conserved motif analysis showed that a high degree of conservation in both exon/intron organization and protein motifs among tobacco and potato DIR genes, especially within members of the same subfamily. Total 8 pairs of tandem duplication genes (3 pairs in tobacco, 5 pairs in potato) and 13 pairs of segmental duplication genes (6 pairs in tobacco, 7 pairs in potato) were identified based on the analysis of gene duplication events. Cis-regulatory elements of the DIR promoters participated in hormone response, stress responses, circadian control, endosperm expression, and meristem expression. Transcriptomic data analysis under biotic stress revealed diverse response patterns among DIR gene family members to pathogens, indicating their functional divergence. After 96 h post-inoculation with Ralstonia solanacearum L. (Ras), tobacco seedlings exhibited typical symptoms of tobacco bacterial wilt. The qRT-PCR analysis of 11 selected NtDIR genes displayed differential expression pattern in response to the bacterial pathogen Ras infection. Using line 392278 of potato as material, typical symptoms of potato late blight manifested on the seedling leaves under Phytophthora infestans infection. The qRT-PCR analysis of 5 selected StDIR genes showed up-regulation in response to pathogen infection. Notably, three clustered genes (NtDIR2, NtDIR4, StDIR3) exhibited a robust response to pathogen infection, highlighting their essential roles in disease resistance. CONCLUSION: The genome-wide identification, evolutionary analysis, and expression profiling of DIR genes in response to various pathogen infection in tobacco and potato have provided valuable insights into the roles of these genes under various stress conditions. Our results could provide a basis for further functional analysis of the DIR gene family under pathogen infection conditions.

Antioxidative Potential and Ameliorative Effects of Rice Bran Fermented with Lactobacillus against High-Fat Diet-Induced Oxidative Stress in Mice.

Rice bran is an important byproduct of the rice polishing process, rich in nutrients, but it is underutilized and often used as feed or discarded, resulting in a huge amount of waste. In this study, rice bran was fermented by Lactobacillus fermentum MF423 to obtain a product with high antioxidant activity. First, a reliable and efficient method for assessing the antioxidant capacity of the fermentation products was established using high-performance liquid chromatography (HPLC), which ensured the consistency of the batch fermentation. The fermented rice bran product (FLRB) exhibited significant antioxidant activity in cells, C. elegans, and hyperlipidemic mice. Transcriptome analysis of mouse livers showed that the expression of plin5 was upregulated in diabetic mice administered FLRB, thereby preventing the excessive production of free fatty acids (FFAs) and the subsequent generation of large amounts of reactive oxygen species (ROS). These studies lay the foundation for the application of rice bran fermentation products.

Probing latent brain dynamics in Alzheimer's disease via recurrent neural network.

The impairment of cognitive function in Alzheimer's disease (AD) is clearly correlated to abnormal changes in cortical rhythm. However, the mechanisms underlying this correlation are still poorly understood. Here, we investigate how network structure and dynamical characteristics alter their abnormal changes in cortical rhythm. To that end, biological data of AD and normal participates are collected. By extracting the energy characteristics of different sub-bands in EEG signals, we find that the rhythm of AD patients is special particularly in theta and alpha bands. The cortical rhythm of normal state is mainly at alpha band, while that of AD state shift to the theta band. Furthermore, recurrent neural network (RNN) is trained to explore the rhythm formation and transformation between two neural states from the perspective view of neurocomputation. It is found that the neural coupling strength decreases significantly under AD state when compared with normal state, which weakens the ability of information transmission in AD state. Besides, the low-dimensional properties of RNN are obtained. By analyzing the relationship between the cortical rhythm transition and the low-dimensional trajectory, it is concluded that the low-dimensional trajectory update is slower and the communication cost is higher in AD state, which explains the abnormal synchronization of AD brain network. Our work reveals the causes for the formation of abnormal brain synchronous functional network status, which may expand our understanding of the mechanism of cognitive impairment in AD and provide an EEG biomarker for early AD.

STCS-Net: a medical image segmentation network that fully utilizes multi-scale information.

In recent years, significant progress has been made in the field of medical image segmentation through the application of deep learning and neural networks. Numerous studies have focused on optimizing encoders to extract more comprehensive key information. However, the importance of decoders in directly influencing the final output of images cannot be overstated. The ability of decoders to effectively leverage diverse information and further refine crucial details is of paramount importance. This paper proposes a medical image segmentation architecture named STCS-Net. The designed decoder in STCS-Net facilitates multi-scale filtering and correction of information from the encoder, thereby enhancing the accuracy of extracting vital features. Additionally, an information enhancement module is introduced in skip connections to highlight essential features and improve the inter-layer information interaction capabilities. Comprehensive evaluations on the ISIC2016, ISIC2018, and Lung datasets validate the superiority of STCS-Net across different scenarios. Experimental results demonstrate the outstanding performance of STCS-Net on all three datasets. Comparative experiments highlight the advantages of our proposed network in terms of accuracy and parameter efficiency. Ablation studies confirm the effectiveness of the introduced decoder and skip connection module. This research introduces a novel approach to the field of medical image segmentation, providing new perspectives and solutions for future developments in medical image processing and analysis.

Effects of lower limb length discrepancy on spinopelvic compensation following total hip arthroplasty in patients with developmental dysplasia of the hip.

BACKGROUND: Limited research has examined the impact of lower limb length discrepancy (LLLD) alteration on spinopelvic compensation in individuals with developmental dysplasia of the hip (DDH). This study aimed to investigate the effects of LLLD on spinopelvic compensation following total hip arthroplasty (THA) and elucidate the complex biomechanical adaptations in the spinopelvic structures. METHODS: A retrospective review of DDH patients undergoing THA from January 2014 to December 2021 categorized individuals with Crowe type I and II into the low dislocation group (LDG, n = 94) and those with Crowe type III and IV into the high dislocation group (HDG, n = 43). Demographic data, as well as preoperative, postoperative, and last follow-up imaging data, including lower limb length (LLL), sacral obliquity (SO), iliac obliquity (IO), hip obliquity (HO), Cobb angle, apical vertebral translation (AVT), and coronal decompensation (CD), were collected for analysis. RESULTS: Patients in the LDG had a significantly higher surgical age and shorter disease duration (P<0.05). In LDG, patients exhibited substantial postoperative reductions in LLLD, SO, IO, and HO (P<0.05), while Cobb Angle, AVT, and CD showed no statistically significant changes (P>0.05). The variation in LLLD correlated significantly with the variations in SO, IO, and HO (P<0.05). Postoperative outcomes in the HDG demonstrated marked decreases in LLLD, SO, IO, HO, and CD (P<0.05), with no significant change in Cobb angle and AVT (P>0.05). The variation in LLLD correlated significantly with the variations in SO, IO, HO, and CD (P<0.05). CONCLUSIONS: THA effectively reduces LLLD in patients with DDH, and the variation in LLLD correlates meaningfully with the recovery of spinopelvic compensatory mechanisms.

Plasma exosomes from patients with active thyroid-associated orbitopathy induce inflammation and fibrosis in orbital fibroblasts.

BACKGROUND: The pathogenesis of thyroid-associated orbitopathy (TAO) remains incompletely understand. The interaction between immunocytes and orbital fibroblasts (OFs) play a critical role in orbital inflammatory and fibrosis. Accumulating reports indicate that a significant portion of plasma exosomes (Pla-Exos) are derived from immune cells; however, their impact upon OFs function is unclear. METHODS: OFs were primary cultured from inactive TAO patients. Exosomes isolated from plasma samples of patients with active TAO and healthy controls (HCs) were utilized for functional and RNA cargo analysis. Functional analysis in thymocyte differentiation antigen-1+ (Thy-1+) OFs measured expression of inflammatory and fibrotic markers (mRNAs and proteins) and cell activity in response to Pla-Exos. RNA cargo analysis was performed by RNA sequencing and RT-qPCR. Thy-1+ OFs were transfected with miR-144-3p mimics/inhibitors to evaluate its regulation of inflammation, fibrosis, and proliferation. RESULTS: Pla-Exos derived from active TAO patients (Pla-ExosTAO-A) induced stronger production of inflammatory cytokines and hyaluronic acid (HA) in Thy-1+ OFs while inhibiting their proliferation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and single sample gene set enrichment analysis (ssGSEA) suggested that the difference in mRNA expression levels between Pla-ExosTAO-A and Pla-ExosHC was closely related to immune cells. Differential expression analysis revealed that 62 upregulated and 45 downregulated miRNAs in Pla-ExosTAO-A, with the elevation of miR-144-3p in both Pla-Exos and PBMCs in active TAO group. KEGG analysis revealed that the target genes of differentially expressed miRNA and miR-144-3p enriched in immune-related signaling pathways. Overexpression of the miR-144-3p mimic significantly upregulated the secretion of inflammatory cytokines and HA in Thy-1+ OFs while inhibiting their proliferation. CONCLUSION: Pla-Exos derived from patients with active TAO were immune-active, which may be a long-term stimulus casual for inflammatory and fibrotic progression of TAO. Our finding suggests that Pla-Exos could be used as biomarkers or treatment targets in TAO patients.