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This study was aimed to investigate the evolution of bone mineral density (BMD) in patients with maintenance hemodialysis (MHD) by using phantom-less quantitative computed tomography (PL-QCT). We collected patients with MHD in Suzhou Hospital of Nanjing Medical University from September 2020 to December 2023 as the prospective observation group. BMD of thoracolumbar vertebra, total hip and femoral neck were measured by PL-QCT. Patients with MHD were divided into 9 groups according to hemodialysis duration. Chest CT scans of patients in prospective observation group were collected during the first three months of MHD and 1 year, 2 years, 3 years after dialysis between January 2017 and December 2023 as the retrospective observation group, and BMD of the twelfth thoracic vertebra was measured. According to the BMD changes among the prospective observation group and the retrospective observation group, the evolution of thoracolumbar vertebral BMD, whole hip BMD and femoral neck BMD were comprehensively analyzed. BMD of thoracolumbar vertebra gradually decreased within 36 months in patients with MHD. Thoracolumbar vertebral BMD tended to increase when hemodialysis duration was more than 36–48 months, and thoracolumbar vertebral BMD increased significantly with hemodialysis duration when hemodialysis duration was more than 60 months, and significantly exceeded the BMD before MHD. BMD of total hip and femoral neck gradually decreased within 36 months in patients with MHD. BMD of total hip and femoral neck increased with hemodialysis duration when hemodialysis duration was more than 72 months, but was almost the same as that of the first year of MHD. In the follow-up evaluation of BMD in MHD patients, it is recommended to use QCT to measure BMD in thoracolumbar vertebrae or hip the first 3 years of MHD, and use QCT to measure BMD in thoracolumbar vertebrae to evaluate changes over 5 years of MHD.

China’s cities are shifting from expansion to renewal. In cold-climate cities, street use often drops in winter, so human-centred street quality matters. However, few studies measure behavioural activity using the same indicators for winter and non-winter periods. We propose an “activity portraits” framework and an Activity Portrait Index (API) that combines activity density, activity-type propensity, and age-group diversity. We used street-view images and field surveys from 37 street segments in Harbin, covering commercial, living, and landscape streets. Streetscape elements were extracted, and separate regression models were built for winter and non-winter conditions. In winter, seven streetscape factors were significant and were entered into the regression as four PCA components. In non-winter conditions, the model retained four predictors: street width-to-height (W/H) ratio, road clutter, greenery visibility, and signage density (R2 = 0.802). The models show season-specific links between activity and street space and support a seasonal API measurement system for cold-region streets. The results inform targeted design and renewal principles to improve street usability and vitality year-round.

Liver fibrosis, a progressive condition with limited pharmacotherapies, poses a global health challenge. Scutellarin (SCU), a flavonoid derived from Erigeron breviscapus, has demonstrated anti-fibrotic activity and modulates gut microbiota. Emerging evidence suggests that SCU may also influence the hepatic microbiome. However, its clinical utility is constrained by poor water solubility and low oral bioavailability. Here, we developed an SCU-loaded nanoemulsion (SCE) to enhance solubility and liver-targeted delivery. In vitro, SCE increased SCU uptake in hepatic stellate cells (HSCs) and significantly inhibited TGF-β1-induced fibrogenesis. In a bile duct ligation (BDL) mouse model, oral administration of SCE improved hepatic SCU accumulation and produced superior anti-fibrotic efficacy. SCE treatment attenuated fibrosis and collagen deposition in the liver and improved liver function markers. Mechanistic investigations using 16S rRNA sequencing revealed that SCU treatment was associated with beneficial microbiota changes, although its main therapeutic effects were achieved through enhanced hepatic targeting. Notably, the SCE formulation was well-tolerated, showing no significant toxicity in vitro or in vivo. In conclusion, the SCU-loaded nanoemulsion achieved enhanced hepatic delivery of SCU and exerted potent anti-fibrotic effects via multiple mechanisms, including direct suppression of fibrogenesis and ancillary modulation of the gut–liver microbiome, offering a promising therapeutic strategy for liver fibrosis.

Abnormal expansions of the CAG trinucleotide repeat within specific gene exons give rise to polyglutamine (polyQ) diseases, a family of inherited disorders characterized by late-onset neurodegeneration. Recently, a new type of polyQ disease was identified and named spinocerebellar ataxia 51 (SCA51). SCA51 is caused by polyQ expansion in THAP domain containing 11 (THAP11), an essential transcription factor for brain development. The pathogenesis of SCA51, particularly how mutant THAP11 with polyQ expansion contributes to neuropathology, remains elusive. Our study of mouse and monkey brains revealed that THAP11 expression is subject to developmental regulation, showing enrichment in the cerebellum. However, knocking down endogenous THAP11 in adult mice did not affect neuronal survival. In contrast, expressing mutant THAP11 with polyQ expansion led to pronounced protein aggregation, cerebellar neurodegeneration, and motor deficits, indicating that gain-of-function mechanisms are central to SCA51 pathogenesis. We discovered activated microglia expressing triggering receptor expressed on myeloid cells 2 (TREM2) in the cerebellum of a newly developed SCA51 knockin mouse model. Mechanistically, mutant THAP11 enhanced the transcription of TREM2, leading to its upregulation. The loss of TREM2 or depletion of microglia mitigated neurodegeneration induced by mutant THAP11. Our study offers the first mechanistic insights to our knowledge into the pathogenesis of SCA51, highlighting the role of TREM2-mediated microglial activation in SCA51 neuropathology.

Osteoarthritis (OA) is a leading cause of pain and disability worldwide. Despite extensive research, no curative treatment is currently available. Most therapies focus on symptom relief or disease modification. Traditional Chinese medicines, particularly Astragalus mongholicus (Huangqi) and Saposhnikovia divaricata (Fangfeng), have demonstrated therapeutic potential for OA, but their molecular mechanisms remain unclear. The synovium plays a key role in OA pathogenesis and disease progression, yet the effects of these herbal extracts on synoviocytes are poorly understood. To explore potential targets, we analyzed all publicly available microarray datasets comparing gene expression in OA and healthy synovium/synoviocytes. Differentially expressed genes (DEGs) were identified and compared with known targets of A. mongholicus and S. divaricata . The intersecting genes were subjected to Gene Ontology, KEGG pathway, and protein‒protein interaction analyses to identify hub genes. Key transcription factors were predicted using the KNOCK.TF database. Expression of hub genes and transcription factors was validated in human synoviocytes treated with A. mongholicus and S. divaricata extracts. We identified ten hub genes, eight of which may serve as OA biomarkers. Three hub transcription factors—AR, CITED2, and SF1—were upregulated by the extracts, while MMP2 and MMP9, two OA-associated genes, were downregulated. Our findings suggest that A. mongholicus and S. divaricata may exert therapeutic effects on OA by modulating synoviocyte gene expression, notably through upregulation of AR and CITED2 and downregulation of MMP2 and MMP9. These herbs may provide molecular targets for novel OA treatments.

Purpose To investigate the value and age- and gender-specific threshold values of bone mineral density (BMD) by quantitative computed tomography (QCT) for the prediction of spontaneous thoracolumbar vertebral fractures and thoracolumbar junction fractures accompanying distant vertebral fractures. Methods Among the 556 patients included, 68 patients had thoracolumbar vertebral fractures (12 patients with distant vertebral fractures, 56 patients without distant vertebral fractures) and 488 patients had no vertebral fractures. All patients were grouped by gender and age. According to the principle of Youden index, the threshold values were calculated from receiver operating characteristic (ROC) curves. Results The threshold values for predicting thoracolumbar vertebral fractures were 89.8 mg/cm 3 for all subjects, 90.1 mg/cm 3 for men, and 88.6 mg/cm 3 for women. The threshold values for men aged < 60 years old and ≥ 60 years old were 117.4 mg/cm 3 and 87.5 mg/cm 3 , respectively. The threshold values for women aged < 60 years old and ≥ 60 years old were 88.6 and 68.4 mg/cm 3 , respectively. The threshold value for predicting spontaneous thoracolumbar junction fractures with distant vertebral fractures was 62.7 mg/cm 3 . Conclusions QCT provides a good ability to predict age- and gender-specific spontaneous thoracolumbar vertebral fractures, and to further predict spontaneous thoracolumbar junction fractures with distant vertebral fractures.

Huntington's disease (HD) is caused by expanded CAG repeats in the huntingtin gene (HTT) and is characterized by late-onset neurodegeneration that primarily affects the striatum. Several studies have shown that mutant HTT can also affect neuronal development, contributing to the late-onset neurodegeneration. However, it is currently unclear whether mutant HTT impairs the development of glial cells, which is important for understanding whether mutant HTT affects glial cells during early brain development. Using HD knock-in mice that express full-length mutant HTT with a 140 glutamine repeat at the endogenous level, we analyzed the numbers of astrocytes and oligodendrocytes from postnatal day 1 to 3 months of age via Western blotting and immunocytochemistry. We also performed electron microscopy, RNAseq analysis, and quantitative RT-PCR. The numbers of astrocytes and oligodendrocytes were not significantly altered in postnatal HD KI mice compared to wild type (WT) mice. Consistently, glial protein expression levels were not significantly different between HD KI and WT mice. However, at 3 months of age, myelin protein expression was reduced in HD KI mice, as evidenced by Western blotting and immunocytochemical results. Electron microscopy revealed a slight but significant reduction in myelin thickness of axons in the HD KI mouse brain at 3 months of age. RNAseq analysis did not show significant reductions in myelin-related genes in postnatal HD KI mice. These data suggest that cytoplasmic mutant HTT, rather than nuclear mutant HTT, mediates myelination defects in the early stages of the disease without impacting the differentiation and maturation of glial cells.

In this paper, polylactic acid/cellulose nanocrystalline composite fiber membranes were prepared by electrospinning technique. The morphology, thermal properties and in vitro degradation of fiber membranes were analyzed by SEM, FTIR, TG, DSC and other methods. The results showed that both the physiological saline solution and the phosphate buffer solution can degrade the polylactic acid/cellulose nanocrystalline composite fiber membrane, and the degradation effect of the phosphate buffer solution was better. At the same time, it is found that the addition of cellulose nanocrystals improves the pre-degradation rate of composite fiber membranes.

Huntington’s disease (HD) arises from the abnormal expansion of CAG repeats in the huntingtin gene (HTT), resulting in the production of the mutant huntingtin protein (mHTT) with a polyglutamine stretch in its N-terminus. The pathogenic mechanisms underlying HD are complex and not yet fully elucidated. However, mHTT forms aggregates and accumulates abnormally in neuronal nuclei and processes, leading to disruptions in multiple cellular functions. Although there is currently no effective curative treatment for HD, significant progress has been made in developing various therapeutic strategies to treat HD. In addition to drugs targeting the neuronal toxicity of mHTT, gene therapy approaches that aim to reduce the expression of the mutant HTT gene hold great promise for effective HD therapy. This review provides an overview of current HD treatments, discusses different therapeutic strategies, and aims to facilitate future therapeutic advancements in the field.

Huntington’s disease (HD) is a hereditary neurodegenerative disorder caused by a CAG tract expansion in the huntingtin gene (HTT). HD is characterized by involuntary movements, cognitive decline, and behavioral changes. Pathologically, patients with HD show selective striatal neuronal vulnerability at the early disease stage, although the mutant protein is ubiquitously expressed. Activation of the immune system and glial cell-mediated neuroinflammatory responses are early pathological features and have been found in all neurodegenerative diseases (NDDs), including HD. However, the role of inflammation in HD, as well as its therapeutic significance, has been less extensively studied compared to other NDDs. This review highlights the significantly elevated levels of inflammatory proteins and cellular markers observed in various HD animal models and HD patient tissues, emphasizing the critical roles of microglia, astrocytes, and oligodendrocytes in mediating neuroinflammation in HD. Moreover, it expands on recent discoveries related to the peripheral immune system’s involvement in HD. Although current immunomodulatory treatments and inflammatory biomarkers for adjunctive diagnosis in HD are limited, targeting inflammation in combination with other therapies, along with comprehensive personalized treatment approaches, shows promising therapeutic potential.