Explore the vast range of titles available.

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by damage to small intrahepatic bile ducts. The etiology and pathogenesis of PBC remain unknown. It is often considered to be related to an immunological disorder induced by genetics and environmental factors. Antimitochondrial antibodies (AMAs) along with specific antinuclear antibodies such as gp210 and Sp100 are specific markers of the disease. Middle-aged and elderly women are the main patients. The clinical manifestations of PBC are non-specific, which presents as fatigue and skin itching usually. However, patients gradually develop cholestasis and liver fibrosis, eventually dying as the disease progressed to cirrhosis and liver failure. Currently, ursodeoxycholic acid (UDCA) is the treatment of choice, which is recommended for all patients. PBC may coexist with other autoimmune disorders that may arise from multiple systems, such as inflammatory bowel disease (IBD), Sjögren’s syndrome (SS) and type 1 diabetes mellitus (T1DM). The causal relationship between PBC and extrahepatic autoimmune diseases (EHAIDs) is unclear. This article summarizes the new developments in the study of primary biliary cholangitis and aims to provide a reference for scientific and clinical workers in the field of research on this disease.

Background Preserved Ratio Impaired Spirometry (PRISm) is defined as FEV1/FVC ≥ 70% and FEV1 < 80%pred by pulmonary function test (PFT). It has highly prevalence and is associated with increased respiratory symptoms, systemic inflammation, and mortality. However, there are few radiological studies related to PRISm. The purpose of this study was to investigate the quantitative high-resolution computed tomography (HRCT) characteristics of PRISm and to evaluate the correlation between quantitative HRCT parameters and pulmonary function parameters, with the goal of establishing a nomogram model for predicting PRISm based on quantitative HRCT. Methods A prospective and continuous study was performed in 488 respiratory outpatients from February 2020 to February 2021. All patients underwent both deep inspiratory and expiratory CT examinations, and received pulmonary function test (PFT) within 1 month. According to the exclusion criteria and Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification standard, 94 cases of normal pulmonary function, 51 cases of PRISm and 48 cases of mild to moderate chronic obstructive lung disease (COPD) were included in the study. The lung parenchyma, parametric response mapping (PRM), airway and vessel parameters were measured by automatic segmentation software (Aview). One-way analysis of variance (ANOVA) was used to compare the differences in clinical features, pulmonary function parameters and quantitative CT parameters. Spearman rank correlation analysis was used to evaluate the correlation between CT quantitative index and pulmonary function parameters. The predictors were obtained by binary logistics regression analysis respectively in normal and PRISm as well as PRISm and mild to moderate COPD, and the nomogram model was established. Results There were significant differences in pulmonary function parameters among the three groups (P < 0.001). The differences in pulmonary parenchyma parameters such as emphysema index (EI), pixel indices-1 (PI-1) and PI-15 were mainly between mild to moderate COPD and the other two groups. The differences of airway parameters and pulmonary vascular parameters were mainly between normal and the other two groups, but were not found between PRISm and mild to moderate COPD. Especially there were significant differences in mean lung density (MLD) and the percent of normal in PRM (PRM Normal ) among the three groups. Most of the pulmonary quantitative CT parameters had mild to moderate correlation with pulmonary function parameters. The predictors of the nomogram model using binary logistics regression analysis to distinguish normal from PRISm were smoking, MLD, the percent of functional small airways disease (fSAD) in PRM (PRM fSAD ) and Lumen area. It had a good goodness of fit (χ 2  = 0.31, P < 0.001) with the area under curve (AUC) value of 0.786. The predictor of distinguishing PRISm from mild to moderate COPD were PRM Emph (P < 0.001, AUC = 0.852). Conclusions PRISm was significantly different from subjects with normal pulmonary function in small airway and vessel lesions, which was more inclined to mild to moderate COPD, but there was no increase in pulmonary parenchymal attenuation. The nomogram based on quantitative HRCT parameters has good predictive value and provide more objective evidence for the early screening of PRISm.

Adoptive cell transfer (ACT) using neoantigen-specific T cells is an effective immunotherapeutic strategy. However, the difficult isolation of neoantigen-specific T cells limits the clinical application of ACT. Here, we propose a method to prepare neoantigen-reactive T cells (NRT) for ACT following immunization with a tumor lysate-loaded dendritic cell (DC) vaccine. We show that the DC vaccine not only induces a neoantigen-reactive immune response in lung cancer-bearing mice in vivo, but also facilitate NRT cell preparation in vitro. Adoptive transfer of the NRTs as combinatorial therapy into DC vaccine-immunized, LL/2 tumor-bearing mice allows infiltration of the infused NRTs, as well as the enrichment of neoantigen reactive, non-ACT/NRT T cells into the tumor microenvironment with the function of these neoantigen-reactive T-cell receptors validated in vitro. In summary, we propose a method for preparing NRTs that increases ACT efficacy and paves the way to the design of personalized immunotherapies. The generation of neoantigen-specific T cells for adoptive cell therapy (ACT) is challenging. Here the authors conveniently produce ACT-amenable neoantigen-reactive T cells (NRT) by inducing neoantigen-specific immune responses in vivo via dendritic cell vaccination and find adoptive transfer of such NRTs in a pre-immunized mouse model of lung cancer improves ACT efficacy and induces tumor regression.

As an overarching policy and development model, transitoriented development (TOD) is widely used to promote the integration of land use and transit services, which arguably brings about many benefits. TOD advocates have continuously paid much attention to metro station areas (MSAs), i.e., areas within a reasonable walking distance to a metro station. To TOD advocates, well-planned MSAs should have a sufficient supply of TOD-nesses encapsulating characteristics such as destinations, density, diversity, and design. In the existing scholarship, however, little has been done on (a) TOD-nesses’ potential “consumers,” the population that is only a short metro ride away from an MSA, i.e., the metro-based accessibility (MBA) to the consumers of the MSA; and (b) whether and how TOD-nesses of one MSA and several MSAs in proximity are affected by the MBA. With the help of big and/or open data, we examine whether and to what degree the MBA of an MSA cluster (MSAC), a set of MSAs within t minutes of a metro ride from a metro station is correlated to that MSAC’s TOD-nesses in Shenzhen, China. We measure the MBA by the daytime/nighttime population in the same MSAC. We quantify TOD-nesses using the published indices or the averages of the indices in a refereed article. Coefficient of geography association, Gini index, pairwise correlation, and linear regression analyses are carried out. We find that the MBA in one period significantly predicts MSAC-level TOD-nesses in ensuing periods. However, the MBA’s prediction power decreases or even disappears over time. Besides, metro station characteristics such as the jurisdiction membership significantly predict the overall TOD-nesses and individual aspects of the TOD-nesses after controlling for the MBA. Our study thus sheds new light on meso-or MSAC-level TOD-nesses and related policy and planning evaluation.

Background Panax notoginseng (PN) is a medicinal plant containing essential ginsenosides. Given the therapeutic significance of ginsenosides, we delved into the mechanisms of ginsenoside Rb3 biosynthesis in PN flowers. We examined this process from the pre-differentiation stage to the end of flowering, aiming to uncover the biochemical pathways underlying ginsenoside production in PN. Results Budding stage (T2) was found critical for enhanced Rb3 production. Transcriptomic analysis revealed a marked shift in gene expression beginning at T2, with upregulation in pathways associated with secondary metabolite production. Gene set enrichment analysis (GSEA) illuminated the upregulation of genes involved in terpenoid backbone biosynthesis, amino acid degradation, and terpenoid modifications, specifically at T2. We correlated the fluctuating hormone levels with the activity of the transcription factor MYC2 to underscore hormonal influence on ginsenoside biosynthesis. Biosynthesis pathway reconstruction revealed the dominance of the mevalonate pathway. Critical enzymes such as ACAT, PPDS, DDS, and LUP4 were vital in precursor biosynthesis and modification. Notably, key genes such as HMGCS , FDPS , and DDS , as well as transcription factors MYC2, MYB124, and MYB61.1, showed a concerted surge in activity at T2. Conclusions These findings provide insights into the complex gene networks and molecular pathways that regulate ginsenoside biosynthesis, thereby promoting the medicinal properties of PN.

With the rapid development of smart medical care, copyright security for medical images is becoming increasingly important. To improve medical images storage and transmission safety, this paper proposes a robust zero-watermarking algorithm for medical images by fusing Dual-Tree Complex Wavelet Transform (DTCWT), Hessenberg decomposition, and Multi-level Discrete Cosine Transform (MDCT). First, the low-frequency sub-band of the medical image is obtained through the DTCWT and MDCT. Then Hessenberg decomposition is used to construct the visual feature vector. Meanwhile, the encryption of the watermarking image by combining cryptographic algorithms, third-party concepts, and chaotic sequences enhances the algorithm’s security. In the proposed algorithm, zero-watermarking technology is utilized to assure the medical images’ completeness. Compared with the existing algorithms, the proposed algorithm has good robustness and invisibility and can efficiently extract the watermarking image and resist different attacks.

Background UV-induced cutaneous squamous cell carcinoma (cSCC) is one of the most common skin cancers. The constant alterations of the lymphatic-centered immune microenvironment are essential in transforming from photoaging to cSCC. Studying the mechanism will be beneficial for new targets exploration to the early prediction of cSCC. Aims To investigate the dynamic changes and mechanism of the lymphatic-centered immune microenvironment in transforming from photoaging to cSCC induced by ultraviolet irradiation (UVR). Methods TIMER2.0 was used to analyze whether YAP1/VEGFC signaling pathway is involved in lymphangiogenesis in head and neck squamous cell carcinoma (HNSCC). Meanwhile, lymphatic-centered immune microenvironments alterations and the related cumulative survival time were also analyzed. With the accumulated UVR, skin photoaging developed and gradually progressed into actinic keratosis and cSCC on SKH-1 hairless mice. The skin lymphatic-centered immune microenvironment was evaluated at the 0th, 8th, 12th, 16-18th, and 20-24th week of UVR. Skin phenotype was assessed using optical coherence tomography (OCT) and skin image. H&E and Masson’s trichrome staining evaluated epidermis and dermis. The structure of lymphatic vessels (LVs), blood vessels, and different types of T cells were evaluated by immunohistochemistry staining. The expression of Piezo1 whose deletion in adult lymphatics led to substantial valve degeneration, VE-cadherin that maintained the permeability of LVs, and YAP1 were evaluated by immunohistochemistry staining as well. Besides, the drainage function of LVs was assessed by Evans Blue assay in vivo. Results The lymphatic function and immune cell infiltration underwent adaptive changes under continuous UVR. TIMER2.0 analysis indicated that VEGFC genes high expressed in HNSCC. YAP1 gene expression was positive correlated with VEGFC in HNSCC. LV density increased in human cSCC. More LVs in HNSCC were beneficial to prolong the survival time. VEGFC gene overexpression was positive correlated to CD8 + T cell infiltration. More CD8A + T cells and CD8B + T cell infiltration in HNSCC extended survival time. When YAP1 gene overexpression and high infiltration of endothelial cells took place simultaneously might prolong the survival time of HNSCC patients. And high infiltration of CD8 + T cells prolonged the survival time as well. In animal studies, UVR-induced eight weeks (photoaging) and 16–18 weeks (precancerous) were two turning points. The density of LVs in UV-8w was the least. When photoaged skin developed into AK lesions (UV-16-18w), LV slightly exceeded healthy skin and proliferated sharply in cSCC (UV-20-24w). YAP1 expression was almost consistent with LV but rose after the photoaging stage. The drainage of cSCC mice induced by UVR was better than that of photoaged skin and worse than that of health skin. The dynamic alterations of LVs number, Piezo1 expression, and collagen might be reasons for it. The expression of Piezo1 was in the highest point after 8 weeks of UVR, then gradually descended to the platform. The total T cells increased slowly, but the infiltration of CD4 + T cells increased, and CD8 + T cells decreased after eight weeks of UVR. The CD8 + T cells and CD4 + T cells increased sharply in UV-16-18w and UV-20-24w groups. Conclusion The lymphatic-centered immune microenvironment underwent adaptive changes under continuous UVR via regulating YAP1/VEGFC and Piezo1. During the formation of cSCC, there are two turning points, eight weeks (photoaging) and 16–18 weeks (precancerous). YAP1, Piezo1, LVs, and immune cells constantly changed with the skin state induced by UVR. According to these changes the process of cSCC can be identified in advance and intervene timely. Key points It investigated the dynamic changes of the lymphatic-centered immune microenvironment firstly in cSCC formation process induced by UVR. The lymphatic-centered immune microenvironment has adapted under continuous UVR via regulating YAP1/VEGFC and Piezo1. There are two turning points of lymphatic changes occurred during UV-induced cSCC formation. YAP1, Piezo1, LVs, and immune cells constantly changed with the skin state induced by UVR. According to these changes, the process of cSCC can be identified in advance and intervene timely.

Neonatal necrotizing enterocolitis (NEC) is a life-threatening gastrointestinal disease of premature infants, characterized by immune dysregulation and compromised intestinal barrier integrity. Interleukin-27 receptor α (IL-27Ra), a critical component of the JAK-STAT signaling pathway, exhibits dual pro- and anti-inflammatory roles in various inflammatory conditions. However, its role in NEC pathogenesis remains unclear. To elucidate the functional role of IL-27Ra in NEC development and assess its potential as a therapeutic target. A multi-tiered approach was employed, including integrative analysis of clinical NEC specimens by single-cell and bulk RNA sequencing, and a neonatal mouse NEC model. NEC was induced in mice via hyperosmolar formula feeding combined with LPS gavage, intermittent hypoxia, and cold stress. Additional experiments included immunofluorescence staining for IL-27Ra, cytokine profiling (ELISA, quantitative real-time PCR (qPCR)), use of IL-27Ra knockout (IL-27Ra -/- ) mice, and histopathological scoring of intestinal injury. In NEC patient intestinal tissues, IL-27Ra expression was significantly upregulated in immune cells, with expression levels positively correlating with pro-inflammatory mediators (e.g., IL-6) and inversely correlating with barrier-associated proteins (e.g., TJP1). In the neonatal mouse NEC model, genetic ablation of IL-27Ra (IL-27Ra -/- ) led to reduced histopathology scores, decreased IL-6 production (ELISA and qPCR), and restored tight junction protein expression (TJP1, OCLN). IL-27Ra promotes NEC by amplifying intestinal inflammation and damaging the mucosal barrier. Thus, IL-27Ra is identified as a promising therapeutic target. Pharmacological blockade of IL-27Ra signaling may provide a dual benefit in NEC—mitigating excessive inflammation while restoring barrier integrity. These findings are primarily derived from NEC mouse models and await clinical validation.

Background There are two types of testicular torsion: complete and incomplete. The degree and duration of symptoms of this condition are critical for treatment decision-making, as the consequences for untimely diagnosis and management can be serious. The preoperative assessment of the degree of acute testicular torsion using ultrasonography is particularly important for determining the appropriate intervention. The purpose of this study was to compare the effectiveness of high-frequency versus contrast-enhanced ultrasonography in determining the degree of acute testicular torsion. Methods Fifteen patients with clinically diagnosed acute testicular torsion underwent both high-frequency and contrast-enhanced ultrasonography. We compared the characteristics of the ultrasonographic images of the testicular parenchyma in both the afflicted and contralateral (healthy) testes to determine the reliability of contrast-enhanced ultrasonography in assessing the degree of acute testicular torsion. Results The high-frequency ultrasound and contrast-enhanced ultrasound diagnosis of 4 complete testicular torsion and 11 incomplete testicular torsion were correct before operation. However, 5 patients with incomplete testicular torsion were misdiagnosed as complete testicular torsion because no blood flow was detected by high frequency ultrasound. Finally, low speed blood flow was detected by contrast-enhanced ultrasound and the diagnosis was corrected. The accuracy of diagnosing incomplete testicular torsion was 100% using contrast-enhanced ultrasonography and 66.7% using high-frequency ultrasonography; the difference between the two methods was statistically significant (χ 2  = 2.50, P  ≤ 0.05). Conclusion Contrast-enhanced ultrasonography can diagnose testicular torsion with high accuracy and can detect low-velocity blood flow and show microcirculatory blood perfusion in the testicular parenchyma. This can avoid misdiagnosing incomplete testicular torsion as complete, thus averting unnecessary orchiectomy.

Kinetic resolution (KR) of racemic starting materials is a powerful and practical alternative to prepare valuable enantiomerically enriched compounds. A magnesium-catalyzed kinetic resolution based on a designed intramolecular vinylogous Michael reaction is disclosed. Here we show a synergistic catalytic strategy based on the development of chiral ligands. Substrates containing linear allylic ester structures are designed and synthesized to construct key [6.6.5]-tricyclic chiral skeletons via this kinetic resolution process. Detailed mechanistic studies reveal a rational mechanism for the current intramolecular vinylogous KR reaction. The desired direct intramolecular asymmetric vinylogous Michael reaction of linear allylic esters is realized in high efficiency and enantioselectivity with the synergistic catalytic system. Kinetic resolution allows to obtain enantioenriched compounds from racemic mixtures. Here, the authors report a synergistic magnesium catalyst promoting kinetic resolution of an intramolecular vinylogous Michael reaction to access [6.6.5]-tricyclic chiral skeletons.