Altered CD226/TIGIT expressions were associated with NK phenotypes in primary antiphospholipid syndrome and affected by IL-4/JAK pathway.

Natural killer (NK) cells were reported to be involved in the pathogenesis of primary antiphospholipid syndrome (pAPS). Immunosuppressive receptor T-cell immunoreceptor with Ig and ITIM domains (TIGIT) and activating receptor cluster of differentiation 226 (CD226) are specifically expressed on NK cells with competitive functions. This study aims to investigate the expression diversities of CD226/TIGIT on NK subsets and their associations with NK subsets activation phenotypes and potential clinical significance, furthermore, to explore potential cause for CD226/TIGIT expression diversities in pAPS. We comparatively assessed the changes of CD56brightNK, CD56dimNK, and NK-like cells in 70 pAPS patients compared with control groups, including systemic lupus erythematosus, asymptomatic antiphospholipid antibodies carriers (asymp-aPLs carriers), and healthy controls and their expression diversities of CD226/TIGIT by flow cytometry. CD25, CD69, CD107α expression, and interferon gamma (IFN-γ) secretion levels of NK subsets were detected to determine the potential association of CD226/TIGIT expression with NK subsets phenotypes. CD226/TIGIT expression levels were compared among different subgroups divided by aPLs status. Moreover, in vitro cultures were conducted to explore the potential mechanisms of CD226/TIGIT expression imbalance. CD56brightNK and CD3+CD56+NK-like cells were significantly increased while CD56dimNK cells were obviously decreased in pAPS, and CD56brightNK and NK-like cells exhibited significantly higher CD226 but lower TIGIT expressions. CD226+CD56brightNK and TIGIT-CD56brightNK cells show higher CD69 expression and IFN-γ secretion capacity, and CD226+NK-like and TIGIT-NK-like cells showed higher expressions of CD25 and CD69 but lower apoptosis rate than CD226- and TIGIT+CD56brightNK/NK-like cells, respectively. The imbalanced CD226/TIGIT expressions were most significant in aPLs triple-positive group. Imbalanced expressions of CD226/TIGIT on CD56brightNK and NK-like cells were aggravated after interleukin-4 (IL-4) stimulation and recovered after tofacitinib blocking. Our data revealed significant imbalanced CD226/TIGIT expressions on NK subsets in pAPS, which closely associated with NK subsets phenotypes and more complicated autoantibody status. CD226/TIGIT imbalanced may be affected by IL-4/Janus Kinase (JAK) pathway activation.

Recent Toolboxes for Chemoselective Dual Modifications of Proteins.

Site-selective chemical modifications of proteins have emerged as a potent technology in chemical biology, materials science, and medicine, facilitating precise manipulation of proteins with tailored functionalities for basic biology research and developing innovative therapeutics. Compared to traditional recombinant expression methods, one of the prominent advantages of chemical protein modification lies in its capacity to decorate proteins with a wide range of functional moieties, including non-genetically encoded ones, enabling the generation of novel protein conjugates with enhanced or previously unexplored properties. Among these, approaches for dual or multiple protein modifications are increasingly garnering attention, as it has been found that single modifications of proteins are inadequate to meet current demands. Therefore, in light of the rapid developments in this field, this review provides a timely and comprehensive overview of the latest advancements in chemical and biological approaches for protein dual functionalization. It further discusses their advantages, limitations, and potential future directions in this relatively nascent area.

microRNA-622 upregulates cell cycle process by targeting FOLR2 to promote CRC proliferation.

BACKGROUND: Epigenetic alterations contribute greatly to the development and progression of colorectal cancer, and effect of aberrant miR-622 expression is still controversial. This study aimed to discover miR-622 regulation in CRC proliferation. METHODS: miR-622 expression and prognosis were analyzed in clinical CRC samples from Nanfang Hospital. miR-622 regulation on cell cycle and tumor proliferation was discovered, and FOLR2 was screened as functional target of miR-622 using bioinformatics analysis, which was validated via dual luciferase assay and gain-of-function and loss-of-function experiments both in vitro and in vivo. RESULTS: miR-622 overexpression in CRC indicated unfavorable prognosis and it regulated cell cycle to promote tumor growth both in vitro and in vivo. FOLR2 is a specific, functional target of miR-622, which negatively correlates with signature genes in cell cycle process to promote CRC proliferation. CONCLUSIONS: miR-622 upregulates cell cycle process by targeting FOLR2 to promote CRC proliferation, proposing a novel mechanism and treatment target in CRC epigenetic regulation of miR-622.

Effects of the Fasting-Postprandial State on Arterial Spin Labeling MRI-Based Cerebral Perfusion Quantification in Alzheimer's Disease.

BACKGROUND: The fasting-postprandial state remains an underrecognized confounding factor for quantifying cerebral blood flow (CBF) in the cognitive assessment and differential diagnosis of Alzheimer's disease (AD). PURPOSE: To investigate the effects of fasting-postprandial state on arterial spin labeling (ASL)-based CBF in AD patients. STUDY TYPE: Prospective. SUBJECTS: Ninety-two subjects (mean age = 62.5 ± 6.4 years; females 29.3%), including 30 with AD, 32 with mild cognitive impairment (MCI), and 30 healthy controls (HCs). Differential diagnostic models were developed with a 4:1 training to testing set ratio. FIELD STRENGTH/SEQUENCE: 3-T, T1-weighted imaging using gradient echo and pseudocontinuous ASL imaging using turbo spin echo. ASSESSMENT: Two ASL scans were acquired to quantify fasting state and postprandial state regional CBFs based on an automated anatomical labeling atlas. Two-way ANOVA was used to assess the effects of fasting/postprandial state and disease state (AD, MCI, and HC) on regional CBF. Pearson's correlation analysis was conducted between regional CBF and cognitive scores (Mini-Mental State Examination [MMSE] and Montreal Cognitive Assessment [MoCA]). The diagnostic performances of the fasting state, postprandial state, and mixed state (random mixing of the fasting and postprandial state CBF) in differential diagnosis of AD were conducted using support vector machine and logistic regression models. STATISTICAL TESTS: Two-way ANOVA, Pearson's correlation, and area under the curve (AUC) of diagnostic model were performed. P values <0.05 indicated statistical significance. RESULTS: Fasting-state CBF was correlated with cognitive scores in more brain regions (17 vs. 4 [MMSE] and 15 vs. 9 [MoCA]) and had higher absolute correlation coefficients than postprandial-state CBF. In the differential diagnosis of AD patients from MCI patients and HCs, fasting-state CBF outperformed mixed-state CBF, which itself outperformed postprandial-state CBF. DATA CONCLUSION: Compared with postprandial CBF, fasting-state CBF performed better in terms of cognitive score correlations and in differentiating AD patients from MCI patients and HCs. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

Quantitative trait locus analysis of gray leaf spot resistance in the maize IBM Syn10 DH population.

KEY MESSAGE: The exploration and dissection of a set of QTLs and candidate genes for gray leaf spot disease resistance using two fully assembled parental genomes may help expedite maize resistance breeding. The fungal disease of maize known as gray leaf spot (GLS), caused by Cercospora zeae-maydis and Cercospora zeina, is a significant concern in China, Southern Africa, and the USA. Resistance to GLS is governed by multiple genes with an additive effect and is influenced by both genotype and environment. The most effective way to reduce the cost of production is to develop resistant hybrids. In this study, we utilized the IBM Syn 10 Doubled Haploid (IBM Syn10 DH) population to identify quantitative trait loci (QTLs) associated with resistance to gray leaf spot (GLS) in multiple locations. Analysis of seven distinct environments revealed a total of 58 QTLs, 49 of which formed 12 discrete clusters distributed across chromosomes 1, 2, 3, 4, 8 and 10. By comparing these findings with published research, we identified colocalized QTLs or GWAS loci within eleven clustering intervals. By integrating transcriptome data with genomic structural variations between parental individuals, we identified a total of 110 genes that exhibit both robust disparities in gene expression and structural alterations. Further analysis revealed 19 potential candidate genes encoding conserved resistance gene domains, including putative leucine-rich repeat receptors, NLP transcription factors, fucosyltransferases, and putative xyloglucan galactosyltransferases. Our results provide a valuable resource and linked loci for GLS marker resistance selection breeding in maize.

Association Between HLA-DRB1 Alleles and Graves' Disease in Asian Populations: A Meta-Analysis.

Graves' disease (GD) is an autoimmune disease that primarily affects the thyroid gland. It is the most common cause of hyperthyroidism. Genetic studies have shown that human leukocyte antigen (HLA) plays an important role in the development of GD. In this article, we performed a meta-analysis determined to evaluate the relationship between HLA-DRB1 alleles and GD. This meta-analysis included 9 studies (3582 cases in the case group and 23070 cases in the control group) and 27 alleles was performed. The combined results showed that, compared with the control group, GD patients have a significant increase in the frequency of DRB1*1403 (OR=2.50, 95% CI=1.78-3.51, pc<0.0001) and have a significant decrease in frequencies of DRB1* 0101 (OR=0.45, 95% CI=0.34-0.59, pc<0.0001) and DRB1*0701 (OR=0.44, 95% CI=0.35-0.55, pc<0.0001). The meta-analysis indicated that, in Asian populations, DRB1*1403 is a risk allele for GD, and DRB1*0101 and DRB1*0701 are protective against the occurrence of GD. We surprisingly discovered that the susceptibility alleles for GD in Asian populations are completely different from Caucasians and the protective alleles for GD in Asians are quite similar to those of Caucasians. The results of our study may provide new opportunities for gene-targeted therapy for GD in Asian populations.

Intrauterine interventions options for preventing recurrence after hysteroscopic adhesiolysis: a systematic review and network meta-analysis of randomized controlled trials.

PURPOSE: Recurrence of adhesions after hysteroscopic adhesiolysis is a challenging clinical problem without a unified management approach. Therefore, we conducted a network meta-analysis that considered both direct and indirect comparisons between interventions to identify optimal strategies for preventing recurrence. METHODS: We searched for research trials published up to July 2023 from PubMed, Embase and the Cochrane Database. We selected randomized controlled trials comparing the use of different interventions for the prevention of adhesion recurrence, with no language or regional restrictions. We used random-effects models to assess odds ratios (OR) and mean difference (MD) with 95% confidence intervals (CI). Adverse events associated with the interventions were also assessed. This study was registered on PROSPERO, CRD42023449068. RESULTS: Data from 21 randomized controlled trials involving 2406 patients were synthesized, including interventions with balloon, amnion, platelet-rich plasma (PRP), intrauterine device (IUD), hyaluronic acid (HA), platelet-rich fibrin (PRF), and granulocyte colony-stimulating factor (G-CSF). The top 5 interventions for change in AFS scores were: PRP + Balloon (MD = 5.44; 95% CI, 2.63-8.25), Amnion + Balloon (MD = 5.08; 95% CI, 2.71-7.44), IUD + Balloon (MD = 4.89; 95% CI, 2.49-7.30), HA + Balloon (MD = 3.80; 95% CI, 1.78-5.82), and G-CSF + Balloon (MD = 3.84; 95% CI, 1.05-6.63). There were no statistically significant differences between interventions in the recurrence rate of moderate-to-severe uterine adhesions and the clinical pregnancy rate. Most interventions were safe. CONCLUSIONS: To our knowledge, this is the most comprehensive network meta-analysis to date of interventions for preventing postoperative intrauterine adhesion recurrence. Our results indicate that PRP + Balloon seems to be the most effective approach.

Synergistic Leaching of Titanium, Aluminum, and Magnesium Components during Dilute Acid Pressure Treatment of High-Titanium Blast Furnace Slag.

This study focuses on an improved leaching process through the combination of pressurized conditions and direct filtration of acid leaching slurry, which is conductive to improving the filterability of acid leaching systems and the extraction rates of Ti, Al, and Mg components. The effects of sulfuric acid concentration, reaction temperature, particle size of materials, acid-slag ratio, and reaction time on the leaching efficiency were systematically investigated. The results showed that pressurization significantly enhances the filtration efficiency of the reaction slurry. Under the same filtration time, the filtration efficiency increased from 46% under ordinary pressure to 78% under pressurized conditions. Moreover, under the optimal reaction conditions, the extraction rates of Ti, Al, and Mg components were more than 88.21%, 97.8%, and 96.31%, respectively. Additionally, XRD and FTIR showed that titanium oxide sulfate hydrate crystals were produced in the acid-leached residues when the reaction temperature exceeded 190 °C, thereby reducing the extraction rate of Ti component. And the XRD pattern shows that when the reaction temperature is maintained at 190 °C and the reaction time is extended to 150 min, titanium oxide sulfate hydrate crystals will be formed to reduce the extraction rate of the Ti component. In summary, this study not only provides important theoretical support for the resource utilization of high-titanium blast furnace slag but also offers a feasible solution for efficient extraction and convenient filtration, thus holding significant academic and practical implications.

Genome-Wide Identification, Characterization, and Expression Analysis of the Copper-Containing Amine Oxidase Gene Family in Mangrove Kandelia obovata.

Copper-containing amine oxidases (CuAOs) are known to have significant involvement in the process of polyamine catabolism, as well as serving crucial functions in plant development and response to abiotic stress. A genome-wide investigation of the CuAO protein family was previously carried out in sweet orange (Citrus sinensis) and sweet cherry (Prunus avium L.). Six CuAO (KoCuAO1-KoCuAO6) genes were discovered for the first time in the Kandelia obovata (Ko) genome through a genome-wide analysis conducted to better understand the key roles of the CuAO gene family in Kandelia obovata. This study encompassed an investigation into various aspects of gene analysis, including gene characterization and identification, subcellular localization, chromosomal distributions, phylogenetic tree analysis, gene structure analysis, motif analysis, duplication analysis, cis-regulatory element identification, domain and 3D structural variation analysis, as well as expression profiling in leaves under five different treatments of copper (CuCl2). Phylogenetic analysis suggests that these KoCuAOs, like sweet cherry, may be subdivided into three subgroups. Examining the chromosomal location revealed an unequal distribution of the KoCuAO genes across four out of the 18 chromosomes in Kandelia obovata. Six KoCuAO genes have coding regions with 106 and 159 amino acids and exons with 4 and 12 amino acids. Additionally, we discovered that the 2.5 kb upstream promoter region of the KoCuAOs predicted many cis elements linked to phytohormones and stress responses. According to the expression investigations, CuCl2 treatments caused up- and downregulation of all six genes. In conclusion, our work provides a comprehensive overview of the expression pattern and functional variety of the Kandelia obovata CuAO gene family, which will facilitate future functional characterization of each KoCuAO gene.

Effects of acute aerobic exercise on resting state functional connectivity of motor cortex in college students.

This study intends to inspect the effects of acute aerobic exercise (AE) on resting state functional connectivity (RSFC) in motor cortex of college students and the moderating effect of fitness level. METHODS: 20 high fitness level college students and 20 ordinary college students were recruited in public. Subjects completed 25 min of moderate- and high-intensity acute aerobic exercise respectively by a bicycle ergometer, and the motor cortex's blood oxygen signals in resting state were monitored by functional Near Infrared Spectroscopy (fNIRS, the Shimadzu portable Light NIRS, Japan) in pre- and post-test. RESULTS: At the moderate intensity level, the total mean value of RSFC pre- and post-test was significantly different in the high fitness level group (pre-test 0.62 ± 0.18, post-test 0.51 ± 0.17, t(19) = 2.61, p = 0.02, d = 0.58), but no significant change was found in the low fitness level group. At the high-intensity level, there was no significant difference in the difference of total RSFC between pre- and post-test in the high and low fitness group. According to and change trend of 190 "edges": at the moderate-intensity level, the number of difference edges in the high fitness group (d = 0.58, 23) were significantly higher than those in the low fitness group (d = 0.32, 15), while at high-intensity level, there was a reverse trend between the high fitness group (d = 0.25, 18) and the low fitness group (d = 0.39, 23). CONCLUSIONS: moderate-intensity AE can cause significant changes of RSFC in the motor cortex of college students with high fitness, while high fitness has a moderating effect on the relationship between exercise intensity and RSFC. RSFC of people with high fitness is more likely to be affected by AE and show a wider range of changes.

Cathelicidin LL-37 promotes wound healing in diabetic mice by regulating TFEB-dependent autophagy.

Diabetic patients often experience impaired wound healing. Human cathelicidin LL-37 possesses various biological functions, such as anti-microbial, anti-inflammatory, and pro-wound healing activities. Autophagy has important effects on skin wound healing. However, little is known about whether LL-37 accelerates diabetic wound healing by regulating autophagy. In the study, we aimed to investigate the role of autophagy in LL-37-induced wound healing and uncover the underlying mechanisms involved. A full-thickness wound closure model was established in diabetic mice to evaluate the effects of LL-37 and an autophagy inhibitor (3-MA) on wound healing. The roles of LL-37 and 3-MA in regulating keratinocyte migration were assessed using transwell migration and wound healing assays. The activation of transcription factor EB (TFEB) was measured using western blotting and immunofluorescence (IF) assays of its nuclear translocation. The results showed that LL-37 treatment improved wound healing in diabetic mice, whereas these effects were reversed by 3-MA. In vitro, 3-MA decreased the effects of LL-37 on promoting HaCat keratinocyte migration in the presence of high glucose (HG). Mechanistically, LL-37 promoted TFEB activation and resulted in subsequent activation of autophagy, as evidenced by increased nuclear translocation of TFEB and increased expression of ATG5, ATG7, and beclin 1 (BECN1), whereas these changes were blocked by TFEB knockdown. As expected, TFEB knockdown damaged the effects of LL-37 on promoting keratinocyte migration. Collectively, these results suggest that LL-37 accelerates wound healing in diabetic mice by activating TFEB-dependent autophagy, providing new insights into the mechanism by which LL-37 promotes diabetic wound healing.

Clinical and neuroimaging association between neuropsychiatric symptoms and nutritional status across the Alzheimer's disease continuum: a longitudinal cohort study.

OBJECTIVES: To investigate the association between neuropsychiatric symptoms (NPS) and nutritional status, and explore their shared regulatory brain regions on the Alzheimer's disease (AD) continuum. DESIGN: A longitudinal, observational cohort study. SETTING: Data were collected from the Chinese Imaging, Biomarkers, and Lifestyle study between June 1, 2021 and December 31, 2022. PARTICIPANTS: Overall, 432 patients on the AD continuum, including amnestic mild cognitive impairment and AD dementia, were assessed at baseline, and only 165 patients completed the (10.37 ± 6.08) months' follow-up. MEASUREMENTS: The Mini-Nutritional Assessment (MNA) and Neuropsychiatric Inventory (NPI) were used to evaluate nutritional status and NPS, respectively. The corrected cerebral blood flow (cCBF) measured by pseudo-continuous arterial spin labeling of the dietary nutrition-related brain regions was analyzed. The association between the NPS at baseline and subsequent change in nutritional status and the association between the changes in the severity of NPS and nutritional status were examined using generalized linear mixed models. RESULTS: Increased cCBF in the left putamen was associated with malnutrition, general NPS, affective symptoms, and hyperactivity (P < 0.05). The presence of general NPS (ß = -1.317, P = 0.003), affective symptoms (ß = -1.887, P < 0.001), and appetite/eating disorders (ß = -1.714, P < 0.001) at baseline were associated with a decline in the MNA scores during follow-up. The higher scores of general NPI (ß = -0.048), affective symptoms (ß = -0.181), and appetite/eating disorders (ß = -0.416; all P < 0.001) were longitudinally associated with lower MNA scores after adjusting for confounding factors. CONCLUSIONS: We found that baseline NPS were predictors of a decline in nutritional status on the AD continuum. The worse the severity of affective symptoms and appetite/eating disorders, the poorer the nutritional status. Furthermore, abnormal perfusion of the putamen may regulate the association between malnutrition and NPS, which suggests their potentially common neural regulatory basis.

Mediation of Regional Cerebral Blood Flow in the Relationship between Specific Gut Microbiota and Cognition in Vascular Cognitive Impairment.

BACKGROUND: Gut microbiota could affect the onset and development of vascular cognitive impairment (VCI) through modulating metabolic and immune pathways. However, the vascular mechanisms involved remain unclear. OBJECTIVE: To investigate the gut microbiota associated with VCI and examine the mediating effects of regional cerebral blood flow (CBF) to explore potential therapeutic targets for VCI. METHODS: This prospective study enrolled patients with VCI (n = 16) and healthy controls (n = 18) from the Chinese Imaging, Biomarkers, and Lifestyle study between January 1 and June 30, 2022. The gut microbiota composition and diversity were determined by 16 S ribosomal RNA gene sequencing. The association between gut microbiota and Montreal Cognitive Assessment (MoCA) scores was determined using Spearman's correlation analysis. Regional CBF was calculated using pseudo-continuous arterial spin labeling. The mediating effects of regional CBF on the relationship between specific gut microbiota and cognition in VCI were investigated using mediation analysis. RESULTS: Compared to healthy controls, patients with VCI had significantly greater abundance of Bifidobacterium, Veillonella, R uminococcus gnavus , Fusobacterium, and Erysipelatoclostridium and smaller abundance of Collinsella. The abundance of Ruminococcus gnavus was negatively associated with MoCA scores in patients with VCI, with the CBF in the left hypothalamus, right hypothalamus, and left amygdala accounting for 63.96%, 48.22%, and 36.51%, respectively, of this association after adjusting for confounders. CONCLUSIONS: Ruminococcus gnavus is associated with cognition in VCI, which is strongly mediated by CBF in the bilateral hypothalamus and left amygdala. These findings highlight the potential regulatory roles of nutrition and metabolism-related areas of the brain in VCI.

Digital health interventions to promote healthy lifestyle in hemodialysis patients: an interventional pilot study.

Low physical activity has been associated with poor prognosis in hemodialysis (HD) patients. Interventions to maintain healthy lifestyle in this population are important to reduce mortality. This study aimed to evaluate the effectiveness of digital health interventions (DHIs) for improving the physical activity and health-related quality of life (HRQoL) in HD patients. The 24-week prospective study enrolled 31 clinically stable HD patients. All participants were assigned home exercises and provided with wearable devices. Dietary and exercise information was uploaded to a health management platform. Suggestions about diet and exercise were provided, and a social media group was created. Physical performance testing was performed at baseline and during weeks 4, 8, 12, 16 and 24. HRQoL and nutritional status were evaluated. A total of 25 participants completed the study. After the interventions, the daily step count increased 1658 steps. The 10-time-repeated sit-to-stand test reduced by 4.4 s, the sit-to-stand transfers in 60 s increased 12 repetitions, the distance of six-minute walk test (6MWT) increased by 55.4 m. The mental health components and burden of kidney disease of the Kidney Disease Quality of Life survey, and subjective global assessment (SGA) scores improved. By Spearman correlation, the monthly step count correlated positively with 6MWT and SGA. DHIs that combined wearable devices, a health management platform, and social media could strengthen physical activity and improve the HRQoL and nutrition of maintenance HD patients. The results outline a new model to promote healthy lifestyle behaviors in HD patients.

IV Flat Detector CT Angiography in Flat Detector CT Image-Guided Minimally Invasive Surgery for the Treatment of Intracerebral Hypertensive Hemorrhage.

BACKGROUND AND PURPOSE: Spontaneous intracerebral hemorrhage is a serious stroke subtype with high mortality and morbidity. Minimally invasive surgery plus thrombolysis is a promising treatment option, but it requires accurate catheter placement and real-time monitoring. The authors introduced IV flat detector CT angiography (ivFDCTA) into the minimally invasive surgery procedure for the first time, to provide vascular information and guidance for hematoma evacuation. MATERIALS AND METHODS: Thirty-six patients with hypertensive intracerebral hemorrhage were treated with minimally invasive surgery under the guidance of ivFDCTA and flat detector CT (FDCT) in the angiography suite. The needle path and puncture depth were planned and calculated using software on the DSA workstation. The hematoma volume reduction, operation time, complications, and clinical outcomes were recorded and evaluated. RESULTS: The mean preoperative hematoma volume of 36 patients was 35 (SD, 12) mL, the mean intraoperative volume reduction was 19 (SD, 11) mL, and the mean postoperative residual hematoma volume was 15 (SD, 8) mL. The average operation time was 59 (SD, 22) minutes. One patient had an intraoperative epidural hematoma, which improved after conservative treatment. The mean Glasgow Outcome Scale score at discharge was 4.3 (SD, 0.8), and the mean mRS score at 90 days was 2.4 (SD, 1.1). CONCLUSIONS: The use of ivFDCTA in the evacuation of an intracerebral hemorrhage hematoma could improve the safety and efficiency of minimally invasive surgery and has shown great potential in hemorrhagic stroke management in selected patients.

Regulatory T cells and IFN-γ-producing Th1 cells play a critical role in the pathogenesis of Sjögren's Syndrome.

Objectives: Sjögren's Disease (SjD) is an autoimmune disorder characterized by progressive dysfunction, inflammation and destruction of salivary and lacrimal glands, and by extraglandular manifestations. Its etiology and pathophysiology remain incompletely understood, though a role for autoreactive B cells has been considered key. Here, we investigated the role of effector and regulatory T cells in the pathogenesis of SjD. Methods: Histological analysis, RNA-sequencing and flow cytometry were conducted on glands, lungs, eyes and lymphoid tissues of mice with regulatory T cell-specific deletion of stromal interaction proteins (STIM) 1 and 2 ( Stim1/2 Foxp3 ), which play key roles in calcium signaling and T cell function. The pathogenicity of T cells from Stim1/2 Foxp3 mice was investigated through adoptively transfer into lymphopenic host mice. Additionally, single-cell transcriptomic analysis was performed on peripheral blood mononuclear cells (PBMCs) of patients with SjD and control subjects. Results: Stim1/2 Foxp3 mice develop a severe SjD-like disorder including salivary gland (SG) and lacrimal gland (LG) inflammation and dysfunction, autoantibodies and extraglandular symptoms. SG inflammation in Stim1/2 Foxp3 mice is characterized by T and B cell infiltration, and transcriptionally by a Th1 immune response that correlates strongly with the dysregulation observed in patients with SjD. Adoptive transfer of effector T cells from Stim1/2 Foxp3 mice demonstrates that the SjD-like disease is driven by interferon (IFN)-γ producing autoreactive CD4 + T cells independently of B cells and autoantiboodies. scRNA-seq analysis identifies increased Th1 responses and attenuated memory Treg function in PBMCs of patients with SjD. Conclusions: We report a more accurate mouse model of SjD while providing evidence for a critical role of Treg cells and IFN-γ producing Th1 cells in the pathogenesis of SjD, which may be effective targets for therapy.

Choroid plexus volume as a novel candidate neuroimaging marker of the Alzheimer's continuum.

BACKGROUND: Enlarged choroid plexus (ChP) volume has been reported in patients with Alzheimer's disease (AD) and inversely correlated with cognitive performance. However, its clinical diagnostic and predictive value, and mechanisms by which ChP impacts the AD continuum remain unclear. METHODS: This prospective cohort study enrolled 607 participants [healthy control (HC): 110, mild cognitive impairment (MCI): 269, AD dementia: 228] from the Chinese Imaging, Biomarkers, and Lifestyle study between January 1, 2021, and December 31, 2022. Of the 497 patients on the AD continuum, 138 underwent lumbar puncture for cerebrospinal fluid (CSF) hallmark testing. The relationships between ChP volume and CSF pathological hallmarks (Aß42, Aß40, Aß42/40, tTau, and pTau181), neuropsychological tests [Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Neuropsychiatric Inventory (NPI), and Activities of Daily Living (ADL) scores], and multimodal neuroimaging measures [gray matter volume, cortical thickness, and corrected cerebral blood flow (cCBF)] were analyzed using partial Spearman's correlation. The mediating effects of four neuroimaging measures [ChP volume, hippocampal volume, lateral ventricular volume (LVV), and entorhinal cortical thickness (ECT)] on the relationship between CSF hallmarks and neuropsychological tests were examined. The ability of the four neuroimaging measures to identify cerebral Aß42 changes or differentiate among patients with AD dementia, MCI and HCs was determined using receiver operating characteristic analysis, and their associations with neuropsychological test scores at baseline were evaluated by linear regression. Longitudinal associations between the rate of change in the four neuroimaging measures and neuropsychological tests scores were evaluated on the AD continuum using generalized linear mixed-effects models. RESULTS: The participants' mean age was 65.99 ± 8.79 years. Patients with AD dementia exhibited the largest baseline ChP volume than the other groups (P < 0.05). ChP volume enlargement correlated with decreased Aß42 and Aß40 levels; lower MMSE and MoCA and higher NPI and ADL scores; and lower volume, cortical thickness, and cCBF in other cognition-related regions (all P < 0.05). ChP volume mediated the association of Aß42 and Aß40 levels with MMSE scores (19.08% and 36.57%), and Aß42 levels mediated the association of ChP volume and MMSE or MoCA scores (39.49% and 34.36%). ChP volume alone better identified cerebral Aß42 changes than LVV alone (AUC = 0.81 vs. 0.67, P = 0.04) and EC thickness alone (AUC = 0.81 vs.0.63, P = 0.01) and better differentiated patients with MCI from HCs than hippocampal volume alone (AUC = 0.85 vs. 0.81, P = 0.01), and LVV alone (AUC = 0.85 vs.0.82, P = 0.03). Combined ChP and hippocampal volumes significantly increased the ability to differentiate cerebral Aß42 changes and patients among AD dementia, MCI, and HCs groups compared with hippocampal volume alone (all P < 0.05). After correcting for age, sex, years of education, APOE ε4 status, eTIV, and hippocampal volume, ChP volume was associated with MMSE, MoCA, NPI, and ADL score at baseline, and rapid ChP volume enlargement was associated with faster deterioration in NPI scores with an average follow-up of 10.03 ± 4.45 months (all P < 0.05). CONCLUSIONS: ChP volume may be a novel neuroimaging marker associated with neurodegenerative changes and clinical AD manifestations. It could better detect the early stages of the AD and predict prognosis, and significantly enhance the differential diagnostic ability of hippocampus on the AD continuum.

CBCT-based three-dimensional dual-phase vascular image fusion: a novel technique for interventional real-time TIPS guidance.

BACKGROUND: Due to the invisibility of the portal vein (PV), how to puncture the PV accurately and safely in transjugular intrahepatic portosystemic shunt (TIPS) creation remains a challenge of the procedure. OBJECTIVES: We aimed to provide the first evaluation of the safety, feasibility, and efficiency of cone beam computed tomography (CBCT)-based three-dimensional (3D) dual-phase vascular image fusion for interventional real-time guided PV puncture during TIPS procedures. MATERIALS AND METHODS: From January 2021 to May 2021, 13 patients undergoing TIPS were prospectively enrolled in this study. Images of the hepatic artery (HA) and PV in 3D were acquired and overlaid on interventional fluoroscopy images in a dual-phase display mode for real-time PV puncture guidance. The number of PV puncture attempts, puncture time, overlaid image accuracy, dose area product, fluoroscopy time, and interventional complications were recorded. RESULTS: Portal vein puncture guided by CBCT-based 3D dual-phase vascular image fusion was successfully performed on 92.3% (12/13) patients. The mean number of PV puncture attempts was 1.8 ± 0.7 (1-3). The mean puncture time and fluoroscopy time was 3.5 ± 1.2 (2-6) min and 25.1 ± 9.4 (15-45) min, respectively. The mean dose area product was 39.49 ± 7.88 (28.81-52.87) mGym2. The error between the reference position of the fusion image and the interventional PV angiography image was less than 0.5 cm. No interventional complication was observed. CONCLUSION: Our results show that 3D dual-phase vascular image fusion might be a safe and feasible technique for interventional real-time guided PV puncture during TIPS. This novel technique might help to reduce the number of PV puncture attempts and the puncture time as well as lower the risks of interventional complications.

Multiple cutaneous carcinoma arising from arsenic-containing traditional Chinese medicine in a patient with psoriasis: A case report.

Background: Arsenic exposure is closely related to keratosis and cutaneous carcinoma, but a few studies have focused on patients with psoriasis presenting carcinoma after long-term medication of arsenic-containing traditional Chinese medicine (TCM). Case description: We presented a psoriasis patient showing multiple cutaneous carcinoma arising from arsenic containing TCM. A 60-year-old gentleman with psoriasis for nearly 30 years presented to our department with severe keratosis in hands, trunk and feet. He received oral administration of realgar (with As4S4 as the major component) for at least 15 years. There were keratotic plaques, ulcer and exudate in the middle finger and forefinger of left hand, and middle finger, forefinger and ring finger of the right hand. Moreover, brown papule was seen in right sole, together with keratotic plaques and ulcer in the left heel. Pathological analysis revealed basal cell carcinoma (BCC) in the anterior chest, right hand and right foot, Bowen disease in left hand and right hand, as well as squamous cell carcinomas (SCC) in right hand. Conclusion: This is a rare arsenic-exposure psoriasis patient showed coexistence of Bowen disease in left hand and right hand, BCC in the thoracic site, right hand and right foot, as well as SCC in right hand.