PDIA3 orchestrates effector T cell program by serving as a chaperone to facilitate the non-canonical nuclear import of STAT1 and PKM2.

Dysregulated T cell activation underpins the immunopathology of rheumatoid arthritis (RA), yet the machineries that orchestrate T cell effector program remain incompletely understood. Herein, we leveraged bulk and single-cell RNA sequencing data from RA patients and validated protein disulfide isomerase family A member 3 (PDIA3) as a potential therapeutic target. PDIA3 is remarkably upregulated in pathogenic CD4 T cells derived from RA patients and positively correlates with C-reactive protein level and disease activity score 28. Pharmacological inhibition or genetic ablation of PDIA3 alleviates RA-associated articular pathology and autoimmune responses. Mechanistically, T cell receptor signaling triggers intracellular calcium flux to activate NFAT1, a process that is further potentiated by Wnt5a under RA settings. Activated NFAT1 then directly binds to the Pdia3 promoter to enhance the expression of PDIA3, which complexes with STAT1 or PKM2 to facilitate their nuclear import for transcribing T helper 1 (Th1) and Th17 lineage-related genes, respectively. This non-canonical regulatory mechanism likely occurs under pathological conditions, as PDIA3 could only be highly induced following aberrant external stimuli. Together, our data support that targeting PDIA3 is a vital strategy to mitigate autoimmune diseases, such as RA, in clinical settings.

Genomic insights into the seawater adaptation in Cyprinidae.

BACKGROUND: Cyprinidae, the largest fish family, encompasses approximately 367 genera and 3006 species. While they exhibit remarkable adaptability to diverse aquatic environments, it is exceptionally rare to find them in seawater, with the Far Eastern daces being of few exceptions. Therefore, the Far Eastern daces serve as a valuable model for studying the genetic mechanisms underlying seawater adaptation in Cyprinidae. RESULTS: Here, we sequenced the chromosome-level genomes of two Far Eastern daces (Pseudaspius brandtii and P. hakonensis), the two known cyprinid fishes found in seawater, and performed comparative genomic analyses to investigate their genetic mechanism of seawater adaptation. Demographic history reconstruction of the two species reveals that their population dynamics are correlated with the glacial-interglacial cycles and sea level changes. Genomic analyses identified Pseudaspius-specific genetic innovations related to seawater adaptation, including positively selected genes, rapidly evolving genes, and conserved non-coding elements (CNEs). Functional assays of Pseudaspius-specific variants of the prolactin (prl) gene showed enhanced cell adaptation to greater osmolarity. Functional assays of Pseudaspius specific CNEs near atg7 and usp45 genes suggest that they exhibit higher promoter activity and significantly induced at high osmolarity. CONCLUSIONS: Our results reveal the genome-wide evidence for the evolutionary adaptation of cyprinid fishes to seawater, offering valuable insights into the molecular mechanisms supporting the survival of migratory fish in marine environments. These findings are significant as they contribute to our understanding of how cyprinid fishes navigate and thrive in diverse aquatic habitats, providing useful implications for the conservation and management of marine ecosystems.

Landscape of the gut mycobiome dynamics during pregnancy and its relationship with host metabolism and pregnancy health.

OBJECTIVE: The remodelling of gut mycobiome (ie, fungi) during pregnancy and its potential influence on host metabolism and pregnancy health remains largely unexplored. Here, we aim to examine the characteristics of gut fungi in pregnant women, and reveal the associations between gut mycobiome, host metabolome and pregnancy health. DESIGN: Based on a prospective birth cohort in central China (2017 to 2020): Tongji-Huaxi-Shuangliu Birth Cohort, we included 4800 participants who had available ITS2 sequencing data, dietary information and clinical records during their pregnancy. Additionally, we established a subcohort of 1059 participants, which included 514 women who gave birth to preterm, low birthweight or macrosomia infants, as well as 545 randomly selected controls. In this subcohort, a total of 750, 748 and 709 participants had ITS2 sequencing data, 16S sequencing data and serum metabolome data available, respectively, across all trimesters. RESULTS: The composition of gut fungi changes dramatically from early to late pregnancy, exhibiting a greater degree of variability and individuality compared with changes observed in gut bacteria. The multiomics data provide a landscape of the networks among gut mycobiome, biological functionality, serum metabolites and pregnancy health, pinpointing the link between Mucor and adverse pregnancy outcomes. The prepregnancy overweight status is a key factor influencing both gut mycobiome compositional alteration and the pattern of metabolic remodelling during pregnancy. CONCLUSION: This study provides a landscape of gut mycobiome dynamics during pregnancy and its relationship with host metabolism and pregnancy health, which lays the foundation of the future gut mycobiome investigation for healthy pregnancy.

Fluvoxamine inhibits Th1 and Th17 polarization and function by repressing glycolysis to attenuate autoimmune progression in type 1 diabetes.

BACKGROUND: Fluvoxamine is one of the selective serotonin reuptake inhibitors (SSRIs) that are regarded as the first-line drugs to manage mental disorders. It has been also recognized with the potential to treat inflammatory diseases and viral infection. However, the effect of fluvoxamine on autoimmune diseases, particularly type 1 diabetes (T1D) and the related cellular and molecular mechanisms, are yet to be addressed. METHOD: Herein in this report, we treated NOD mice with fluvoxamine for 2 weeks starting from 10-week of age to dissect the impact of fluvoxamine on the prevention of type 1 diabetes. We compared the differences of immune cells between 12-week-old control and fluvoxamine-treated mice by flow cytometry analysis. To study the mechanism involved, we extensively examined the characteristics of CD4+ T cells with fluvoxamine stimulation using RNA-seq analysis, real-time PCR, Western blot, and seahorse assay. Furthermore, we investigated the relevance of our data to human autoimmune diabetes. RESULT: Fluvoxamine not only delayed T1D onset, but also decreased T1D incidence. Moreover, fluvoxamine-treated NOD mice showed significantly attenuated insulitis coupled with well-preserved ß cell function, and decreased Th1 and Th17 cells in the peripheral blood, pancreatic lymph nodes (PLNs), and spleen. Mechanistic studies revealed that fluvoxamine downregulated glycolytic process by inhibiting phosphatidylinositol 3-kinase (PI3K)-AKT signaling, by which it restrained effector T (Teff) cell differentiation and production of proinflammatory cytokines. CONCLUSION: Collectively, our study supports that fluvoxamine could be a viable therapeutic drug against autoimmunity in T1D setting.

Carbon Corrosion Induced by Surface Defects Accelerates Degradation of Platinum/Graphene Catalysts in Oxygen Reduction Reaction.

Graphene supported electrocatalysts have demonstrated remarkable catalytic performance for oxygen reduction reaction (ORR). However, their durability and cycling performance are greatly limited by Oswald ripening of platinum (Pt) and graphene support corrosion. Moreover, comprehensive studies on the mechanisms of catalysts degradation under 0.6-1.6 V versus RHE (Reversible Hydrogen Electrode) is still lacking. Herein, degradation mechanisms triggered by different defects on graphene supports are investigated by two cycling protocols. In the start-up/shutdown cycling (1.0-1.6 V vs. RHE), carbon oxidation reaction (COR) leads to shedding or swarm-like aggregation of Pt nanoparticles (NPs). Theoretical simulation results show that the expansion of vacancy defects promotes reaction kinetics of the decisive step in COR, reducing its reaction overpotential. While under the load cycling (0.6-1.0 V vs. RHE), oxygen containing defects lead to an elevated content of Pt in its oxidation state which intensifies Oswald ripening of Pt. The presence of vacancy defects can enhance the transfer of electrons from graphene to the Pt surface, reducing the d-band center of Pt and making it more difficult for the oxidation state of platinum to form in the cycling. This work will provide comprehensive understanding on Pt/Graphene catalysts degradation mechanisms.

Cancer drugs and acute kidney injury: new therapies and new challenges.

PURPOSE OF REVIEW: Cancer therapies continue to evolve at a rapid pace and although novel treatments, including immunotherapies and targeted therapies have allowed for substantial improvements in cancer survival, they carry associated risks of acute kidney injury (AKI). We aim to summarize the existing literature on AKI associated with the spectrum of systemic cancer treatments, including conventional chemotherapies, newer immunotherapies, and the growing number of targeted cancer therapies, which may be associated with both AKI and 'pseudo-AKI'. RECENT FINDINGS: Conventional cytotoxic chemotherapies (e.g. cisplatin and other platinum-based agents, methotrexate, pemetrexed, ifosfamide, etc.) with well recognized nephrotoxicities (predominantly tubulointerstitial injury) remain in widespread use. Immunotherapies (e.g., immune checkpoint inhibitors and CAR-T therapies) may be associated with kidney immune-related adverse events, most often acute interstitial nephritis, and rarely, glomerular disease. Recently, multiple targeted cancer therapies have been associated with reduced renal tubular secretion of creatinine, causing elevations in serum creatinine and apparent 'pseudo-AKI'. To complicate matters further, these agents have had biopsy-proven, 'true' kidney injury attributed to them in numerous case reports. SUMMARY: Clinicians in nephrology and oncology must be aware of the various potential kidney risks with these agents and recognize those with clinically meaningful impact on both cancer and kidney outcomes.

Maternal overweight and obesity modify the association of serum fibroblast growth factor 21 levels with gestational diabetes mellitus: A nested case-control study.

AIMS: To examine the prospective association between fibroblast growth factor 21 (FGF21) and risk of gestational diabetes mellitus (GDM) and the modifying effect of overweight/obesity for this association. METHODS: Serum FGF21 levels were measured at 6-15 weeks of gestation among 332 GDM cases and 664 matched controls. Conditional logistic regression was used to evaluate its association with GDM risk. Interaction analyses on multiplicative and additive scales were conducted to investigate the modifying effect of overweight/obesity. RESULTS: Elevated FGF21 levels were associated with a higher risk of GDM in multivariable models, but the positive association was attenuated after further adjustment for pre-pregnancy body mass index (BMI). A significant multiplicative interaction was noted between FGF21 (both continuous and dichotomous) and pre-pregnancy BMI (p for interaction = 0.049 and 0.03), and the association was only significant in participants with pre-pregnancy BMI ≥24 kg/m2 . When participants were grouped based on pre-pregnancy BMI (≥24 and <24 kg/m2 ) and FGF21 levels (≥median and

Adhesion molecule-targeted magnetic particle imaging nanoprobe for visualization of inflammation in acute lung injury.

PURPOSE: Uncontrolled intra-alveolar inflammation is a central pathogenic feature, and its severity translates into a valid prognostic indicator of acute lung injury (ALI). Unfortunately, current clinical imaging approaches are unsuitable for visualizing and quantifying intra-alveolar inflammation. This study aimed to construct a small-sized vascular cell adhesion molecule-1 (VCAM-1)-targeted magnetic particle imaging (MPI) nanoprobe (ESPVPN) to visualize and accurately quantify intra-alveolar inflammation at the molecular level. METHODS: ESPVPN was engineered by conjugating a peptide (VHPKQHRGGSK(Cy7)GC) onto a polydopamine-functionalized superparamagnetic iron oxide core. The MPI performance, targeting, and biosafety of the ESPVPN were characterized. VCAM-1 expression in HUVECs and mouse models was evaluated by western blot. The degree of inflammation and distribution of VCAM-1 in the lungs were assessed using histopathology. The expression of pro-inflammatory markers and VCAM-1 in lung tissue lysates was measured using ELISA. After intravenous administration of ESPVPN, MPI and CT imaging were used to analyze the distribution of ESPVPN in the lungs of the LPS-induced ALI models. RESULTS: The small-sized (~10 nm) ESPVPN exhibited superior MPI performance compared to commercial MagImaging® and Vivotrax, and ESPVPN had effective targeting and biosafety. VCAM-1 was highly expressed in LPS-induced ALI mice. VCAM-1 expression was positively correlated with the LPS-induced dose (R = 0.9381). The in vivo MPI signal showed positive correlations with both VCAM-1 expression (R = 0.9186) and representative pro-inflammatory markers (MPO, TNF-α, IL-6, IL-8, and IL-1ß, R > 0.7). CONCLUSION: ESPVPN effectively targeted inflammatory lungs and combined the advantages of MPI quantitative imaging to visualize and evaluate the degree of ALI inflammation.

Association between Biomarkers of Phthalate Exposure and Serum Folate Concentrations in Children: A Population-Based Cross-Sectional Study of the NHANES from 2011 to 2016.

BACKGROUND: Although adverse health effects of phthalates have been reported, very few studies have assessed the associations between biomarkers of phthalate exposure and serum folate concentrations in children. OBJECTIVES: We aimed to examine the association between urinary phthalate metabolites, as biomarkers of exposure to phthalates, and total serum folate concentrations in children using national data from the United States. METHODS: We conducted cross-sectional analyses of 2100 individuals aged 6-18 y enrolled in the National Health and Nutrition Examination Survey, 2011-2016. Multivariable linear regression was applied to examine the relationship between natural logarithm (ln)-transformed urinary phthalate metabolites and serum folate concentrations. The quantile-based g-computation was used to assess the association of urinary phthalate metabolite mixture with serum folate levels. Subgroup analyses were conducted by sex, age, and race/ethnicity, and the interactions were assessed by adding interaction terms of these stratifying variables and phthalates and modeling through the Wald test. RESULTS: In multiple linear regression models, for participants in the highest tertile of MEHHP, MEOHP, DEHP, MCPP, and MCOP, total serum folate concentrations were 1.566 [ß: -1.566; 95% confidence interval: -2.935, -0.196], 1.423 (-1.423; -2.689, -0.157), 1.309 (-1.309; -2.573, -0.044), 1.530 (-1.530; -2.918, -0.142), and 1.381 (-1.381; -2.641, -0.122) ng/mL lower than those in the lowest tertile. The inverse associations were consistent in different subgroups by sex, age, and race/ethnicity (P for interaction ≥0.083 for all). In addition, the phthalate mixture showed a strong inverse correlation with serum folate; a quartile increase in the phthalate mixture on the ln scale was associated with 0.888 (-0.888; -1.677, -0.099) ng/mL decrease in the serum folate. CONCLUSIONS: Higher concentrations of urinary phthalate metabolites were associated with lower serum folate concentrations in children. Although our findings should be validated through additional population and mechanistic studies, they support a potential adverse effect of phthalate exposure on folate metabolism in children.

Attapulgite-Reinforced Cellulose Hydrogels with High Conductivity and Antifreezing Property for Flexible Sensors.

Ionic conductive cellulose hydrogels are some of the most promising candidates for flexible sensors. However, it is difficult to simultaneously prepare cellulose hydrogels with high mechanical strength, good ionic conductivity, and antifreeze performance. In this work, a natural clay (attapulgite)-reinforced cellulose hydrogel was fabricated. Through a one-pot method, cellulose and attapulgite were dispersed in a concentrated ZnCl2 solution. The obtained hydrogel exhibited a dual network of hydrogen bonds and Zn2+-induced ionic interactions. Attapulgite serves as an inorganic filler that can regulate the hydrogen-bonding density among cellulose molecules and provides abundant channels for fast ion transport. By optimizing the attapulgite loading, a mechanically strong (compressive strength up to 1.10 MPa), tough (fracture energy up to 0.36 MJ m-3), highly ionic conductive (4.15 S m-1), and freezing-tolerant hydrogel was prepared. These hydrogels can be used for sensitive and stable human motion sensing, demonstrating their great potential for healthcare applications.

Self-Healing and Wide Temperature-Tolerant Cellulose-Based Eutectogels for Reversible Humidity Detection.

A kind of ionic conductive gel (also named eutectogel) is developed from an inorganic salt (ZnCl2)-based deep eutectic solvent (DES). The ternary DES consists of ZnCl2, acrylic acid, and water, and cotton linter cellulose is introduced into the DES system to tailor its mechanical and conductive properties. Enabled by the extensive hydrogen bonds and ion-dipole interactions, the obtained eutectogel displays superior ionic conductivity (0.33 S/m), high stretchability (up to 2050%), large tensile strength (1.82 MPa), and wide temperature tolerance (-40 to 60 °C). In particular, the water-induced coordination interactions can tune the strength of hydrogen/ionic bonds in the eutectogels, imparting them with appealing humidity sensing ability in complex and extreme conditions.

Far-infrared radiation and its therapeutic parameters: A superior alternative for future regenerative medicine?

In future regenerative medicine, far-infrared radiation (FIR) may be an essential component of optical therapy. Many studies have confirmed or validated the efficacy and safety of FIR in various diseases, benefiting from new insights into FIR mechanisms and the excellent performance of many applications. However, the lack of consensus on the biological effects and therapeutic parameters of FIR limits its practical applications in the clinic. In this review, the definition, characteristics, and underlying principles of the FIR are systematically illustrated. We outline the therapeutic parameters of FIR, including the wavelength range, power density, irradiation time, and distance. In addition, the biological effects, potential molecular mechanisms, and preclinical and clinical applications of FIR are discussed. Furthermore, the future development and applications of FIR are described in this review. By applying optimal therapeutic parameters, FIR can influence various cells, animal models, and patients, eliciting diverse underlying mechanisms and offering therapeutic potential for many diseases. FIR could represent a superior alternative with broad prospects for application in future regenerative medicine.

Highly accelerated free-breathing real-time 2D flow imaging using compressed sensing and shared velocity encoding.

OBJECTIVES: 2D real-time (RT) phase-contrast (PC) MRI is a promising alternative to conventional PC MRI, which overcomes problems due to irregular heartbeats or poor respiratory control. This study aims to evaluate a prototype compressed sensing (CS)-accelerated 2D RT-PC MRI technique with shared velocity encoding (SVE) for accurate beat-to-beat flow measurements. METHODS: The CS RT-PC technique was implemented using a single-shot fast RF-spoiled gradient echo with SVE by symmetric velocity encoding, and acquired with a temporal resolution of 51-56.5 ms in 1-5 heartbeats. Both aortic dissection phantom (n = 8) and volunteer (n = 7) studies were conducted using the prototype CS RT (CS, R = 8), the conventional (GRAPPA, R = 2), and the fully sampled PC sequences on a 3T clinical system. Flow parameters including peak velocity, peak flow rate, net flow rate, and maximum velocity were calculated to compare the performance between different methods using linear regression, intraclass correlation (ICC), and Bland-Altman analyses. RESULTS: Comparisons of the flow measurements at all locations in the phantoms demonstrated an excellent correlation (all R2 ≥ 0.93) and agreement (all ICC ≥ 0.97) with negligible means of differences. In healthy volunteers, a similarly good correlation (all R2 ≥ 0.80) and agreement (all ICC ≥ 0.90) were observed; however, CS RT slightly underestimated the maximum velocities and flow rates (~ 12%). CONCLUSION: The highly accelerated CS RT-PC technique is feasible for the evaluation of flow patterns without requiring breath-holding, and it allows for rapid flow assessment in patients with arrhythmia or poor breath-hold capacity. CLINICAL RELEVANCE STATEMENT: The free-breathing real-time flow MRI technique offers improved spatial and temporal resolutions, as well as the ability to image individual cardiac cycles, resulting in superior image quality compared to the conventional PC technique when imaging patients with arrhythmias, especially those with atrial fibrillation. KEY POINTS: • The highly accelerated prototype CS RT-PC MRI technique with improved temporal resolution by the concept of SVE is feasible for beat-to-beat flow evaluation without requiring breath-holding. • The results of the phantom and in vivo quantitative flow evaluation show the ability of the prototype CS RT-PC technique to obtain reliable flow measurements similarly to the conventional PC MRI. • With less than 12% underestimation, excellent agreements between the two techniques were shown for the measurements of peak velocities and flow rates.

Sex-specific associations between skeletal muscle mass and incident diabetes: A population-based cohort study.

AIMS: To investigate the sex-specific associations between predicted skeletal muscle mass index (pSMI) and incident type 2 diabetes in a retrospective longitudinal cohort of Chinese men and women. MATERIALS AND METHODS: We enrolled Chinese adults without diabetes at baseline from WATCH (West chinA adulT health CoHort), a large health check-up-based database. We calculated pSMI to estimate skeletal muscular mass, and measured blood glucose variables and assessed self-reported history to identify new-onset diabetes. The nonlinear association between pSMI and incident type 2 diabetes was modelled using the penalized spline method. The piecewise association was estimated using segmented linear splines in weighted Cox proportional hazards regression models. RESULTS: Of 47 885 adults (53.2% women) with a median age of 40 years, 1836 developed type 2 diabetes after a 5-year median follow-up. In women, higher pSMI was associated with a lower risk of incident type 2 diabetes (Pnonlinearity = 0.09, hazard ratio [HR] per standard deviation increment in pSMI: 0.79 [95% confidence interval {CI} 0.68, 0.91]). A nonlinear association of pSMI with incident type 2 diabetes was detected in men (Pnonlinearity < 0.001). In men with pSMI lower than 8.1, higher pSMI was associated with a lower risk of incident type 2 diabetes (HR 0.58 [95% CI 0.40, 0.84]), whereas pSMI was not significantly associated with incident diabetes in men with pSMI equal to or greater than 8.1 (HR 1.08 [95% CI 0.93, 1.25]). CONCLUSIONS: In females, a larger muscular mass is associated with a lower risk of type 2 diabetes. For males, this association is significant only among those with diminished muscle mass.

Synthesis of 1,1-Diarylvinylsulfides via Visible-Light-Promoted Cascade Reaction of Alkynoates with Phenyl Disulfides.

Without any additives and photocatalysts, the visible-light-promoted radical cascade reaction between alkynoates and phenyl disulfides has been developed at room temperature. Through S-S bond photolysis and homolytic cleavage, addition of a sulfur radical, aryl migration, decarboxylation, and H atom abstraction, the cascade reaction provides an efficient and practical route to trisubstituted 1,1-diarylvinylsulfides with a wide scope of substrates and good to excellent yields.

Electronic Structure Modulation Via Iron-Incorporated NiO to Boost Urea Oxidation/Oxygen Evolution Reaction.

The urea-assisted water splitting not only enables a reduction in energy consumption during hydrogen production but also addresses the issue of environmental pollution caused by urea. Doping heterogeneous atoms in Ni-based electrocatalysts is considered an efficient means for regulating the electronic structure of Ni sites in catalytic processes. However, the current methodologies for synthesizing heteroatom-doped Ni-based electrocatalysts exhibit certain limitations, including intricate experimental procedures, prolonged reaction durations, and low product yield. Herein, Fe-doped NiO electrocatalysts were successfully synthesized using a rapid and facile solution combustion method, enabling the synthesis of 1.1107 g within a mere 5 min. The incorporation of iron atoms facilitates the modulation of the electronic environment around Ni atoms, generating a substantial decrease in the Gibbs free energy of intermediate species for the Fe-NiO catalyst. This modification promotes efficient cleavage of C-N bonds and consequently enhances the catalytic performance of UOR. Benefiting from the tunability of the electronic environment around the active sites and its efficient electron transfer, Fe-NiO electrocatalysts only needs 1.334 V to achieve 50 mA cm-2 during UOR. Moreover, Fe-NiO catalysts were integrated into a dual electrode urea electrolytic system, requiring only 1.43 V of cell voltage at 10 mA cm-2.

Current development and structure-activity relationship study of berberine derivatives.

Berberine is a quaternary ammonium isoquinoline alkaloid derived from traditional Chinese medicines Coptis chinensis and Phellodendron chinense. It has many pharmacological activities such as hypoglycemic, hypolipidemic, anti-tumor, antimicrobial and anti-inflammatory. Through structural modifications at various sites of berberine, the introduction of different groups can change berberine's physical and chemical properties, thereby improving the biological activity and clinical efficacy, and expanding the scope of application. This paper reviews the research progress and structure-activity relationships of berberine in recent years, aiming to provide valuable insights for the exploration of novel berberine derivatives.

Development and validation of a prognostic model for 90-day survival in patients with alcohol-associated cirrhosis and acute decompensation.

BACKGROUND/PURPOSE: Patients with alcohol-associated cirrhosis and acute decompensation are considered critically ill and have a higher risk of short-term mortality. This study aimed to establish a nomogram to evaluate their 90-day survival and identify factors that affect disease progression. METHODS: We included patients from September 2008 to December 2016 (n = 387 in the derivation group) and from January 2017 to August 2020 (n = 157 in the validation group). LASSO regression and Cox multivariate risk regression were used to analyze the influencing factors of the 90-day mortality risk, and a nomogram was constructed. The performance of a model was analyzed based on the C-index, area under the receiver operating curve, calibration curve, and decision curve analysis. RESULTS: Total bilirubin >10 upper limit of normal, high-density lipoprotein cholesterol, lymphocyte and monocyte ratios ≤2.33, white blood cells, and hemoglobin were identified as independent risk factors affecting the 90-day mortality risk of patients and the nomogram was developed. A nomogram demonstrated excellent model predictive accuracy in both the derivation and validation cohorts (C-index: 0.976 and 0.945), which was better than other commonly used liver scoring models (p < 0.05). The nomogram also performed good calibration ability and more clinical net benefit. According to the nomogram score, patients were divided into high- and low-risk groups. Mortality was significantly higher in the high-risk group than in the low-risk group (p < 0.0001). CONCLUSION: The nomogram could accurately predict the 90-day mortality risk in patients with alcohol-associated cirrhosis and acute decompensation, helping to identify high-risk patients and personalize treatment at their first admission.

Progressive white matter degeneration in patients with spinocerebellar ataxia type 2.

PURPOSE: Spinocerebellar ataxia type 2 (SCA2) is a progressive neurodegenerative disorder characterized by cerebellar atrophy. However, studies to elucidate the longitudinal progression of the neuropathology are limited. We sought to identify brain macrostructural and microstructural alterations in patients with SCA2 using fixel-based analysis (FBA) to better understand its distribution patterns and progression. METHODS: We enrolled 9 patients with SCA2 and 16 age- and gender-matched controls. Longitudinal clinical and imaging data were collected at baseline, and 3.5 years later. Fiber density (FD), fiber-bundle cross-section (FC), and a combination of FD and FC (FDC) were calculated. The paired t-test was used to examine longitudinal differences. The associations between fixel-based metrics and clinical variables were explored in SCA2 patients. RESULTS: At baseline, patients with SCA2 displayed multiple white matter tracts with significantly decreased FD, FC, and FDC in the corticospinal tract, cerebellar peduncles, brainstem, corpus callosum, thalamus, striatum, and prefrontal cortex, compared to controls. Over time, many of these macrostructural and microstructural alterations progressed, manifesting lower FD, FC, and FDC in corticospinal tract, middle cerebellar peduncle, brainstem, striatum, fornix, and cingulum. No significant brain white matter alterations were found in the healthy controls over time. There was no association between the FBA-derived metrics and clinical variables in SCA2. CONCLUSION: This study provides evidence of brain macrostructural and microstructural alterations and of progression over time in SCA2. The FBA-derived metrics may serve as potential biomarkers of SCA2 progression.

Decreased DTI-ALPS index in delirium: a preliminary MRI study.

PURPOSE: Delirium is linked to brain abnormalities, yet the role of the glymphatic system is not well understood. This study aims to examine alterations in brain physiology in delirium by using diffusion-tensor imaging (DTI) to assess water diffusion along the perivascular space (ALPS) and to explore its correlation with clinical symptoms. METHODS: We examined 15 patients with delirium and 15 healthy controls, measuring water diffusion metrics along the x-, y-, and z-axes in both projection and association fibers to determine the DTI-ALPS index. We used a general linear model, adjusted for age and sex, to compare the DTI-ALPS index between groups. We also investigated the relationship between the DTI-ALPS index and clinical symptoms using partial correlations. RESULTS: Patients with delirium exhibited significantly lower DTI-ALPS indices compared to healthy controls (1.25 ± 0.15 vs. 1.38 ± 0.10, t = 2.903, p = 0.007; 1.27 ± 0.16 vs. 1.39 ± 0.08, 1.22 ± 0.16 vs. 1.37 ± 0.14, t = 2.617, p = 0.014; t = 2.719, p = 0.011; respectively). However, there was no significant correlation between the DTI-ALPS index and clinical symptoms. CONCLUSION: Our findings indicate a decreased DTI-ALPS index in patients with delirium, suggesting potential alterations in brain physiology that may contribute to the pathophysiology of delirium. This study provides new insights into the mechanisms underlying delirium.