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PurposeTo evaluate the efficacy of high b-value diffusion-weighted imaging (DWI) with a continuous-time random-walk (CTRW) diffusion model in determining the pathological grade and variant histology (VH) of bladder cancer (BCa).MethodsA total of 81 patients (median age, 70 years; range, 35-92 years; 18 females; 66 high grades; 30 with VH) with pathologically confirmed bladder urothelial carcinoma were retrospectively enrolled and underwent bladder MRI on a 3.0T MRI scanner. Multi-b-value DWI was performed using 11 b-values. Three CTRW model parameters were obtained: an anomalous diffusion coefficient (D) and two parameters reflecting temporal (α) and spatial (β) diffusion heterogeneity. The apparent diffusion coefficient (ADC) was calculated using b0 and b800. D, α, β, and ADC were statistically compared between high- and low-grade BCa, and between pure urothelial cancer (pUC) and VH. Comparisons were made using the Mann–Whitney U test between different pathological states. Receiver operating characteristic curve analysis was used to assess performance in differentiating the pathological states of BCa.ResultsADC, D, and α were significantly lower in high-grade BCa compared to low-grade, and in VH compared to pUC (p < 0.001), while β showed no significant differences (p > 0.05). The combination of D and α yielded the best performance for determining BCa grade and VH (area under the curves = 0.913, 0.811), significantly outperforming ADC (area under the curves = 0.823, 0.761).ConclusionThe CTRW model effectively discriminated pathological grades and variants in BCa, highlighting its potential as a noninvasive diagnostic tool.

Parkinson's disease can affect not only motor functions but also cognitive abilities, leading to cognitive impairment. One common issue in Parkinson's disease with cognitive dysfunction is the difficulty in executive functioning. Executive functions help us plan, organize, and control our actions based on our goals. The brain area responsible for executive functions is called the prefrontal cortex. It acts as the command center for the brain, especially when it comes to regulating executive functions. The role of the prefrontal cortex in cognitive processes is influenced by a chemical messenger called dopamine. However, little is known about how dopamine affects the cognitive functions of patients with Parkinson's disease. In this article, the authors review the latest research on this topic. They start by looking at how the dopaminergic system, is altered in Parkinson's disease with executive dysfunction. Then, they explore how these changes in dopamine impact the synaptic structure, electrical activity, and connection components of the prefrontal cortex. The authors also summarize the relationship between Parkinson's disease and dopamine-related cognitive issues. This information may offer valuable insights and directions for further research and improvement in the clinical treatment of cognitive impairment in Parkinson's disease.

BackgroundSLE is a complex autoimmune disease with deleterious effects on various organs. Accumulating evidence has shown abnormal vitamin B12 and one-carbon flux contribute to immune dysfunction. Transcobalamin II (TCN2) belongs to the vitamin B12-binding protein family responsible for the cellular uptake of vitamin B12. The role of TCN2 in SLE is still unclear.MethodsWe collected clinical information and blood from 51 patients with SLE and 28 healthy controls. RNA sequencing analysis, qPCR, and western blot confirmed the alteration of TCN2 in disease monocytes. The correlation between TCN2 expression and clinical features and serological abnormalities was analyzed. TCN2 heterozygous knockout THP1 cells were used to explore the effects of TCN2 dysfunction on monocytes. CCK-8 assay and EdU staining were used to detect cell proliferation. ELISA was conducted to assess vitamin B12, glutathione, and cytokines changes. UHPLC-MRM-MS/MS was used to detect changes in the intermediates of the one-carbon cycle. Flow cytometry is used to detect cell cycle, ROS, mitoROS, and CD14 changes.ResultsElevated TCN2 in monocytes was correlated positively with disease progression and specific tissue injuries. Using CD14+ monocytes and TCN2 genetically modified THP1 cell lines, we found that the TCN2 was induced by LPS in serum from SLE patients. TCN2 heterozygous knockout inhibited cellular vitamin B12 uptake and one-carbon metabolism, leading to cell proliferation arrest and decreased Toll-like receptor 4 (TLR4)-mediated CCL2 release. Methionine cycle metabolites, s-adenosylmethionine and homocysteine, rescued these effects, whereas folate treatment proved to be ineffective. Folate deficiency also failed to replicate the impact of TCN2 downregulation on THP1 inflammatory response.ConclusionOur study elucidated the unique involvement of TCN2-driven one-carbon flux on SLE-associated monocyte behavior. Increased TCN2 may promote disease progression and tissue damage by enhancing one-carbon flux, fostering monocyte proliferation, and exacerbating TLR4 mediated inflammatory responses. The inhibition of TCN2 may be a promising therapeutic approach to ameliorate SLE.

BackgroundDistinguishing between prostatic cancer (PCa) and chronic prostatitis (CP) is sometimes challenging, and Gleason grading is strongly associated with prognosis in PCa. The continuous-time random-walk diffusion (CTRW) model has shown potential in distinguishing between PCa and CP as well as predicting Gleason grading.PurposeThis study aimed to quantify the CTRW parameters (α, β & Dm) and apparent diffusion coefficient (ADC) of PCa and CP tissues; and then assess the diagnostic value of CTRW and ADC parameters in differentiating CP from PCa and low-grade PCa from high-grade PCa lesions.Study typeRetrospective (retrospective analysis using prospective designed data).PopulationThirty-one PCa patients undergoing prostatectomy (mean age 74 years, range 64–91 years), and thirty CP patients undergoing prostate needle biopsies (mean age 68 years, range 46–79 years).Field strength/SequenceMRI scans on a 3.0T scanner (uMR790, United Imaging Healthcare, Shanghai, China). DWI were acquired with 12 b-values (0, 50, 100, 150, 200, 500, 800, 1200, 1500, 2000, 2500, 3000 s/mm2).AssessmentCTRW parameters and ADC were quantified in PCa and CP lesions.Statistical testsThe Mann-Whitney U test was used to evaluate the differences in CTRW parameters and ADC between PCa and CP, high-grade PCa, and low-grade PCa. Spearman’s correlation of the pathologic grading group (GG) with CTRW parameters and ADC was evaluated. The usefulness of CTRW parameters, ADC, and their combinations (Dm, α and β; Dm, α, β, and ADC) to differentiate PCa from CP and high-grade PCa from low-grade PCa was determined by logistic regression and receiver operating characteristic curve (ROC) analysis. Delong test was used to compare the differences among AUCs.ResultsSignificant differences were found for the CTRW parameters (α, Dm) between CP and PCa (all P

Abstract Neutrophils have a pathogenic function in inflammation via releasing pro-inflammatory mediators or neutrophil extracellular traps (NETs). However, their heterogeneity and pro-inflammatory mechanisms remain unclear. Here, we demonstrate that CXCR4hi neutrophils accumulate in the blood and inflamed skin in human psoriasis, and correlate with disease severity. Compared to CXCR4lo neutrophils, CXCR4hi neutrophils have enhanced NETs formation, phagocytic function, neutrophil degranulation, and overexpression of pro-inflammatory cytokines and chemokines in vitro. This is accompanied by a metabolic shift in CXCR4hi neutrophils toward glycolysis and lactate release, thereby promoting vascular permeability and remodeling. CXCR4 expression in neutrophils is dependent on CREB1, a transcription factor activated by TNF and CXCL12, and regulated by de novo synthesis. In vivo, CXCR4hi neutrophil infiltration amplifies skin inflammation, whereas blockade of CXCR4hi neutrophils through CXCR4 or CXCL12 inhibition leads to suppression of immune responses. In this work, our study identifies CREB1 as a critical regulator of CXCR4hi neutrophil development and characterizes the contribution of CXCR4hi neutrophils to vascular remodeling and inflammatory responses in skin.

Introduction: Meteorin-like hormone (Metrnl) is ubiquitously expressed in skeletal muscle, heart, and adipose with beneficial roles in obesity, insulin resistance, and inflammation. Metrnl is found to protect against cardiac hypertrophy and doxorubicin-induced cardiotoxicity. However, its role in diabetic cardiomyopathy (DCM) is undefined. Objectives: We aimed to elucidate the potential roles of Metrnl in DCM. Methods: Gain- and loss-of-function experiments were utilized to determine the roles of Metrnl in the pathological processes of DCM. Results: We found that plasma Metrnl levels, myocardial Metrnl protein and mRNA expressions were significantly downregulated in both streptozotocin (STZ)-induced (T1D) mice and leptin receptor deficiency (db/db) (T2D) mice. Cardiac-specific overexpression (OE) of Metrnl markedly ameliorated cardiac injury and dysfunction in both T1D and T2D mice. In sharp contrast, specific deletion of Metrnl in the heart had the opposite phenotypes. In parallel, Metrnl OE ameliorated, whereas Metrnl downregulation exacerbated high glucose (HG)-elicited hypertrophy, apoptosis and oxidative damage in primary neonatal rat cardiomyocytes. Antibody-induced blockade of Metrnl eliminated the effects of benefits of Metrnl in vitro and in vivo. Mechanistically, Metrnl activated the autophagy pathway and inhibited the cGAS/STING signaling in a LKB1/AMPK/ULK1-dependent mechanism in cardiomyocytes. Besides, Metrnl-induced ULK1 phosphorylation facilitated the dephosphorylation and mitochondrial translocation of STING where it interacted with tumor necrosis factor receptor-associated factor 2 (TRAF2), a scaffold protein and E3 ubiquitin ligase that was responsible for ubiquitination and degradation of STING, rendering cardiomyocytes sensitive to autophagy activation. Conclusion: Thus, Metrnl may be an attractive therapeutic target or regimen for treating DCM.

The Taiji program is dedicated to the detection of middle and low-frequency gravitational waves, targeting the 0.1 mHz to 1 Hz frequency band. The project requires an acceleration residual sensitivity of 3 × 10−15 ms−2/Hz1/2, which necessitates a capacitance sensing resolution of 1 aF/Hz1/2 for the capacitive sensing system within the specified frequency range. The noise level of the resonant bridge significantly influences the resolution. Addressing the challenges in enhancing transformer performance parameters in existing resonant capacitance bridges and the constraints on improving the characteristics of resonant capacitance bridges, this study introduces a novel approach to reduce bridge thermal noise without optimizing existing parameters. The simulation results demonstrate that this scheme can reduce the noise to 0.7 times the original level and further reduce bridge thermal noise when other parameters affecting noise are optimized. This not only mitigates the demands for other performance parameters but also increases the range of maximum acceptable resonant frequency deviations and reduces its sensitivity to such variations. Experimental validation confirms that the proposed scheme effectively reduces noise by 0.7 times and improves the resolution of capacitance sensing to 0.6 aF/Hz1/2, thereby advancing the Taiji program gravitational wave detection capabilities.

The high sensitivity to color browning during room-temperature storage was a significant factor in limiting the development of fresh spinach noodles (FSN). The practice of humidity-controlled heat treatment (HCHT) at varying temperatures, relative humidity, and time was carried out to limit enzyme activity and improve the quality of FSN. Results showed that HCHT could maximize the color preservation of fresh spinach noodle quality while effectively inactivating polyphenol oxidase and the yeasts, and mold count in FSN during storage was almost undetectable after mild conditions (80 °C). The hardness and chewiness of HCHT noodles were significantly increased, but the free sulfhydryl content was reduced. At 80 °C, 90 %, 5 min, protein structural aggregation was found in the microstructure of HCHT fresh spinach noodles. HCHT also caused partial gelatinization, as evidenced by the decrease in starch gelatinization enthalpy from 5.49 to 4.77 J/g, although the gelatinization degree of FSN was comparatively low.