Distinct virtual histology of grey matter atrophy in four neuroinflammatory diseases.

Gray matter (GM) atrophies were observed in multiple sclerosis, neuromyelitis optica spectrum disorders (both anti-aquaporin-4 antibody-positive [AQP4+], and -negative [AQP4-] subtypes NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Revealing the pathogenesis of brain atrophy in these disorders would help their differential diagnosis and guide therapeutic strategies. To determine the neurobiological underpinnings of GM atrophies in multiple sclerosis, AQP4+ NMOSD, AQP4- NMOSD, and MOGAD, we conducted a virtual histology analysis that links T1-weighted image derived GM atrophy and gene expression using a multicenter cohort of 324 patients with multiple sclerosis, 197 patients with AQP4+ NMOSD, 75 patients with AQP4- NMOSD, 47 patients with MOGAD, and 2,169 healthy controls (HCs). First, interregional GM atrophy profiles across the cortical and subcortical regions were determined by Cohen's d between patients with multiple sclerosis, AQP4+ NMOSD, AQP4- NMOSD, MOGAD and HCs. Then, the GM atrophy profiles were spatially correlated with the gene expressions extracted from the Allen Human Brain Atlas, respectively. Finally, we explored the virtual histology of clinical feature relevant GM atrophy by subgroup analysis that stratified by physical disability, disease duration, number of relapses, lesion burden, and cognitive function. Multiple sclerosis showed severe widespread GM atrophy pattern, mainly involving subcortical nuclei and brainstem. AQP4+ NMOSD showed obvious widespread GM atrophy pattern, predominately located in occipital cortex as well as cerebellum. AQP4- NMOSD showed mild widespread GM atrophy pattern, mainly located in frontal and parietal cortices. MOGAD showed GM atrophy mainly involving the frontal and temporal cortices. High expression of genes specific to microglia, astrocytes, oligodendrocytes, and endothelial cells in multiple sclerosis, S1 pyramidal cells in AQP4+ NMOSD, as well as S1 and CA1 pyramidal cells in MOGAD had spatial correlations with GM atrophy profiles were observed, while no atrophy profile related gene expression was found in AQP4- NMOSD. Virtual histology of clinical feature relevant GM atrophy mainly pointed to the shared neuronal and endothelial cells among the four neuroinflammatory diseases. The unique underlying virtual histology patterns were microglia, astrocytes, and oligodendrocytes for multiple sclerosis; astrocytes for AQP4+ NMOSD; and oligodendrocytes for MOGAD. Neuronal and endothelial cells were shared potential targets across these neuroinflammatory diseases. These findings might help their differential diagnosis and optimal therapeutic strategies.

Choosing the optimal target area for repeated transcranial magnetic stimulation in treating neuropathic pain in spinal cord injury patients: a comparative analysis.

Objective: The specific target area of repeated transcranial magnetic stimulation (rTMS) in treating neuropathic pain resulting from spinal cord injury (SCI-NP) remains uncertain. Methods: Thirty-four participants with SCI-NP were allocated into three groups, namely, the motor cortex (M1, A) group, the left dorsolateral prefrontal cortex (LDLPFC, B) group, and the control (sham stimulation, C) group. The intervention was administered totally 10 times. Outcome measures assessed pre-(T0) and post-(T1)intervention, including Numerical Rating scale (NRS), anxiety (SAS), depression (SDS), sleep quality (PSQI), brief pain inventory (BPI), and impression of change. Results: All outcomes in groups A and B significantly changed after intervention (p < 0.05), and the delta value (T1-T0) also significantly changed than group C (p < 0.05). The delta value of SDS in the group B was better than the group A, and the change of pain degree in the group B was moderately correlated with the change in PSQI (r = 0.575, p < 0.05). Both patients in the groups A and B showed significant impression of change about their received therapy (p < 0.05). Conclusion: Both targets are effective, but LDLPFC is more effective in reducing depression in SCI-NP. Healthcare providers might select the suitable area according to the specific attributes of their patients.

The role of payment sources in the continuation of rehabilitation therapy in tertiary hospitals for patients with traumatic spinal cord injury: a study in Southwest China.

Medical security support for rehabilitation therapy in China is different from that in other countries. We investigated whether the discharge plan to continue rehabilitation therapy in tertiary hospitals for patients after traumatic spinal cord injury (TSCI) was influenced by payment sources or other conditions. This was a cross-sectional, observational study. Information was collected on the general condition, caregiver, types of payment sources for continued rehabilitation, American Spinal Injury Association Impairment Scale (AIS) scores, and discharge plans. In total, 135 patients with TSCI (107 male, mean age 41.00 ± 13.73 years, mean spinal cord injury duration 238.43 ± 345.54 days) were enrolled. Medical insurance (43%) and out-of-pocket payments (27.4%) were the primary payment sources. Although most patients were beyond the acute phase, 40% continued rehabilitation therapy at other tertiary hospitals. The caregiver, payment sources, injury level, AIS level, and complete urinary tract infection (UTI) were different due to discharge plans (p > .05). Patients seemingly consider a higher AIS level and co-UTI as the requirement for tertiary hospital therapy. In non-medical insurance payment source patients, the discharge plan also differed due to the AIS level and co-UTI (p > .05). However, in medical insurance patients, the discharge plan differed only in terms of TSCI duration (p > .05). The restricted duration of medical coverage restricted the continuation of rehabilitation therapy and influenced the discharge plan of most patients with TSCI.

Spinal cord and brain atrophy patterns in neuromyelitis optica spectrum disorder and multiple sclerosis.

BACKGROUND: Spinal cord and brain atrophy are common in neuromyelitis optica spectrum disorder (NMOSD) and relapsing-remitting multiple sclerosis (RRMS) but harbor distinct patterns accounting for disability and cognitive impairment. METHODS: This study included 209 NMOSD and 304 RRMS patients and 436 healthy controls. Non-negative matrix factorization was used to parse differences in spinal cord and brain atrophy at subject level into distinct patterns based on structural MRI. The weights of patterns were obtained using a linear regression model and associated with Expanded Disability Status Scale (EDSS) and cognitive scores. Additionally, patients were divided into cognitive impairment (CI) and cognitive preservation (CP) groups. RESULTS: Three patterns were observed in NMOSD: (1) Spinal Cord-Deep Grey Matter (SC-DGM) pattern was associated with high EDSS scores and decline of visuospatial memory function; (2) Frontal-Temporal pattern was associated with decline of language learning function; and (3) Cerebellum-Brainstem pattern had no observed association. Patients with CI had higher weights of SC-DGM pattern than CP group. Three patterns were observed in RRMS: (1) DGM pattern was associated with high EDSS scores, decreased information processing speed, and decreased language learning and visuospatial memory functions; (2) Frontal-Temporal pattern was associated with overall cognitive decline; and (3) Occipital pattern had no observed association. Patients with CI trended to have higher weights of DGM and Frontal-Temporal patterns than CP group. CONCLUSION: This study estimated the heterogeneity of spinal cord and brain atrophy patterns in NMOSD and RRMS patients at individual level, and evaluated the clinical relevance of these patterns, which may contribute to stratifying participants for targeted therapy.

Deep learning-assisted diagnosis of large vessel occlusion in acute ischemic stroke based on four-dimensional computed tomography angiography.

Purpose: To develop deep learning models based on four-dimensional computed tomography angiography (4D-CTA) images for automatic detection of large vessel occlusion (LVO) in the anterior circulation that cause acute ischemic stroke. Methods: This retrospective study included 104 LVO patients and 105 non-LVO patients for deep learning models development. Another 30 LVO patients and 31 non-LVO patients formed the time-independent validation set. Four phases of 4D-CTA (arterial phase P1, arterial-venous phase P2, venous phase P3 and late venous phase P4) were arranged and combined and two input methods was used: combined input and superimposed input. Totally 26 models were constructed using a modified HRNet network. Assessment metrics included the areas under the curve (AUC), accuracy, sensitivity, specificity and F1 score. Kappa analysis was performed to assess inter-rater agreement between the best model and radiologists of different seniority. Results: The P1 + P2 model (combined input) had the best diagnostic performance. In the internal validation set, the AUC was 0.975 (95%CI: 0.878-0.999), accuracy was 0.911, sensitivity was 0.889, specificity was 0.944, and the F1 score was 0.909. In the time-independent validation set, the model demonstrated consistently high performance with an AUC of 0.942 (95%CI: 0.851-0.986), accuracy of 0.902, sensitivity of 0.867, specificity of 0.935, and an F1 score of 0.901. The best model showed strong consistency with the diagnostic efficacy of three radiologists of different seniority (k = 0.84, 0.80, 0.70, respectively). Conclusion: The deep learning model, using combined arterial and arterial-venous phase, was highly effective in detecting LVO, alerting radiologists to speed up the diagnosis.

A Phase I Clinical Study Comparing the Pharmacokinetics, Safety, and Immunogenicity of GB221 Injection and Trastuzumab (Herceptin®) in Healthy Chinese Adults.

BACKGROUND AND OBJECTIVE: GB221 is a recombinant humanized anti-HER2 monoclonal antibody. The purpose of this study was to evaluate the pharmacokinetic, safety, and immunogenicity of GB221 in healthy Chinese adults in comparison to trastuzumab (Herceptin®). METHODS: In this randomized, double-blind, parallel-group phase I clinical trial, 88 subjects were randomized 1:1 to receive a single intravenous infusion (90-100 min) of GB221 or trastuzumab (6 mg/kg). The primary pharmacokinetic parameters-maximum observed serum concentration (Cmax), area under the serum concentration-time curve from zero to the last quantifiable concentration at time t (AUC0-t), and area under the serum concentration-time curve from time zero to infinity (AUC0-∞)-of GB221 and trastuzumab were compared to establish whether the 90% confidence interval (CI) attained the 80-125% bioequivalence standard. Safety and immunogenicity were also evaluated. RESULTS: The GB221 group (n = 43) and the trastuzumab group (n = 44) showed similar pharmacokinetic characteristics. The geometric mean ratios (90% CI) of Cmax, AUC0-t, and AUC0-∞ between the two groups were 107.53% (102.25-113.07%), 108.31% (103.57-113.26%), and 108.34% (103.57-113.33%), respectively. The incidence of treatment-emergent adverse events (TEAEs) was 83.7% (36/43) of the subjects in the GB221 group and 95.5% (42/44) of the subjects in the trastuzumab group. No subjects withdrew from the trial due to TEAEs, and there were no occurrences of serious adverse events. All subjects tested negative for antidrug antibodies (ADA). CONCLUSION: GB221 demonstrated similar pharmacokinetics to trastuzumab and comparable safety and immunogenicity in healthy Chinese adults.

The role of the sensory input intervention in recovery of the motor function in hypoxic ischemic encephalopathy rat model.

Motor disturbances predominantly characterize hypoxic-ischemic encephalopathy (HIE). Among its intervention methods, environmental enrichment (EE) is strictly considered a form of sensory intervention. However, limited research uses EE as a single sensory input intervention to validate outcomes postintervention. A Sprague-Dawley rat model subjected to left common carotid artery ligation and exposure to oxygen-hypoxic conditions is used in this study. EE was achieved by enhancing the recreational and stress-relief items within the cage, increasing the duration of sunlight, colorful items exposure, and introducing background music. JZL184 (JZL) was administered as neuroprotective drugs. EE was performed 21 days postoperatively and the rats were randomly assigned to the standard environment and EE groups, the two groups were redivided into control, JZL, and vehicle injection subgroups. The Western blotting and behavior test indicated that EE and JZL injections were efficacious in promoting cognitive function in rats following HIE. In addition, the motor function performance in the EE-alone intervention group and the JZL-alone group after HIE was significantly improved compared with the control group. The combined EE and JZL intervention group exhibited even more pronounced improvements in these performances. EE may enhance motor function through sensory input different from the direct neuroprotective effect of pharmacological treatment.NEW & NOTEWORTHY Rarely does literature assess motor function, even though it is common after hypoxia ischemic encephalopathy (HIE). Previously used environmental enrichment (EE) components have not been solely used as sensory inputs. Physical factors were minimized in our study to observe the effects of purely sensory inputs.

Antihypertensive Medication and Fracture Risk in Older Veterans Health Administration Nursing Home Residents.

Importance: Limited evidence exists on the association between initiation of antihypertensive medication and risk of fractures in older long-term nursing home residents. Objective: To assess the association between antihypertensive medication initiation and risk of fracture. Design, Setting, and Participants: This was a retrospective cohort study using target trial emulation for data derived from 29 648 older long-term care nursing home residents in the Veterans Health Administration (VA) from January 1, 2006, to October 31, 2019. Data were analyzed from December 1, 2021, to November 11, 2023. Exposure: Episodes of antihypertensive medication initiation were identified, and eligible initiation episodes were matched with comparable controls who did not initiate therapy. Main Outcome and Measures: The primary outcome was nontraumatic fracture of the humerus, hip, pelvis, radius, or ulna within 30 days of antihypertensive medication initiation. Results were computed among subgroups of residents with dementia, across systolic and diastolic blood pressure thresholds of 140 and 80 mm Hg, respectively, and with use of prior antihypertensive therapies. Analyses were adjusted for more than 50 baseline covariates using 1:4 propensity score matching. Results: Data from 29 648 individuals were included in this study (mean [SD] age, 78.0 [8.4] years; 28 952 [97.7%] male). In the propensity score-matched cohort of 64 710 residents (mean [SD] age, 77.9 [8.5] years), the incidence rate of fractures per 100 person-years in residents initiating antihypertensive medication was 5.4 compared with 2.2 in the control arm. This finding corresponded to an adjusted hazard ratio (HR) of 2.42 (95% CI, 1.43-4.08) and an adjusted excess risk per 100 person-years of 3.12 (95% CI, 0.95-6.78). Antihypertensive medication initiation was also associated with higher risk of severe falls requiring hospitalizations or emergency department visits (HR, 1.80 [95% CI, 1.53-2.13]) and syncope (HR, 1.69 [95% CI, 1.30-2.19]). The magnitude of fracture risk was numerically higher among subgroups of residents with dementia (HR, 3.28 [95% CI, 1.76-6.10]), systolic blood pressure of 140 mm Hg or higher (HR, 3.12 [95% CI, 1.71-5.69]), diastolic blood pressure of 80 mm Hg or higher (HR, 4.41 [95% CI, 1.67-11.68]), and no recent antihypertensive medication use (HR, 4.77 [95% CI, 1.49-15.32]). Conclusions and Relevance: Findings indicated that initiation of antihypertensive medication was associated with elevated risks of fractures and falls. These risks were numerically higher among residents with dementia, higher baseline blood pressures values, and no recent antihypertensive medication use. Caution and additional monitoring are advised when initiating antihypertensive medication in this vulnerable population.

Effects of residential socioeconomic polarization on high blood pressure among nursing home residents.

OBJECTIVE: Neighborhood concentration of racial, income, education, and housing deprivation is known to be associated with higher rates of hypertension. The objective of this study is to examine the association between tract-level spatial social polarization and hypertension in a cohort with relatively equal access to health care, a Veterans Affairs nursing home. METHODS: 41,973 long-term care residents aged ≥65 years were matched with tract-level Indices of Concentration at the Extremes across four socioeconomic domains. We modeled high blood pressure against these indices controlling for individual-level cardiovascular confounders. RESULTS: We found participants who had resided in the most disadvantaged quintile had a 1.10 (95% 1.01, 1.19) relative risk of high blood pressure compared to those in the other quintiles for the joint measuring race/ethnicity and income domain. CONCLUSIONS: We achieved our objective by demonstrating that concentrated deprivation is associated with worse cardiovascular outcomes even in a population with equal access to care. Measures that jointly consider economic and racial/ethnic polarization elucidate larger disparities than single domain measures.

Advanced Biological Applications of Cerium Oxide Nanozymes in Disease Related to Oxidative Damage.

Due to their excellent catalytic activities, cerium oxide nanoparticles have promise as biological nanoenzymes. A redox reaction occurs between Ce3+ ions and Ce4+ ions during which they undergo conversion by acquiring or losing electrons as well as forming oxygen vacancies (or defects) in the lattice structure, which can act as antioxidant enzymes and simulate various enzyme activities. A number of cerium oxide nanoparticles have been engineered with multienzyme activities, including catalase, superoxide oxidase, peroxidase, and oxidase mimetic properties. Cerium oxide nanoparticles have nitric oxide radical clearing and radical scavenging properties and have been widely used in a number of fields of biology, including biomedicine, disease diagnosis, and treatment. This review provides a comprehensive introduction to the catalytic mechanisms and multiple enzyme activities of cerium oxide nanoparticles, along with their potential applications in the treatment of diseases of the brain, bones, nerves, and blood vessels.

[Effects of Continuous Annual Crop Rotation and Fallow on Soil Aggregate Stability and Organic Carbon].

In order to explore the effects of continuous annual crop rotation and fallow on aggregate stability and organic carbon content in red soil, the red soil in sloping farmland was taken as the research object, and the water-stable aggregates and organic carbon content were determined using the wet sieve method and potassium dichromate-concentrated sulfuric acid external heating method, respectively. The changes in soil aggregate stability and organic carbon content under the four treatments of maize-vetch-maize rotation (M-V-M), maize-pea-maize rotation (M-P-M), maize-fallow-maize (M-F-M), and annual fallow (F-F-F) from 2020 to 2022 and the relationships between them were analyzed. The results showed that in 2021 and 2022, the contents of > 2 mm aggregates treated with F-F-F, M-V-M, and M-P-M were significantly increased by 67.01%-100.92%, 29.71%-33.67%, and 29.68%-38.07%, respectively, compared with that treated with M-F-M. In 2021 and 2022, the stability parameters of F-F-F and M-V-M were significantly higher than those of M-F-M (P < 0.05). The content of > 2 mm aggregates, geometric mean diameter (GMD), and mean weight diameter (MWD) under the M-V-M treatment and R0.25 (> 0.25 mm aggregate contents), MWD and > 2 mm aggregate contents under the F-F-F treatment increased with the increase in fallow years, whereas the content of 1-2 mm and < 0.25 mm under the F-F-F treatment decreased with the increase in fallow years. Both green manure rotation and fallow treatment could increase the SOC content, and the SOC content of F-F-F and M-V-M treatment increased with the extension in age. Correlation analysis showed that SOC content was significantly positively correlated with R0.25 and GMD under all treatments. R0.25 and GMD under the F-F-F treatment and GMD and MWD under M-V-M were significantly positively correlated with SOC content. The results showed that continuous annual crop rotation and fallow was beneficial to improve the content of soil macro-aggregates, aggregate stability, and SOC content, which could provide theoretical basis for the implementation of reasonable continuous annual crop rotation and fallow patterns and soil erosion control in red soil areas of sloping farmland in southern China.

Quantitative Fluorescent Lateral Flow Strip Sensor for Myocardial Infarction Using Purity-Color Upconversion Nanoparticles.

Acute myocardial infarction is a serious cardiovascular disease and poses significant risks to human health. Its early diagnosis and real-time detection are of great importance. Herein, we design a low-cost device that has a high sensitivity of cTnT and cTnI detection. Dual-color upconversion nanoparticles (UCNPs) are prepared as probes, which not only have high-purity red upconversion luminescence (UCL) under 980 or 808 nm excitation but also achieve good temperature sensing. Temperature-dependent multicolor emission excitation is obtained, and the color turns from white to orange and red with increasing temperature. In particular, the maximum SR and SA values based on nonthermally coupled levels are 4.76% K-1 and 8.6% K-1, which are higher than those based on thermally coupled levels. With the UCNPs-based lateral flow strip (LFS), the specific detection of cTnI and cTnT antigens in samples is achieved with a detection limit of 0.001 ng/mL, which is 1 order of magnitude lower than that of their clinical cutoff. The UCNPs-LFS device has a low-cost laser diode and a simplified laser and permits a mobile-phone camera to collect the results, which has an important influence on the field of biomarker sensing.

Exploring a multiparameter MRI-based radiomics approach to predict tumor proliferation status of serous ovarian carcinoma.

OBJECTIVES: To develop a multiparameter magnetic resonance imaging (MRI)-based radiomics approach that can accurately predict the tumor cell proliferation status of serous ovarian carcinoma (SOC). MATERIALS AND METHODS: A total of 134 patients with SOC who met the inclusion and exclusion criteria were retrospectively screened from institution A, spanning from January 2016 to March 2022. Additionally, an external validation set comprising 42 SOC patients from institution B was also included. The region of interest was determined by drawing each ovarian mass boundaries manually slice-by-slice on T2-weighted imaging fat-suppressed fast spin-echo (T2FSE) and T1 with contrast enhancement (T1CE) images using ITK-SNAP software. The handcrafted radiomic features were extracted, and then were selected using variance threshold algorithm, SelectKBest algorithm, and least absolute shrinkage and selection operator. The optimal radiomic scores and the clinical/radiological independent predictors were integrated as a combined model. RESULTS: Compared with the area under the curve (AUC) values of each radiomic signature of T2FSE and T1CE, respectively, the AUC value of the radiomic signature (T1CE-T2FSE) was the highest in the training set (0.999 vs. 0.965 and 0.860). The homogeneous solid component of the ovarian mass was considered the only independent predictor of tumor cell proliferation status among the clinical/radiological variables. The AUC of the radiomic-radiological model was 0.999. CONCLUSIONS: The radiomic-radiological model combining radiomic scores and the homogeneous solid component of the ovarian mass can accurately predict tumor cell proliferation status of SOC which has high repeatability and may enable more targeted and effective treatment strategies. CRITICAL RELEVANCE STATEMENT: The proposed radiomic-radiological model combining radiomic scores and the homogeneous solid component of the ovarian mass can predict tumor cell proliferation status of SOC which has high repeatability and may guide individualized treatment programs. KEY POINTS: • The radiomic-radiological nomogram may guide individualized treatment programs of SOC. • This radiomic-radiological nomogram showed a favorable prediction ability. • Homogeneous slightly higher signal intensity on T2FSE is vital for Ki-67.

Enhancing precision medicine: a nomogram for predicting platinum resistance in epithelial ovarian cancer.

BACKGROUND: This study aimed to develop a novel nomogram that can accurately estimate platinum resistance to enhance precision medicine in epithelial ovarian cancer(EOC). METHODS: EOC patients who received primary therapy at the General Hospital of Ningxia Medical University between January 31, 2019, and June 30, 2021 were included. The LASSO analysis was utilized to screen the variables which contained clinical features and platinum-resistance gene immunohistochemistry scores. A nomogram was created after the logistic regression analysis to develop the prediction model. The consistency index (C-index), calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to assess the nomogram's performance. RESULTS: The logistic regression analysis created a prediction model based on 11 factors filtered down by LASSO regression. As predictors, the immunohistochemical scores of CXLC1, CXCL2, IL6, ABCC1, LRP, BCL2, vascular tumor thrombus, ascites cancer cells, maximum tumor diameter, neoadjuvant chemotherapy, and HE4 were employed. The C-index of the nomogram was found to be 0.975. The nomogram's specificity is 95.35% and its sensitivity, with a cut-off value of 165.6, is 92.59%, as seen by the ROC curve. After the nomogram was externally validated in the test cohort, the coincidence rate was determined to be 84%, and the ROC curve indicated that the nomogram's AUC was 0.949. CONCLUSION: A nomogram containing clinical characteristics and platinum gene IHC scores was developed and validated to predict the risk of EOC platinum resistance.

Protecting against ferroptosis in hyperuricemic nephropathy: The potential of ferrostatin-1 and its inhibitory effect on URAT1.

Hyperuricemic nephropathy (HN) is characterized by renal fibrosis and tubular necrosis caused by elevated uric acid levels. Ferroptosis, an iron-dependent type of cell death, has been implicated in the pathogenesis of kidney diseases. The objective of this study was to explore the role of ferroptosis in HN and the impact of a ferroptosis inhibitor, ferrostatin-1 (Fer-1). The study combined adenine and potassium oxonate administration to establish a HN model in mice and treated HK-2 cells with uric acid to simulate HN conditions. The effects of Fer-1 on the renal function, fibrosis, and ferroptosis-associated molecules were investigated in HN mice and HK-2 cells treated with uric acid. The HN mice presented with renal dysfunction characterized by elevated tissue iron levels and diminished antioxidant capacity. There was a significant decrease in the mRNA and protein expression levels of SLC7A11, GPX4, FTL-1 and FTH-1 in HN mice. Conversely, treatment with Fer-1 reduced serum uric acid, serum creatinine, and blood urea nitrogen, while increasing uric acid levels in urine. Fer-1 administration also ameliorated renal tubule dilatation and reduced renal collagen deposition. Additionally, Fer-1 also upregulated the expression levels of SLC7A11, GPX4, FTL-1, and FTH-1, decreased malondialdehyde and iron levels, and enhanced glutathione in vivo and in vitro. Furthermore, we first found that Fer-1 exhibited a dose-dependent inhibition of URAT1, with the IC50 value of 7.37 ± 0.66 µM. Collectively, the current study demonstrated that Fer-1 effectively mitigated HN by suppressing ferroptosis, highlighting the potential of targeting ferroptosis as a therapeutic strategy for HN.

Piperine Improves Hyperuricemic Nephropathy by Inhibiting URAT1/GLUT9 and the AKT-mTOR Pathway.

Uncontrolled hyperuricemia often leads to the development of hyperuricemic nephropathy (HN), characterized by excessive inflammation and oxidative stress. Piperine, a cinnamic acid alkaloid, possesses various pharmacological activities, such as antioxidant and anti-inflammatory effects. In this study, we intended to investigate the protective effects of piperine on adenine and potassium oxonate-induced HN mice and a uric-acid-induced injury model in renal tubular epithelial cells (mRTECs). We observed that treatment with piperine for 3 weeks significantly reduced serum uric acid levels and reversed kidney function impairment in mice with HN. Piperine (5 µM) alleviated uric acid-induced damage in mRTECs. Moreover, piperine inhibited transporter expression and dose-dependently inhibited the activity of both transporters. The results revealed that piperine regulated the AKT/mTOR signaling pathway both in vivo and in vitro. Overall, piperine inhibits URAT1/GLUT9 and ameliorates HN by inhibiting the AKT/mTOR pathway, making it a promising candidate for patients with HN.

Interpretable and Intuitive Machine Learning Approaches for Predicting Disability Progression in Relapsing-Remitting Multiple Sclerosis Based on Clinical and Gray Matter Atrophy Indicators.

RATIONALE AND OBJECTIVES: To investigate whether clinical and gray matter (GM) atrophy indicators can predict disability in relapsing-remitting multiple sclerosis (RRMS) and to enhance the interpretability and intuitiveness of a predictive machine learning model. MATERIALS AND METHODS: 145 and 50 RRMS patients with structural MRI and at least 1-year follow-up Expanded Disability Status Scale (EDSS) results were retrospectively enrolled and placed in the discovery and external test cohorts, respectively. Six clinical and radiomics feature-based machine learning classifiers were trained and tested to predict disability progression in the discovery cohort and validated in the external test set. Partial dependence plot (PDP) analysis and a Shiny web application were conducted to enhance the interpretability and intuitiveness. RESULTS: In the discovery cohort, 98 patients had disability stability, and 47 patients were classified as having disability progression. In the external test set, 35 patients were disability stable, and 15 patients had disability progression. Models trained with both clinical and radiomics features (area under the curve (AUC), 0.725-0.950) outperformed those trained with clinical (AUC, 0.600-0.740) or radiomics features only (AUC, 0.615-0.945). Among clinical+ radiomics feature models, the logistic regression (LR) classifier-based model performed best, with an AUC of 0.950. Only the radiomics feature-only models were applied in the external test set due to the data collection problem and showed fair performance, with AUCs ranging from 0.617 to 0.753. PDP analysis showed that female patients and those with lower volume, surface area, and symbol digit modalities test (SDMT) scores; greater mean curvature and age; and no disease modifying therapy (DMT) had increased probabilities of disease progression. Finally, a Shiny web application (https://lauralin1104.shinyapps.io/LRshiny/) was developed to calculate the risk of disability progression. CONCLUSION: Interpretable and intuitive machine learning approaches based on clinical and GM atrophy indicators can help physicians predict disability progression in RRMS patients for clinical decision-making and patient management.

Influence of weeding methods on rhizosphere soil and root endophytic microbial communities in tea plants.

Introduction: Polyethylene mulch is a kind of inorganic mulch widely used in agriculture. The effects of plastic mulch debris on the structure of plant soil and root growth have been fully studied, but their effects on endophytic microbial communities have not been explored to a large extent. Methods: In this study, High-throughput sequencing of bacterial 16S rRNA genes and fungal ITS region sequences were used to analyze microbial community structure and composition in rhizosphere soil and root endophytic of tea plant under three different weeding methods: polyethylene mulching, hand weeding and no weeding (CK). Results: The results showed that the weeding methods had no significant effect on the rhizosphere and root endophytic microbial abundance, but the rhizosphere bacterial structure covered by polyethylene mulch was significantly different than hand weeding and CK. The rhizosphere fungal diversity was also significantly higher than the other two analyzed treatments. The community abundance of rhizosphere microorganisms Acidobacteria, Candidatus Rokubacteria and Aspergillus covered by polyethylene mulch decreased significantly, whereas Bradyrhizobium, Solirubrobacterales and Alphaproteobacteria increased significantly. The abundance of bacteria Ktedonobacter, Reticulibacter, Ktedonosporobacter and Dictyobacter communities covered by polyethylene mulch was significantly changed, and the abundance of Fusarium and Nitrobacteraceae was significantly increased. Rhizosphere dominant bacteria were negatively correlated with soil available nitrogen content, while dominant fungi were significantly correlated with soil pH, total nitrogen and total potassium. Discussion: Polyethylene mulch forms an independent micro-ecological environment. At the same time, the soil nutrient environment was enriched by affecting the nitrogen cycle, and the composition of microbial community was affected. This study elucidated the effects of polyethylene mulch on soil microbial community in tea garden and provided a new theoretical understanding for weed management.

Radiomics derived from T2-FLAIR: the value of 2- and 3-classification tasks for different lesions in multiple sclerosis.

Background: White matter (WM) lesions can be classified into contrast enhancement lesions (CELs), iron rim lesions (IRLs), and non-iron rim lesions (NIRLs) based on different pathological mechanism in relapsing-remitting multiple sclerosis (RRMS). The application of radiomics established by T2-FLAIR to classify WM lesions in RRMS is limited, especially for 3-class classification among CELs, IRLs, and NIRLs. Methods: A total of 875 WM lesions (92 CELs, 367 IRLs, 416 NIRLs) were included in this study. The 2-class classification was only performed between IRLs and NIRLs. For the 2- and 3-class classification tasks, all the lesions were randomly divided into training and testing sets with a ratio of 8:2. We used least absolute shrinkage and selection operator (LASSO), reliefF algorithm, and mutual information (MI) for feature selection, then eXtreme gradient boosting (XGBoost), random forest (RF), and support vector machine (SVM) were used to establish discrimination models. Finally, the area under the curve (AUC), accuracy, sensitivity, specificity, and precision were used to evaluate the performance of the models. Results: For the 2-class classification model, LASSO classifier with RF model showed the best discrimination performance with the AUC of 0.893 (95% CI: 0.838-0.942), accuracy of 0.813, sensitivity of 0.833, specificity of 0.781, and precision of 0.851. However, the 3-class classification model of LASSO with XGBoost displayed the highest performance with the AUC of 0.920 (95% CI: 0.887-0.950), accuracy of 0.796, sensitivity of 0.839, specificity of 0.881, and precision of 0.846. Conclusions: Radiomics models based on T2-FLAIR images have the potential for discriminating among CELs, IRLs, and NIRLs in RRMS.

Revolutionizing vascular imaging: trends and future directions of 4D flow MRI based on a 20-year bibliometric analysis.

Background: Four-dimensional flow magnetic resonance imaging (4D flow MRI) is a promising new technology with potential clinical value in hemodynamic quantification. Although an increasing number of articles on 4D flow MRI have been published over the past decades, few studies have statistically analyzed these published articles. In this study, we aimed to perform a systematic and comprehensive bibliometric analysis of 4D flow MRI to explore the current hotspots and potential future directions. Methods: The Web of Science Core Collection searched for literature on 4D flow MRI between 2003 and 2022. CiteSpace was utilized to analyze the literature data, including co-citation, cooperative network, cluster, and burst keyword analysis. Results: A total of 1,069 articles were extracted for this study. The main research hotspots included the following: quantification and visualization of blood flow in different clinical settings, with keywords such as "cerebral aneurysm", "heart", "great vessel", "tetralogy of Fallot", "portal hypertension", and "stiffness"; optimization of image acquisition schemes, such as "resolution" and "reconstruction"; measurement and analysis of flow components and patterns, as indicated by keywords "pattern", "KE", "WSS", and "fluid dynamics". In addition, international consensus for metrics derived from 4D flow MRI and multimodality imaging may also be the future research direction. Conclusions: The global domain of 4D flow MRI has grown over the last 2 decades. In the future, 4D flow MRI will evolve towards becoming a relatively short scan duration with adequate spatiotemporal resolution, expansion into the diagnosis and treatment of vascular disease in other related organs, and a shift in focus from vascular structure to function. In addition, artificial intelligence (AI) will assist in the clinical promotion and application of 4D flow MRI.