ERRα promotes glycolytic metabolism and targets the NLRP3/caspase-1/GSDMD pathway to regulate pyroptosis in endometrial cancer.

BACKGROUND: Tumor cells can resist chemotherapy-induced pyroptosis through glycolytic reprogramming. Estrogen-related receptor alpha (ERRα) is a central regulator of cellular energy metabolism associated with poor cancer prognosis. Herein, we refine the oncogenic role of ERRα in the pyroptosis pathway and glycolytic metabolism. METHODS: The interaction between ERRα and HIF-1α was verified using co-immunoprecipitation. The transcriptional binding sites of ERRα and NLRP3 were confirmed using dual-luciferase reporter assay and cleavage under targets and tagmentation (CUT&Tag). Flow cytometry, transmission electron microscopy, scanning electron microscopy, cell mito stress test, and extracellular acidification rate analysis were performed to investigate the effects of ERRα on the pyroptosis pathway and glycolytic metabolism. The results of these experiments were further confirmed in endometrial cancer (EC)-derived organoids and nude mice. In addition, the expression of ERRα-related pyroptosis genes was analyzed using The Cancer Genome Atlas and Gene Expression Omnibus database. RESULTS: Triggered by a hypoxic microenvironment, highly expressed ERRα could bind to the promoter of NLRP3 and inhibit caspase-1/GSDMD signaling, which reduced inflammasome activation and increased pyroptosis resistance, thereby resulting in the resistance of cancer cells to cisplatin. Moreover, ERRα activated glycolytic rate-limiting enzyme to bridge glycolytic metabolism and pyroptosis in EC. This phenomenon was further confirmed in EC-derived organoids and nude mice. CUT & Tag sequencing and The Cancer Genome Atlas database analysis showed that ERRα participated in glycolysis and programmed cell death, which resulted in EC progression. CONCLUSIONS: ERRα inhibits pyroptosis in an NLRP3-dependent manner and induces glycolytic metabolism, resulting in cisplatin resistance in EC cells.

Impaired T1 mapping and Tmax during the first 7 days after ischemic stroke. A retrospective observational study.

OBJECTIVE: To measure the relative T1 (rT1) value in different hypo-perfused regions after ischemic stroke using T1 mapping derived by Strategically Acquired Gradient Echo (STAGE) and assess its relationship with onset time and severity of ischemia. MATERIALS AND METHODS: Sixty-three patients with acute anterior circulation ischemic stroke from 2017 to 2022 who underwent STAGE, diffusion weighted imaging (DWI) and dynamic susceptibility contrast perfusion weighted imaging (DSC-PWI) within 7 days were retrospectively enrolled. The areas with reduced diffusion and hypo-perfusion were segmented based on apparent diffusion coefficient (ADC) value < 0.62 × 10-3mm2/s and time-to-maximum (Tmax) thresholds (4, 6, 8, and 10 seconds). We measured the T1 value in the diffusion reduced and every 2 s Tmax strata regions and calculated rT1 (T1ipsi/T1contra) to explore the relationship between rT1 value, Tmax, and onset time. RESULTS: rT1 value was increased in diffusion reduced (1.42) and hypo-perfused regions (1.02, 1.06, 1.12, 1.27, Tmax 4-6 s, 6-8 s, 8-10 s, > 10 s, respectively; all different from 1, P < 0.001). rT1 value was positively correlated with Tmax (rs = 0.61, P < 0.001) and onset time in area with reduced diffusion (rs = 0.39, P = 0.014). CONCLUSIONS: Increased rT1 value in different hypo-perfused brain regions using T1 mapping derived by STAGE may reflect the edema; it was associated with the severity of Tmax and showed a weak correlation with the onset time in diffusion reduced areas.

Peripheral blood lymphocytes influence human papillomavirus infection and clearance: a retrospective cohort study.

BACKGROUND: There is a close correlation between HPV infection and systemic immune status. The purpose of this study was to determine which lymphocytes in peripheral blood influence human papillomavirus (HPV) infection and to identify whether peripheral blood lymphocyte (PBL) subsets could be used as biomarkers to predict HPV clearance in the short term. METHODS: This study involved 716 women undergoing colposcopy from 2019 to 2021. Logistic and Cox regression were used to analyze the association of PBLs with HPV infection and clearance. Using Cox regression, bidirectional stepwise regression and the Akaike information criterion (AIC), lymphocyte prediction models were developed, with the C-index assessing performance. ROC analysis determined optimal cutoff values, and their accuracy for HPV clearance risk stratification was evaluated via Kaplan‒Meier and time-dependent ROC. Bootstrap resampling validated the model and cutoff values. RESULTS: Lower CD4 + T cells were associated with a higher risk of HPV, high-risk HPV, HPV18 and HPV52 infections, with corresponding ORs (95% CI) of 1.58 (1.16-2.15), 1.71 (1.23-2.36), 2.37 (1.12-5.02), and 3.67 (1.78-7.54), respectively. PBL subsets mainly affect the natural clearance of HPV, but their impact on postoperative HPV outcomes is not significant (P > 0.05). Lower T-cell and CD8 + T-cell counts, as well as a higher NK cell count, are unfavorable factors for natural HPV clearance (P < 0.05). The optimal cutoff values determined by the PBL prognostic model (T-cell percentage: 67.39%, NK cell percentage: 22.65%, CD8 + T-cell model risk score: 0.95) can effectively divide the population into high-risk and low-risk groups, accurately predicting the natural clearance of HPV. After internal validation with bootstrap resampling, the above conclusions still hold. CONCLUSIONS: CD4 + T cells were important determinants of HPV infection. T cells, NK cells, and CD8 + T cells can serve as potential biomarkers for predicting natural HPV clearance, which can aid in patient risk stratification, individualized treatment, and follow-up management.

Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) Is Associated with Cervical Stromal Involvement in Endometrial Cancer Patients: A Cross-Sectional Study in South China.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a significant health issue closely associated with multiple extrahepatic cancers. The association between MAFLD and clinical outcomes of endometrial cancer (EC) remains unknown. METHODS: We retrospectively included 725 EC patients between January 2012 and December 2020. The odds ratios (ORs) were calculated using logistic regression analyses. Kaplan-Meier survival curves were used for survival analysis. RESULTS: Among EC patients, the prevalence of MAFLD was 27.7% (201/725, 95% confidence interval (Cl) = 0.245-0.311). MAFLD was significantly associated with cervical stromal involvement (CSI) (OR = 1.974, 95% confidence interval (Cl) = 1.065-3.659, p = 0.031). There was a significant correlation between overall survival (OS) and CSI (HR = 0.31; 95%CI: 0.12-0.83; p = 0.020), while patients with MAFLD had a similar OS to those without MAFLD (p = 0.952). Moreover, MAFLD was significantly associated with CSI in the type I EC subgroup (OR = 2.092, 95% confidence interval (Cl) = 1.060-4.129, p = 0.033), but not in the type II EC subgroup (p = 0.838). Further logistic regression analysis suggested that the hepatic steatosis index (HSI) was significantly associated with CSI among type I EC patients without type 2 diabetes mellitus (T2DM) (OR = 1.079, 95% confidence interval (Cl) = 1.020-1.139, p = 0.012). CONCLUSIONS: About one-quarter of our cohort had MAFLD. MAFLD was associated with the risk of CSI in EC patients, and this association existed in type I EC patients but not in type II EC patients. Furthermore, the HSI can help predict CSI in type I EC patients without T2DM.

Integrated Assessment of Water Environmental Health Risk through Drinking Water Ingestion in Lhasa River Basin: Quantitative Analysis and Environmental Significance.

An integrated assessment of water environmental health risk through drinking water ingestion in Lhasa River has been implemented. The health risks caused by different pollutants in different age groups (children, juvenile and adult groups) are in the order of 10-8 ~ 10-7, 10-7 ~ 10-5 and 10-13 ~ 10-8 a-1, respectively. The total health risks for all age groups are lower than the International Commission on Radiation Protection recommended value and the U.S. Environmental Protection Agency recommended value at all points except LS4, LS12 and LS13. The total health risk levels in different age groups at most points are class III or II, which means that there are low or negligible negative effect in these points and age groups. It is more important to monitor the arsenic concentration. The water environment quality protecting in Lhasa River Basin must be consistent with the clear water and blue sky protecting in Tibet Autonomous Region and the national ecological security barrier construction on the Tibetan Plateau.

Co-existing intracranial and extracranial carotid atherosclerosis predicts large-artery atherosclerosis stroke recurrence: a single-center prospective study utilizing combined head-and-neck vessel wall imaging.

OBJECTIVES: Intracranial and extracranial plaque features on high-resolution vessel wall imaging (HR-VWI) are associated with large-artery atherosclerosis (LAA) stroke recurrence. However, most studies have focused on a single vascular bed, and the prognostic value of combined intracranial and extracranial plaque features has yet to be studied. This study aimed to investigate the roles of plaque features, plaque number, and co-existing atherosclerosis in predicting stroke recurrence, utilizing combined head-and-neck HR-VWI. METHODS: From September 2016 to March 2020, participants with acute LAA ischemic strokes were prospectively enrolled and underwent combined head-and-neck HR-VWI. The participants were followed for stroke recurrence for at least 12 months or until a subsequent event occurred. The imaging features at baseline, including conventional and histogram plaque features, plaque number, and co-existing atherosclerosis, were evaluated. Univariable Cox regression analysis and the least absolute shrinkage and selection operator (lasso) method were used for variable screening. Multivariable Cox regression analyses were used to determine the independent risk factors of stroke recurrence. RESULTS: A total of 97 participants (59 ± 12 years, 63 men) were followed for a median of 30.9 months, and 21 participants experienced recurrent strokes. Multivariable Cox analysis identified co-existing intracranial high signal on T1-weighted fat-suppressed images (HST1) and extracranial carotid atherosclerosis (HR, 6.12; 95% CI, 2.52-14.82; p = 0.001) as an independent imaging predictor of stroke recurrence. CONCLUSION: Co-existing intracranial HST1 and extracranial carotid atherosclerosis independently predicted LAA stroke recurrence. Combined head-and-neck HR-VWI is a promising technique for atherosclerosis imaging. CLINICAL RELEVANCE STATEMENT: This prospective study using combined head-and-neck HR-VWI highlighted the necessity of both intracranial culprit plaque evaluation and multi-vascular bed assessment, adding value to the prediction of stroke recurrence. KEY POINTS: • This study highlighted the necessity of both intracranial culprit plaque evaluation and multi-vascular bed assessment, adding value to the prediction of stroke recurrence. • This prospective study using combined head-and-neck HR-VWI found co-existing intracranial HST1 and extracranial carotid atherosclerosis to be independent predictors of stroke recurrence.

ADCY7 mRNA Is a Novel Biomarker in HPV Infection and Cervical High-Grade Squamous Lesions or Higher.

The effect of cervical cancer immunotherapy is limited. Combination therapy will be a new direction for cervical cancer. Thus, it is essential to discover a novel and available predictive biomarker to stratify patients who may benefit from immunotherapy for cervical cancer. In this study, 563 participants were enrolled. Adenylate cyclase 7 (ADCY7) mRNA was detected by real-time quantitative PCR (qPCR) with cervical cytology specimens. The relationship between ADCY7 and cervical intraepithelial neoplasia in grade 2 and higher (CIN2+) was analyzed, and the optimal cut-off values of the relative expression of ADCY7 mRNA to predict CIN2+ were calculated. In addition, the clinical significance of ADCY7 in cervical cancer was determined by the Kaplan-Meier Cox regression based on the TCGA database. The mean ADCY7 mRNA expression increased significantly with cervical lesion development, especially compared with CIN2+ (p < 0.05). Moreover, the expression of ADCY7 increased significantly in high-risk human papillomavirus (HR-HPV) infection but not in HPV-A5/6 species. The area under the receiver operating characteristic curve (AUC) of ADCY7 was 0.897, and an optimal cut-off was 0.435. Furthermore, ADCY7 had the highest OR (OR= 8.589; 95% CI (2.281-22.339)) for detecting CIN 2+, followed by HPV genotyping, TCT, and age (OR = 4.487, OR = 2.071, and OR = 1.345; 95% CI (1.156-10.518), (0.370-8.137), and (0.171-4.694), respectively). Moreover, this study indicated that higher ADCY7 levels could be a suitable predictor for poor prognosis in cervical cancer due to immune cell infiltration. A new auxiliary predictor of CIN2+ in cervical cytology specimens is ADCY7 ≥ 0.435. Furthermore, it may be a promising prognosis predictor and potential immunotherapy target for the combined treatment of cervical cancer and possibly further block HR-HPV persistent infection.

Follow-Up Infarct Volume Prediction by CTP-Based Hypoperfusion Index, and the Discrepancy between Small Follow-Up Infarct Volume and Poor Functional Outcome-A Multicenter Study.

(1) Background: Follow-up infarct volume (FIV) may have implications for prognostication in acute ischemic stroke patients. Factors predicting the discrepancy between FIV and 90-day outcomes are poorly understood. We aimed to develop a comprehensive predictive model of FIV and explore factors associated with the discrepancy. (2) Methods: Patients with acute anterior circulation large vessel occlusion were included. Baseline clinical and CT features were extracted and analyzed, including the CTP-based hypoperfusion index (HI) and the NCCT-based e-ASPECT, measured by automated software. FIV was assessed on follow-up NCCT at 3−7 days. Multiple linear regression was used to construct the predictive model. Subgroup analysis was performed to explore factors associated with poor outcomes (90-mRS scores 3−6) in small FIV (<70 mL). (3) Results: There were 170 patients included. Baseline e-ASPECT, infarct core volume, hypoperfusion volume, HI, baseline international normalized ratio, and successful recanalization were associated with FIV and included in constructing the predictive model. Baseline NIHSS, baseline hypertension, stroke history, and current tobacco use were associated with poor outcomes in small FIV. (4) Conclusions: A comprehensive predictive model (including HI) of FIV was constructed. We also emphasized the importance of hypertension and smoking status at baseline for the functional outcomes in patients with a small FIV.

Peripheral Blood Lymphocyte Subsets as a Risk Predictor of Patients with Endometrioid Endometrial Cancer.

Purpose: This study aimed to explore lymphocyte subsets for the personalized prediction of endometrioid endometrial cancer (EEC) risk and evaluated the correlation between immune cells and International Federation of Gynecology and Obstetrics (FIGO) staging in patients with EEC. Patients and Methods: A case-control study was conducted to analyze the clinical data of 421 patients admitted to Fujian Maternity and Child Health Hospital from October 2017 to December 2021. t-tests or Mann-Whitney U-tests were used to analyze the percentages and absolute counts of peripheral blood lymphocyte subsets in patients with EEC and patients without cancer. The independent risk factors for ECC and FIGO stage were analyzed via multivariate binary logistic regression. The receiver operating characteristic curve was calculated to evaluate the prediction efficacy of risk factors on ECC. Results: The CD4+ T% in the 121 patients with EEC was lower than in the 300 patients without cancer (P = 0.013). The absolute counts of peripheral CD4+ T (P = 0.002) and T cells (P = 0.007) in 37 patients with EEC were lower than in 51 patients without cancer. Multivariate binary logistic regression analysis showed that CD4+ T% and natural killer cell (NK)% were independent risk factors for FIGO staging in patients with EEC. NK% was significantly higher in patients with advanced stage (FIGO III and IV) than those with early EEC (FIGO I and II) (P = 0.004). To determine the early and advance FIGO stage of EEC, the cutoff value of NK% was calculated as 19.94%. Conclusion: With the decrease of CD4+ T counts, the immune status of patients with EEC is impaired. NK cells may help in the evaluation of the prognosis of patients with EEC and are likely to be an independent risk factor for FIGO staging in patients with EEC.

Lactate-Lactylation Hands between Metabolic Reprogramming and Immunosuppression.

Immune evasion and metabolic reprogramming are two fundamental hallmarks of cancer. Interestingly, lactate closely links them together. However, lactate has long been recognized as a metabolic waste product. Lactate and the acidification of the tumor microenvironment (TME) promote key carcinogenesis processes, including angiogenesis, invasion, metastasis, and immune escape. Notably, histone lysine lactylation (Kla) was identified as a novel post-modification (PTM), providing a new perspective on the mechanism by which lactate functions and providing a promising and potential therapy for tumors target. Further studies have confirmed that protein lactylation is essential for lactate to function; it involves important life activities such as glycolysis-related cell functions and macrophage polarization. This review systematically elucidates the role of lactate as an immunosuppressive molecule from the aspects of lactate metabolism and the effects of histone lysine or non-histone lactylation on immune cells; it provides new ideas for further understanding protein lactylation in elucidating lactate regulation of cell metabolism and immune function. We explored the possibility of targeting potential targets in lactate metabolism for cancer treatment. Finally, it is promising to propose a combined strategy inhibiting the glycolytic pathway and immunotherapy.

High-Efficiency and Stable Perovskite Photodetectors with an F4-TCNQ-Modified Interface of NiOx and Perovskite Layers.

Nickel oxide (NiOx), a typical p-type semiconductor, is emerging as the most promising hole transport layer material. However, the inferior interfacial contact of the NiOx/perovskite interface has limited the improvement of the performance of photodetectors (PDs). In this work, 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4-TCNQ) is introduced to modify the NiOx/perovskite interface to prepare high-performance PDs. This study shows that the F4-TCNQ layer interacts with the NiOx/perovskite layers. It can increase the Ni3+/Ni2+ ratio and then enhance the hole extraction and charge carrier mobility; on the contrary, it can form a new Lewis adduct and passivate the undercoordinated Pb2+ ions. Furthermore, with the F4-TCNQ modification, the perovskite film exhibits good thermal stability and photostability. The PDs demonstrate excellent photoelectric properties and long-term stability in the atmosphere. This finding provides a simple and efficient way to further develop the NiOx/perovskite interface.

Surface Plasmon Enhancement of an InGaN Quantum Well Using Nanoparticles Made of Different Metals and Their Combinations.

Surface plasmon (SP) enhancement of photoluminescence (PL) from a green-emitting InGaN/GaN quantum well (QW) using nanoparticles (NPs) made of different metals and their combinations was investigated. The NPs were formed by annealing the metal films in N2 followed by rapid cooling. Four-fold enhancement in PL intensity was achieved using random metal NPs made of Cu on Mg (Cu-Mg) double metal film that was more than two folds of the enhancement observed by AgNPs. Reversing the order of metal film deposition (Mg on Cu) resulted in much lower PL intensity due to significantly different NPs size distribution as the given annealing conditions did not cause homogeneous alloying of the two metals. The results pave the way for the application of NPs of relatively low-cost unconventional metals and their combinations in the SP enhancement of LEDs.

In-Situ Crystallization and Characteristics of Alkali-Activated Materials-Supported Analcime-C from a By-Product of the Lithium Carbonate Industry.

The present study proposes a new process for synthesis of alkali-activated materials (AAM)-supported analcime-C foam materials (AFs), utilizing a by-product of the lithium carbonate industry. This material has great application value as a bulk-type solid adsorbent. Characterization analyses show that the alkaline activator modulus greatly affects the crystallinity of analcime-C in AFs. Furthermore, the compressive strength, zeolite yield, and microstructure of AFs are significantly affected by the saturated steam parameters, including crystallization pressure, temperature, and time. The synthesized materials comprise pores of different sizes (micro to macro). They combine the functional micro-porosity of the analcime-C, the meso-porosity of the gel matrix, and the macro-porosity of the foamed AAM. The maximum compressive strength, density, total porosity, and Pb2+ adsorption capacity of AFs investigated in this study are 1.15 MPa, 350 kg/m3, 76.5%, and 69.3 mg/g Pb2+, respectively. Unlike many granular adsorbents, the bulk AFs adsorbent produced by this process is easy to recycle. In addition, it also contributes to the comprehensive utilization of a by-product of the lithium carbonate industry.

Regional cerebral gray matter atrophy is associated with cognitive impairment in hemodialysis patients: a cross-sectional and longitudinal voxel-based morphological MRI study.

This study aimed to explore gray matter volume (GMV) changes in patients undergoing hemodialysis and assess the clinical risk factors associated with GMV changes and the relationship between GMV changes and neuropsychologic test results. Eighty-eight hemodialysis patients and 76 healthy controls (HCs) were recruited in this study. Fifty patients underwent follow-up examinations (follow-up duration: 1.75 ± 0.55 years), including magnetic resonance imaging, blood biochemical, and neuropsychologic testing. Changes in GMV between the patients and HCs were assessed. Longitudinal GMV changes were also explored in the patients. The clinical risk factors associated with longitudinal GMV changes and the correlations between longitudinal GMV changes and neuropsychologic test results were analyzed in the patients. Patients undergoing hemodialysis had diffusely decreased GMV compared with HCs (with age, sex, and total intracranial volume [TIV] as covariates, P<0.001, voxel-wise threshold false discovery rate [FDR] corrected). Compared with patients at baseline, regional decreased GMV were found in patients at follow-up (with age and TIV as covariates, P<0.05, voxel-wise threshold FDR corrected). Increased serum urea concentrations, parathyroid hormone levels, and hemodialysis duration were independent risk factors for decreased GMV in patients undergoing hemodialysis (all P<0.05, FDR corrected). Patients undergoing hemodialysis had lower mini-mental state examination (MMSE) (27[26, 29]) and Montreal cognitive assessment (MoCA) (22[19.5, 24.0]) scores than those of the HCs (30[29, 30] and 28[26.9, 29]) (all P<0.05). The MMSE scores of the patients at follow-up (26[25, 28.5]) were lower than those of patients at baseline (28[25, 29.5]) (P=0.02). The decreased left caudate volumes were positively correlated with reduced MMSE scores in hemodialysis patients (rs=0.437, P=0.033). Patients undergoing hemodialysis had noticeable GM atrophy over time, related to cognitive impairments.

Prediction of Early Treatment Response in Multiple Myeloma Using MY-RADS Total Burden Score, ADC, and Fat Fraction From Whole-Body MRI: Impact of Anemia on Predictive Performance.

BACKGROUND. The recently released Myeloma Response Assessment and Diagnosis System (MY-RADS) for multiple myeloma (MM) evaluation using whole-body MRI (WB-MRI) describes the total burden score. However, assessment is confounded by red bone marrow hyperplasia in anemia. OBJECTIVE. The purpose of this study is to assess the utility of the MY-RADS total burden score, ADC, and fat fraction (FF) from WB-MRI in predicting early treatment response in patients with newly diagnosed MM and to compare the utility of these measures between patients with and without anemia. METHODS. This retrospective study included 56 patients (40 men, 16 women; mean age, 57.4 ± 9.6 [SD] years) with newly diagnosed MM who underwent baseline WB-MRI including DWI and modified Dixon sequences. Two radiologists recorded total burden score using MY-RADS and measured the ADC and FF of diffuse and focal disease sites. Mean values across sites were derived. Interobserver agreement was evaluated, and the mean assessments of the readers were used for further analyses. Presence of deep response after four cycles of induction chemotherapy was recorded. Patients were classified as having anemia if their hemoglobin level was less than 100 g/L. The utility of WBMRI parameters in predicting deep response was assessed. RESULTS. A total of 24 of 56 patients showed deep response, and 25 of 56 patients had anemia. Interobserver agreement, which was expressed using intraclass correlation coefficients, ranged from 0.95 to 0.99. Among patients without anemia, those with deep response compared with those without deep response had a lower total burden score (9.0 vs 18.0), a lower ADC (0.79 × 10-3 mm2/s vs 1.08 × 10-3 mm2/s), and a higher FF (0.21 vs 0.10) (all p < .001). The combination of these three parameters (optimal cutoffs: ≤ 15 for total burden score, ≤ 0.84 × 10-3 mm2/s for ADC, and > 0.16 for FF) achieved sensitivity of 93.8%, specificity of 93.3%, and accuracy of 93.5% for predicting deep response. In patients with anemia, none of the three parameters were significantly different between patients with and without deep response (all p > .05), and the combination of parameters achieved sensitivity of 56.3%, specificity of 100.0%, and accuracy of 72.0%. CONCLUSION. Low total burden score, low ADC, and high FF from WB-MRI may predict deep response in patients with MM, although only among those without anemia. CLINICAL IMPACT. WB-MRI findings may help guide determination of prognosis and initial treatment selection in MM.

Different cerebral functional segregation in Sjogren's syndrome with or without systemic lupus erythematosus revealed by amplitude of low-frequency fluctuation.

BACKGROUND: Sjögren's syndrome (SjS) associated with systemic lupus erythematosus (SjS-SLE) was considered a standalone but often-overlooked entity. PURPOSE: To assess altered spontaneous brain activity in SjS-SLE and SjS using amplitude of low-frequency fluctuation (ALFF). MATERIAL AND METHODS: Sixteen patients with SjS-SLE, 17 patients with SjS, and 17 matched controls underwent neuropsychological tests and subsequent resting-state functional magnetic resonance imaging (fMRI) examinations. The ALFF value was calculated based on blood oxygen level dependent (BOLD) fMRI. Statistical parametric mapping was utilized to analyze between-group differences and multiple comparison was corrected with Analysis of Functional NeuroImages 3dClustSim. Then, the ALFFs of brain regions with significant differences among the three groups were correlated to corresponding clinical and neuropsychological variables by Pearson correlation. RESULTS: ALFF differences in the bilateral precuneus/posterior cingulate cortex (PCC), right parahippocampal gyrus/caudate/insula, and left insula were found among the three groups. Both SjS-SLE and SjS displayed decreased ALFF in the right parahippocampal gyrus, right insula, and left insula than HC. Moreover, SjS-SLE showed wider decreased ALFF in the bilateral precuneus and right caudate, while the SjS group exhibited increased ALFF in the bilateral PCC. Additionally, patients with SjS-SLE exhibited lower ALFF values in the bilateral PCC and precuneus than SjS. Moreover, ALFF values in the right parahippocampal gyrus and PCC were negatively correlated to fatigue score and disease duration, respectively, in SjS-SLE. CONCLUSION: SjS-SLE and SjS exhibited common and different alteration of cerebral functional segregation revealed by AlFF analysis. This result appeared to indicate that SjS-SLE might be different from SjS with a neuroimaging standpoint.

Impact of Encephalomalacia and White Matter Hyperintensities on ASPECTS in Patients With Acute Ischemic Stroke: Comparison of Automated and Radiologist-Derived Scores.

BACKGROUND. Automated software-based Alberta Stroke Program Early CT Score (ASPECTS) on unenhanced CT is associated with clinical outcomes after acute stroke. However, encephalomalacia or white matter hyperintensities (WMH) may result in a falsely low automated ASPECTS if such findings are interpreted as early ischemia. OBJECTIVE. The purpose of this study was to assess the impact of encephalomalacia and WMH on the automated ASPECTS in patients with acute stroke, in comparison with the radiologist-derived ASPECTS and clinical outcomes. METHODS. This retrospective three-center study included 459 patients (322 men, 137 women; median age, 65 years) with acute ischemic stroke treated by IV thrombolysis who underwent baseline unenhanced CT within 6 hours after symptom onset and MRI within 24 hours after treatment. ASPECTS was determined by automated software and by three radiologists in consensus. Presence of encephalomalacia and extent of WMH (categorized using the modified Scheltens score [mSS]) were also determined using MRI. Kappa coefficients were used to compare the ASPECTS between automated- and radiologist-derived methods. Multivariable logistic regression analyses and ROC analyses were performed to explore the predictive utility of the baseline ASPECTS for unfavorable clinical outcomes (90-day modified Rankin score of 3-6) after thrombolysis. RESULTS. The median automated software-derived ASPECTS was 9, and the median radiologist consensus-derived ASPECTS was 10. Agreement between automated and radiologist-consensus ASPECTS, expressed as kappa, was 0.68, though agreement was 0.76 in patients without encephalomalacia and 0.08 in patients with encephalomalacia. In patients without encephalomalacia, agreement decreased as the mSS increased (e.g., 0.78 in subgroup with mSS < 10 vs 0.19 in subgroup with mSS > 20). By anatomic region, agreement was highest for the lateral middle cerebral artery (κ, 0.52) and lowest for the internal capsule (κ, 0.18). In multivariable analyses, both the automated (odds ratio, 0.69) and the radiologist-consensus (odds ratio, 0.57) ASPECTS independently predicted an unfavorable clinical outcome. For unfavorable outcome, the automated ASPECTS had an AUC of 0.70, sensitivity of 60.4%, and specificity of 70.7%, whereas the radiologist-consensus ASPECTS had an AUC of 0.72, sensitivity of 60.4%, and specificity of 80.5%. CONCLUSION. Presence of encephalomalacia or extensive WMH results in a lower automated than radiologist-consensus ASPECTS, which may impact predictive utility of automated ASPECTS. CLINICAL IMPACT. When using an automated software-derived ASPECTS, radiologists should manually confirm the score in patients with encephalomalacia or extensive leukoencephalopathy.

Transcriptomics and metabolomics reveal tolerance new mechanism of rice roots to Al stress.

The prevalence of soluble aluminum (Al) ions is one of the major limitations to crop production worldwide on acid soils. Therefore, understanding the Al tolerance mechanism of rice and applying Al tolerance functional genes in sensitive plants can significantly improve Al stress resistance. In this study, transcriptomics and metabolomics analyses were performed to reveal the mechanism of Al tolerance differences between two rice landraces (Al-tolerant genotype Shibanzhan (KR) and Al-sensitive genotype Hekedanuo (MR) with different Al tolerance. The results showed that DEG related to phenylpropanoid biosynthesis was highly enriched in KR and MR after Al stress, indicating that phenylpropanoid biosynthesis may be closely related to Al tolerance. E1.11.1.7 (peroxidase) was the most significant enzyme of phenylpropanoid biosynthesis in KR and MR under Al stress and is regulated by multiple genes. We further identified that two candidate genes Os02g0770800 and Os06g0521900 may be involved in the regulation of Al tolerance in rice. Our results not only reveal the resistance mechanism of rice to Al stress to some extent, but also provide a useful reference for the molecular mechanism of different effects of Al poisoning on plants.

Neuromarkers from Whole-Brain Functional Connectivity Reveal the Cognitive Recovery Scheme for Overt Hepatic Encephalopathy after Liver Transplantation.

Neurocognitive impairment is present in cirrhosis and may be more severe in cirrhosis with overt hepatic encephalopathy (OHE). Liver transplantation (LT) can restore liver function, but how it reverses the impaired brain function is still unclear. MRI of resting-state functional connectivity can help reveal the underlying mechanisms that lead to these cognitive deficits and cognitive recovery. In this study, 64 patients with cirrhosis (28 with OHE; 36 without OHE) and 32 healthy control subjects were recruited for resting-state fMRI. The patients were scanned before and after LT. We evaluated presurgical and postsurgical neurocognitive performance in cirrhosis patients using psychomotor tests. Network-based statistics found significant disrupted connectivity in both groups of cirrhotic patients, with OHE and without OHE, compared with control subjects. However, the presurgical connectivity disruption in patients with OHE affected a greater number of connections than those without OHE. The decrease in functional connectivity for both OHE and non-OHE patient groups was reversed after LT to the level of control subjects. An additional hyperconnected network (i.e., higher connected than control subjects) was observed in OHE patients after LT. Regarding the neural-behavior relationship, the functional network that predicted cognitive performance in healthy individuals showed no correlation in presurgical cirrhotic patients. The impaired neural-behavior relationship was re-established after LT for non-OHE patients, but not for OHE patients. OHE patients displayed abnormal hyperconnectivity and a persistently impaired neural-behavior relationship after LT. Our results suggest that patients with OHE may undergo a different trajectory of postsurgical neurofunctional recovery compared with those without, which needs further clarification in future studies.

Nomogram to Assess the Risk of Central Cervical Lymph Node Metastasis in Patients With Clinical N0 Papillary Thyroid Carcinoma.

OBJECTIVE: To develop and validate an individualized risk prediction model for the need for central cervical lymph node dissection in patients with clinical N0 papillary thyroid carcinoma (PTC) diagnosed using ultrasound. METHODS: Upon retrospective review, derivation and internal validation cohorts comprised 1585 consecutive patients with PTC treated from January 2017 to December 2019 at hospital A. The external validation cohort consisted of 406 consecutive patients treated at hospital B from January 2016 to June 2020. Independent risk factors for central cervical lymph node metastasis (CLNM) were determined through univariable and multivariable logistic regression analysis. An individualized risk prediction model was constructed and illustrated as a nomogram, which was internally and externally validated. RESULTS: The following risk factors of CLNM were established: a solitary primary thyroid nodule's diameter, shape, calcification, and capsular abutment-to-lesion perimeter ratio. The areas under the receiver operating characteristic curves of the risk prediction model for the internal and external validation cohorts were 0.921 and 0.923, respectively. The calibration curve showed good agreement between the nomogram-estimated probability of CLNM and the actual CLNM rates in the 3 cohorts. The decision curve analysis confirmed the clinical usefulness of the nomogram. CONCLUSION: This study developed and validated a model for predicting the risk of CLNM in individual patients with clinical N0 PTC, which should be an efficient tool for guiding clinical treatment.