Magnetic resonance imaging-based Classifications for Symptom of Adenomyosis.

OBJECTIVES: To identify an optimal magnetic resonance imaging (MRI)-based classification for the severity of adenomyosis and explore the factors associated with disease severity (dysmenorrhea or menorrhagia). DESIGN AND PARTICIPANTS: Several classifications based on MRI have been proposed, and their phenotypes are reported to be associated with the severity of adenomyosis. However, a consensus classification based on MRI findings has not yet been reached. Our study was designed to retrospectively analyze data from a cohort of patients in the Affiliated Nanchong Central Hospital of North Sichuan Medical College from June 2017 to December 2021 before focused ultrasound ablation surgery (FUAS), to identify the optimal classification of adenomyosis severity from different classification criteria and explore factors associated with the presence of symptoms. METHODS: The proportions of disease severity among different classification groups were compared to obtain the one generating the most considerable chi-square value, which was identified as the optimal classification for informing disease severity. A logistic regression model was constructed to explore factors associated with disease severity. RESULTS: Classification of Kobayashi H (classification 4) concerning the affected areas and size (volumes of lesions) was recognized as the optimal one, which identified dysmenorrhea (χ2=18.550, p-value=0.002) and menorrhagia (χ2=15.060, p-value=0.010) secondary to adenomyosis. For volumes of uterine wall <2/3, the dysmenorrhea rate in subtype-4 was higher than that in subtype-1 (χ2=4.114, p-value=0.043), and the dysmenorrhea rate in subtype-5 was higher than that in subtype-2 (χ2=4.357, p-value=0.037). Age (OR=0.899, 95%CI=0.810～0.997, p-value=0.044) and external phenotype (OR=3.588, 95%CI=CI 1.018～12.643, p-value=0.047) were associated with dysmenorrhea. Concerning volumes of uterine wall ≥2/3, the menorrhagia rate in subtype-3 remarkably increased compared with that in subtype-6 (χ2=9.776, p-value=0.002), and internal phenotype was identified as an independent factor associated with menorrhagia (OR=1.706, 95%CI=1.131～2.573, p-value=0.011). LIMITATIONS: Patients in our study were all included before FUAS, which limited our result interpretation for the general patient population. CONCLUSIONS: MRI-based classification 4 is identified as an optimal classification for informing the severity of adenomyosis. The phenotype of classification is the main characteristic associated with disease severity.

Magnetic Resonance Imaging-Based Classification Systems for Informing Better Outcomes of Adenomyosis After Ultrasound-Guided High-Intensity Focused Ultrasound Ablating Surgery.

BACKGROUND: A referenced MRI-based classification associated with focused ultrasound ablation surgery (FUAS) outcomes is lacking in adenomyosis. PURPOSE: To identify an MRI-based classification system for informing the FUAS outcomes. STUDY TYPE: Retrospective. POPULATION: Patients with FUAS for adenomyosis, were divided into a training set (N = 643; 355 with post-FUAS gonadotropin-releasing hormone/levonorgestrel, 288 without post-FUAS therapy) and an external validation set (N = 135; all without post-FUAS therapy). FIELD STRENGTH/SEQUENCE: 1.5 T, turbo spin-echo T2-weighted imaging and single-shot echo-planar diffusion-weighted imaging sequences. ASSESSMENT: Five MRI-based adenomyosis classifications: classification 1 (C1) (diffuse, focal, and mild), C2 (intrinsic, extrinsic, intramural, and indeterminate), C3 (internal, adenomyomas, and external), C4 (six subtypes on areas [internal or external] and volumes [<1/3 or ≥2/3]), and C5 (internal [asymmetric or symmetric], external, intramural, full thickness [asymmetric or symmetric]) for FUAS outcomes (symptom relief and recurrence). STATISTICAL TESTS: The optimal classification was significantly associated with the most subtypes of FUAS outcomes. Relating to the timing of recurrence was measured using Cox regression analysis and median recurrence time was estimated by a Kaplan-Meier curve. A P value <0.05 was considered statistically significant. RESULTS: Dysmenorrhea relief and recurrence were only associated with C2 in training patients undergoing FUAS alone. Compared with other subtypes, the extrinsic subtype of C2 was significantly associated with dysmenorrhea recurrence in the FUAS group. Besides, the median dysmenorrhea recurrence time of extrinsic subtype was significantly shorter than that of other subtypes (42.0 months vs. 50.3 months). In the validation cohort, C2 was confirmed as the optimal system and its extrinsic subtype was confirmed to have a significantly shorter dysmenorrhea recurrence time than other subtypes. DATA CONCLUSION: Classification 2 can inform dysmenorrhea relief and recurrence in patients with adenomyosis undergoing FAUS only. Itsextrinsic subtype was associated with an earlier onset of dysmenorrhea recurrence after treatment. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 5.

SORC: an integrated spatial omics resource in cancer.

The interactions between tumor cells and the microenvironment play pivotal roles in the initiation, progression and metastasis of cancer. The advent of spatial transcriptomics data offers an opportunity to unravel the intricate dynamics of cellular states and cell-cell interactions in cancer. Herein, we have developed an integrated spatial omics resource in cancer (SORC, http://bio-bigdata.hrbmu.edu.cn/SORC), which interactively visualizes and analyzes the spatial transcriptomics data in cancer. We manually curated currently available spatial transcriptomics datasets for 17 types of cancer, comprising 722 899 spots across 269 slices. Furthermore, we matched reference single-cell RNA sequencing data in the majority of spatial transcriptomics datasets, involving 334 379 cells and 46 distinct cell types. SORC offers five major analytical modules that address the primary requirements of spatial transcriptomics analysis, including slice annotation, identification of spatially variable genes, co-occurrence of immune cells and tumor cells, functional analysis and cell-cell communications. All these spatial transcriptomics data and in-depth analyses have been integrated into easy-to-browse and explore pages, visualized through intuitive tables and various image formats. In summary, SORC serves as a valuable resource for providing an unprecedented spatially resolved cellular map of cancer and identifying specific genes and functional pathways to enhance our understanding of the tumor microenvironment.

CancerProteome: a resource to functionally decipher the proteome landscape in cancer.

Advancements in mass spectrometry (MS)-based proteomics have greatly facilitated the large-scale quantification of proteins and microproteins, thereby revealing altered signalling pathways across many different cancer types. However, specialized and comprehensive resources are lacking for cancer proteomics. Here, we describe CancerProteome (http://bio-bigdata.hrbmu.edu.cn/CancerProteome), which functionally deciphers and visualizes the proteome landscape in cancer. We manually curated and re-analyzed publicly available MS-based quantification and post-translational modification (PTM) proteomes, including 7406 samples from 21 different cancer types, and also examined protein abundances and PTM levels in 31 120 proteins and 4111 microproteins. Six major analytical modules were developed with a view to describe protein contributions to carcinogenesis using proteome analysis, including conventional analyses of quantitative and the PTM proteome, functional enrichment, protein-protein associations by integrating known interactions with co-expression signatures, drug sensitivity and clinical relevance analyses. Moreover, protein abundances, which correlated with corresponding transcript or PTM levels, were evaluated. CancerProteome is convenient as it allows users to access specific proteins/microproteins of interest using quick searches or query options to generate multiple visualization results. In summary, CancerProteome is an important resource, which functionally deciphers the cancer proteome landscape and provides a novel insight for the identification of tumor protein markers in cancer.

Systematic analysis of DNA methylation-mediated TF dysregulation on lncRNAs reveals critical roles in tumor immunity.

Emerging evidence suggests that DNA methylation affects transcriptional regulation and expression perturbations of long non-coding RNAs (lncRNAs) in cancer. However, a comprehensive investigation into the transcriptional control of DNA methylation-mediated dysregulation of transcription factors (TFs) on lncRNAs has been lacking. Here, we integrated the transcriptome, methylome, and regulatome across 21 human cancers and systematically identified the transcriptional regulation of DNA methylation-mediated TF dysregulations (DMTDs) on lncRNAs. Our findings reveal that TF regulation of lncRNAs is significantly impacted by DNA methylation. Comparative analysis of DMTDs on mRNAs revealed a conserved pattern of TFs involvement. Pan-cancer Methylation TFs (MethTFs) and Methylation LncRNAs (MethLncRNAs) were identified, and were found to be closely associated with cancer hallmarks and clinical features. In-depth analysis of co-expressed mRNAs with pan-cancer MethLncRNAs unveiled frequent disruptions in cancer immunity, particularly in the context of inflammatory response. Furthermore, we identified five immune-related network modules that contribute to immune cell infiltration in cancer. Immune-related subtypes were subsequently classified, characterized by high levels of immune cell infiltration, expression of immunomodulatory genes, and relevant immune cytolytic activity score, major histocompatibility complex score, response to chemotherapy, and prognosis. Our findings provide valuable insights into cancer immunity from the epigenetic and transcriptional regulation perspective.

PHF5A is a potential diagnostic, prognostic, and immunological biomarker in pan-cancer.

Studying the molecular mechanisms and regulatory functions of genes is crucial for exploring new approaches and tactics in cancer therapy. Studies have shown that the aberrant expression of PHF5A in tumors is linked to the origin and advancement of multiple cancers. However, its role in diagnosis, prognosis, and immunological prediction has not been comprehensively investigated in a pan-cancer analysis. Using several bioinformatic tools, we conducted a systematic examination of the potential carcinogenesis of PHF5A in various tumors from multiple aspects. Our analysis indicated that PHF5A expression varied between normal and tumor tissues and was linked to clinical diagnosis and prognosis in various cancers. The results confirmed a notable variation in the levels of PHF5A promoter methylation among several types of primary tumor and normal tissues and methylation of the PHF5A promoter played a guiding role in prognosis in some cancers. According to our findings, PHF5A played a critical role in tumor immunity and it might be an excellent target for anticancer immunotherapy. To sum up, PHF5A can be used in pan-cancer diagnostics, prognostics, and immunotherapy.

Spatial dynamics of pH in the rhizosphere of Leersia hexandra Swartz at different chromium exposure.

The roots of hyperaccumulators can significantly alter soil pH and thus change the chromium (Cr) availability in the rhizosphere. The pH dynamics in the rhizosphere of Cr hyperaccumulator Leersia hexandra Swartz remains unknown. In this study, the spatial dynamics of pH in the rhizosphere of L. hexandra at different Cr exposure were examined using planar optode (PO). The effects of different Cr concentrations on the biomass, physiological parameters, and soil enzyme activity were investigated. The results showed that pH in the rhizosphere of L. hexandra was highly heterogeneous and followed the root shape. There were obvious soil acidification in all groups and the average pH values in the control, Cr50, and Cr100 groups decreased by 0.26, 0.27, and 0.35 pH unit, respectively. At a certain concentration (50 mg kg-1), Cr significantly increased the plant height and biomass of L. hexandra compared to the control (p < 0.05). The concentrations of chlorophyll a, chlorophyll b, and total chlorophyll in the leaves increased with increasing Cr concentrations. The acid phosphatase, urease, and catalase activities in the rhizosphere were higher than those in the bulk soil. These results provide new insights into elucidating the hyperaccumulating mechanism of Cr and improving the phytoremediation efficiency.

Insight into the regulatory mechanism of dynamic chromatin 3D interactions during cardiomyocyte differentiation in human.

Cardiogenesis is an extremely complicated process involved with DNA regulatory elements, and trans factors regulate gene expression pattern spatiotemporally. Enhancers, as the well-known DNA elements, activate target gene expression by transcription factors (TFs) occupied to organize dynamic three-dimensional (3D) interactions, which when affected or interrupted might cause heart defects or diseases. In this study, we integrated transcriptome, 3D genome, and regulatome to reorganize the global 3D genome in cardiomyogenesis, showing a gradually decreased trend of both chromatin interactions and topological associating domains (TADs) during cardiomyocyte differentiation. And almost all of the chromatin interactions occurred within the same or between adjacent TADs involved with enhancers, indicating that dynamical rewiring of enhancer-related chromatin interactions in the continuous expansive TADs is closely correlated to cardiogenesis. Moreover, we found stage-specific interactions activate stage-specific expression to be involved within corresponding biological functions, and the stage-specific combined regulations of enhancers and binding TFs form connected networks to control stage-specific expression and biological processes, which promote cardiomyocyte differentiation. Finally, we identified markers based on regulatory networks, which might drive cardiac development. This study demonstrates the power of enhancer interactome combined with active TFs to reveal insights into transcriptional regulatory networks during cardiomyogenesis.

High-resolution imaging of O2 dynamics and metal solubilization in the rhizosphere of the hyperaccumulator Leersia hexandra Swartz.

The mobilization of trace metals in the rhizosphere can be affected by the redox potential, which is closely related to the O2 dynamics. This study examined the distributions of O2 and trace metals in the rhizosphere of the subaquatic hyperaccumulator Leersia hexandra Swartz under chromium (Cr) stress using planar optodes and the diffusive gradients in thin films technique coupled with laser ablation inductively coupled plasma mass spectrometry. The O2 concentrations and oxidized areas in the rhizosphere significantly increased with increases in the light intensity, air humidity, and atmospheric CO2 concentrations (p < 0.05). The O2 concentration first increased with increasing ambient temperatures, then decreased when the temperature increased from 25 to 32 â„ƒ. The O2 concentration in the rhizosphere was significantly decreased under Cr stress (p < 0.05), with a prolonged response time to the altered ambient temperature. Cr stress led to decreased mobilities of As, Cd, Co, Cr, Cu, Fe, Mn, Mo, Ni, Sb, V, W, and Zn in the rhizosphere, which were negatively correlated with the concentrations of O2. These results provide new insights into the role of changes in the O2 concentration induced by the roots of hyperaccumulator plants in controlling the mobility of trace metals in soils.

The Role of Peroxiredoxins in Cancer Development.

Peroxiredoxins (Prxs) are antioxidant enzymes with ubiquitous expression in human tissues. Prxs are expressed in archaea, bacteria, and eukaryota, often in multiple isoforms. Because of their abundant expression in different cellular organelles and extraordinary sensitivity to H2O2, Prxs are among the first defenses against oxidative stress. Prxs undergo reversible oxidation to disulfides, and some family members perform chaperone or phospholipase functions upon further oxidation. Prxs are upregulated in cancer cells. Research has suggested that Prxs can function as tumor promoters in various cancers. The major objective of this review is to summarize novel findings regarding the roles of Prxs in common cancer types. Prxs have been shown to influence differentiation of inflammatory cells and fibroblasts, remodeling of extracellular matrix, and regulation of stemness. Since aggressive cancer cells have higher intracellular levels of ROS that they can utilize to proliferate and metastasize compared to normal cells, it is critical that we understand the regulation and functions of primary antioxidants such as Prxs. These small but mighty proteins could prove to be key for improving cancer therapeutics and patient survival.

Handgrip Strength and Muscle Quality: Results from the National Health and Nutrition Examination Survey Database.

BACKGROUND: Handgrip strength (HGS) and the appendicular lean mass index (ALMI) are important determinants of sarcopenia. Muscle quality (MQ) is a measure of muscle strength relative to muscle mass. We examined trends in handgrip strength, the appendicular lean mass index, and analyzed their relationship with age, anthropometry, and body composition in a sample of participants in the United States (US). METHODS: This cross-sectional study analyzed data from 14,741 US males (49.7%) and females (50.3%) 6-80 years old who responded to the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014. Dual X-ray absorptiometry was used to measure appendicular skeletal muscle mass. HGS was evaluated using the Takei Digital Grip Strength Dynamometer. Smoothed normative curves for HGS and the ALMI were constructed using a generalized additive model. Multiple regression analyses were used to examine associations of HGS and the ALMI with age, nutrition-related factors, physical activity, and body composition. RESULTS: Mean HGS and the ALMI declined with advancing age. While mean HGS increased with the ALMI, it decreased with the fat mass index. HGS increased in males with an increase in body mass index, energy intake, the ALMI, and vitamins; however, HGS in females increased with albumin, but it had a negative association with the fat mass index and age, but not with increasing adiposity. CONCLUSIONS: HGS and the ALMI change with age: HGS increases with age, then stabilizes and declines; the ALMI increases with age, then stabilizes. In addition, we provide evidence for the effect of anthropometry, nutrition, physical activity, and body composition on HGS and the ALMI in US population.

Loss of Peroxiredoxin IV Protects Mice from Azoxymethane/Dextran Sulfate Sodium-Induced Colorectal Cancer Development.

Peroxiredoxin IV (Prx4), a typical two-cysteine-containing member of the peroxidase family, functions as an antioxidant to maintain cellular redox homeostasis through the reduction of reactive oxygen species (ROS) via cycles of oxidation-reduction reactions. Under oxidative stress, all Prxs including Prx4 are inactivated as their catalytic cysteines undergo hyperoxidation, and hyperoxidized two-cysteine Prxs can be exclusively repaired and revitalized through the reduction cycle catalyzed by sulfiredoxin (Srx). Previously, we showed that Prx4 is a preferred substrate of Srx, and knockout of Srx in mice leads to resistance to azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colon carcinogenesis. To further understand the significance of the Srx/Prx4 axis in colorectal cancer development, Prx4-/- mice were established and subjected to standard AOM/DSS protocol. Compared with wildtype littermates, mice with Prx4-/- genotype had significantly fewer and smaller tumors. Histopathological analysis revealed that loss of Prx4 leads to increased cell death through lipid peroxidation and lower infiltration of inflammatory cells in the knockout tumors compared to wildtype. Treatment with DSS alone also showed decreased infiltration of macrophages and lymphocytes in the colon of knockout mice, suggesting a role for Prx4 in inflammatory response. In addition, loss of Prx4 caused alterations in plasma cytokines and chemokines after DSS and AOM/DSS treatments. These findings suggest that loss of Prx4 protects mice from AOM/DSS-induced colon tumorigenesis. Thus, targeting Prx4 may provide novel strategies for colon cancer prevention and treatment.

Critical Role of the Sulfiredoxin-Peroxiredoxin IV Axis in Urethane-Induced Non-Small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC), the most common type of lung cancer, etiologically associates with tobacco smoking which mechanistically contributes to oxidative stress to facilitate the occurrence of mutations, oncogenic transformation and aberrantly activated signaling pathways. Our previous reports suggested an essential role of Sulfiredoxin (Srx) in promoting the development of lung cancer in humans, and was causally related to Peroxiredoxin IV (Prx4), the major downstream substrate and mediator of Srx-enhanced signaling. To further explore the role of the Srx-Prx4 axis in de novo lung tumorigenesis, we established Prx4-/- and Srx-/-/Prx4-/- mice in pure FVB/N background. Together with wild-type litter mates, these mice were exposed to carcinogenic urethane and the development of lung tumorigenesis was evaluated. We found that disruption of the Srx-Prx4 axis, either through knockout of Srx/Prx4 alone or together, led to a reduced number and size of lung tumors in mice. Immunohistological studies found that loss of Srx/Prx4 led to reduced rate of cell proliferation and less intratumoral macrophage infiltration. Mechanistically, we found that exposure to urethane increased the levels of reactive oxygen species, activated the expression of and Prx4 in normal lung epithelial cells, while knockout of Prx4 inhibited urethane-induced cell transformation. Moreover, bioinformatics analysis found that the Srx-Prx4 axis is activated in many human cancers, and their increased expression is tightly correlated with poor prognosis in NSCLC patients.

Single-cell RNA binding protein regulatory network analyses reveal oncogenic HNRNPK-MYC signalling pathway in cancer.

RNA-binding proteins (RBPs) are key players of gene expression and perturbations of RBP-RNA regulatory network have been observed in various cancer types. Here, we propose a computational method, RBPreg, to identify the RBP regulators by integration of single cell RNA-Seq (N = 233,591) and RBP binding data. Pan-cancer analyses suggest that RBP regulators exhibit cancer and cell specificity and perturbations of RBP regulatory network are involved in cancer hallmark-related functions. We prioritize an oncogenic RBP-HNRNPK, which is highly expressed in tumors and associated with poor prognosis of patients. Functional assays performed in cancer cells reveal that HNRNPK promotes cancer cell proliferation, migration, and invasion in vitro and in vivo. Mechanistic investigations further demonstrate that HNRNPK promotes tumorigenesis and progression by directly binding to MYC and perturbed the MYC targets pathway in lung cancer. Our results provide a valuable resource for characterizing RBP regulatory networks in cancer, yielding potential biomarkers for precision medicine.

ImmCluster: an ensemble resource for immunology cell type clustering and annotations in normal and cancerous tissues.

Single-cell transcriptome has enabled the transcriptional profiling of thousands of immune cells in complex tissues and cancers. However, subtle transcriptomic differences in immune cell subpopulations and the high dimensionality of transcriptomic data make the clustering and annotation of immune cells challenging. Herein, we introduce ImmCluster (http://bio-bigdata.hrbmu.edu.cn/ImmCluster) for immunology cell type clustering and annotation. We manually curated 346 well-known marker genes from 1163 studies. ImmCluster integrates over 420 000 immune cells from nine healthy tissues and over 648 000 cells from different tumour samples of 17 cancer types to generate stable marker-gene sets and develop context-specific immunology references. In addition, ImmCluster provides cell clustering using seven reference-based and four marker gene-based computational methods, and the ensemble method was developed to provide consistent cell clustering than individual methods. Five major analytic modules were provided for interactively exploring the annotations of immune cells, including clustering and annotating immune cell clusters, gene expression of markers, functional assignment in cancer hallmarks, cell states and immune pathways, cell-cell communications and the corresponding ligand-receptor interactions, as well as online tools. ImmCluster generates diverse plots and tables, enabling users to identify significant associations in immune cell clusters simultaneously. ImmCluster is a valuable resource for analysing cellular heterogeneity in cancer microenvironments.

IEAtlas: an atlas of HLA-presented immune epitopes derived from non-coding regions.

Cancer-related epitopes can engage the immune system against tumor cells, thus exploring epitopes derived from non-coding regions is emerging as a fascinating field in cancer immunotherapies. Here, we described a database, IEAtlas (http://bio-bigdata.hrbmu.edu.cn/IEAtlas), which aims to provide and visualize the comprehensive atlas of human leukocyte antigen (HLA)-presented immunogenic epitopes derived from non-coding regions. IEAtlas reanalyzed publicly available mass spectrometry-based HLA immunopeptidome datasets against our integrated benchmarked non-canonical open reading frame information. The current IEAtlas identified 245 870 non-canonical epitopes binding to HLA-I/II allotypes across 15 cancer types and 30 non-cancerous tissues, greatly expanding the cancer immunopeptidome. IEAtlas further evaluates the immunogenicity via several commonly used immunogenic features, including HLA binding affinity, stability and T-cell receptor recognition. In addition, IEAtlas provides the biochemical properties of epitopes as well as the clinical relevance of corresponding genes across major cancer types and normal tissues. Several flexible tools were also developed to aid retrieval and to analyze the epitopes derived from non-coding regions. Overall, IEAtlas will serve as a valuable resource for investigating the immunogenic capacity of non-canonical epitopes and the potential as therapeutic cancer vaccines.

Macrophage migration inhibitory factor levels are associated with disease activity and possible complications in membranous nephropathy.

Membranous nephropathy (MN) is an autoimmune disease characterized by the deposition of immunoglobulin G (IgG) and complementary components in the epithelium of the glomerular capillary wall. Macrophage migration inhibitory factor (MIF) is an inflammatory mediator released by macrophages. MIF plays a key regulatory function in the pathogenesis of immune-mediated glomerulonephritis. This study aimed to investigate whether MIF level could be associated with the activity of MN. Plasma and urine samples from 57 MN patients and 20 healthy controls were collected. The MIF levels in plasma and urine were determined by an enzyme-linked immunosorbent assay (ELISA) kit. The expression of MIF in the renal specimens from 5 MN patients was detected by immunohistochemistry (IHC). The associations of the plasma and urinary levels of MIF and glomerular MIF expression with clinical and pathological characteristics were analyzed. It was revealed that with the increase of MIF levels in plasma and urine, the severity of renal pathological injury in MN patients gradually increased. Correlation analysis showed that the MIF levels in plasma were positively correlated with the platelet (PLT) count (r = 0.302, P = 0.022), and inversely correlated with the prothrombin time (PT) (r = - 0.292, P = 0.028) in MN patients. The MIF levels in plasma were positively correlated with the C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR) (r = 0.651, P < 0.0001; r = 0.669, P < 0.0001) in MN patients. The urinary levels of MIF were positively correlated with ESR (r = 0.562, P < 0.0001). IHC suggested that MIF was expressed in glomerular basement membrane and tubulointerstitial areas. MIF levels in plasma and urine could reflect the severity of MN, and MIF levels in plasma and urine could be associated with venous thrombosis and infectious complications in MN patients. The glomerular MIF expression could be used to indicate the activity of MN.

Triglyceride Glucose-Body Mass Index Is a Reliable Indicator of Bone Mineral Density and Risk of Osteoporotic Fracture in Middle-Aged and Elderly Nondiabetic Chinese Individuals.

(1) Background: This study aimed to investigate the relationship of triglyceride glucose−body mass index (TyG-BMI) with bone mineral density (BMD), femoral neck geometry, and risk of fracture in middle-aged and elderly Chinese individuals. (2) Methods: A total of 832 nondiabetic individuals were selected from the prospective population-based HOPE cohort. All individuals underwent DXA for assessment of BMD at the lumbar spine, femoral neck, and total hip, as well as femoral neck geometry. The 10-year probabilities of both major osteoporotic (MOFs) and hip fractures (HFs) were calculated. (3) Results: Cortical thickness, compression strength index, cross-sectional moment of inertia, cross-sectional area, section modulus, and 25(OH)D levels were significantly lower in women (all p < 0.001). The presence of osteoporosis was related to age, BMI, BMD and femoral neck geometry, TyG-BMI, MOF, and HF. TyG-BMI was positively correlated with BMD. In men, TyG-BMI showed significant negative correlation with HF but not with MOF, the correlation exists only after adjusting for other variables in women. Femoral neck geometries were significantly impaired in individuals with low TyG-BMI. (4) Conclusion: TyG-BMI is positively associated with BMD and geometry, and negatively associated with risk of fracture in nondiabetic middle-aged and elderly Chinese men and women.

Essential Roles of Peroxiredoxin IV in Inflammation and Cancer.

Peroxiredoxin IV (Prx4) is a 2-Cysteine peroxidase with ubiquitous expression in human tissues. Prx4 scavenges hydrogen peroxide and participates in oxidative protein folding in the endoplasmic reticulum. In addition, Prx4 is secreted outside the cell. Prx4 is upregulated in several cancers and is a potential therapeutic target. We have summarized historical and recent advances in the structure, function and biological roles of Prx4, focusing on inflammatory diseases and cancer. Oxidative stress is known to activate pro-inflammatory pathways. Chronic inflammation is a risk factor for cancer development. Hence, redox enzymes such as Prx4 are important players in the crosstalk between inflammation and cancer. Understanding molecular mechanisms of regulation of Prx4 expression and associated signaling pathways in normal physiological and disease conditions should reveal new therapeutic strategies. Thus, although Prx4 is a promising therapeutic target for inflammatory diseases and cancer, further research needs to be conducted to bridge the gap to clinical application.