Computed tomography (CT)-based skeletal muscle vertebral-related index to assess low muscle mass in patients with non-small cell lung cancer.

Background: Patients with lung cancer accompanied by sarcopenia may have a poor prognosis. Normally, low muscle mass associated with sarcopenia is assessed using the skeletal muscle index (SMI). It remains unclear whether the standardized skeletal muscle area (SMA) using 2-dimensional (2D) vertebral metrics (called the skeletal muscle vertebral related index, SMVI) could substitute for SMI when it is missing. The aim of this study was to investigate the feasibility of SMVI as an alternative to SMI, and their associations with overall survival (OS) in patients with non-small cell lung cancer (NSCLC). Methods: In this single-center study, a retrospective analysis was conducted on 433 NSCLC patients who underwent computed tomography (CT) scans. At the third lumbar vertebra (L3) level, measurements were taken for SMA, vertebral body area, transverse vertebral diameter (TVD), longitudinal vertebral diameter (LVD), and vertebral height (VH). The 4 SMVIs were skeletal muscle vertebral ratio (SMVR) (SMA/vertebral body area), skeletal muscle transverse vertebral diameter index (SMTVDI) (SMA/TVD2), skeletal muscle longitudinal vertebral diameter index (SMLVDI) (SMA/LVD2), and skeletal muscle vertebral height index (SMVHI) (SMA/VH2). The patients were categorized into low and high muscle mass groups based on SMI, and the differences in SMVIs between the 2 groups were compared to assess their correlation with SMI. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were utilized to assess the discriminatory ability. Kaplan-Meier curves were employed to compare the survival disparity between the 2 groups. Results: We included 191 male and 242 female patients in this study. Compared to the high muscle mass group, patients in the low muscle mass group exhibited significantly lower SMVR, SMTVDI, SMLVDI, and SMVHI (all P<0.05). All 4 SMVIs showed a positive correlation with SMI, with Spearman correlation coefficients of 0.83, 0.76, 0.75, and 0.67, respectively (all P<0.001). The AUC for diagnosing low muscle mass was higher than 0.8 for all 4 SMVI parameters. The Kaplan-Meier curve revealed that the low-risk group had a better survival probability than the high-risk group in the SMVR, SMTVDI, and SMLVDI. Conclusions: The SMVI functions as an alternative metric for evaluating skeletal muscle mass in the assessment of NSCLC based on SMI.

Association of MRI findings with paraspinal muscles fat infiltration at lower lumbar levels in patients with chronic low back pain: a multicenter prospective study.

OBJECTIVE: In chronic low back pain (CLBP), the relationship between spinal pathologies and paraspinal muscles fat infiltration remains unclear. This study aims to evaluate the relationship between MRI findings and paraspinal muscles morphology and fat infiltration in CLBP patients by quantitative MRI. METHODS: All the CLBP patients were enrolled from July 2021 to December 2022 in four medical institutions. The cross-sectional area (CSA) and proton density fat fraction (PDFF) of the multifidus (MF) and erector spinae (ES) muscles at the central level of the L4/5 and L5/S1 intervertebral discs were measured. MRI findings included degenerative lumbar spondylolisthesis (DLS), intervertebral disc degeneration (IVDD), facet arthrosis, disc bulge or herniation, and disease duration. The relationship between MRI findings and the paraspinal muscles PDFF and CSA in CLBP patients was analyzed. RESULTS: A total of 493 CLBP patients were included in the study (198 females, 295 males), with an average age of 45.68 ± 12.91 years. Our research indicates that the number of MRI findings are correlated with the paraspinal muscles PDFF at the L4/5 level, but is not significant. Moreover, the grading of IVDD is the primary factor influencing the paraspinal muscles PDFF at the L4-S1 level (BES at L4/5=1.845, P < 0.05); DLS was a significant factor affecting the PDFF of MF at the L4/5 level (B = 4.774, P < 0.05). After including age, gender, and Body Mass Index (BMI) as control variables in the multivariable regression analysis, age has a significant positive impact on the paraspinal muscles PDFF at the L4-S1 level, with the largest AUC for ES PDFF at the L4/5 level (AUC = 0.646, cut-off value = 47.5), while males have lower PDFF compared to females. BMI has a positive impact on the ES PDFF only at the L4/5 level (AUC = 0.559, cut-off value = 24.535). CONCLUSION: The degree of paraspinal muscles fat infiltration in CLBP patients is related to the cumulative or synergistic effects of multiple factors, especially at the L4/L5 level. Although age and BMI are important factors affecting the degree of paraspinal muscles PDFF in CLBP patients, their diagnostic efficacy is moderate.

Vertebral bone quality score was associated with paraspinal muscles fat infiltration, but not modic classification in patients with chronic low back pain: a prospective cross-sectional study.

BACKGROUND: The lumbar vertebra and paraspinal muscles play an important role in maintaining the stability of the lumbar spine. Therefore, the aim of this study was to investigate the relationship between paraspinal muscles fat infiltration and vertebral body related changes [vertebral bone quality (VBQ) score and Modic changes (MCs)] in patients with chronic low back pain (CLBP). METHODS: Patients with CLBP were prospectively collected in four hospitals and all patients underwent 3.0T magnetic resonance scanning. Basic clinical information was collected, including age, sex, course of disease (COD), and body mass index (BMI). MCs were divided into 3 types based on their signal intensity on T1 and T2-weighted imaging. VBQ was obtained by midsagittal T1-weighted imaging (T1WI) and calculated using the formula: SIL1-4/SICSF. The Proton density fat fraction (PDFF) values and cross-sectional area (CSA) of paraspinal muscles were measured on the fat fraction map from the iterative decomposition of water and fat with the echo asymmetry and least-squares estimation quantitation (IDEAL-IQ) sequences and in/out phase images at the central level of the L4/5 and L5/S1 discs. RESULTS: This study included 476 patients with CLBP, including 189 males and 287 females. 69% had no Modic changes and 31% had Modic changes. There was no difference in CSA and PDFF for multifidus(MF) and erector spinae (ES) at both levels between Modic type I and type II, all P values>0.05. Spearman correlation analysis showed that VBQ was weakly negatively correlated with paraspinal muscles CSA (all r values < 0.3 and all p values < 0.05), moderately positive correlation with PDFF of MF at L4/5 level (r values = 0.304, p values<0.001) and weakly positively correlated with PDFF of other muscles (all r values<0.3 and all p values<0.001). Multivariate linear regression analysis showed that age (ß = 0.141, p < 0.001), gender (ß = 4.285, p < 0.001) and VBQ (ß = 1.310, p = 0.001) were related to the total PDFF of muscles. For MCs, binary logistic regression showed that the odds ratio values of age, BMI and COD were 1.092, 1.082 and 1.004, respectively (all p values ＜ 0.05). CONCLUSIONS: PDFF of paraspinal muscles was not associated with Modic classification. In addition to age and gender, PDFF of paraspinal muscles is also affected by VBQ. Age and BMI are considered risk factors for the MCs in CLBP patients.

Diffusion-tensor magnetic resonance imaging as a non-invasive assessment of extracellular matrix remodeling in lumbar paravertebral muscles of rats with sarcopenia.

BACKGROUND: Extracellular matrix (ECM) remodeling in skeletal muscle is a significant factor in the development of sarcopenia. This study aims to evaluate changes in ECM remodeling in the lumbar paravertebral muscles of sarcopenic rats using diffusion-tensor magnetic resonance imaging (DT-MRI) and compare them with histology. METHODS: Twenty 6-month-old female Sprague Dawley rats were randomly divided into the dexamethasone (DEX) group and the control (CON) group. Both groups underwent 3.0T MRI scanning, including Mensa, T2WI, and DT-MRI sequences. The changes in muscle fibers and extracellular matrix (ECM) of the erector spinal muscle were observed using hematoxylineosin and sirius red staining. The expressions of collagen I, III, and fibronectin in the erector spinae were detected by western blot. Pearson correlation analysis was employed to assess the correlation between MRI quantitative parameters and corresponding histopathology markers. RESULTS: The cross-sectional area and fractional anisotropy values of the erector spinae in the DEX group rats were significantly lower than those in the CON group (p < 0.05). Hematoxylin eosin staining revealed muscle fiber atrophy and disordered arrangement in the DEX group, while sirius red staining showed a significant increase in collagen volume fraction in the DEX group. The western blot results indicate a significant increase in the expression of collagen I, collagen III, and fibronectin in the DEX group (p < 0.001 for all). Correlation coefficients between fractional anisotropy values and collagen volume fraction, collagen I, collagen III, and fibronectin were - 0.71, -0.94, -0.85, and - 0.88, respectively (p < 0.05 for all). CONCLUSIONS: The fractional anisotropy value is strongly correlated with the pathological collagen volume fraction, collagen I, collagen III, and fibronectin. This indicates that DT-MRI can non-invasively evaluate the changes in extracellular matrix remodeling in the erector spinal muscle of sarcopenia. It provides a potential imaging biomarker for the diagnosis of sarcopenia.

ER calcium depletion as a key driver for impaired ER-to-mitochondria calcium transfer and mitochondrial dysfunction in Wolfram syndrome.

Wolfram syndrome is a rare genetic disease caused by mutations in the WFS1 or CISD2 gene. A primary defect in Wolfram syndrome involves poor ER Ca2+ handling, but how this disturbance leads to the disease is not known. The current study, performed in primary neurons, the most affected and disease-relevant cells, involving both Wolfram syndrome genes, explains how the disturbed ER Ca2+ handling compromises mitochondrial function and affects neuronal health. Loss of ER Ca2+ content and impaired ER-mitochondrial contact sites in the WFS1- or CISD2-deficient neurons is associated with lower IP3R-mediated Ca2+ transfer from ER to mitochondria and decreased mitochondrial Ca2+ uptake. In turn, reduced mitochondrial Ca2+ content inhibits mitochondrial ATP production leading to an increased NADH/NAD+ ratio. The resulting bioenergetic deficit and reductive stress compromise the health of the neurons. Our work also identifies pharmacological targets and compounds that restore Ca2+ homeostasis, enhance mitochondrial function and improve neuronal health.

Advances in the interaction between lumbar intervertebral disc degeneration and fat infiltration of paraspinal muscles: critical summarization, classification, and perspectives.

More than 619 million people in the world suffer from low back pain (LBP). As two potential inducers of LBP, intervertebral disc degeneration (IVDD) and fat infiltration of paraspinal muscles (PSMs) have attracted extensive attention in recent years. So far, only one review has been presented to summarize their relationship and relevant mechanisms. Nevertheless, it has several noticeable drawbacks, such as incomplete categorization and discussion, lack of practical proposals, etc. Consequently, this paper aims to systematically summarize and classify the interaction between IVDD and fat infiltration of PSMs, thus providing a one-stop search handbook for future studies. As a result, four mechanisms of IVDD leading to fat infiltration of PSMs and three mechanisms of fat infiltration in PSMs causing IVDD are thoroughly analyzed and summarized. The typical reseaches are tabulated and evaluated from four aspects, i.e., methods, conclusions, benefits, and drawbacks. We find that IVDD and fat infiltration of PSMs is a vicious cycle that can promote the occurrence and development of each other, ultimately leading to LBP and disability. Finally, eight perspectives are proposed for future in-depth research.

Fecal Carriage of Multidrug-Resistant Organisms Increases the Risk of Hepatic Encephalopathy in Cirrhotic Patients: Insights from Gut Microbiota and Metabolite Features.

Background: Impact of fecal colonization by multidrug-resistant organisms (MDROs) on changes in gut microbiota and associated metabolites, as well as its role in cirrhosis-associated outcomes, has not been thoroughly investigated. Methods: Eighty-eight cirrhotic patients and 22 healthy volunteers were prospectively enrolled with analysis conducted on plasma metabolites, fecal MDROs, and microbiota. Patients were followed for a minimum of one year. Predictive factors for cirrhosis-associated outcomes were identified using Cox proportional hazards regression models, and risk factors for fecal MDRO carriage were assessed using logistic regression model. Correlations between microbiota and metabolic profiles were evaluated through Spearman's rank test. Results: Twenty-nine (33%) cirrhotic patients exhibited MDRO carriage, with a notably higher rate of hepatic encephalopathy (HE) in MDRO carriers (20.7% vs. 3.2%, p = 0.008). Cox regression analysis identified higher serum lipopolysaccharide levels and fecal MDRO carriage as predictors for HE development. Logistic regression analysis showed that MDRO carriage is an independent risk factor for developing HE. Microbiota analysis showed a significant dissimilarity of fecal microbiota between cirrhotic patients with and without MDRO carriage (p = 0.033). Thirty-two metabolites exhibiting significantly different expression levels among healthy controls, cirrhotic patients with and without MDRO carriage were identified. Six of the metabolites showed correlation with specific bacterial taxa expression in MDRO carriers, with isoaustin showing significantly higher levels in MDRO carriers experiencing HE compared to those who did not. Conclusion: Fecal MDRO carriage is associated with altered gut microbiota, metabolite modulation, and an elevated risk of HE occurrence within a year.

Molecular mechanism of Achyranthis bidentatae radix and Morindae officinalis radix in osteoporosis therapy: An investigation based on network pharmacology, molecular docking, and molecular dynamics simulations.

Objective: To investigate the targets and mechanism of Achyranthis bidentatae radix and Morindae officinalis radix (ABR-MOR) for the treatment of osteoporosis (OP) by utilizing network pharmacology, molecular docking technology (MDT) and molecular dynamics simulation (MDS). Methods: The main drug active ingredients (DAIs) and target genes of ABR-MOR were screened by the TCMSP database. The relevant targets of OP were obtained from GeneCards, DisGeNET, and CTD databases. Venny mapping is used to determine the potential target of ABR-MOR in the treatment of OP. The potential targets were analyzed using a protein‒protein interaction network and the MCODE module, and were subjected to GO and KEGG enrichment analysis. The binding sites and conditions of potential key DAIs and core targets were verified through MDT and MDS. Result: The 32 DAIs and 212 targets of ABR-MOR were screened; 1453 OP-related targets were obtained, and 118 targets were mapped. The results of GO and KEGG enrichment analysis showed that the targets of DAIs-OP were mainly enriched in biological processes such as response to hormones, peptides, oxygen levels and reactive oxygen species, and positive regulation of cell migration. The main signaling pathways enriched in the regulation of the immune-inflammatory response, cell proliferation, senescence, apoptosis, angiogenesis, and estrogen signaling pathway. Additionally, the targets were also enriched in bone metabolism-related cell differentiation biological processes and the osteoclast differentiation signaling pathway. MDT and MDS results showed that wogonin, beta-sitosterol, and americanin A, the core DAIs of ABR-MOR, were able to form good ligand‒protein complexes with key targets such as PTGS2, PTGS1, PRKACA, PGR, MAPK1, AKT1, and RELA. Conclusion: This study preliminarily investigated the key targets, biological processes, and signaling pathways involved in the combined application of ABR and MOR for the treatment of OP. The results revealed that ABR-MOR may play a therapeutic role mainly by regulating immune-inflammatory responses, cellular biological processes, and osteoblast differentiation, which provides a theoretical basis for further experimental validation and a new strategy for the treatment of OP.

An experimental study for quantitative assessment of fatty infiltration and blood flow perfusion in quadriceps muscle of rats using IDEAL-IQ and BOLD-MRI for early diagnosis of sarcopenia.

BACKGROUND: Severe sarcopenia may result in severe disability. Early diagnosis is currently the key to enhancing the treatment of sarcopenia, and there is an urgent need for a highly sensitive and dependable tool to evaluate the course of early sarcopenia in clinical practice. This study aims to investigate longitudinally the early diagnosability of magnetic resonance imaging (MRI)-based fat infiltration and blood flow perfusion technology in sarcopenia progression. METHODS: 48 Sprague-Dawley rats were randomly assigned into six groups that were based on different periods of dexamethasone (DEX) injection (0, 2, 4, 6, 8, 10 days). Multimodal MRI was scanned to assess muscle mass. Grip strength and swimming exhaustion time of rats were measured to assess muscle strength and function. Immunofluorescence staining for CD31 was employed to assess skeletal muscle capillary formation, and western blot was used to detect vascular endothelial growth factor-A (VEGF-A) and muscle ring finger-1 (MuRF-1) protein expression. Subsequently, we analyzed the correlation between imaging and histopathologic parameters. A receiver operating characteristic (ROC) analysis was conducted to assess the effectiveness of quantitative MRI parameters for discriminating diagnosis in both pre- and post-modeling of DEX-induced sarcopenic rats. RESULTS: Significant differences were found in PDFF, R2* and T2 values on day 2 of DEX-induction compared to the control group, occurring prior to the MRI-CSA values and limb grip strength on day 6 of induction and swimming exhaustion time on day 8 of induction. There is a strong correlation between MRI-CSA with HE-CSA values (r = 0.67; p < 0.001), oil red O (ORO) area with PDFF (r = 0.67; p < 0.001), microvascular density (MVD) (r = -0.79; p < 0.001) and VEGF-A (r = -0.73; p < 0.001) with R2*, MuRF-1 with MRI-CSA (r = -0.82; p < 0.001). The AUC of PDFF, R2*, and T2 values used for modeling evaluation are 0.81, 0.93, and 0.98, respectively. CONCLUSION: Imaging parameters PDFF, R2*, and T2 can be used to sensitively evaluate early pathological changes in sarcopenia. The successful construction of a sarcopenia rat model can be assessed when PDFF exceeds 1.25, R2* exceeds 53.85, and T2 exceeds 33.88.

A Novel PTH-Related Peptide Combined With 3D Printed Macroporous Titanium Alloy Scaffold Enhances Osteoporotic Osseointegration.

Previous parathyroid hormone (PTH)-related peptides (PTHrPs) cannot be used to prevent implant loosening in osteoporosis patients due to the catabolic effect of local sustained release. A novel PTHrP (PTHrP-2) that can be used locally to promote osseointegration of macroporous titanium alloy scaffold (mTAS) and counteract implant slippage in osteoporosis patients is designed. In vitro, PTHrP-2 enhances the proliferation, adhesion, and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) within the mTAS. Further, it promotes proliferation, migration, angiogenesis-related protein expression, and angiogenesis in human umbilical vein endothelial cells (HUVECs). Compared to PTH(1-34), PTHrP-2 can partially weaken the osteoclast differentiation of RAW 264.7 cells. Even in an oxidative stress microenvironment, PTHrP-2 safeguards the proliferation and migration of BMSCs and HUVECs, reduces reactive oxygen species generation and mitochondrial damage, and partially preserves the angiogenesis of HUVECs. In the Sprague-Dawley (SD) rat osteoporosis model, the therapeutic benefits of PTHrP-2-releasing mTAS (mTASP2 ) and ordinary mTAS implanted for 12 weeks via micro-CT, sequential fluorescent labeling, and histology are compared. The results demonstrate that mTASP2 exhibits high bone growth rate, without osteophyte formation. Consequently, PTHrP-2 exhibits unique local synthesis properties and holds the potential for assisting the osseointegration of alloy implants in osteoporosis patients.

Multidimensional risk factor analysis of acute low back pain progressing to chronicity: a longitudinal cohort study protocol.

Introduction: Approximately 40% of patients with acute low back pain (LBP) develop chronic low back pain, which significantly increases the risk of poor prognosis. To reduce the risk of acute LBP becoming chronic, effective preventive strategies are needed. Early identification of risk factors for the development of chronic LBP can help clinicians choose appropriate treatment options and improve patient outcomes. However, previous screening tools have not considered medical imaging findings. The aim of this study is to identify factors that can predict the risk of acute LBP becoming chronic based on clinical information, pain and disability assessment, and MRI imaging findings. This protocol describes the methodology and plan for investigating multidimensional risk factors for acute LBP becoming chronic, in order to better understand the development of acute LBP and prevent chronic LBP. Methods: This is a prospective multicenter study. We plan to recruit 1,000 adult patients with acute low back pain from four centers. In order to select four representative centers, we find the larger hospitals from different regions in Yunnan Province. The study will use a longitudinal cohort design. Patients will undergo baseline assessments upon admission and will be followed up for 5 years to collect the time of chronicity and associated risk factors. Upon admission, patients will be collected detailed demographic information, subjective and objective pain scores, disability scale, and lumbar spine MRI scanning. In addition, patient's medical history, lifestyle, psychological factors will be collected. Patients will be followed up at 3 months, 6 months, 1 year, 2 years and up for 5 years after admission to collect the time of chronicity and associated factors. Multivariate analysis will be used to explore the multidimensional risk factors affecting the chronicity of acute LBP patients (such as age, gender, BMI, degree of intervertebral disc degeneration, etc.), and survival analysis will be performed to explore the impact of each factor on the time of chronicity. Ethics and dissemination: The study has been approved by the institutional research ethics committee of each study center (main center number: 2022-L-305). Results will be disseminated through scientific conferences and peer-reviewed publications, as well as meetings with stakeholders.

Functional magnetic resonance imaging reveals dysfunction of the paraspinal muscles in patients with chronic low back pain: a cross-sectional study.

Background: Patients with chronic low back pain (CLBP) undergo structural changes of the paraspinal muscles; however, it is unclear if functional changes also occur. This study aimed to examine the metabolic and perfusion function changes in the paraspinal muscles of patients with CLBP as indirectly reflected by blood oxygen level-dependent (BOLD) imaging and T2 mapping. Methods: All participants were consecutively enrolled at our local hospital from December 2019 to November 2020. Patients were diagnosed with CLBP in the outpatient clinic, and asymptomatic participants were considered to be those with no CLBP or other diseases. This study was not registered on a clinical trial platform. Participants underwent BOLD imaging and T2 mapping scans at the L4-S1 disc level. The effective transverse relaxation rate (R2* values) and transverse relaxation time (T2 values) of the paraspinal muscles were measured on the central plane of the L4/5 and L5/S1 intervertebral discs. Finally, the independent samples t-test was used to assess the differences in R2* and T2 values between the 2 groups, while Pearson correlation analysis was used to determine their correlation with age. Results: A total of 60 patients with CLBP and 20 asymptomatic participants were enrolled. The paraspinal muscles of the CLBP group had higher total R2* values [46.7±2.9 vs. 44.0±2.9 s-1; 95% confidence interval (CI): 1.2-4.2; P=0.001] and lower total T2 values (45.4±4.2 vs. 47.1±3.7 ms; 95% CI: -3.8 to 0.4; P=0.109) than did the asymptomatic participants. For the different muscles, R2* values for the erector spinae (ES) (L4/5: 45.5±2.6 vs. 43.0±3.0 s-1, 95% CI: 1.1-4.0, P=0.001; L5/S1: 48.5±4.9 vs. 45.9±4.2 s-1; 95% CI: 0.2-5.1; P=0.035) and the R2* values of the multifidus (MF) muscles (L4/5: 46.4±2.9 vs. 43.7±3.5 s-1, 95% CI: 1.1-4.3, P=0.001; L5/S1: 46.3±3.5 vs. 42.5±2.8 s-1, 95% CI: 2.1-5.5, P<0.001) of the CLBP group at both spinal levels were higher than those of the asymptomatic participants. In the patients with CLBP, the R2* values at the L4/5 (45.9±2.1 s-1) were lower than those at the L5/S1 (47.4±3.6 s-1; 95% CI: -2.6 to -0.4; P=0.007). The R2* values were positively correlated with age in both groups (CLBP group: r=0.501, 95% CI: 0.271-0.694, P<0.001; asymptomatic group: r=0.499, 95% CI: -0.047 to 0.771; P=0.025). Conclusions: The R2* values were higher in the paraspinal muscles of patients with CLPB and may suggest metabolic and perfusion dysfunction of the paraspinal muscles in these patients.

Sequential multi-parametric MRI in assessment of the histological subtype and features in the malignant pleural mesothelioma xenografts.

Objective: It is still a challenge to find a noninvasive technique to distinguish the histological subtypes of malignant pleural mesothelioma (MPM) and characterize the development of related histological features. We investigated the potential value of multiparametric MRI in the assessment of the histological subtype and development of histologic features in the MPM xenograft model. Methods: MPM xenograft models were developed by injecting tumour cells into the right axillary space of nude mice. The T1, T2, R2*, T2*, apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo diffusion coefficient (D*), and perfusion fraction (f) at 14 d, 28 d, and 42 d were measured and compared between the epithelial and biphasic MPM. Correlations between multiparametric MRI parameters and histologic features, including necrotic fraction (NF) and microvessel density (MVD), were analysed. Results: This study found that T2, T2* and IVIM-DWI parameters can reflect the spatial and temporal heterogeneity of MPM. Compared to the epithelial MPM, T2 and T2* were higher and ADC, D, D*, and f were lower in the biphasic MPM (P < 0.05). MRI parameters were different in different stages of epithelial and biphasic MPM. Moderate correlations were found between ADC and tumor volume and NF in the epithelial MPM, and there was a correlation between f and tumor volume and NF and MVD in the two groups. Conclusion: MRI parameters changed with tumor progression in a xenograft model of MPM. MRI parameters may provide useful biomarkers for evaluating the histological subtype and histological features development of MPM.

Sebacic Acid as a Potential Age-Related Biomarker of Liver Aging: Evidence Linking Mice and Human.

The aging process is complicated and involves diverse organ dysfunction; furthermore, the biomarkers that are able to reflect biological aging are eagerly sought after to monitor the system-wide decline associated with the aging process. To address this, we performed a metabolomics analysis using a longitudinal cohort study from Taiwan (N = 710) and established plasma metabolomic age using a machine learning algorithm. The resulting estimation of age acceleration among the older adults was found to be correlated with HOMA-insulin resistance. In addition, a sliding window analysis was used to investigate the undulating decrease in hexanoic and heptanoic acids that occurs among the older adults at different ages. A comparison of the metabolomic alterations associated with aging between humans and mice implied that ω-oxidation of medium-chain fatty acids was commonly dysregulated in older subjects. Among these fatty acids, sebacic acid, an ω-oxidation product produced by the liver, was significantly decreased in the plasma of both older humans and aged mice. Notably, an increase in the production and consumption of sebacic acid within the liver tissue of aged mice was observed, along with an elevation of pyruvate-to-lactate conversion. Taken together, our study reveals that sebacic acid and metabolites of ω-oxidation are the common aging biomarkers in both humans and mice. The further analysis suggests that sebacic acid may play an energetic role in supporting the production of acetyl-CoA during liver aging, and thus its alteration in plasma concentration potentially reflects the aging process.

From collapse to the health of the aquatic ecosystem in Dasha River (2006-2021): a case study of Shenzhen city in the Guangdong-Hong Kong-Macao Greater Bay Area, China.

Compared with the aquatic ecosystem destruction caused by rapid urban development, substantial ecological restoration usually requires long periods and is a challenging process. Although river ecological restoration has been successful in different regions, the relationship between biodiversity, water quality, and effective measures applicable to developing countries remains poorly understood. This study was conducted in the Dasha River in Shenzhen city, one of the fastest-growing cities in China. The rehabilitation measures were sorted out in four phases to study the impact on water quality and biodiversity. In response, three campaigns were carried out to take phytoplankton, zooplankton, and benthos samples within the last three engineering stages, in 2007, 2012, and 2021. Synchronized investigations of water quality were conducted monthly from 2006 to 2021. Our analysis showed that the biodiversity of benthos has improved in recent years, which marks a turnaround for the aquatic ecological environment. According to the Hilsenhoff family biotic index (FBI), the water quality level in the 2021 campaign was promoted to "Good" in the downstream and "Fair" in the upper and middle streams. By analyzing Pearson's correlations between response ratios of water quality parameters and the Shannon-Wiener index of phytoplankton, zooplankton, and benthos, we concluded that biodiversity is significantly related to water quality. Specifically, the biodiversity of zooplankton is associated with ammonia nitrogen (NH3-N) (R2 = - 0.77, P < 0.05), and benthos diversity is strongly negatively correlated with NH3-N, total nitrogen, chemical oxygen demand, and biochemical oxygen demand (R2 ≥ -0.82, P < 0.01). Despite the temporary negative impact of along-river interception on aquatic organisms in the campaign of 2012, the measures quickly and effectively improved water quality, which is the foundation for biodiversity improvement in 2021. This study provides insights into relationships among biodiversity, water quality, and regulation projects and can offer a reference for selecting aquatic ecosystem restoration measures in developing areas.

Low thigh muscle strength in relation to myosteatosis in patients with type 2 diabetes mellitus.

This study aimed to investigate the association of thigh muscle fat infiltration by quantitative MRI with muscle strength in patients with type 2 diabetes mellitus (T2DM). Seventy T2DM patients and sixty control subjects (71 males; age: 52 ± 8 years) underwent 3.0T MRI and isokinetic muscle strength measurements to obtain the skeletal muscle index (SMI), intermuscular adipose tissue (IMAT) proton density fat fraction (PDFF), intramuscular fat (IMF) PDFF, peak torque (PT) and total work (TW) of knee extensors and flexors. The differences of measurements between T2DM patients and asymptomatic volunteers were compared. Multivariate regression analysis was used to determine significant predictors of thigh extension and flexion strength. The SMI, IMAT and IMF PDFF of thigh muscles in T2DM patients were higher than that in the control group (p < 0.001), while PT and TW were lower than those in the control subjects (p < 0.05). Both IMF and IMAT PDFF were negatively correlated with PT, TW in participants with T2DM (extensors: r = - 0.72, - 0.70, p < 0.001; r = - 0.62, - 0.56, p < 0.05. flexors: r = - 0.37, - 0.43, p < 0.05; r = - 0.39, - 0.46, p < 0.05). Moderate and strong correlations between HOMA-IR and muscle strength measurements, muscle PDFFs were observed in extensors and flexors. IMF PDFF and age were the statistically significant predictor of PT and TW of extensors of thigh in multivariate regression analysis. Therefore, the thigh muscle PDFF increased was associated with muscle strength decreased in T2DM patients beyond SMI. Age are also important factors influencing thigh muscle PDFF and strength in T2DM patients.

Anti-tumor necrosis factor-α is potentially better than tumor necrosis factor-α as the biomarker for sarcopenia: Results from the I-Lan longitudinal aging study.

Tumor necrosis factor (TNF)-α is a proinflammatory cytokine involved in the pathogenesis of sarcopenia, but its short half-life and inconsistent reproducibility limit the potential of TNF-α to be an ideal sarcopenia biomarker. Anti-TNF-α, a natural consequent autoantibody to TNF-α, is an indicator of relatively prolonged TNF-α exposure, has more stable concentrations than TNF-α and should be a better alternative as a biomarker of sarcopenia. Data from 484 participants from the I-Lan Longitudinal Aging Study were used for this study, and sarcopenia was defined by the Asian Working Group for Sarcopenia 2019 consensus. Plasma levels of anti-TNF-α were determined by a sandwich ELISA approach, and levels of TNF-α were determined by an immunoassay. Compared to nonsarcopenic participants, 43 sarcopenic participants had higher levels of anti-TNF-α (0.73 ± 0.19 vs. 0.79 ± 0.25 OD, p = 0.045). Plasma levels of anti-TNF-α were positively correlated with TNF-α (r = 0.24, p < 0.001), and plasma levels of anti-TNF-α were positively correlated with adiposity (r = 0.16, p < 0.001) and negatively correlated with lean body mass (r = -0.14, p = 0.003). Individuals with increasing levels of anti-TNF-α had higher odds of being sarcopenic (OR 5.4, 95 % CI: 1.1-25.8, p = 0.035), and these associations were stronger among women and younger adults. An association between TNF-α and sarcopenia was noted only in middle-aged adults (OR 6.2, 95 % CI: 1.8-21.7, p = 0.004). Plasma anti-TNF-α levels were positively correlated with TNF-α and were significantly associated with sarcopenia. Anti-TNF-α may be a more appropriate biomarker than TNF-α for sarcopenia, but further investigations are needed to confirm its roles in sarcopenia diagnosis and treatment response evaluation.