Role of integrin ß1 and tenascin C mediate TGF-SMAD2/3 signaling in chondrogenic differentiation of BMSCs induced by type I collagen hydrogel.

Cartilage defects may lead to severe degenerative joint diseases. Tissue engineering based on type I collagen hydrogel that has chondrogenic potential is ideal for cartilage repair. However, the underlying mechanisms of chondrogenic differentiation driven by type I collagen hydrogel have not been fully clarified. Herein, we explored potential collagen receptors and chondrogenic signaling pathways through bioinformatical analysis to investigate the mechanism of collagen-induced chondrogenesis. Results showed that the super enhancer-related genes induced by collagen hydrogel were significantly enriched in the TGF-ß signaling pathway, and integrin-ß1 (ITGB1), a receptor of collagen, was highly expressed in bone marrow mesenchymal stem cells (BMSCs). Further analysis showed genes such as COL2A1 and Tenascin C (TNC) that interacted with ITGB1 were significantly enriched in extracellular matrix (ECM) structural constituents in the chondrogenic induction group. Knockdown of ITGB1 led to the downregulation of cartilage-specific genes (SOX9, ACAN, COL2A1), SMAD2 and TNC, as well as the downregulation of phosphorylation of SMAD2/3. Knockdown of TNC also resulted in the decrease of cartilage markers, ITGB1 and the SMAD2/3 phosphorylation but overexpression of TNC showed the opposite trend. Finally, in vitro and in vivo experiments confirmed the involvement of ITGB1 and TNC in collagen-mediated chondrogenic differentiation and cartilage regeneration. In summary, we demonstrated that ITGB1 was a crucial receptor for chondrogenic differentiation of BMSCs induced by collagen hydrogel. It can activate TGF-SMAD2/3 signaling, followed by impacting TNC expression, which in turn promotes the interaction of ITGB1 and TGF-SMAD2/3 signaling to enhance chondrogenesis. These may provide concernful support for cartilage tissue engineering and biomaterials development.

Songorine modulates macrophage polarization and metabolic reprogramming to alleviate inflammation in osteoarthritis.

Introduction: Osteoarthritis (OA) is a prevalent joint disorder characterized by multifaceted pathogenesis, with macrophage dysregulation playing a critical role in perpetuating inflammation and joint degeneration. Methods: This study focuses on Songorine, derived from Aconitum soongaricum Stapf, aiming to unravel its therapeutic mechanisms in OA. Comprehensive analyses, including PCR, Western blot, and immunofluorescence, were employed to evaluate Songorine's impact on the joint microenvironment and macrophage polarization. RNA-seq analysis was conducted to unravel its anti-inflammatory mechanisms in macrophages. Metabolic alterations were explored through extracellular acidification rate monitoring, molecular docking simulations, and PCR assays. Oxygen consumption rate measurements were used to assess mitochondrial oxidative phosphorylation, and Songorine's influence on macrophage oxidative stress was evaluated through gene expression and ROS assays. Results: Songorine effectively shifted macrophage polarization from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype. Notably, Songorine induced metabolic reprogramming, inhibiting glycolysis and promoting mitochondrial oxidative phosphorylation. This metabolic shift correlated with a reduction in macrophage oxidative stress, highlighting Songorine's potential as an oxidative stress inhibitor. Discussion: In an in vivo rat model of OA, Songorine exhibited protective effects against cartilage damage and synovial inflammation, emphasizing its therapeutic potential. This comprehensive study elucidates Songorine's multifaceted impact on macrophage modulation, metabolic reprogramming, and the inflammatory microenvironment, providing a theoretical foundation for its therapeutic potential in OA.

Insights into the coexistence of birds and humans in cropland through meta-analyses of bird exclosure studies, crop loss mitigation experiments, and social surveys.

Birds share lands with humans at a substantial scale and affect crops. Yet, at a global scale, systematic evaluations of human-bird coexistence in croplands are scarce. Here, we compiled and used meta-analysis approaches to synthesize multiple global datasets of ecological and social dimensions to understand this complex coexistence system. Our result shows that birds usually increase woody, but not herbaceous, crop production, implying that crop loss mitigation efforts are critical for a better coexistence. We reveal that many nonlethal technical measures are more effective in reducing crop loss, e.g., using scaring devices and changing sow practices, than other available methods. Besides, we find that stakeholders from low-income countries are more likely to perceive the crop losses caused by birds and are less positive toward birds than those from high-income ones. Based on our evidence, we identified potential regional clusters, particularly in tropical areas, for implementing win-win coexistence strategies. Overall, we provide an evidence-based knowledge flow and solutions for stakeholders to integrate the conservation and management of birds in croplands.

Biomonitoring trace metal contamination in Guangzhou urban parks using Asian tramp snails (Bradybaena similaris).

Anthropogenic activities have caused environmental metal contamination in urban areas. Biomonitoring using organisms such as invertebrates can evaluate metal pollution, supplementing chemical monitoring, which cannot comprehensively reflect how metals influence organisms in the urban environment. To assess metal contamination in Guangzhou urban parks and its source, Asian tramp snails (Bradybaena similaris) were collected from ten parks in Guangzhou in 2021. The metal concentrations (Al, Cd, Cu, Fe, Mn, Pb, and Zn) were measured by ICP-AES and ICP-MS. We evaluated the metal distribution characteristics and correlations among metals. The probable sources of metals were determined by the positive matrix factorization (PMF) model. The metal pollution levels were analysed using the pollution index and the Nemerow comprehensive pollution index. The mean metal concentrations were ranked Al > Fe > Zn > Cu > Mn > Cd > Pb; metal pollution level in the snails was ranked Al > Mn > CuFe > Cd > Zn > Pb. Pb-Zn-Al-Fe-Mn and Cd-Cu-Zn were positively correlated in all samples. Six major metal sources were identified: an Al-Fe factor corresponding to crustal rock and dust, an Al factor related to Al-containing products, a Pb factor indicative of traffic and industries, a Cu-Zn-Cd factor dominated by the electroplating industry and vehicle sources, an Mn factor reflecting fossil fuel combustion, and a Cd-Zn factor related to agricultural product use. The pollution evaluation suggested heavy Al pollution, moderate Mn pollution, and light Cd, Cu, Fe, Pb, and Zn pollution in the snails. Dafushan Forest Park was heavily polluted; Chentian Garden and Huadu Lake National Wetland Park were not widely contaminated. The results indicated that B. similaris snails can be used as effective biomarkers for monitoring and evaluating environmental metal pollution in megacity urban areas. The findings show that snail biomonitoring provides a valuable understanding of the migration and accumulation pathways of anthropogenic metal pollutants in soil‒plant-snail food chains.

Liquid chromatography-mass spectrometry-based metabolomic profiling reveals sex differences of lipid metabolism among the elderly from Southwest China.

BACKGROUND: The sexual dimorphism represents one of the triggers of the metabolic disparities while the identification of sex-specific metabolites in the elderly has not been achieved. METHODS: A group of aged healthy population from Southwest China were recruited and clinical characteristics were collected. Fasting plasma samples were obtained and untargeted liquid chromatography-mass spectrometry-based metabolomic analyses were performed. Differentially expressed metabolites between males and females were identified from the metabolomic analysis and metabolite sets enrichment analysis was employed. RESULTS: Sixteen males and fifteen females were finally enrolled. According to clinical characteristics, no significant differences can be found except for smoking history. There were thirty-six differentially expressed metabolites between different sexes, most of which were lipids and lipid-like molecules. Twenty-three metabolites of males were increased while thirteen were decreased compared with females. The top four classes of metabolites were fatty acids and conjugates (30.6%), glycerophosphocholines (22.2%), sphingomyelins (11.1%), and flavonoids (8.3%). Fatty acids and conjugates, glycerophosphocholines, and sphingomyelins were significantly enriched in metabolite sets enrichment analysis. CONCLUSIONS: Significant lipid metabolic differences were found between males and females among the elderly. Fatty acids and conjugates, glycerophosphocholines, and sphingomyelins may partly account for sex differences and can be potential treatment targets for sex-specific diseases.

Early Perihematomal Edema Expansion: Definition, Significance, and Association with Outcomes after Intracerebral Hemorrhage.

OBJECTIVE: To investigate the association between early perihematomal edema (PHE) expansion and functional outcome in patients with intracerebral hemorrhage (ICH). METHODS: Patients with ICH who underwent initial computed tomography (CT) scans within 6 hours after the onset of symptoms and follow-up CT scans within 24 ± 12 hours were included. Absolute PHE increase was defined as the absolute increase in PHE volume from baseline to 24 hours. A receiver-operating characteristic (ROC) curve was generated to determine the cutoff value for early PHE expansion, which was operationally defined as an absolute increase in PHE volume of >6 mL. The outcome of interest was 3-month poor outcome defined as modified Rankin scale score of ≥4. A multivariable logistic regression procedure was used to assess the association between early PHE expansion and outcome after ICH. RESULTS: In 233 patients with ICH, 89 (38.2%) patients had poor outcome at 3-month follow-up. Early PHE expansion was observed in 56 of 233 (24.0%) patients. Patients with early PHE expansion were more likely to have poor functional outcome than those without (43.8% vs. 11.8%, p < 0.001). After adjusting for age, admission systolic blood pressure, admission Glasgow Coma Scale score, baseline ICH volume and the presence of intraventricular hemorrhage, and time from onset to CT, early PHE expansion was associated with poor outcome (adjusted odds ratio, 4.25; 95% confidence interval, 1.70-10.60; p = 0.002). CONCLUSIONS: The early PHE expansion was not uncommon in patients with ICH and was correlated with poor outcome following ICH.

Serum Butyrylcholinesterase Activity: A Biomarker for Parkinson's Disease and Related Dementia.

OBJECTIVE: This study aim to determine changes of serum butyrylcholinesterase (BChE) activity in PD patients and related dementia. PATIENTS AND METHODS: Consecutive PD patients and healthy controls were included and clinical data were collected. Fast serum BChE activity was determined and compared between healthy controls and PD patients. Independent risk factors were performed for BChE activity, PD, and related dementia. The relationship between BChE activity and disease severity was also evaluated. Receiver operating characteristic (ROC) curves were obtained to explore serum BChE activity in distinguishing PD patients and related dementia. RESULTS: Serum BChE activity mainly independently correlated with gender, albumin, triglyceride, body mass index, and PD. Serum BChE activity decreased in PD patients compared with healthy controls. Based on the ROC curve, the optimal cut-off point was 6864.08 IU/L for distinguishing PD patients, and the sensitivity and specificity values were 61.8% and 72.1%. It inversely correlated with Unified Parkinson's Disease Rating Scale score. BChE activity decreased in PD-related dementia compared with those without dementia. The sensitivity and specificity values were 70.6% and 76.3%, respectively, with an optimal cut-off point of 6550.00 IU/L. CONCLUSIONS: Serum BChE activity can be regarded as a biomarker for PD and related dementia.

Cerebrovascular risk factors for patients with cerebral watershed infarction: A case-control study based on computed tomography angiography in a population from Southwest China.

To determine cerebrovascular risk factors for patients with cerebral watershed infarction (CWI) from Southwest China.Patients suffering from acute ischemic stroke were categorized into internal CWI (I-CWI), external CWI (E-CWI), or non-CWI (patients without CWI) groups. Clinical data were collected and degrees of steno-occlusion of all cerebral arteries were scored. Arteries associated with the circle of Willis were also assessed. Data were compared using Pearson chi-squared tests for categorical data and 1-way analysis of variance with Bonferroni post hoc tests for continuous data, as appropriate. Multivariate binary logistic regression analysis was performed to determine independent cerebrovascular risk factors for CWI.Compared with non-CWI, I-CWI had higher degrees of steno-occlusion of the ipsilateral middle cerebral artery, ipsilateral carotid artery, and contralateral middle cerebral artery. E-CWI showed no significant differences. All the 3 arteries were independent cerebrovascular risk factors for I-CWI confirmed by multivariate binary logistic regression analysis. I-CWI had higher degrees of steno-occlusion of the ipsilateral middle cerebral artery compared with E-CWI. No significant differences were found among arteries associated with the circle of Willis.The ipsilateral middle cerebral artery, carotid artery, and contralateral middle cerebral artery were independent cerebrovascular risk factors for I-CWI. No cerebrovascular risk factor was identified for E-CWI.

Blend Sign on Computed Tomography: Novel and Reliable Predictor for Early Hematoma Growth in Patients With Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Early hematoma growth is not uncommon in patients with intracerebral hemorrhage and is an independent predictor of poor functional outcome. The purpose of our study was to report and validate the use of our newly identified computed tomographic (CT) blend sign in predicting early hematoma growth. METHODS: Patients with intracerebral hemorrhage who underwent baseline CT scan within 6 hours after onset of symptoms were included. The follow-up CT scan was performed within 24 hours after the baseline CT scan. Significant hematoma growth was defined as an increase in hematoma volume of >33% or an absolute increase of hematoma volume of >12.5 mL. The blend sign on admission nonenhanced CT was defined as blending of hypoattenuating area and hyperattenuating region with a well-defined margin. Univariate and multivariable logistic regression analyses were performed to assess the relationship between the presence of the blend sign on nonenhanced admission CT and early hematoma growth. RESULTS: A total of 172 patients were included in our study. Blend sign was observed in 29 of 172 (16.9%) patients with intracerebral hemorrhage on baseline nonenhanced CT scan. Of the 61 patients with hematoma growth, 24 (39.3%) had blend sign on admission CT scan. Interobserver agreement for identifying blend sign was excellent between the 2 readers (κ=0.957). The multivariate logistic regression analysis demonstrated that the time to baseline CT scan, initial hematoma volume, and presence of blend sign on baseline CT scan to be independent predictors of early hematoma growth. The sensitivity, specificity, positive and negative predictive values of blend sign for predicting hematoma growth were 39.3%, 95.5%, 82.7%, and 74.1%, respectively. CONCLUSIONS: The CT blend sign could be easily identified on regular nonenhanced CT and is highly specific for predicting hematoma growth.

Intraventricular Hemorrhage and Early Hematoma Expansion in Patients with Intracerebral Hemorrhage.

Intraventricular hemorrhage is associated with poor functional outcomes in patients with intracerebral hemorrhage (ICH). We aimed to investigate the association between intraventricular hemorrhage and early hematoma expansion in patients with ICH. Patients with ICH who underwent a baseline CT scan within six hours after onset of symptoms were included. The follow-up CT scan was performed within 24 hours after the baseline CT scan. Univariate and multivariable logistic regression were used to assess the relationship between presence of intraventricular hemorrhage and early hematoma expansion. A total of 160 patients were included in the study. Significant hematoma growth was observed in 52 (32.5%) patients presenting within six hours after onset of symptoms. Intraventricular hemorrhage was observed in 66 (41.25%) patients with ICH. Multivariate analyses demonstrated that a short time from onset to baseline CT scan, the initial hematoma volume, and the presence of intraventricular hemorrhage on follow-up CT scan were independently associated with hematoma enlargement. The presence of intraventricular hemorrhage on follow-up CT scan can be associated with hematoma expansion in patients with ICH.

A novel urinary metabolite signature for diagnosing major depressive disorder.

Major depressive disorder (MDD) is a prevalent and debilitating mental disorder. Yet, there are no objective biomarkers available to support diagnostic laboratory testing for this disease. Here, gas chromatography-mass spectrometry was applied to urine metabolic profiling of 126 MDD and 134 control subjects. Orthogonal partial least-squares discriminant analysis (OPLS-DA) was used to identify the differential metabolites in MDD subjects relative to healthy controls. The OPLS-DA analysis of data from training samples (82 first-episode, drug-naïve MDD subjects and 82 well-matched healthy controls) showed that the depressed group was significantly distinguishable from the control group. Totally, 23 differential urinary metabolites responsible for the discrimination between the two groups were identified. Postanalysis, 6 of the 23 metabolites (sorbitol, uric acid, azelaic acid, quinolinic acid, hippuric acid, and tyrosine) were defined as candidate diagnostic biomarkers for MDD. Receiver operating characteristic analysis of combined levels of these six biomarkers yielded an area under the receiver operating characteristic curve (AUC) of 0.905 in distinguishing training samples; this simplified metabolite signature classified blinded test samples (44 MDD subjects and 52 healthy controls) with an AUC of 0.837. Furthermore, a composite panel by the addition of previously identified urine biomarker (N-methylnicotinamide) to this biomarker panel achieved a more satisfactory accuracy, yielding an AUC of 0.909 in the training samples and 0.917 in the test samples. Taken together, these results suggest this composite urinary metabolite signature should facilitate development of a urine-based diagnostic test for MDD.