Under the dual effect of inflammation and pulmonary fibrosis, CTD-ILD patients possess a greater susceptibility to VTE.

As an autoimmune disease, the persistent systemic inflammatory response associated with connective tissue disease (CTD) is involved in the development of venous thromboembolism (VTE). However, clinical data showed that the risk of VTE in patients differed between subtypes of CTD, suggesting that different subtypes may have independent mechanisms to promote the development of VTE, but the specific mechanism lacks sufficient research at present. The development of pulmonary fibrosis also contributes to the development of VTE, and therefore, patients with CTD-associated interstitial lung disease (CTD-ILD) may be at higher risk of VTE than patients with CTD alone or patients with ILD alone. In addition, the activation of the coagulation cascade response will drive further progression of the patient's pre-existing pulmonary fibrosis, which will continue to increase the patient's risk of VTE and adversely affect prognosis. Currently, the treatment for CTD-ILD is mainly immunosuppressive and antirheumatic therapy, such as the use of glucocorticoids and janus kinase-inhibitors (JAKis), but, paradoxically, these drugs are also involved in the formation of patients' coagulation tendency, making the clinical treatment of CTD-ILD patients with a higher risk of developing VTE challenging. In this article, we review the potential risk factors and related mechanisms for the development of VTE in CTD-ILD patients to provide a reference for clinical treatment and prevention.

Bridging the biochemistry lecture and laboratory courses: Construction and application of the "Innovative Experimental Design" module.

Both lecture and laboratory courses of biochemistry are important professional courses for undergraduates with biology related majors. Course optimization and update is crucial but challenging, especially for the laboratory course. Although taught separately, here we showed a strategy to bridge the two courses and promote the improvement of both. In addition to knowledge teaching, we implanted the "Innovative Experimental Design" module in the lecture course in which students were required to design and present their own experimental ideas. After evaluation by the faculty group, the best idea was supported for further experimental test. Here we described the preliminary experiments and optimization procedures about the idea of microbial fuel cells. This experiment is ready to be included into the laboratory course program in spring 2023.

[Triterpenoids in Sorbus pohuashanensis suspension cell treated with yeast extract].

This study induced biological stress in Sorbus pohuashanensis suspension cell(SPSC) with yeast extract(YE) as a bio-tic elicitor and isolated and identified secondary metabolites of triterpenoids produced under stress conditions. Twenty-six triterpenoids, including fifteen ursane-type triterpenoids(1-15), two 18,19-seco-ursane-type triterpenoids(16-17), four lupine-type triterpenoids(18-21), two cycloartane-type triterpenoids(22-23), and three squalene-type triterpenoids(24-26), were isolated and purified from the methanol extract of SPSC by chromatography on silica gel, MCI, Sephadex LH-20, and MPLC. Their structures were elucidated by spectroscopic analyses. All triterpenoids were isolated from SPSC for the first time and 22-O-acetyltripterygic acid A(1) was identified as a new compound. Selected compounds were evaluated for antifungal, antitumor, and anti-inflammatory activities, and compound 1 showed an inhibitory effect on NO production in LPS-induced RAW264.7 cells.

Astragalus polysaccharides attenuate rat aortic endothelial senescence via regulation of the SIRT-1/p53 signaling pathway.

BACKGROUND: Astragalus polysaccharides (APS) have been verified to have antioxidative and antiaging activities in the mouse liver and brain. However, the effect of APS on aortic endothelial senescence in old rats and its underlying mechanism are currently unclear. Here, we aimed to elucidate the effects of APS on rat aortic endothelial oxidative stress and senescence in vitro and in vivo and investigate the potential molecular targets. METHODS: Twenty-month-old natural aging male rats were treated with APS (200 mg/kg, 400 mg/kg, 800 mg/kg daily) for 3 months. Serum parameters were tested using corresponding assay kits. Aortic morphology was observed by staining with hematoxylin and eosin (H&E) and Verhoeff Van Gieson (VVG). Aging-related protein levels were evaluated using immunofluorescence and western blot analysis. Primary rat aortic endothelial cells (RAECs) were isolated by tissue explant method. RAEC mitochondrial function was evaluated by the mitochondrial membrane potential (MMP) measured with the fluorescent lipophilic cationic dye JC­1. Intracellular total antioxidant capacity (T-AOC) was detected by a commercial kit. Cellular senescence was assessed using senescence-associated-ß-galactosidase (SA-ß-Gal) staining. RESULTS: Treatment of APS for three months was found to lessen aortic wall thickness, renovate vascular elastic tissue, improve vascular endothelial function, and reduce oxidative stress levels in 20-month-old rats. Primary mechanism analysis showed that APS treatment enhanced Sirtuin 1 (SIRT-1) protein expression and decreased the levels of the aging marker proteins p53, p21 and p16 in rat aortic tissue. Furthermore, APS abated hydrogen peroxide (H2O2)-induced cell senescence and restored H2O2-induced impairment of the MMP and T-AOC in RAECs. Similarly, APS increased SIRT-1 and decreased p53, p21 and p16 protein levels in senescent RAECs isolated from old rats. Knockdown of SIRT-1 diminished the protective effect of APS against H2O2-induced RAEC senescence and T-AOC loss, increased the levels of the downstream proteins p53 and p21, and abolished the inhibitory effect of APS on the expression of these proteins in RAECs. CONCLUSION: APS may reduce rat aortic endothelial oxidative stress and senescence via the SIRT-1/p53 signaling pathway.

[Spatial Constraints of Rectangular Hydrogel Microgrooves Regulate the Morphology and Arrangement of Human Umbilical Vein Endothelial Cells]. / çŸ©å½¢æ°´å‡èƒ¶å¾®å‡¹æ§½çš„ç©ºé—´çº¦æŸè°ƒæŽ§äººè„é™è„‰å† çš®ç»†èƒžçš„å½¢æ€å’ŒæŽ’åˆ—.

Objective: To construct microscale rectangular hydrogel grooves and to investigate the morphology and alignment of human umbilical vein endothelial cells (HUVECs) under spatial constraints. Vascular endothelial cell morphology and alignment are important factors in vascular development and the maintenance of homeostasis. Methods: A 4-arm polyethylene glycol-acrylate (PEG-acrylate) hydrogel was used to fabricate rectangular microgrooves of the widths of 60 µm, 100 µm, and 140 µm. The sizes and the fibronectin (FN) adhesion of these hydrogel microgrooves were measured. HUVECs were seeded onto the FN-coated microgrooves, while the flat surface without micropatterns was used as the control. After 48 hours of incubation, the morphology and orientation of the cells were examined. The cytoskeleton was labelled with phalloidine and the orientation of the cytoskeleton in the hydrogel microgrooves was observed by laser confocal microscopy. Results: The hydrogel microgrooves constructed exhibited uniform and well-defined morphology, a complete structure, and clear edges, with the width deviation being less than 3.5%. The depth differences between the hydrogel microgrooves of different widths were small and the FN adhesion is uniform, providing a micro-patterned growth interface for cells. In the control group, the cells were arranged haphazardly in random orientations and the cell orientation angle was (46.9±1.8)°. In contrast, the cell orientation angle in the hydrogel microgrooves was significantly reduced (P<0.001). However, the cell orientation angles increased with the increase in hydrogel microgroove width. For the 60 µm, 100 µm, and 140 µm hydrogel microgrooves, the cell orientation angles were (16.4±2.8)°, (24.5±3.2)°, and (30.3±3.5)°, respectively. Compared to that of the control group (35.7%), the number of cells with orientation angles <30° increased significantly in the hydrogel microgrooves of different widths (P<0.001). However, as the width of the hydrogel microgrooves increased, the number of cells with orientation angles <30° gradually decreased (79.9%, 62.3%, 54.7%, respectively), while the number of cells with orientation angles between 60°-90° increased (P<0.001). The cell bodies in the microgrooves were smaller and more rounded in shape. The cells were aligned along the direction of the microgrooves and corresponding changes occurred in the arrangement of the cell cytoskeleton. In the control group, cytoskeletal filaments were aligned in random directions, presenting an orientation angle of (45.5±3.7)°. Cytoskeletal filaments were distributed evenly within various orientation angles. However, in the 60 µm, 100 µm, and 140 µm hydrogel microgrooves, the orientation angles of the cytoskeletal filaments were significantly decreased, measuring (14.4±3.1)°, (24.7±3.5)°, and (31.9±3.3)°, respectively. The number of cytoskeletal filaments with orientation angles <30° significantly increased in hydrogel microgrooves of different widths (P<0.001). However, as the width of the hydrogel microgrooves increased, the number of cytoskeletal filaments with orientation angles <30° gradually decreased, while the number of cytoskeletal filaments with orientation angles between 60°-90° gradually increased (P<0.001). Conclusion: Hydrogel microgrooves can regulate the morphology and orientation of HUVECs and mimic to a certain extent the in vivo microenvironment of vascular endothelial cells, providing an experimental model that bears better resemblance to human physiology for the study of the unique physiological functions of vascular endothelial cells. Nonetheless, the molecular mechanism of spatial constraints on the morphology and the assembly of vascular endothelial cell needs to be further investigated.

The therapeutic effect of Picroside II in renal ischemia-reperfusion induced acute kidney injury: An experimental study.

The microcirculation hemodynamics change and inflammatory response are the two main pathophysiological mechanisms of renal ischemia-reperfusion injury (IRI) induced acute kidney injury (AKI). The treatment of microcirculation hemodynamics and inflammatory response can effectively alleviate renal injury and correct renal function. Picroside II (P II) has a wide range of pharmacological effects. Still, there are few studies on protecting IRI-AKI, and whether P II can improve renal microcirculation perfusion is still being determined. This study aims to explore the protective effect of P II on IRI-AKI and evaluate its ability to enhance renal microcirculation perfusion. In this study, a bilateral renal IRI-AKI model in mice was established, and the changes in renal microcirculation and inflammatory response were quantitatively evaluated before and after P II intervention by contrast-enhanced ultrasound (CEUS). At the same time, serum and tissue markers were measured to assess the changes in renal function. The results showed that after P II intervention, the levels of serum creatinine (Scr), blood urea nitrogen (BUN), serum cystatin C (Cys-C), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA), and superoxide dismutase (SOD), as well as the time-to-peak (TTP), peak intensity (PI) and area under the curve (AUC), and the normalized intensity difference (NID) were all alleviated. In conclusion, P II can improve renal microcirculation perfusion changes caused by IRI-AKI, reduce inflammatory reactions during AKI, and enhance renal antioxidant stress capacity. P II may be a new and promising drug for treating IRI-AKI.

Effect of UV pretreatment on the source control of floR during subsequent biotreatment of florfenicol wastewater.

UV photolysis has been recommended as an alternative pretreatment method for the elimination of antibacterial activity of antibiotics against the indicator strain, but the pretreated antibiotic intermediates might not lose their potential to induce antibiotic resistance genes (ARGs) proliferation during subsequent biotreatment processes. The presence of florfenicol (FLO) in wastewater seriously inhibits the metabolic performance of anaerobic sludge microorganisms, especially the positive correlation between UV irradiation doses and ATP content, while it did not significantly affect the organics utilization ability and protein biosynthetic process of aerobic microorganisms. After sufficient UV pretreatment, the relative abundances of floR from genomic or plasmid DNA in subsequent aerobic and anaerobic biotreatment processes both decreased by two orders of magnitude, maintained at the level of the groups without FLO selective pressure. Meanwhile, the abundances of floR under anaerobic condition were always lower than that under aerobic condition, suggesting that anaerobic biotreatment systems might be more suitable for the effective control of target ARGs. The higher abundance of floR in plasmid DNA than in genome also indicated that the potential transmission risk of mobile ARGs should not be ignored. In addition, the relative abundance of intI1 was positively correlated with floR in its corresponding genomic or plasmid DNA (p < 0.05), which also increased the potential horizontal transfer risk of target ARGs. This study provides new insights into the effect of preferential UV photolysis as a pretreatment method for the enhancement of metabolic performance and source control of target ARGs in subsequent biotreatment processes. KEY POINTS: • Sufficient UV photolytic pretreatment efficiently controlled the abundance of floR • A synchronous decrease in abundance of intI1 reduced the risk of horizontal transfer • An appreciable abundance of floR in plasmid DNA was a potential source of total ARGs.

Immunological dynamic characteristics in acute myeloid leukemia predict the long-term outcomes and graft-versus host-disease occurrences post-transplantation.

To investigate the relationship between immune dynamic and graft-versus-host-disease (GVHD) risk, 111 initial diagnostic acute myeloid leukemia patients were reviewed. The flow cytometry data of 12 major lymphocyte subsets in bone marrow (BM) from 60 transplant patients at four different time points were analyzed. Additionally, 90 immune subsets in peripheral blood (PB) of 11 post-transplantation on day 100 were reviewed. Our results demonstrated that transplant patients had longer OS compared to non-transplant patients (P < 0.001). Among transplant patients, those who developed GVHD showed longer OS than those without GVHD (P < 0.05). URD donors and CMV-negative status donors were associated with improved OS in transplant patients (P < 0.05). Importantly, we observed a decreased Th/Tc ratio in BM at initial diagnostic in patients with GVHD compared to those without GVHD (P = 0.034). Receiver operating characteristic analysis indicated that a low Th/Tc ratio predicted an increased risk of GVHD with a sensitivity of 44.44% and specificity of 87.50%. Moreover, an increased T/NK ratio in BM of post-induction chemotherapy was found to be associated with GVHD, with a sensitivity of 75.76% and specificity of 65.22%. Additionally, we observed a decreased percentage of NK1 (CD56-CD16+NK) in PB on day 100 post-transplantation in the GVHD group (P < 0.05). These three indicators exhibit promising potential as specific and useful biomarkers for predicting GVHD. These findings provide valuable insights for the early identification and management of GVHD risk, thereby facilitating the possibility of improving patient outcomes.

Association between metabolic dysfunction-associated fatty liver disease and abdominal aortic aneurysm.

BACKGROUND AND AIMS: Abdominal aortic aneurysm (AAA) is the second most common aortic pathological manifestation. Metabolic dysfunction-associated fatty liver disease (MAFLD) has a wide impact on the cardiovascular system and may be a risk factor for AAA. The aim of this study was to investigate whether MAFLD is associated with the risk of AAA. METHODS AND RESULTS: We used data from the prospective UK Biobank cohort study. MAFLD is defined as hepatic steatosis plus metabolic abnormality, type 2 diabetes, or overweight/obesity. AAA is collected by ICD-10 code. Cox regression was established to analyze the association between MAFLD and AAA. A total of 370203 participants were included; the average age of the participants was 56.7 ± 8.0 years, and 134649 (36.4 %) were diagnosed with MAFLD. During the 12.5 years of follow-up, 1561 (0.4 %) participants developed AAA. After fully adjusting for confounding factors, individuals with MAFLD had a significantly increased risk of AAA (HR 1.521, 95 % CI 1.351-1.712, p < 0.001). Importantly, the risk of AAA increases with the severity of MAFLD as assessed by fibrosis scores. These associations were consistent according to sex, weight, and alcohol consumption but weaker in elderly or diabetics (P for interaction <0.05). The association between the MAFLD phenotype and AAA was independent of the polygenic risk score. Additionally, MAFLD was not associated with thoracic aortic aneurysm or aortic dissection events. CONCLUSIONS: There was a significant relationship between MAFLD and AAA. These findings strongly recommend early prevention of AAA by intervening in MAFLD.

Value of Contrast-Enhanced Microflow Imaging in Diagnosis of Breast Masses in Comparison with Contrast-Enhanced Ultrasound.

RATIONALE AND OBJECTIVES: To investigate the value of contrast-enhanced microflow imaging (CEUS-MFI) in distinguishing benign and malignant breast masses. METHODS: A total of 116 breast masses classified as Breast Imaging Reporting and Data System (BI-RADS) category 3-5 by ultrasound (US) were included. Both contrast-enhanced ultrasound (CEUS) and CEUS-MFI were performed before excision or biopsy, with features and diagnostic efficiency analyzed. The US and CEUS BI-RADS 4A masses were also re-assessed by CEUS-MFI. RESULTS: The features of CEUS-MFI including both interior and peripheral enlarged, twisted vessels (both P < 0.05), penetrating vessels (P = 0.007), and radial/spiculated vessels (P < 0.001) were more frequently detected in malignant masses, while peripheral annular vessels were mostly observed in benign masses (P < 0.001). Interestingly, a significant difference in the orientation of penetrating vessels between benign and malignant masses was found (P < 0.001), with parallel orientation mostly displayed in benign masses, while vertical or multiple-direction orientation mostly displayed in malignant masses. The microvascular architecture of breast masses was categorized into five patterns: avascular, line-like, tree-like, root hair-like, and crab claw-like pattern. Benign masses mainly displayed tree-like pattern (77.1% vs 10.9%, P < 0.05); malignant masses mainly displayed root hair-like (34.8% vs 5.7%, P < 0.05) and crab claw-like patterns (50.0% vs 1.4%, P < 0.05). The diagnostic efficiency of CEUS-MFI was higher relative to CEUS and US. In addition, CEUS-MFI decreased the biopsy rates of US and CEUS BI-RADS 4A masses without missing malignancies. CONCLUSION: CEUS-MFI could be a valuable and promising technique in diagnosis of breast masses, and could provide more diagnostic information for radiologists.

Whole-transcriptome defines novel glucose metabolic subtypes in colorectal cancer.

Colorectal cancer (CRC) is the most prevalent malignancy of the digestive system. Glucose metabolism plays a crucial role in CRC development. However, the heterogeneity of glucose metabolic patterns in CRC is not well characterized. Here, we classified CRC into specific glucose metabolic subtypes and identified the key regulators. 2228 carbohydrate metabolism-related genes were screened out from the GeneCards database, 202 of them were identified as prognosis genes in the TCGA database. Based on the expression patterns of the 202 genes, three metabolic subtypes were obtained by the non-negative matrix factorization clustering method. The C1 subtype had the worst survival outcome and was characterized with higher immune cell infiltration and more activation in extracellular matrix pathways than the other two subtypes. The C2 subtype was the most prevalent in CRC and was characterized by low immune cell infiltration. The C3 subtype had the smallest number of individuals and had a better prognosis, with higher levels of NRF2 and TP53 pathway expression. Secreted frizzled-related protein 2 (SFRP2) and thrombospondin-2 (THBS2) were confirmed as biomarkers for the C1 subtype. Their expression levels were elevated in high glucose condition, while their knockdown inhibited migration and invasion of HCT 116 cells. The analysis of therapeutic potential found that the C1 subtype was more sensitive to immune and PI3K-Akt pathway inhibitors than the other subtypes. To sum up, this study revealed a novel glucose-related CRC subtype, characterized by SFRP2 and THBS2, with poor prognosis but possible therapeutic benefits from immune and targeted therapies.

Two New Compounds from the Endophytic Fungi of Dryopteris crassirhizoma and Their Antimicrobial Activities.

Two endophytic fungi Trichoderma afroharzianum (HP-3) and Alternaria alstroemeriae (HP-7) were isolated and purified from the fresh root of Dryopteris crassirhizoma. Chemical investigation of the two fungi resulted in the isolation of two new phenols 2,4-dihydroxy-3-farnesyl-5-methoxy benzoic acid (1) and 2-hydroxyphenethyl 2-phenylacetate (2), together with 22 known compounds. Their structures were elucidated by NMR, UV, IR, HRESIMS, and comparison to the literature data. Compounds 15 and 16 showed significant antibacterial activity against Micrococcus lysodeikticus with MIC value of 6.25 µg/mL, while 8 and 14 displayed moderate inhibitory activities against several plant pathogenic fungi and clinically important bacterial strains. This is the first study to report the isolation, identification, and antimicrobial properties of metabolites from endophytic fungi of D. crassirhizoma. Our findings may provide lead compounds for the development of new antibacterial agents.

Multi-system diseases and death trajectory of metabolic dysfunction-associated fatty liver disease: findings from the UK Biobank.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a newly defined condition encompassing hepatic steatosis and metabolic dysfunction. However, the relationship between MAFLD and multi-system diseases remains unclear, and the time-dependent sequence of these diseases requires further clarification. METHODS: After propensity score matching, 163,303 MAFLD subjects and 163,303 matched subjects were included in the community-based UK Biobank study. The International Classification of Diseases, Tenth Revision (ICD-10), was used to reclassify medical conditions into 490 and 16 specific causes of death. We conducted a disease trajectory analysis to map the key pathways linking MAFLD to various health conditions, providing an overview of their interconnections. RESULTS: Participants aged 59 (51-64) years, predominantly males (62.5%), were included in the study. During the 12.9-year follow-up period, MAFLD participants were found to have a higher risk of 113 medical conditions and eight causes of death, determined through phenome-wide association analysis using Cox regression models. Temporal disease trajectories of MAFLD were established using disease pairing, revealing intermediary diseases such as asthma, diabetes, hypertension, hypothyroid conditions, tobacco abuse, diverticulosis, chronic ischemic heart disease, obesity, benign tumors, and inflammatory arthritis. These trajectories primarily resulted in acute myocardial infarction, disorders of fluid, electrolyte, and acid-base balance, infectious gastroenteritis and colitis, and functional intestinal disorders. Regarding death trajectories of MAFLD, malignant neoplasms, cardiovascular diseases, and respiratory system deaths were the main causes, and organ failure, infective disease, and internal environment disorder were the primary end-stage conditions. Disease trajectory analysis based on the level of genetic susceptibility to MAFLD yielded consistent results. CONCLUSIONS: Individuals with MAFLD have a risk of a number of different medical conditions and causes of death. Notably, these diseases and potential causes of death constitute many pathways that may be promising targets for preventing general health decline in patients with MAFLD.

Association between cognitive impairment and risk of atrial fibrillation: The Atherosclerosis Risk in Communities study.

BACKGROUND: Atrial fibrillation (AF) is reportedly a risk factor for cognitive impairment. Interestingly, recent studies have emphasized that impaired cognition is probably an initiating factor of cardiovascular disease. Thus, we aimed to explore the association between impaired cognition and the risk of AF, and clarify the potential mechanisms. METHODS: Participants of visit 2 (1991-1993) in the Atherosclerosis Risk in Communities study were included. Global cognition z-scores and factor scores were calculated using the word fluency, delayed word recall, and digit symbol substitution tests. AF incidents were diagnosed by electrocardiography and inpatient records. The association of cognitive decline with AF risk and left atrial volume index (LAVI) was explored using Cox proportional hazards and linear regression models, respectively. RESULTS: During the median follow-up of 18.2 ± 6.2 years, 2056/11,675 (17.6%) participants developed AF. Participants in the lowest quartile of global cognition z- and factor scores had a higher risk of AF (hazard ratio [HR]: 1.271, 95% confidence interval [CI]: 1.094-1.477, p = 0.002; HR: 1.305, 95% CI: 1.110-1.535, p = 0.001, respectively) than those in the highest quartile. Global cognition z- and factor scores were negatively correlated with the LAVI (B: -0.411, 95% CI: -0.749 to -0.074, p = 0.017; B: -0.425, 95% CI: -0.833 to -0.017, p = 0.041, respectively). CONCLUSION: S: : Cognitive decline is significantly associated with a higher risk of AF, with atrial remodeling being a potential mechanism. Our results extend previous findings of the brain-heart axis and indicate the effects of cognitive injury on cardiac function and structure. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; unique identifier: NCT00005131.

The value of combined ultrasound contrast arthrography and subacromial-subdeltoid bursography for detecting and differentiating the rotator cuff tear subtypes in patients with the uncertain rotator cuff tear.

OBJECTIVES: In this study, ultrasound (US) contrast arthrography and subacromial-subdeltoid bursography with the contrast agent of SonoVue were performed to evaluate their value for detecting and differentiating the rotator cuff tear (RCT) subtypes in patients with the uncertain RCT. METHODS: A total of 102 patients with the clinically suspected RCTs in the orthopedic clinic were prospectively recruited and underwent conventional high-frequency US for the category of undoubted full-thickness RCT, uncertain RCT, and intact rotator cuff. Among these patients, the patients with uncertain RCT underwent the subsequent US contrast arthrography and subacromial-subdeltoid bursography. The arthroscopic findings were used as the gold standard in this study. RESULTS: After the conventional US screening, 62 patients with uncertain RCT underwent the subsequent US contrast arthrography and subacromial-subdeltoid bursography. All the US contrast arthrography and subacromial-subdeltoid bursography were successfully performed and no severe side effects were observed in all the patients. For full-thickness tears, the sensitivity and specificity of the combined US contrast arthrography and subacromial-subdeltoid bursography were 94.7% (CI: 0.72-1.0) and 81.4% (CI: 0.66-0.91), respectively, and for articular-side tears 100% (CI: 0.51-1) and 100% (CI: 0.92-1), respectively, and for the bursal-side tears 84.6% (CI: 0.54-0.97) and 97.9% (CI: 0.88-1.0), respectively. The main inconsistency between the contrast-enhanced US and arthroscopy was that 7 patients with arthroscopic proved concurrent articular- and bursal-side tears were indicated as full-thickness RCTs on contrast-enhanced US. CONCLUSIONS: Combined US contrast arthrography and subacromial-subdeltoid bursography are useful for detecting the RCT subtypes in patients with the uncertain RCTs. CLINICAL RELEVANCE STATEMENT: When conventional high-frequency US has some difficulty in differentiating the full-thickness from partial-thickness RCTs, combined US contrast arthrography and subacromial-subdeltoid bursography could be used to improve the detection accuracy of RCT subtypes. KEY POINTS: • This is the first study by injection of the US contrast agent SonoVue into the shoulder joint cavity and subacromial-subdeltoid bursa for the detection and differentiation of the RCT subtypes among the people with the uncertain RCT by conventional US screening. • The SonoVue was injected into the glenohumeral joint cavity under US guidance to differentiate the full-thickness RCTs from partial-thickness RCTs. • Combined US contrast arthrography and subacromial-subdeltoid bursography are useful for detecting the RCT subtypes in patients with the uncertain RCTs.

Sensitive detection of extracellular hydrogen peroxide using plasmon-enhanced electrochemical activity on Pd-tipped Au nanobipyramids.

The fabrication of electroactive nanostructures with high electron concentration and specific electron transport is crucial for electrochemical sensing. In this study, a plasmon-enhanced electrochemical sensor has been developed for the detection of extracellular hydrogen peroxide (H2O2) from cancer cells, utilizing Pd-tipped Au nanobipyramids (PTA NBPs) as the electrocatalysts. Plasmonic PTA NBPs were synthesized by depositing Pd nanoparticles onto the tips of Au nanobipyramids (Au NBPs). Under excitation of localized surface plasmon resonance (LSPR), the PTA NBPs generate high-energy electron-hole pairs (e-/h+) on their surface. The generated electrons (e-) significantly enhance the electrochemical reduction of H2O2. Based on this, a plasmon-enhanced H2O2 electrochemical sensor is constructed with high sensitivity (986.57 µA mM-1 cm-2), low detection limit (0.02 µM), wide linear range (0.1 µM to 980 µM), and good stability and repeatability. Moreover, this sensor also enables the measurement of extracellular H2O2 derived from cancer cells (MCF-7), highlighting its potential applications in cellular biology and biomedical research.

Value of Multimodality Ultrasound in Quantitative Evaluation of the Intra-compartmental Pressure and Perfusion Pressure in Acute Compartment Syndrome in a Rabbit Model.

OBJECTIVE: The aim of the work described here was to investigate the feasibility of using multimodality ultrasound in quantitative evaluation of the intra-compartmental pressure (ICP) and perfusion pressure (PP) changes in acute compartment syndrome (ACS). METHODS: Infusion technique was used to increase the ICP of the anterior compartment of 10 rabbits from baseline to 20, 30, 40, 50, 60, 70 and 80 mmHg. The anterior compartment was evaluated with conventional ultrasound, shear wave elastography (SWE) and contrast-enhanced ultrasound (CEUS). The shape of the anterior compartment, shear wave velocity (SWV) of the tibialis anterior (TA) muscle and CEUS parameters of the TA muscle were measured. RESULTS: When the ICP exceeded 30 mmHg, the shape of the anterior compartment did not expand significantly with increasing ICP. There was a strong correlation between the SWV of TA muscle and measured ICP (ρ = 0.927). Arrival time (AT), time to peak (TTP), peak intensity (PI) and area under the curve (AUC) were significantly correlated with PP (AT, ρ = -0.763; TTP, ρ = -0.900; PI, ρ = 0.665; AUC, ρ = 0.706), whereas mean transit time (MTT) was not. CONCLUSION: Multimodality ultrasound can be used to quantitatively evaluate ICP and PP and, thus, could provide more information for the rapid diagnosis and monitoring of ACS.

Discovery of an OTUD3 inhibitor for the treatment of non-small cell lung cancer.

The ubiquitin-proteasome system (UPS) controls protein turnover, and its dysfunction contributes to human diseases including cancer. Deubiquitinating enzymes (DUBs) remove ubiquitin from proteins to maintain their stability. Inhibition of DUBs could induce the degradation of selected oncoproteins and has therefore become a potential therapeutic strategy for cancer. The deubiquitylase OTUD3 was reported to promote lung tumorigenesis by stabilizing oncoprotein GRP78, implying that inhibition of OTUD3 may be a therapeutic strategy for lung cancer. Here, we report a small-molecule inhibitor of OTUD3 (named OTUDin3) by computer-aided virtual screening and biological experimental verification. OTUDin3 exhibited pronounced antiproliferative and proapoptotic effects by inhibiting deubiquitinating activity of OTUD3 in non-small-cell lung cancer (NSCLC) cell lines. Moreover, OTUDin3 efficaciously inhibited growth of lung cancer xenografts in mice. In summary, our results support OTUDin3 as a potent inhibitor of OTUD3, the inhibition of which may be a promising therapeutic strategy for NSCLC.

A Novel Assay for Investigating the Role of Exosomes in Tumor Cell-Endothelial Cell Crosstalk.

Exosomes have critical role in regulating the tumor development and progression and resistance following antiangiogenesis therapies (AATs). Exosomes could be released by both tumor cells and surrounding endothelial cells (ECs). Here, we describe the methods to explore the cargo transfer between tumor cells and ECs by a novel four-compartment co-culture methods and to investigate the effect of tumor cells on angiogenic ability of ECs by Transwell co-culture methods.

[Human Platelet-Rich Plasma-Derived Exosomes Promote the Proliferation of Schwann Cells Cultured in Vitro].

Objective To investigate the effect of human platelet-rich plasma-derived exosomes(PRP-exos)on the proliferation of Schwann cell(SC)cultured in vitro. Methods PRP-exos were extracted by polymerization-precipitation combined with ultracentrifugation.The morphology of PRP-exos was observed by transmission electron microscopy,and the concentration and particle size distribution of PRP-exos were determined by nanoparticle tracking analysis.Western blotting was employed to determine the expression of the marker proteins CD63,CD81,and CD9 on exosome surface and the platelet membrane glycoprotein CD41.The SCs of rats were isolated and cultured,and the expression of the SC marker S100ß was detected by immunofluorescence staining.The fluorescently labeled PRP-exos were co-cultured with SCs in vitro for observation of their interaction.EdU assay was employed to detect the effect of PRP-exos on SC proliferation,and CCK-8 assay to detect the effects of PRP-exos at different concentrations(0,10,20,40,80,and 160 µg/ml)on SC proliferation. Results The extracted PRP-exos appeared as uniform saucer-shaped vesicles with the average particle size of(122.8±38.7)nm and the concentration of 3.5×1012 particles/ml.CD63,CD81,CD9,and CD41 were highly expressed on PRP-exos surface(P<0.001,P=0.025,P=0.004,and P=0.032).The isolated SCs expressed S100ß,and PRP-exos could be taken up by SCs.PRP-exos of 40,80,and 160 µg/ml promoted the proliferation of SCs,and that of 40 µg/ml showed the best performance(all P<0.01). Conclusions High concentrations of PRP-exos can be extracted from PRP.PRP-exos can be taken up by SCs and promote the proliferation of SCs cultured in vitro.