HDL-C and creatinine levels at 1 month are associated with patient 12-month survival rate after kidney transplantation.

BACKGROUND: Many factors affect the survival rate after kidney transplantation, including laboratory tests, medicine therapy and pharmacogenomics. Tacrolimus, mycophenolate mofetil and methylprednisolone were used as an immunosuppressive regimen after kidney transplantation. The primary goal of this study was to investigate the factors affecting the tacrolimus concentrations and mycophenolate mofetil area under the curve of mycophenolic acid AUC-MPA. Secondary goals were to study the association between perioperative period laboratory tests, medicine therapy, CYP3A5 genetic polymorphisms, and survival rate in kidney renal transplant patients. METHODS: A total of 303 patients aged above 18 years were enrolled in this study. Their clinical characteristics, laboratory tests, and medicine therapy regimens were collected. We followed the patients for survival for 1 year after kidney transplantation. RESULTS: Multivariable logistic analyses reveal that age greater than 50 years, and the CY3A5 *3*3 genotype were independently, positively, and significantly related to tacrolimus C/D ratio at 7 days. At 1 month of follow-up, only CYP3A5 *3*3 was associated with tacrolimus C/D ratio. Basiliximab, Imipenem and cilastatin sodium, sex were associated with mycophenolate mofetil AUC-MPA at 7 days. In the COX regression analysis, a high-density lipoprotein cholesterol level≥1 mmol/L was identified as a positive independent risk factors for the survival rate, while a creatinine level ≥200 µmol/L was a negatively independent risk factors for survival rate. CONCLUSION: These results suggest that age, genes, and drug-drug interaction can affect the concentration of tacrolimus.

Reversible Recognition-Based Boronic Acid Probes for Glucose Detection in Live Cells and Zebrafish.

Glucose, a critical source of energy, directly determines the homeostasis of the human body. However, due to the lack of robust imaging probes, the mechanism underlying the changes of glucose homeostasis in the human body remains unclear. Herein, diboronic acid probes with good biocompatibility and high sensitivity were synthesized based on an ortho-aminomethylphenylboronic acid probe, phenyl(di)boronic acid (PDBA). Significantly, by introducing the water-solubilizing group -CN directly opposite the boronic acid group and -COOCH3 or -COOH groups to the ß site of the anthracene in PDBA, we obtained the water-soluble probe Mc-CDBA with sensitive response (F/F0 = 47.8, detection limit (LOD) = 1.37 µM) and Ca-CDBA with the highest affinity for glucose (Ka = 4.5 × 103 M-1). On this basis, Mc-CDBA was used to identify glucose heterogeneity between normal and tumor cells. Finally, Mc-CDBA and Ca-CDBA were used for imaging glucose in zebrafish. Our research provides a new strategy for designing efficient boronic acid glucose probes and powerful new tools for the evaluation of glucose-related diseases.

Alteromonas salexigens sp. nov., isolated from coastal seawater.

A Gram-negative, aerobic, short rod-shaped bacterium, designated ASW11-19T, was isolated from a coastal seawater sample of the Yellow Sea, PR China. Strain ASW11-19T grew optimally at 37 °C, 3.0-5.0% (w/v) NaCl and pH 7.5. Phylogenetic analysis based on the 16S rRNA gene sequences revealed that strain ASW11-19T belonged to the genus Alteromonas and most closely related to Alteromonas profundi 345S023T and Alteromonas fortis 1T (98.4%, both). The draft genome was 3.55 Mb with 3150 protein-coding genes, 18 contigs, and a DNA G+C content was 44.4%. The digital DNA-DNA hybridization and average nucleotide identity values were below the species-delineating thresholds. The major fatty acids were summed feature 3 (C16:1ω7c/C16:1ω6c), summed feature 8 (C18:1ω7c/C18:1ω6c), and C16:0. The sole respiratory quinone was ubiquinone 8. The polar lipids were phosphatidylethanolamine, phosphatidylglycerol, phospholipid, and two unidentified lipids. Based on these genomic data, phenotypic and chemotaxonomic properties, strain ASW11-19T is considered to represent a novel species of the genus Alteromonas. The name Alteromonas salexigens sp.nov. is proposed for ASW11-19T (=MCCC 1K07239T=KCTC 92247T).

Alteromonas Aquimaris sp. nov., Isolated from Surface Seawater.

A Gram-negative, aerobic, motile by flagellum, and rod-shaped bacterium, designated ASW11-7T, was isolated from coastal surface seawater sample collected from the Yellow Sea, PR China. Strain ASW11-7T grew optimally at 37℃, 4.0% (w/v) NaCl and pH 7.0. Phylogenetic analysis based on the 16S rRNA gene sequences revealed that strain ASW11-7T belongs to the genus Alteromonas and most closely related to Alteromonas ponticola MYP5T (99.6% similarity), followed by Alteromonas confluentis DSSK2-12T (98.2%), Alteromonas lipolytica JW12T (98.2%), and Alteromonas hispanica F-32T (98.0%). The draft genome of strain ASW11-7T had a length of 3,530,922 bp with a G + C content of 44.9%, predicting 3108 coding sequences, 5 rRNA, 4 ncRNAs, 49 tRNAs genes, and 18 pseudogenes. The average nucleotide identity and digital DNA-DNA hybridization values between genomic sequences of strain ASW11-7T and closely related species of Alteromonas were in ranges of 66.9-77.8% and 18.3-27.5%, respectively. The major fatty acids of strain ASW11-7T were C16:0, summed feature 3 (C16:1ω7c/C16:1ω6c), and summed feature 8 (C18:1ω7c/C18:1ω6c). The predominant respiratory quinone was Q-8 and the major polar lipids were phosphatidylethanolamine and phosphatidylglycerol. Based on the phenotypic properties, genotypic distinctiveness, and chemotaxonomic features, strain ASW11-7T is considered to represent a novel Alteromonas species, for which the name Alteromonas aquimaris sp. nov. is proposed. The type strain is ASW11-7T (= KCTC 92853T = MCCC 1K07240T).

Oncological prognosis and morbidity of hepatectomy in elderly patients with hepatocellular carcinoma: a propensity score matching and multicentre study.

PURPOSE: With increasing life expectancy, the number of elderly patients (≥ 65 years) with hepatocellular carcinoma (HCC) has steadily increased. Hepatectomy remains the first-line treatment for HCC patients. However, the prognosis of hepatectomy for elderly patients with HCC remains unclear. METHODS: Clinical and follow-up data from 1331 HCC patients who underwent surgery between 2008 and 2020 were retrospectively retrieved from a multicentre database. Patients were divided into elderly (≥ 65 years) and non-elderly (< 65 years) groups, and PSM was used to balance differences in the baseline characteristics. The postoperative major morbidity and cancer-specific survival (CSS) of the two groups were compared and the independent factors that were associated with the two study endpoints were identified by multivariable regression analysis. RESULTS: Of the 1331 HCC patients enrolled in this study, 363 (27.27%) were elderly, while 968 (72.73%) were not. After PSM, 334 matched samples were obtained. In the propensity score matching (PSM) cohort, a higher rate of major morbidity was found in elderly patients (P = 0.040) but the CSS was similar in the two groups (P = 0.087). Multivariate analysis revealed that elderly age was not an independent risk factor associated with high rates of major morbidity (P = 0.117) or poor CSS (P = 0.873). The 1-, 3- and 5-year CSS rates in the elderly and non-elderly groups were 91.0% versus 86.2%, 71.3% versus 68.8% and 55.9% versus 58.0%, respectively. Preoperative alpha fetoprotein (AFP) level, Child‒Pugh grade, intraoperative blood transfusion, extended hemi hepatectomy, and tumour diameter could affect the postoperative major morbidity and preoperative AFP level, cirrhosis, Child‒Pugh grade, macrovascular invasion, microvascular invasion (MVI), satellite nodules, and tumor diameter were independently and significantly associated with CSS. CONCLUSION: Age itself had no significant effect on the prognosis of elderly patients with HCC after hepatectomy. Hepatectomy can be safely performed in elderly patients after cautious perioperative management.

Oral Metal-Organic Gel Protected Whole-Cell Biosensor for in Situ Monitoring Nitrosamines in the Gastrointestinal Tract.

Nitrite, a type of food additive, has been proved convertible to genotoxic nitrosamines in the gastrointestinal tract by intestinal flora. There is no appropriate method for in situ detection of nitrosamines. Herein, plasmid-introduced Saccharomyces cerevisiae, which can respond to nitrosamine-induced DNA damage and activate pMAG1-based DNA damage repair (DDR), was designed as whole-cell biosensors (WCBs) for monitoring the in situ generated nitrosamines by a reporter gene expressing enhanced green fluorescent protein (EGFP). In order to protect the validity of WCBs (pMAG1 yeast) from the gastric acid environment, a type of metal-organic gel (MOG), coordinated by Fe3+ and 2,2'-thiodiacetic acid (TDA), was prepared to embed the WCBs. The MOG(Fe-TDA) is gastric acid resistant and can deliver the pMAG1 yeast to the gut without compromising the performance of pMAG1 yeast to detect in situ generated nitrosamines. The genotoxicity of nitrosamines converted from nitrite was successfully detected in the gastrointestinal tract of mice.

Cancer drug resistance related microRNAs: recent advances in detection methods.

Drug resistance is a significant factor that hinders the success of cancer chemotherapy. The widely recognized mechanisms of drug resistance include changes to cell proliferation, cycle/apoptosis, drug metabolism/transport, DNA damage and the epithelial to mesenchymal transition. MicroRNAs (miRNAs), short non-coding RNAs with lengths of approximately 19-25 nucleotides, are related to cancer drug resistance, which is regulated by the aforementioned mechanisms. Based on the importance of miRNAs in regulating drug resistance, it is also necessary to take appropriate miRNA detection methods into consideration. To date, a number of advanced miRNA detection methods with high specificity and sensitivity have been developed, such as isothermal amplification-based methods, nanomaterial-based methods, chromatography-based methods, mass spectrometry-based methods and so on. Herein, biogenesis of miRNAs, the relationship between miRNAs and cancer drug resistance, and miRNA detection methods are introduced and discussed to facilitate the development of non-invasive diagnosis and inhibition of cancer drug resistance.

Deaminative Arylation and Alkenyaltion of Aliphatic Tertiary Amines with Aryl and Alkenylboronic Acids via Nitrogen Ylides.

Transition-metal-catalyzed Suzuki-Miyaura coupling has significantly advanced C-C bond formation and has been well recognized in organic synthesis, pharmaceuticals, materials science and other fields. In this rapid development, cross coupling without transition metal catalyst is a big challenge in this field, and using widely existing tertiary amines as electrophiles to directly couple with boronic acids has great hurdles yet significant application prospects. Herein, we report an efficient and general deaminative arylation and alkenylation of tertiary amines (propargyl amines, allyl amines and 1H-indol-3-yl methane amines) with ary and alkenylboronic acids enabled by difluorocarbene under transition-metal-free conditions. Preliminary mechanism experiments suggest that in situ formed difluoromethyl quaternary amine salt, nitrogen ylide and tetracoordinate boron species are the key intermediates, the subsequent 1,2-metallate shift and protodeboronation complete the new coupling reaction.

Plexin C1 deficiency permits synaptotagmin 7-mediated macrophage migration and enhances mammalian lung fibrosis.

Pulmonary fibrosis is a progressive and often fatal condition that is believed to be partially orchestrated by macrophages. Mechanisms that control migration of these cells into and within the lung remain undefined. We evaluated the contributions of the semaphorin receptor, plexin C1 (PLXNC1), and the exocytic calcium sensor, synaptotagmin 7 (Syt7), in these processes. We evaluated the role of PLXNC1 in macrophage migration by using Boyden chambers and scratch tests, characterized its contribution to experimentally induced lung fibrosis in mice, and defined the mechanism for our observations. Our findings reveal that relative to control participants, patients with idiopathic pulmonary fibrosis demonstrate excessive monocyte migration and underexpression of PLXNC1 in the lungs and circulation, a finding that is recapitulated in the setting of scleroderma-related interstitial lung disease. Relative to wild type, PLXNC1-/- mouse macrophages are excessively migratory, and PLXNC1-/- mice show exacerbated collagen accumulation in response to either inhaled bleomycin or inducible lung targeted TGF-ß1 overexpression. These findings are ameliorated by replacement of PLXNC1 on bone marrow-derived cells or by genetic deletion of Syt7. These data demonstrate the previously unrecognized observation that PLXNC1 deficiency permits Syt7-mediated macrophage migration and enhances mammalian lung fibrosis.-Peng, X., Moore, M., Mathur, A., Zhou, Y., Sun, H., Gan, Y., Herazo-Maya, J. D., Kaminski, N., Hu, X., Pan, H., Ryu, C., Osafo-Addo, A., Homer, R. J., Feghali-Bostwick, C., Fares, W. H., Gulati, M., Hu, B., Lee, C.-G., Elias, J. A., Herzog, E. L. Plexin C1 deficiency permits synaptotagmin 7-mediated macrophage migration and enhances mammalian lung fibrosis.

Study of Herbs Cortex Moutan, Poria cocos, and Alisma orientale and Periodontitis.

INTRODUCTION: The Chinese traditional herbs Cortex Moutan, Poria cocos, and Alisma orientale are considered to have potential to ameliorate periodontitis, although the possible underlying mechanisms remain mostly unknown. Due to the complex formulation of Chinese herbs, it is important to understand the mechanisms of pharmacologic effects of traditional herbs for better application in modern medical treatment. METHODS: Network pharmacology was applied to explore the mechanism of Cortex Moutan, Poria cocos, and Alisma orientale. First we analysed their chemical ingredients using the Traditional Chinese Medicine Systems Pharmacology database and identified 20 active ingredients. Then we analysed the target genes of these 20 active ingredients as well as genes associated with periodontitis and found 74 co-target genes. We further analysed the protein-protein interaction network of these 74 co-target genes using the STRING database and enriched the pathways using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. RESULTS: The top 10 core targets elicited were vascular endothelial growth factor A (VEGFA), interlukin-6 (IL-6), tumour necrosis factor (TNF), matrix metalloproteinase-2 (MMP2), matrix metalloproteinase-9 (MMP9), AKT serine/threonine kinase 1 (AKT1), prostaglandin-endoperoxide synthase 2 (PTGS2), kinase insert domain receptor (KDR), fibroblast growth factor 2 (FGF2), and serpin family E member 1 (SERPINE1). Using these a network of "herbs-ingredients-targetgenes-KEGG pathways." was constructed. CONCLUSIONS: The target and bioprocess network suggested that the pharmacologic effects of Cortex Moutan, Poria cocos, and Alisma orientale may be mainly dependent on their anti-inflammatory potential. Further work is required to eucidate their detailed mechanisms of activity.

Absolute distance meter without dead zone based on free-running dual femtosecond lasers.

Absolute distance measurements based on femtosecond lasers have been extensively studied for precision metrology and advanced manufacturing, with the advantages of traceability, high speed, and nanometer precision. However, in previous studies, the dual femtosecond laser ranging system showed limitations such as system complexity, lower integration, dead zone problems in single optical path detection, and high requirements for laser coherence. It is challenging to achieve a high degree of integration and large-scale continuous measurements using femtosecond lasers, ineluctably limiting practical applications in engineering fields. Here, based on the free-running dual femtosecond lasers and the nonlinear asynchronous optical sampling method, we design a highly integrated absolute distance meter. In particular, the dead zone problem is solved by the polarization multiplexing technique, and the digital control system and signal processing system are completed by the Field Programmable Gate Array (FPGA). The absolute distance meter enables rapid, continuous, and accurate measurements over a considerable range without dead zones, which paves a promising way for the integration, instrumentation, and industrial applications of femtosecond laser ranging systems.

Observation of discrete-light temporal refraction by moving potentials with broken Galilean invariance.

Refraction is a basic beam bending effect at two media's interface. While traditional studies focus on stationary boundaries, moving boundaries or potentials could enable new laws of refractions. Meanwhile, media's discretization plays a pivotal role in refraction owing to Galilean invariance breaking principle in discrete-wave mechanics, making refraction highly moving-speed dependent. Here, by harnessing a synthetic temporal lattice in a fiber-loop circuit, we observe discrete time refraction by a moving gauge-potential barrier. We unveil the selection rules for the potential moving speed, which can only take an integer v = 1 or fractional v = 1/q (odd q) value to guarantee a well-defined refraction. We observe reflectionless/reflective refractions for v = 1 and v = 1/3 speeds, transparent potentials with vanishing refraction/reflection, refraction of dynamic moving potential and refraction for relativistic Zitterbewegung effect. Our findings may feature applications in versatile time control and measurement for optical communications and signal processing.

Quantitative analysis of pre-treatment dynamic contrast-enhanced ultrasound for assessing the response of colorectal liver metastases to chemotherapy plus targeted therapy: a dual-institutional study.

OBJECTIVES: To investigate the clinical value of pre-treatment quantitative contrast-enhanced ultrasound (CEUS) in assessing the response of colorectal liver metastases (CRLM) to chemotherapy plus targeted therapy. METHODS: This study retrospectively enrolled 50 CRLM patients from the Zhongshan Hospital, Fudan University as the training cohort and 14 patients from Shanghai Tenth People's Hospital as the testing cohort. Patients underwent the CEUS examination before receiving chemotherapy (CAPOX, FOLFOX, FOLFIRI, or FOLFOXIRI) plus targeted therapy (Bevacizumab or Cetuximab). The therapy response was determined according to Response Evaluation Criteria in Solid Tumors version 1.1 based on pre-treatment CT and 3-month follow-up CT after therapy. Dynamic analysis was performed by VueBox® software. Time-intensity curves with quantitative perfusion parameters were obtained. In the training cohort, univariable and multivariable logistic regression analyses were used to develop the predictive model of therapy response. The predictive performance of the developed model was validated in the testing cohort. RESULTS: After the logistic regression analyses, the peak enhancement (PE) (odds ratio = 1.640; 95% confidence intervals [CI] 1.022-2.633) and time to peak (TTP) (odds ratio = 0.495; 95% CI 0.246-0.996) were determined as independent predictive factors. PE and TTP generated from VueBox® were not affected by ultrasound instruments and contrast agent dosage in therapy response evaluation (P > 0.05). The logistic regression model achieved satisfactory prediction performance (area under the curve: 0.923 in the training cohort and 0.854 in the testing cohort). CONCLUSION: CEUS with dynamic quantitative perfusion analysis, which presents high consistency, has potential practical value in predicting the response of CRLM to chemotherapy plus targeted therapy.

Subtype prediction of intrahepatic cholangiocarcinoma using dynamic contrast-enhanced ultrasound.

OBJECTIVE: The study aimed to investigate the predictive value of dynamic contrast-enhanced ultrasound (DCE-US) in differentiating small-duct (SD) and large-duct (LD) types of intrahepatic cholangiocarcinoma (ICC). METHODS: This study retrospectively enrolled 110 patients with pathologically confirmed ICC lesions who were subject to preoperative contrast-enhanced ultrasound (CEUS) examinations between January 2022 and February 2023. Patients were further classified according to the subtype: SD-type and LD-type, and an optimal predictive model was established and validated using the above pilot cohort. The test cohort, consisting of 48 patients prospectively enrolled from March 2023 to September 2023, was evaluated. RESULTS: In the pilot cohort, compared with SD-type ICCs, more LD-type ICCs showed elevated carcinoembryonic antigen (p < 0.001), carbohydrate antigen 19-9 (p = 0.004), ill-defined margin (p = 0.018), intrahepatic bile duct dilation (p < 0.001). Among DCE-US quantitative parameters, the wash-out area under the curve (WoAUC), wash-in and wash-out area under the curve (WiWoAUC), and fall time (FT) at the margin of lesions were higher in the SD-type group (all p < 0.05). Meanwhile, the mean transit time (mTT) and wash-out rate (WoR) at the margin of the lesion were higher in the LD-type group (p = 0.041 and 0.007, respectively). Logistic regression analysis showed that intrahepatic bile duct dilation, mTT, and WoR were significant predictive factors for predicting ICC subtypes, and the AUC of the predictive model achieved 0.833 in the test cohort. CONCLUSIONS: Preoperative DCE-US has the potential to become a novel complementary method for predicting the pathological subtype of ICC. CRITICAL RELEVANCE STATEMENT: DCE-US has the potential to assess the subtypes of ICC lesions quantitatively and preoperatively, which allows for more accurate and objective differential diagnoses, and more appropriate treatments and follow-up or additional examination strategies for the two subtypes. KEY POINTS: Preoperative determination of intrahepatic cholangiocarcinoma (ICC) subtype aids in surgical decision-making. Quantitative parameters from dynamic contrast-enhanced US (DCE-US) allow for the prediction of the ICC subtype. DCE-US-based imaging has the potential to become a novel complementary method for predicting ICC subtypes.

A multi-parameter intrahepatic cholangiocarcinoma scoring system based on modified contrast-enhanced ultrasound LI-RADS M criteria for differentiating intrahepatic cholangiocarcinoma from hepatocellular carcinoma.

PURPOSE: To develop a multi-parameter intrahepatic cholangiocarcinoma (ICC) scoring system and compare its diagnostic performance with contrast-enhanced ultrasound (CEUS) liver imaging reporting and data system M (LR-M) criteria for differentiating ICC from hepatocellular carcinoma (HCC). METHODS: This retrospective study enrolled 62 high-risk patients with ICCs and 62 high-risk patients with matched HCCs between January 2022 and December 2022 from two institutions. The CEUS LR-M criteria was modified by adjusting the early wash-out onset (within 45 s) and the marked wash-out (within 3 min). Then, a multi-parameter ICC scoring system was established based on clinical features, B-mode ultrasound features, and modified LR-M criteria. RESULT: We found that elevated CA 19-9 (OR=12.647), lesion boundary (OR=11.601), peripheral rim-like arterial phase hyperenhancement (OR=23.654), early wash-out onset (OR=7.211), and marked wash-out (OR=19.605) were positive predictors of ICC, whereas elevated alpha-fetoprotein (OR=0.078) was a negative predictor. Based on these findings, an ICC scoring system was established. Compared with the modified LR-M and LR-M criteria, the ICC scoring system showed the highest area under the curve (0.911 vs. 0.831 and 0.750, both p<0.05) and specificity (0.935 vs. 0.774 and 0.565, both p<0.05). Moreover, the numbers of HCCs categorized as LR-M decreased from 27 (43.5%) to 14 (22.6%) and 4 (6.5%) using the modified LR-M criteria and ICC scoring system, respectively. CONCLUSION: The modified LR-M criteria-based multi-parameter ICC scoring system had the highest specificity for diagnosing ICC and reduced the number of HCC cases diagnosed as LR-M category.

Impact of the PEAR1 polymorphism on clinical outcomes in Chinese patients receiving dual antiplatelet therapy after percutaneous coronary intervention.

Background: Patients might still experience major adverse cardiovascular events even with dual antiplatelet therapy after percutaneous coronary intervention. Our study aimed to explore the impact of gene polymorphism on clinical outcomes in one-year follow-up. Methods: A total of 171 patients treated with dual antiplatelet therapy after percutaneous coronary intervention from April to December 2020 in the first hospital of Jilin University enrolled in this study. Results: PEAR1 genetic polymorphisms was associated with the arachidonic acid (AA) and adenosine diphosphate (ADP) platelet aggregation. Hyperglycemia was associated with the rate of major adverse cardiovascular events. PEAR1 GA+AA genetic genetic polymorphisms is associated with hyperglycemia. Conclusion:PEAR1 GG is a risk factor for AA and ADP platelet aggregation. Hyperglycemia can effect the one-year outcome. PEAR1 GA+AA genetic polymorphisms are associated with hyperglycemia.

Circular RNA Derived from Vacuolar ATPase Assembly Factor VMA21 Suppresses Lipopolysaccharide-Induced Apoptosis of Chondrocytes in Osteoarthritis (OA) by Decreasing Mature miR-103 Production.

Circular RNA derived from vacuolar ATPase assembly factor (VMA21) has been proven to be an inflammation suppressor in many diseases, while its role in osteoarthritis (OA) is unknown. We predicted that VMA21 participates in OA via interacting with miR-103, an OA promoter. Therefore, we analyzed the crosstalk between VMA21 and miR-103 in OA. In this study, the levels of VMA21, pre-miR-103, and mature miR-103 in synovial fluid samples from OA patients (n = 56) and controls (n = 56) were analyzed using RT-qPCR. Nuclear and cytoplasm samples were prepared from chondrocytes, and VMA21 expression was detected by RT-PCR. RNA-RNA pulldown assay was applied to analyze the direct interaction between VMA21 and pre-miR-103. The involvement of VMA21 and miR-103 in lipopolysaccharide (LPS)-induced chondrocyte apoptosis and viability was analyzed using cell apoptosis assay and 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, respectively. We found that compared to the control group, VMA21 expression was decreased in OA, and miR-103 maturation was increased in OA. VMA21 could be detected in both nuclear and cytoplasm, and VMA21 directly interacted with pre-miR-103. VMA21 overexpression reduced miR-103 maturation. VMA21 suppressed the role of miR-103 in enhancing chondrocyte apoptosis and reducing cell viability after LPS treatment. In conclusion, VMA21 might suppress LPS-induced chondrocyte apoptosis in OA by decreasing the production of mature miR-103.

MiR-29a-3p Inhibits Proliferation and Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells via Targeting FOXO3 and Repressing Wnt/ß-Catenin Signaling in Steroid-Associated Osteonecrosis.

Background and Objectives: This study was to investigate the role of microRNA-29a-3p (miR-29a-3p) in human bone marrow mesenchymal stem cells (hBMSCs), and its relationship with steroid-associated osteonecrosis. Methods and Results: The online tool GEO2R was used to screen out the differentially expressed genes (DEGs) in GSE123568 dataset. Quantitative real time-polymerase chain reaction (qRT-PCR) was performed to detect the expression of miR-29a-3p, forkhead box O3 (FOXO3), alkaline phosphatase (ALP), bone gamma-carboxyglutamate protein (OCN) and RUNX family transcription factor 2 (Runx2) in the hBMSCs isolated from the patients with steroid- associated osteonecrosis. CCK-8 assay was executed to measure cell viability; western blot assay was utilized to detect FOXO3, ALP, Runx2, OCN and ß-catenin expression. Cell apoptosis and cell cycle were detected by flow cytometry. Immunofluorescence assay was used to detect the sub-cellular localization of ß-catenin. Bioinformatics analysis and luciferase reporter gene assay were performed to confirm whether miR-29a-3p can combine with FOXO3 3'UTR. MiR-29a-3p was markedly up-regulated in the hBMSCs of patients with steroid-associated osteonecrosis, while FOXO3 mRNA was significantly down-regulated. Transfection of miR-29a-3p mimics significantly inhibited the hBMSCs' proliferation, osteogenic differentiation markers' expressions, including ALP, Runx2, OCN, and repressed the ALP activity, as well as promoted cell apoptosis and cell-cycle arrest. FOXO3 was identified as a target gene of miR-29a-3p, and miR-29a-3p can inhibit the expression of FOXO3 and ß-catenin, and inhibition of miR-29a-3p promoted translocation of ß-catenin to the nucleus. Conclusions: MiR-29a-3p can modulate FOXO3 expression and Wnt/ß-catenin signaling to inhibit viability and osteogenic differentiation of hBMSCs, thereby promoting the development of steroid-associated osteonecrosis.

Fluorescent intracellular imaging of reactive oxygen species and pH levels moderated by a hydrogenase mimic in living cells.

The catalytic generation of H2 in living cells provides a method for antioxidant therapy. In this study, an [FeFe]-hydrogenase mimic [Ru + Fe2S2@F127(80)] was synthesized by self-assembling polymeric pluronic F-127, catalytic [Fe2S2] sites, and photosensitizer Ru(bpy)3 2+. Under blue light irradiation, hydrated protons were photochemically reduced to H2, which increased the local pH in living cells (HeLa cells). The generated H2 was subsequently used as an antioxidant to decrease reactive oxygen species (ROS) levels in living cells (HEK 293T, HepG2, MCF-7, and HeLa cells). Our findings revealed that the proliferation of HEK 293T cells increased by a factor of about six times, relative to that of other cells (HepG2, MCF-7, and HeLa cells). Intracellular ROS and pH levels were then monitored using fluorescent cell imaging. Our study showed that cell imaging can be used to evaluate the ability of Ru + Fe2S2@F127 to eliminate oxidative stress and prevent ROS-related diseases.

Small extracellular vesicles derived from mesenchymal stem cell facilitate functional recovery in spinal cord injury by activating neural stem cells via the ERK1/2 pathway.

Spinal cord injury (SCI) causes severe neurological dysfunction leading to a devastating disease of the central nervous system that is associated with high rates of disability and mortality. Small extracellular vesicles (sEVs) derived from human umbilical cord mesenchymal stem cells (hucMSC-sEVs) have been explored as a promising strategy for treating SCI. In this study, we investigated the therapeutic effects of the intralesional administration of hucMSC-sEVs after SCI and determined the potential mechanisms of successful repair by hucMSC-sEVs. In vivo, we established the rat model of SCI. The Basso, Beattie, Bresnahan (BBB) scores showed that hucMSC-sEVs dramatically promoted the recovery of spinal cord function. The results of the hematoxylin-eosin (HE) staining, Enzyme-Linked Immunosorbent Assay (ELISA), and immunohistochemistry showed that hucMSC-sEVs inhibited inflammation and the activation of glia, and promoted neurogenesis. Furthermore, we studied the effect of hucMSC-sEVs on neural stem cells(NSCs) in vitro. We found that hucMSC-sEVs did not improve the migration ability of NSCs, but promoted NSCs to proliferate and differentiate via the ERK1/2 signaling pathway. Collectively, these findings suggested that hucMSC-sEVs promoted the functional recovery of SCI by activating neural stem cells via the ERK1/2 pathway and may provide a new perspective and therapeutic strategy for the clinical application of hucMSC-sEVs in SCI treatment.