Beneficial mechanisms of dimethyl fumarate in autoimmune uveitis: insights from single-cell RNA sequencing.

BACKGROUND: Dimethyl fumarate (DMF) is a fumaric acid ester that exhibits immunoregulatory and anti-inflammatory properties. However, the function of DMF in autoimmune uveitis (AU) is incompletely understood, and studies comprehensively exploring the impact of DMF on immune cells are still lacking. METHODS: To explore the function of DMF in uveitis and its underlying mechanisms, we conducted single-cell RNA sequencing (scRNA-seq) on the cervical draining lymph node (CDLN) cells of normal, experimental autoimmune uveitis (EAU), and DMF-treated EAU mice. Additionally, we integrated scRNA-seq data of the retina and CDLNs to identify the potential impact of DMF on ocular immune cell infiltration. Flow cytometry was conducted to verify the potential target molecules of DMF. RESULTS: Our study showed that DMF treatment effectively ameliorated EAU symptoms. The proportional and transcriptional alterations in each immune cell type during EAU were reversed by DMF treatment. Bioinformatics analysis in our study indicated that the enhanced expression of Pim1 and Cxcr4 in EAU was reversed by DMF treatment. Further experiments demonstrated that DMF restored the balance between effector T (Teff) /regulatory T (Treg) cells through inhibiting the pathway of PIM1-protein kinase B (AKT)-Forkhead box O1 (FOXO1). By incorporating the scRNA-seq data of the retina from EAU mice into analysis, our study identified that T cells highly expressing Pim1 and Cxcr4 were enriched in the retina. DMF repressed the ocular infiltration of Teff cells, and this effect might depend on its inhibition of PIM1 and CXCR4 expression. Additionally, our study indicated that DMF might reduce the proportion of plasma cells by inhibiting PIM1 expression in B cells. CONCLUSIONS: DMF effectively attenuated EAU symptoms. During EAU, DMF reversed the Teff/Treg cell imbalance and suppressed the ocular infiltration of Teff cells by inhibiting PIM1 and CXCR4 expression. Thus, DMF may act as a new drug option for the treatment of AU.

Single-cell sequencing of the retina shows that LDHA regulates pathogenesis of autoimmune uveitis.

Autoimmune uveitis (AU) is a severe disorder causing poor vision and blindness. However, the cellular dynamics and pathogenic mechanisms underlying retinal injury in uveitis remain unclear. In this study, single-cell RNA sequencing of the retina and cervical draining lymph nodes in experimental autoimmune uveitis mice was conducted to identify the cellular spatiotemporal dynamics and upregulation of the glycolysis-related gene LDHA. Suppression of LDHA can rescue the imbalance of T effector (Teff) cells/T regulator (Treg) cells under inflammation via downregulation of the glycolysis-PI3K signaling circuit and inhibition of the migration of CXCR4+ Teff cells towards retinal tissue. Furthermore, LDHA and CXCR4 are upregulated in the peripheral blood mononuclear cells of Vogt-Koyanagi-Harada patients. The LDHA inhibitor suppresses CD4+ T cell proliferation in humans. Therefore, our data indicate that the autoimmune environment of uveitis regulates Teff cell accumulation in the retina via glycolysis-associated LDHA. Modulation of this target may provide a novel therapeutic strategy for treating AU.

Application of Deferoxamine in Tissue Regeneration Attributed to Promoted Angiogenesis.

Deferoxamine, an iron chelator used to treat diseases caused by excess iron, has had a Food and Drug Administration-approved status for many years. A large number of studies have confirmed that deferoxamine can reduce inflammatory response and promote angiogenesis. Blood vessels play a crucial role in sustaining vital life by facilitating the delivery of immune cells, oxygen, and nutrients, as well as eliminating waste products generated during cellular metabolism. Dysfunction in blood vessels may contribute significantly to the development of life-threatening diseases. Anti-angiogenesis therapy and pro-angiogenesis/angiogenesis strategies have been frequently recommended for various diseases. Herein, we describe the mechanism by which deferoxamine promotes angiogenesis and summarize its application in chronic wounds, bone repair, and diseases of the respiratory system. Furthermore, we discuss the drug delivery system of deferoxamine for treating various diseases, providing constructive ideas and inspiration for the development of new treatment strategies.

Serum levels of specific IgE to cow's milk and its components as predictors of anaphylaxis in Chinese children with cow's milk allergy.

BACKGROUND: Cow's milk allergy (CMA) is one of the most common food allergies in young children. As improved diagnostic tools, allergic tests are inconsistent and limited in predicting anaphylaxis. OBJECTIVE: To explore risk factors for anaphylaxis and to determine practical cut-offs for allergic tests in predicting anaphylaxis. METHODS: This is a prospective cohort study. Children with IgE-mediated CMA were enrolled and divided into three groups (Group 1: non-anaphylaxis; Group 2: GRADE I anaphylaxis; Group 3: GRADE II-IV anaphylaxis that warranted epinephrine). Prick-to-prick tests (PTPs) using fresh cow's milk (CM) were performed. Serum specific IgE (sIgE) against CM and its components, including casein, alpha-lactalbumin, beta-lactoglobulin, and bovine serum albumin were measured. The 90% and 95% positive predictive value (PPV) decision points for predicting anaphylaxis were determined. Potential predictors of anaphylaxis were evaluated in logistic regression models. RESULTS: This study included 134 CMA patients with a median age of 14.4 months. The sensitization rate to any CM component was 89%. Group 3 was more likely to be sensitized to multiple CM components and have higher sIgE levels. The 95% PPV diagnostic decision points of casein-sIgE in predicting anaphylaxis was 13.0 kUA/L. For GRADE II-IV anaphylaxis, casein-sIgE ≥ 54.9 kUA/L could provide a PPV of 88.9%. The elevated casein-sIgE level (OR 14.0, P=0.025) and complicating respiratory allergic diseases (OR 4.8, P=0.022) were independent risk factors for GRADE II-IV anaphylaxis. CONCLUSION: High casein-sIgE levels are strongly associated with CM anaphylaxis. Detection of casein-sIgE may offer an additional value for the prediction of CM anaphylaxis.

Myocardial First-Pass Perfusion With Increased Anatomic Coverage at 3 T Using Autocalibrated Multiband Imaging.

BACKGROUND: Myocardial first-pass perfusion (FPP) imaging is a useful cardiac MRI method for the diagnosis of coronary artery disease. However, conventional 2D multislice FPP acquisitions usually have gaps between myocardium slices, which limits the overall assessment of myocardial ischemia. PURPOSE: To increase the anatomic coverage of myocardial FPP imaging at 3 T by implementing both autocalibrated multiband (MB) acquisition and k-t space acceleration with compress sensing (CS) reconstruction, without the need for additional reference scans. STUDY TYPE: Phantom and prospective human studies. PHANTOM/SUBJECTS: A T1MES (T1 Mapping and ECV Standardization in cardiovascular magnetic resonance) phantom and 20 subjects (12 healthy subjects and 8 patients, 10 males, age 42 ± 16 years). FIELD STRENGTH/SEQUENCE: A 3 T/saturation recovery prepared gradient echo sequence with contrast administration. ASSESSMENT: Phantom experiments were performed to compare the performance of autocalibrated MB-FPP with k-t acceleration using slice-GRAPPA and CS reconstructions. In vivo experiments were performed to compare the performance of conventional FPP (2.5× acceleration) with autocalibrated MB + CS-FPP (6× acceleration). In phantom experiments, the error maps were calculated. In in vivo experiments, the contrast ratio (CR) and blurring were quantitatively measured, while image quality, perceived signal-to-noise ratio (SNR), and artifact level were qualitatively graded by three cardiologists on a 4-point scale. STATISTICAL TESTS: Wilcoxon signed-rank test, paired t-test. A P value <0.05 was considered statistically significant. RESULTS: In phantom experiments, residual artifact was reduced using the MB + CS-FPP reconstruction method compared with using the MB + slice-GRAPPA reconstruction method. In in vivo experiments, the proposed autocalibrated MB + CS-FPP method demonstrated significantly higher CR (3.52 ± 0.78 vs 2.91 ± 0.81) and had significantly better perceived SNR (2.69 ± 0.29 vs 2.48 ± 0.31) compared to the conventional sequence. Compared with conventional FPP, MB + CS-FPP doubled the spatial coverage (MB + CS-FPP vs conventional FPP) without compromising the image quality (2.69 ± 0.26 vs 2.60 ± 0.30) or increasing the artifact level (2.60 ± 0.26 vs 2.52 ± 0.31). CONCLUSION: Autocalibrated MB + CS-FPP improved the myocardial coverage and achieved comparable image quality with the same spatial resolution and scan time as conventional FPP and is a promising technique for clinical myocardial perfusion imaging. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

Hysteroscopic Fenestration with Precise Incision of the Cavity Septum: A Novel Minimally Invasive Surgery of Complete Septate Uterus with Double Cervix.

STUDY OBJECTIVE: This study aimed to develop and describe a novel surgical procedure that involves hysteroscopic fenestration with precise incision of the complete uterine septum and double cervix preservation after magnetic resonance imaging (MRI) evaluation in patients and to evaluate its efficacy. DESIGN: A prospective consecutive clinical study. SETTING: A university teaching hospital. PATIENTS: Twenty-four patients with complete septate uterus and double cervix. INTERVENTIONS: Three-dimensional reconstruction of uterus was performed with pelvic MRI and three-dimensional SPACE sequence scanning. Hysteroscopic fenestration with precise incision of the cavity septum and double cervix preservation was performed in patients. Three months after operation, follow-up pelvic MRI and second-look hysteroscopy were performed conventionally. MEASUREMENTS AND MAIN RESULTS: Operating time, blood loss, operative complications, MRI and hysteroscopic changes of uterus, symptoms improvement, and reproductive outcomes were assessed. The surgery was successfully completed without any intraoperative complications in all patients. Operating time was 21.71 ± 8.28 minutes (range, 10-40 minutes) and blood loss was 9.92 ± 7.14 mL (range, 5-30 mL). Postoperative MRI showed the uterine anteroposterior diameter (3.66 cm vs 3.92 cm; p <.05) was increased. Postoperative MRI and the second-look hysteroscopy showed the cavity shape and uterine volume were expanded to the normal. Symptoms of dysmenorrhea, abnormal uterine bleeding, and dyspareunia were ameliorated after the surgery in 70% of patients (7 of 10), 60% of patients (3 of 5), and 1 patient, respectively. The preoperative spontaneous abortion rate was 80% (4 of 5) and the postoperative spontaneous abortion rate was 11.11% (1 of 9). After the surgery, there were 2 ongoing pregnancies and 6 pregnancies ended in term births. Two live births were delivered by cesarean section and 4 by vaginal delivery without cervical incompetence during pregnancy. CONCLUSIONS: Hysteroscopic fenestration with precise incision of the uterine septum and double cervix preservation is an effective surgical procedure.

Application value of T2 fluid-attenuated inversion recovery sequence based on deep learning in static lacunar infarction.

BACKGROUND: Regular monitoring of static lacunar infarction (SLI) lesions plays an important role in preventing disease development and managing prognosis. Magnetic resonance imaging is one method used to monitor SLI lesions. PURPOSE: To evaluate the image quality of the T2 fluid-attenuated inversion recovery (T2-FLAIR) sequence using artificial intelligence-assisted compressed sensing (ACS) in detecting SLI lesions and assess its clinical applicability. METHODS: A total of 42 patients were prospectively enrolled and scanned by T2-FLAIR. Two independent readers reviewed the images acquired with accelerated modes 1D (acceleration factor 2) and ACS (acceleration factors 2, 3, and 4). The overall image quality and lesion image quality were analyzed, as were signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and number of lesions between groups. RESULTS: The subjective assessment of overall brain image quality and lesion image quality was consistent between the two readers. The lesion display quality and the overall image quality were better with the traditional 1D acceleration method than with the ACS accelerated method. There was no significant difference in the SNR of the lacunar infarction in the images between the groups. The CNR of the images with the 1D acceleration mode was significantly lower than that of images with the ACS acceleration mode. Images with the 1D, ACS2, and ACS3 acceleration modes showed no significant differences in terms of detecting lesions but scan time can be reduced by 40% (1D vs. ACS3). CONCLUSION: ACS acceleration mode can greatly reduce the scan time. In addition, the images have good SNR, high CNR, and strong SLI lesion detection ability.

Synthesis, In Vitro, and In Vivo Investigations of Pterostilbene-Tethered Analogues as Anti-Breast Cancer Candidates.

Pterostilbene has been found to be an active scaffold with anti-breast cancer (BC) action. In this study, fourteen pterostilbene-tethered analogues (2A-2N) were prepared and screened in vitro against MDA-MB-231 and MCF-7 cells. Meanwhile, their structures were characterized using 1H-NMR, 13C-NMR, and HRMS (ESI) spectroscopy techniques. Among them, analogue 2L displayed the most potent anti-proliferation effect on MDA-MB-231 (IC50 = 10.39 µM) and MCF-7 cells (IC50 = 11.73 µM). Furthermore, the meaningful structure-activity relationships suggested that the introduction of a saturated six-membered nitrogen heterocyclic ring into the side chain favored anti-BC capacity. Biological observations indicated that 2L could cause the typical morphological changes in apoptosis, namely an increase in reactive oxygen species level and a loss of mitochondrial membrane potential in BC cells. Importantly, 2L could induce mitochondrial-mediated apoptosis by regulating the expression of caspase-related proteins. Consistent with the results of our in vitro study, 2L apparently inhibited tumor growth in MDA-MB-231 xenograft mice without obvious toxicity. These findings revealed that 2L is expected to be a promising anti-BC lead compound that merits further investigations.

Quantitative MR evaluation of the infrapatellar fat pad for knee osteoarthritis: using proton density fat fraction and T2* relaxation based on DIXON.

OBJECTIVES: To investigate the efficacy of fat fraction (FF) and T2* relaxation based on DIXON in the assessment of infrapatellar fat pad (IFP) for knee osteoarthritis (KOA) progression in older adults. METHODS: Ninety volunteers (age range 51-70 years, 65 females) were enrolled in this study. Participants were grouped based on the Kellgren-Lawrence grading (KLG). The FF and T2* values were measured based on the 3D-modified DXION technique. Cartilage defects, bone marrow lesions, and synovitis were assessed based on a modified version of whole-organ magnetic resonance imaging score (WORMS). Knee pain was assessed by self-administered Western Ontario and McMaster Osteoarthritis Index (WOMAC) questionnaire. The differences of FF and T2* measurement and the correlation with WORMS and WOMAC assessments were analyzed. Diagnostic efficiency was analyzed by using receiver operating characteristic (ROC) curves. RESULTS: A total of 60 knees were finally included (n = 20 in each group). The values were 82.6 ± 3.7%, 74.7 ± 5.4%, and 60.5 ± 14.1% for FF is the no OA, mild OA, and advanced OA groups, and were 50.7 ± 6.6 ms, 44.1 ± 6.6 ms, and 39.1 ± 4.2 ms for T2*, respectively (all p values < 0.001). The WORMS assessment and WOMAC pain assessment showed negative correlation with FF and T2* values. The ROC showed the area under the curve (AUC), sensitivity, and specificity for diagnosing OA were 0.93, 77.5%, and 100% using FF, and were 0.86, 75.0%, and 90.0% using T2*, respectively. CONCLUSIONS: FF and T2* alternations in IFP are associated with knee structural abnormalities and clinical symptoms cross-sectionally and may have the potential to predict the severity of KOA. KEY POINTS: • Fat fraction (FF) and T2* relaxation based on DIXON imaging are novel methods to quantitatively assess the infrapatellar fat pad for knee osteoarthritis (KOA) progression in older adults. • The alterations of FF and T2* using mDIXON technique in IFP were associated with knee structural abnormalities and clinical symptoms. • FF and T2* alternations in IFP can serve as the new imaging biomarkers for fast, simple, and noninvasive assessment in KOA.

Biomarkers of Mycoplasma pneumoniae pneumonia in children by urine metabolomics based on Q Exactive liquid chromatography/tandem mass spectrometry.

RATIONALE: Mycoplasma pneumoniae has become one of the common pathogens causing pediatric respiratory infections. In clinical diagnosis, throat swabs are very difficult to obtain from children, and there is a possibility of false positive results; hence, there are few clinically available diagnostic methods. METHODS: In this study, Q Exactive liquid chromatography/tandem mass spectrometry was used to analyze the metabolites in the urine of healthy children (HC) and M. pneumoniae pneumonia in children (MPPC) patients. A multivariate statistical analysis was performed to screen the differential metabolites. Based on the HMDB and KEGG, the possible metabolic pathways subject to biological alteration were identified. RESULTS: Compared with HC, 73 different metabolites in MPPC patients disrupted nine metabolic pathways through different change trends; after integrating various parameters, 20 significantly different metabolites were identified as MPPC potential biomarkers. Through the above two analysis modes, acetylphosphate and 2,5-dioxopentanoate were both screened out and used as potential biomarkers for the early diagnosis of MPPC for the first time. CONCLUSIONS: The characterization of 20 potential biomarkers provides a scientific basis for predicting and diagnosing MPPC. This article further indicates that urine metabolic profiling has great potential in diagnosing MPPC and can effectively prevent the disease from causing further deterioration.

High sensitivity detection of tumor cells in biological samples using a multivalent aptamer strand displacement strategy.

Monitoring the cell surface-expressed nucleolin facilitates early cancer diagnosis. Herein, we developed a multivalent aptamer displacement strand duplex strategy on cell membranes using a multi-receptor co-recognition design for improving the sensitivity and specificity of cancer cell recognition with an ultra-low background. The AS1411 aptamer labeled with the FAM fluorophore can be quenched using a partial complementary sequence modified with a BHQ1 tag which is partially hybridized with the AS1411 aptamer to create a receptor-activating aptamer. The multi-AS1411 activable probe based on the strand displacement strategy was constructed using multiple copies of the structure-switching AS1411 aptamer (bearing a short poly-A tail) linked together using the poly-T long chain (as a scaffold) which was synthesized by Terminal Deoxynucleotidyl Transferase (TDT)-mediated extension. We demonstrated the promising efficacy and sensitivity of our method in recognizing tumor cells in both cell mixtures and clinical cytology specimens. Due to its simple and fast operation with excellent cell recognition sensitivity and accuracy, it is expected to achieve the detection of low abundance target cells. Our approach will have broad application in clinical rapid detection and personalized medicine.

Thermoresponsive Dual-Structured Gel Emulsions Stabilized by Glycyrrhizic Acid Nanofibrils in Combination with Monoglyceride Crystals.

Responsive dual-structured emulsions and gel emulsions have attracted more and more attention due to their complex microstructures, on-demand responsive properties, and controlled release of active cargoes. In this work, the effect of monoglyceride (MG)-based oil phase structuring on the formation and stability, structural properties, and thermoresponsive and cargo release behavior of gel emulsions stabilized by glycyrrhizic acid (GA) nanofibrils were investigated. Owing to the formation of GA fibrillar networks in the aqueous phase and MG crystalline networks in the oil phase, a stable dual-structured gel emulsion can be successfully developed. The microstructure of the dual-structured gel emulsions largely depended on the concentration of MG in the oil phase. At low MG concentrations (1-2 wt%), the larger formed and lamellar MG crystals may pierce the interfacial fibrillar film, inducing the formation of partially coalesced droplets. In contrast, at high MG concentrations (4 wt% or above), the smaller MG crystals with enhanced interfacial activity can lead to the formation of a bilayer shell of GA nanofibrils and MG crystals, thus efficiently inhibiting the interfacial film damage and forming a jamming structure with homogeneously distributed small droplets. Compared to pure GA nanofibril gel emulsions, the GA-MG dual-structured gel emulsions showed significantly improved mechanical performance as well as good thermoresponsive behavior. Moreover, these stable GA-MG gel emulsions can be used as food-grade delivery vehicles for encapsulating and protecting hydrophobic and hydrophilic bioactive cargoes. They also have great potential as novel and efficient aroma delivery systems showing highly controlled volatile release. The dual-structured emulsion strategy is expected to broaden the applications of natural saponin GA-based gel emulsions in the food, pharmaceutical, and personal care industries.

Quality of internet videos related to exercise therapy of ankylosing spondylitis from mainland China : Content analysis.

OBJECTIVE: The aim of this study is to assess the quality and reliability of online videos on ankylosing spondylitis (AS) exercises from the five most popular video websites in China. DESIGN: Cross-sectional and descriptive study. METHODS: We searched the video websites of Youku, Tencent, Tudou, IQiYi, and bilibili on February 15, 2020, using the keywords "Ankylosing spondylitis exercise" "Ankylosing spondylitis rehabilitation" and "Ankylosing spondylitis therapy" A total of 114 videos were included in the study and evaluated according to the Global Quality Scale (GQS) and modified DISCERN tool. RESULTS: According to the GQS, the videos were classified as high quality (12.3%, n = 14), intermediate quality (63.2%, n = 72), and low quality (24.6%, n = 28). Using the modified DISCERN tool, the videos were divided into useless (53.5%, n = 61), useful (35.1%, n = 40), and misleading (11.4%, n = 13). CONCLUSION: The analysis shows that the quality and reliability of online videos related to exercise therapy for Ankylosing spondylitis (AS) should be improved and supervised in China. Hospitals, universities, and medical doctors should make more useful and high-quality videos to provide effective exercise guidance for AS patients.

Clinical characteristics and risk factors for death in patients with Candida bloodstream infection in Intensive Care Unit. / ICUå¿µç èŒè¡€æµæ„ŸæŸ“æ‚£è€ çš„ä¸´åºŠç‰¹ç‚¹åŠæ­»äº¡çš„å±é™©å› ç´ .

OBJECTIVES: To analyze the distribution of pathogens and risk factors of mortality in Candida bloodstream infection patients in Intensive Care Unit (ICU). METHODS: The clinical data, infection relevant indexes, and prognosis of patients with Candida bloodstream infection in ICU of Xiangya Hospital of Central South University from January 2016 to December 2020 were retrospectively collected. The distribution of pathogenic bacteria and clinical characteristics of patients with Candida bloodstream infection were analyzed. The patients were assigned into a death group and a survival group according to their survival status, and single factor analysis and logistic regression analysis were used to analyze risk factors for death. RESULTS: A total of 80 patients with Candida bloodstream infection were enrolled, with the highest infection rate (36.3%) of Candidaalbicans. According to the drug sensitivity, all kinds of Candidas were wide type and relatively sensitive to amphotericin B. Candidaalbicans was highly sensitive to fluconazole, itraconazole, and voriconazole (≥96.6%), while non-Candidaalbicans were more resistant to fluconazole, itraconazole, and voriconazole. The overall mortality rate was 36.3%. Univariate analysis showed that the risk factors for the death of patients with Candida bloodstream infection were acute physiology and chronic health evaluation II (APACHE II) score≥20, diabetes mellitus, and mechanical ventilation. Logistic regression analysis showed that the APACHE II score≥20 was an independent risk factor for the death of patients with Candida bloodstream infection (OR=0.220, 95% CI 0.078 to 0.619, P=0.004). CONCLUSIONS: The most common strain of Candida bloodstream infection in ICU patients is Candidaalbicans. The APACHE II score≥20 is an independent risk factor for the death of patients with Candida bloodstream infection.

Effects of exercise programmes on pain, disease activity and function in ankylosing spondylitis: A meta-analysis of randomized controlled trials.

BACKGROUND: To evaluate the effects of exercise programmes on pain, function and disease activity in patients with ankylosing spondylitis (AS). MATERIALS AND METHODS: We searched PubMed, Embase, CNKI and Wanfang from inception to February 2020. Randomized controlled trials comparing exercises with nonexercise interventions in AS patients were applied. Studies that assessed the visual analogue scale (VAS) pain score, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were included. Outcomes of home-based exercise intervention were also reported independently. RESULTS: Ten studies met the inclusion criteria in all, including 534 patients (278 exercise, 256 control). Compared with the nonexercise group, exercise group had statistically significant improvements in pain (weighted mean difference [WMD]: -1.02 [95% CI: -1.50 to -0.55]) (I2 : 31%, P <.0001), BASDAI (WMD: -0.85 [95% CI: -1.09 to -0.61]) (I2 : 20%, P <.00001), and BASFI (WMD: -0.66 [95% CI: -0.95 to -0.38]) (I2 : 0%, P <.00001), but not in CRP and ESR. What's more, home-based exercise programmes had positive impacts on BASFI, BASDAI and pain. CONCLUSIONS: For patients with AS, exercise programmes improve pain, function and disease activity. To confirm the results, more well-designed randomized controlled trials with large number of patients are required.

The Application of Biomass-Based Catalytic Materials in the Synthesis of Cyclic Carbonates from CO2 and Epoxides.

The synthesis of cyclic carbonates from carbon dioxide (CO2) and epoxides is a 100% atom economical reaction and an attractive pathway for CO2 utilisation. Because CO2 is a thermodynamically stable molecule, the use of catalysts is mandatory in reducing the activation energy of the CO2 conversion. Considering environmental compatibility and the high-efficiency catalytic conversion of CO2, there is the strong need to develop green catalysts. Biomass-based catalysts, a type of renewable resource, have attracted considerable attention due to their unique properties-non-toxic, low-cost, pollution-free, etc. In this review, recent advances in the development of biomass-based catalysts for the synthesis of cyclic carbonates by CO2 and epoxides coupling are summarized and discussed in detail. The effect of biomass-based catalysts, functional groups, reaction conditions, and co-catalysts on the catalytic efficiency and selectivity of synthesizing cyclic carbonates process is discussed. We intend to provide a comprehensive understanding of recent experimental and theoretical progress of CO2 and epoxides coupling reaction and pave the way for both CO2 conversion and biomass unitization.

Schisandrin B attenuates renal fibrosis via miR-30e-mediated inhibition of EMT.

Tubulointerstitial fibrosis (TIF) is the main pathologic feature of end-stage renal disease. Epithelial-mesenchymal transition (EMT) of proximal tubular cells (PTCs) is one of the most significant features of TIF. MicroRNAs play critical roles during EMT in TIF. However, whether miRNAs can be used as therapeutic targets in TIF therapy remains undetermined. We found that miR-30e, a member of the miR-30 family, is deregulated in TGF-ß1-induced PTCs, TIF mice and human fibrotic kidney tissues. Moreover, transcription factors that induce EMT, such as snail, slug, and Zeb2, were direct targets of miR-30e. Using a cell-based miR-30e promoter luciferase reporter system, Schisandrin B (Sch B) was selected for the enhancement of miR-30e transcriptional activity. Our results indicate that Sch B can decrease the expression of snail, slug, and Zeb2, thereby attenuating the EMT of PTCs during TIF by upregulating miR-30e, both in vivo and in vitro. This study shows that miR-30e can serve as a therapeutic target in the treatment of patients with TIF and that Sch B may potentially be used in therapy against renal fibrosis.

Evodiamine induces apoptosis and promotes hepatocellular carcinoma cell death induced by vorinostat via downregulating HIF-1α under hypoxia.

Hypoxia promotes HCC progression and therapy resistance, and there is no systemic treatment for HCC patients after sorafenib resistance. Thus, it is urgent to develop potential therapeutic regimens for HCC patients by targeting hypoxia signaling. In this study, we showed that evodiamine might be a potential therapeutic medicine for HCC by suppressing HIF-1α. In addition, evodiamine could sensitize the anti-HCC effect of vorinostat in HCC cells under hypoxia. Furthermore, evodiamine plus vorinostat accelerated the degradation of HIF-1α in HCC cells under hypoxia. In general, evodiamine might be a potential therapeutic candidate for HCC patients, and evodiamine combining with vorinostat might be an attractive chemotherapy strategy for HCC treatment.

A Morphological identification cell cytotoxicity assay using cytoplasm-localized fluorescent probe (CLFP) to distinguish living and dead cells.

Cell cytotoxicity assays include cell activity assays and morphological identification assays. Currently, all frequently used cytotoxicity assays belong to cell activity assays but suffer from detection limitations. Morphological identification of cell death remains as the gold standard, although the method is difficult to scale up. At present there is no generally accepted morphological identification based cell cytotoxicity assay. In this study, we applied previous developed cell cytoplasm-localized fluorescent probe (CLFP) to display cell morphologies. Under fluorescence microscopy, the fluorescence morphology and intensity of living cells are distinct from dead cells. Based on these characters we extracted the images of living cells from series of samples via computational analysis. Thus, a novel cell morphological identification cytotoxicity assay (CLFP assay) is developed. The performance of the CLFP assay was similar to cell activity assay (MTT assay), but the accuracy of the CLFP assay was superior when measuring the cytotoxicity of active compounds.