Inhibition of UHRF1 Improves Motor Function in Mice with Spinal Cord Injury.

Spinal-cord injury (SCI) is a severe condition that can lead to limb paralysis and motor dysfunction, and its pathogenesis is not fully understood. The objective of this study was to characterize the differential gene expression and molecular mechanisms in the spinal cord of mice three days after spinal cord injury. By analyzing RNA sequencing data, we identified differentially expressed genes and discovered that the immune system and various metabolic processes play crucial roles in SCI. Additionally, we identified UHRF1 as a key gene that plays a significant role in SCI and found that SCI can be improved by suppressing UHRF1. These findings provide important insights into the molecular mechanisms of SCI and identify potential therapeutic targets that could greatly contribute to the development of new treatment strategies for SCI.

Umpolung Strategy for the One-Pot Synthesis of Highly Steric Bispirooxindoles via the l-Amino Acid Ester-Promoted In Situ Reduction/Nucleophilic Addition/Cyclization Cascade Reaction.

On the basis of a novel umpolung strategy, an efficient l-amino acid ester-mediated in situ reduction of 2-(2-oxoindolin-3-ylidene)malononitrile and sequential nucleophilic addition/cyclization cascade reaction is reported. Various densely substituted cyclopentene bispirooxindoles and dihydrofuran bispirooxindoles with two quaternary spirocenters were constructed in high yields (≤93%) with excellent diastereoselectivities (>20:1 dr). The method has advantages of readily available starting materials, mild reaction conditions, a one-pot process, a metal-free biomimetic reducing agent, a wide substrate scope, and operational simplicity (single filtration without column chromatography).

Chondroitin sulfate-modified tragacanth gum-gelatin composite nanocapsules loaded with curcumin nanocrystals for the treatment of arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease of yet undetermined etiology that is accompanied by significant oxidative stress, inflammatory responses,  and damage to joint tissues. In this study, we designed chondroitin sulfate (CS)-modified tragacanth gum-gelatin composite nanocapsules (CS-Cur-TGNCs) loaded with curcumin nanocrystals (Cur-NCs), which rely on the ability of CS to target CD44 to accumulate drugs in inflamed joints. Cur was encapsulated in the form of nanocrystals into tragacanth gum-gelatin composite nanocapsules (TGNCs) by using an inborn microcrystallization method, which produced CS-Cur-TGNCs with a particle size of approximately 80 ± 11.54 nm and a drug loading capacity of 54.18 ± 5.17%. In an in vitro drug release assay, CS-Cur-TGNCs showed MMP-2-responsive properties. During the treatment of RA, CS-Cur-TGNCs significantly inhibited oxidative stress, promoted the polarization of M2-type macrophages to M1-type macrophages, and decreased the expression of inflammatory factors (TNF-α, IL-1ß, and IL-6). In addition, it also exerted excellent anti-inflammatory effects, and significantly alleviated the swelling of joints during the treatment of gouty arthritis (GA). Therefore, CS-Cur-TGNCs, as a novel drug delivery system, could lead to new ideas for clinical therapeutic regimens for RA and GA.

Inhibition and Mechanism of Citral on Bacillus cereus Vegetative Cells, Spores, and Biofilms.

Bacillus cereus causes food poisoning by producing toxins that cause diarrhea and vomiting and, in severe cases, endocarditis, meningitis, and other diseases. It also tends to form biofilms and spores that lead to contamination of the food production environment. Citral is a potent natural antibacterial agent, but its antibacterial activity against B. cereus has not been extensively studied. In this study, we first determined the minimum inhibitory concentrations and minimum bactericidal concentrations, growth curves, killing effect in different media, membrane potential, intracellular adenosine triphosphate (ATP), reactive oxygen species levels, and morphology of vegetative cells, followed by germination rate, morphology, germination state of spores, and finally biofilm clearance effect. The results showed that the minimum inhibitory concentrations and minimum bactericidal concentrations of citral against bacteria ranged from 100 to 800 µg/mL. The lag phase of bacteria was effectively prolonged by citral, and the growth rate of bacteria was slowed down. Bacteria in Luria-Bertani broth were reduced to below the detection limit by citral at 800 µg/mL within 0.5 h. Bacteria in rice were reduced to 3 log CFU/g by citral at 4000 µg/mL within 0.5 h. After treatment with citral, intracellular ATP concentration was reduced, membrane potential was altered, intracellular reactive oxygen species concentration was increased, and normal cell morphology was altered. After treatment with citral at 400 µg/mL, spore germination rate was reduced to 16.71%, spore morphology was affected, and spore germination state was altered. It also had a good effect on biofilm removal. The present study showed that citral had good bacteriostatic activity against B. cereus vegetative cells and its spores and also had a good clearance effect on its biofilm. Citral has the potential to be used as a bacteriostatic substance for the control of B. cereus in food industry production.

Enhanced acetate utilization for value-added chemicals production in Yarrowia lipolytica by integration of metabolic engineering and microbial electrosynthesis.

The limited supply of reducing power restricts the efficient utilization of acetate in Yarrowia lipolytica. Here, microbial electrosynthesis (MES) system, enabling direct conversion of inward electrons to NAD(P)H, was used to improve the production of fatty alcohols from acetate based on pathway engineering. First, the conversion efficiency of acetate to acetyl-CoA was reinforced by heterogenous expression of ackA-pta genes. Second, a small amount of glucose was used as cosubstrate to activate the pentose phosphate pathway and promote intracellular reducing cofactors synthesis. Third, through the employment of MES system, the final fatty alcohols production of the engineered strain YLFL-11 reached 83.8 mg/g dry cell weight (DCW), which was 6.17-fold higher than the initial production of YLFL-2 in shake flask. Furthermore, these strategies were also applied for the elevation of lupeol and betulinic acid synthesis from acetate in Y. lipolytica, demonstrating that our work provides a practical solution for cofactor supply and the assimilation of inferior carbon sources.

Citral and trans-cinnamaldehyde, two plant-derived antimicrobial agents can induce Staphylococcus aureus into VBNC state with different characteristics.

Viable but nonculturable (VBNC) state bacteria are difficult to detect in the food industry due to their nonculturable nature and their recovery characteristics pose a potential threat to human health. The results of this study indicated that S. aureus was found to enter the VBNC state completely after induced by citral (1 and 2 mg/mL) for 2 h, and after induced by trans-cinnamaldehyde (0.5 and 1 mg/mL) for 1 h and 3 h, respectively. Except for VBNC state cells induced by 2 mg/mL citral, the VBNC state cells induced by the other three conditions (1 mg/mL citral, 0.5 and 1 mg/mL trans-cinnamaldehyde) were able to be resuscitated in TSB media. In the VBNC state cells induced by citral and trans-cinnamaldehyde, the ATP concentration was reduced, the hemolysin-producing ability was significantly decreased, but the intracellular ROS level was elevated. The results of heat and simulated gastric fluid experiments showed different environment resistance on VBNC state cells induced by citral and trans-cinnamaldehyde. In addition, by observing the VBNC state cells showed that irregular folds on the surface, increased electron density inside and vacuoles in the nuclear region. What's more, S. aureus was found to enter the VBNC state completely after induced by meat-based broth containing citral (1 and 2 mg/mL) for 7 h and 5 h, after induced by meat-based broth containing trans-cinnamaldehyde (0.5 and 1 mg/mL) for 8 h and 7 h. In summary, citral and trans-cinnamaldehyde can induce S. aureus into VBNC state and food industry needs to comprehensively evaluate the antibacterial capacity of these two plant-derived antimicrobial agents.

Inhibitory Effects of Trans-Cinnamaldehyde Against Pseudomonas aeruginosa Biofilm Formation.

Pseudomonas aeruginosa biofilm formation has been considered to be an important determinant of its pathogenicity in most infections. The antibiofilm activity of trans-cinnamaldehyde (TC) against P. aeruginosa was investigated in this study. Results demonstrated that the minimum inhibitory concentration (MIC) of TC against P. aeruginosa was 0.8 mg/mL, and subinhibitory concentrations (SICs) was 0.2 mg/mL and below. Crystal violet staining showed that TC at 0.05-0.2 mg/mL reduced biofilm biomass in 48 h in a concentration-dependent mode. The formation area of TC-treated biofilms was significantly declined (p < 0.01) on the glass slides observed by light microscopy. Field-emission scanning electron microscopy further demonstrated that TC destroyed the biofilm morphology and structure. Confocal laser scanning microscopic observed the dispersion of biofilms and the reduction of exopolysaccharides after TC treatment stained with concanavalin A (Con-A)-fluorescein isothiocyanate conjugate and Hoechst 33258. Meanwhile, TC caused a significant decrease (p < 0.01) in the component of polysaccharides, proteins, and DNA in extracellular polymeric substance. The swimming and swarming motility and quorum sensing of P. aeruginosa was also found to be significantly inhibited (p < 0.01) by TC at SICs. Furthermore, SICs of TC repressed the several genes transcription associated with biofilm formation as determined by real-time quantitative polymerase chain reaction. Overall, our findings suggest that TC could be applied as natural and safe antibiofilm agent to inhibit the biofilm formation of P. aeruginosa.

Association of Genetic Polymorphisms of TERT with Telomere Length in Coke Oven Emissions-Exposed Workers.

We explored the association between variations in the telomere maintenance genes and change in telomere length (TL) in workers. The TL of peripheral blood leukocytes from 544 coke oven workers and 238 controls were detected using the Real-time PCR method. Variations in four genes were then detected using the PCR based restriction fragment length polymorphism. The effects of environmental and genetic factors on TL were subsequently analyzed through covariance analysis and a generalized linear model .The TL of subjects with GG genotypes were longer than those with AG genotype in the TERT rs2736098 locus amongst the controls (P = .032). The combined effect of COEs exposure and AG+AA genotypes had a significant effect on TL (P < .001). The interaction between the COEs exposure factor and the rs2736098AG+AA genotypes had a significant effect on the TL (P < .05). The TL in coke oven workers is associated with the interactions between TERT rs2736098 AG+AA and COEs exposure.

Global divergent trends of algal blooms detected by satellite during 1982-2018.

Algal blooms (ABs) in inland lakes have caused adverse ecological effects, and health impairment of animals and humans. We used archived Landsat images to examine ABs in lakes (>1 km2 ) around the globe over a 37-year time span (1982-2018). Out of the 176032 lakes with area >1 km2 detected globally, 863 were impacted by ABs, 708 had sufficiently long records to define a trend, and 66% exhibited increasing trends in frequency ratio (FRQR, ratio of the number of ABs events observed in a year in a given lake to the number of available Landsat images for that lake) or area ratio (AR, ratio of annual maximum area covered by ABs observed in a lake to the surface area of that lake), while 34% showed a decreasing trend. Across North America, an intensification of ABs severity was observed for FRQR (p < .01) and AR (p < .01) before 1999, followed by a decrease in ABs FRQR (p < .01) and AR (p < .05) after the 2000s. The strongest intensification of ABs was observed in Asia, followed by South America, Africa, and Europe. No clear trend was detected for the Oceania. Across climatic zones, the contributions of anthropogenic factors to ABs intensification (16.5% for fertilizer, 19.4% for gross domestic product, and 18.7% for population) were slightly stronger than climatic drivers (10.1% for temperature, 11.7% for wind speed, 16.8% for pressure, and for 11.6% for rainfall). Collectively, these divergent trends indicate that consideration of anthropogenic factors as well as climate change should be at the forefront of management policies aimed at reducing the severity and frequency of ABs in inland waters.

Porous Nitrogen-Defected Carbon Nitride Derived from A Precursor Pretreatment Strategy for Efficient Photocatalytic Degradation and Hydrogen Evolution.

Graphitic carbon nitride (g-C3N4) has attracted extensive research attention because of its virtues of a metal-free nature, feasible synthesis, and excellent properties. However, the low specific surface area and mediocre charge separation dramatically limit the practical applications of g-C3N4. Herein, porous nitrogen defective g-C3N4 (PDCN) was successfully fabricated by the integration of urea-assisted supramolecular assembly with the polymerization process. Advanced characterization results suggested that PDCN exhibited a much larger specific surface area and dramatically improved charge separation compared to bulk g-C3N4, leading to the formation of more active sites and the improvement in mass transfer. The synthesized PDCN rendered a 16-fold increase in photocatalytic tetracycline degradation efficiency compared to g-C3N4. Additionally, the hydrogen evolution rate of PDCN was 10.2 times higher than that of g-C3N4. Meanwhile, the quenching experiments and electron spin resonance (ESR) spectra suggested that the superoxide radicals and holes are the predominant reactive species for the photocatalytic degradation process. This study may inspire the new construction design of efficient g-C3N4-based visible-light photocatalysts.

Identification of the prognostic value of ferroptosis-related gene signature in breast cancer patients.

BACKGROUND: Breast cancer (BRCA) is a malignant tumor with high morbidity and mortality, which is a threat to women's health worldwide. Ferroptosis is closely related to the occurrence and development of breast cancer. Here, we aimed to establish a ferroptosis-related prognostic gene signature for predicting patients' survival. METHODS: Gene expression profile and corresponding clinical information of patients from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database. The Least absolute shrinkage and selection operator (LASSO)-penalized Cox regression analysis model was utilized to construct a multigene signature. The Kaplan-Meier (K-M) and Receiver Operating Characteristic (ROC) curves were plotted to validate the predictive effect of the prognostic signature. Gene Ontology (GO) and Kyoto Encyclopedia of Genes, Genomes (KEGG) pathway and single-sample gene set enrichment analysis (ssGSEA) were performed for patients between the high-risk and low-risk groups divided by the median value of risk score. RESULTS: We constructed a prognostic signature consisted of nine ferroptosis-related genes (ALOX15, CISD1, CS, GCLC, GPX4, SLC7A11, EMC2, G6PD and ACSF2). The Kaplan-Meier curves validated the fine predictive accuracy of the prognostic signature (p < 0.001). The area under the curve (AUC) of the ROC curves manifested that the ferroptosis-related signature had moderate predictive power. GO and KEGG functional analysis revealed that immune-related responses were largely enriched, and immune cells, including activated dendritic cells (aDCs), dendritic cells (DCs), T-helper 1 (Th1), were higher in high-risk groups (p < 0.001). Oppositely, type I IFN response and type II IFN response were lower in high-risk groups (p < 0.001). CONCLUSION: Our study indicated that the ferroptosis-related prognostic signature gene could serve as a novel biomarker for predicting breast cancer patients' prognosis. Furthermore, we found that immunotherapy might play a vital role in therapeutic schedule based on the level and difference of immune-related cells and pathways in different risk groups for breast cancer patients.

Remote sensing of CDOM and DOC in alpine lakes across the Qinghai-Tibet Plateau using Sentinel-2A imagery data.

As important components of dissolved organic matter (DOM) in an aquatic environment, colored DOM (CDOM) and dissolved organic carbon (DOC) play an essential role in the carbon cycle of an inland aquatic system. Traditionally, CDOM and DOC in inland waters have been primarily determined using in situ observations and laboratory measurements. Most of past lake investigations on CDOM and DOC focused on easily accessible regions and covered a small fraction of lakes worldwide. To our knowledge, little is known about lakes in less accessible areas like the Qinghai-Tibet Plateau (QTP). To address this challenge, optical satellite remote sensing might be useful for capturing a synoptic view of CDOM and DOC with high frequency at large scales, complementing in situ sampling methods for inland waters. In this study, 216 samples collected from 36 lakes across the QTP (2014-2017) were examined to determine the relationships between CDOM absorption coefficient at 350 nm (a350) and Sentinel-2A Multi Spectral Instrument (MSI) imagery reflectance data. A strong positive linear correlation with a350 was observed with B4/B2 (R2 = 0.78, p < 0.01) and with B4/B3 (R2 = 0.62). A multi-step regression model was established for estimating a350 with B4/B2 and B4/B3 as input variables (R2 = 0.81, p < 0.01). A scattered CDOM-DOC relationship was revealed (R2 = 0.34, p < 0.05) using a pooled dataset. By dividing the inland waters into four separate groups in accordance with their salinity gradients, we were able to develop much stronger relationships (R2 > 0.8, p < 0.01) for CDOM-DOC. Significant differences between fresh and saline waters were demonstrated using satellite-derived CDOM and DOC, where high CDOM (0.86 ± 0.67 m-1) and low DOC (3.76 ± 4.92 mg L-1) concentrations were observed for freshwaters, while inverse trends of CDOM (0.53 ± 0.72 m-1) and DOC (15.76 ± 17.07 mg L-1) were demonstrated for saline lakes in the Tibetan Plateau. This study confirmed that satellite optical imagery can be used for the monitoring of CDOM and DOC of the lakes of the Tibetan Plateau, which are sensitive to a changing climate and are infrequently investigated due to the harsh environment and poor accessibility. Moreover, it highlighted the importance of combining salinity and remote sensing data in the process of estimating lake DOC.

Prognostic factors in patients with persistent/recurrent differentiated thyroid carcinoma after comprehensive treatment

Objective: To investigate the prognostic factors of patients with persistent/recurrent differentiated thyroid carcinoma (DTC) especially with external invasive persistent recurrent DTC after comprehensive treatment. Methods: The clinical data of 525 patients with persistent/recurrent DTC who underwent surgical treatment from August 2011 to June 2021 in the Department of Head and Neck Surgery of Jiangsu Cancer Hospital were retrospectively analyzed. The prognostic factors affecting overall survival (OS) and relapse-free survival (RFS) of persistent/recurrent DTC, especially external invasive persistent/recurrent DTC were analyzed. Results: Among 525 patients, 318 patients underwent thyroidectomy, 359 patients underwent central lymph node dissection, and 409 patients underwent lateral cervical lymph node dissection. Among 493 followed-up patients, 5-year OS and RFS were 95.10% and 89.60%, 8-year OS and RFS were 91.80% and 81.30%. Cox regression analysis showed that in patients with persistent/recurrent DTC after comprehensive treatment, age ≥55 years at reoperation after recurrence, male gender and distant metastasis were independent risk factors of OS (all P<0.05); while the simultaneous invasion of thyroid and lymph nodes, multiple organ invasion and the number of previous operations ≥2 were independent risk factors of RFS (all P<0.05). In patients with external invasive persistent/recurrent DTC after comprehensive treatment, age ≥55 years at reoperation after recurrence and male gender were independent risk factors of OS (both P<0.05); while multiple organ invasion and the number of previous operations ≥2 were independent risk factors of RFS (both P<0.05). Conclusions: Male patients aged 55 years old and above, with distant metastasis have a higher risk of poorer prognosis in persistent/recurrent DTC; while patients with simultaneous external invasion of thyroid and lymph nodes, multiple organ invasion and the number of previous operations ≥2 are more likely to relapse. For external invasive persistent/recurrent DTC, male patients aged 55 years old and above have a higher risk of poorer prognosis; while patients with multiple organ invasion and the number of previous operations ≥2 are more likely to have recurrence.

[A new quinoline alkaloid from Scolopendra subspinipes mutilans].

Three compounds, including scolosprine C(1), uracil(2) and hypoxanthine(3), were isolated and purified from the ethyl acetate fraction of centipede by silica gel normal-phase column chromatography, reversed-phase medium pressure preparation chromatography, and high-pressure semi-preparative HPLC. The structure was elucidated through a combination of spectroscopic analyses [such as nuclear magnetic resonance(NMR) and mass spectrometry(MS)] and literature review. Among them, compound 1 was a new quinoline alkaloid. In previous reports, we have described the isolation and structure elucidation of one new and two known quinoline alkaloids. In this paper, we would report the isolation and structure elucidation of scolosprine C in detail.

Circulatory CD4-Positive T-Lymphocyte Imbalance Mediated by Homocysteine-Induced AIM2 and NLRP1 Inflammasome Upregulation and Activation Is Associated with Human Abdominal Aortic Aneurysm.

INTRODUCTION: CD4-positive T lymphocytes (CD4 cells) play a significant role in human abdominal aortic aneurysm (AAA). However, we know little about the role of the different CD4 subtypes. OBJECTIVE: We aimed to discover the circulatory CD4 phenotypic marker profile and the roles of the newly found T helper cell 9 (Th9) and follicular helper T cells (Tfh) and that of inflammasomes in CD4 cells from AAA patients. METHODS: We extracted CD4 cells from 30 AAA patients and 21 age-matched controls. Phenotype-specific transcription factors (TFs) and inflammasomes were analyzed with qRT-PCR. RESULTS: Th17-, Th1-, Th9-, and Tfh-specific TFs and inflammasome components NLRP1 (NLR family pyrin domain-containing 1), NLRP3, NLRC4, AIM2 (absent in melanoma 2), PYCARD (apoptosis speck-like protein containing a CARD), and CASP1 (caspase 1) were upregulated, and T regulatory cell- and Th2-specific TFs were downregulated in the patients' peripheral blood CD4 cells. Homocysteine was involved in Tfh and Th17 imbalance by AIM2 and NLRP1 inflammasome upregulation. Blood total cholesterol level correlated positively with NLRP1 expression, and blood low-density lipoprotein level correlated negatively with FOXP3 expression. CONCLUSIONS: Inflammasome-induced CD4 cell imbalance was involved in AAA. We thought that AAA might be a consequence of synergism between systemic immune imbalance and local autoimmunity.

Variability of chlorophyll and the influence factors during winter in seasonally ice-covered lakes.

Lake ice is an essential and integral part of the cryosphere and freshwater systems. The formation of lake ice affects the physical, hydrological, and biological conditions of ecological systems. Global warming may contribute to even shorter periods of ice cover in the lakes of the Frigid Zone, which adversely affects the growth of phytoplankton and primary productivity. This study was conducted for the purpose of evaluating the growth of phytoplankton and factors involved, in 28 ice-covered lakes across the Songnen Plain, in the Northeast of China, to understand how they take part in the whole-ecosystem functioning. A total of 1026 water samples were collected in April, September, and January during the period 2014-2018. In the frozen period, the concentration levels of dissolved organic carbon (DOC), total nitrogen (TN), and total phosphorus (TP) were all comparable with the spring and autumn. Despite the limited light availability and low temperature, the phytoplankton survived in sub-ice waters during winter with a low concentration of chlorophyll a (Chla). Its average concentration was positively correlated with the concentration observed in the previous autumn (rp = 0.563, p < 0.01). According to the regression tree analysis, during the winter period, Chla was mainly related to the concentration of TN in sub-ice water (TNwater) and with the difference of concentration of TP between water and ice (TPcd). Furthermore, either in ice or in sub-ice water, the concentration of Chla was also significantly affected by total suspended matter (TSM) (p < 0.05). The levels of TNwater, TPcd, and TSM could explain the 77.8% of the variance in the concentration of Chla during winter with contributions in the ranges of 25.5%-35.0%, 9.2%-11.3%, and 21.5%-34.0%, respectively (p < 0.05). This research substantially contributes to comprehending how the existing conditions under-ice affect the whole ecosystem when the ice cover is reduced lakes or rivers.

Depletion of DNA damage binding protein 2 sensitizes triple-negative breast cancer cells to poly ADP-ribose polymerase inhibition by destabilizing Rad51.

Poly ADP-ribose polymerase inhibitors (PARPi) have shown promising therapeutic efficacy in triple-negative breast cancer (TNBC) patients. However, resistance ultimately develops, preventing a curative effect from being attained. Extensive investigations have indicated the diversity in the mechanisms underlying the PARPi sensitivity of breast cancer. In this study, we found that DNA damage binding protein 2 (DDB2), a DNA damage-recognition factor, could protect TNBC cells from PARPi by regulating DNA double-strand break repair through the homologous recombination pathway, whereas the depletion of DDB2 sensitizes TNBC cells to PARPi. Furthermore, we found that DDB2 was able to stabilize Rad51 by physical association and disrupting its ubiquitination pathway-induced proteasomal degradation. These findings highlight an essential role of DDB2 in modulating homologous recombination pathway activity and suggest a promising therapeutic target for TNBC.

Construction of medical equipment-based doctor health monitoring system.

The health status of doctors has been overlooked by the society and even the doctors themselves, especially those doctors who work long hours. Their attention is always on patients, so they are more likely to ignore their own health problems. Therefore, in this paper, we propose a medical equipment-based doctor health monitoring system (hereinafter referred to as Doc-care). Doc-care can be used as a private health manager for doctors, and doctors can monitor their health indicators in real time while using medical equipment to aid diagnosis and treatment. When the doctor's health status is neglected, Doc-care can protect the doctor's health; combining with the convolutional neural network method to detect and grade the doctor's health indicators, to assess the doctor's real-time health status. After referring to the doctor's past health data in the cloud server, giving appropriate advice and predictions about the doctor's health status.

Correction to: Construction of Medical Equipment-Based Doctor Health Monitoring System.

The original version of this article unfortunately contained a mistake. Corrections in equations which were highlighted in a doc file were not carried out. The original version has been corrected.

Ramosissimin, a new flavonol from Tararix ramosissima, induces apoptosis in rheumatoid arthritis fibroblast-like synoviocytes.

Tamarix ramosissima is a traditional Chinese herbal medicine used for rheumatoid arthritis (RA) treatment in Northwest China. Chemical investigation of EtOH/H2O extracts of T. ramosissima led to the discovery of a new flavonol, ramosissimin (1), together with the known flavonoids compounds quercetin (2), quercetin-3'4'-dimethylether (3) and kaempferol (4). By means of high resolution electrospray ionization mass spectroscopy (HRESIMS) and 1D and 2D-NMR experiments, and after comparison with literature data, the structures of the compounds were determined. The effect of compound 1 on the viability of RA fibroblast-like synoviocytes (RA-FLS) was evaluated by MTT assay. Apoptosis-inducing effect of compound 1 in RA-FLS was further investigated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay and activated caspase-3/7 level assessment using luminescent assay. The results revealed that ramosissimin displayed remarkable proliferation inhibitory effect in RA-FLS. Furthermore, compound 1 could significantly induce cellular apoptosis of RA-FLS and increase activated caspase-3/7 levels. It is suggested that ramosissimin may inhibit the proliferation of RA-FLS by inducing apoptosis.