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Yan-Yan Zhao,1,* Chun Wang,1,* Wei-Xiao Wang,2 Li-Mei Han,1 Caiyun Zhang,2 Jiao-Yang Yu,3 Wei Chen,2 Chun-Mei Hu1,4 1Department of Tuberculosis, the Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003, People’s Republic of China; 2Clinical Research Center, the Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, 210003, People’s Republic of China; 3Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, College of Life Sciences, Northwest University, Xi’an, 710069, People’s Republic of China; 4The Clinical Infectious Disease Center of Nanjing, Nanjing, 210003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Chen; Chun-Mei Hu, Email njyy039@njucm.edu.cn; njyy003@njucm.edu.cnBackground: Drug-resistant tuberculosis (TB) is an emerging threat to public health worldwide. Antimicrobial peptide (AMP) is a promising solution to solve the antimicrobial resistance crisis. The apolipoprotein E mimetic peptide COG1410 has been confirmed to simultaneously have neuroprotective, anti-inflammatory, and antibacterial activity. However, whether it is effective to inhibit growth of mycobacteria has not been investigated yet.Methods: The peptide COG1410 was synthesized with conventional solid-phase peptide synthesis and qualified by HPLC and mass spectrometry. Micro-dilution method was used to determine the minimal inhibitory concentration. A time-kill assay was used to determine the bactericidal dynamics of antimicrobial peptide and relative antibiotics. Static biofilm formation was conducted in 24-well plate and the biofilm was separated from planktonic cells and collected. The mechanism of action of COG1410 was explored by TEM observation and ATP leak assay. The localization of COG1410 was observed by confocal laser scan microscopy. The drug–drug interaction was determined by a checkerboard assay.Results: COG1410 was a potent bactericidal agent against M. smegmatis in vitro and within the macrophages with MIC 16 μg/mL, but invalid against M. abscess and M. tuberculosis. A time-kill assay showed that COG1410 killed M. smegmatis as potent as clarithromycin, but faster than LL-37, another short synthetic cationic peptide. 1× MIC COG1410 almost reduced 90% biofilm formation of M. smegmatis. Additionally, COG1410 was able to penetrate the cell membrane of macrophage and inhibit intracellular M. smegmatis growth. TEM observation and ATP leak assay found that COG1410 disrupted cell membrane and caused release of cell contents. Confocal fluorescence microscopy showed that FITC-COG1410 aggregated around cell membrane instead of entering the cytoplasm. Although COG1410 had relative high cytotoxicity, it exhibited strong additive interaction with regular anti-TB antibiotics, which reduced the working concentration of COG1410 and expanding safety window. After 30 passages, there was no induced drug resistance for COG1410.Conclusion: COG1410 was a novel and potent AMP against M. smegmatis by disrupting the integrity of cell membrane.Keywords: antimicrobial peptide, COG1410, Mycobacterium smegmatis, additive interaction

Aims The ESC/EACTS myocardial revascularization guidelines recently standardized the definition of patients at high ischemic risk (HIR). However, the ability of ESC/EACTS-HIR criteria to stratify ischemic and bleeding risk in a contemporary real-world East Asian cohort remains unexplored. Methods A total of 10,167 consecutive patients undergoing PCI from prospective Fuwai PCI Registry (January 2013 to December 2013) were reviewed. ESC/EACTS-HIR features was defined as having at least one of the eight clinical and angiographic characteristics. The primary ischemic endpoint was target vessel failure (cardiac death, target vessel myocardial infarction [MI], or target vessel revascularization [TVR]); bleeding outcome was assessed using the BARC type 2, 3, or 5 bleeding. Median follow-up was 29 months. Results Compared with non-HIR patients, HIR patients (n=5,149, 50.6%) were associated with increased risk for target vessel failure (adjusted hazard ratio [HRadjust]: 1.48 [1.25-1.74]) and patient-oriented composite outcome (HRadjust: 1.44 [1.28-1.63]), as well as cardiac death, MI, and TVR. By contrast, the risk of clinically relevant bleeding was not significantly different between the two groups. (HRadjust: 0.84 [0.66-1.06]). Greater than or equal to three implanted stents and diabetic patients with diffuse multivessel coronary disease emerged as independent predictors for long-term adverse outcomes. There was no significant interaction between high bleeding risk (HBR) status and clinical outcomes associated with ESC/EACTS-HIR criteria (all Pinteraction ＞0.05). Conclusion The ESC/EACTS-HIR features identified patients at increased risk of thrombotic events, including cardiac death, but not for clinically relevant bleeding. Importantly, HBR did not modify cardiovascular risk subsequent to patients with ESC/EACTS-HIR features, suggesting its potential clinical applicability in tailoring antithrombotic therapy.

Objectives: To investigate the mechanism of astragaloside IV (AS-IV) inhibiting the invasion and metastasis of vulvar squamous cell carcinoma (VSCC). Material and methods: MTT and plate colony-formation assays were used to examine the cell proliferation of VSCC (SW962 cell line). Transwell and scratch wound-healing assays were used to analyse cell migration and invasion. Western blot was used to detect the expression of relevant proteins in terms of cell proliferation, invasion and metastasis, as well as the TGF-β1/FAK/AKT signaling pathway. Results: The results showed that AS-IV inhibited the proliferation of SW962 cells in a concentration-dependent manner, as demonstrated by the upregulation of P53 and P21 expression and the downregulation of cyclin D1 expression. AS-IV decreased the ability of cell invasion and metastasis by the downregulation of MMP-2 and MMP-9 expression. When TGF-β1 was added to SW962 cells, the expression of the N-cadherin and Vimentin were upregulated and that of the E-cadherin was downregulated. Subsequently, fibroblast-like elongated spindle-shaped cells appeared, which suggests that TGF-β1 could induce EMT in SW962 cells. Furthermore, the expression of p-FAK, p-AKT, MMP-2 and MMP-9 were upregulated. The expression of these proteins exhibited the opposite effect after AS-IV intervention. Cell invasion and metastasis were suppressed. Conclusions: AS-IV inhibits cell invasion and metastasis in VSCC through the TGF-β1/FAK/AKT signalling pathway.

OBJECTIVES: To assess the correlation between triglyceride glucose (TyG) index and in-hospital mortality in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: A total of 2190 patients with STEMI who underwent primary angiography within 12 h from symptom onset were selected from the prospective, nationwide, multicenter CAMI registry. TyG index was calculated with the formula: Ln [fasting triglycerides (mmol/L) × fasting glucose (mmol/L)/2]. Patients were divided into three groups according to the tertiles of TyG index. The primary endpoint was in-hospital mortality. RESULTS: Overall, 46 patients died during hospitalization, in-hospital mortality was 1.5%, 2.2%, 2.6% for tertile 1, tertile 2, and tertile 3, respectively. However, TyG index was not significantly correlated with in-hospital mortality in single-variable logistic regression analysis. Nonetheless, after adjusting for age and sex, TyG index was significantly associated with higher mortality when regarded as a continuous variable (adjusted OR = 1.75, 95% CI: 1.16-2.63) or categorical variable (tertile 3 vs. tertile 1: adjusted OR = 2.50, 95% CI: 1.14-5.49). Furthermore, TyG index, either as a continuous variable (adjusted OR = 2.54, 95% CI: 1.42-4.54) or categorical variable (tertile 3 vs. tertile 1: adjusted OR = 3.57, 95% CI: 1.24-10.29), was an independent predictor of in-hospital mortality after adjusting for multiple confounders in multivariable logistic regression analysis. In subgroup analysis, the prognostic effect of high TyG index was more significant in patients with body mass index < 18.5 kg/m(2) (P(interaction) = 0.006). CONCLUSIONS: This study showed that TyG index was positively correlated with in-hospital mortality in STEMI patients who underwent primary angiography, especially in underweight patients.

Although the DNA damage response (DDR) is associated with the radioresistance characteristics of lung cancer cells, the specific regulators and underlying mechanisms of the DDR are unclear. Here, we identified the serine proteinase inhibitor clade E member 2 (SERPINE2) as a modulator of radiosensitivity and the DDR in lung cancer. Cells exhibiting radioresistance after ionizing radiation show upregulation of SERPINE2, and SERPINE2 knockdown improves tumor radiosensitivity in vitro and in vivo. Functionally, SERPINE2 deficiency causes a reduction in homologous recombination repair, rapid recovery of cell cycle checkpoints, and suppression of migration and invasion. Mechanistically, SERPINE2 knockdown inhibits the accumulation of p-ATM and the downstream repair protein RAD51 during DNA repair, and RAD51 can restore DNA damage and radioresistance phenotypes in lung cancer cells. Furthermore, SERPINE2 can directly interact with MRE11 and ATM to facilitate its phosphorylation in HR-mediated DSB repair. In addition, high SERPINE2 expression correlates with dismal prognosis in lung adenocarcinoma patients, and a high serum SERPINE2 concentration predicts a poor response to radiotherapy in non-small cell lung cancer patients. In summary, these findings indicate a novel regulatory mechanism by which SERPINE2 modulates the DDR and radioresistance in lung cancer.

Elevated thioredoxin-interacting protein (TXNIP)-induced pyroptosis contributes to the pathology of diabetic kidney disease (DKD). However, the molecular mechanisms in dysregulated TXNIP in DKD remain largely unclear.Transcriptomic analysis identified a novel long noncoding RNA-Prader Willi/Angelman region RNA, SNRPN neighbour (PWARSN)-which was highly expressed in a proximal tubular epithelial cell (PTEC) under high glucose conditions. We focused on revealing the functions of PWARSN in regulating TXNIP-mediated pyroptosis in PTECs by targeting PWARSN expression via lentivirus-mediated overexpression and CRISPR-Cas9-based knockout in vitro and overexpressing PWARSN in the renal cortex by AAV-9 targeted injection in vivo. A number of molecular techniques disclosed the mechanisms of PWARSN in regulating TXNIP induced-pyroptosis in DKD.TXNIP-NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome and PTEC pyroptosis were activated in the renal tubules of patients with DKD and in diabetic mice. Then we explored that PWARSN enhanced TXNIP-driven PTECs pyroptosis in vitro and in vivo. Mechanistically, cytoplasmic PWARSN sponged miR-372-3p to promote TXNIP expression. Moreover, nuclear PWARSN interacted and facilitated RNA binding motif protein X-linked (RBMX) degradation through ubiquitination, resulting in the initiation of TXNIP transcription by reducing H3K9me3-enrichment at the TXNIP promoter. Further analysis indicated that PWARSN might be a potential biomarker for DKD.These findings illustrate distinct dual molecular mechanisms for PWARSN-modulated TXNIP and PTECs pyroptosis in DKD, presenting PWARSN as a promising therapeutic target for DKD.

Recent evidence shows that the expression levels of histamine receptor H3 (Hrh3) are upregulated in several types of cancer. However, the role of Hrh3 in non-small cell lung cancer (NSCLC) has not been elucidated. In the present study, we showed that the expression levels of Hrh3 were significantly increased in NSCLC samples, and high levels of Hrh3 were associated with poor overall survival (OS) in NSCLC patients. In five human NSCLC cell lines tested, Hrh3 was significantly upregulated. In NSCLC cell lines H1975, H460, and A549, Hrh3 antagonist ciproxifan (CPX, 10-80 μM) exerted moderate and concentration-dependent inhibition on the cell growth and induced apoptosis, whereas its agonist RAMH (80 μM) reversed these effects. Furthermore, inhibition of Hrh3 by CPX or siRNA retarded the migration and invasion of NSCLC cells through inhibiting epithelial-mesenchymal transition (EMT) progression via reducing the phosphorylation of PI3K/Akt/mTOR and MEK/ERK signaling pathways. In nude mice bearing H1975 cell xenograft or A549 cell xenograft, administration of CPX (3 mg/kg every other day, intraperitoneal) significantly inhibited the tumor growth with increased E-cadherin and ZO-1 expression and decreased Fibronectin expression in tumor tissue. In conclusion, this study reveals that Hrh3 plays an important role in the growth and metastasis of NSCLC; it might be a potential therapeutic target against the lung cancer.

Chalcomoracin (CMR) is a kind of Diels-Alder adduct extracted from the mulberry leaves. Recent studies showed that CMR has a broad spectrum of anticancer activities and induces paraptosis in breast cancer and prostate cancer cells. In this study, we investigated the effects of CMR against human non-small cell lung cancer cells and the underlying mechanisms. We found that CMR dose-dependently inhibited the proliferation of human lung cancer H460, A549 and PC-9 cells. Furthermore, exposure to low and median doses of CMR induced paraptosis but not apoptosis, which was presented as the formation of extensive cytoplasmic vacuolation with increased expression of endoplasmic reticulum stress markers, Bip and Chop, as well as activation of MAPK pathway in the lung cancer cells. Knockdown of Bip with siRNA not only reduced the cell-killing effect of CMR, but also decreased the percentage of cytoplasmic vacuoles in H460 cells. Moreover, CMR also increased the sensitivity of lung cancer cells to radiotherapy through enhanced endoplasmic reticulum stress. In lung cancer H460 cell xenograft nude mice, combined treatment of CMR and radiation caused greatly enhanced tumor growth inhibition with upregulation of endoplasmic reticulum stress proteins and activation of pErk in xenograft tumor tissue. These data demonstrate that the anticancer activity and radiosensitization effect of CMR result from inducing paraptosis, suggesting that CMR could be considered as a potential anticancer agent and radiation sensitizer in the future cancer therapeutics.

We investigated the characteristics of nitrogen uptake, distribution, and utilization in the three-year-old bearing Huangguan pear trees following以3年生黄冠梨为材料,探讨了早春施用

Glutathione (GSH) plays an important role in cells, which is an essential endogenous antioxidant. Here, we have developed a new detection platform to analyze GSH levels. In our system, fluorescent polydopamine (PDA) nanoparticles, as signal indicators, were obtained by oxidation through cobalt oxyhydroxide (CoOOH) nanosheets. When CoOOH was present, CoOOH could quickly oxidize dopamine to fluorescent PDA nanoparticles. However, once GSH existed, CoOOH nanosheets were decomposed into Co2+, and oxidation between CoOOH and dopamine was prevented with weaker fluorescence occurring. Thus, we could realize detection of the GSH concentration according to the decreased fluorescence value of the fluorescent polydopamine. This method provides a fast, simple, high sensitivity and desirable selectivity platform for GSH monitoring.

PhyllostacShys bambusoides, Phyllostachys nigra var. henonis, and Pseudosasa japonica are Bambusoideae species widely cultivated in Korea. They are used in herbal medicines due to their potent bioactivities. However, the various chemical compositions of the different Bambusoideae species have not been documented; on the market, all are typically being labeled as bamboo, without species discrimination. Therefore, the present study aimed to evaluate the differences between these three Bambusoideae species based on simultaneous quantitative determination of several compounds. An analysis platform, consisting of ultrasound-assisted liquid-liquid extraction combined with high-performance liquid chromatography equipped with a diode array detector (HPLC-DAD) and a triple quadrupole mass spectrometer in multiple reaction monitoring mode (HPLC-MRM/MS), was developed and validated to analyze the biochemical compounds in these three Bambusoideae species. Multivariate statistical analysis was applied to discriminate samples, data visualization, and identification of sample clustering. As a result, nine compounds were identified as marker compounds for species differentiation. This study demonstrated that the chemotaxonomic application of three common Bambusoideae species could be achieved using our analytical platform coupled with appropriate multivariate statistical analysis. These abilities will help prevent possible side effects and unexpected biological activity resulting from incorrect species identification.

Fibroblast growth factor 21 (FGF21) functions as a polypeptide hormone to regulate glucose and lipid metabolism, and its expression is regulated by cellular metabolic stress. Pyruvate is an important intermediate metabolite that acts as a key hub for cellular fuel metabolism. However, the effect of pyruvate on hepatic FGF21 expression and secretion remains unknown. Herein, we examined the gene expression and protein levels of FGF21 in human hepatoma HepG2 cells and mouse AML12 hepatocytes in vitro, as well as in mice in vivo. In HepG2 and AML12 cells, pyruvate at concentrations above 0.1 mM significantly increased FGF21 expression and secretion. The increase in cellular cAMP levels by adenylyl cyclase activation, phosphodiesterase (PDE) inhibition and 8-Bromo-cAMP administration significantly restrained pyruvate-stimulated FGF21 expression. Pyruvate significantly increased PDE activities, reduced cAMP levels and decreased CREB phosphorylation. The inhibition of exchange protein directed activated by cAMP (Epac) and cAMP response element binding protein (CREB) upregulated FGF21 expression, upon which pyruvate no longer increased FGF21 expression. The increase in plasma pyruvate levels in mice induced by the intraperitoneal injection of pyruvate significantly increased FGF21 gene expression and PDE activity with a reduction in cAMP levels and CREB phosphorylation in the mouse liver compared with the control. In conclusion, pyruvate activates PDEs to reduce cAMP and then inhibits the cAMP–Epac–CREB signaling pathway to upregulate FGF21 expression in hepatocytes.

Background: As an emergent and fulminant infectious disease, Corona Virus Disease 2019 (COVID-19) has caused a worldwide pandemic. The early identification and timely treatment of severe patients are crucial to reducing the mortality of COVID-19. This study aimed to investigate the clinical characteristics and early predictors for severe COVID-19, and to establish a prediction model for the identification and triage of severe patients. Methods: All confirmed patients with COVID-19 admitted by the Second Affiliated Hospital of Air Force Medical University were enrolled in this retrospective non-interventional study. The patients were divided into a mild group and a severe group, and the clinical data were compared between the two groups. Univariate and multivariate analysis were used to identify the independent early predictors for severe COVID-19, and the prediction model was constructed by multivariate logistic regression analysis. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the prediction model and each early predictor. Results: A total of 40 patients were enrolled in this study, of whom 19 were mild and 21 were severe. The proportions of patients with venerable age (≥60 years old), comorbidities, and hypertension in severe patients were higher than that of the mild (P < 0.05). The duration of fever and respiratory symptoms, and the interval from illness onset to viral clearance were longer in severe patients (P < 0.05). Most patients received at least one form of oxygen treatments, while severe patients required more mechanical ventilation (P < 0.05). Univariate and multivariate analysis showed that venerable age, hypertension, lymphopenia, hypoalbuminemia and elevated neutrophil lymphocyte ratio (NLR) were the independent high-risk factors for severe COVID-19. ROC curves demonstrated significant predictive value of age, lymphocyte count, albumin and NLR for severe COVID-19. The sensitivity and specificity of the newly constructed prediction model for predicting severe COVID-19 was 90.5% and 84.2%, respectively, and whose positive predictive value, negative predictive value and crude agreement were all over 85%. Conclusions: The severe COVID-19 risk model might help clinicians quickly identify severe patients at an early stage and timely take optimal therapeutic schedule for them.

The Space-based multi-band astronomical Variable Objects Monitor (SVOM) is a Chinese-French satellite dedicated to the observation and study of Gamma-Ray Bursts (GRBs) and other variable sources. Among the four scientific payloads onboard SVOM, the Gamma-Ray Monitor (GRM) is designed to detect GRBs in the 15 keV to 5 MeV energy range. The final performance of GRM can be affected by the space environment background during the flight. In this paper, the authors present the in-orbit background simulation results by using the GEANT4 Monte-Carlo simulation toolkit. Additionally, we studied the Earth occultation effect of the space background due to the anti-solar pointing strategy of SVOM. The total background count rate of each spectrometer of GRM fluctuates between about 840 counts/s and 1341 counts/s, and is dominated by the cosmic X-ray background. Finally, we discuss the emission lines of the background and their potential use for in-orbit calibration of GRM. Our simulation study results can help to understand the impact of the space radiation environment on GRM with the latest geometrical model and can be further compared and updated with the real in-orbit measurement in the future.

The present study was aimed to clarify the signaling molecular mechanism by which fibroblast growth factor 21 (FGF21) regulates leptin gene expression in adipocytes. Differentiated 3T3-F442A adipocytes were used as study object. The mRNA expression level of leptin was detected by fluorescence quantitative RT-PCR. The phosphorylation levels of proteins of signal transduction pathways were detected by Western blot. The results showed that FGF21 significantly down-regulated the mRNA expression level of leptin in adipocytes, and FGF21 receptor inhibitor BGJ-398 could completely block this effect. FGF21 up-regulated the phosphorylation levels of ERK1/2 and AMPK in adipocytes. Either ERK1/2 inhibitor SCH772984 or AMPK inhibitor Compound C could partially block the inhibitory effect of FGF21, and the combined application of these two inhibitors completely blocked the effect of FGF21. Neither PI3K inhibitor LY294002 nor Akt inhibitor AZD5363 affected the inhibitory effect of FGF21 on leptin gene expression. These results suggest that FGF21 may inhibit leptin gene expression by activating ERK1/2 and AMPK signaling pathways in adipocytes.

During male gametogenesis in Arabidopsis, the haploid microspore undergoes an asymmetric division to produce a vegetative and a generative cell, the latter of which continues to divide symmetrically to form two sperms. This simple system couples cell cycle with cell fate specification. Here we addressed the role of DNA replication in male gametogenesis using a mutant bicellular pollen 1 (bice1), which produces bicellular, rather than tricellular, pollen grains as in the wild-type plant at anthesis. The mutation prolonged DNA synthesis of the generative cell, which resulted in c. 40% of pollen grains arrested at the two-nucleate stage. The extended S phase did not impact the cell fate of the generative cell as shown by cell-specific markers. BICE1 encodes a plant homolog of human D123 protein that is required for G1 progression, but the underlying mechanism is unknown. Here we showed that BICE1 interacts with MCM4 and MCM7 of the pre-replication complex. Consistently, double mutations in BICE1 and MCM4, or MCM7, also led to bicellular pollen and condensed chromosomes. These suggest that BICE1 plays a role in modulating DNA replication via interaction with MCM4 and MCM7.

Background This study aimed to study the osteo-preservative effects of captopril, an inhibitor on angiotensin-converting enzyme (ACE), on bone mass, micro-architecture and histomorphology as well as the modulation of captopril on skeletal renin-angiotensin system (RAS) and regulators for bone metabolism in mice with bilateral orchidectomy. Methods The orchidectomized (ORX) mice were orally administered with vehicle or captopril at low dose (10 mg/kg) and high dose (50 mg/kg) for six weeks. The distal femoral end, the proximal tibial head and the lumbar vertebra (LV) were stained by hematoxylin and eosin, Safranin O/Fast Green and masson-trichrome. Micro-computed tomography was performed to measure bone mineral density (BMD). Results Treatment with captopril increased trabecular bone area at distal metaphysis of femur, proximal metaphysis of tibia and LV-4, moreover, high dose of captopril significantly elevated trabecular BMD of LV-2 and LV-5. The mRNA expressions of renin receptor, angiotensinogen, carbonic anhydrase II, matrix metalloproteinase-9, and tumor necrosis factor-alpha were significantly decreased in tibia of ORX mice following treatment with captopril. The administration with captopril enhanced the ratio of OPG/RANKL mRNA expression, the mRNA expression of transforming growth factor-beta and the protein expression of bradykinin receptor-1. Conclusions The inhibition on ACE by captopril exerts beneficial effects on trabecular bone of ORX mice. The therapeutic efficacy may be attributed to the regulation of captopril on local RAS and cytokines in bone.

A novel fluorescence sensing platform based on polydopamine nanospheres and 6′-carboxyfluorescein labeled single-stranded DNA has been developed for monitoring the concentration of exonuclease I. D...

Cyanophages, widespread in aquatic systems, are a class of viruses that specifically infect cyanobacteria. Though they play important roles in modulating the homeostasis of cyanobacterial populations, little is known about the freshwater cyanophages, especially those hypothetical proteins of unknown function. Mic1 is a freshwater siphocyanophage isolated from the Lake Chaohu. It encodes three hypothetical proteins Gp65, Gp66, and Gp72, which share an identity of 61.6% to 83%. However, we find these three homologous proteins differ from each other in oligomeric state. Moreover, we solve the crystal structure of Gp72 at 2.3 A, which represents a novel fold in the α + β class. Structural analyses combined with redox assays enable us to propose a model of disulfide bond mediated oligomerization for Gp72. Altogether, these findings provide structural and biochemical basis for further investigations on the freshwater cyanophage Mic1.

To observe the effect of electroacupuncture (EA) of "Baihui" (GV20) and "Zusanli" (ST36) on the expression of stromal cell derived factor-1α (SDF-1α) and CD34 in ischemic cortex tissue of cerebral ische-mia /reperfusion injury (CI/RI) rats, so as to study its mechanisms underlying improving CI/RI.Thirty male SD rats were equally and randomly divided into sham operation, model and EA groups (After modeling, the neurological deficit score, and the numbers of SDF-1α and CD34-positive cells in the ischemic cerebral cortex tissue were significantly increased in the model group (EA of GV20 and ST36 can improve neurological function of CI/RI rats, which may be associated with its effect in up-regulating the expression of SDF-1α and CD34 proteins in the ischemic cerebral cortex tissues.

Tubulointerstitial fibrosis (TIF) plays an important role in the progression of renal fibrosis in diabetic nephropathy (DN). Accumulating evidence supports a crucial inhibitory effect of dapagliflozin, a SGLT2 inhibitor, on TIF, but the underlying mechanisms remain largely unknown. This study aimed to shed light on the efficacy of dapagliflozin in reducing TIF as well as its possible impact on renal function. TIF in human kidney biopsies obtained from patients with DN was quantified by histopathological staining. In vitro, HK-2 cells were incubated in high glucose with dapagliflozin or fludarabine, and epithelial-mesenchymal transition (EMT) was determined. In vivo experiments were performed in streptozotocin (STZ)-induced type 1 diabetic mice treated with dapagliflozin by gavage for 16 weeks, after which specific functional characteristics and TIF were analyzed. In both DN patients and diabetic mice, fibronectin and Col IV, as well as STAT1 protein in the kidneys were increased as compared with controls. Dapagliflozin significantly decreased blood glucose, and renal STAT1 and TGF-beta 1 expression in mice. Furthermore, dapagliflozin improved renal function, and attenuated diabetes-induced TIE In HK-2 cells, dapagliflozin, and fludarabine directly decreased aberrant STAT1 expression and reversed high glucose-induced downregulation of E-cadherin and a-SMA induction. Thus, the results demonstrate that dapagliflozin not only improves hyperglycemia but also slows down the progression of diabetes-associated renal TIF by improving hyperglycemia-induced activation of the STAT1/TGF-beta 1 pathway.

Background Small RNAs play an important role in regulating plant responses to abiotic stress through modulation of the processing, stability, and translation of larger RNAs. Plants employ complex mechanisms of gene regulation to respond to salinity stress. Results In this study, we constructed 12 small RNA libraries, 12 mRNA libraries, and a degradome library to systematically investigate the miRNAs response to salt stress. A total of 312 cotton miRNAs were identified and of these, 80 were known ghr-miRNAs. 144 genes showed significant differential expression under salt stress combined with the targeting relationship between the sRNA data and mRNA data. We found 56 miRNA-mRNA pairs which were positively correlated, and 91 pairs which were negatively correlated. Using degradome sequencing, 72 target genes were identified associated with 25 miRNA families. Gene ontology and KEGG analysis indicated some targets were involved in vital biological pathways of salinity stress tolerance: 14 were involved in responses to abiotic stress, two were associated with an environmental adaptation pathway, and a total of 16 NAC and MYB family transcription factors were related to salinity stress. Conclusions The present study identified a large number of cotton miRNAs and identified relationships between miRNA and mRNA, with function annotation revealing their possible biological roles in response to salt stress. Our findings will further functional studies of cotton miRNAs and the salt tolerance mechanism.

Carboxysome, encapsulating an enzymatic core within an icosahedral-shaped semipermeable protein shell, could enhance CO2 fixation under low CO2 conditions in the environment. The shell of Halothiobacillus neapolitanus α-carboxysome possesses two 38% sequence-identical pentameric proteins, namely CsoS4A and CsoS4B. However, the functions of two paralogous pentameric proteins in α-carboxysome assembly remain unknown. Here we report the crystal structure of CsoS4B at 2.15 A resolution. It displays as a stable pentamer, each subunit of which consists of a β-barrel core domain, in addition to an insertion of helix α1 that forms the central pore. Structural comparisons and multiple-sequence alignment strongly indicate that CsoS4A and CsoS4B differ from each other in interacting with various components of α-carboxysome, despite they share a similar overall structure. These findings provide the structural basis for further investigations on the self-assembly process of carboxysome.

Facilitative glucose transporters (GLUT) are proteins that mediate glucose transmembrane transport in the form of facilitated diffusion, which play an important role in regulating cell energy metabolism. There are many breakthroughs in researches of facilitative GLUT in recent years. It has been known that there are 14 subtypes of facilitative GLUT with obvious tissue specificity in distribution and physiological function. In the present review, the tissue and cellular distribution, subcellular localization, expression regulation, physiological function and the relationship to diseases of facilitative GLUT subtypes were summarized, in order to further understand their physiological and pathophysiological significances.

As an important biological small molecule, ascorbic acid (AA) plays a key role in many bioprocesses. Here, we developed a novel method to evaluate AA based on the redox reaction between CoOOH and AA. In our work, a nanosystem was constructed with fluorescent polydopamine (PDA) nanoparticles and CoOOH nanosheets, which were used as signal indicators and an oxidant respectively. This is the first time that fluorescent PDA nanoparticles were synthesized through oxidation by CoOOH nanosheets. In the absence of AA, dopamine was oxidized to quinone derivatives and further spontaneously polymerized into fluorescent PDA nanoparticles which had strong fluorescence signals. When there was AA in the reaction system, CoOOH nanosheets would be reduced to Co2+, which would prevent the synthesis of fluorescent PDA nanoparticles due to the absence of oxidant CoOOH, resulting in weak fluorescence. We hence used the fluorescence intensity of the PDA nanoparticles to detect AA concentration. The fluorescence of this sensing platform was linear with the concentration of AA in the range of 0–500 μM with a detection limit of 4.8 μM. In addition, the sensor was simple, fast, label-free, and low cost, and may be used to detect other small molecules based on the redox reaction.

A new pseurotin A 3 ( 3 ), which was obtained from the fungus Aspergillus terreus was converted into its acetyl derivative ( 4 ). Optical rotation (OR), 13 C NMR, electronic circular dichroism (ECD) and vibrational circular dichroism (VCD) were measured for (+)- 4 and computed for four possible isomers using quantum theory. Absolute configuration of (+)- 4 was finally assigned as (5 S ,8 S ,9 R ,10 S ,11 R, 12 Z ) by comparing the predicted OR, ECD and VCD spectra to the experimental data. Therefore, the new compound 3 should have the (5 S ,8 S ,9 R ,10 S ,11 R, 12 Z ) too.

BACKGROUND This study aims to assess the efficacy and safety of weekly paclitaxel (WP) for the treatment of advanced ovarian cancer (AOC). METHODS This study will systematically search bibliographic databases (MEDLINE, EMBASE, Cochrane Library, Web of Science, CINAHL, PSYCINFO, Allied and Complementary Medicine Database, CNKI, WANGFANG, and Chinese Biomedical Literature Database) and other literature sources from inception to the March 1, 2020 without language and publication time limitations. Two authors will independently complete all literature selection, data collection, and study quality evaluation. Any disagreements will be solved by a third author through discussion. We will analyze data by RevMan V.5.3 software. RESULTS This study will systematically generate a comprehensive summary on the efficacy and safety of WP for the treatment of AOC. CONCLUSION This study may provide beneficial evidence of WP for the treatment of AOC. SYSTEMATIC REVIEW REGISTRATION INPLASY202040193.

Objective Small coronary vessel disease (disease affecting coronary vessels with main branch diameters of ≤ 2.75 mm) is a common and intractable problem in percutaneous coronary intervention (PCI). This study was designed to test the theory that the effectiveness and safety of drug-eluting balloons for the treatment of de novo lesions in small coronary vessels are non-inferior to those of drug-eluting stents. Methods We designed a prospective, multicenter, randomized, controlled clinical trial aiming to assess the effectiveness and safety of the RESTORE® (Cardionovum, Bonn, Germany) drug-eluting balloon (DEB) versus the RESOLUTE® (Medtronic, USA) drug-eluting stent (DES) in the treatment of small coronary vessel disease. This trial started in August 2016. A total of 230 patients with a reference vessel diameter (RVD) ≥ 2.25 mm and ≤ 2.75 mm were randomly assigned to treatment with a DEB or a DES at a 1:1 ratio. The study was also designed to enroll 30 patients with an RVD ≥ 2.00 mm and ≤ 2.25 mm in the tiny vessel cohort. Results The key baseline data include demographic characteristics, relative medical history, baseline angiographic values and baseline procedural characteristics. The primary endpoint is in-segment diameter stenosis at nine months after the index procedure. Secondary endpoints include acute success, all-cause death, myocardial infarction, target vessel revascularization, target lesion revascularization and stent thrombosis. Conclusions The study will evaluate the clinical efficacy, angiographic outcomes, and safety of DEBs compared to DESs in the treatment of de novo coronary artery lesions in small vessels.