Drug resistance in ovarian cancer: from mechanism to clinical trial.

Ovarian cancer is the leading cause of gynecological cancer-related death. Drug resistance is the bottleneck in ovarian cancer treatment. The increasing use of novel drugs in clinical practice poses challenges for the treatment of drug-resistant ovarian cancer. Continuing to classify drug resistance according to drug type without understanding the underlying mechanisms is unsuitable for current clinical practice. We reviewed the literature regarding various drug resistance mechanisms in ovarian cancer and found that the main resistance mechanisms are as follows: abnormalities in transmembrane transport, alterations in DNA damage repair, dysregulation of cancer-associated signaling pathways, and epigenetic modifications. DNA methylation, histone modifications and noncoding RNA activity, three key classes of epigenetic modifications, constitute pivotal mechanisms of drug resistance. One drug can have multiple resistance mechanisms. Moreover, common chemotherapies and targeted drugs may have cross (overlapping) resistance mechanisms. MicroRNAs (miRNAs) can interfere with and thus regulate the abovementioned pathways. A subclass of miRNAs, "epi-miRNAs", can modulate epigenetic regulators to impact therapeutic responses. Thus, we also reviewed the regulatory influence of miRNAs on resistance mechanisms. Moreover, we summarized recent phase I/II clinical trials of novel drugs for ovarian cancer based on the abovementioned resistance mechanisms. A multitude of new therapies are under evaluation, and the preliminary results are encouraging. This review provides new insight into the classification of drug resistance mechanisms in ovarian cancer and may facilitate in the successful treatment of resistant ovarian cancer.

Enhanced Electrochemical Catalysis: Hydrogen Evolution Using Bimetallic Sulfides on Nickel Foam.

Hydrogen is considered clean energy with broad application prospects for the 21st century, and water electrolysis plays a crucial role in hydrogen production. However, economic limitations and large overpotential values hinder its development. In this study, we deposited nickel (Ni), iron (Fe), and sulfur (S) onto nickel foam (NF) using the constant potential method to form the Ni-S-Fe/NF catalyst, which exhibited an exceptionally low overpotential (31 mV) at a current density of -10 mA cm-2, and a Tafel slope of 75.1 mV dec-1 in 1 M sodium hydroxide. It showed a minor charge resistance (1.256 Ω). The amorphous phase structure and optimized catalyst composition promoted outstanding hydrogen evolution activity. This work offers valuable perspectives on the industrial application of hydrogen production.

Bi/CeO2-Decorated CuS Electrocatalysts for CO2-to-Formate Conversion.

The electrocatalytic carbon dioxide (CO2) reduction reaction (CO2RR) is extensively regarded as a promising strategy to reach carbon neutralization. Copper sulfide (CuS) has been widely studied for its ability to produce C1 products with high selectivity. However, challenges still remain owing to the poor selectivity of formate. Here, a Bi/CeO2/CuS composite was synthesized using a simple solvothermal method. Bi/CeO2-decorated CuS possessed high formate selectivity, with the Faraday efficiency and current density reaching 88% and 17 mA cm-2, respectively, in an H-cell. The Bi/CeO2/CuS structure significantly reduces the energy barrier formed by OCHO*, resulting in the high activity and selectivity of the CO2 conversion to formate. Ce4+ readily undergoes reduction to Ce3+, allowing the formation of a conductive network of Ce4+/Ce3+. This network facilitates electron transfer, stabilizes the Cu+ species, and enhances the adsorption and activation of CO2. Furthermore, sulfur catalyzes the OCHO* transformation to formate. This work describes a highly efficient catalyst for CO2 to formate, which will aid in catalyst design for CO2RR to target products.

Construct of an Electrodeposited Cobalt-Molybdenum Film and Evaluation of Its Efficiency in Hydrogen Evolution.

Hydrogen is a valuable clean energy source, and electrolysis to produce hydrogen from water is a crucial component. However, a major problem of hydrogen generation by electrolysis is its large overpotential and poor economics. To reduce the overpotential, we mainly use nickel foam and Co-Mo ions as feedstock and create an efficient catalytic material by electrodeposition. The Co-Mo interaction improves the current efficiency. In 1 mol/L NaOH solution, the overpotential of the Co-Mo-NF composites was low when the current density is -10 mA/cm2, with the best value reaching 45.3 mV, which is less than those of Co-NF (94.4 mV) and Mo-NF (88.2 mV). All deposits had similar Tafel slopes in the 77.9 mV/decade range. The catalyst does not just have a favorable effect on hydrogen formation but also has a surprisingly high double-layer capacitance (up to 180 mF/cm2) and good stability. This research provides an impactful approach for developing a non-precious metal HER catalyst for industrial hydrogen production.

The predictive value of relative wall thickness on the prognosis of the patients with ST-segment elevation myocardial infarction.

OBJECTIVE: The study aimed to evaluate the prognostic value of relative wall thickness (RWT) in the patients with ST-segment elevation myocardial infarction (STEMI). METHODS: A total of 866 patients with STEMI admitted in Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School from November 2010 to December 2018 were enrolled in the current study retrospectively. Three methods were used to calculate RWT: RWTPW, RWTIVS+PW and RWTIVS. The included patients were divided according to the median values of RWTPW, RWTIVS+PW, and RWTIVS, respectively. Survival analysis were performed with Kaplan-Meier plot and multivariate Cox proportional hazard model was established to evaluate the adjusted hazard ratio of the three kinds of RWT for all cause death, cardiac death and MACE (major adverse cardiac death). RESULTS: There was no significance for the survival analysis between the low and high groups of RWTPW, RWTIVS+PW and RWTIVS at 30 days and 12 months. Nonetheless, the cumulative incidence of all cause death and cardiac death in the low group of RWTPW and RWTIVS+PW was higher than those in the high group at 60 months. The cumulative incidence of MACE in the low group of RWTPW was higher than the high group at 60 months. Multivariate Cox regression model showed that RWTPW were inversely associated with long-term cardiac death and MACE in STEMI patients. In the subgroup analysis, three calculations of RWT had no predictive value for the patients with anterior myocardial infarction. By contrast, RWTPW was the most stable independent predictor for the long-term outcomes of the patients with non-anterior myocardial infarction. CONCLUSION: RWTPW, RWTIVS+PW and RWTIVS had no predictive value for the long-term clinical outcomes of patients with anterior myocardial infarction, whereas RWTPW was a reliable predictor for all cause death, cardiac death and MACE in patients with non-anterior myocardial infarction.

Characteristics of attentional bias in meditators: An ERP study.

Attentional bias is closely related to individual mental health. To explore the effect of mindfulness meditation on attentional bias, we use the dot-probe task to measure and compare the attentional bias of 16 Shaolin monks with meditation experience (meditator group) and 18 ordinary people without meditation experience (control group). The results were as follows: (1) The control group showed attentional bias to anger stimuli, while the meditator group did not show attentional bias; (2) The P1 amplitude induced by emotion stimuli was significantly less in the meditator group than in the control group; (3) When the control group observed angry-neutral faces, the P2 amplitude was greater than when they saw neutral-neutral faces. In comparison, there was no significant difference in P2 amplitude when the meditator group viewed faces with different emotions. This leads us to contend that people highly practiced in meditation can reduce their attentional bias to negative information, and show the cognitive characteristics of "impartial" treatment to external information.

Genome Sequencing Explores Complexity of Chromosomal Abnormalities in Recurrent Miscarriage.

Recurrent miscarriage (RM) affects millions of couples globally, and half of them have no demonstrated etiology. Genome sequencing (GS) is an enhanced and novel cytogenetic tool to define the contribution of chromosomal abnormalities in human diseases. In this study we evaluated its utility in RM-affected couples. We performed low-pass GS retrospectively for 1,090 RM-affected couples, all of whom had routine chromosome analysis. A customized sequencing and interpretation pipeline was developed to identify chromosomal rearrangements and deletions/duplications with confirmation by fluorescence in situ hybridization, chromosomal microarray analysis, and PCR studies. Low-pass GS yielded results in 1,077 of 1,090 couples (98.8%) and detected 127 chromosomal abnormalities in 11.7% (126/1,077) of couples; both members of one couple were identified with inversions. Of the 126 couples, 39.7% (50/126) had received former diagnostic results by karyotyping characteristic of normal human male or female karyotypes. Low-pass GS revealed additional chromosomal abnormalities in 50 (4.0%) couples, including eight with balanced translocations and 42 inversions. Follow-up studies of these couples showed a higher miscarriage/fetal-anomaly rate of 5/10 (50%) compared to 21/93 (22.6%) in couples with normal GS, resulting in a relative risk of 2.2 (95% confidence interval, 1.1 to 4.6). In these couples, this protocol significantly increased the diagnostic yield of chromosomal abnormalities per couple (11.7%) in comparison to chromosome analysis (8.0%, chi-square test p = 0.000751). In summary, low-pass GS identified underlying chromosomal aberrations in 1 in 9 RM-affected couples, enabling identification of a subgroup of couples with increased risk of subsequent miscarriage who would benefit from a personalized intervention.

The effects of extracellular vesicles derived from Krüppel-Like Factor 2 overexpressing endothelial cells on the regulation of cardiac inflammation in the dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) is one of the common causes of heart failure. Myocardial injury triggers an inflammatory response and recruits immune cells into the heart. High expression of Krüppel-like factor 2 (KLF2) in endothelial cells (ECs) potentially exerts an anti-inflammatory effect. However, the role of extracellular vesicles (EVs) from KLF2-overexpressing ECs (KLF2-EVs) in DCM remains unclear. METHODS AND RESULTS: EVs were separated from the supernatant of KLF2-overexpressing ECs by gradient centrifugation. Mice were repeatedly administered low-dose doxorubicin (DOX) and then received KLF2-EVs through an intravenous injection. Treatment with KLF2-EVs prevented doxorubicin-induced left ventricular dysfunction and reduced the recruitment of Ly6high Mo/Mø in the myocardium. We used flow cytometry to detect Ly6high monocytes in bone marrow and spleen tissues and to elucidate the mechanisms underlying this beneficial effect. KLF2-EVs increased the retention of Ly6Chigh monocytes in the bone marrow but not in the spleen tissue. KLF2-EVs also significantly downregulated C-C chemokine receptor 2 (CCR2) protein expression in cells from the bone marrow. CONCLUSIONS: EVs derived from KLF2-overexpressing ECs reduced cardiac inflammation and ameliorated left ventricular dysfunction in DCM mice by targeting the CCR2 protein to inhibit Ly6Chigh monocyte mobilization from the bone marrow.

hsa_circ_0000285 facilitates thyroid cancer progression by regulating miR-127-5p/CDH2.

Thyroid cancer (THCA) is a leading endocrine cancer and becomes the fifth most commonly diagnosed malignancy in females. It is confirmed that circular RNAs (circRNAs) perform regulatory potencies in the pathological progress of THCA. Our purpose was to certify the trait of hsa_circ_0000285 (circ_0000285) and investigate its modulatory mechanism in THCA progression. We identified the expression profile of hsa_circ_0000285 in THCA by conducting qRT-PCR assay. Therewith, the potential of hsa_circ_0000285 in THCA development was determined with a set of functional experiments, including CCK-8, wound healing assay, Western blot, and xenograft model. The molecular mechanism underlying hsa_circ_0000285 was investigated with bioinformatic analysis, RIP and dual-luciferase reporter experiments. As opposed to normal samples and cells, hsa_circ_0000285 level was overtly increased in THCA specimens and cells. The downregulation of hsa_circ_0000285 weakened the proliferative and migratory capacity of THCA cells and promoted cell apoptosis. In addition, hsa_circ_0000285 silence suppressed the tumor growth of xenograft model mice in vivo. Notably, we demonstrated that hsa_circ_0000285 might target miR-127-5p/CDH2 axis in THCA. Afterward, our findings manifested that miR-127-5p attenuation blocked the function of hsa_circ_0000285 depletion in THCA cells. In the final step, CDH2 was proven to mediate the repressive potency of miR-127-5p in the malignant behaviors of THCA. Mechanistically, hsa_circ_0000285 induced the development of THCA via functioning as a competing endogenous RNA (ceRNA) of miR-127-5p to enhance CDH2 expression, which provided a new perspective for THCA therapy.

First report of Atractylodes lancea leaf spot caused by Fusarium acuminatum in China.

Atractylodes lancea Thunb. DC (cangzhu) is a traditional Chinese medicinal plant (Cai et al., 2020). In June 2020, leaf spots were observed in A. lancea plants at the Chongqing Institute of Medicinal Plant Cultivation located in Nanchuan District, Chongqing, China (29°8'26.46″ N, 107°13'23'21″ E). Approximately 75% of the plants displayed leaf spot, partial leaf wilting, and stunted growth, and some plants died. To determine the cause of this disease, five typical leaf spots were cut into small pieces. The pieces were successively surface-disinfected with 0.5% NaClO for 1 min and 75% ethanol for 30 s, washed thrice with sterile water, and placed on potato dextrose agar (PDA) to incubate at 25 ℃. These isolates initially formed abundant white aerial mycelium, then gradually developed a rose pigmentation with a brownish color in the center and grayish rose at the periphery of the colony (Li et al. 2019). Mycelial tips were picked and placed on carnation leaf agar (CLA) and inoculated for 7 days. The macroconidia of the isolates were slender, distinctively curved in the bottom half of the apical cell, and sickle-shaped, with 3-4 septa. They ranged in size from 16.68-26.49 × 1.48-2.34 µm (n=50). The microconidia were fusiform with or without one septum. Their size ranged from 6.19-11.02 × 1.25-1.43 µm (n=50) (Li et al. 2019). The morphological characteristics of the isolates were consistent with those of Fusarium spp. PCR amplification and DNA sequencing of the internal transcribed spacer (ITS) region and ß-tubulin (TUB2) gene were performed using the primers ITS1/ITS4 (White et al. 1990) and Bt-2a/Bt-2b (Robideau et al. 2011), respectively. BLASTn analysis revealed that the ITS sequences of the isolates were 100% identical to those of the F. acuminatum isolates from the Fusarium MLST database (http://isolate.fusariumdb.org/guide.php). Further analysis revealed that the TUB2 sequences were 99.14% identical to those of the F. acuminatum strain S16 isolates (MF662644) from the GeneBank database of the NCBI server. Based on the morphology and sequence analyses, the isolates were identified as F. acuminatum. Pathogenicity tests were conducted on 1.5-year-old A. lancea plants by inoculating spore suspensions under greenhouse conditions (25°C). For this, wound were made on leaves by piercing with sterilized toothpicks. 30 µl of spore suspension containing 2 × 106 conidia/ml was placed on each wound. Wounds on the leaves of control plants were inoculated with 10 µl of sterile distilled water. There were three plants for each treatment. After incubation at 25 °C for 5 days in a greenhouse, the leaves of the treated plants all showed partial wilting, consistent with the field observations. No symptoms were observed in controlled plants. The fungi were again isolated from the symptomatic tissues and were identical to the original isolate. The experiment was repeated twice with similar results. Pathogenicity symptoms were similar to what was first observed in the field and the isolated fungi were verified based on morphological characteristics, thus fulfilling Koch's postulate. To the best of our knowledge, this is the first time that A. lancea leaf spot caused by F. acuminatum has been discovered in China. The leaf spot caused by F. acuminatum on A. lancea has serious yield loss, and proper control measures should be applied.

Characterization and identification of SFDC-1, a novel AmpC-type ß-lactamase in Serratia fonticola.

The clinical and environmental infections caused by AmpC ß-lactamases have been increasingly reported recently. In this study, we characterize the novel chromosome-encoded AmpC ß-lactamase SFDC-1 identified in Serratia fonticola strain R28, which was isolated from a rabbit raised on a farm in southern China. SFDC-1 shared the highest amino acid identity of 79.6% with the functionally characterized AmpC ß-lactamase gene blaYRC-1 , although it had highly homologous functionally uncharacterized relatives in the same species from different sources, including some of the clinical significance. The cloned blaSFDC-1 exhibited resistance to a broad spectrum of ß-lactam antibiotics, including most cephalosporins with the highest resistance to ampicillin, cefazolin and ceftazidime, with increased MIC levels ≥128-fold compared with the control strains. The purified SFDC-1 showed catalytic activities against ß-lactams with the highest catalytic activity to cefazolin. The genetic context of blaSFDC-1 and its relatives was conserved in the chromosome, and no mobile genetic elements were found surrounding them.

Identification and characteristics of a novel aminoglycoside phosphotransferase, APH(3')-IId, from an MDR clinical isolate of Brucella intermedia.

OBJECTIVES: To describe a novel chromosomal aminoglycoside phosphotransferase named APH(3')-IId identified in an MDR Brucella intermedia ZJ499 isolate from a cancer patient. METHODS: Species identity was determined by PCR and MALDI-TOF MS analysis. WGS was performed to determine the genetic elements conferring antimicrobial resistance. Gene cloning, transcriptional analysis and targeted gene deletion, as well as protein purification and kinetic analysis, were performed to investigate the mechanism of resistance. RESULTS: APH(3')-IId consists of 266 amino acids and shares the highest identity (48.25%) with the previously known APH(3')-IIb. Expression of aph(3')-IId in Escherichia coli decreased susceptibility to kanamycin, neomycin, paromomycin and ribostamycin. The aph(3')-IId gene in ZJ499 was transcriptionally active under laboratory conditions and the relative abundance of this transcript was unaffected by treatment with the above four antibiotics. However, deletion of aph(3')-IId in ZJ499 results in decreased MICs of these drugs. The purified APH(3')-IId showed phosphotransferase activity against kanamycin, neomycin, paromomycin and ribostamycin, with catalytic efficiencies (kcat/Km) ranging from ∼105 to 107 M-1 s-1. Genetic environment and comparative genomic analyses suggested that aph(3')-IId is probably a ubiquitous gene in Brucella, with no mobile genetic elements detected in its surrounding region. CONCLUSIONS: APH(3')-IId is a novel chromosomal aminoglycoside phosphotransferase and plays an important role in the resistance of B. intermedia ZJ499 to kanamycin, neomycin, paromomycin and ribostamycin. To the best of our knowledge, APH(3')-IId represents the fourth characterized example of an APH(3')-II enzyme.

A composite triboelectric nanogenerator based on flexible and transparent film impregnated with ZIF-8 nanocrystals.

The triboelectric nanogenerator (TENG), based on the triboelectrification coupled with electrostatic induction, can directly convert ambient mechanical energy into electric energy. However, the output performance of TENG is still low and demands further improvement to speed up the commercial application. In this work, we demonstrate a TENG based on a flexible and transparent composite film made of PDMS and ZIF-8. When the amount of the ZIF-8 is 4 wt%, the generated output current and voltage of the TENG are gradually increased up to 16.3µA and 176 V, which are 210% and 230% higher than that of TENG without ZIF-8, respectively. Impregnated ZIF-8 which exhibits a positive polarity lowers the effective work function of the PDMS and enhance the surface charge density, verified by Kelvin probe force microscope measurement.

Metagenomic analysis revealed the sulfur- and iron- oxidation capabilities of heterotrophic denitrifying sludge.

Heterotrophic denitrification is widely applied in wastewater treatment processes to remove nitrate. However, the ability of the heterotrophic denitrifying sludge to use inorganic matter as electron donors to perform autotrophic denitrification has rarely been investigated. In this study, we enriched heterotrophic denitrifying sludge and demonstrated its sulfur- and iron- oxidizing abilities and denitrification performance with batch experiments. Based on high-throughput sequencing of 16S rRNA genes, high diversity and abundance of sulfur-oxidizing bacteria (SOB) (e.g., Sulfuritalea, Thiobacillus, and Thiothrix) and iron (II)-oxidizing bacteria (FeOB) (e.g., Azospira and Thiobacillus) were observed. Metagenomic sequencing and genome binning results further suggested that the SOB in the heterotrophic denitrifying sludge were mainly Alphaproteobacteria and Betaproteobacteria instead of Gammaproteobacteria and Epsilonproteobacteria. The similarities of potential iron-oxidizing genes with known sequences were very low (32-51%), indicating potentially novel FeOB species in this system. The findings of this study suggested that the heterotrophic denitrifying sludge harbors diverse mixotrophic denitrifying bacterial species, and based on this finding, we proposed that organic carbon and inorganic electron donors (e.g., sulfur, thiosulfate, and iron) could be jointly used in engineering practices according to the quality and quantity of wastewater to balance the cost and efficiency of the denitrification process.

The Tannins from Sanguisorba officinalis L. (Rosaceae): A Systematic Study on the Metabolites of Rats Based on HPLC-LTQ-Orbitrap MS2 Analysis.

Sanguisorba tannins are the major active ingredients in Sanguisorba ofJicinalis L. (Rosaceae), one of the most popular herbal medicines in China, is widely prescribed for hemostasis. In this study, three kinds of tannins extract from Sanguisorba officinalis L. (Rosaceae), and the metabolites in vivo and in vitro were detected and identified by high-pressure liquid chromatography, coupled with linear ion trap orbitrap tandem mass spectrometry (HPLC-LTQ-Orbitrap). For in vivo assessment, the rats were administered at a single dose of 150 mg/kg, after which 12 metabolites were found in urine, 6 metabolites were found in feces, and 8 metabolites were found in bile, while metabolites were barely found in plasma and tissues. For in vitro assessment, 100 µM Sanguisorba tannins were incubated with rat liver microsomes, liver cytosol, and feces, after which nine metabolites were found in intestinal microbiota and five metabolites were found in liver microsomes and liver cytosol. Moreover, the metabolic pathways of Sanguisorba tannins were proposed, which shed light on their mechanism.

The cyclic adenosine monophosphate elevating medicine, forskolin, reduces neointimal formation and atherogenesis in mice.

Neointimal formation and atherogenesis are major vascular complications following percutaneous coronary intervention, and there is lack of pharmacological therapy. This study was aimed to examine the effect of forskolin (FSK), a cyclic adenosine monophosphate (cAMP)-elevating agent, on vascular response to angioplasty wire injury and on atherogenesis in mice. Forskolin treatment reduced neointima formation at 7 and 28 days after wire injury. Early morphometrics of the injured vessels revealed that FSK treatment enhanced endothelial repair and reduced inflammatory cell infiltration. In vitro treatment of primary aortic cells with FSK, at 3-100 µmol/L, increased endothelial cell proliferation, whereas FSK, at 30-100 µmol/L, inhibited smooth muscle cell proliferation. FSK inhibited lipopolysaccharide-induced leucocyte-endothelial interaction in vitro and in vivo. In a mouse model of atherosclerosis driven by dyslipidaemia and hypertension, FSK administration increased endothelial repair and reduced atherosclerotic plaque formation, without affecting blood pressure, plasma lipids or aortic aneurysms formation. In summary, FSK, at doses relevant to human therapeutic use, protects against neointimal hyperplasia and atherogenesis, and this is attributable to its activities on pro-endothelial repair and anti-inflammation. This study raises a potential of clinical use of FSK as an adjunct therapy to prevent restenosis and atherosclerosis after percutaneous coronary intervention.

Prevalence of Aminoglycoside Resistance Genes and Molecular Characterization of a Novel Gene, aac(3)-IIg, among Clinical Isolates of the Enterobacter cloacae Complex from a Chinese Teaching Hospital.

Members of the Enterobacter cloacae complex are important opportunistic human pathogens capable of causing a wide variety of infections. During recent decades, aminoglycoside-resistant E. cloacae complex isolates have increasingly been reported and have become a major concern. Here, we employed high-throughput sequencing in combination with specific PCR assays to investigate the prevalence of aminoglycoside resistance genes among 170 isolates of the E. cloacae complex collected from a teaching hospital in Wenzhou, China. A total of 12 known genes [aphA-1, strA, strB, aac(6')-IIc, aadA2, aac(3)-IId, aadB, aadA1, rmtB, armA, aadA5, and aac(6')-Ie-aph(2'')-Ia] and 1 novel gene [aac(3)-IIg] were identified, with aphA-1 (71.18%), strA (55.29%), and strB (52.35%) being the most prevalent, and aac(3)-IIg was detected with a positive rate of 21.76% (37/170). The aac(3)-IIg gene was 810 bp in length and encoded a protein that shared 72 to 78% identities with previously known AAC(3)-II aminoglycoside 3-N-acetyltransferases. The MICs of gentamicin and tobramycin were 512 µg/ml and 64 µg/ml, respectively, when aac(3)-IIg was cloned into Escherichia coli DH5α. All aac(3)-IIg-positive isolates exerted broad aminoglycoside resistance profiles, mediated by the coexistence of multiple resistance genes. Moreover, aminoglycoside resistance and resistance genes were found to be transferable in most strains (24/37). Nevertheless, pulsed-field gel electrophoresis (PFGE) and dendrogram analysis showed clonal diversity among these isolates. S1 nuclease PFGE, Southern hybridization, and whole-genome sequencing indicated that aac(3)-IIg was located on transferable as well as nontransferable plasmids of various sizes. The analysis of the genetic environment suggested that aac(3)-IIg is embedded within a class 1 integron, with IS26 playing an important role in its mobility.

Synthesis of Perovskite CsPbBr3 Quantum Dots/Porous Boron Nitride Nanofiber Composites with Improved Stability and Their Reversible Optical Response to Ammonia.

All-inorganic CsPbX3 (X = Cl, Br, I) perovskite quantum dots (QDs) have great potential for various applications due to their excellent photoluminescence properties. However, poor stability under long-term storage hinders their applications. Herein we report the utilization of porous boron nitride nanofibers (BNNFs) as a promising carrier for anchoring of CsPbBr3 QDs. Due to the good dispersion and immobilization of CsPbBr3 QDs, the resulting CsPbBr3/BNNF composites show excellent photostability and superior long-term storage stability in an air environment. Moreover, the CsPbBr3/BNNF composites exhibit an interesting ammonia-responsive behavior: i.e., a distinct decrease in photoluminescence intensity upon exposure to ammonia gas and the subsequent photoluminescence recovery after post-treatment in nitrogen gas. Even after treatment with ammonia gas for 3 h, the composites can still be recovered under nitrogen gas treatment. The fast response, reversibility, and stability of CsPbBr3/BNNF composites in the presence of ammonia gas could inspire a broader range of applications.

Drug Discovery for Coronary Artery Disease.

Cardiovascular disease is the number one cause of human morbidity and mortality worldwide. Although cholesterol-lowering drugs, including statins and recently approved PCSK9 inhibitors, together with antithrombotic drugs have been historically successful in reducing the occurrence of coronary artery disease (CAD), the high incidence of CAD remains imposing the largest disease burden on our healthcare systems. We reviewed cardiovascular drugs recently approved or under clinical development, with a particular focus on their pharmacology and limitations. New agents targeting cholesterol/triglyceride lowering bear promise of further cardiovascular risk reduction. Some new antidiabetic agents show cardiovascular benefit in patients with diabetes. Improved antithrombotic agents with diminished bleeding risk are in clinical development. The recent clinical success of the IL-1ß antibody in reducing atherothrombosis opens a new era of therapeutic discovery that targets inflammation. Chinese traditional medicine and cardiac regeneration are also discussed. Human genetics studies of CAD and further delineation of key determinants/pathways underlying the residual risk of CAD under current standard therapy will continue to fuel the pipeline of cardiovascular drug discovery.

Long non-coding RNA MEG3 knockdown attenuates endoplasmic reticulum stress-mediated apoptosis by targeting p53 following myocardial infarction.

Mounting evidence has indicated that long non-coding RNA maternally expressed gene 3 (lncRNA MEG3) regulates cell apoptosis, and is involved in a variety of diseases. However, its exact role in myocardial infarction (MI) has not been fully elucidated. In the present study, we firstly observed that the expression levels of the lncRNA MEG3 in infarct hearts and hypoxic neonatal mice ventricular myocytes (NMVMs) were up-regulated by quantitative real-time PCR (qRT-PCR). Then, we knocked down lncRNA MEG3 by lentiviral delivery in the myocardial border region following multipoint injection. Following 28 days of MI, the lncRNA MEG3 knockdown mice indicated better cardiac function, and less cardiac remodelling by ultrasonic cardiogram and histological analysis. In addition, we indicated that lncRNA MEG3 knockdown reduced myocyte apoptosis and reactive oxygen species production in MI mice model and hypoxic NMVMs. Furthermore, we revealed that knockdown of lncRNA MEG3 protected against endoplasmic reticulum stress (ERS)-mediated myocardial apoptosis including the induction of PERK-eIF2α and caspase 12 pathways. At last, we provided evidence that p53 was identified as a protein target of lncRNA MEG3 to regulate NF-κB- and ERS-associated apoptosis. Taken collectively, our findings demonstrated that lncRNA MEG3 knockdown exerted cardioprotection by reducing ERS-mediated apoptosis through targeting p53 post-MI.