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Background: There have been ambiguous findings on the empirical relationship 24 between perceived stress and emotional eating. The mediating roles of negative-focused cognitive emotion regulation and reward sensitivity of these relationships, particularly for adolescents, are often overlooked. The objective of this study was to assess the association between perceived stress, negative-focused cognitive emotion regulation, reward sensitivity, and emotional eating in a sample of Chinese adolescents. Methods: In this cross-sectional study, 562 adolescents were selected and evaluated based on perceived stress, negative-focused cognitive emotion regulation, reward sensitivity, and emotional eating. Model tests were conducted using serial multiple mediation analyses, controlling for sex, age, household income, and body mass index. Results: Results showed that perceived stress directly affected adolescents’ emotional eating. In addition, perceived stress indirectly affected emotional eating through negative-focused cognitive emotion regulation and reward sensitivity. Conclusions: Findings support the hypothesis that perceived stress increases negative-focused cognitive emotion regulation, which increases reward sensitivity and thus increases emotional eating. Implications of these findings for preventive and therapeutic intervention are discussed, and future research recommendations are provided.

KRAS plays an essential role in regulating cell proliferation, differentiation, migration and survival. Mutated KRAS is a major driver of malignant transformation in multiple human cancers. We showed previously that fendiline (6) is an effective inhibitor of KRAS plasma membrane (PM) localization and function. In this study, we designed, synthesized and evaluated a series of new fendiline analogs to optimize its drug properties. Systemic structure-activity relationship studies by scaffold repurposing led to the discovery of several more active KRAS PM localization inhibitors such as compounds 12f (NY0244), 12h (NY0331) and 22 (NY0335) which exhibit nanomolar potencies. These compounds inhibited oncogenic KRAS-driven cancer cell proliferation at single-digit micromolar concentrations in vitro. In vivo studies in a xenograft model of pancreatic cancer revealed that 12h and 22 suppressed oncogenic KRAS-expressing MiaPaCa-2 tumor growth at a low dose range of 1–5 mg/kg with no vasodilatory effects, indicating their potential as chemical probes and anticancer therapeutics.

This investigation attempted to discern whether formononetin restrained progression of triple-negative breast cancer (TNBC) by blocking lncRNA AFAP1-AS1-miR-195/miR-545 axis. We prepared TNBC cell lines (i.e. MDA-MB-231 and BT-549) and normal human mammary epithelial cell line (i.e. MCF-10A) in advance, and the TNBC cell lines were, respectively, transfected by pcDNA3.1-lncRNA AFAP1-AS1, si-lncRNA AFAP1-AS1, pcDNA6.2/GW/EmGFP-miR-545 or pcDNA6.2/GW/EmGFP-miR-195. Resistance of TNBC cells in response to 5-Fu, adriamycin, paclitaxel and cisplatin was evaluated through MTT assay, while potentials of TNBC cells in proliferation, migration and invasion were assessed via CCK8 assay and Transwell assay. Consequently, silencing of lncRNA AFAP1-AS1 impaired chemo-resistance, proliferation, migration and invasion of TNBC cells (P

An effective therapy for human adenovirus (HAdV) infections in immunocompromised patients and healthy individuals with community-acquired pneumonia remains an unmet medical need. We herein reported a series of novel substituted

The sigma-1 (σ1) receptor, an enigmatic protein originally classified as an opioid receptor subtype, is now understood to possess unique structural and functional features of its own and play critical roles to widely impact signaling transduction by interacting with receptors, ion channels, lipids, and kinases. The σ1 receptor is implicated in modulating learning, memory, emotion, sensory systems, neuronal development, and cognition and accordingly is now an actively pursued drug target for various neurological and neuropsychiatric disorders. Evaluation of the five selective σ1 receptor drug candidates (pridopidine, ANAVEX2-73, SA4503, S1RA, and T-817MA) that have entered clinical trials has shown that reaching clinical approval remains an evasive and important goal. This review provides up-to-date information on the selective targeting of σ1 receptors, including their history, function, reported crystal structures, and roles in neurological diseases, as well as a useful collation of new chemical entities as σ1 selective orthosteric ligands or allosteric modulators.

Commercially available tunas and billfishes are generally processed as steaks, making it difficult to visually distinguish between the two. We developed and validated species-specific primers to prevent the adulteration of tunas by billfishes. Tunas and billfishes primers were designed on the cytochrome oxidase subunit I. Multiplex PCR bands obtained were 579 bp, 291 bp and 114 bp for tunas, billfishes and internal control. Sensitivity was determined to be 5 ng for tunas and billfishes. A total of 50 samples were monitored: 49 for tunas and 1 for billfish. As a result of the monitoring, the fake tunas did not show due to the agreement between product name and the raw material of the wrapping paper. Our results indicate that the species-specific primers developed in this study are suitable for differentiating tunas and billfishes. The newly developed multiplex PCR assay is a time and cost effective technique for determining the authenticity of tunas and billfishes.

Background and aimsNumerous studies have shown that people who have Internet addiction (IA) are more likely to experience poor sleep quality than people who do not. However, few studies have explored mechanisms underlying the relation between IA and poor sleep quality. As a first attempt to address this knowledge gap, a cross-sectional design was applied, and structural equation modeling was used to explore the direct relationship between IA and poor sleep quality, as well as the potential mediating roles of rumination and bedtime procrastination.MethodsA convenience sample, consisting of 1,104 Chinese University students (696 females or 63%), completed an online survey that included the following measures: Young’s 8-item Internet Addiction Diagnosis Questionnaire, the Pittsburgh Sleep Quality Index, the Ruminative Responses Scale, and the Bedtime Procrastination Scale.ResultsWhile the direct path between IA and poor sleep quality was not found to be significant, rumination and bedtime procrastination were each shown to separately mediate the predictive effect of IA on poor sleep quality. However, the greatest level of support was found for the sequential mediating effects of rumination and bedtime procrastination between IA and poor sleep quality.ConclusionWhile rumination and bedtime procrastination were both shown to be important independent mediators for the relation between IA and poor sleep quality, their combined effect was as great as either alone.

Although G protein-coupled receptors (GPCRs) are recognized as pivotal drug targets involved in multiple physiological and pathological processes, the majority of GPCRs including orphan GPCRs (oGPCRs) are unexploited. GPR88, a brain-specific oGPCR with particularly robust expression in the striatum, regulates diverse brain and behavioral functions, including cognition, mood, movement control, and reward-based learning, and is thus emerging as a novel drug target for central nervous system disorders including schizophrenia, Parkinson's disease, anxiety, and addiction. Nevertheless, no effective GPR88 synthetic ligands have yet entered into clinical trials, and GPR88 endogenous ligands remain unknown. Despite the recent discovery and early stage study of several GPR88 agonists, such as 2-PCCA, RTI-13951-33, and phenylglycinol derivatives, further research into GPR88 pharmacology, medicinal chemistry, and chemical biology is urgently needed to yield structurally diversified GPR88-specific ligands. Drug-like pharmacological tool function and relevant signaling elucidation will also accelerate the evaluation of this receptor as a viable neurotherapeutic target.

In this article, we provided a one-step hydrothermal method to prepare composite AlZr pillaring agents, and synthesized AlZr-pillared clays (AlZr-PILC) via ion exchange. Compared with conventional methods, our method successfully shortened synthetic routes and greatly reduced consumption of the materials. Then, AlZr-PILC-supported manganese and cerium oxide catalysts were obtained by impregnation method. The compositions and properties of these catalysts were characterized by some technical means. The energy dispersive X-ray spectroscopy clearly shows the existence of Mn, Ce, and O, which indicates the successful loading of the active components on the surface of AlZr-PILC. Meanwhile, the results of X-ray diffraction (XRD) and N2 adsorption experiments demonstrate that the synthesized AlZr-PILC outperforms the raw clays (Na-mmt) and mononuclear Al-PILC in the catalytic combustion of chlorobenzene. XRD and high-resolution transmission electron microscopy also proves that the high activity of them is related to the high dispersion of the oxides and the exposure of more active sites. H2-temperature-programmed reduction shows that cerium can promote the redox cycles of the manganese system through the strong interactions between MnO2, CeO2 and AlZr-PILC. In particular, MnCe(9:1)/AlZr-PILC shows the best catalytic activity in the catalytic combustion of chlorobenzene.

The study investigated the level of contamination by total aerobic bacteria, coliform bacteria and food poisoning bacteria in commercial spices for the evaluation of microbiological safety. A total of 119 commercial spices was used for this study. The total aerobic bacterial count was 6.2 log CFU/g in HACCP certificated spices and 5.4 log CFU/g in HACCP non-certificated spices. Coliform bacteria were detected in 13 (35.1%) out of 37 HACCP certificated spices and 27 (32.9%) out of 82 HACCP non-certificated spices. Bacillus cereus was detected in 7 (18.9%) out of 37 HACCP certificated spices and 10 (11.8%) out of 82 non-certificated spices. All the B. cereus detected in this study possessed at least one toxin gene, and hemolysin BL enterotoxin was detected in 9 (52.9%) out of 17 B. cereus isolates. Overall, these results indicated that contamination with total aerobic bacteria was higher in HACCP certified spices, with more coliform bacteria and B. cereus detected, than in non-certificated spices. Hence, it is necessary to refine the HACCP system and introduce good agricultural practices for the improvement of microbiological safety of spices.

Background Platinum-based drugs are used extensively in neoadjuvant chemotherapy for triple-negative breast cancer (TNBC), but their use can be limited by resistance. In this study, we established cisplatin (DDP) resistant TNBC cells to investigate the potential relationship among ETS1, IKKα/NF-κB and resistance. Methods The sensitivity was evaluated by MTT, apoptosis analysis. The intracellular DDP concentration difference was tested by inductively coupled plasma mass spectrometry (ICP-MS) method. Molecular pathological mechanism of DDP resistance was explored by microarray analysis and PPI network analysis. The ETS1, NF-κB signaling change were assessed by western blot and q-PCR in vitro and vivo. The existing binds between ETS1 and the core IKKα promoter were found by luciferase assay and chromatin immunoprecipitation technique (ChIP). Results MDA-MB-231/DDP (231/DDP) cell had a higher IC50 value of cisplatin, lower intracellular DDP concentration, and lower apoptosis ratio than MDA-MB-231 (231/wt) cell line treated with DDP. Increased ABC transporters were induced by the activation of NF-κB pathway in 231/DDP cells. ETS1, RPL6, RBBP8, BIRC2, PIK3A and RARS were six important genes for DDP-resistance based on PPI network and expression validation. Protein expression of ETS1 and IKKα were significantly up-regulated in 231/DDP cells. However, inhibition of ETS1 expression enhances chemo-sensitivity to DDP and reversed the activation of NF-κB pathway in 231/DDP cells and subcutaneous transplantation tumor in vivo. Moreover, there is existing binds between ETS1 and the core IKKα promoter though luciferase assay and ChIP. Conclusion This study enables us to understand the functions of ETS1 in TNBC chemotherapy and suggests that ETS1 could be used as a novel marker of poor response to DDP and a potential therapeutic target for TNBC chemotherapy.

The CO2 diffusion coefficient in polymethyl methacrylate (PMMA) was measured to investigate the relationship between the saturation time and cell nucleation in batch foaming. Measurements were conducted using a visualized high-pressure cell at various temperatures from 303 to 343 K and CO2 pressures of 6, 12, and 18 MPa. The CO2 diffusion coefficient depended strongly on the temperature but weakly on the pressure. Additionally, the CO2 diffusion was promoted by the glass transition behavior of PMMA but was suppressed by the hydrostatic pressure at high pressures. Based on the sorption isotherms of CO2 in PMMA, microcellular PMMA foams were prepared with saturation times from 1800 to 12600 s. Cell nucleation was initiated when the CO2 concentration, which depended upon the CO2 diffusion and saturation time, was sufficient to minimize the energy barrier. Furthermore, the critical CO2 concentration to initiate cell nucleation decreased with an increase in temperature.

Olivine LiMPO4 (M = Mn, Fe, Co and Ni, LMP) materials are considered to be the most promising cathode candidates for high energy storage devices. In this work, the feasibility of the thermodynamics of powder formation is discussed for explaining such a reaction mechanism, as well as the recent progress of conventional and supercritical hydro/solvothermal syntheses, are summarized. The association among synthesis conditions, structure, morphology and electrochemical properties, especially for rate capability and tap density under hydro/solvothermal condition, are highlighted. Notably, this work primarily concentrates on the processes in which additives participate in the hydrothermal synthesis of LMP and considers less the subsequent treatments of synthesized LMP with extra additives. In other words, the modifications during the synthesis process with additives are the primary topic. Recently, supercritical hydro/solvothermal synthesis has been demonstrated to be a promising approach for generating high-crystalline micro-nanoparticles with short reaction times (less than 2 min) and high crystallization rates affected by the specific characteristics in supercritical fluids. Additionally, the smallest powders among the reported LFP nanoparticles (less than 15 nm) had been synthesized via SHS (supercritical hydrothermal synthesis). Inspired by the structure-function relationships that are gained by hydro/solvothermal synthesis, rapid and continuous supercritical hydro/solvothermal synthesis is of interest for the commercial production of high-performance micro/nanocrystals due to its environmental friendliness and easy scale-up.

Lack of targeted strategies for preventing and treating estrogen receptor (ER)-negative breast cancer (ENBC) is an unmet clinical challenge. ENBCs including triple-negative BCs (TNBC) constitute 30-40% of BC cases and are prone to develop remote metastasis and local recurrence, resulting in the majority of deaths in BC patients. Dysregulated glucose and energy metabolism is critically involved in the development and progression of various cancers via promoting aberrant cell growth, malignant transformation and metastasis. Nevertheless, the potential role of glucose/energy metabolism in ENBC carcinogenesis has sparsely been explored, thus representing a key knowledge gap and a potential avenue for effective targeted therapies. Despite a substantial amount of effort has been made towards anticancer metabolic and biogenetic medications, none has progressed into clinical use, due to their limited potency, specificity or drug properties such as toxicity and poor bioavailability. We recently developed HJC0152, a novel small molecule anticancer agent, using structure- and fragment-based drug design strategies and molecular modeling techniques in our initial attempt to develop non-peptide STAT3 inhibitors for anticancer use. HJC0152 significantly inhibits proliferation of BC cells, induces apoptosis, reduces ER-negative mammary tumor development, suppresses ENBC xenograft tumor growth, and blocks lung metastasis in vivo. Intriguingly, HJC0152 differentially modulates expression of glycolytic enzymes including HK1, PFK-L, PFKFB2, ENO2, PDH, PDK1, PGAM1 and ALDOA in a time-dependent manner. HJC0152 also regulates the transcription of genes involved in glucose and mitochondrial energy metabolism, including the subunits of mitochondrial respiratory chain complexes. Functional assessments further demonstrate that HJC0152 significantly modulates respiratory chain complex function. Via in silico and Unique Polymer Technology (UPT) strategy, we identified a number of putative HJC0152-interacting targets for validation studies. Our findings suggest that HJC0152 is capable of reprogramming/restoring the dysregulated glucose metabolism by inducing specific glycolytic enzyme expression and mitochondrial respiratory chain function, likely via targeting upstream key signal molecule(s) that regulates glucose and energy metabolism, thereby suppressing breast cancer development and progression to metastasis. This work was supported by Grants P50 CA097007, and P30DA028821 (JZ) from the NIH, CPRIT (JZ), John Sealy Memorial Endowment Fund (JZ), DFI Grants from MD Anderson Cancer Center (QS), Holden Family Research Grant in BC Prevention (QS), and NCI PREVENT Program HHSN26100002 (QS). Citation Format: Dong J, Kim H, Xu J, Li D, Zhang Z, Zheng Z, Ye N, Chen H, Zhou J, Shen Q. Suppression of breast carcinogenesis and metastasis by targeting glucose metabolism with HJC0152 [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-21-19.

In this study, twenty novel cinnamic acid magnolol derivatives were synthesized, and screened for their anti-hyperglycemic potential. All synthesized compounds exhibited good to moderate α-glucosidase and α-amylase inhibitory activities with IC50 values: 5.11 ± 1.46–90.26 ± 1.85 µM and 4.27 ± 1.51–49.28 ± 2.54 µM as compared to the standard acarbose (IC50: 255.44 ± 1.89 μM and 80.33 ± 2.95 μM, respectively). Compound 6j showed the strongest inhibitory activity against α-glucosidase (IC50 = 5.11 ± 1.46 µM) and α-amylase (IC50 = 4.27 ± 1.51 µM). Kinetic study indicated that compound 6j was reversible and a mixed type inhibitor against α-glucosidase and α-amylase. In silico studies revealed the binding interaction between 6j and two enzymes, respectively. Finally, cells cytotoxicity assay revealed that compound 6j showed low toxicity against 3 T3-L1 cells and HepG2 cells.

Visible-light-driven photocatalysis holds a broad prospect for alleviating the energy crises. Here we report novel CuS nanoparticles/CdS nanowires Schottky heterojunctions via a two-step hydrothermal synthesis and used for photocatalytic H2 generation driven by visible-light (λ ≥ 420 nm). Compared with pure CdS NWs, the CuS/CdS nanocomposites show outstanding visible light H2 evolution, with an optimal rate reaching 2076.5 μmol h−1 g−1. The intrinsic properties of CuS/CdS nanocomposites, such as structure, optical properties, and combined configuration are systematically analyzed by experimental characterizations and theoretical calculations. The comprehensive results show that the Schottky junction between CuS NPs and CdS NWs accelerates photoinduced electron drift from semi-conductive CdS to metallic CuS, improving their activities of water splitting. This work offers a simple route to synthesize one-dimensional CdS-based nanocomposites for efficient visible-light driven energy conversion.

Exchange proteins directly activated by cAMP (EPACs) are critical cAMP-dependent signaling pathway mediators. The discovery of EPAC proteins has significantly facilitated understanding on cAMP-dependent signaling pathway and efforts along this line open new avenues for developing novel therapeutics for cancer, diabetes, heart failure, inflammation, infections, neurological disorders and other human diseases. Over the past decade, important progress has been made in the identification of EPAC agonists, antagonists and their biological and pharmacological applications. In this review, we briefly summarize recently reported novel functions of EPACs and the discovery of their small molecule modulators. The challenges and future perspectives are also discussed.

Poly(ADP-ribose)polymerase (PARP)1/2 inhibitors have been proved to be clinically effective anticancer drugs. Here we report a new PARP1/2 inhibitor, simmiparib, displaying apparently improved preclinical anticancer activities relative to the first approved inhibitor olaparib. Simmiparib inhibited PARP1/2 approximately 2-fold more potently than olaparib, with more than 90-fold selectivity over the other tested PARP family members. Simmiparib and olaparib caused similar cellular PARP1-DNA trapping. Simmiparib selectively induced the accumulation of DNA double-strand breaks, G2/M arrest and apoptosis in homologous recombination repair (HR)-deficient cells. Consistently, simmiparib showed 26- to 235-fold selectivity in its antiproliferative activity against HR-deficient cells over the corresponding isogenic HR-proficient cells. Notably, its antiproliferative activity was 43.8-fold more potent than that of olaparib in 11 HR-deficient cancer cell lines. Simmiparib also potentiated the proliferative inhibition of several conventional anticancer drugs. Simmiparib reduced the poly(ADP-ribose) formation in HR-deficient cancer cells and xenografts. When orally administered to nude mice bearing xenografts, simmiparib revealed excellent pharmacokinetic properties. Simmiparib caused approximately 10-fold greater growth inhibition than olaparib against HR-deficient human cancer cell- or tissue-derived xenografts in nude mice. Collectively, these findings support the undergoing clinical trials of simmiparib.

The 5-HT

A metal-free K

Due to the lack of explicit markers in Chinese text to define the boundaries of words, it is often more difficult to identify named entities in Chinese than in English. At present, the pretreatment of the character or word vector models is adopted in the training of the Chinese named entity recognition model. Aimed at the problems that taking character vector as an input of the neural network cannot use the words’ semantic meanings and give up the words’ explicit boundary information, and taking the word vector as an input of the neural network relies on the accuracy of the segmentation algorithms, a Chinese named entity recognition model based on character word vector fusion CWVF-BiLSTM-CRF (Character Word Vector Fusion-Bidirectional Long-Short Term Memory Networks-Conditional Random Field) is proposed in this paper. First, the Word2Vec is used to obtain the corresponding dictionaries of character-character vector and word-word vector. Second, the character-word vector is integrated as the input unit of the BiLSTM (Bidirectional Long-Short Term Memory) network, and then, the problem of an unreasonable tag sequence is solved using the CRF (conditional random field). By using the presented model, the dependence on the accuracy of the word segmentation algorithm is reduced, and the words’ semantic characteristics are effectively applied. The experimental results show that the model based on character-word vector fusion improves the recognition effect of the Chinese named entity.

An effective therapy for human adenovirus (HAdV) infections in immunocompromised patients and healthy individuals with community-acquired pneumonia remains an unmet medical need. We herein reported a series of novel substituted N-(4-amino-2-chlorophenyl)-5-chloro-2-hydroxybenzamide analogues as potent HAdV inhibitors. Compounds 6, 15, 29, 40, 43, 46, 47, and 54 exhibited increased selectivity indexes (SI > 100) compared to the lead compound niclosamide, while maintaining sub-micromolar to low micromolar potency against HAdV. The preliminary mechanistic studies indicated that compounds 6 and 43 possibly target the HAdV DNA replication process, while compounds 46 and 47 suppress later steps of HAdV life cycle. Notably, among these derivatives, compound 15 showed improved anti-HAdV activity (IC50 = 0.27 μM), significantly decreased cytotoxicity (CC50 = 156.8 μM), and low in vivo toxicity (maximum tolerated dose = 150 mg/kg in hamster) as compared with niclosamide, supporting its further in vivo efficacy studies for the treatment of HAdV infections., This work was supported by UTMB Technology Commercialization Program, John Sealy Memorial Endowment Fund, and Institute for Translational Sciences (ITS) at UTMB, Plan Nacional de I + D + i 2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009), co-financed by European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 20142020, the Instituto de Salud Carlos III, Proyectos de Investigación en Salud (PI17/01055; PI18/01191) and Proyectos de Desarrollo Tecnológico en Salud (DTS17/00130), the Spanish Adenovirus Network (AdenoNet, BIO2015/68990-REDT), and the program “Nicolás Monardes” (C-0059-2018), Servicio Andaluz de Salud, Junta de Andalucía. J.Z. is also partially supported by John D. Stobo, M.D., Distinguished Chair Endowment Fund at UTMB. M.E.P.I. is a postdoctoral researcher belonging to the program “Nicolás Monardes” (C1-0038-2019), Servicio Andaluz de Salud, Junta de Andalucía, Spain.

Subtype selectivity and functional bias are vital in current drug discovery for G protein-coupled receptors (GPCRs) as selective and biased ligands are expected to yield drug leads with optimal on-target benefits and minimal side-effects. However, structure-based design and medicinal chemistry exploration remain challenging in part because of highly conserved binding pockets within subfamilies. Herein, we present an affinity mass spectrometry approach for screening herbal extracts to identify active ligands of a GPCR, the 5-HT2C receptor. Using this method, we discovered a naturally occurring aporphine 1857 that displayed strong selectivity for activating 5-HT2C without activating the 5-HT2A or 5-HT2B receptors. Remarkably, this novel ligand exhibited exclusive bias towards G protein signaling for which key residues were identified, and it showed comparable in vivo efficacy for food intake suppression and weight loss as the anti-obesity drug, lorcaserin. Our study establishes an efficient approach to discovering novel GPCR ligands by exploring the largely untapped chemical space of natural products.

In a magnetic nanoparticle-mediated hyperthermia, the temperature is a key factor for thermal therapy to treat cancer. A harmonic amplitude detection algorithm determines the measurement accuracy of magnetic nanoparticle thermometer. In this paper, we introduce a harmonic detection algorithm, digital phase sensitive detection (DPSD), study DPSD how to affect the measurement accuracy of magnetic nanoparticle thermometer, and analyze the anti-noise performance of DPSD, including the static magnetic noise, industrial frequency magnetic noise, higher frequency magnetic noise, and Gauss noise. The optimum system parameters are proposed, and verified in numerical simulation experiments by use of MATLAB. The simulation results show that the DPSD with optimum system parameter can attach a high measurement accuracy of magnetic nanoparticle thermometer.

A series of substituted 4,6-dihydrospiro[[1,2,3]triazolo[4,5

Background Abnormally expressed long non-coding RNA (lncRNA) is associated with the development of breast cancer and multidrug resistance. However, the molecular mechanism by which lncRNA regulates cisplatin (DDP) in triple-negative breast cancer (TNBC) remains unclear. Methods DDP resistant cell line MDA-MB-231/DDP was established by gradually increasing doses of DDP. Abnormal expression of lncRNA between MDA-MB-231 and MDA-MB-231/DDP was evaluated with microarray. In addition, cell proliferation was evaluated by CCK-8 and Ki67 assays. Furthermore, cell apoptosis was evaluated by cell apoptosis and TUNEL assays. Western blotting assay was used to detect the protein expression. In vivo animal study was performed finally. Results HCP5 were significantly decreased in MDA-MB-231/DDP cells compared with MDA-MB-231 cells. Downregulation of HCP5 promoted DDP resistance in MDA-MB-231 cells by inhibiting PTEN expression. In contrast, overexpression of HCP5 reversed DDP resistance in MDA-MB-231/DDP cells by upregulating PTEN. In vivo experiments confirmed that overexpression of HCP5 inhibited DDP resistance in TNBC xenograft. Conclusion We found that downregulation of HCP5 contributed to DDP resistance in TNBC, while overexpression of HCP5 reversed the resistance via upregulating PTEN level. Therefore, DDP combined with overexpression of HCP5 might be considered as a therapeutic approach for the treatment of DDP-resistant TNBC.

Cells are the basic unit of life structure and life activities. Because of the complex micro-environment of cells, the content of components that play a key role is relatively small, so single-cell analysis is extremely challenging. In recent years, single-cell sequencing technology has been developed and matured. Single-cell sequencing can reveal the composition and physiological diversity of cells, and the existing single-cell separation technology, single-cell whole genome amplification technology, single The principles and applications of cell whole transcriptome amplification technology and single cell transcriptome sequencing are summarized and summarized.

Introduction The traditional treatment of myocardial infarction with ventricular septal rupture is surgical treatment. For the elderly patients with cardiac insufficiency, surgical treatment is very risky. The successful treatment of this case by interventional occlusion is a new method. No relevant literature reports have been found. Case A 77-year-old man with a past medical history of old myocardial infarction presented to the physician with sudden onset of palpitation and shortness of breath. Echocardiography showed thinning of the interventricular septum near the apex and bulging toward the right ventricular side with “paradoxical motion”, on which a rupture of about 8 mm in diameter was seen. CDFI: left ventricular blood shunted to the right ventricle through the rupture.Echocardiographic diagnosis: old left ventricular anteroseptal myocardial infarction with ventricular septal rupture. Due to the older age of the patient and reduced left ventricular function, surgical repair of the ventricular septal rupture site was more difficult. After multidisciplinary discussion, it was agreed that the patient could not afford thoracotomy and was not suitable for thoracotomy, and echocardiography guided interventional occlusion of the ruptured interventricular septum could be performed. Conclusion Transesophageal echocardiography-guided interventional occlusion of myocardial infarction with ventricular septal rupture in elderly patients with cardiac insufficiency is a new attempt, the successful treatment of this case shows that this method is feasible, for some patients is an appropriate treatment.

In this study, both AlFe composite pillaring agents and AlFe pillared clays (AlFe-PILC) were synthesized via a facile process developed by our group, after which mixed Cr and Ce precursors were impregnated on AlFe-PILC. Catalytic combustion of organic pollutant chlorobenzene (CB) on CrCe/AlFe-PILC catalysts were systematically studied. AlFe-PILC displayed very high thermal stability and large BET surface area (SBET). After 4 h of calcination at 550 &deg, C, the basal spacing (d001) and SBET of AlFe-PILC was still maintained at 1.91 nm and 318 m2/g, respectively. Large SBET and d001-value, along with the strong interaction between the carrier and active components, improved the adsorption/desorption of CB and O2. When the desorption temperatures of CB and O2 got closer to the CB combustion temperature, the CB conversion could be increased to a higher level. CB combustion on CrCe/AlFe-PILC catalyst was determined using a Langmuir&ndash, Hinshelwood mechanism. Adsorption/desorption/oxidation properties were critical to design highly efficient catalysts for CB degradation. Besides, CrCe/AlFe-PILC also displayed good durability for CB combustion, whether in a humid environment or in the presence of volatile organic compound (VOC), making the catalyst an excellent material for eliminating chlorinated VOCs.

The Michael reaction is widely used for the C-C coupling of electron-poor olefins and C(sp3)-H pronucleophiles. Herein, an effective Michael reaction approach between electron-rich aromatic and heteroaromatic substrates as C(sp2)-H nucleophiles with maleimides as electrophiles in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) was first presented without the need for any additional metal catalysts or reagents. This reaction provides a concise and environmentally friendly strategy for the facile construction of 3-aryl succinimides from N,N-disubstituted anilines and maleimides with high para selectivity.

For the first time, PdCu/TaN C catalyst with a special core-shell structure is assembled, which exhibits high catalytic performance for methanol oxidation reaction (MOR) in alkaline medium (1326.95 A gPd−1) and formic acid oxidation reaction (FAOR) in acidic medium (1052.63 A gPd−1), 6.3 and 4.9 times those of the commercial Pd/C, respectively. According to the results of Tafel, Electrochemical Impedance Spectroscopy (EIS), CO stripping and chronoamperometry (CA), it is revealed that the reaction kinetics, anti-CO poisoning ability and stability of PdCu/TaN C for MOR and FAOR are all enhanced significantly. Density Functional Theory (DFT) calculations also indicate that the adsorption intensity of CO is weakened and the binding intensity of OH is enhanced on the Pd3Cu1/TaN(001) surface, which are beneficial to the removal of adsorbed CO and enhancement of the anti-CO poisoning ability. Combined with the characterization analysis and theoretical calculations, the good catalytic performance of PdCu/TaN C for MOR and FAOR can be attributed to the unique electronic structure and morphology from the effective interface, geometric effects and proper d-band center.

Chemical fixation of carbon dioxide into commodity chemicals is an appealing approach for CO2 transformations and utilizations. The challenge is to develop highly efficient and reusable heterogeneous catalysts. Herein, a cobalt-porphyrin modified graphene oxide (GOPCoCl) has been prepared with chemical functionalization by the acylation and amidation process on the graphene oxide support, and applied as a heterogeneous catalyst for the solvent-free cycloaddition of carbon dioxide and epoxides. The as-received GOPCoCl has been characterized by different methods, demonstrating that the metalloporphyrin is covalently linked to the graphene oxide (GO) surface. Owing to the uniform active sites and support effects, the catalyst behaved efficient catalytic performance, excellent recyclability, and good substrate expansibility for this solvent-free cycloaddition. Moreover, a synergetic catalytic mechanism has been prudently proposed based on the catalytic system and experimental results.

Barker first used transcranial magnetic stimulation in 1985 in human brain function research. Since then, it has gradually been developed into a secure and non-invasive treatment method for neurological diseases. In 1994, Pascual Leone first used it for the treatment of Parkinson's disease (PD) and observed an improvement in the motor symptoms of most of the patients. Recent studies have confirmed that both motor and non-motor symptoms of patients with PD could be improved through biochemical, electrophysiological, and functional magnetic resonance imaging analysis. Different therapeutic applications can be achieved by adjusting the stimulation parameters. Physical factors affecting the therapeutic effect include the shape and size of the coil, array orientation, materials and intensity, frequency of stimulus, etc.; the biological factors include stimulating targets, baseline, circadian rhythms, cerebral cortex thickness, and so on. This paper will review these factors and provide a reference for future research.

Stroke is a life-threatening disease that results in significant disability in the human population. Despite the advances in current stroke therapies, a host of patients do not benefit from the conventional treatments. Thus, more effective therapies are required. It has been previously reported that leucine-rich-α2-glycoprotein 1 (LRG1) is crucial during the formation of new blood vessels in retinal diseases. However, the function of LRG1 in the brain during the neovessel growth process following ischemic stroke has not been fully elucidated and the mechanism underlying its effect on angiogenesis remains unclear. The purpose of the current study was to demonstrate whether LRG1 may promote angiogenesis through the transforming growth factor (TGF)-β1 signaling pathway in ischemic rat brain following middle cerebral artery occlusion (MCAO). In the present study, the spatial and temporal expression of LRG1, TGF-β1, vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) were detected in ischemic rat brain following MCAO using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot analysis and immunohistochemistry. CD34 immunohistochemistry staining was used as an indicator of microvessel density (MVD). The RT-qPCR and western blotting results revealed that the levels of LRG1 and TGF-β1 mRNA and protein expression were significantly increased as early as 6 and 12 h after MCAO (P

Objective Azathioprine (AZA) is widely used in Crohn's disease (CD) patients with a recommended dose, 2-2.5 mg/kg/d, for Westerners. Asian patients are suggested with a lower dose. However, many clinicians reported a poor efficacy with a reduced dose. Our prospective study aims to find a safe dose providing the best efficacy for Chinese CD patients. Methods Fifty active Chinese CD patients were enrolled in our test and randomly split into 2 groups, 25 each. All other treatments were the same except that group A took 1 mg/kg/d and group B took 2 mg/kg/d of AZA. We analysed the complete remission (CR) rate and the response rate on week 12, 24, 48 and with the method of intent-to-treat (ITT) and Per-Protocol (PP) analysis to evaluate the efficacy. Meantime, we evaluated the adverse events and the recurrence rate in both groups. Results On week 48, the CR rate and response rate in group B (ITT: 50.0% and 59.1%; PP: 57.9% and 68.4%) were significantly higher than those in group A (ITT: 13.0% and 17.4%; PP: 16.7% and 22.2%) (P

Overexpression of B cell lymphoma 2 (Bcl-2) proteins is associated with therapy resistance in various human cancers. Traditional approaches target the Bcl-2 homology (BH)3 domain of Bcl-2; however, the BH4 domain represents a superior therapeutic target in light of its unique structure and crucial involvement in many cellular functions. In this critical review, we focus on the structural and functional basis of targeting the BH4 domain of Bcl-2, and highlight the recent advances in drug discovery efforts toward small-molecule BH4 domain inhibitors (e.g. BDA-366). The proof-of-concept studies support the hypothesis that targeting the BH4 domain of Bcl-2 holds promise to offer a novel anticancer therapy through the induction of apoptosis and an increased potential to overcome therapeutic resistance.

Taking the regional logistics of Guangdong Province as the research object, this paper uses the relevant data of logistics and economy of Guangdong Province from 2015 to 2019, and applies the grey correlation analysis method to study the correlation degree between the relevant indicators of economic development of Guangdong Province and the development level of regional logistics. Through quantitative calculation, it clearly shows the relevant economic factors that have a greater impact on regional logistics, and provides good suggestions and Countermeasures for the healthy development of regional logistics.

Three cyano-containing ligands with varied size and shape, i.e. 1,4-dicyano benzene (1,4-dcb), 4,4'-biphenyldicarbonitrile (bpcn) and p-phenylenediacetonitrile (p-phda), were selected as ligands to self-assemble with AgCF3COO and 4,4'-dihydroxyoctafluorobipheny (ofbp) affording five new compounds. Complexes 1-3 ([Ag2(CF3COO)2(1,4-dcb)(S)]·2ofbp·H2O, 1, S benzene, 2, S toluene 3, S m-xylene) were synthesized by the same linear spacer (1,4-dcb) in different solvents, and they exhibit similar 2D networks assembled by 1,4-dcb ligand bridging with 1D chains composing of anions and different coordinating solvents. Complex 4 ([Ag2(CF3COO)2(bpcn)2]·C6H6·2ofbp·H2O) was isolated by replacing 1,4-dcb to the longer linear spacer (bpcn) however it shows a quite different 1D chain structure from those of 1-3. Further changing ligand to p-phda resulted only compound c as a co-crystal of p-phda and ofbp. These totally different crystal structures suggest the ligand-controlled self-assembly processes. The followed antimicrobial assay results demonstrate that all complexes have effective antimicrobial activities with broad spectra. They exhibit excellent antimicrobial activities with low MICs towards both Gram-negative bacteria, Gram-positive bacteria and yeast. Especially, they illustrate encouraging antibacterial activities against antibiotic resistant bacteria (P. aeruginosa). It’s found that these frameworks have discriminating capacities to release Ag+ ions in water sustainably. Complex 4 demonstrated the best antimicrobial efficacy among five complexes. It’s revealed that the ligand exchangeability plays an important role in the antimicrobial activities. The lower concentration of Ag+ ions release of complex 3 is attributed to its compact packing structure on the basis of structure-property discussions.

Direct methanol fuel cells (DMFCs) have attracted extensive attention due to clean, efficient characteristics and portable applications. In this work, a series of PdxCuy/reduced graphene oxide (rGO) catalysts are assembled and the catalytic performances are investigated for methanol oxidation reaction (MOR) in alkaline media. The intrinsic surface electronic structures of the PdxCuy/rGO bimetallic catalysts are also studied to clarify the reaction mechanism. The results reveal that Pd1.2Cu0.2/rGO exhibits superior catalytic activity (1101.58 A gPd−1), 4.2 and 5.2 times higher than those of the commercial PtRu/C and Pd/C catalysts. CO stripping suggests that the onset potential for CO oxidation on the Pd1.2Cu0.2/rGO catalyst is lower than those on the commercial PtRu/C and Pd/C catalysts, implying that the anti-CO poisoning ability is enhanced. Combined with the analysis of X-ray diffraction (XRD), high-resolution transmission electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS) and Raman, the enhanced catalytic activity and anti-CO poisoning ability are attributed to the charge transfer and lattice compression between Pd and Cu, which modify the d-band center and weaken the adsorption of CO. Furthermore, a volcano plot is found between the MOR activity and d-band center, indicating that the excellent MOR activity is attributed to the optimal d-band center with the moderate adsorption strength of CO-like intermediates.