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Prunus mume Sieb. Et Zucc (P. mume) is an acidic fruit native to China (named Chinese Mei or greengage plum). It is currently cultivated in several Asian countries, including Japan ("Ume"), Korea (Maesil), and Vietnam (Mai or Mo). Due to its myriad nutritional and functional properties, it is accepted in different countries, and its characteristics account for its commercialization. In this review, we summarize the information on the bioactive compounds from the fruit of P. mume and their structure-activity relationships (SAR); the pulp has the highest enrichment of bioactive chemicals. The nutritional properties of P. mume and the numerous uses of its by-products make it a potential functional food. P. mume extracts exhibit antioxidant, anticancer, antimicrobial, and anti-hyperuricaemic properties, cardiovascular protective effects, and hormone regulatory properties in various in vitro and in vivo assays. SAR shows that the water solubility, molecular weight, and chemical conformation of P. mume extracts are closely related to their biological activity. However, further studies are needed to evaluate the fruit's potential nutritional and functional therapeutic mechanisms. The industrial process of large-scale production of P. mume and its extracts as functional foods or nutraceuticals needs to be further optimized. [ABSTRACT FROM AUTHOR]

Last several years, a rapid increase in drug resistance to traditional antibiotics has driven the emergence and development of antimicrobial peptides (AMPs). AMPs have also gained considerable attention from scientists due to their high potency in combatting infectious pathogens. A subset of analogues and their derivatives with specific targets have been successfully designed based on natural peptide patterns. In this review, scientific knowledge on the mechanisms of action related to biological activity and structure-activity relationship (SAR) of AMPs are summarized, and the biological applications in several important fields are critically discussed. SAR shows that the positive charge, secondary structure, special amino acid residues, hydrophobicity, and helicity of AMPs are closely related to their biological activities. The combination of nanotechnology, bioinformatics, and genetic engineering can accelerate to achieve the application of AMPs as effective, safe, economical, and nonresistant antimicrobial agents in medicine, the food and feed industries, and agriculture in coming years. Given the intense interest in AMPs, further investigations are needed in the future to evaluate the specific structure and function that make their use favorable in several industries. This review may provide a comprehensive reference for future studies on chemical modifications, mechanistic exploration, and applications of AMPs. [ABSTRACT FROM AUTHOR]

[Display omitted] • Enterococci with optrA increased in mesophilic and thermophilic anaerobic digestion. • IS 1216E in plasmid plays key role in horizontal transfer of optrA. • Chromosomal optrA linked to Tn 554 spread vertically in dominate E. faecalis ST631. • Hyper-thermophilic anaerobic pretreatment reduced plasmid-borne optrA in enterococci. The extensive use of florfenicol in poultry industry results in the emergence of optrA gene, which also confers resistance to clinically important antibiotic linezolid. This study investigated the occurrence, genetic environments, and removal of optrA in enterococci in mesophilic (37 °C) and thermophilic (55 °C) anaerobic digestion systems, and a hyper-thermophilic (70 °C) anaerobic pretreatment system for chicken waste. A total of 331 enterococci were isolated and analyzed for antibiotic resistance against linezolid and florfenicol. The optrA gene was frequently detected in enterococci from chicken waste (42.7%) and effluents from mesophilic (72%) and thermophilic (56.8%) reactors, but rarely detected in the hyper-thermophilic (5.8%) effluent. Whole-genome sequencing revealed that optrA -carrying Enterococcus faecalis sequence type (ST) 368 and ST631 were the dominant clones in chicken waste, and they remained dominant in mesophilic and thermophilic effluents, respectively. The plasmid-borne IS 1216E - fexA - optrA - erm (A)-IS 1216E was the core genetic element for optrA in ST368, whereas chromosomal Tn 554 - fexA - optrA was the key one in ST631. IS 1216E might play a key role in horizontal transfer of optrA due to its presence in different clones. Hyper-thermophilic pretreatment removed enterococci with plasmid-borne IS 1216E - fexA - optrA - erm (A)-IS 1216E. A hyper-thermophilic pretreatment is recommended for chicken waste to mitigate dissemination of optrA from animal waste to the environment. [ABSTRACT FROM AUTHOR]

Immunotherapy is a novel treatment option for various types of cancers. However, the optimal timing for response evaluation has not been well defined. Here, we present a gastric cancer (GC) patient with microsatellite instability-high who experienced recurrence 5 years and 11 months after radical gastrectomy. Then, the patient was treated with radiotherapy, targeted drugs, and immunotherapy. Immunotherapy resulted in 5 months of continuous progression, accompanied by significantly increased tumor marker CA19-9. However, the patient exhibited a satisfactory response without altering the treatment. Based on this, we hypothesized that some persistent progression with elevated tumor markers, known as pseudoprogression (PsP), might be observed in patients with recurrent GC during immunotherapy. This process might be prolonged, but if the treatment is continued, it will eventually produce remarkable therapeutic effects. PsP might challenge the globally accepted immune response evaluation criteria for solid tumors. [ABSTRACT FROM AUTHOR]

Acid stress is one of the most common adverse conditions during fermentation of fruit wines, and the acid tolerance of yeasts is, therefore, critical for fruit wine production. However, the biological mechanism underlying the acquired tolerance of yeasts against acid stress is poorly understood. We have previously obtained an evolved Saccharomyces cerevisiae strain ET008-c54 with increased tolerance against acid stress, and potentially, it serves as a promising yeast strain for greengage wine fermentation. In the current study, we further revealed the alterations responsible for the adaptation of ET008-c54 to low pH by whole-genome re-sequencing, transcriptomic, and metabolic analyses. Results confirmed the outstanding fermenting performance of ET008-c54 at low pH as compared with the parental ET008. More specifically, the growth rate of ET008-c54 at low pH was increased by 6.24 times and the fermentation time was shortened by 70%. Differences were also observed in the physiology of the strains through ergosterol, H+-ATPase activity, and aroma determinations. By integrating both RNA-seq and whole-genome re-sequencing data, we demonstrated some metabolic pathways in ET008-c54, namely ergosterol synthesis and ferrous iron uptake, in which several acid-responsive genes were involved being upregulated. Also, upregulation of the pathways responsible for aroma compound formation, including fatty acid ethyl ester synthesis and aromatic amino acid biosynthesis, was identified. Thus, the enhanced fermentation ability of ET008-c54 at low pH should be, at least partly, contributed by the altered gene expressions associated with the aforementioned pathways. By elucidating the biological mechanism of yeasts against acid stress, this current study allows better-defined targets for future studies of genetic improvement of wine yeasts and enhancement of the fermentation processes. Key points: • Metabolic analysis confirmed the excellent fermentation performance of ET008-c54. • Acid tolerance genes for ergosterol synthesis and ferrous iron uptake were upregulated. • Aroma genes for fatty acid ethyl ester and aromatic amino acid synthesis were upregulated. [ABSTRACT FROM AUTHOR]

The idea of constructing the biological neural system model as realistic as possible can not only provide a new artificial neural network (ANN), but also offer an effective object to study biological neural systems. As a very meaningful attempt about the idea, a bionic model of olfactory neural system, KIII model, is introduced in this paper. There are the unique characteristics of KIII model different from those of general ANNs. The KIII model realistically simulates the structure of the real olfactory neural system and the process of odor molecules gradually transformed by the core components of the olfactory system including olfactory receptor, olfactory bulb and olfactory cortex. The neuron model of the KIII model is constructed and optimized based on neurophysiological experimental data and accurately reflects the response of olfactory neurons to odor stimulation. In particular, the noise introduced to KIII model can further improve the performance of the model. In addition, the KIII model is analyzed based on the idea of deep learning. The qualitative analysis shows that there are obvious similarities between the KIII model and the deep learning model. Furthermore, with the epileptic electroencephalograph (EEG) recognition task, two groups of experiments are designed to comprehensively analyze the performance of the KIII model. In the first group of experiments, a typical pattern recognition experiment with feature extraction stage is shown. The features of epileptic EEG were extracted based on Empirical Mode Decomposition (EMD), and the KIII model was used as a classifier. The experimental results show that the KIII model only needs a small number of iterations to memorize different modes and has a high recognition rate, over 91%. In the second group of experiments, a direct recognition experiment without feature extraction stage is shown. The original epileptic EEG signals as KIII model inputs directly were recognized. The experimental results show that there is still an excellent performance in the KIII model, over 96%, and the recognition result is similar to the characteristics of the deep learning model. The theoretical analysis and experimental results prove that KIII model with the idea of deep learning is an excellent bionic model of olfactory neural system and gets a good balance between high bionics and good performance, which is a good reference for related research. [ABSTRACT FROM AUTHOR]

Acid tolerance and aroma profile are crucial factors for wine production in Saccharomyces cerevisiae. However, most wine yeasts to date fail to endure low-pH environments, therefore resulting in problems such as lengthened fermentation and poor flavor during acidic fruit wine production. In the present study, we established a multiple-step screening strategy, which was composed of atmospheric and room temperature plasma (ARTP), high-throughput screening (HTS), and laboratory adaptive evolution (ALE), to screen yeast strains for potential wine-producing with enhanced performances during low pH conditions. Importantly, we obtained the S. cerevisiae strain from the mutant library, ET008-c54, which displayed exhibited excellent performances in survival rate, fermentation time, aroma profile, and genetic stability. More specifically, the survival rate of ET008-c54 at low pH was increased by 10-fold, the fermentation time of greengage plum wine was shortened by about 70%, and the content of main aroma compounds was significantly increased by 52%. Collectively, we demonstrate the practical application of the screening platform designed for discovering mutant strains in winemaking technology. Key Points • A novel multi-step method was developed for screening wine-producing yeast. • Acid tolerance and aroma profiles of yeast were improved by the proposed method. • ET008-c54 showed excellent fermenting performance and stability at low pH. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD), cancer and diabetes are serious threat to human health and more and more aroused people's attention. It is important to find the safe and effective prevention and treatment methods for the three deadly diseases. At present, a generally attention in the possible positive effects of edible berries for the three deadly diseases has been noted. Berry phytochemical compounds regulate different signaling pathways about cell survival, growth and differentiation. They contribute to the prevention and treatment of CVD, cancer and diabetes. This article reviews previous experimental evidence, several common berry phytochemical compounds and their possible mechanisms involved in three deadly diseases were summarized. [ABSTRACT FROM AUTHOR]

Nuclear receptor binding SET domain protein 3 (NSD3) has recently been recognized as a new epigenetic target in the fight against cancer. NSD3, which is amplified, overexpressed or mutated in a variety of tumors, promotes tumor development by regulating the cell cycle, apoptosis, DNA repair and EMT. Therefore, the inhibition, silencing or knockdown of NSD3 are highly promising antitumor strategies. This paper summarizes the structure and biological functions of NSD3 with an emphasis on its carcinogenic or cancer-promoting activity. The development of NSD3-specific inhibitors or degraders is also discussed and reviewed in this paper. [Display omitted] [ABSTRACT FROM AUTHOR]

Greengage wine is a popular alcoholic beverage that is consumed in China, Korea, and Japan. The main objective of this study was to optimize the fermentation conditions and compare the flavor compounds for three fermented greengage wines (Optimized sample, Wuliangye, and Choya). The relevant parameters of greengage wine were optimized using response surface methodology and central composite design experiments by studying the individual and interactive effects of three variables, including fermentation temperature, material–liquid ratio, and sugar content. The results demonstrated that second–order polynomial models could predict and describe the biochemical responses of alcohol content ( P < 0.0001) and sensory evaluation ( P < 0.001). The optimized conditions (fermentation temperature, material–liquid ratio, and sugar content) for fermented greengage wine were 20 °C, 1:2.0, and 180 g/L, respectively. According to the statistical analysis, there were significant differences of flavor compounds and their concentrations in three fermented greengage wines ( p < 0.05). A total of 53, 30, and 32 flavor compounds were identified in the Optimized sample, Wuliangye, and Choya, respectively. Among these compounds, 5, 2, and 3 quantified compounds (odor activity values > 1) can be found in three fermented greengage wines, and they probably contribute to the wine aroma. [ABSTRACT FROM AUTHOR]

Objective: This study was to evaluate the potential of Erbium:Yttrium Aluminum Garnet laser-activated sodium hypochlorite irrigation (Er:YAG + NaOCl) for minimally invasive endodontics (MIE). Background data: Er:YAG laser irradiation can dramatically enhance the penetration of NaOCl, which may be a promising protocol for MIE. Methods: Extracted human teeth were contaminated with Enterococcus faecalis for 4 weeks. The infected canals were then shaped to different apical terminal working widths (ATWW, 15#/0.04, 20#/0.04, 25#/0.04, 30#/0.04, and 40#/0.04) and treated with either Er:YAG + NaOCl (0.3 W, 20 sec) or NaOCl alone. Then, the ATWW were fixed at 15#/0.04, and the canals were treated with Er:YAG + NaOCl at 0.3 W for 40 and 60 sec, or at 0.5 and 1.0 W for 20 sec. Finally, bacterial reductions were evaluated using the cell count method. Results: Er:YAG + NaOCl showed a higher disinfection efficacy at each ATWW compared with NaOCl alone ( p < 0.001). The maximum bacterial reduction was 99.9% for the 40#/Er:YAG + NaOCl group and 93.6% for the 40#/NaOCl group. To achieve similar disinfection efficacy, the Er:YAG + NaOCl group needed a smaller ATWW than the NaOCl group. At a fixed ATWW, increasing the output power of the Er:YAG laser was more effective than increasing the radiation time to improve the disinfection efficacy of Er:YAG + NaOCl. The 15#/Er:YAG + NaOCl group reached the maximum bacterial reduction of 99.2% when the Er:YAG laser was activated at 1.0 W for 20 sec. Conclusions: The 15#/Er:YAG + NaOCl with the Er:YAG laser irradiation at 1.0 W for 20 sec may be considered a promising procedure for MIE. [ABSTRACT FROM AUTHOR]

Chromogranin A (CgA), present in the chromaffin granules of neuroendocrine cells, is a useful biomarker for the diagnosis of patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). This study was conducted to investigate the potential role of circulating CgA in monitoring clinical response in Chinese patients with advanced GEP-NETs. Eighty patients with advanced GEP-NETs treated in Peking University Cancer Hospital from September 2011 to May 2014 and 65 healthy individuals were included in this study. Serum CgA levels were analyzed for relationship with patient’s baseline characteristics and clinical outcome. Median CgA levels were significantly higher in patients with advanced GEP-NETs than in healthy individuals (93.8 ng/mL vs. 37.1 ng/mL; P<0.01), as well as significantly higher in patients with carcinoid syndrome or liver metastasis than in those without carcinoid syndrome (298.8 ng/mL vs. 82.9 ng/mL; P = 0.011) or liver metastasis (137.0 ng/mL vs. 64.4 ng/mL; P = 0.023). A CgA cutoff value of 46.2 ng/mL was used in this study with a sensitivity of 78.8% and specificity of 73.8%. Patients with CgA levels higher than 46.2 ng/mL had a worse prognosis than patients with CgA levels lower than 46.2 ng/mL (P = 0.045). Notably, a weak correlation was observed between changes in serum CgA levels and clinical response to the IP regimen as well as SSAs. Our data also indicate that serum CgA could be a useful indicator of patient prognosis though there is more research required in order to validate such claims. [ABSTRACT FROM AUTHOR]

The present study investigated the variations in main flavor compounds of a Chinese brandy during the second distillation process using headspace-solid-phase microextraction coupled with gas chromatography-mass spectrometry. A total of 97 volatile compounds involving esters, alcohols, aldehydes, ketones, furans, benzene derivatives and terpenes were quantified, and 28 components were identified as key ingredients. By monitoring the second distillation process, it was found that most ethyl esters (ethyl hexanoate, ethyl octanoate, etc.), alcohols (3-methylbutanol, etc.), terpenes (linalool, etc.), acetaldehyde and ionone all had higher values at the beginning of the distillation, but declined gradually or sharply along with the distillation process. However, two esters (ethyl lactate and diethyl succinate), acids (acetic acid, hexanoic acid), benzene derivatives (2-phenylethanol, etc.) and furan (furfural) showed lower levels when the distillation was just started, and gradually increased, accumulating as a large quantity at the end of the distillation. [ABSTRACT FROM AUTHOR]

• Thirteen key flavor compounds are most likely to be important for wine quality. • Twelve taste-active compounds had a strong correlation with sensory attributes. • Nine flavor compounds had a strong correlation with sensory attributes. This study is sought to identify the components in greengage wine that predict the sensory properties. Taste-active compounds and aroma-active compounds of 20 commercially available greengage wines from different regions were characterized. The relationship between these compounds, wine samples and sensory attributes was modeled by partial least squares regression. The regression analysis indicated the taste-active compounds, alanine, leucine, proline, glutamic acid, lysine, malic acid, citric acid, sucrose, glucose, gallic acid, caffeic acid and tannin made a great contribution to the characteristic taste or mouthfeel of greengage wine. Meanwhile, the aroma-active compounds, including ethyl acetate, ethyl butanoate, ethyl hexanoate, ethyl octanoate, ethyl decanoate, 3-methylbutanol, 5-hydroxymethylfurfural, octanoic acid and benzaldehyde, modeled well with the flavor characteristic of greengage wine. The study revealed new insights into the relationship between chemistry and wine sensory characters, which has implications for developing an objective measurement system for determining greengage wine quality. [ABSTRACT FROM AUTHOR]

Multidrug-resistant Escherichia coli and antibiotic-resistance genes (ARGs) present a danger to public health. However, information on the dissemination potentials of antibiotic resistance among bacteria from different environments is lacking. We isolated multiple antibiotic-resistant Escherichia spp. from animal farms, hospitals, and municipal wastewater-treatment plants (MWWTPs) using culture-based methods, and carried out resistance phenotype and gene analyses. Thirty-five isolates of multiple antibiotic-resistant Escherichia spp. were further screened to detect 61 ARGs, 18 mobile genetic elements (MGEs), and gene cassettes. The isolates from livestock manure and MWWTPs showed greater diversity in plasmid profiling than hospital wastewater. Each Escherichia sp. carried 21–26 ARGs and 8–12 MGEs. In addition, 11 gene cassettes were detected in 34 Escherichia isolates, with greater diversity in livestock manure and MWWTPs than in hospital wastewater. The results indicated that the potential for ARG transfer was higher in livestock manure and MWWTPs compared with human clinical sources, possibly related to the high occurrence of both residual antibiotics and heavy metals in these environments. Image 1 • The transfer potential of ARGs was compared in Escherichia from different sources. • Each of the Escherichia strains carried at least 1 plasmid, 21 ARGs and 8 MGEs. • High prevalence of gene bla CTX-M was detected in the Escherichia isolates. • Higher ARGs transfer potential in livestock manure and MWWTPs than hospital source. [ABSTRACT FROM AUTHOR]

• DOC was the first factor affecting browning of pear wine. • Total phenols was the second factor affecting browning of pear wine. • Browning in pear wine was dominated by non-enzymatic browning. • OPLS model accurately predicted the browning degree according to the quality index. The effects of different dissolved oxygen concentrations (DOC) on the browning degree, amino acids, total phenols, reducing sugars, polyphenoloxidase (PPO), peroxidase (POD), phenylalanine ammonia-lyase (PAL) of pear wine, and the relationship between various quality indicators and browning degree were investigated. Dynamic model fitting analysis of the changes of physiochemical indicators of pear wine in the storage process were performed. The importance of the physiochemical indicators effect on the browning of pear wine during the storage process was analyzed by OPLS (orthogonal partial least squares discriminant analysis), and the effect of dissolved oxygen on the browning of pear wine was systematically revealed. The results showed that dissolved oxygen, total phenols and amino acids had the greatest influence on the browning degree of pear wine. It provided a theoretical basis for revealing the browning mechanism and inhibiting the browning of pear wine. [ABSTRACT FROM AUTHOR]

[Display omitted] • MeHg may induce inflammatory response and autophagy in microglia through the activation of NLRP3 inflammasome via ROS production. • Induction of autophagy can prevent the neurotoxicity of MeHg. • There is an association between the inflammatory response and autophagy in BV2 cells induced by MeHg. Methylmercury (MeHg) is a global environmental pollutant with neurotoxicity, which can easily crosses the blood–brain barrier and cause irreversible damage to the human central nervous system (CNS). CNS inflammation and autophagy are known to be involved in the pathology of neurodegenerative diseases. Meanwhile, MeHg has the potential to induce microglia-mediated neuroinflammation as well as autophagy. This study aims to further explore the exact molecular mechanism of MeHg neurotoxicity. We conducted in vitro studies using BV2 microglial cell from the central nervous system of mice. The role of inflammation and autophagy in the damage of BV2 cells induced by MeHg was determined by detecting cell viability, cell morphology and structure, reactive oxygen species (ROS), antioxidant function, inflammatory factors, autophagosomes, inflammation and autophagy-related proteins. We further investigated the relationship between the inflammatory response and autophagy induced by MeHg by inhibiting them separately. The results indicated that MeHg could invade cells, change cell structure, activate NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome and autophagosome, release a large amount of inflammatory factors and trigger the inflammatory response and autophagy. It was also found that MeHg could disrupt the antioxidant function of cells. In addition, the inhibition of NLRP3 inflammasome alleviated both cellular inflammation and autophagy, while inhibition of autophagy increased cellular inflammation. Our current research suggests that MeHg might induce BV2 cytotoxicity through inflammatory response and autophagy, which may be mediated by the NLRP3 inflammasome activated by oxidative stress. [ABSTRACT FROM AUTHOR]

Sinomenine is an active substance extracted from the traditional Chinese medicine Sinomenium acutum. Sinomenine has been shown to mediate a wide range of pharmacological actions and is known to possess good anti‐inflammatory, immunosuppressive, antitumor, neuroprotective, antiarrhythmic and other pharmacological effects. Understanding the underlying mechanisms and the association between the targets and the pharmaceutical effects on different diseases is crucial to the discovery and design of new treatment strategies. In this review, we aim to give a systematic and comprehensive overview of the research progress of sinomenine over the past 20 years. We first describe the metabolism of sinomenine in vivo and then summarize the pharmacological actions of sinomenine on different diseases. Furthermore, the potential binding properties of sinomenine and the potential of developing new sinomenine‐based drugs are also reviewed. [ABSTRACT FROM AUTHOR]

The patient-derived tumor xenograft (PDTX) model has become the most realistic model for preclinical studies. PDTX models of gastric cancer using surgical tissues are reported occasionally; however, the PDTX models using gastroscopic biopsies, which are best for evaluating new drugs, are unreported. In our study, a total of 185 fresh gastroscopic biopsies of gastric cancer were subcutaneously transplanted into NOD/SCID (Nonobese Diabetic/Severe Combined Immunodeficiency) mice. Sixty-three PDTX models were successfully established (34.1%, 63/185) and passaged to maintain tumors in vivo, and the mean latency period of xenografts was 65.86 ± 32.84 days (11-160 days). Biopsies of prior chemotherapy had a higher transplantation rate (52.1%, 37/71) than biopsies after chemotherapy (21.9%, 25/114; P = 0.000). No differences were found between the latency period of xenografts and characteristics of patients. The pathological and molecular features of PDTX as well as chemosensitivity were highly consistent with those of primary tumors of patients. The genetic characteristics were stable during passaging of PDTX models. In summary PDTX models using gastroscopic biopsies in gastric cancer were demonstrated for the first time, and the biological characteristics of the PDTX models were highly consistent with patients, which provided the best preclinical study platform for gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Pyrotinib was well tolerated but its efficacy was unsatisfactory in patients with HER2‐positive gastric cancer (GC) (NCT02378389). This study was to optimize the efficacy of pyrotinib. Methods: Human GC cell lines and AVATAR mice were used to explore the refractory mechanisms of pyrotinib. A pyrotinib‐combined strategy was proposed, which was validated in preclinical AVATAR mouse and in clinical patients enrolled in a phase I clinical trial (NCT03480256). Results: Dysregulation of CCND1‐CDK4/6‐Rb axis might be the key to pyrotinib refractory. The strategy of pyrotinib combined with a CDK4/6 inhibitor SHR6390 was proposed and validated in preclinical AVATAR mouse, which was successfully verified in clinical patients. For five patients treated with pyrotinib plus SHR6390 who had available response evaluation, the best response was partial response in three patients, stable disease in one patient, and progressive disease in one patient. The progression‐free survival times were 120, 200, 532, 109, and 57 days, respectively. Conclusions: This translational study suggests that pyrotinib combined with SHR6390 may serve as a promising strategy for patients with HER2‐positive GC. Trial registration: The ClinicalTrials.gov identifiers are NCT02378389 (https://clinicaltrials.gov/ct2/show/study/NCT02378389, registered in 11 February 2015) and NCT03480256 (https://clinicaltrials.gov/ct2/show/study/NCT03480256, registered in 8 March 2018). [ABSTRACT FROM AUTHOR]

Three commercial yeasts strains, namely, Saccharomyces cerevisiae SY, DV10, and Drop Acid Yeast, were used for Dangshan pear wine fermentation. Monitoring main physical and chemical indexes and scoring comprehensive sensory characteristics to find a suitable yeast to produce Dangshan pear wine. The fermentation cycle of SY was short (15 days), and the SY‐fermented wine had a suitable sugar‐acid ratio, with a residual sugar content of 3.13 ± 0.05 g/L, total acid content of 3.40 ± 0.11 g/L, and ethanol content of 14.1 ± 0.27% (v/v). Additionally, 42 flavor compounds were detected in fermented Dangshan pear wine, and the total amount of flavor compounds was highest in the SY wine (2,584.72 μg/L). Combined with the comprehensive sensory evaluation scores, these results suggest that Saccharomyces cerevisiae SY was the most suitable strain to produce Dangshan pear wine. Practical applications: In this study, we compared the physical and chemical indicators of pear wine brewed by different Saccharomyces cerevisiae in the process of fermentation and the final quality of pear wine products. It was concluded that the pear wine produced by Saccharomyces cerevisiae SY had good quality. The study found a strain suitable for the fermentation of pear wine and provided a theoretical basis for the industrial production of pear wine. Next, we can try to use Saccharomyces cerevisiae SY for large‐scale production of pear wine and try to sell it on the market. [ABSTRACT FROM AUTHOR]

Histone lysine-specific demethylase 1 (LSD1) is a promising target for cancer therapy. Here, we performed the design, synthesis, and extensive structure-activity relationship (SAR) studies based on our previously discovered natural LSD1 inhibitor, higenamine. We found that the tetracyclic tetrahydroisoquinoline FY-21 is a potent and selective inhibitor of LSD1 (IC 50 = 340 nM). FY-21 inhibited leukemia cell proliferation and colony formation and increased the level of p53 expression. Meanwhile, FY-21 reduced the mRNA levels of the transcription factors HOXA9 and MEIS1. Furthermore, FY-21 significantly induced leukemia cell differentiation. In vivo studies showed that FY-21 prolonged the survival rate of leukemia mice. Collectively, FY-21 is a potent, selective LSD1 inhibitor and can serve as a lead compound for the development of novel and highly effective LSD1 inhibitors for AML treatment. New tetrahydroisoquinoline as potent and selective LSD1 inhibitor for AML treatment. [Display omitted] • FY-21 was identified as a novel LSD1 inhibitor. • FY-21 exhibited potent antiproliferation activity against MLL-rearranged leukemia cells. • FY-21 induced cell apoptosis in MLL-rearranged leukemia cells by upregulating the expression of p53. • In vivo anti-tumor studies showed that FY-21 significantly extended the lifespan of leukemia mice. [ABSTRACT FROM AUTHOR]

Background: Patient-derived xenograft (PDX) models with definite molecular signature are attractive preclinical models for development of novel targeted drugs. Here, we profiled and explored potential therapeutic targets based on characterized PDX models for advanced gastric cancer (AGC). Methods: The genomic variation and molecular profile of 50 PDX models from AGC patients were analyzed by targeted next-generation sequencing, in situ hybridization, and immunohistochemistry. The antitumor activities of several targeted drugs were investigated in the PDX models. Furthermore, response biomarkers were explored. Results: Each PDX model had individual histopathological and molecular features, and recurrent alterations in the MAPK, ErbB, VEGF, mTOR, and cell cycle signaling pathways were major events in these PDX models. Several potential drug targets, such as EGFR, MET, and CCNE1, were selected and validated in this study. Volitinib demonstrated strong antitumor activity in PDX models with MET and phosphorylated MET (pMET) overexpression. The EGFR monoclonal antibodies BK011 and cetuximab inhibited tumor growth in a PDX model with EGFR amplification. Afatinib inhibited tumor growth in the PDX models with EGFR amplification, EGFR overexpression, or HER2 amplification. Apatinib was more sensitive in the PDX models with high microvessel density. The CDK1/2/9 inhibitor AZD5438 had superior anti-tumor activity in two models with higher copy number of CCNE1. Conclusions: PDX models with defined molecular signature are useful for preclinical studies with targeted drugs, and the results should be validated in larger studies with PDX models or in clinical trials. [ABSTRACT FROM AUTHOR]

Clostridium difficile is the causative pathogen for antibiotic-related nosocomial diarrhea. For epidemiological study and identification of virulent clones, a new binary typing method was developed for C. difficile in this study. The usefulness of this newly developed optimized 10-loci binary typing method was compared with two widely used methods ribotyping and multilocus sequence typing (MLST) in 189 C. difficile samples. The binary typing, ribotyping and MLST typed the samples into 53 binary types (BTs), 26 ribotypes (RTs), and 33 MLST sequence types (STs), respectively. The typing ability of the binary method was better than that of either ribotyping or MLST expressed in Simpson Index (SI) at 0.937, 0.892 and 0.859, respectively. The ease of testing, portability and cost-effectiveness of the new binary typing would make it a useful typing alternative for outbreak investigations within healthcare facilities and epidemiological research. [ABSTRACT FROM AUTHOR]

The anti-HER2 monoclonal antibody trastuzumab is central to the treatment of HER2-positive gastric cancer (GC); however, its responses are limited. HER3 seems to be the preferred dimerization partner with HER2 and is emerging as a key target for complete blockade of downstream pathways and better clinical response. In this study, we report that novel anti-HER3 antibodies (1A5-3D4) that can neutralize multiple modes of HER3 activation, combined with trastuzumab, exhibited synergistic inhibitory effect on the cell proliferation in HER2-positive GC cell lines. Follow-up studies revealed that the combination treatment significantly inhibited phosphorylation of HER3 as well as AKT and ERK signals. In vivo experiments further showed that the anti-tumor effect of trastuzumab was enhanced by its combination with 1A5-3D4 in NCI-N87 xenograft and patient derived xenografts (PDX). Particularly in an HER2-negative whereas neuregulin1 (a ligand of HER3) positive PDX, the combination was also superior to monotherapy. 1A5-3D4 in combination with trastuzumab exhibits a synergistic inhibitory effect on tumor activity, suggesting that targeting both HER2 and HER3 resulted in an improved treatment effects on HER2-positive GC. [ABSTRACT FROM AUTHOR]

Dengue is an acute tropical infectious disease transmitted by mosquitoes, which has posed a major challenge to global public health. Unfortunately, there is a lack of clinically proven dengue-specific drugs for its prevention and treatment. As the pathogenesis of dengue has not been fully elucidated, the development of specific drugs is seriously hindered. This article briefly describes the pathogenesis of dengue fever, the molecular characteristics, and epidemiology of dengue virus, and focuses on the potential small-molecule inhibitors of dengue virus, including on-target and multi-targeted inhibitors, which have been reported in the past two years. [Display omitted] • Potential targets for the development of anti-dengue drugs are summarized. • Elaboration on the infection and pathogenesis of dengue fever. • Natural products or Chinese herbal medicines are important candidate resources for developing anti-dengue drugs. [ABSTRACT FROM AUTHOR]

Background: To investigate the in vitro and in vivo antitumor activity of dual PI3K/mTOR inhibitor BEZ235 (NVP-BEZ235) in HER2-positive gastric cancer.Methods: HER2-positive breast cancer cell line (BT474), HER2-positive (NCI-N87 and SNU216), and HER2-negative (MKN45) gastric cancer cell lines were used in this study. Cell viability, cell cycle, and HER2 downstream signaling pathways were analyzed using the MTS assay, flow cytometry, and western blotting, respectively. For the in vivo experiments, HER2-positive gastric cancer patient-derived xenografts were treated with BEZ235 to assess its antitumor activity.Results: The sensitivity of trastuzumab in BT474 cells was higher than that for NCI-N87 and SNU216 cells, which may be partially attributed to continuously active HER2 downstream signaling pathway. BEZ235 inhibited the proliferation of NCI-N87 and SNU216 cells in vitro in a dose-dependent manner by inducing the cell cycle arrest at the G1 phase. BEZ235 demonstrated greater inhibitory effects than trastuzumab, a unique targeted drug, in both the in vitro and in vivo set of experiments. Additionally, our results indicate that BEZ235 displayed some synergism with trastuzumab. BEZ235 exhibited its antitumor activity in gastric cancer by inhibiting important HER2 downstream signaling pathways, as indicated by the inhibition of phosphorylated AKT and S6.Conclusion: The present study has demonstrated, for the first time, the antitumor activity of BEZ235 against HER2-positive gastric cancer in patient-derived xenografts, as well its synergistic interaction with trastuzumab. These important findings can be utilized to facilitate the design of future clinical trials. [ABSTRACT FROM AUTHOR]