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Due to the growing global population, reduction in arable land and effects of climate change, incongruity between food supply and demand has become increasingly severe. Nowadays, with awareness of the elementary nutrients required for human growth, increasing attention is being paid to the health and medical functions of food. Along with increased food production achieved by modern agricultural techniques, underutilised functional foods are an important strategy for solving food security problems and maintaining the nutritional quality of the human diet. Rosa roxburghii Tratt (RRT) is a natural fruit that contains unique functional and nutritional constituents, which are characterised by a high anti-oxidant potential. This review summarises the biological characteristics, chemical composition, health-promoting properties and development status of RRT products to inspire investigations on the use of RRT fruit as a functional food, dietary supplement and pharmaceutical additive. The nutrients and functional ingredients of RRT fruit are described in detail to provide more reference information for nutritionists and pharmacists.

Chronic kidney disease (CKD) is a severe health problem worldwide, and vascular calcification (VC) contributes substantially to the cardiovascular morbidity and high mortality of CKD. CKD is often accompanied by a variety of pathophysiological states, such as inflammation, oxidative stress, hyperglycaemia, hyperparathyroidism and haemodynamic derangement, that can cause injuries to smooth muscle cells (SMCs) and endothelial cells (ECs) to promote VC. Similar to SMCs, whose role has been widely explored in VC, ECs may contribute to VC via osteochondral transdifferentiation, apoptosis, etc. In addition, given their location in the innermost layer of the blood vessel lumen and preferential reception of various pro-calcification stimuli, ECs can pass messages to vascular wall cells and communicate with them. Crosstalk between ECs and SMCs via cytokines through a paracrine mechanism, extracellular vesicles, miRNAs and myoendothelial gap junctions also plays a role in VC. In this review, we emphasize the role of intercellular crosstalk between ECs and SMCs in VC associated with CKD., (© 2021 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.)

Objective: To investigate the relationship between peroxisome proliferator-activated receptor gamma (PPARγ) mRNA, serum adiponectin (ADP) and lipids in paediatric patients with Kawasaki disease (KD)., Methods: This prospective study enrolled paediatric patients with KD and grouped them according to the presence or absence of coronary artery lesions (CAL). A group of healthy age-matched children were recruited as the control group. The levels of PPARγ mRNA, serum ADP and lipids were compared between the groups. Receiver operating characteristic (ROC) curve analysis was undertaken to determine if the PPARγ mRNA level could be used as a predictive biomarker of CAL prognosis., Results: The study enrolled 42 patients with KD (18 with CAL [CAL group] and 24 without CAL [NCAL group]) and 20 age-matched controls. PPARγ mRNA levels in patients with KD were significantly higher than those in the controls; but significantly lower in the CAL group than the NCAL group. ROC curve analysis demonstrated that the PPARγ mRNA level provided good predictive accuracy for the prognosis of CAL. There was no association between PPARγ, ADP and lipid levels., Conclusion: There was dyslipidaemia in children with KD, but there was no correlation with PPARγ and ADP. PPARγ may be a predictor of CAL in patients with KD with good predictive accuracy.

Hyperlipidemia, an important risk factor for cardiovascular and end-stage renal diseases, often aggravates renal injury and compromises kidney function. Here, histological analysis of human kidney samples revealed that high lipid levels induced the development of renal fibrosis. To elucidate the mechanism underlying lipid nephrotoxicity, we used two types of mouse models (Apoe -/- and C57BL/6 mice fed a 45 and 60% high-fat diet, respectively). Histological analysis of kidney tissues revealed high-lipid-induced renal fibrosis and inflammation; this was confirmed by examining fibrotic and inflammatory marker expression using Western blotting and real-time polymerase chain reaction. Oxidized low-density lipoprotein (OX-LDL) significantly induced the fibrotic response in HK-2 tubular epithelial cells. RNA-sequencing and Gene Ontology analysis of differentially expressed mRNAs in OX-LDL-treated HK-2 tubular epithelial cells and real-time PCR validation in Apoe -/- mice showed that the expression of thrombospondin-1 ( THBS1 ) in the high-fat group was significantly higher than that of the other top known genes, along with significant overexpression of its receptor CD47. THBS1 knockdown cells verified its relation to OX-LDL-induced fibrosis and inflammation. Liquid chromatography tandem mass spectrometry and STRING functional protein association network analyses predicted that THBS1/CD47 modulated the interaction between γ-catenin and E-cadherin and was involved in epithelial-mesenchymal transition, which was supported by immunoprecipitation and immunohistochemistry. CD47 downregulation following transfection with small-hairpin RNA in OX-LDL-treated tubular epithelial cells and treatment with anti-CD47 antibody restored the expression of E-cadherin and attenuated renal injury, fibrosis, and inflammatory response in OX-LDL-treated cells and in type 2 diabetes mellitus. These findings indicate that CD47 may serve as a potential therapeutic target in long-term lipid-induced kidney injury., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gao, Yang, Zhang, Liu, Cai, Wang, Wang, Li, Gao, Zhang, Cao, Ji, Yang, Han, Wang, He, Nie, Liu, Meng and He.)

Hypervirulent Klebsiella pneumoniae (hvKP) strains cause extra-pulmonary infections such as intra-abdominal infection (IAI) even in healthy individuals due to its resistance to polymorphonuclear neutrophil (PMN) killing and a high incidence of multidrug resistance. To assess whether human placental mesenchymal stem cell (PMSC) therapy can be an effective treatment option, we established a murine model of hvKP- IAI to evaluate immune cell modulation and bacterial clearance for this highly lethal infection. This protocol can rapidly assess potential therapies for severe bacterial IAIs. For complete details on the use and execution of this protocol, please refer to Wang et al. (2020)., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Background: To investigate the effect of lactic acid (LA) on the progression of bone metastasis from colorectal cancer (CRC) and its regulatory effects on primary CD115 (+) osteoclast (OC) precursors., Methods: The BrdU assay, Annexin-V/PI assay, TRAP staining and immunofluorescence were performed to explore the effect of LA on the proliferation, apoptosis and differentiation of OC precursors in vitro and in vivo. Flow cytometry was performed to sort primary osteoclast precursors and CD4(+) T cells and to analyze the change in the expression of target proteins in osteoclast precursors. A recruitment assay was used to test how LA and Cadhein-11 regulate the recruitment of OC precursors. RT-PCR and Western blotting were performed to analyze the changes in the mRNA and protein expression of genes related to the PI3K-AKT pathway and profibrotic genes. Safranin O-fast green staining, H&E staining and TRAP staining were performed to analyze the severity of bone resorption and accumulation of osteoclasts., Results: LA promoted the expression of CXCL10 and Cadherin-11 in CD115(+) precursors through the PI3K-AKT pathway. We found that CXCL10 and Cadherin-11 were regulated by the activation of CREB and mTOR, respectively. LA-induced overexpression of CXCL10 in CD115(+) precursors indirectly promoted the differentiation of osteoclast precursors through the recruitment of CD4(+) T cells, and the crosstalk between these two cells promoted bone resorption in bone metastasis from CRC. On the other hand, Cadherin-11 mediated the adhesion between osteoclast precursors and upregulated the production of specific collagens, especially Collagen 5, which facilitated fibrotic changes in the tumor microenvironment. Blockade of the PI3K-AKT pathway efficiently prevented the progression of bone metastasis caused by lactate., Conclusion: LA promoted metastatic niche formation in the tumor microenvironment through the PI3K-AKT pathway. Our study provides new insight into the role of LA in the progression of bone metastasis from CRC. Video Abstract.

The rapid aging of worldwide populations had led to epidemic increases in the incidence of osteoporosis (OP), but while treatments are available, high cost, adverse effects, and poor compliance continue to be significant problems. Naturally occurring plant-based compounds including phytoestrogens can be good and safe candidates to treat OP, but screening for osteogenic capacity has been difficult to achieve, largely due to the requirement of using primary osteoblasts or mesenchymal stem cells (MSCs), the progenitors of osteoblasts, to conduct time-consuming in vitro and in vivo osteogenic assay. Taking advantage of MSC osteogenic capacity and utilizing a promoter reporter assay for Runx2, the master osteogenesis transcription factor, we developed a rapid in vitro screening platform to screen osteogenic small molecules including natural plant-based compounds. We screened eight plant-derived compounds from different families including flavonoids, polyphenolic compounds, alkaloids, and isothiocyanates for osteogenic capacity using the human RUNX2-promoter luciferase reporter (hRUNX2-luc) transduced into the mouse MSC line, C3H10T1/2, with daidzein-a well-studied osteogenic phytoestrogen-as a positive control. Classical in vitro and in vivo osteogenesis assays were performed using primary murine and human bone marrow MSCs (BMMSCs) to validate the accuracy of this rapid screening platform. Using the MSC/hRUNX2-luc screening platform, we were able not only to shorten the selection process for osteogenic compounds from 3∼4 weeks to just a few days but also simultaneously perform comparisons between multiple compounds to assess relative osteogenic potency. Predictive analyses revealed nearly absolute correlation of the MSC/hRUNX2-luc reporter platform to the in vitro classical functional assay of mineralization using murine BMMSCs. Validation using human BMMSCs with in vitro mineralization and in vivo osteogenesis assays also demonstrated nearly absolute correlation to the MSC/hRUNX2-luc reporter results. Our findings therefore demonstrate that the MSC/hRUNX2 reporter platform can accurately, rapidly, and robustly screen for candidate osteogenic compounds and thus be relevant for therapeutic application in OP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Lee, Bai, Chiang, Wang, Yen and Yen.)

The emergence of clinically relevant β-lactam-resistant bacteria poses a serious threat to human health and presents a major challenge for medical treatment. How opportunistic pathogenic bacteria acquire antibiotic resistance and the prevalence of antibiotic-resistant opportunistic pathogenic bacteria in the environment are still unclear. In this study, we further confirmed that the selective pressure of heavy metals contributes to the increase in ampicillin-resistant opportunistic pathogens in the Xiangjiang River. Four ampicillin-resistant opportunistic pathogenic bacteria (Pseudomonas monteilii, Aeromonas hydrophila, Acinetobacter baumannii, and Staphylococcus epidermidis) were isolated on Luria-Bertani (LB) agar plates and identified by 16S rRNA sequencing. The abundance of these opportunistic pathogenic bacteria significantly increased in the sites downstream of the Xiangjiang River that were heavily influenced by metal mining activities. A microcosm experiment showed that the abundance of β-lactam resistance genes carried by opportunistic pathogenic bacteria in the heavy metal (Cu 2+ and Zn 2+ ) treatment group was 2-10 times higher than that in the control. Moreover, heavy metals (Cu 2+ and Zn 2+ ) significantly increased the horizontal transfer of plasmids in pathogenic bacteria. Of particular interest is that heavy metals facilitated the horizontal transfer of conjugative plasmids, which may lead to the prevalence of multidrug-resistant pathogenic bacteria in the Xiangjiang River., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: Symptoms of depression and high risk of sarcopenia are common among the older population; however, the associations between these remain unclear. Thus, the present study identified whether depressive symptoms are associated with older adults' sarcopenia risks., Participants: This nationally representative study in Taiwan investigated the older adult population ( ≥ 65 years) using a telephone survey conducted between 2019 and 2020., Design: Self-reported data obtained included depressive symptoms (5-item from Center for Epidemiological Studies-Depression scale), sarcopenia risks (SARC-F questionnaire), and individual characteristics. The generalized additive models were used to examine the nonlinear associations between depressive symptoms and the risk of sarcopenia., Results: A total of 1,068 older Taiwanese adults (72.15 ± 5.71 years; 52.7% women) participated in the survey. In the unadjusted model, the results showed a significant nonlinear association between high scores on the CES-D and sarcopenia scores (p < .001). Even after adjusting for covariates (sex, age, residential areas, education, marital status, working status, living status, smoking, drinking, and BMI), it still showed a significant non-linear association (p < .001)., Conclusion: The results indicated that depressive symptoms were nonlinearly related to older adults' sarcopenia risks. Interventions or programs aiming to alleviate depression can be an effective strategy to prevent sarcopenia in the older adult population., Competing Interests: The authors declare no conflict of interests.

Bullous pemphigoid (BP) is an autoimmune disease that requires immunosuppressive therapy. Systemic corticosteroids are considered the standard treatment for moderate-to-severe BP. Kaposi's sarcoma (KS) is a rare multifocal endothelial tumour that affects the skin, mucosa and viscera. As an angioproliferative disease of obscure aetiopathogenesis and histogenesis, KS is associated with human herpesvirus 8 (HHV-8). This current case report describes a rare occurrence of extensive cutaneous KS in a 60-year-old Chinese male patient after oral methylprednisolone treatment for BP with an emphasis on its pathological characterization. A total of more than 40 nodules were found on his trunk and lower limbs covering more than 20% of his body surface area. Immunohistochemical staining of biopsy samples from the lesion showed the patient was positive for HHV-8, CD31, CD34, XIIIa, ERG and Ki-67. The Epstein-Barr virus test showed the patient tested negative for immunoglobulin (Ig)A and IgM, but was positive for IgG. Immunosuppression associated with the treatment for BP may activate a latent HHV-8 infection and induce the development of KS.

Objective: To explore the natural mutations in Spike protein (S protein) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the changes of affinity between virus and associated receptors or drug molecules before and after the mutation based on whole length sequencing results., Methods: In the study, the bioinformatics analysis of all the published sequences of SARS-CoV-2 was conducted and thus the high frequency mutation sites were affirmed. Taking advantages of PolyPhen-2, the functional influence of each mutation in S protein was prospected. The 3D homologous modelling was performed by SWISS-MODEL to establish mutated S protein structural model, in which the protein-docking was then implemented with angiotensin-converting enzyme 2 (ACE2), dipeptidyl peptidase-4 (DPP4) and aminopeptidase N (APN) by ZDOCK, and the combining capacity of each mutated S protein evaluated by FiPD. Finally, the binding ability between mutated S proteins and anti-virus drugs were prospected and evaluated through AutoDock-Chimera 1.14., Results: The mutations in specific region of S protein had greater tendency to destroy the S protein function by analysis of mutated S protein structure. Protein-receptor docking analysis between naturally mutated S protein and host receptors showed that, in the case of spontaneous mutation, the binding ability of S protein to ACE2 tended to be weakened, while the binding ability of DPP4 tended to be enhanced, and there was no significant change in the binding ability of APN. According to the computational simulation results of affinity binding between small molecular drugs and S protein, the affinity of aplaviroc with S protein was significantly higher than that of other small molecule drug candidates., Conclusion: The region from 400-1 100 amino acid in S protein of SARS-CoV-2 is the mutation sensitive part during natural state, which was more potential to mutate than other part in S protein during natural state. The mutated SARS-CoV-2 might tend to target human cells with DPP4 as a new receptor rather than keep ACE2 as its unique receptor for human infection. At the same time, aplaviroc, which was used for the treatment of human immunodeficiency virus (HIV) infection, may become a new promising treatment for SARS-CoV-2 and could be a potential choice for the development of SARS-CoV-2 drugs.

In various infections or vaccinations of mice or humans, reports of the persistence and the requirements for restimulation of the cytotoxic mediators granzyme B (GrB) and perforin (PRF) in CD8 + T cells have yielded disparate results. In this study, we examined the kinetics of PRF and GrB mRNA and protein expression after stimulation and associated changes in cytotoxic capacity in virus-specific memory cells in detail. In patients with controlled HIV or cleared respiratory syncytial virus (RSV) or influenza virus infections, all virus-specific CD8 + T cells expressed low PRF levels without restimulation. Following stimulation, they displayed similarly delayed kinetics for lytic protein expression, with significant increases occurring by days 1 to 3 before peaking on days 4 to 6. These increases were strongly correlated with, but were not dependent upon, proliferation. Incremental changes in PRF and GrB percent expression and mean fluorescence intensity (MFI) were highly correlated with increases in HIV-specific cytotoxicity. mRNA levels in HIV-specific CD8 + T-cells exhibited delayed kinetics after stimulation as with protein expression, peaking on day 5. In contrast to GrB, PRF mRNA transcripts were little changed over 5 days of stimulation (94-fold versus 2.8-fold, respectively), consistent with posttranscriptional regulation. Changes in expression of some microRNAs, including miR-17, miR-150, and miR-155, suggested that microRNAs might play a significant role in regulation of PRF expression. Therefore, under conditions of extremely low or absent antigen levels, memory virus-specific CD8 + T cells require prolonged stimulation over days to achieve maximal lytic protein expression and cytotoxic capacity. IMPORTANCE Antigen-specific CD8 + T cells play a major role in controlling most virus infections, primarily by perforin (PRF)- and granzyme B (GrB)-mediated apoptosis. There is considerable controversy regarding whether PRF is constitutively expressed, rapidly increased similarly to a cytokine, or delayed in its expression with more prolonged stimulation in virus-specific memory CD8 + T cells. In this study, the degree of cytotoxic capacity of virus-specific memory CD8 + T cells was directly proportional to the content of lytic molecules, which required antigenic stimulation over several days for maximal levels. This appeared to be modulated by increases in GrB transcription and microRNA-mediated posttranscriptional regulation of PRF expression. Clarifying the requirements for maximal cytotoxic capacity is critical to understanding how viral clearance might be mediated by memory cells and what functions should be induced by vaccines and immunotherapies., (Copyright © 2020 American Society for Microbiology.)

Discovering potent human monoclonal antibodies (mAbs) targeting the Plasmodium falciparum circumsporozoite protein (PfCSP) on sporozoites (SPZ) and elucidating their mechanisms of neutralization will facilitate translation for passive prophylaxis and aid next-generation vaccine development. Here, we isolated a neutralizing human mAb, L9 that preferentially bound NVDP minor repeats of PfCSP with high affinity while cross-reacting with NANP major repeats. L9 was more potent than six published neutralizing human PfCSP mAbs at mediating protection against mosquito bite challenge in mice. Isothermal titration calorimetry and multiphoton microscopy showed that L9 and the other most protective mAbs bound PfCSP with two binding events and mediated protection by killing SPZ in the liver and by preventing their egress from sinusoids and traversal of hepatocytes. This study defines the subdominant PfCSP minor repeats as neutralizing epitopes, identifies an in vitro biophysical correlate of SPZ neutralization, and demonstrates that the liver is an important site for antibodies to prevent malaria., Competing Interests: Declaration of Interests R.A.S., J.R.F., L.T.W., and R.V. have submitted US Provisional Patent Application 62/842,590, filed 3 May 2019, describing mAb L9. All other authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The broad immunomodulatory properties of human mesenchymal stem cells (MSCs) have allowed for wide application in regenerative medicine as well as immune/inflammatory diseases, including unmatched allogeneic use. The novel coronavirus disease COVID-19 has unleashed a pandemic in record time accompanied by an alarming mortality rate mainly due to pulmonary injury and acute respiratory distress syndrome. Because there are no effective preventive or curative therapies currently, MSC therapy (MSCT) has emerged as a possible candidate despite the lack of preclinical data of MSCs for COVID-19. Interestingly, MSCT preclinical data specifically on immune/inflammatory disorders of the lungs were among the earliest to be reported in 2003, with the first clinical use of MSCT for graft-vs-host disease reported in 2004. Since these first reports, preclinical data showing beneficial effects of MSC immunomodulation have accumulated substantially, and as a consequence, over a third of MSCT clinical trials now target immune/inflammatory diseases. There is much preclinical evidence for MSCT in noninfectious-including chronic obstructive pulmonary disease, asthma, and idiopathic pulmonary fibrosis-as well as infectious bacterial immune/inflammatory lung disorders, with data generally demonstrating therapeutic effects; however, for infectious viral pulmonary conditions, the preclinical evidence is more scarce with some inconsistent outcomes. In this article, we review the mechanistic evidence for clinical use of MSCs in pulmonary immune/inflammatory disorders, and survey the ongoing clinical trials-including for COVID-19-of MSCT for these diseases, with some perspectives and comment on MSCT for COVID-19., (© 2020 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Hypervirulent Klebsiella pneumoniae (hvKP) causes severe infections even in healthy individuals by escaping surveillance and killing from polymorphonuclear neutrophils (PMNs), the first-line leukocytes in bacterial infections; moreover, the emergence of multidrug-resistant strains further limits treatment options. We therefore assess whether multilineage mesenchymal stem cells (MSCs), best known for immunomodulation toward T cells, could be therapeutic for highly virulent bacterial infections via modulation of PMNs. We find that both bone marrow MSCs and placental MSCs (PMSCs) preserve in vitro PMN survival, but only PMSCs significantly enhance multiple PMN bactericidal functions, including phagocytosis, through secretion of interleukin-1β (IL-1β). PMSC treatment of hvKP-infected mice suppresses T and natural killer (NK) cell responses as expected but can preferentially recruit PMNs and enhance antibacterial functions to allow for disease survival; IL-1β knockdown in PMSCs significantly decreases hvKP clearance, worsening survival and resulting in 100% lethality. Our data strongly implicate the possible use of PMSCs for infections of PMN-resistant hvKP strains., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

The XENON1T collaboration has observed an excess in electronic recoil events below 5 keV over the known background, which could originate from beyond-the-standard-model physics. The solar axion is a well-motivated model that has been proposed to explain the excess, though it has tension with astrophysical observations. The axions traveling from the Sun can be absorbed by the electrons in the xenon atoms via the axion-electron coupling. Meanwhile, they can also scatter with the atoms through the inverse Primakoff process via the axion-photon coupling, which emits a photon and mimics the electronic recoil signals. We found that the latter process cannot be neglected. After including the keV photon produced via the inverse Primakoff process in the detection, the tension with the astrophysical constraints can be significantly reduced. We also explore scenarios involving additional new physics to further alleviate the tension with the astrophysical bounds.

Background: Patients newly diagnosed with lung adenocarcinoma with bone metastases (LABM) have poor survival rates after treatment with conventional therapies. To improve outcomes, we retrospectively investigated whether the application of a more comprehensive genetic test of tumor biopsies samples from LABM patients could provide the basis for treatment with more effective tyrosine kinase inhibitors (TKIs) regimens., Methods: Fine needle biopsies were taken from the primary tumor (PT) and a secondary bone metastasis (BM) of 17 LABM patients before treatment. Simple genetic profiles for selecting therapies were initially obtained using an ARMS-PCR test for EGFR and ALK fusion mutations. More detailed genetic profiles of somatic exon SNVs and CNVs in 457 cancer-related genes were retrospectively derived using capture single molecule amplification and resequencing technology (capSMART)., Results: ARMS-PCR identified 14 EGFR positive, 3 EGFR negative and 1 ALK fusion positive patient. A therapy regimen incorporating TKIs Gefitinib and Crizotinib was offered to the EGFR and ALK fusion positive patients, respectively. With the exception of two patients, molecular profiling of matching PT and BM biopsies identified a highly shared somatic variant fingerprint, although the BMs exhibited additional genomic instability. In six of 13 EGFR positive patients and in all three EGFR negative patients, examination of the genetic profiles identified additional clinically significant mutations that are known or experimental drug targets for treatment of lung cancer., Conclusion: Our findings firstly suggest that treatment regimens based on comprehensive genetic assessment of newly diagnosed LABM patients should target both the PT and secondary BMs, including rogue clones with potential to form new BMs. Second, the additional information gained should allow clinicians to design and implement more personalized treatment regimens and potentially improve outcomes for LABM patients.

A Gram-negative, psychrophilic bacterium, designated strain GS1 T , was isolated from a forest soil sample collected from the West Peak of Mt. Yushan, Yushan National Park, Taiwan. Cells grown in broth cultures were mostly non-motile and non-flagellated, whereas motile cells with monotrichous, subpolar flagella were also observed. The novel strain grew over a temperature range of 4-25 °C with optimum growth at 10-15 °C. It grew aerobically and was not capable of anaerobic growth by fermentation of D-glucose or other carbohydrates. Ubiquinone 8 was the predominant isoprenoid quinone. The major polar lipids comprised phosphatidylethanolamine, diphosphatidylglycerol and dimethylaminoethanol. Cellular fatty acids were dominated by C 16:1 ω7c (35.2%), C 16:0 (19.5%), C 18:1 ω7c (18.8%) and C 17:0 ω7c cyclo (15.5%). The DNA G + C content was 49.2 mol% evaluated according to the genomic sequencing data. Strain GS1 T shared more than 96.5% 16S rRNA gene sequence similarities with type strains of four Collimonas species (97.2-97.5%), three Glaciimonas species (97.3% for each of the three) and Oxalicibacterium solurbis (96.5%). Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain GS1 T formed a stable genus-level clade with type strains of species in the genus Glaciimonas in the family Oxalobacteraceae and GS1 T was an outgroup with respect to these Glaciimonas species. Characteristically, strain GS1 T could be easily distinguished from the recognised Glaciimonas species by exhibition of swimming motility with monotrichous, subpolar flagellum in some of the cells, ability to grow in NaCl at 2% but not at 3% and the distinguishable fatty acid profiles. On the basis of the polyphasic taxonomic data from this study, strain GS1 T is considered to represent a novel species of the genus Glaciimonas, for which the name Glaciimonas soli sp. nov. is proposed. The type strain is GS1 T (= JCM 33275 T  = BCRC 81091 T ).

Multipotent human mesenchymal stem cells (MSCs) harbor clinically relevant immunomodulation, and HLA-G, a non-classical MHC class I molecule with highly restricted tissue expression, is one important molecule involved in these processes. Understanding of the natural regulatory mechanisms involved in expression of this elusive molecule has been difficult, with near exclusive reliance on cancer cell lines. We therefore studied the transcriptional control of HLA-G in primary isolated human bone marrow- (BM), human embryonic stem cell-derived (hE-), as well as placenta-derived MSCs (P-MSCs), and found that all 3 types of MSCs express 3 of the 7 HLA-G isoforms at the gene level; however, fibroblasts did not express HLA-G. Protein validation using BM- and P-MSCs demonstrated expression of 2 isoforms including a larger HLA-G-like protein. Interferon-γ (IFN-γ) stimulation upregulated both gene and protein expression in MSCs but not the constitutively expressing JEG-3 cell line. Most interestingly in human MSCs and placental tissue, hypomethylation of CpG islands not only occurs on the HLA-G proximal promoter but also on the gene body as well, a pattern not seen in either of the 2 commonly used choriocarcinoma cell lines which may contribute to the unique HLA-G expression patterns and IFN-γ-responsiveness in MSCs. Our study implicates the importance of using normal cells and tissues for physiologic understanding of tissue-specific transcriptional regulation, and highlight the utility of human MSCs in unraveling the transcriptional regulation of HLA-G for better therapeutic application.

Exosomes are increasingly recognized as vehicles of intercellular communication. However, the role of exosome in maintaining cellular homeostasis under stress conditions remained unclear. Here we show that Rab27a expression was upregulated exclusively in tubular epithelial cells (TECs) during proteinuria nephropathy established by adriamycin (ADR) injection and 5/6 nephrectomy as well as in chronic kidney disease patients, leading to the increased secretion of exosomes carrying albumin. The active exosome production promoted tubule injury and inflammation in neighboring and the producing cells. Interferon regulatory factor 1 (IRF-1) was found as the transcription factor contributed to the upregulation of Rab27a. Albumin could be detected in exosome fraction and co-localized with exosome marker CD63 indicating the secretion of albumin into extracellular space by exosomes. Interestingly, inhibition of exosome release accelerated albumin degradation which reversed tubule injury with albumin overload, while lysosome suppression augmented exosome secretion and tubule inflammation. Our findings revealed that IRF-1/Rab27a mediated exosome secretion constituted a coordinated approach to lysosome degradation for albumin handling, which lead to the augment of albumin toxicity as a maladaptive response to maintain cell homeostasis. The findings may suggest a novel therapeutic strategy for proteinuric kidney disease by targeting exosome secretion.

Background: Host-associated microbial communities play an important role in the fitness of insect hosts. However, the factors shaping microbial communities in wild populations, including genetic background, ecological factors, and interactions among microbial species, remain largely unknown., Results: Here, we surveyed microbial communities of the small brown planthopper (SBPH, Laodelphax striatellus) across 17 geographical populations in China and Japan by using 16S rRNA amplicon sequencing. Using structural equation models (SEM) and Mantel analyses, we show that variation in microbial community structure is likely associated with longitude, annual mean precipitation (Bio12), and mitochondrial DNA variation. However, a Wolbachia infection, which is spreading to northern populations of SBPH, seems to have a relatively greater role than abiotic factors in shaping microbial community structure, leading to sharp decreases in bacterial taxon diversity and abundance in host-associated microbial communities. Comparative RNA-Seq analyses between Wolbachia-infected and -uninfected strains indicate that the Wolbachia do not seem to alter the immune reaction of SBPH, although Wolbachia affected expression of metabolism genes., Conclusion: Together, our results identify potential factors and interactions among different microbial species in the microbial communities of SBPH, which can have effects on insect physiology, ecology, and evolution. Video Abstract.

Background: This study aims to analyze the effect of the body mass index (BMI) on E 2 , P and LH values in females who received intrauterine insemination (IUI) treatment on human chorionic gonadotropin (HCG) day., Methods: A total of 2319 cycles of IUI-assisted pregnancy treatment were selected in our hospital. Based on the BMI, female infertility patients are divided into three groups: normal weight group, overweight and obese group., Results: For patients with natural cycles and ≤ 35 years old, there were 440, 178 and 197 cases in the three groups, respectively. For patients with natural cycles and > 35 years old, there were 90, 83 and 81 cycles in the three groups, respectively. For patients with induced ovulation cycle and ≤ 35 years old, there were 425, 203 and 516 cases in the three groups, respectively. For patients with induced ovulation cycle and > 35 years old, there were 26, 26 and 54 cases in the three groups, respectively., Conclusion: When a patient is ≤35 years old, the BMI affects the E 2 , LH and P values on the day of artificial insemination. However, the BMI is negatively correlated with E 2 , LH and P in IUI on HCG day. After controlling for age and assisted pregnancy, the correlation analysis revealed that the BMI is negatively correlated with hormone E 2 and LH. The higher the BMI was, the lower the levels of hormones E 2 , LH and P became. However, in the present study, the BMI did not significantly improve the clinical pregnancy rate of patients who received IUI.

Four Gram-stain-positive strains, R7 T , R11, R19 T and R27, were isolated from suan-tsai, a traditional fermented mustard green product of Taiwan. Cells were rod-shaped, non-motile, non-haemolytic, asporogenous, facultatively anaerobic, heterofermentative, and did not exhibit catalase and oxidase activities. Comparative analyses of 16S rRNA, pheS and rpoA gene sequences demonstrated that these novel strains were members of the genus Lactobacillus . 16S rRNA and the concatenated pheS and rpoA gene sequence similarities between strains R7 T and R11, and strains R19 T and R27 were very high (>99.8 % similarity), respectively. On the basis of 16S rRNA gene sequence similarities, the type strains of Lactobacillus paralimentarius (98.5 %), Lactobacillus kimchii (98.5 %), Lactobacillus alimentarius (98.1 %) and Lactobacillus bobalius (98.1 %) were the closest neighbours to strains R7 T and R11, and the type strains of Lactobacillus brevis (98.9 %), Lactobacillus cerevisiae (98.4 %), Lactobacillus hammesii (98.4 %), Lactobacillus koreensis (98.4 %) and Lactobacillus yonginensis (98.0 %) were the closest neighbours to strains R19 T and R27, respectively. The average nucleotide identity values of R7 T and R19 T with the closely related type strains were 78.9-80.1% and 75.7-80.5 %, respectively. The digital DNA-DNA hybridization values were 22.8-23.6% and 21.0-23.1 %, respectively. Phenotypic and genotypic test results demonstrated that these strains represent two novel species of the genus Lactobacillus , for which the name Lactobacillus suantsaicola sp. nov. (R7 T =BCRC 81127 T =NBRC 113530 T ) and Lactobacillus suantsaiihabitans sp. nov. (R19 T =BCRC 81129 T =NBRC 113532 T ) are proposed.

Enteroviruses, which may cause neurological complications, have become a public health threat worldwide in recent years. Interactions between cellular proteins and enteroviral proteins could interfere with cellular biological processes to facilitate viral replication in infected cells. Enteroviral RNA-dependent RNA polymerase (RdRP), known as 3D protein, mainly functions as a replicase for viral RNA synthesis in infected cells. However, the 3D protein encoded by enterovirus A71 (EV-A71) could also interact with several cellular proteins to regulate cellular events and responses during infection. To globally investigate the functions of the EV-A71 3D protein in regulating biological processes in host cells, we performed immunoprecipitation coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify host proteins that may associate with the 3D protein. We found that the 3D protein interacts with factors involved in translation-related biological processes, including ribosomal proteins. In addition, polysome profiling analysis showed that the 3D protein cosediments with small and large subunits of ribosomes. We further discovered that the EV-A71 3D protein could enhance EV-A71 internal ribosome entry site (IRES)-dependent translation as well as cap-dependent translation. Collectively, this research demonstrated that the RNA polymerase encoded by EV-A71 could join a functional ribosomal complex and positively regulate viral and host translation.

Food fermentation can improve food nutritional value and sensory performance, it is considered as an ecofriendly bioprocessing technology. In this work, a fermented natto chestnut food was firstly developed and its active ingredients and functional properties were systematically studied. Through systematic experimental screening, including a single factor experiment and Box-Behnken design, the fermentation parameters of chestnut were optimized and selected. Under the optimal fermentation conditions, fermentation time 56 h, temperature 38 ℃ and 5% inoculum concentration, the fibrinolytic activity of the natto-chestnut reached 6479 IU/g. Meanwhile, higher antioxidant activity of the natto-chestnut was obtained due to the increased contents of total phenolic, total flavonoid and VC. In addition, α-glucosidase inhibition activity was also improved in the natto-chestnut. These results indicated that fermented chestnut could be a new dietary supplement with higher quality and better activities for people's health., Competing Interests: Declaration of Competing Interest The authors declared that there is no conflict of interest., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Taxanes are natural anticancer constituents, and the sample preparation from matrix normally depends on organochlorine solvents. In this study, green and natural menthol-based aqueous deep eutectic solvent was synthesized and used for sample preparation for taxanes. Five key parameters were optimized and the optimal preparation conditions were as follows: menthol/1-propanol ratio 1:1 (mol/mol), solid-liquid ratio 1:30 g/mL, extraction time 30 min, ultrasonic power 250 W, and water content 80%. Under the above conditions, the total extraction efficiency of seven main taxanes was 1.25- to 1.44-fold to the conventional methods. In addition, a high-performance liquid chromatography method with C 18 column was established for quantitation of seven main taxanes in <25 min, which had excellent linearity (R 2  > 0.9986), precision (relative standard deviation < 3.00%), repeatability (relative standard deviation < 3.69%), and recovery (90.26-109.00%). This method performed the extraction, and enrichment processes simultaneously, and it had advantages such as high extraction efficiency, simple operation, low cost, and eco-friendliness. This work indicated that the natural menthol-based deep eutectic solvent aqueous could be an excellent alternative to the sample preparation from Taxus or other plants., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Epithelial cell polarity defects support cancer progression. It is thus crucial to decipher the functional interactions within the polarity protein network. Here we show that Drosophila Girdin and its human ortholog (GIRDIN) sustain the function of crucial lateral polarity proteins by inhibiting the apical kinase aPKC. Loss of GIRDIN expression is also associated with overgrowth of disorganized cell cysts. Moreover, we observed cell dissemination from GIRDIN knockdown cysts and tumorspheres, thereby showing that GIRDIN supports the cohesion of multicellular epithelial structures. Consistent with these observations, alteration of GIRDIN expression is associated with poor overall survival in subtypes of breast and lung cancers. Overall, we discovered a core mechanism contributing to epithelial cell polarization from flies to humans. Our data also indicate that GIRDIN has the potential to impair the progression of epithelial cancers by preserving cell polarity and restricting cell dissemination., Competing Interests: The authors have declared that no competing interests exist.

Neochlorogenic acid (nCGA) is a phenolic compound isolated from mulberry leaf ( Morus alba L. ), which possesses multiple pharmacological activities containing antioxidant and anti-inflammatory effects. However, the role of nCGA in the treatment of acute pneumonia and the underlying molecular mechanism are still unclear. Hence, the aim of study is to investigate the anti-inflammatory properties of nCGA on LPS-stimulated inflammation in A549 cells. In the present study, results reported that nCGA without cytotoxicity significantly reduced the production of TNF-α, IL-6, and NO, and further suppressed the proteins of iNOS, COX2, TNF-α, IL-6 expression. Furthermore, nCGA also inhibited NF-κB activation and blocked MAPKs signaling pathway phosphorylation. In addition, we found nCGA significantly increased the expression of HO-1 via activating the AMPK/Nrf2 signaling pathway to attenuate the inflammatory response, whereas this protective effect of nCGA was reversed by pre-treatment with compound C (C.C, an AMPK inhibitor). Therefore, all these results indicated that nCGA might act as a natural anti-inflammatory agent for the treatment of acute pneumonia.

A Gram-stain-positive strain, 8 H-2 T , was isolated from faeces of Reeves' muntjac ( Muntiacus reevesi ) barking deer in Taiwan. Cells of the strain were short rod-shaped, non-motile, non-haemolytic, asporogenous, facultatively anaerobic, heterofermentative and did not exhibit catalase and oxidase activities. Comparative analyses of 16S rRNA, pheS and dnaA gene sequences demonstrated that the novel strain was a member of the genus Weissella . On the basis of 16S rRNA gene sequence similarities, the type strains of Weissella oryzae (99.2 %), Weissella confusa (97.8 %), Weissella cibaria (97.6 %) and Weissella soli (97.3 %) were the closest neighbours to strain 8 H-2 T . The concatenated housekeeping gene sequence ( pheS and dnaA ) similarities of 8 H-2 T to closely related type strains were 72.5-84.9 %, respectively. The genomic DNA G+C content was 40.5 mol%. The average nucleotide identity and digital DNA-DNA hybridization values with these type strains were 70.2-75.4% and 25.1-30.1 %, respectively. Phenotypic and genotypic test results demonstrated that strain 8 H-2 T represents a novel species belonging to the genus Weissella , for which the name Weissella muntiaci sp. nov. is proposed. The type strain is 8 H-2 T (=BCRC 81133 T =NBRC 113537 T ).

A novel lactic acid bacterium, strain MB7 T , was isolated from lychee in Taiwan. MB7 T is Gram-staining-positive, catalase-negative, non-motile, non-haemolytic, facultatively anaerobic, coccoid-shaped, heterofermentative and mainly produces d-lactic acid from glucose. Comparative analysis of 16S rRNA, pheS and rpoA gene sequences has demonstrated that the novel strain represented a member of the genus Leuconostoc . 16S rRNA gene sequencing results indicated that MB7 T had the same sequence similarity of 99.25 % to four type strains of members of the genus Leuconostoc : Leuconostoc mesenteroides subsp. dextranicum DSM 20484 T , Leuconostoc mesenteroides subsp. jonggajibkimchii DRC 1506 T , Leuconostoc mesenteroides subsp. mesenteroides ATCC 8293 T and Leuconostoc suionicum DSM 20241 T . Additionally, high 16S rRNA sequence similarities were also observed with Leuconostoc mesenteroides subsp. cremoris ATCC 19254 T (99.12 %) and Leuconostoc pseudomesenteroides NRIC 1777 T (98.69 %). When comparing the genomes of these type strains, the average nucleotide identity values and digital DNA-DNA hybridization values of MB7 T with these type strains were 76.57-80.53 and 22.0-22.6 %, respectively. MB7 T also showed different phenotypic characteristics to other most closely related species of the genus Leuconostoc , such as carbohydrate metabolizing ability, halotolerance and growth at various pHs. On the basis of phenotypic and genotypic properties, strain MB7 T represents a novel species belonging to the genus Leuconostoc , for which the name Leuconostoc litchii sp. nov. is proposed. The type strain is MB7 T (=BCRC 81077 T =NBRC 113542 T ).

A Gram-stain-positive, coccus- or oval-shaped, non-motile, haemolytic, asporogenous, catalase- and oxidase-negative, and facultatively anaerobic strain, 2B-2 T , was isolated from a brewer's grain used to make silage in Taiwan. Comparative analyses of 16S rRNA, hsp60 and pheS gene sequences demonstrated that strain 2B-2 T was a member of the genus Vagococcus . On the basis of 16S rRNA gene sequence similarity, the type strains of Vagococcus teuberi (98.4 % similarity), Vagococcus carniphilus (98.4 %), Vagococcus martis (98.2 %), Vagococcus penaei (98.2 %) and Vagococcus fluvialis (98.0 %) were the closest neighbours to this novel strain. The similarity levels of concatenated housekeeping gene sequences ( hsp60 and pheS ) between strain 2B-2 T and these closely related species ranged from 84.5 to 88.0 %. The average nucleotide identity and in silico DNA-DNA hybridization values between strain 2B-2 T and its closest relatives were lower than 72.9 and 21.6 %, respectively. The DNA G+C content was 34.7 mol%. Phenotypic and genotypic features demonstrated that strain 2B-2 T represents a novel species of the genus Vagococcus , for which the name Vagococcus silagei sp. nov. is proposed. The type strain is 2B-2 T (=BCRC 81132 T =NBRC 113536 T ).

Molybdenum disulfide (MoS 2 ) is a promising nanomaterial which has been extensively investigated in photo-/electro-catalysis, sensors, and batteries due to its excellent physical/chemical properties. In this manuscript, MoS 2 hierarchical nanotubes with hollow nanostructure are successfully synthesized via a facile hydrothermal method. SEM indicates that such MoS 2 nanotubes have perfect uniformity while TEM demonstrates the hollow structure. Specifically, the ratio of MoS 2 to the randomly produced polysulfide in the synthesized MoS 2 nanotubes is 4.29 which confirms that the synthesized MoS 2 nanotubes have quite high quality. Compared with the previous studies, our MoS 2 nanotubes show superior rate capability and cyclability (127 mAh g -1 at 200 mA g -1 after 100 cycles) in the potassium ion battery., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Recently, the discovery and development of lead-free perovskite quantum dots (QDs) that are eco-friendly and stable has become an active research area in low-cost lighting and display fields. However, the low photoluminescence quantum yield (PLQY) caused by the residual surface states of such QDs severely hinders their practical applications and commercialization. In this work, a strategy of employing water-induced nanocomposites was proposed to improve the PLQY of cesium bismuth halide (Cs 3 Bi 2 X 9 ) QDs, and a substantial enhancement by ∼130% (from 20.2% to 46.4%) was achieved by an optimized water treatment of Cs 3 Bi 2 Br 9 QDs. A detailed analysis indicated that Cs 3 Bi 2 Br 9 /BiOBr nanocomposites, in which the Cs 3 Bi 2 Br 9 QD core was encapsulated into a BiOBr matrix, can effectively suppress the surface defects of QDs, resulting in a longer PL lifetime and a larger exciton binding energy compared with the pristine sample. Finally, the Cs 3 Bi 2 Br 9 /BiOBr nanocomposites were used as the color-converting phosphors for down-conversion white light-emitting devices, which show a good operation stability in ambient air, significantly better than the reference device constructed with conventional lead-halide perovskites. We believe that the method used here provides an effective strategy to improve the fluorescence efficiency of lead-free perovskite QDs, which will create opportunities for their applications in lighting and displays.

Epigenetic regulation is important for cancer progression; however, the underlying mechanisms, particularly those involving protein acetylation, remain to be fully understood. Here, we show that p300/CBP-associated factor (PCAF)-dependent acetylation of the transcription factor intestine-specific homeobox (ISX) regulates epithelial-mesenchymal transition (EMT) and promotes cancer metastasis. Mechanistically, PCAF acetylation of ISX at lysine 69 promotes the interaction with acetylated bromodomain-containing protein 4 (BRD4) at lysine 332 in tumor cells, and the translocation of the resulting complex into the nucleus. There, it binds to promoters of EMT genes, where acetylation of histone 3 at lysines 9, 14, and 18 initiates chromatin remodeling and subsequent transcriptional activation. Ectopic ISX expression enhances EMT marker expression, including TWIST1, Snail1, and VEGF, induces cancer metastasis, but suppresses E-cadherin expression. In lung cancer, ectopic expression of PCAF-ISX-BRD4 axis components correlates with clinical metastatic features and poor prognosis. These results suggest that the PCAF-ISX-BRD4 axis mediates EMT signaling and regulates tumor initiation and metastasis., (© 2020 The Authors. Published under the terms of the CC BY 4.0 license.)

Antibiotics ingested in the human gut may create selective pressure to change the composition of the gut microbiota, which could adversely effect the immune system of the host. However, the occurrence and distribution of antibiotics in the human gut remains unclear. A total population of 180 individuals, across three Chinses regions with different economic development levels, including children, adults, and elders, were sampled in 2017. A total of 19 representative antibiotics, including both clinical and veterinary antibiotics, were investigated in human faeces. While clinical use and prescriptions were the main exposure pathways for children, environmental media were the exposure pathway to adults. In addition, significant differences (P < 0.05) in antibiotic residues in human faeces were observed amongst various economic development levels, where human faeces from underdeveloped areas were mostly associated with higher levels of antibiotics. This study first to investigate the occurrence and distribution of typical antibiotics in the faeces of a Chinese population and thereby provide a reference for the intensive study of the effects and mechanisms of antibiotics on human gut microbiota., (Copyright © 2019. Published by Elsevier B.V.)

Objective: To investigate the risk factors for cow's milk protein allergy (CMPA) among infants through a multicenter clinical study., Methods: A total of 1 829 infants, aged 1-12 months, who attended the outpatient service of the pediatric department in six hospitals in Shenzhen, China from June 2016 to May 2017 were enrolled as subjects. A questionnaire survey was performed to screen out suspected cases of CMPA. Food avoidance and oral food challenge tests were used to make a confirmed diagnosis of CMPA CMPA. A multivariate logistic regression analysis was used to investigate the risk factors for CMPA., Results: Among the 1 829 infants, 82 (4.48%) were diagnosed with CMPA. The multivariate logistic regression analysis showed that maternal food allergy (OR=4.91, 95%CI: 2.24-10.76, P<0.05), antibiotic exposure during pregnancy (OR=3.18, 95%CI: 1.32-7.65, P<0.05), and the introduction of complementary food at an age of <4 months (OR=3.55, 95%CI: 1.52-8.27, P<0.05) were risk factors for CMPA, while exclusive breastfeeding (OR=0.21, 95%CI: 0.08-0.58, P<0.05) and the introduction of complementary food at an age of >6 months (OR=0.38, 95%CI: 0.17-0.86, P<0.05) were protective factors., Conclusions: The introduction of complementary food at an age of <4 months, maternal food allergy, and antibiotic exposure during pregnancy are risk factors for CMPA in infants.

Purpose: No study has investigated the precise perioperative dynamic changes in circulating tumor DNA (ctDNA) in any patients with early-stage cancer. This study (DYNAMIC) investigated perioperative dynamic changes in ctDNA and determined the appropriate detection time of ctDNA-based surveillance for surgical patients with lung cancer. Experimental Design: Consecutive patients who underwent curative-intent lung resections were enrolled prospectively (NCT02965391). Plasma samples were obtained at multiple prespecified time points including before surgery (time A), during surgery after tumor resection (time B-time D), and after surgery (time P1-time P3). Next-generation sequencing-based detection platform was performed to calculate the plasma mutation allele frequency. The primary endpoint was ctDNA half-life after radical tumor resection., Results: Thirty-six patients showed detectable mutations in time A. The plasma ctDNA concentration showed a rapid decreasing trend after radical tumor resection, with the average mutant allele fraction at times A, B, C, and D being 2.72%, 2.11%, 1.14%, and 0.17%, respectively. The median ctDNA half-life was 35.0 minutes. Patients with minimal residual disease (MRD) detection had a significant slower ctDNA half-life than those with negative MRD (103.2 minutes vs. 29.7 minutes, P = 0.001). The recurrence-free survival of patients with detectable and undetectable ctDNA concentrations at time P1 was 528 days and 543 days, respectively ( P = 0.657), whereas at time P2 was 278 days and 637 days, respectively ( P = 0.002)., Conclusions: ctDNA decays rapidly after radical tumor resection. The ctDNA detection on the third day after R0 resection can be used as the baseline value for postoperative lung cancer surveillance., (©2019 American Association for Cancer Research.)

Two isolates of heterotrophic, facultatively anaerobic, marine bacteria, designated DM1 and DM2 T , were recovered from a lagoon sediment sample of Dongsha Island, Taiwan. Cells were Gram-reaction-negative rods. Nearly all of the cells were non-motile and non-flagellated during the late exponential to early stationary phase of growth, while a few of the cells exhibited motility with monotrichous flagellation. The two isolates required NaCl for growth and grew optimally at about 30 °C, 2-3 % NaCl and pH 7-8. They grew aerobically and could achieve anaerobic growth by fermenting d-glucose or other carbohydrates with production of acids and the gases, including CO 2 and H 2 . Ubiquinone Q-8 was the only respiratory quinone. Cellular fatty acids were predominated by C 16 : 0 , C 18 : 1 ω7 c and C 16 : 1 ω7 c . The major polar lipid was phosphatidylethanolamine. Strains DM1 and DM2 T had DNA G+C contents of 52.0 and 51.8 mol%, respectively, as determined by HPLC analysis. Phylogenetic analyses based on 16S rRNA gene sequences clearly indicated that the two isolates formed a distinct genus-level lineage in the family Aeromonadaceae of the class Gammaproteobacteria and was an outgroup with respect to a stable supragenic clade comprising species of the genera Oceanimonas , Oceanisphaera and Zobellella . The phylogenetic data and those from chemotaxonomic, physiological and morphological characterizations support the establishment of a novel species and genus inside the family Aeromonadaceae , for which the name Dongshaea marina gen. nov., sp. nov. is proposed. The type strain is DM2 T (=BCRC 81069 T =JCM 32096 T ).

Natural deep eutectic solvents (NADES) have been growing interest as an alternative to the traditional organic solvents. They not only have the merit of high efficiency but also have the possibility to readily applicable to pharmaceutical and food applications. In the present study, NADES with high-speed homogenization and cavitation-burst extraction (HSH-CBE) was performed on fresh mulberry for anthocyanins extraction. The extraction conditions were statistically investigated by Plackett-Burman design (PBD) and Box-Behnken design (BBD). The optimal conditions were obtained as follows: chloride-citric acid-glucose formed a NADES with the mole ratio of 1:1:1, 30% water content, liquid-solid ratio 22 mL/g, homogenization time 60 s, homogenization speed 12,000 rpm, extraction time 30 min, negative pressure -0.08 MPa and extraction two times. The total maximum extraction of anthocyanins reached 6.05 mg/g fresh weight, which was 1.24 folds to those by the traditional organic solvents extraction. Moreover, NADES exhibited higher stability of anthocyanins extraction than traditional organic solvents, which was benefit for the analysis and preservation of anthocyanins. Consequently, this result revealed that the developed method could be taken as a sustainable, green and effective approach for anthocyanins extraction., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Aryl hydrocarbon receptor (AhR), a cellular chemical sensor, controls cellular homeostasis, and sphingosine-1-phosphate (S1P), a bioactive intermediate of sphingolipid metabolism, is believed to have a role in immunity and inflammation, but their potential crosstalk is currently unknown. We aimed to determine whether there is a functional linkage between AhR signaling and sphingolipid metabolism. We showed that AhR ligands, including an environmental polycyclic aromatic hydrocarbon (PAH), induced S1P generation, and inhibited S1P lyase (S1PL) activity in resting cells, antigen/IgE-activated mast cells, and mouse lungs exposed to the AhR ligand alone or in combination with antigen challenge. The reduction of S1PL activity was due to AhR-mediated oxidation of S1PL at residue 317, which was reversible by the addition of an antioxidant or in cells with knockdown of the ORMDL3 gene encoding an ER transmembrane protein, whereas C317A S1PL mutant-transfected cells were resistant to the AhR-mediated effect. Furthermore, analysis of AhR ligand-treated cells showed a time-dependent increase of the ORMDL3-S1PL complex, which was confirmed by FRET analysis. This change increased the S1P levels, which in turn, induced mast cell degranulation via S1PR2 signaling. In addition, elevated levels of plasma S1P were found in children with asthma compared to non-asthmatic subjects. These results suggest a new regulatory pathway whereby the AhR-ligand axis induces ORMDL3-dependent S1P generation by inhibiting S1PL, which may contribute to the expression of allergic diseases.

Juglone (JG) exhibits a broad-spectrum of cytotoxicity against some cancer cells. However, its molecular mechanisms have not been investigated well. Here, the present results showed that JG significantly inhibited tumor growth in vivo. CCK-8 assays, flow cytometric analysis, western blotting and immunohistochemistry revealed that JG effectively inhibited cell proliferation and induced apoptosis through extrinsic pathways. We also observed that JG treatment induced autophagy flux via activiting the AMPK-mTOR signaling pathway. In addition, we found that JG enhanced p53 activation by increasing down-regulation of ubiquitin-mediated degradation. Inhibition of p53 by siRNA attenuated JG-induced cell death and autophagy. Moreover, JG enhanced the generation of hydrogen peroxide (H 2 O 2 ) and superoxide anion radical (O 2 • - ). Further experiments proved that H 2 O 2 was a major factor since the H 2 O 2 scavenger catalase (CAT) reduced both autophagy and cell death to a greater extent than the O 2 • - scavenger SOD. Overall, our results illustrated that JG caused apoptosis and autophagy via activating the ROS-mediated p53 pathway in human liver cancer cells in vitro and in vivo, which provided basic scientific evidence that JG serves as a potential anti-cancer agent., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Morus alba L. is a medicinal plant that contains a high amount of caffeoylquinic acids such as 3-caffeoylquinic acid (3-CQA), 5-caffeoylquinic acid (5-CQA) and 4-caffeoylquinic acid (4-CQA). This study aimed to establish a fast and efficient method for separating caffeoylquinic acids from mulberry leaves by using high-speed countercurrent chromatography coupled with macroporous resin. D101 resin showed better adsorption and desorption capacity for three caffeoylquinic acids among six macroporous resin adsorbents. The contents of 3-CQA, 5-CQA and 4-CQA reached for 4.77%, 18.95% and 9.84% through one cycle of D101 resin, which were 3.13-fold, 4.57-fold and 4.78-fold more than those in crude extracts, respectively. With a two-phase solvent system of ethyl acetate-water (1:1, V/V), >93% purity of target compounds were obtained in one cycle during 150 min with the recovery yields of 80.59%, 99.56% and 94.21% for 3-CQA, 5-CQA and 4-CQA, respectively. The structural identification of target compounds was carried out by ESI-MS, 1H NMR and 13C NMR spectra. The present result represented an easy and efficient separation strategy for the utilization of mulberry resource., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Male late-onset hypogonadism (LOH) is reported as one of the most common age-related diseases occurred in middle-aging men. Testosterone replacement therapy (TRT) is currently the main clinical treatment for LOH, however it has obvious side effects. A 2-methylpyrimidine-fused tricyclic diterpene analog 7 was afforded as anti-LOH hit, which was screened out from our small synthetic library. Then a series of derivates were designed and synthesized based on the hit and their effects in promoting testosterone production and cytotoxicities were evaluated in mouse TM3 Leydig cells. The most potent and safe compound 29 (SH379) was obtained, which significantly promoted the expression of the key testosterone synthesis-related enzymes StAR and 3β-HSD. Further studies discovered that 29 could stimulate autophagy through regulating AMPK/mTOR signaling pathway. More importantly, 29 increased the testosterone levels and the sperm viability and motility in PADAM (partial androgen deficiency in aging males) rats obviously and displayed almost no side effects. Furthermore, Preliminary pharmacokinetics evaluation also indicated an excellent oral bioavailability of 29. Therefore, these methylpyrimidine-fused tricyclic diterpene analogs could be used as leads for the development of a new type of potential anti-LOH agent., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: The morbidity of knee arthritis is increasing among aged people and total knee arthroplasty has been its mainstream treatment to date. Postoperative rehabilitation is an important part of the procedure. However, the intense pain during the functional exercise involved has always been a challenge for both patients and health care professionals. The aim of this study is to test the analgesic effect of a mixture of nitrous oxide/oxygeb (1:1) inhalation for patients who are doing functional exercise 1 month after total knee arthroplasty., Methods/design: This double-blind, randomized, placebo-controlled study will be implemented in the Rehabilitation Department in the General Hospital of Ningxia Medical University. Patients aged between 50 and 75 years who underwent a primary unilateral total knee arthroplasty are eligible for inclusion. The key exclusion criteria include: epilepsy, pulmonary embolism, intestinal obstruction, aerothorax. The treatment group (A) will receive a pre-prepared nitrous oxide/oxygen mixture plus conventional treatment (no analgesics), and the control group (B) will receive oxygen plus conventional treatment (no analgesics). Patients, physicians, therapists, and data collectors are all blind to the experiment. Assessments will be taken immediately after functional exercise begins (T0), 5 min (T1) after functional exercise begins, and 5 min after functional exercise has finished (T2). Patients will be randomly allocated between a treatment group (A) and a control group (B) in a ratio of 1:1. Primary outcome, including pain severity in the procedure, will be taken for each group. Secondary outcomes include blood pressure, heart rate, oxygen saturation, side effects, knee joint range of motion, Knee Society Score (KSS), rescue analgesia need, and satisfaction from both therapists and patients., Discussion: This study will focus on exploring a fast and efficient analgesic for patients who are doing functional exercise after total knee arthroplasty. Our previous studies suggested that the prefixed nitrous oxide/oxygen mixture was an efficacious analgesic for the management of burn-dressing pain and breakthrough cancer pain. The results of this study should provide a more in-depth insight into the effects of this analgesic method. If this treatment proves successful, it could be implemented widely for patients doing functional exercise in the rehabilitation department., Trial Registration: ChiCTR-INR-17012891 . Registered on 6 October 2017.

Background: Recently, cinacalcet (CINA) has been shown to be effective for attenuating bone loss in the treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD), which might be associated with the reduction in serum parathyroid hormone (PTH) levels. However, the exact mechanism is largely unclear. Emerging studies have revealed that an increased number of bone marrow adipocytes (BMAs) are involved in bone loss and the endothelial-to-adipocyte transition via the endothelial-to-mesenchymal transition (EndMT) might play a key role in this pathological process. Here, we assessed whether CINA could attenuate bone loss via inhibiting endothelial-to-adipocyte transition in CKD rats., Methods: A rat model of CKD was induced by adenine and a high phosphorus diet. CINA was orally administrated to CKD animals (10 mg/kg once a day). Dual energy X-ray absorptiometry, micro-computed tomography, bone histomorphometry, and bone mechanical tests were used to determine the skeletal changes. The bone marrow expression of EndMT markers was also examined. The effect of elevated PTH levels on the endothelial-to-adipocyte transition was studied in endothelial cells (ECs)., Results: Elevation of serum PTH levels, remarkable bone loss and increased numbers of BMAs were observed in rats with CKD compared with the controls, and these changes were attenuated after treatment with CINA. Furthermore, the CINA treatment abolished the upregulation of mesenchymal markers (FSP1 and α-SMA) and the downregulation of an endothelial marker (CD31) in bone tissues from rats with CKD. The serum PTH concentrations were correlated with the bone marrow protein levels of these EndMT-related proteins. An in vitro treatment in ECs demonstrated that PTH induced the EndMT in a concentration- and time-dependent manner. Accordingly, ECs treated with PTH exhibited adipogenic potential following growth in adipogenic culture medium., Conclusions: Our study indicated CINA treatment attenuated bone loss in CKD rats, which might be associated with inhibiting PTH-induced endothelial-to-adipocyte transition in CKD rats., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: We conducted a network meta-analysis (NMA) to evaluate the efficacy and safety of cinacalcet, active vitamin D and cinacalcet plus active vitamin D in the treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD)., Methods: A systematic literature search was performed using the Cochrane Library, PubMed, EMBASE, Web of Science, Google Scholar, China National Knowledge Internet (CNKI) and Wanfang databases. In total, eight randomized controlled trials (RCTs) with 1,443 patients were eligible for this meta-analysis. Pairwise meta-analysis was performed to evaluate the compliance of intact parathyroid hormone (iPTH), Ca, P, etc., and the mortality and safety of cinacalcet plus active vitamin D and active vitamin D alone. Then, NMA was used to estimate the safety and efficacy of the administration of active vitamin D and different drugs in the control group., Results: The results of the pairwise meta-analysis revealed that compared with active vitamin D monotherapy, cinacalcet plus active vitamin D did not improve the survival of patients but significantly improved the blood calcium compliance rate [relative risk (RR) =1.82, 95% confidence interval (CI): 1.51-2.21, P<0.00001]. Furthermore, it is worth noting that compared with the corresponding incidence with other treatments, the incidence of vomiting was significantly increased with cinacalcet plus active vitamin D treatment (RR =2.07, 95% CI: 1.18-3.65, P=0.01). Through direct and indirect comparisons, the NMA revealed the following results: (I) compared with oral or intravenous (IV) administration of vitamin D, the solely oral administration of active vitamin D increased mortality, and (II) cinacalcet monotherapy increased the risk of hypocalcemia, and that risk was even higher for cinacalcet plus active vitamin D. However, the results should be treated with caution because the prediction interval (PrI) crossed the invalid line., Conclusions: This pairwise meta-analysis and NMA provided a comprehensive analysis of the currently utilized CKD-SHPT treatment interventions. This network identified some highly ranked interventions through analyses that were included in a small number of trials; these interventions merit further examination on a larger scale in the context of well-designed RCTs., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: Inonotus obliquus, namely as Chaga mushroom, is a medicinal and edible fungus, which is widely used in food and medical fields. Inotodiol, a natural lanostane-type triterpenoid with remarkable pharmacological activities, was isolated from Inonotus obliquus, which its potential anti-tumor molecular mechanism was elaborated poorly., Purpose: The aim of the present study was to investigate the effect of Inotodiol on HeLa cell migration, invasion and apoptosis through p53-dependent pathway., Study Design and Methods: The potential mechanisms of Inotodiol on HeLa cell anti-metastatic and pro-apoptosis via wound healing assay, trans-well invasion assay, flow cytometry, caspase-3 activity assay and western blot analysis were studied, as well as the involvement of p53 signaling pathway in anti-metastatic and pro-apoptosis of Inotodiol. Besides, the function of tumor suppressor p53 was further verified by small interfering RNA., Results: Firstly, the cell viability assay showed that low-concentration of Inotodiol had no cytotoxicity to HeLa cells and whereas the concentration above 25 μM significantly inhibited HeLa cell growth and even induced apoptosis. This result was further demonstrated by cell proliferation and morphology assay. Secondly, in vitro wound healing and trans-well invasion assays reported that low-concentration treatment of Inotodiol significantly inhibited cells migration and invasion in a dose-dependent manner, the western blot analysis of matrix mettalloprotinase-2 (MMP2) and matrix mettalloprotinase-9 (MMP9) levels were also decreased. Moreover, Inotodiol notably induced tumor cell apoptosis by Annexin-V-FITC apoptosis assay, which is associated with activation pro-apoptotic proteins of PARP, cleaved caspase-3 and Bax expression, inhibition anti-apoptotic protein Bcl-2 expression. Finally, the anti-tumor activity of Inotodiol was attenuated by silencing p53 tumor suppressor, the result revealed that pre-treatment with p53-specific small interfering RNA (si-p53) markedly inhibited Intodiol-indeuced HeLa cell apoptosis and decreased the caspase-3 activity. What is more, the inhibitory effect of Inotodiol on tumor migration and invasion was blocked under p53 knockdown., Conclusion: To sum up, the present study indicated that Inotodiol possessed the potential to prevent malignant tumor migration and invasion, and it might be a natural active compound candidate for clinical treatment of human cervical cancer., (Copyright © 2019. Published by Elsevier GmbH.)