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Malaria, an infectious disease caused by Plasmodium parasites, still accounts for amounts of deaths annually in last decades. Despite the significance of Plasmodium falciparum as a model organism of malaria parasites, our understanding of gene expression of this parasite remains largely elusive since lots of progress on its genome and transcriptome are based on assembly with short sequencing reads. Herein, we report the new version of transcriptome dataset containing all full-length transcripts over the whole asexual blood stages by adopting a full-length sequencing approach with optimized experimental conditions of cDNA library preparation. We have identified a total of 393 alternative splicing (AS) events, 3,623 long non-coding RNAs (lncRNAs), 1,555 alternative polyadenylation (APA) events, 57 transcription factors (TF), 1,721 fusion transcripts in P. falciparum. Furthermore, the shotgun proteome was performed to validate the full-length transcriptome of P. falciparum. More importantly, integration of full-length transcriptomic and proteomic data identified 160 novel small proteins in lncRNA regions. Collectively, this full-length transcriptome dataset with high quality and accuracy and the shotgun proteome analyses shed light on the complex gene expression in malaria parasites and provide a valuable resource for related functional and mechanistic researches on P. falciparum genes.

Tryptophan is an essential amino acid from dietary proteins. It can be metabolized into different metabolites in both the gut microbiota and tissue cells. Tryptophan metabolites such as indole-3-lactate (ILA), indole-3-acrylate (IAC), indole-3-propionate (IPA), indole-3-aldehyde (IAID), indoleacetic acid (IAA), indole-3-acetaldehyde and Kyn can be produced by intestinal microorganisms through direct Trp transformation and also, partly, the kynurenine (Kyn) pathway. These metabolites play a critical role in maintaining the homeostasis of the gut and systematic immunity and also potentially affect the occurrence and development of diseases such as inflammatory bowel diseases, tumors, obesity and metabolic syndrome, diseases in the nervous system, infectious diseases, vascular inflammation and cardiovascular diseases and hepatic fibrosis. They can not only promote the differentiation and function of anti-inflammatory macrophages, Treg cells, CD4+CD8αα+ regulatory cells, IL-10+ and/or IL-35+B regulatory cells but also IL-22-producing innate lymphoid cells 3 (ILC3), which are involved in maintaining the gut mucosal homeostasis. These findings have important consequences in the immunotherapy against tumor and other immune-associated diseases. We will summarize here the recent advances in understanding the generation and regulation of tryptophan metabolites in the gut microbiota, the role of gut microbiota-derived tryptophan metabolites in different immune cells, the occurrence and development of diseases and immunotherapy against immune-associated diseases.

Large-scale floods are one of the major events that impact the national economy and people’s livelihood every year during the flood season. Predicting the factors of flood evolution is a worldwide problem. We use the two-dimensional Saint-Venant equations as an example and for high-performance computing in modelling the flood behavior. Discretization of the two-dimensional Saint-Venant equations with initial and boundary conditions with the finite difference method in the explicit leapfrog scheme is carried out. Afterwards, we employed a large-scale heterogeneous parallel solution on the “SunRising-1” supercomputer system using MPI, OpenMP, Pthread, and OpenCL runtime libraries. On this basis, we applied communication/calculation overlapping and the local memory acceleration to optimize the performance. Finally, various performance tests of the parallel scheme are carried out from different perspectives. We have found this method is efficient and recommend this approach be used in solving systems of partial differential equations similar to the Saint-Venant equations.

The T-spherical fuzzy set (TSFS) is a modification of the fuzzy set (FS), intuitionistic fuzzy set (IFS), Pythagorean fuzzy set (PyFS), q-rung orthopair fuzzy set (q-ROFS), and picture fuzzy set (PFS), with three characteristic functions: the membership degree (MD) denoted by S, the nonmembership degree (NMD) denoted by D, and the abstinence degree (AD) denoted by I. It can be used to solve problems of uncertain information with no restrictions. The distance measure (DM) is a tool that sums up the difference between points, while the similarity measure (SM) is a method applied to calculate the similarity between objects within an interval of [0,1]. The current work aims to introduce novel DMs and SMs in the environment of TSFSs to show the limitations of the previously defined DMs and SMs. The suggested DMs and SMs provide more room for all three degrees to be selected without restriction. We investigated the effectiveness of the proposed DMs and SMs by applying a pattern-recognition technique, and we determined their applicability for multicriteria decision making (MCDM) using numerical examples. The newly proposed DMs and SMs are briefly compared to existing DMs and SMs, and appropriate conclusions are drawn.

Aims: The endoscopic evaluation is crucial for the management and treatment of ulcerative colitis (UC). Currently, the Mayo Endoscopic Score (MES) and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) are two major endoscopic score systems to evaluate the status of mucosal inflammation and disease activity. However, in both MES and UCEIS systems, the disease extent is not included. The Degree of Ulcerative Colitis Burden of Luminal Inflammation (DUBLIN) score is a simple clinical score which is calculated as a product of the MES (0–3) and the extent of disease (E1–E3). The objective of this study was to compare the correlation among DUBLIN, UCEIS and MES, and also investigate the clinical characteristics for predicting treatment failure in patients with active UC. Methods: Between March 2015 and April 2019, 172 patients who were previously diagnosed with UC and had undergone colonoscopy were recruited in this study. We retrospectively reviewed the endoscopic scores and clinical characteristics at the time of the colonoscopy and assessed the prognosis of the patients. Endoscopic response was defined as the decrease in MES ⩾1 grade. Results: DUBLIN showed significant correlation with MES ( r = 0.748) and partial Mayo score (pMayo) ( r = 0.707), and moderately correlated with CRP ( r = 0.590). UCEIS also showed strong correlation with MES ( r = 0.712) but moderate correlation with pMayo ( r = 0.609) and CRP ( r = 0.588). Compared with the UCEIS (cut-off value: 4; sensitivity: 75.73%), DUBLIN score (cut-off value: 4; sensitivity: 86.41%) showed higher diagnostic sensitivity than UCEIS score (McNemar test, p

Summary: Feedback circuits are one of the major causes underlying tumor resistance. Thus, compounds that target one oncogenic pathway with simultaneously blocking its compensatory pathway will be of great value for cancer treatment. Here, we develop a new MEK inhibitor designated as KZ-02 that exhibits unexpectedly higher cytotoxicity than its starting compound AZD6244, a well-known MEK inhibitor, in colorectal cancer (CRC). Subsequent kinase selectivity study identified Pim-1 as an additional cellular target for KZ-02. Further studies showed that AZD6244 and Pim-1 1 (a Pim-1 inhibitor) have a synergistic effect on CRC suppression. Mechanistic study revealed that MEK inhibition by AZD6244 leads to increased Pim-1 expression, which could be a general mechanism behind the compromised cell-killing activity of MEK inhibitors. KZ-02, despite increasing Pim-1 mRNA expression, simultaneously promotes Pim-1 proteasomal degradation. Therefore, we uncover a new MEK inhibitor KZ-02 with significantly enhanced antitumor activity by co-targeting MEK and Pim-1.

Allan–Herndon–Dudley syndrome (AHDS) is a rare, X-chromosome-linked inherited disorder that affects brain development and is caused by a mutation in SLC16A2. Herein, we generated an induced pluripotent stem cell (iPSC) line from the peripheral blood mononuclear cells of a one-year-old male infant with AHDS using Sendai-virus-mediated reprogramming. These iPSCs exhibited stable amplification, expressed pluripotent markers, and differentiated spontaneously into three germ layers in vitro. Additionally, this iPSC line was found to maintain a normal karyotype and retain the pathogenic mutation in SLC16A2, facilitating the study of disease mechanisms and development of new therapies of AHDS.

Mediator complex subunit 12 (MED12)-related disorders are recessive-X-linked intellectual disabilities present primarily in male patients. We came across a female patient with a heterozygous mutation (c.1249-1G > C) related to MED12-related syndrome. MED12 expression was significantly lower than that in her parents, and another X chromosome was inactive. We established an induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells (PBMCs) of a 1-year old Chinese girl with a heterozygous mutation (c.1249-1G > C) in MED12. PBMCs were reprogrammed using nonintegrative Sendai viral vectors. The iPSCs showed stable amplification, pluripotency-related gene expression, trilineage differentiation potential, and a normal karyotype.

While carbapenem use is prohibited in the poultry production chain and carbapenem-resistant Enterobacteriaceae (CRE) are absent from hatchery farms, New Delhi metallo-β-lactamase-producing CRE contamination of commercial broiler chicken farms (grow-out farms) can occur via living hosts such as flies. However, it is not known whether the inanimate factors from in-house environment play a role in the persistence of CRE on commercial farms. Herein, we monitored one typical broiler house in Hebei Province, China, from January 2017 to April 2018. We collected 350 cloacal samples from four broiler batches along with 582 environmental samples (194 in the raising period and 388 in the vacancy period) from sites including the surfaces of drooping boards, feeding troughs, nipple drinkers, corridor floors, sewage trenches, and air. All samples were screened for blaNDM and cultured for NDM-producing isolates. The resistance profiles, genotypes, and genetic context of blaNDM in CRE isolates were further characterized. Results showed that 1-day-old broilers, which were transferred from a hatchery farm and negative for CRE, acquired blaNDM within 24 h of transfer (2 days of age), with a detection rate of up to 18.6%. High blaNDM detection rates (26.8%–31.4%) were obtained among all environmental samples except air after standard cleaning and disinfection during the vacancy period. blaNDM carriage rates (52.9%–72.9%) within the flocks remain stable and high across the next three broiler batches. Overall, 279 NDM-producing bacteria, including 259 Enterobacteriaceae (8 species), 14 Morganellaceae (3 species), three Alcaligenes faecalis and three Pseudomonas putida isolates, were recovered from 85 (24.3%) cloacal and 101 (17.4%) environmental samples. Three NDM variants, including NDM-5 (n = 181), NDM-1 (n = 92), and NDM-9 (n = 3), and a novel NDM-like-metallo-β-lactamase (NLM, n = 3) were identified among the samples. The predominant NDM-producing CRE species among the samples were Klebsiella pneumoniae (CRKP; 32.6%, n = 91) and Escherichia coli (CREC; 27.2%, n = 76). Both clonal and horizontal transmission of blaNDM and an overlap of sequence types (STs) were observed in both CREC and CRKP from chicken and environmental samples. Notably, ST6751 CREC and ST37 CRKP persisted throughout the 16-month surveillance period. IncX3 (n = 197, 7 species), IncA/C2 (n = 41, 5 species), and IncFII (n = 8, E. coli) were the three major blaNDM-carrying plasmid types among the isolates. Although routine cleaning and disinfection procedures and “all-in/all-out” management were performed, once introduced to the farm environment, a diverse range of NDM-positive isolates may survive and persist, becoming an important reservoir of NDM-positive CRE for broiler chickens. Therefore, cleaning and disinfection procedures should be improved on poultry farms to avoid cross-contamination of NDM-producing bacteria between different batches of chickens, as well as further downstream in the poultry production chain.

ABSTRACT The heterochromatin environment plays a central role in silencing genes associated with the malaria parasite’s development, survival in the host, and transmission to the mosquito vector. However, the underlying mechanism regulating the dynamic chromatin structure is not understood yet. Here, we have uncovered that Plasmodium falciparum Rrp6, an orthologue of eukaryotic RNA exosome-associated RNase, controls the silencing of heterochromatic genes. PfRrp6 knockdown disrupted the singular expression of the GC-rich ncRNA RUF6 family, a known critical regulator of virulence gene expression, through the stabilization of the nascent transcripts. Mechanistic investigation showed that the accumulation of the multiple RUF6 ncRNAs triggered local chromatin remodeling in situ, which activated their adjacent var genes. Strikingly, chromatin isolation by RNA purification analysis (ChIRP-seq) revealed that a remarkable RUF6 ncRNA had interacted with distal heterochromatin regions directly and stimulated a global derepression effect on heterochromatic genes, including all variant gene families and the sexual commitment-associated regulator ap2-g gene. Collectively, Rrp6 appears to conduct the epigenetic surveillance of heterochromatic gene expression through controlling RUF6 levels, thereby securing antigenic variation and sexual commitment of malaria parasites during the infection of the host. IMPORTANCE Malaria remains a major public health and economic burden. The heterochromatin environment controls the silencing of genes associated with the fate of malaria parasites. Previous studies have demonstrated that a group of GC-rich ncRNAs (RUF6) is associated with the mutually exclusive expression of var genes, but the underlying mechanisms remain elusive. Here, through a series of genetic manipulation and genome-wide multiomics analysis, we have identified the plasmodial orthologue of RNA exosome-associated Rrp6 as an upstream regulator of RUF6 expression and revealed that the dysregulation of RUF6 upon Rrp6 knockdown triggered local chromatin alteration, thereby activating most heterochromatic genes via direct interaction of RUF6 and distal gene loci. This finding not only uncovered the in-depth mechanism of RUF6-mediated regulation of heterochromatic genes but also identified Rrp6 as a novel regulator of gene expression in human malaria parasites, which provides a new target for developing intervention strategies against malaria.

Mitochondrial DNA depletion syndrome-13 (MTDPS13) is a rare autosomal recessive mitochondrial disease caused by mutations in the FBXL4 (F-box and leucine-rich repeat protein 4) gene. Using Sendai virus-mediated reprogramming, we established an induced pluripotent stem cell (iPSC) line from PBMCs collected from a one-year-old female patient with MTDPS13. The iPSCs were stable during amplification, expressed pluripotent genes, maintained a normal karyotype, and showed characteristics of the three germs layers in an in vitro differentiation assay.

Aim: The aim of this study was to investigate the significance of positive tuberculosis interferon gamma release assay (TB-IGRA) in the differential diagnosis of intestinal tuberculosis (ITB) and Crohn’s disease (CD) patients, and to find a suitable threshold to help distinguishing CD from tuberculosis (TB), so as to provide better recommendations for clinical treatment. Methods: A retrospective study was performed including 484 patients who underwent TB-IGRA testing for suspected CD or ITB treated in the Shanghai Tenth People’s Hospital of Tongji University between January 2015 and May 2018. According to the diagnostic criteria, 307 patients, including 272 CD and 35 ITB patients, were recruited for the final analysis. We comprehensively and systematically collected their clinical manifestations, and analyzed the influence of TB-IGRA values referring to diagnosis criteria, and the possible causes of false positives. The receiver operator characteristic (ROC) curve and the cut-off value were applied to distinguish between ITB and CD patients. Results: Of the 56 patients with suspected CD enrolled, 23 were finally diagnosed with CD and 33 with ITB. In patients with TB-IGRA ⩾ 100 pg/ml, 4 cases were CD and 29 cases were ITB, while 19 cases were CD and 4 cases were ITB in patients with TB-IGRA

The RNA polymerase II transcription subunit 12 homolog (MED12) is a member of the mediator complex, which plays a critical role in RNA transcription. Mutations in MED12 cause X-linked intellectual disability and other anomalies collectively grouped as MED12-related disorders. While MED12 mutations have been most commonly reported in male patients, we present the case of a 1-year-old girl with clinical characteristics similar to MED12-related disorders. To explore the clinical characteristics of the condition and its possible pathogenesis, we analyzed the patient’s clinical data; genetic testing by whole-exome sequencing revealed a de novo heterozygous mutation (c.1249-1G > C) in MED12. Further cDNA experiments revealed that the patient had an abnormal splicing at the skipping of exon9, which may have produced a truncated protein. qPCR showed decreased MED12 gene expression level in the patient, and an X-chromosome inactivation test confirmed a skewed inactivation of the X-chromosome. The lymphoblast transcription levels of the genes involved in the Gli3-dependent sonic hedgehog (SHH) signaling pathway, namely, CREB5, BMP4, and NEUROG2, were found to be significantly elevated compared with those of her parents and sex- and age-matched controls. Our results support the view that MED12 mutations may dysregulate the SHH signaling pathway, which may have accounted for the aberrant craniofacial morphology of our patient.

ABSTRACT The cell wall-targeting echinocandin antifungals, although potent and well tolerated, are inadequate in treating fungal infections due to their narrow spectrum of activity and their propensity to induce pathogen resistance. A promising strategy to overcome these drawbacks is to combine echinocandins with a molecule that improves their activity and also disrupts drug adaptation pathways. In this study, we show that puupehenone (PUUP), a marine-sponge-derived sesquiterpene quinone, potentiates the echinocandin drug caspofungin (CAS) in CAS-resistant fungal pathogens. We have conducted RNA sequencing (RNA-seq) analysis, followed by genetic and molecular studies, to elucidate PUUP’s CAS-potentiating mechanism. We found that the combination of CAS and PUUP blocked the induction of CAS-responding genes required for the adaptation to cell wall stress through the cell wall integrity (CWI) pathway. Further analysis showed that PUUP inhibited the activation of Slt2 (Mpk1), the terminal mitogen-activated protein (MAP) kinase in this pathway. We also found that PUUP induced heat shock response genes and inhibited the activity of heat shock protein 90 (Hsp90). Molecular docking studies predicted that PUUP occupies a binding site on Hsp90 required for the interaction between Hsp90 and its cochaperone Cdc37. Thus, we show that PUUP potentiates CAS activity by a previously undescribed mechanism which involves a disruption of Hsp90 activity and the CWI pathway. Given the requirement of the Hsp90-Cdc37 complex in Slt2 activation, we suggest that inhibitors of this complex would disrupt the CWI pathway and synergize with echinocandins. Therefore, the identification of PUUP’s CAS-potentiating mechanism has important implications in the development of new antifungal combination therapies. IMPORTANCE Fungal infections cause more fatalities worldwide each year than malaria or tuberculosis. Currently available antifungal drugs have various limitations, including host toxicity, narrow spectrum of activity, and pathogen resistance. Combining these drugs with small molecules that can overcome these limitations is a useful strategy for extending their clinical use. We have investigated the molecular mechanism by which a marine-derived compound potentiates the activity of the antifungal echinocandin caspofungin. Our findings revealed a mechanism, different from previously reported caspofungin potentiators, in which potentiation is achieved by the disruption of Hsp90 activity and signaling through the cell wall integrity pathway, processes that play important roles in the adaptation to caspofungin in fungal pathogens. Given the importance of stress adaptation in the development of echinocandin resistance, this work will serve as a starting point in the development of new combination therapies that will likely be more effective and less prone to pathogen resistance.

Natural carotenoids (CARs), viz. β-carotene, lutein, astaxanthin, bixin, norbixin, capsanthin, lycopene, canthaxanthin, β-Apo-8-carotenal, zeaxanthin, and β-apo-8-carotenal-ester, are being studied as potential candidates in fields such as food, feed, nutraceuticals, and cosmeceuticals. CAR research is advancing in the following three major fields: (1) CAR production from natural sources and optimization of its downstream processing; (2) encapsulation for enhanced physical and chemical properties; and (3) preclinical, clinical, and epidemiological studies of CARs’ health benefits. This review critically discusses the recent developments in studies of the chemistry and antioxidant activity, marketing trends, dietary sources, extraction, bioaccessibility and bioavailability, encapsulation methods, dietary intake, and health benefits of CARs. Preclinical, clinical, and epidemiological studies on cancer, obesity, type 2 diabetes (T2D), cardiovascular diseases (CVD), osteoporosis, neurodegenerative disease, mental health, eye, and skin health are also discussed.

Abstract The CRISPR/Cas9 system has recently been engineered to confer resistance to geminiviruses in plants. However, we show here that the usefulness of this antiviral strategy is undermined by off-target effects identified by deep sequencing in Arabidopsis. We construct two virus-inducible CRISPR/Cas9 vectors that efficiently inhibit beet severe curly top virus (BSCTV) accumulation in both transient assays (Nicotiana benthamiana) and transgenic lines (Arabidopsis). Deep sequencing detects no off-target effect in candidate sites of the transgenic Arabidopsis. This kind of virus-inducible genome-editing system should be widely applicable for generating virus-resistant plants without off-target costs.

With an increasing proportion of sedentary lifestyle related chronic diseases, an efficient way to help fight the growing world epidemic of non-communicable diseases (NCDs) and promote public health in a fast-changing world is urgently needed. Exercise and medicine science have played an important role in prevention and control of NCDs. However, the current status and future development directions regarding the integration of exercise science and medicine (IESM) in China have not been well discussed. During 2017 Belt and Road Initiative Global Health International Congress & 2017 Chinese Preventive Medicine Association-Chinese Society on Global Health Annual Meeting, Xi’an Jiaotong University Global Health Institute, and the Integration of Sport and Medicine Innovation Research Center, China Institute of Sport Science organized the IESM Forum on September 27. Six leaders and experts from China and abroad presented excellent research reports in the IESM Forum from several aspects. Experts reached a consensus at the end of their discussions that, in the near future, the IESM will be a key part of a sustainable health care system and as such should contribute to prosperity in China and around the world. However, compared with European, American and Japanese universities, the development of the IESM in China is in its early stages with huge development potential.

A number of gut epithelial cells derived immunological factors such as cytokines and chemokines, which are stimulated by the gut microbiota, can regulate host immune responses to maintain a well-balance between gut microbes and host immune system. Multiple specialized immune cell populations, such as macrophages, dendritic cells (DCs), innate lymphoid cells, and T regulatory (Treg) cells, can communicate with intestinal epithelial cells (IEC) and/or the gut microbiota bi-directionally. The gut microbiota contributes to the differentiation and function of resident macrophages. Situated at the interface between the gut commensals and macrophages, the gut epithelium is crucial for gut homeostasis in microbial recognition, signaling transformation, and immune interactions, apart from being a physical barrier. Thus, three distinct but interactive components—macrophages, microbiota, and IEC—can form a network for the delicate and dynamic regulation of intestinal homeostasis. In this review, we will discuss the crucial features of gut microbiota, macrophages, and IEC. We will also summarize recent advances in understanding the cooperative and dynamic interactions among the gut microbiota, gut macrophages, and IEC, which constitute a special network for gut homeostasis.

The increased consumption of fruits, vegetables, and whole grains contributes to the reduced risk of many diseases related to metabolic syndrome, including neurodegenerative diseases, cardiovascular disease (CVD), diabetes, and cancer. Citrus, the genus Citrus L., is one of the most important fruit crops, rich in carotenoids, flavonoids, terpenes, limonoids, and many other bioactive compounds of nutritional and nutraceutical value. Moreover, polymethoxylated flavones (PMFs), a unique class of bioactive flavonoids, abundantly occur in citrus fruits. In addition, citrus essential oil, rich in limonoids and terpenes, is an economically important product due to its potent antioxidant, antimicrobial, and flavoring properties. Mechanistic, observational, and intervention studies have demonstrated the health benefits of citrus bioactives in minimizing the risk of metabolic syndrome. This review provides a comprehensive view of the composition of carotenoids, flavonoids, terpenes, and limonoids of citrus fruits and their associated health benefits.

The present study was aimed to investigate the composition and contents and the major lipophilic compounds, including the sterols, fatty acids, and tocols of shellfish species. Moreover, to explore the antitumor activity of these lipophilic constituents, their cytotoxicity potentials were determined against five different human cancer cells, including colon carcinoma (HCT116), epithelial melanoma (A2058), glioblastoma multiforme (T98G), lung carcinoma (A549), and adenocarcinoma (HeLa). The results show a significant variation in the contents and composition of lipophilic constituents among the studied species. The highest omega-3 (n-3) polyunsaturated fatty acids (PUFAs) were recorded from arrow squid and pacific oysters, accounting for 53.2% and 53.0% of their total fatty acids, respectively. However, the highest cholesterol content was also recorded in arrow squid (154.4 mg/100 g; 92.6% of total sterols). In contrast, in the Japanese littleneck, Yesso scallop, and common orient clam, cholesterol was just 17.1%, 18.3%, and 18.9% of total sterols, respectively, making them the richest source of non-cholesterol sterols (NCS). Lipids extracted from shellfish species showed ABTS+•- and DPPH•-scavenging activities. In the cytotoxicity analysis, lipids extracted from the Argentine red shrimp showed the highest cytotoxicity against glioblastoma multiforme T98G cells, with an IC50 value of 12.3 µg/mL. The composition and cytotoxicity data reported herein may help explore the nutritional and anticancer potentials of shellfish species.

The omega−3 (n−3) polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic (DHA) acid are well known to protect against numerous metabolic disorders. In view of the alarming increase in the incidence of chronic diseases, consumer interest and demand are rapidly increasing for natural dietary sources of n−3 PUFAs. Among the plant sources, seed oils from chia (Salvia hispanica), flax (Linum usitatissimum), and garden cress (Lepidium sativum) are now widely considered to increase α-linolenic acid (ALA) in the diet. Moreover, seed oil of Echium plantagineum, Buglossoides arvensis, and Ribes sp. are widely explored as a source of stearidonic acid (SDA), a more effective source than is ALA for increasing the EPA and DHA status in the body. Further, the oil from microalgae and thraustochytrids can also directly supply EPA and DHA. Thus, these microbial sources are currently used for the commercial production of vegan EPA and DHA. Considering the nutritional and commercial importance of n−3 PUFAs, this review critically discusses the nutritional aspects of commercially exploited sources of n−3 PUFAs from plants, microalgae, macroalgae, and thraustochytrids. Moreover, we discuss issues related to oxidative stability and bioavailability of n−3 PUFAs and future prospects in these areas.

Phytosterols are nutritionally vital phytoconstituent owing to their cholesterol (low-density plasma lipoprotein-cholesterol, LDL-C)-lowering, anti-inflammatory, and antioxidant properties. Among the widely used spices and herbs, the seeds spices of the Apiaceae family represented the healthiest fatty acid profile. Thus, to explore the other health-beneficial lipids, the present study was aimed to analyze the phytosterol profile of eight seed spices of the Apiaceae family, utilizing gas chromatography (GC)-mass spectrometry (MS). The sterols contents calculated on an oil (mg/100 g of oil) and spice weight (mg/100 g spices; dry weight) basis varied significantly among the seed spices (p < 0.05; Turkey HSD). The β-sitosterol and stigmasterol were the most dominating sterols among the studied spices, together accounted for 40.3 (Ajwain) to 69.8% (celery) of total sterols in the seed oil. Among the studied spices, the oil extracted from caraway seeds showed the highest total sterols (602.2 mg/100 g of oil). Interestingly, based on spice weight, fennel seeds also showed the similar highest number of total sterols (134.2 mg/100 g in fennel and 133.3 mg/100 g in caraway), owing to the high contents of oil (25.9%) in fennel seeds. Overall, celery, caraway, fennel, and anise seeds oil are rich sources of health-beneficial phytosterols.

With the rapid development of new technologies and global trade and increasing collaboration among countries worldwide, public health has become a global issue. Global health, as a new discipline, has been drawing more attention from both academia and governments. The Belt and Road Initiative (BRI), proposed by China in 2013, aimed to promote trade and resource exchange, including education, research, and health issues, with over 60 countries in Asia, Africa, and Europe. The BRI provides good opportunities for involved countries to address health problems jointly as well. In response to the BRI and to promote international collaboration on global health issues, “The 2017 Belt and Road Initiative Global Health International Congress & 2017 Chinese Preventive Medicine Association-Chinese Society on Global Health Annual Meeting” was held on September 24-27, 2017 in Xi’an, China. Thus far, this is the largest high-quality international conference held in China that focused on the BRI global health issues. This article summarized the background, key sessions and topics covered during the congress, and important events, and highlights different perspectives of the BRI and global health by invited experts from China and abroad. The conference included 14 sessions (three keynote speech forums and ten scientific sessions and a research poster session) and about 100 speakers, around 40 of which were leading experts outside of China. All the major sessions were held in English. More than 40 leaders and experts of health sectors from 13 countries presented their work in the congress. Approximately 400 delegates from 29 countries attended the congress. Delegates had extensive discussions about global health related issues, future cooperation and development in global health. The congress fostered international exchange and collaboration.

Abstract Background The risk factors for recurrence and death after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) remain poorly known. This study was aimed to study the 10-year overall survival (OS) of HCC treated by ultrasound (US)-guided RFA and the risk factors for recurrence and death. Methods Between June 2005 and June 2016, 1000 patients with HCC treated by US-guided RFA at 4 hospitals in China; among them, 525 patients met the criteria for radical ablation and 410 had high AFP levels before RFA treatment. Clinical and biochemical factors were tested for association with recurrence and survival. Patients were divided into the recurrence (n = 348) and no recurrence groups (n = 62). Results The 5- and 10-year survival rates were 66 and 35%, respectively. Tumor size (HR = 1.36, 95% CI 1.12–1.65), albumin levels (HR = 0.76, 95% CI 0.65–0.91), prothrombin time (HR = 2.18, 95% CI 1.54–3.10), and α-fetoprotein levels (HR = 1.13, 95% CI 1.00–1.26) were independently associated with mortality after RFA for HCC. Tumor size (HR = 1.27, 95% CI: 1.15–1.40), HBV-DNA (HR = 7.70, 95% CI 3.57–16.63), AFP levels before treatment (HR = 2.172, 95% CI 1.256–3.756, P = 0.006), and AFP response (HR = 4.722, 95% CI 1.053–21.184, P = 0.0427) were independently associated with the risk of recurrence of HCC after RFA. The median survival of the patients with and without recurrence after RFA was 54 (95% CI 45–58) and 62 (95% CI 48–80) months, respectively (log-rank, P = 0.04). Conclusions Tumor size, albumin, prothrombin time, and α-fetoprotein levels were independently associated with mortality after US-guided RFA for HCC, while tumor size and HBV-DNA were independently associated with recurrence. Patients with recurrence had a poorer survival compared with those without.

Objectives: Infections with Vibrio vulnificus are commonly fatal, and the speed and accuracy of diagnosis and treatment is directly linked to mortality. The main aims of this study were to investigate the clinical characteristics of six patients with V. vulnificus infections retrospectively and to determine the effect of treatment with tigecycline (TGC) alone compared with doxycycline plus ceftazidime (DOX/CAZ). Methods: The medical records of patients were reviewed. The species-specific and pathogenic gene markers were detected by PCR, and multilocus sequence typing (MLST) was performed. Furthermore, the effects of TGC and of DOX/CAZ were determined using time–kill assays. Results: MLST revealed six different sequence types and five of them were novel. The complete clinical pattern (vcg type C, CPS operon allele 1, 16S-rRNA type B) was found in one strain and the others had a mixed pattern. The lesion was mainly located at the distal end of the extremities and the most common clinical symptoms were fever, pain, erythema, and local swelling. The in vitro time–kill assay indicated that TGC monotherapy at a concentration of 0.1 mg/l had a rapid bactericidal effect against the six tested V. vulnificus strains at 24 h. Conclusions: TGC alone might be a better potential therapeutic option than the traditional combination of DOX/CAZ against V. vulnificus.

Hepatic macrophages are a remarkably heterogeneous population consisting of self-renewing tissue-resident phagocytes, termed Kupffer cells (KCs), and recruited macrophages derived from peritoneal cavity as well as the bone marrow. KCs are located in the liver sinusoid where they scavenge the microbe from the portal vein to maintain liver homeostasis. Liver injury may trigger hepatic recruitment of peritoneal macrophages and monocyte-derived macrophages. Studies describing macrophage accumulation have shown that hepatic macrophages are involved in the initiation and progression of various liver diseases. They act as tolerogenic antigen-presenting cells to inhibit T-cell activation by producing distinct sets of cytokines, chemokines, and mediators to maintain or resolve inflammation. Furthermore, by releasing regenerative growth factors, matrix metalloproteinase arginase, they promote tissue repair. Recent experiments found that KCs and recruited macrophages may play different roles in the development of liver disease. Given that hepatic macrophages are considerably plastic populations, their phenotypes and functions are likely switching along disease progression. In this review, we summarize current knowledge about the role of tissue-resident macrophages and recruited macrophages in pathogenesis of alcoholic liver disease (ALD), non-alcoholic steatohepatitis (NASH), viral hepatitis, and hepatocellular carcinoma (HCC).

Small cell lung cancer (SCLC) is a carcinoma of the lungs with strong invasion, poor prognosis and resistant to multiple chemotherapeutic drugs. It has posed severe challenges for the effective treatment of lung cancer. Therefore, searching for genes related to the development and prognosis of SCLC and uncovering their underlying molecular mechanisms are urgent problems to be resolved. This study is aimed at exploring the potential pathogenic and prognostic crucial genes and key pathways of SCLC via bioinformatic analysis of public datasets. Firstly, 117 SCLC samples and 51 normal lung samples were collected and analyzed from three gene expression datasets. Then, 102 up-regulated and 106 down-regulated differentially expressed genes (DEGs) were observed. And then, functional annotation and pathway enrichment analyzes of DEGs was performed utilizing the FunRich. The protein-protein interaction (PPI) network of the DEGs was constructed through the STRING website, visualized by Cytoscape. Finally, the expression levels of eight hub genes were confirmed in Oncomine database and human samples from SCLC patients. It showed that CDC20, BUB1, TOP2A, RRM2, CCNA2, UBE2C, MAD2L1, and BUB1B were upregulated in SCLC tissues compared to paired adjacent non-cancerous tissues. These suggested that eight hub genes might be viewed as new biomarkers for prognosis of SCLC or to guide individualized medication for the therapy of SCLC.

Objective. To evaluate the relationship between serum 25-hydroxyvitamin (25(OH)D) levels and metabolic risk factor levels in patients with type 2 diabetes mellitus (T2DM) on a sex-specific basis. Methods. Our study comprised 507 patients with T2DM (321 men, 186 women; median age, 59 years). The metabolic risk factors examined included lipoprotein(a), glycated albumin (GA-L), and random blood glucose (RBG); the levels of these parameters were determined enzymatically. Serum 25(OH)D levels were measured by commercial ELISA kits. Participants were divided into low and high 25(OH)D groups according to the median 25(OH)D concentration (13.2 ng/mL). Two-way analysis of covariance and multiple linear regression analysis were performed. Results. The median 25(OH)D concentration was 13.9 ng/mL in men and 12.2 ng/mL in women. 25(OH)D levels inversely correlated with levels of three metabolic risk factors in a sex-dependent manner after adjusting for several confounding factors. These were lipoprotein(a) in men (141.3 ± 137.9 and 195.3 ± 204.8 mg/L in high and low 25(OH)D groups, respectively; P

Regulatory T cells (Tregs) are engaged in maintaining immune homeostasis and preventing autoimmunity. Treg cells include thymic Treg cells and peripheral Treg cells, both of which can suppress the immune response via multiple distinct mechanisms. The differentiation, proliferation, suppressive function and survival of Treg cells are affected by distinct energy metabolic programs. Tissue-resident Treg cells hold unique features in comparison with the lymphoid organ Treg cells. Foxp3 transcription factor is a lineage master regulator for Treg cell development and suppressive activity. Accumulating evidence indicates that the activity of Foxp3 protein is modulated by various post-translational modifications (PTMs), including phosphorylation, O-GlcNAcylation, acetylation, ubiquitylation and methylation. These modifications affect multiple aspects of Foxp3 function. In this review, we define features of Treg cells and roles of Foxp3 in Treg biology, and summarize current research in PTMs of Foxp3 protein involved in modulating Treg function. This review also attempts to define Foxp3 dimer modifications relevant to mediating Foxp3 activity and Treg suppression. Understanding Foxp3 protein features and modulation mechanisms may help in the design of rational therapies for immune diseases and cancer.

To address the need for a valid and reliable scale of youth leadership potential based on the development theory of leadership, the current study developed the Youth Leadership Potential Scale (YLPS) and investigated its factor structure and psychometric properties in a sample of 696 students (grades 7–9) in China. Exploratory structural equation modeling (ESEM) identified a five-factor solution comprising leadership information, leadership attitude, communication skills, decision-making skills, and stress management skills. ESEM within confirmatory factor analysis demonstrated an adequate fit for this structure. The scale showed good composite reliability and measurement invariance across different gender and grade/age groups. The scale also showed sufficient concurrent validity with the Coping Self-Efficacy Scale, the Chinese Roets Rating Scale for Leadership, and the Leadership Skills Inventory. Furthermore, criterion-related validity was supported by the relationship between YLPS scores and the length of student leadership positions. The results suggest that the YLPS is a valid and pragmatic measure for assessing youth leadership potential. The current study is the first to develop a youth leadership potential scale based on the development theory of leadership.

Background: Frailty is a common syndrome in elderly people, but has not been fully studied in China. We aimed to investigate the epidemiological characteristics of frailty and analyze its risk factors in elderly people in rural areas of China. Methods: This cross-sectional study was conducted between September and October 2016. Overall, 4323 elderly people over 60 yr were enrolled by cluster random sampling method from the Fengxian District of Shanghai, China. These subjects voluntarily participated in the health examination of the 2016 National Basic Public Health Service Program. In addition to regular examination items, frailty assessment was performed on the basis of Fried frailty phenotype criteria. Results: The prevalence of pre-frailty and frailty was 49.4% and 6.8%, respectively. Advanced age (OR=1.44 for pre-frailty and OR=2.01 for frailty, 65-74 years old; OR=3.02 for pre-frailty and OR=14.13 for frailty,75-84 years old; OR=8.17 for pre-frailty and OR=71.71 for frailty, ≥85 years old), female (OR=1.32 for pre-frailty and OR=1.97 for frailty), stroke history (OR=1.75 for pre-frailty and OR=2.43 for frailty), vision decrease (OR=1.98 for pre-frailty and OR=2.70 for frailty), and anemia (OR=1.95 for pre-frailty and OR=3.64 for frailty) were common risk factors for both pre-frailty and frailty. Conclusion: Healthy elderly people in the rural areas of Shanghai have relatively high prevalence of pre-frailty and frailty. Advanced age, female, stroke history, decreased vision, and anemia are the risk factors for pre-frailty and frailty.

Abstract Background The seizure threshold 2 (SZT2) gene encodes a large, highly conserved protein that lowers seizure threshold and may also enhance epileptogenesis. In this study, three patients diagnosed with SZT2‐related developmental and epileptic encephalopathies (DEEs) were reviewed aiming to expand knowledge of the genotype and phenotype of SZT2 mutations. Methods Targeted next‐generation sequencing was performed to identify pathogenic mutations in 205 cases with DEEs of unknown etiology. Detailed clinical and genetic data were collected from SZT2‐associated patients. Results Four novel mutations were found (c.1626 + 1G>A, c.5772dupA, c.4209C > A, c.7307_7308insG) in three patients. All the variants were inherited from their parents. Two patients were siblings and harbored the same mutations and presented developmental delay prior to the onset of seizures. All the individuals were diagnosed as DEEs, drug refractory epilepsy, and experienced status epilepticus (SE); one patient died of SE. One subject showed subependymal nodules as similar as those of tuberous sclerosis complex (TSC) in cranial magnetic resonance imaging (MRI). Conclusion Our results expand the genotype and phenotypes of SZT2‐related DEEs, suggesting that SZT2 mutations play a role in developmental delay and epileptic encephalopathy, with high susceptibility to SE and relatively specific MRI findings.

Greed is one of the most common features of human nature, and it has recently attracted increasing research interest. The aims of this paper are to provide one of the first empirical investigations of the effects of greed on job performance and to explore the mediating role of the need for social status and perceived distributive justice. Using a working sample (N = 315) from China, the current study found that greed promoted both task and contextual performance through the intermediary effect of the need for social status. At the same time, greed inhibited both types of performance through perceived distributive justice. These results confirmed our hypothesis that greed is a double-edged sword with opposite effects on one’s performance. The findings suggest that organizations should both address greedy employees’ social status concerns and ensure that they are treated fairly so that organizations can fully utilize the talents of greedy people and channel their energy in a beneficial direction.

Background and study aims There is a high prevalence of Helicobacter pylori infection. White light endoscopy (WLE) can be used for evaluating the mucosal lesions, but it does not have high diagnostic efficiency. Linked color imaging (LCI) is a newly developed endoscopic imaging technique. The aim of this study was to compare LCI with WLE in detecting and staging H. pylori infection in the stomach in a randomized controlled clinical trial. Patients and methods A total of 253 patients who had indications for gastroduodenoscopy were enrolled and randomized into Group A (n = 127), who underwent WLE followed by LCI, and Group B (n = 126), who underwent LCI followed by WLE. Clinical data were collected and the diagnostic accuracy of WLE and LCI was calculated and compared. Results The overall diagnostic accuracy of WLE and LCI for H. pylori infection was 31.5 % (n = 40) and 50.4 % (n = 64) in Group A (P = 0.001), and 36.5 % (n = 46) and 49.2 % (n = 62) in Group B (P = 0.029). In both groups, LCI had higher sensitivity, specificity, and Youden index scores than WLE. Four stages were defined in the course of H. pylori infection in the stomach. LCI staging results were more highly consistent with pathological staging than were WLE staging results (kappa value 0.772 vs. 0.516). The LCI observations were closely correlated with the pathology. Conclusion LCI had a higher diagnostic efficacy for H. pylori infection in the stomach. Endoscopic color features under LCI can help to stage and profile H. pylori-associated gastritis.

T cells play critical roles in anti-tumor immunity. Up-regulation of immune checkpoint molecules (PD-1, PD-L1, CTLA-4, TIM-3, Lag-3, TIGIT, CD73, VISTA, B7-H3) in the tumor microenvironment is an important mechanism that restrains effector T cells from the anti-tumor activity. To date, immune checkpoint antibodies have demonstrated significant clinical benefits for cancer patients treated with mono- or combination immunotherapies. However, many tumors do not respond to the treatment well, and merely blocking the immune suppression pathways by checkpoint-regulatory antibodies may not render optimal tumor growth inhibition. Binding of the antibody Fc-hinge region to Fc gamma receptors (FcγRs) has been shown to exert a profound impact on antibody function and in vivo efficacy. Investigation of immune checkpoint antibodies regarding their effector functions and impact on therapeutic efficacy has gained more attention in recent years. In this review, we discuss Fc variants of antibodies against immune checkpoint targets and the potential mechanisms of how FcγR-binding could influence the anti-tumor activity of these antibodies.

Commensal microbes are necessary for a healthy gut immune system. However, the mechanism involving these microbes that establish and maintain gut immune responses is largely unknown. Here, we have found that the gut immune receptor leucine-rich repeat (LRR) C19 is involved in host-microbiota interactions. LRRC19 deficiency not only impairs the gut immune system but also reduces inflammatory responses in gut tissues. We demonstrate that the LRRC19-associated chemokines CCL6, CCL9, CXCL9, and CXCL10 play a critical role in immune cell recruitment and intestinal inflammation. The expression of these chemokines is associated with regenerating islet-derived (REG) protein-mediated microbiotas. We also found that the expression of REGs may be regulated by gut Lactobacillus through LRRC19-mediated activation of NF-κB. Therefore, our study establishes a regulatory axis of LRRC19, REGs, altered microbiotas, and chemokines for the recruitment of immune cells and the regulation of intestinal inflammation.

Accurate estimates of evapotranspiration (ET) are essential for the conservation of ecosystems and sustainable management of water resources in arid and semiarid regions. Over the last two decades, several empirical remotely sensed ET models (ERSETMs) had been developed and extensively used for regional-scale ET estimation in arid and semiarid ecosystems. These ERSETMs were constructed by combining datasets from different sites and relating measured daily ET to corresponding meteorological data and vegetation indices at the site scale. Then, regional-scale ET on a pixel basis can be estimated, using the established ERSETMs. The estimation accuracy of these ERSETMs at the site scale plays a fundamental and crucial role in regional-scale ET estimation. Recent studies have revealed that ET estimates from some of these models have significant uncertainties at different spatiotemporal scales. However, little information is available on the performance of these ERSETMs at the site scale. In this study, we compared eight ERSETMs, using ET measurements from 2013 to 2018 for two typical eddy covariance sites (Tamarix site and Populus site) in an arid riparian ecosystem of Northwestern China, intending to provide a guide for the selection of these models. Results showed that the Nagler-2013 model and the Yuan-2016 model outperformed the other models. There were substantial differences in the ET estimation of the eight ERSETMs at daily, monthly, and seasonal scales. The mean ET of the growing season from 2013 to 2018 ranged from 465.93 to 519.65 mm for the Tamarix site and from 386.22 to 437.05 mm for the Populus site, respectively. The differences in model structures and characterization of both meteorological conditions and vegetation factors were the primary sources of different model performance. Our findings provide useful information for choosing models and obtaining accurate ET estimation in arid regions.

The histone H3 lysine 4 (H3K4) presenter WDR5 forms protein complexes with H3K4 methyltransferases MLL1-MLL4 and binding partner proteins including RBBP5, ASH2L, and DPY30, and plays a key role in histone H3K4 trimethylation, chromatin remodeling, transcriptional activation of target genes, normal biology, and diseases such as MLL-rearranged leukemia. By forming protein complexes with other proteins such as Myc, WDR5 induces transcriptional activation of key oncogenes, tumor cell cycle progression, DNA replication, cell proliferation, survival, tumor initiation, progression, invasion, and metastasis of cancer of a variety of organ origins. Several small molecule MLL/WDR5 protein-protein interaction inhibitors, such as MM-401, MM-589, WDR5-0103, Piribedil, and OICR-9429, have been confirmed to reduce H3K4 trimethylation, oncogenic gene expression, cell cycle progression, cancer cell proliferation, survival and resistance to chemotherapy without general toxicity to normal cells. Derivatives of the MLL/WDR5 interaction inhibitors with improved pharmacokinetic properties and in vivo bioavailability are expected to have the potential to be trialed in cancer patients.

The liver is one of the most important immunological organs that remains tolerogenic in homeostasis yet promotes rapid responses to pathogens in the presence of a systemic infection. The composition of leucocytes in the liver is highly distinct from that of the blood and other lymphoid organs, particularly with respect to enrichment of innate T cells, i.e., invariant NKT cells (iNKT cells) and Mucosal-Associated Invariant T cells (MAIT cells). In recent years, studies have revealed insights into their biology and potential roles in maintaining the immune-environment in the liver. As the primary liver-resident immune cells, they are emerging as significant players in the human immune system and are associated with an increasing number of clinical diseases. As such, innate T cells are promising targets for modifying host defense and inflammation of various liver diseases, including viral, autoimmune, and those of tumor origin. In this review, we emphasize and discuss some of the recent discoveries and advances in the biology of innate T cells, their recruitment and diversity in the liver, and their role in various liver diseases, postulating on their potential application in immunotherapy.

Rogue access point attack is one of the most important security threats for wireless local networks and has attracted great attention from both academia and industry. Utilizing received signal strength information is an effective solution to detect rogue access points. However, the received signal strength information is formed by multi-dimensional received signal strength vectors that are collected by multiple sniffers, and these received signal strength vectors are inevitably lacking in some dimensions due to the limited wireless transmission range and link instability. This will result in high false alarm rate for rogue access point detection. To solve this issue, we propose a received signal strength–based practical rogue access point detection approach, considering missing received signal strength values in received signal strength vectors collected in practical environment. First, we present a preprocessing scheme for received signal strength vectors, eliminating missing values by means of data filling, filtering, and averaging. Then, we perform clustering analysis on the received signal strength vectors, where we design a distance measurement method that dynamically uses partial components in received signal strength vectors to minimize the distance deviation due to missing values. Finally, we conduct the experiments to evaluate the performance of the practical rogue access point detection. The results demonstrate that the practical rogue access point detection can significantly reduce the false alarm rate while ensuring a high detection rate.

Water use efficiency (WUE) is a useful indicator to illustrate the interaction of carbon and water cycles in terrestrial ecosystems. MODIS gross primary production (GPP) and evapotranspiration (ET) products have been used to analyze the spatial and temporal patterns of WUE and their relationships with environmental factors at regional and global scales. Although MODIS GPP and ET products have been evaluated using eddy covariance flux measurements, the accuracy of WUE estimated from MODIS products has not been well quantified. In this paper, we evaluated WUE estimated from MODIS GPP and ET products against eddy covariance measurements of GPP and ET during 2003–2008 at eight sites of the Chinese flux observation and research network (ChinaFLUX) and conducted sensitivity analysis to investigate the possible key contributors to the bias of MODIS products. Results show that MODIS products underestimate eight-day water use efficiency in four forest ecosystems and one cropland ecosystem with the bias from −0.36–−2.28 g·C·kg−1 H2O, while overestimating it in three grassland ecosystems with the bias from 0.26–1.11 g·C·kg−1 H2O. Mean annual WUE was underestimated by 14%–54% at four forest sites, 45% at one cropland site and 7% at an alpine grassland site, but overestimated by 66% and 9% at a temperate grassland site and an alpine meadow site, respectively. The underestimation of WUE by MODIS data results from underestimated GPP and overestimated ET at four forest sites, while MODIS WUE values are significantly overvalued mainly due to underestimated ET in the three grassland ecosystems. The maximum light use efficiency and fraction of photosynthetically-active radiation (FPAR) were the two most sensitive factors to the estimation of WUE derived from the MODIS GPP and ET algorithms. The error in meteorological data partly caused the overestimation of ET and accordingly underestimation in WUE in subtropical and tropical forests. The bias of MODIS-produced WUE was also derived from the uncertainties in eddy flux data due to gap-filling processes and unbalanced surface energy issue. Their contributions to the uncertainty in estimated WUE at both eight-day and annual scales still need to be further quantified.

Previous work in our laboratory demonstrated that exosomes derived from human amniotic epithelial cells (hAECs) accelerated wound healing by promoting the proliferation and migration of fibroblasts. It is reported that exosomes, which are carriers of the microRNAs (miRNAs) and proteins, play an important role in the regulation of cell-to-cell communication. However, it is still unclear precisely which molecule or which group of molecules carried within hAEC-derived exosomes (hAEC-Exos) mediated wound healing. Here, we explored purified hAEC-Exos together with either proteinase K (PROse) or RNase A on the effect of fibroblasts and cutaneous wound healing. Our experiments demonstrated that hAEC-Exos were positive for exosomal markers CD9, CD63, and CD81. Also, we found that hAEC-Exos could be internalized by fibroblasts and then stimulated cell migration and proliferation. However, the promotive effect of hAEC-Exos was abolished by pretreating hAEC-Exos with RNase A, not PROse. Importantly, in vivo wound healing assay showed that local injection of hAEC-Exos or PROse pretreated hAEC-Exos at skin wounds significantly accelerated wound healing. Our findings revealed an important role of exosomal miRNAs in wound healing.

The aim of the study was to develop a multiplex assay for rapid detection of mcr-1, mcr-2, and mcr-3, a group of genes of conferring resistance to colistin mediated by plasmid in Enterobacteriaceae. A SYBR Green based real-time PCR assay has been designed to detect the mcr genes, and applied to cultured bacteria, feces and soil samples. All three mcr genes could be detected with a lower limit of 102 cultured bacteria. This test was highly specific and sensitive, and generated no false-positive results. The assay was also conclusive when applied to feces and soil samples containing mcr-1-positive Escherichia coli, which could facilitate the screening of mcr genes not only in the bacteria, but also directly from the environment. This simple, rapid, sensitive, and specific multiplex assay will be useful for rapid screening of the colistin resistance in both clinical medicine and animal husbandry.

Gut microbiota may not only affect composition of local immune cells but also affect systemic immune cells. However, it is not completely clear how gut microbiota modulate these immune systems. Here, we found that there exist expanded macrophage pools in huREG3γtgIEC mice. REG3γ-associated Lactobacillus, which is homology to Lactobacillus Taiwanese, could enlarge macrophage pools not only in the small intestinal lamina propria but also in the spleen and adipose tissues. STAT3-mediated signal(s) was a critical factor in the Lactobacillus-mediated anti-inflammatory macrophages. We also offered evidence for critical cellular links among REG3γ-associated Lactobacillus, tissue macrophages, and obesity diseases. Anti-inflammatory macrophages in the lamina propria, which are induced by REG3γ-associated Lactobacillus, may migrate into adipose tissues and are involved in resistance against high-fat diet-mediated obesity. Thus, REG3γ-associated Lactobacillus-induced anti-inflammatory macrophages in gut tissues may play a role in adipose tissue homeostasis.

Yellow catfish (Pelteobagrus fulvidraco) is one of the most important freshwater fish due to its delicious flesh and high nutritional value. However, lack of sufficient simple sequence repeat (SSR) markers has hampered the progress of genetic selection breeding and molecular research for yellow catfish. To this end, we aimed to develop and characterize polymorphic expressed sequence tag (EST)–SSRs from the 454 pyrosequencing transcriptome of yellow catfish. Totally, 82,794 potential EST-SSR markers were identified and distributed in the coding and non-coding regions. Di-nucleotide (53,933) is the most abundant motif type, and AC/GT, AAT/ATT, AAAT/ATTT are respective the most frequent di-, tri-, tetra-nucleotide repeats. We designed primer pairs for all of the identified EST-SSRs and randomly selected 300 of these pairs for further validation. Finally, 263 primer pairs were successfully amplified and 57 primer pairs were found to be consistently polymorphic when four populations of 48 individuals were tested. The number of alleles for the 57 loci ranged from 2 to 17, with an average of 8.23. The observed heterozygosity (HO), expected heterozygosity (HE), polymorphism information content (PIC) and fixation index (fis) values ranged from 0.04 to 1.00, 0.12 to 0.92, 0.12 to 0.91 and −0.83 to 0.93, respectively. These EST-SSR markers generated in this study could greatly facilitate future studies of genetic diversity and molecular breeding in yellow catfish.

Background: Sonodynamic therapy (SDT) is an alternative strategy that manages malignancies via the generation of cytotoxic factors during ultrasound-activated sono-sensitive agents. However, the detailed mechanisms are not clear. This study was to identify the cytotoxic effects of ultrasound-activated protoporphyrin IX (PpIX) on U937 cells. Methods: Flow cytometry was performed to detect the time course for PpIX uptake in U937 cells. Sub-cellular localization of PpIX in U937 cells was visualized by inverted confocal laser scanning microscope. Following PpIX-mediated SDT treatment, cell viability was evaluated by the 3-(4, 5- dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide (MTT) assay; nuclear damage was observed under fluorescent microscope; DNA fragmentation and mitochondrial membrane potential disruption were measured by flow cytometry. The role of reactive oxygen species (ROS) in SDT-induced cell death was also evaluated. Results: We observed that PpIX is mainly localized in the mitochondria, with a maximal uptake within 2 h. Compared with PpIX or ultrasound alone, PpIX plus ultrasound treatment significantly declined cell viability, caused more serious damage of cell morphology, DNA and mitochondria. In the combined treatment group, the intracellular ROS was greatly higher than in other groups; ROS scavenger N-acetylcysteine could effectively rescue the loss of mitochondria membrane potential and cell viability induced by SDT. Conclusion: Taken together, these findings primarily indicated that fatal damage could be induced by PpIX-mediated SDT in U937 cells, and the intracellular ROS was involved during this process.

Seasonal variations of photosynthetic capacity parameters, notably the maximum carboxylation rate, Vcmax, play an important role in accurate estimation of CO2 assimilation in gas-exchange models. Satellite-derived normalised difference vegetation index (NDVI), enhanced vegetation index (EVI) and model-data fusion can provide means to predict seasonal variation in Vcmax. In this study, Vcmax was obtained from a process-based model inversion, based on an ensemble Kalman filter (EnKF), and gross primary productivity, and sensible and latent heat fluxes measured using eddy covariance technique at two deciduous broadleaf forest sites and a mixed forest site. Optimised Vcmax showed considerable seasonal and inter-annual variations in both mixed and deciduous forest ecosystems. There was noticeable seasonal hysteresis in Vcmax in relation to EVI and NDVI from 8 d composites of satellite data during the growing period. When the growing period was phenologically divided into two phases (increasing VIs and decreasing VIs phases), significant seasonal correlations were found between Vcmax and VIs, mostly showing R2>0.95. Vcmax varied exponentially with increasing VIs during the first phase (increasing VIs), but second and third-order polynomials provided the best fits of Vcmax to VIs in the second phase (decreasing VIs). The relationships between NDVI and EVI with Vcmax were different. Further efforts are needed to investigate Vcmax–VIs relationships at more ecosystem sites to the use of satellite-based VIs for estimating Vcmax.

During the mid-1980s, there were 31 stations in China that successfully participated in the Global Network of Isotopes in Precipitation. However, most observations were suspended after the mid-1990s. The discontinuous data hindered the application of precipitation isotopes, which are strongly affected in China by the Asian monsoon and are thus of intrinsic interest for palaeoclimatologists. Therefore, to continuously observe precipitation isotopes nationwide, the Chinese Network of Isotopes in Precipitation was established in 2004. The current study reviewed the major characteristics of the 928 samples that were collected from 2005 to 2010. The ranges of δD and δ18O values generally followed the pattern NE>NW>TP>NC>SC, and the amount-weighted δ-values followed the pattern SC>NW>NC>TP>NE. Temporal variations presented a ‘V’-shaped pattern at the SC region and reverse ‘V’-shaped patterns at the NE and NW regions. Decreasing trends with the advent of the rainy season were found at the NC and TP regions. The Chinese Meteoric Water Line has been established as δD=7.48δ18O+1.01. The distributions of scattering along the line demonstrated different water vapour origins and characteristics. The values of δ18O showed strong temperature dependence at the NE (0.27‰/°C) and NW stations (0.37‰/°C), and this dependent variable switched to water vapour pressure and vapour pressure at the SC stations. The geographical controls of δ18O were −0.22‰/° and −0.13‰/100 m for latitude and altitude, respectively. The δ18O/Latitude gradient increased from south to north at the Eastern Monsoon Region, and the δ18O/Altitude gradient (−0.30‰/100 m) was especially significant for the TP region. The results of this study could provide basic isotopic information for on-going investigations in hydrology, meteorology, palaeoclimatology and ecology at different regions of China.