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This study investigates the effect of low miR-29b expression derived from bone marrow mesenchymal stem cells (BMSC) on AML. miR-29b expression in acute leukemia drug resistant cell line as K562/ADM was detected with RT-PCR. Cell proliferation was tested with MTT assay and apoptosis was analyzed by flow cytometry. The correlation between miR-29b and PDGFRα level was analyzed. miR-29b expression was reduced after si-miR-29b transfection. PDGFRα expression was increased by the low miR-29b expression in AML cells so as to prompt the progression of AML. Cell proliferation in K562/ADM was increased after miR-29b expression was reduced and quantity of apoptosis was decreased. There was a correlation of miR-29b and PDGFRα in the staging of AML (P α, resulting in increased drug tolerance.

In this study, dielectric elastomers offering intrinsically good integrated performances are achieved by introducing AlN particles grafted with γ-methacryloxypropyl trimethoxy silane (KH570). The C=C of KH570 participated in the vulcanization of NR, which could increase the dispersions and interfacial interactions. By incorporating 10 phr AlN-KH570 fillers, the dielectric and mechanical properties of the composite are increased compared with the pristine DEA, and the breakdown strength remains above 93.9 kV/mm. Correspondingly, the actuation strain of 10 phr AlN-KH570/NR composite is 7 times higher than that of pristine DEA under the same driving voltage. Consequently, the AlN particles developed here are promising candidates as dielectric in actuators, and their excellent electromechanical properties could be applied in future industrial applications of DEs.

Psoriasis is a chronic and multifactorial skin disease which is caused by inflammatory infiltrates, keratinocyte hyperproliferation, and accumulation of immune cells. As part of the Aconitum species, Benzoylaconitine (BAC) shows potential antiviral, anti-tumor, and anti-inflammatory effects. In this study, we investigated the effects and mechanisms of BAC on tumor necrosis factor-alpha (TNF-α)/LPS-induced HaCaT keratinocytes in a imiquimod(IMQ)-induced mice model. The results showed that BAC could relieve the symptoms of psoriasis by inhibiting cell proliferation, the release of inflammatory factors, and the accumulation of Th17 cells, while no obvious effect on cell viability and safety was observed both in vitro and in vivo. Additionally, BAC can markedly inhibit the protein and mRNA levels of inflammatory cytokines in TNF-α/LPS-induced HaCaT keratinocytes by inhibiting the phosphorylation of STAT3. In brief, our data indicated that BAC could alleviate the progression of psoriasis and may be a potential therapeutic agent for treating psoriasis in clinical practice.

Supplementary information contains materials, spectroscopic characterization, telodendrimer synthesis; Figures S1-S24 for synthetic pathway, NMR spectra, MALDI-TOF MS spectra, spectrometry studies, drug release, cellular uptake; Table S1-S2 for synergistic cytotoxicity and blood cell counting studies.

Supplementary Figures

Purpose:Immunotherapies targeting immune checkpoint molecules have shown promising treatment for a subset of cancers; however, many “cold” tumors, such as prostate cancer, remain unresponsive. We aimed to identify a potential targetable marker relevant to prostate cancer and develop novel immunotherapy.Experimental Design:Analysis of transcriptomic profiles at single-cell resolution was performed in clinical patients' samples, along with integrated analysis of multiple RNA-sequencing datasets. The antitumor activity of YY001, a novel EP4 antagonist, combined with anti–programmed cell death protein 1 (PD-1) antibody was evaluated both in vitro and in vivo.Results:We identified EP4 (PTGER4) as expressed in epithelial cells and various immune cells and involved in modulating the prostate cancer immune microenvironment. YY001, a novel EP4 antagonist, inhibited the differentiation, maturation, and immunosuppressive function of myeloid-derived suppressor cells (MDSC) while enhancing the proliferation and anticancer functions of T cells. Furthermore, it reversed the infiltration levels of MDSCs and T cells in the tumor microenvironment by overturning the chemokine profile of tumor cells in vitro and in vivo. The combined immunotherapy demonstrated a robust antitumor immune response as indicated by the robust accumulation and activation of CD8+ cytotoxic T cells, with a significantly decreased MDSC ratio and reduced MDSC immunosuppression function.Conclusions:Our study identified EP4 as a specific target for prostate cancer immunotherapy and demonstrated that YY001 inhibited the growth of prostate tumors by regulating the immune microenvironment and strongly synergized with anti–PD-1 antibodies to convert completely unresponsive prostate cancers into responsive cancers, resulting in marked tumor regression, long-term survival, and lasting immunologic memory.

We have developed multifunctional nanoparticles for codelivery of bortezomib and doxorubicin to synchronize their pharmacokinetic profiles and synergize their activities in solid tumor treatment, a need still unmet in the clinic. Micellar nanoparticles were formed by a spatially segregated, linear-dendritic telodendrimer containing three segments: a hydrophilic polyethylene glycol (PEG), a bortezomib-conjugating intermediate, and a dendritic doxorubicin-affinitive interior. Bortezomib-conjugated telodendrimers, together with doxorubicin, self-assembled into monodispersed micelles [NP(BTZ-DOX)] with small particle sizes (20–30 nm) for dual drug delivery. NP(BTZ-DOX) displayed excellent drug-loading capacity and stability, which minimized premature drug leakage and synchronized drug release profiles. Bortezomib release was accelerated significantly by acidic pH, facilitating drug availability in the acidic tumor microenvironment. Synergistic anticancer effects of combined bortezomib and doxorubicin were observed in vitro against both multiple myeloma and ovarian cancer cells. NP(BTZ-DOX) prolonged payload circulation and targeted tumors in vivo efficiently with superior signal ratios of tumor to normal organs. In vitro and in vivo proteasome inhibition analysis and biodistribution studies revealed decreased toxicity and efficient intratumoral bortezomib and doxorubicin delivery by nanoformulation. NP(BTZ-DOX) exhibited significantly improved ovarian cancer treatment in SKOV-3 xenograft mouse models in comparison with free drugs and their combinations, including bortezomib and Doxil. In summary, tumor-targeted and synchronized delivery system elicits enhanced anticancer effects and merits further development in the clinical setting. Cancer Res; 77(12); 3293–305. ©2017 AACR.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent malignancy worldwide. Accumulating evidence suggests that persistent HPV infection is closely related to a subset of HNSCC types, and the incidence of human papillomavirus (HPV)-positive HNSCC has been annually increasing in recent decades. Although the carcinogenesis of HPV-positive HNSCC has not been completely elucidated, it has been well confirmed that E6 and E7, the main viral oncoproteins are responsible for the maintenance of malignant transformation, promotion of cell proliferation, and increase in tumor invasion. Moreover, compared with HPV-negative HNSCC, HPV-positive HNSCC shows some special clinical-pathological features, which are possibly related to HPV infection and their specific regulatory mechanisms. Non-coding RNA (ncRNA) is a class of RNA lacking the protein-coding function and playing a critical regulatory role via multiple complex molecular mechanisms. NcRNA is an important regulatory pattern of epigenetic modification, which can exert significant effects on HPV-induced tumorigenesis and progression by deregulating downstream genes. However, the knowledge of ncRNAs is still limited, hence, a better understanding of ncRNAs could provide some insights for exploring the carcinogenesis mechanism and identifying valuable biomarkers in HPV-positive HNSCC. Therefore, in this review, we mainly focused on the expression profile of ncRNAs (including lncRNA, miRNA, and circRNA) and explored their regulatory role in HPV-positive HNSCC, aiming to clarify the regulatory mechanism of ncRNAs and identify valuable biomarkers for HPV-positive HNSCC.

Background NK cell is one of innate immune cells and can protect the body from cancer-initiating cells. It has been reported that GPR116 receptor is involved in inflammation and tumors. However, the effect of GPR116 receptor on the NK cells remains largely unclear. Results We discovered that GPR116−/− mice could efficiently eliminate pancreatic cancer through enhancing the proportion and function of NK cells in tumor. Moreover, the expression of GPR116 receptor was decreased upon the activation of the NK cells. Besides, GPR116−/− NK cells showed higher cytotoxicity and antitumor activity in vitro and in vivo by producing more GzmB and IFNγ than wild-type (WT) NK cells. Mechanistically, GPR116 receptor regulated the function of NK cells via Gαq/HIF1α/NF-κB signaling pathway. Furthermore, downregulation of GPR116 receptor promoted the antitumor activity of NKG2D-CAR-NK92 cells against pancreatic cancer both in vitro and in vivo. Conclusions Our data indicated that GPR116 receptor had a negatively effect on NK cell function and downregulation of GPR116 receptor in NKG2D-CAR-NK92 cells could enhance the antitumor activity, which provides a new idea to enhance the antitumor efficiency of CAR NK cell therapy.

Research shows that childhood trauma has a detrimental impact on an individual's health, including suicidal ideation. In order to intervene with suicidal ideation, it is necessary to study the impact of childhood trauma on emotional and social functioning. This study explored the relationship between childhood trauma and suicidal ideation from the perspectives of indifference, identification with all humanity, and loneliness.A total number of 8,452 college students completed the study. Childhood trauma was measured by the short form of Childhood Trauma Questionnaire (CTQ-SF). The Identification With All Humanity scale (IWAH) was used to measure individual's ability to identify or not identify with humanity. For indifference, we used the Inventory of Callous-Unemotional Traits, and Loneliness was assessed by the Loneliness Scale. The relationship of indifference, identification with all humanity, and loneliness were explored to further understand the relationship between childhood trauma and suicidal ideation's correlations, regression analysis, and path analysis were employed for data analysis.Childhood trauma was positively correlated with indifference, loneliness, and suicidal ideation, and negatively correlated with identification with all humanity (r = -0.140∼0.335, p .001). Suicidal ideation was positively correlated with indifference and loneliness, and negatively correlated with identification with all humanity (r = -0.082∼0.260, p .001). The results indicated that childhood trauma leads to indifference, which increases loneliness, and results in suicidal ideation (β = 0.073∼0.335, p 0.001). If an individual with childhood trauma were to gain more recognition from social groups, this would reduce their loneliness and suicidal ideation (β = -0.125∼0.228, p 0.001).Individuals with childhood trauma were more likely to display apathy, including non-emotional behavior. This makes individuals lonelier and may increase suicidal ideation. However, if individuals are further recognized by others and social groups within their environment it is possible to intervene in this process.

Life on Earth uses a common set of l -amino acids ( l -aa) to construct proteins and d -nucleosides ( d -Nu) to form nucleic acids, which serve as the carrier of genetic information. Herein, we reveal the intrinsic mechanism of chiral selection of l -aa and d -Nu from the perspective of chemical origin of life. This work employed 15N-labeled l -aa and performed one-pot synthesis of nucleotide amidate of amino acid (N-aa-NMP) using equal amounts of l -15N-aa and d -14N-aa with d -/ l -Nu in the aqueous solution of trimetaphosphate, generating l -15N-aa-NMP and d -14N-aa-NMP, respectively. The 31P-NMR data indicated that l -aa was preferentially selected during the formation of N-aa-NMP in the presence of d -Nu. Surprisingly, d -aa was preferred over l -aa in the presence of l -Nu. Further analysis revealed that l -15N-aa- d -NMP vs. d -14N-aa- l -NMP and d -14N-aa- d -NMP vs. l -15N-aa- l -NMP were mirror isomers of each other, respectively. These data suggest that there could be a set of chiral systems opposite to that on Earth, which infers there might be a world of life that is a mirror image of the Earth.

As machine learning algorithms are increasingly deployed for high-impact automated decision-making, the presence of bias (in datasets or tasks) gradually becomes one of the most critical challenges in machine learning applications. Such challenges range from the bias of race in face recognition to the bias of gender in hiring systems, where race and gender can be denoted as sensitive attributes. In recent years, much progress has been made in ensuring fairness and reducing bias in standard machine learning settings. Among them, learning fair representations with respect to the sensitive attributes has attracted increasing attention due to its flexibility in learning the rich representations based on advances in deep learning. In this article, we propose graph-fair, an algorithmic approach to learning fair representations under the graph Laplacian regularization, which reduces the separation between groups and the clustering within a group by encoding the sensitive attribute information into the graph. We have theoretically proved the underlying connection between graph regularization and distance correlation and show that the latter can be regarded as a standardized version of the former, with an additional advantage of being scale-invariant. Therefore, we naturally adopt the distance correlation as the fairness constraint to decrease the dependence between sensitive attributes and latent representations, called dist-fair. In contrast to existing approaches using measures of dependency and adversarial generators, both graph-fair and dist-fair provide simple fairness constraints, which eliminate the need for parameter tuning (e.g., choosing kernels) and introducing adversarial networks. Experiments conducted on real-world corpora indicate that our proposed fairness constraints applied for representation learning can provide better tradeoffs between fairness and utility results than existing approaches.

The application of B?zier type operators is very extensive and has attracted people?s attention. In the year 2017, Ren established a generalized Bernstein-B?zier type operators acting on C[0,1]. Inspired by this, in this paper, a generalized Sz?sz-B?zier type operators, with Gamma function defined on the positive semi-axis, is extended. Then, the equivalent theorem and the Voronovskaja type asymptotic formulas are also obtained.

The active ingredients of Traditional Chinese Medicine are an important source of bioactive molecules and play an important role in the research and development of innovative drugs. FA-30, which is a derivative of natural product ferulic acid, inhibited cervical cancer cell proliferation and induced apoptosis as well. To understand the underlying mechanisms of FA-30, a complementary multi-omics study was conducted. Cysteine and methionine metabolism and aminoacyl-tRNA biosynthesis pathways were significantly changed both at the metabolic level and proteomic level. This may help us to get a better understanding of cervical cancer and FA-30 at the same time.

Abstract: Chloroquine (CQ) was found to exhibit antiviral activity against novel coronaviruses, which makes the preparation of CQ enantiomers particularly important. In this work, we developed an efficient method for the preparation of CQ enantiomers by crystallization resolution and palladium-catalyzed coupling. The obtained chiral CQ had been fully assigned by 1H-1H COSY, 1H-13C HSQC, and 1H-13C HMBC spectra. Moreover, the enantiomeric excess value of CQ was rapidly detected by binaphthol phosphate as a chiral NMR shift reagent.

Glutinous rice has very low amylose content and is a good material for determining the structure and physicochemical properties of amylopectin. We selected 29 glutinous rice varieties and determined the amylopectin structure by high-performance anion exchange chromatography with the pulsed amperometric detection method. We also determined the correlation between amylopectin structure and the physicochemical properties of starch extracted from these varieties. The results showed that the amylopectin chain ratio Σdegree of polymerization (DP) ≤ 11/ΣDP ≤ 24 of 29 glutinous rice varieties was greater than 0.26, signifying that these varieties contained type II amylopectin. The results of the correlation analysis with gelatinization temperature showed that ΣDP 6–11 was significantly negatively correlated with the onset gelatinization temperature (GT) (TO), peak GT (TP), and conclusion GT (TC). Among the thermodynamic properties, ΣDP 12–24 was significantly positively correlated with To, Tp, and Tc, ΣDP 25–36 was significantly negatively correlated with To, Tp, and Tc, and ΣDP ≥ 37 had no correlation with the thermodynamic properties. The results of correlation analysis with RVA spectrum characteristic values showed that ΣDP 6–11 was significantly negatively correlated with hot paste viscosity (HPV), cool paste viscosity (CPV), consistency viscosity (CSV), peak time (PeT), and pasting temperature (PaT) among the Rapid Visco Analyzer (RVA) profile characteristics, ΣDP 12–24 was significantly positively correlated with HPV, CPV, CSV, PeT, and PaT, and ΣDP ≥ 25 had no correlation with the viscosity characteristics. Therefore, we concluded that the amylopectin structure had a greater effect on the TO, TP, TC, ΔH and peak viscosity, HPV, CPV, CSV, PeT, and PaT. The glutinous rice varieties with a higher distribution of short chains and a lower distribution of medium and long chains in the amylopectin structure resulted in lower GT and RVA spectrum characteristic values.

Background NK cell is one of innate immune cells and can protect the body from cancer-initiating cells. It has been reported that GPR116 receptor is involved in inflammation and tumors. However, the effect of GPR116 receptor on the NK cells remains largely unclear. Results We discovered that GPR116−/− mice could efficiently eliminate pancreatic cancer through enhancing the proportion and function of NK cells in tumor. Moreover, the expression of GPR116 receptor was decreased upon the activation of the NK cells. Besides, GPR116−/− NK cells showed higher cytotoxicity and antitumor activity in vitro and in vivo by producing more GzmB and IFNγ than wild-type (WT) NK cells. Mechanistically, GPR116 receptor regulated the function of NK cells via HIF1α/NK-κB signaling pathway. Furthermore, downregulation of GPR116 receptor promoted the antitumor activity of NKG2D-CAR-NK92 cells against pancreatic cancer both in vitro and in vivo. Conclusions Our data indicated that GPR116 receptor had a negatively effect on NK cells function and downregulation of GPR116 receptor in NKG2D-CAR-NK92 cells could enhance the antitumor activity, which provides a new idea to enhance the antitumor efficiency of CAR NK cell therapy.

Inspired by wet-cool/dry-hot cycle drived prebiotic reactions, a green and efficient dry-wet cycle modification method was proposed for the preparation of polypeptide-modified bamboo fiber (P-MBF). Functionalization of P-MBF was characterized by Fourier transform infrared spectroscopy, X-ray diffraction, element analysis and scanning electron microscopy. Compared to raw bamboo fiber materials, P-MBF showed better dispersibility in aqueous solutions, and thus exhibited better adsorption performance for glycopeptide antibiotics in sewage treatment. With vancomycin as the target antibiotic, adsorption performance of P-MBF was studied in aqueous solution. Adsorption kinetics and isotherms were well correlated with pseudo-second-order model and Langmuir model, respectively. Investigation of thermodynamic parameters implied that the adsorption was a spontaneous exothermic process. The adsorption efficiencies in standard solution and drinking water were 97.83% and 91.32% , respectively. This study provides a green, efficient and economical modified bamboo fiber material for the removal of glycopeptide antibiotics from sewage samples.

The distribution of elite soybean (Glycine max) cultivars is limited due to their highly sensitive to photoperiod, which affects the flowering time and plant architecture. The recent emergence of CRISPR/Cas9 technology has uncovered new opportunities for genetic manipulation of soybean. The major maturity gene E1 of soybean plays a critical role in soybean photoperiod response. Here, we performed CRISPR/Cas9-mediated targeted mutation of E1 gene in soybean cultivar Tianlong1 carrying the dominant E1 to investigate its precise function in photoperiod regulation, especially in plant architecture regulation. Four types of mutations in the E1 coding region were generated. No off-target effects were observed, and homozygous trans-clean mutants without T-DNA were obtained. The photoperiod sensitivity of e1 mutants decreased relative to the wild type plants; however, e1 mutants still responded to photoperiod. Further analysis revealed that the homologs of E1, E1-La, and E1-Lb, were up-regulated in the e1 mutants, indicating a genetic compensation response of E1 and its homologs. The e1 mutants exhibited significant changes in the architecture, including initiation of terminal flowering, formation of determinate stems, and decreased branch numbers. To identify E1-regulated genes related to plant architecture, transcriptome deep sequencing (RNA-seq) was used to compare the gene expression profiles in the stem tip of the wild-type soybean cultivar and the e1 mutants. The expression of shoot identity gene Dt1 was significantly decreased, while Dt2 was significantly upregulated. Also, a set of MADS-box genes was up-regulated in the stem tip of e1 mutants which might contribute to the determinate stem growth habit.

Background: Sarcoma is a rare mesenchymal malignant tumor. Recently, pyroptosis has been reported to be a mode of programmed cell death. Nonetheless, levels of pyroptosis-associated genes in sarcoma and its relevance to prognostic outcomes are yet to be elucidated. Results: Sarcoma cases were classified into two subtypes with regards to differentially expressed genes. We established a profile composed of seven genes and classified the sarcoma patients into low- and high-risk groups through least absolute shrinkage and selection operator Cox regression. Survival rate of low-risk sarcoma patients was markedly higher, relative to high-risk group (P

Jing Han,1,&ast; Jie Liu,1– 4,&ast; Yakun Wu,1,5,&ast; Qiuxing Lin,1– 3,5 Dandan Guo,1 Xin Zhang,1 Jun Tu,1– 3,5 Xianjia Ning,1– 3,5 Jinghua Wang1– 3,5 1Department of Neurology, Tianjin Medical University General Hospital, Tianjin, 300052, People’s Republic of China; 2Laboratory of Epidemiology, Tianjin Neurological Institute, Tianjin, 300052, People’s Republic of China; 3Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, 300052, People’s Republic of China; 4Center of Clinical Epidemiology & Evidence-Based Medicine, The Jizhou People’s Hospital, Tianjin, 301999, People’s Republic of China; 5Department of Neurology, Tangshan Gongren Hospital, Tangshan, 063000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinghua Wang; Xianjia Ning Email jwang3@tmu.edu.cn; xning@tmu.edu.cnObjective: Although stroke mortality has remained stable over the past decade, the long-term trends of stroke burden are scarce in China, especially in low-income populations. Thus, we aimed to explore the secular trends in the prognosis of stroke in a low-income population in China.Methods: This was a population-based stroke surveillance study that included all of the participants in the Tianjin Brain Study. Stroke management and outcomes were evaluated for all stroke patients. Trends in the burden of stroke were assessed as annual percentage changes.Results: Overall, 1462 stroke cases occurred from 1992 to 2018, and 58.7% of patients were male. The rates of diagnosis by neuroimaging and of hospitalization increased noticeably across sexes and ages for all stroke types, and the greatest increases were observed among elderly women; diagnosis by neuroimaging increased by 4.7% and the rate of hospitalization increased by 12.4% (all P< 0.001). Stroke fatality decreased by 3.7% annually among those aged < 65 years and by 3.1% among patients aged ≥ 65 years; the corresponding rates were 7.4% and 3.5%, respectively, for women. The recurrence rate of ischemic stroke significantly decreased among all men, by 9.6% for those aged < 65 years and by 3.1% for those aged ≥ 65 years; however, for women, this rate only significantly decreased for those aged ≥ 65 years.Conclusion: Our findings suggest that the allocation of medical resources has improved over the past decades. However, it is crucial to enhance secondary stroke prevention for women aged < 65 years by controlling risk factors in low-income populations.Keywords: stroke burden, case fatality, recurrence, trends, low-income population

Pancreatic carcinoma (PC) is one of the most common malignancies. Chimeric antigen receptor (CAR)-modified T cells has achieved remarkable efficacy in the treatment of hematological malignancies. However, lack of tumor-specific targets and the existence of inhibitory factors limit the function of CAR T cells when treating solid tumors. 4.1R has been reported to suppress the anti-tumor activity of T cell responses. In this study, we investigated the anti-tumor activity of 4.1R deletion in natural killer group 2D (NKG2D)-CAR T cells against PC. The CAR T cells were obtained by transfecting T cells with lentiviral vector carrying NKG2D-CAR, NC-NKG2D-CAR, or KD2-NKG2D-CAR. In vitro, NKG2D-CAR T cells showed higher cytotoxicity than Mock T cells. However, compared to NKG2D-CAR T cells, furtherly higher cytotoxicity against PC cells in a dose-dependent manner was found in KD2-NKG2D-CAR T cells. In addition, the proliferation rate and cytotoxic activity of KD2-NKG2D-CAR T cells were significantly higher than those of NKG2D-CAR T cells. Besides, the inhibitory receptors PD-1 and TIM-3 were expressed in lower level on KD2-NKG2D-CAR T cells. In vivo, KD2-NKG2D-CAR T cells suppressed tumor growth more effectively in a xenograft model compared to NKG2D-CAR T cells. Mechanistically, 4.1R regulated CAR T cell function via activating ERK signaling pathway. Therefore, the study provides a new idea to enhance the anti-tumor efficiency of CAR T therapy.

A rhabditid entomopathogenic nematode (EPN), Oscheius chongmingensis, has a stable symbiotic relationship with the bacterial strain Serratia nematodiphila S1 harbored in its intestines and drastically reduced viability when associated with a non-native strain (186) of the same bacterial species. This nematode is thus a good model for understanding the molecular mechanisms and interactions involved between a nematode host and a member of its intestinal microbiome. Transcriptome analysis and RNA-seq data indicated that expression levels of the majority (8797, 87.59%) of mRNAs in the non-native combination of O. chongmingensis and S. nematodiphila 186 were downregulated compared with the native combination, including strain S1. Accordingly, 88.84% of the total uniq-sRNAs mapped in the O. chongmingensis transcriptome were specific between the two combinations. Six DEGs, including two transcription factors (oc-daf-16 and oc-goa-1) and four kinases (oc-pdk-1, oc-akt-1, oc-rtk, and oc-fak), as well as an up-regulated micro-RNA, oc-miR-71, were found to demonstrate the regulatory mechanisms underlying diminished host viability induced by a non-native bacterial strain. Oc-rtk and oc-fak play key roles in the viability regulation of O. chongmingensis by positively mediating the expression of oc-daf-16 to indirectly impact its longevity and stress tolerances and by negatively regulating the expression of oc-goa-1 to affect the olfactory chemotaxis and fecundity. In response to the stress of invasion by the non-native strain, the expression of oc-miR-71 in the non-native combination was upregulated to downregulate the expression of its targeting oc-pdk-1, which might improve the localization and activation of the transcription factor DAF-16 in the nucleus to induce longevity extension and stress resistance enhancement to some extent. Our findings provide novel insight into comprehension of how nematodes deal with the stress of encountering novel potential bacterial symbionts at the physiological and molecular genetic levels and contribute to improved understanding of host–symbiont relationships generally.

BackgroundColon cancer (CC) is the second most common gastrointestinal malignancy. About one in five patients have already developed distant metastases at the time of initial diagnosis, and up to half of patients develop distant metastases from initial local disease, which leads to a poor prognosis for CC patients. Necroptosis plays a key role in promoting tumor growth in different tumors. The purpose of this study was to construct a prognostic model composed of necroptosis-related genes (NRGs) in CC.MethodsThe Cancer Genome Atlas was used to obtain information on clinical features and gene expression. Gene expression differential analysis, weighted gene co-expression network analysis, univariate Cox regression analysis and the least absolute shrinkage and selection operator regression algorithm were utilized to identify prognostic NRGs. Thereafter, a risk scoring model was established based on the NRGs. Biological processes and pathways were identified by gene ontology and gene set enrichment analysis (GSEA). Further, protein-protein interaction and ceRNA networks were constructed based on mRNA-miRNA-lncRNA. Finally, the effect of necroptosis related risk score on different degrees of immune cell infiltration was evaluated.ResultsCALB1, CHST13, and SLC4A4 were identified as NRGs of prognostic significance and were used to establish a risk scoring model. The time-dependent receiver operating characteristic curve analysis revealed that the model could well predict the 1-, 3-, and 5-year overall survival (OS). Further, GSEA suggested that the NRGs may participate in biological processes, such as the WNT pathway and JAK-Stat pathway. Eight key hub genes were identified, and a ceRNA regulatory network, which comprised 1 lncRNA, 5 miRNAs and 3 mRNAs, was constructed. Immune infiltration analysis revealed that the low-risk group had significantly higher immune-related scores than the high-risk group. A nomogram of the model was constructed based on the risk score, necroptosis, and the clinicopathological features (age and TNM stage). The calibration curves implied that the model was effective at predicting the 1-, 3-, and 5-year OS of CC.ConclusionOur NRG-based prognostic model can assist in the evaluation of CC prognosis and the identification of therapeutic targets for CC.

A rhabditid entomopathogenic nematode (EPN)

The distribution of elite soybean (

Supplemental figures and tables for a manuscript submitted to the journal "International Journal of Molecular Sciences".

BackgroundChina advocates a health insurance system with social health insurance (SHI) as the main body and private health insurance (PHI) as the supplement. The study of PHI's complementary role in health is conducive to providing evidence for PHI's policy expansion and encouraging the public to participate in PHI, which is insufficient in China.MethodsWe used the three-wave balanced panel data of the China Health and Retirement Longitudinal Survey (CHARLS). Taking the ownership of supplementary PHI as the independent variable and EQ-5D index scores as the dependent variable, the panel instrumental variable (IV) method was used to analyze the impact of participation in PHI on health. We also assessed the heterogeneity of the health effects of PHI between chronic and non-chronic disease groups and between low- and high-income groups.ResultsThe coverage rate of PHI at baseline was 10.53%. The regression results showed that participating in PHI on the basis of SHI could result in an additional 8.21% health gain (p < 0.001). At the same time, PHI had greater health gain for chronic disease population than for healthy population (9.25 vs. 6.24%, p < 0.001), and greater health gain for high-income population than for low-income population (8.32 vs. 5.31%, p < 0.001).ConclusionParticipating in supplementary PHI can effectively enhance the health status of the insured, and has a more significant effect on patients with chronic diseases. The development of PHI should be further supported, while the health inequality in different income groups should be paid attention to.

Plant-derived polysaccharides have demonstrated promising anti-cancer effects via immune-regulatory activity. The aim of the current study was to compare the chemical property and the anticancer effects of polysaccharides extracted from the sporoderm-removed spores of the medicinal mushroom Ganoderma lucidum (RSGLP), which removed the sporoderm completely, with polysaccharides extracted from the sporoderm-broken spores of G. lucidum (BSGLP). We found that RSGLP has a higher extraction yield than BSGLP. HPGPC and GC-MS results revealed that both RSGLP and BSGLP are heteropolysaccharides, but RSGLP had a higher molecular weight and a different ratio of monosaccharide composition than BSGLP. MTT and flow cytometry results demonstrated that RSGLP exhibited much higher dose-efficacy in inhibiting cell viability and inducing apoptosis than BSGLP in 8 cancer cell lines representing colon (HCT116 and HT29), liver (HepG2 and Huh-7), breast (MDA-MB-231 and MCF-7), and lung cancers (NCI-H460 and A549). Furthermore, RSGLP is more effective in inhibiting HCT116 and NCI-H460 xenograft tumor growth and inhibiting tumor-induced splenomegaly than BSGLP in nude mice, suggesting a better effect on regulating immunity of RSGLP. Next, we found that RSGLP is more potent in inhibiting the level of serum inflammatory cytokines in nude mice, and in inhibiting the activation of macrophage RAW264.7 and the expression of the inflammatory mediators IL-1β, TNF-α, iNOS, and COX-2 in vitro. This is the first study to compare the chemical properties, anti-cancer, and immune-regulatory effects of RSGLP and BSGLP using multiple cancer cell lines. Our results revealed that the sporoderm-removed spores of G. lucidum (RSGL) and RSGLP may serve as new anticancer agents for their promising immune-regulatory activity.

Background Thermal ablation is widely accepted as a radical HCC therapy. However, the 5-year recurrence rate is high, and whether this local treatment induces a systemic immune response remains unclear. Herein, we investigated the effects of thermal ablation on HCC patients’ immune cytokine profiles and explored predictive biomarkers of tumour recurrence. Methods Twenty-two HCC patients were enrolled. We collected peripheral blood before ablation (baseline) and 5–7 days (week 1) and 28–30 days (week 4) after ablation and measured 27 cytokine/chemokine levels at the three time points. Dynamic changes in cytokine profiles and impacts on tumour recurrence were observed. Results We found that most cytokines/chemokines (12/27) in HCC patients at baseline were significantly decreased, while MCP-1 was elevated compared to that in healthy controls. IL-6 was significantly elevated at week 1 and decreased at week 4 after ablation, and there were positive correlations between IL-6 levels and ALT and WBC at week 1. IL-10 was slightly decreased at week 1 and dramatically decreased at week 4. The MCP-1, MIP-1β and TNF-α dynamics were similar (decreasing at week 1, increasing at week 4). IL-17, PDGF-BB and RANTES were significantly elevated at week 4 compared with baseline and week 1. We also found that patients with high levels of IL-10 at baseline and low levels of TNF-α, PDGF-BB and RANTES at week 4 were at risk of tumour recurrence. Conclusion Our results suggest that thermal ablation relieves tumour immune suppression and activates systemic immune responses by circulating cytokines linked to tumour recurrence.

The zirconium-based porphyrin MOFs sensitized TiO2 (PCN224–TiO2) was synthesized in situ by self-assembly of porphyrin, ZrCl4 with nano TiO2. The composite catalyst was determined by detailed structural and photoelectrochemical characterization. The UV–Vis absorption and fluorescence spectrum confirm that PCN224 and TiO2 are coupled. The PCN224–TiO2 had significant absorption of visible light and the PCN224–TiO2 had the largest photo-generated current, which proved the porphyrin MOFs material has good internal conductivity and has a close combination with TiO2. Compared with carboxyphenyl porphyrin sensitized TiO2 (HTCPP–TiO2), mixture of TCPP and TiO2 (TCPP/TiO2) and PCN224, the PCN224–TiO2 showed better removal performance of methylene blue under visible light. Under low-power xenon lamp irradiation, the removal rate of PCN224–TiO2 (1:3) on methylene blue reached 93.2% in 4 h. And PCN224–TiO2 had stable cycling catalytic performance. The PCN224–TiO2 promoted the degradation process by strengthening the adsorption of organic pollutants, thus improving the removal performance.

Plant-derived polysaccharides have demonstrated promising anti-cancer effects

Background Long non-coding RNAs (lncRNAs) are widely involved in the pathogenesis of cancers. However, biological roles of lncRNAs in occurrence and progression of colorectal cancer (CRC) remain unclear. The current study aimed to evaluate the expression pattern of lncRNAs and messenger RNAs (mRNAs). Methods RNA sequencing (RNA-Seq) in CRC tissues and adjacent normal tissues from 6 CRC patients was performed and functional lncRNA-mRNA co-expression network was constructed afterwards. Gene enrichment analysis was demonstrated using DAVID 6.8 tool. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to validate the expression pattern of differentially expressed lncRNAs. Pearson correlation analysis was applied to evaluate the relationships between selected lncRNAs and mRNAs. Results One thousand seven hundred and sixteenth differentially expressed mRNAs and 311 differentially expressed lncRNAs were screened out. Among these, 568 mRNAs were up-regulated while 1148 mRNAs down-regulated, similarly 125 lncRNAs were up-regulated and 186 lncRNAs down-regulated. In addition, 1448 lncRNA–mRNA co-expression pairs were screened out from 940,905 candidate lncRNA-mRNA pairs. Gene enrichment analysis revealed that these lncRNA-related mRNAs are associated with cell adhesion, collagen adhesion, cell differentiation, and mainly enriched in ECM-receptor interaction and PI3K-Akt signaling pathways. Finally, RT-qPCR results verified the expression pattern of lncRNAs, as well as the relationships between lncRNAs and mRNAs in 60 pairs of CRC tissues. Conclusions In conclusion, these results of the RNA-seq and bioinformatic analysis strongly suggested that the dysregulation of lncRNA is involved in the complicated process of CRC development, and providing important insight regarding the lncRNAs involved in CRC.

BackgroundAblative therapy is a recommended treatment for hepatocellular carcinoma (HCC) not only for its effective eradication of tumors, but also for its induction of host immunity. However, the high 5-year recurrence rate after ablation underlines the poor understanding of the antitumor immunity response. Here, we investigated the effects of thermal ablation on antitumor immunity.MethodsWe analyzed the dynamics of tumor-associated antigen (TAA)-specific immune responses and changes in peripheral blood mononuclear cell phenotype in patients with HCC before and after tumor ablation. We used the IFN-γ ELISPOT assay and immunophenotyping by flow cytometry to evaluate the effects of ablation on host immunity. The correlation between the T cell response and disease outcome was explored to uncover the efficacy of the immune response in inhibiting HCC recurrence.ResultsDifferent TAA-specific T cell responses were identified among patients before and after ablation. One week after ablation, there was an improved immune state, with a switch from the dominance of an AFP-specific T cell response to that of a SMNMS-specific T cell response, which was correlated with better survival. Furthermore, an improvement in immune status was accompanied by a lower level of PD1+ and Tim3+ T cells in CD8+ T cells. Although this functional state was not durable, there was a higher degree of AFP-specific T cell responses at 4-weeks post-ablation. Furthermore, T cells presented a more exhausted phenotype at 4-weeks post-ablation than at the 1-week timepoint.ConclusionsAblation elicits a transient antitumor immune response in patients with HCC by changing the profile of the T cell response and the expression of immune checkpoint molecules, which correlated with longer recurrence-free survival of patients with HCC.