Comparison of metabolic syndrome prevalence and characteristics using five different definitions in China: a population-based retrospective study.

Background: Metabolic syndrome (MetS) is on the rise in developing countries and is characterized by a series of indications of metabolic disturbance. However, the prevalence of MetS varies under different definitions. The study aimed to compare five definitions of MetS in the China adult population, to explore their prevalence, characteristics and agreement. Methods: The data for the retrospective study came from the China Health and Retirement Longitudinal Study (CHARLS), consisting of 9,588 participants (≥45). MetS definitions from International Diabetes Federation (IDF) (2006), National Cholesterol Education Program Adult Treatment Panel III (ATPIII) (2005), National Cholesterol Education Program Adult Treatment Panel III (ATPIII) (2001), Chinese Diabetes society (CDS) (2004) and the World Health Organization (WHO) (1999). We used binary and multivariable logistic analysis to explore factors connected with MetS. Results: The five definitions of MetS led to different prevalence of MetS:34.52% by IDF (2006), 38.63% by ATP (2005), 25.94% by ATP (2001), 26.31% by CDS (2004), 21.57% by WHO (1999). According to the definition of IDF (2006) (22.32% vs. 45.06%), ATPIII (2005) definition (27.99% vs. 47.82%), ATPIII (2001) definition (15.37% vs. 35.07%), CDS (2004) definition (19.96% vs. 31.80%), and WHO (1999) definition (17.44% vs. 25.14%), the prevalence of MetS in men was low but in women was high. The agreement between the five definitions for men was good except for the IDF (2006) definition and ATPIII (2001) definition (kappa = 0.51), with kappa values from 0.64 to 0.85. For women, the agreement between the five definitions was good ranging from 0.67 to 0.95, however, except for the definition of CDS (2004) and the definition of IDF (2006) (kappa = 0.44), the definition of WHO (1999) and the definition of IDF (2006) (kappa = 0.55), and the definition of WHO (1999) and the definition of ATPIII (2005) (kappa = 0.54). Binary logistic analysis indicated that although the impact and relevance varied by sex and definition, age, education, marital status, current residence, current smoking, alcohol using, taking activities and number of chronic diseases were factors connected to MetS. Conclusion: the prevalence and characteristics of the five definitions of MetS are different in the Chinese population. Therefore, it is vital to use the same definition for a country to diagnose MetS. On the other side, a lower prevalence in men than in women and the consistency of five MetS definitions are good in men but relatively poor in women.

Reliability and validity of the cancer-related dysfunctional beliefs and attitudes about sleep scale in cancer patients.

BACKGROUND: Insomnia is a common health problem among cancer patients, which is not only a physical problem but also a psychological problem. Sleep plays an important role in the mental and somatic rehabilitation of cancer patients, and the sleep beliefs and attitudes of cancer patients are key factors in improving their sleep situation and quality of life. The aim of this study was to translate the Cancer-Related Dysfunctional Beliefs and Attitudes about Sleep (C-DBAS-14) scale into Chinese and to validate its reliability and validity in cancer patients. METHOD: The C-DBAS-14 scale was translated into Chinese using the backward and forward translation procedure. The reliability of the scale was measured by internal consistency, split-half reliability and retest reliability. The validity of the scale was assessed through the content validity indicators, exploratory factor analysis and validation factor analysis. RESULT: The Cronbach's ɑ coefficient of the Chinese version of the C-DBAS-14 was 0.932 while the McDonald's omega coefficient (ω t) was 0.934. The split-half reliability coefficient was 0.908, and the test-retest reliability was 0.857. The four-factor model was obtained using exploratory factor analysis, explaining 72.7% of the variance, with each item loading greater than 0.4 on the common factor. The results of the confirmatory factor analysis revealed that all indicators of model fit were within an acceptable range, indicating a well-fitting model. CONCLUSION: The Chinese version of the C-DBAS-14 has good reliability and validity among cancer patients. It can be used to measure the sleep beliefs and attitudes of Chinese cancer patients.

Large-Scale Cell Production Based on GMP-Grade Dissolvable Porous Microcarriers.

Researchers in the cell and gene therapy (CGT) industry have long faced a formidable challenge in the efficient and large-scale expansion of cells. To address the primary shortcomings of the two-dimensional (2D) planar culturing system, we innovatively developed an automated closed industrial scale cell production (ACISCP) platform based on a GMP-grade, dissolvable, and porous microcarrier for the 3D culture of adherent cells, including human mesenchymal stem/stromal cells (hMSCs), HEK293T cells, and Vero cells. To achieve large-scale expansion, a two-stage expansion was conducted with 5 L and 15 L stirred-tank bioreactors to yield 1.1 x 1010 hMSCs with an overall 128-fold expansion within 9 days. The cells were harvested by completely dissolving the microcarriers, concentrated, washed and formulated with a continuous-flow centrifuge-based cell processing system, and then aliquoted with a cell filling system. Compared with 2D planar culture, there are no significant differences in the quality of hMSCs harvested from 3D culture. We have also applied these dissolvable porous microcarriers to other popular cell types in the CGT sector; specifically, HEK293T cells and Vero cells have been cultivated to peak cell densities of 1.68 x 107 cells/mL and 1.08 x 107 cells/mL, respectively. This study provides a protocol for using a bioprocess engineering platform harnessing the characteristics of GMP-grade dissolvable microcarriers and advanced closed equipment to achieve the industrial-scale manufacturing of adherent cells.

Obesity- and lipid-related indices as a predictor of obesity metabolic syndrome in a national cohort study.

Objective: Metabolic syndrome is a common condition among middle-aged and elderly people. Recent studies have reported the association between obesity- and lipid-related indices and metabolic syndrome, but whether those conditions could predict metabolic syndrome is still inconsistent in a few longitudinal studies. In our study, we aimed to predict metabolic syndrome by obesity- and lipid-related indices in middle-aged and elderly Chinese adults. Method: A national cohort study that consisted of 3,640 adults (≥45 years) was conducted. A total of 13 obesity- and lipid-related indices, including body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), conicity index (CI), visceral adiposity index (VAI), Chinese visceral adiposity index (CVAI), lipid accumulation product (LAP), a body shape index (ABSI), body roundness index (BRI), and triglyceride glucose index (TyG-index) and its correlation index (TyG-BMI, TyG-WC, and TyG-WHtR), were recorded. Metabolic syndrome (MetS) was defined based on the criteria of the National Cholesterol Education Program Adult Treatment Panel III (2005). Participants were categorized into two groups according to the different sex. Binary logistic regression analyses were used to evaluate the associations between the 13 obesity- and lipid-related indices and MetS. Receiver operating characteristic (ROC) curve studies were used to identify the best predictor of MetS. Results: A total of 13 obesity- and lipid-related indices were independently associated with MetS risk, even after adjustment for age, sex, educational status, marital status, current residence, history of drinking, history of smoking, taking activities, having regular exercises, and chronic diseases. The ROC analysis revealed that the 12 obesity- and lipid-related indices included in the study were able to discriminate MetS [area under the ROC curves (AUC > 0.6, P < 0.05)] and ABSI was not able to discriminate MetS [area under the ROC curves (AUC < 0.6, P > 0.05)]. The AUC of TyG-BMI was the highest in men, and that of CVAI was the highest in women. The cutoff values for men and women were 187.919 and 86.785, respectively. The AUCs of TyG-BMI, CVAI, TyG-WC, LAP, TyG-WHtR, BMI, WC, WHtR, BRI, VAI, TyG index, CI, and ABSI were 0.755, 0.752, 0.749, 0.745, 0.735, 0.732, 0.730, 0.710, 0.710, 0.674, 0.646, 0.622, and 0.537 for men, respectively. The AUCs of CVAI, LAP, TyG-WC, TyG-WHtR, TyG-BMI, WC, WHtR, BRI, BMI, VAI, TyG-index, CI, and ABSI were 0.687, 0.674, 0.674, 0.663, 0.656, 0.654, 0.645, 0.645, 0.638, 0.632, 0.607, 0.596, and 0.543 for women, respectively. The AUC value for WHtR was equal to that for BRI in predicting MetS. The AUC value for LAP was equal to that for TyG-WC in predicting MetS for women. Conclusion: Among middle-aged and older adults, all obesity- and lipid-related indices, except ABSI, were able to predict MetS. In addition, in men, TyG-BMI is the best indicator to indicate MetS, and in women, CVAI is considered the best hand to indicate MetS. At the same time, TyG-BMI, TyG-WC, and TyG-WHtR performed better than BMI, WC, and WHtR in predicting MetS in both men and women. Therefore, the lipid-related index outperforms the obesity-related index in predicting MetS. In addition to CVAI, LAP showed a good predictive correlation, even more closely than lipid-related factors in predicting MetS in women. It is worth noting that ABSI performed poorly, was not statistically significant in either men or women, and was not predictive of MetS.

A novel form of docetaxel polymeric micelles demonstrates anti-tumor and ascites-inhibitory activities in animal models as monotherapy or in combination with anti-angiogenic agents.

Malignant ascites (MA) is caused by intraperitoneal spread of solid tumor cells and results in a poor quality of life. Chemotherapy is a common first-line treatment for patients with MA. Taxotere ® (DTX) is widely used in solid tumor therapies. However, the low water solubility and side effects caused by additives in the formulation restrict the clinical application of docetaxel. HT001 is a clinical stage docetaxel micelle developed to overcome the solubility issue with improved safety profiles. To support clinical development and expand clinical application of HT001, this study used in vitro and in vivo approaches to investigate the anti-tumor effects of HT001 when applied as monotherapy or in combination with anti-angiogenic agents. HT001 demonstrated comparable anti-proliferative activities as docetaxel in a broad range of cancer cell lines in vitro. Furthermore, HT001 suppressed tumor growth in a dose-dependent manner in A549, MCF-7, and SKOV-3 xenograft tumor mouse models in vivo. In a hepatocellular carcinoma H22 malignant ascites-bearing mouse model, HT001 presented a dose-dependent inhibition of ascites production, prolonged animal survival, and reduced VEGF levels. When dosed at 20 mg/kg, the HT001-treated group exhibited curative results, with no ascites formation in 80% of mice at the end of the study while all the mice in the vehicle control group succumbed. Similar results were obtained in HT001 treatment of mice bearing malignant ascites produced by human ovarian cancer ES-2 cells. Notably, the combination of HT001 with Endostar not only significantly reduced ascites production but also prolonged survival of H22 ascites-bearing mice. HT001 showed similar PK and tissue distribution profiles as DTX in non-rodent hosts. Collectively, these results demonstrate potent anti-tumor activity of HT001 in multiple solid tumor models or malignant ascites models, and reveal synergistic effects with anti-angiogenic agents, supporting the clinical development and clinical expansion plans for HT001.

IDO1 can impair NK cells function against non-small cell lung cancer by downregulation of NKG2D Ligand via ADAM10.

Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the rate-limiting step in tryptophan catabolism along the kynurenine (Kyn) pathway and exerts immunosuppressive properties mainly via activation of transcription factor aryl hydrocarbon receptor (AhR) pathway. IDO1 induces NK cells dysfunction via downregulation of the activating receptor NKG2D on NK cells, but whether and how it affects the expression of NKG2D Ligand (NKG2DL) on tumor cells remains unclear. Since a disintegrin and metalloprotease 10 (ADAM10) plays a potential role in the shedding of NKG2DL and the releasing of soluble NKG2DL (sNKG2DL), we investigated how IDO1 modulates the expression of NKG2DL via ADAM10 in non-small cell lung cancer (NSCLC). We found that IDO1 expression was negatively correlated with NKG2DL expression while positively correlated with ADAM10 expression with human lung cancer brain metastasis tissue, NSCLC cells and LLC tumor-bearing mice. IDO1 could regulate ADAM10 expression via IDO1-Kyn-AhR signaling pathway and subsequently regulate NKG2DL expression. IDO1 deficiency led to retarded tumor growth and improved NK cells function in NSCLC mice. IDO1 inhibitors improved NK cells function in vitro and in vivo. The combo of IDO1 inhibitor and NK cells exhibited more therapeutic efficacy than either of the single IDO1 inhibitor or NK cells treatment.

IDO1/TDO dual inhibitor RY103 targets Kyn-AhR pathway and exhibits preclinical efficacy on pancreatic cancer.

Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzing the conversion of tryptophan (Trp) to kynurenine (Kyn) in kynurenine pathway (KP) is involved in the immunosuppression in pancreatic cancer (PC), but the value of IDO1 as an independent prognostic marker for PC is uncertain. Moreover, the correlation between tryptophan 2,3-dioxygenase (TDO), an isozyme of IDO1, and PC is largely unknown. Using TCGA database, the correlation between IDO1 and/or TDO expression and PC patients' survival was analyzed. The expressions of IDO1 and TDO in PC cells and PC mice were examined. The effects of IDO1, TDO or dual inhibition on IDO1 and TDO effector pathway (Aryl hydrocarbon receptor, AhR) and on migration and invasion of PC cells were investigated. The block effect of IDO1/TDO dual inhibitor RY103 on KP was evaluated. The preclinical efficacy of RY103 and its immunomodulatory effect on KPIC orthotopic PC mice and Pan02 tumor-bearing mice were explored. Results showed that IDO1/TDO co-expression is an independent prognostic marker for PC. RY103 can significantly block KP and target Kyn-AhR pathway to blunt the migration and invasion of PC cells, exhibit preclinical efficacy and ameliorate IDO1/TDO-mediated immunosuppression in PC mice.

Evaluation and comparison of the commonly used bioassays of human indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO).

Inhibitors of indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) are potential drugs for the treatment of tumor and neurological diseases. A variety of bioassays have been developed to evaluate IDO1/TDO (IDO1 and/or TDO) inhibitors, with uncertainty regarding how the differences in the assay methods or protocols may influence the assay outcomes. The enzymatic assays of IDO1/TDO are usually performed with NFK assay and Kyn adduct assay while the cellular assays of IDO1 are carried out with Hela assay and HEK293 assay. The present study focused on the comparison of the most common bioassays of IDO1/TDO. In addition, the effects of major factors of bioassays such as reaction time and culture medium on the assay outcomes were evaluated. The study will provide reference for the researchers to select IDO1/TDO inhibitors with bioassays, and promote the development of IDO1/TDO inhibitors.

The interaction between serum uric acid and triglycerides level on blood pressure in middle-aged and elderly individuals in China: result from a large national cohort study.

BACKGROUND: The purpose of the research was to explore the extent of interaction between triglycerides (TG) and serum uric acid (SUA) level with blood pressure (BP) in middle-aged and elderly individuals in China. METHODS: Data were selected from the China Health and Retirement Longitudinal Study (CHARLS), a cross-sectional study. 3345(46.99%) men with average ages of 60.24 ± 9.24 years and 3774 (53.01%) women with average ages of 59.91 ± 9.95 years were included in the study. Differences between gender, or between categories of blood pressure levels were evaluated by t-test or chi-square test. The adjusted associations between various characteristics and BP status were first compared using linear regression models, as appropriate. Then, A general linear model adjusted for confounding factors (socio-demographic characteristics [age, educational levels, marital status, place of residence], health behaviors [cigarette smoking, alcohol drinking, eating habits, social and leisure activities, accidental injury, physical activities], medical history [history of cardiovascular diseases, hepatitis history, antidiabetic drugs, history of antilipidemic medication, anti-hypertensive therapy], metabolic measures [C-reactive protein (CRP), hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), estimated glomerular filtration rate (eGFR), body mass index (BMI)]) was used to examine the synergistic effect of SUA and TG level on BP in middle-aged and elderly individuals in China. RESULTS: Age-adjusted partial Pearson's correlation coefficient showed that SUA and TG level positively correlated with both systolic blood pressure (SBP) and diastolic blood pressure (DBP) in both men and women. Multiple linear regression analysis showed the TG level was significantly and positively associated with SBP and DBP in both men (SBP: ß =0.068, P = 0.001; DBP: ß =0.064, P = 0.002) and women (SBP: ß =0.061, P = 0.002; DBP: ß =0.084, P = 0.000), but SUA were significantly and positively associated with SBP in both men (SBP: ß =0.047, P = 0.013) and women (SBP: ß =0.040, P = 0.028), regardless of other confounding factors. After adjusting for related potential confounders, evidence of interaction between SUA and TG level on SBP (men: ß = - 1.090, P = 0.726; women: ß = - 0.692, P = 0.861) and DBP (men: ß = - 1.026, P = 0.572; women: ß = - 0.794, P = 0.842) was not observed. CONCLUSION: The interaction effect of SUA and TG level on BP was not observed in our study. Moreover, high SUA level was significantly associated with SBP, while high TG level was strongly related to both DBP and SBP.

A stimuli-responsive combination therapy for recovering p53-inactivation associated drug resistance.

Drug resistance is a major hindrance in the anticancer treatment, which encourages the development of effective therapeutic strategies. For the first time, MDM2-mediated p53 degradation was identified as a critical factor for developing acquired resistance of doxorubicin (DOX) in HepG2 tumor spheroids, which could be effectively reversed by MDM2 inhibitor MI-773, thereby improving anticancer effects. Therefore, a pH-sensitive liposomal formulation of DOX and MI-773 (LipD/M@CMCS) were developed for recovering p53-mediated DOX resistance in hepatocellular carcinoma. LipD/M@CMCS were composed of cationic liposomes covered with carboxymethyl chitosan (pI = 6.8), and were stable in the physiological condition (pH 7.4), but rapidly converted to cationic liposomes in tumor acidic microenvironment (pH 6.5), endowing them with tumor specificity and enhanced cellular uptake. We showed that LipD/M@CMCS could not only effectively induce cell apoptosis in HepG2 tumor spheroids, but significantly inhibit tumor growth with minimal adverse effects. In summary, selective regulation of MDM2 in cancer cells is a promising strategy to overcome DOX resistance, and may provide a perspective on the management of malignant tumors.

An octopus-mimic PEGylated peptide as a specific integrin αvß3 inhibitor for preventing tumor progression.

We have developed a multivalent PEGylated RWrNR, named octopus-R, which exhibits good water solubility, biostability, biocompatibility and cancer targeting ability, endowing it with high anticancer potential. Octopus-R represents a promising theranostic agent and holds great potential for improving the management of malignant tumors.

N-Benzyl/Aryl Substituted Tryptanthrin as Dual Inhibitors of Indoleamine 2,3-Dioxygenase and Tryptophan 2,3-Dioxygenase.

Indoleamine 2,3-dioxygenase 1 (IDO1), which catalyzes the initial and rate-limiting step of the kynurenine pathway of tryptophan catabolism, has emerged as a key target in cancer immunotherapy because of its role in enabling cancers to evade the immune system. Tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase 2 (IDO2) catalyze the same reaction and play a potential role in cancer immunotherapy. Starting from our previously discovered tryptanthrin IDO1 inhibitor scaffold, we synthesized novel N-benzyl/aryl substituted tryptanthrin derivatives and evaluated their inhibitory efficacy on IDO1, TDO, and IDO2. Most compounds showed similar high inhibitory activities on both IDO1 and TDO, which were significantly superior over that of IDO2 with magnitude difference. We showed that N-benzyl/aryl substituted tryptanthrin directly interacted with IDO1, TDO, and IDO2, significantly augmented the proliferation of T cells in vitro, blocked the kynurenine pathway, and suppressed tumor growth when administered to LLC and H22 tumor-bearing mice.

Smart pH-Sensitive Nanogels for Enhancing Synergistic Anticancer Effects of Integrin αvß3 Specific Apoptotic Peptide and Therapeutic Nitric Oxide.

Apoptotic peptide (kla), which can trigger the mitochondria-mediated apoptotic programmed cell death, has been widely recognized as a potential anticancer agent. However, its therapeutic potential has been significantly impaired by its poor biostability, lack of tumor specificity, and particularly low cellular uptake. Herein, a linear peptide Arg-Trp-d-Arg-Asn-Arg (RWrNR) was identified as an integrin αvß3 specific ligand with a nanomolar dissociation constant (Kd = 0.95 nM), which can greatly improve kla antitumor activity (IC50 = 8.81 µM) by improving its cellular uptake, compared to the classic integrin-recognition motif c-RGDyK (IC50 = 37.96 µM). Particularly, the RWrNR-kla conjugate can be entrapped in acidic sensitive nanogels (RK/Parg/CMCS-NGs), composed of poly-l-arginine (Parg) and carboxymethyl chitosan (CMCS, pI = 6.8), which can not only carry out controlled release of RWrNR-kla in response to the tumor acidic microenvironment, and consequently enhance its tumor specificity and cell internalization, but also trigger tumor-associated macrophages to generate nitric oxide, leading to enhanced synergistic anticancer efficacy. Importantly, RK/Parg/CMCS-NGs have been proven to effectively activate the apoptosis signaling pathway in vivo and significantly inhibit tumor growth with minimal adverse effects. To summarize, RK/Parg/CMCS-NGs are a promising apoptotic peptide-based therapeutics with enhanced tumor accumulation, cytosolic delivery, and synergistic anticancer effects, thereby holding great potential for the treatment of malignant tumors.

Novel Integrin αvß3-Specific Ligand for the Sensitive Diagnosis of Glioblastoma.

Integrin αvß3 is a cell adhesion molecule involved in the progression and invasion of glioblastoma, making it an attractive target for the diagnosis of glioblastoma. Although some integrin αvß3 specific ligands, such as RGD and its mimetic peptides (Cilengitide), have been devoted in detecting glioblastoma, their clinical practices have been limited due to low specificity and affinity. Herein, we have identified a linear peptide RWrNK, containing an unnatural d-arginine (r), as the integrin αvß3-specific ligand. RWrNK shows high binding affinity to integrin αvß3 with a Kd value of 1.6 nM, which is 2-fold higher than Cilengitide (3.2 nM), a well-established integrin αvß3 ligand. In addition, RWrNK can not only rapidly transport in human glioblastoma U87MG cells but effectively label U87MG tumor spheroids, compared to Cilengitide, indicating that it possesses an ability to sensitively detect glioblastoma. Importantly, RWrNK can pass through blood-brain tumor barrier (BBTB) and selectively accumulate in orthotopic U87MG tumor within 2 h, allowing for imaging glioblastoma in vivo with high sensitivity and specificity. Overall, RWrNK has the great potential in theranostic applications for glioblastoma, in consideration of its high specificity and affinity for integrin αvß3.

Synergistic Amplification of Oxidative Stress-Mediated Antitumor Activity via Liposomal Dichloroacetic Acid and MOF-Fe2.

Cancer cells are susceptible to oxidative stress; therefore, selective elevation of intracellular reactive oxygen species (ROS) is considered as an effective antitumor treatment. Here, a liposomal formulation of dichloroacetic acid (DCA) and metal-organic framework (MOF)-Fe2+ (MD@Lip) has been developed, which can efficiently stimulate ROS-mediated cancer cell apoptosis in vitro and in vivo. MD@Lip can not only improve aqueous solubility of octahedral MOF-Fe2+ , but also generate an acidic microenvironment to activate a MOF-Fe2+ -based Fenton reaction. Importantly, MD@Lip promotes DCA-mediated mitochondrial aerobic oxidation to increase intracellular hydrogen peroxide (H2 O2 ), which can be consequently converted to highly cytotoxic hydroxyl radicals (•OH) via MOF-Fe2+ , leading to amplification of cancer cell apoptosis. Particularly, MD@Lip can selectively accumulate in tumors, and efficiently inhibit tumor growth with minimal systemic adverse effects. Therefore, liposome-based combination therapy of DCA and MOF-Fe2+ provides a promising oxidative stress-associated antitumor strategy for the management of malignant tumors.

Novel Gold Nanorod-Based HR1 Peptide Inhibitor for Middle East Respiratory Syndrome Coronavirus.

Middle East respiratory syndrome coronavirus (MERS-CoV) causes a severe acute respiratory syndrome-like illness with high pathogenicity and mortality due to the lack of effective therapeutics. Currently, only few antiviral agents are available for the treatment of MERS, but their effects have been greatly impaired by low antiviral activity, poor metabolic stability, and serious adverse effects. Therefore, the development of effective treatment for MERS is urgently needed. In this study, a series of heptad repeat 1 (HR1) peptide inhibitors have been developed to inhibit HR1/HR2-mediated membrane fusion between MERS-CoV and host cells, which is the major pathway of MERS-CoV-induced host infections. Particularly, peptide pregnancy-induced hypertension (PIH) exhibits potent inhibitory activity with IC50 of 1.171 µM, and its inhibitory effects can be further increased to 10-fold by forming a gold nanorod complex (PIH-AuNRs). In addition, PIH-AuNRs display enhanced metabolic stability and biocompatibility in vitro and in vivo and, therefore, effectively prevent MERS-CoV-associated membrane fusion. In summary, PIH-AuNRs represent a novel class of antiviral agents and have a great potential in treating MERS in the clinic.

Effect of the loam inter-layer on the migration and breakthrough of benzene under constant flow in the unsaturated zone: column experiments.

The reliable prediction of transport and attenuation of dissolved-phase contamination in the unsaturated zone is a complex and multi-process problem. Based on the adsorption properties of soil samples to solutes, the soil column test and laboratory analysis were carried out in this study. The effects of the loam inter-layer on the migration and breakthrough of the characteristic pollutant benzene and non-absorbent Br- were studied. The results showed that the relatively high clay content of the inter-layer significantly changed the BTC (breakthrough curve). It not only delayed the migration time of benzene into the aquifer but also to some extent produced an attenuation effect, effectively reducing the content of the characteristic pollutants through the unsaturated zone. The dispersion coefficient was obtained through the measured Br-. The theoretical values were calculated and compared with the experimental data by using a one-dimensional unsaturated solute transport equation. The result was basically consistent, which proved the validity and reliability of the model. Through the BTC of benzene, the retardation factor was obtained and used to describe the influence of the loam inter-layer on the migration and breakthrough, which could provide the basis for the accurate modeling of groundwater remediation projects.

Autotaxin determines colitis severity in mice and is secreted by B cells in the colon.

Autotaxin (ATX or ENPP2) is a secreted lysophospholipase D that produces lysophosphatidic acid (LPA), a pleiotropic lipid mediator acting on specific GPCRs. ATX and LPA have been implicated in key (patho)physiologic processes, including embryonic development, lymphocyte homing, inflammation, and cancer progression. Using LPA receptor knockout mice, we previously uncovered a role for LPA signaling in promoting colitis and colorectal cancer. Here, we examined the role of ATX in experimental colitis through inducible deletion of Enpp2 in adult mice. ATX expression was increased upon induction of colitis, whereas ATX deletion reduced the severity of inflammation in both acute and chronic colitis, accompanied by transient weight loss. ATX expression in lymphocytes was strongly reduced in Rag1-/- and µMT mice, suggesting B cells as a major ATX-producing source, which was validated by immunofluorescence and biochemical analyses. ATX secretion by B cells from control, but not Enpp2 knockout, mice led to ERK activation in colorectal cancer cells and promoted T cell migration. We conclude that ATX deletion suppresses experimental colitis and that B cells are a major source of ATX in the colon. Our study suggests that pharmacological inhibition of ATX could be a therapeutic strategy in colitis.-Lin, S., Haque, A., Raeman, R., Guo, L., He, P., Denning, T. L., El-Rayes, B., Moolenaar, W. H., Yun, C. C. Autotaxin determines colitis severity in mice and is secreted by B cells in the colon.