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Androgen receptor (AR) plays a central role in driving prostate cancer (PCa) progression. How AR promotes this process is still not completely clear. Herein, we used single-cell transcriptome analysis to reconstruct the transcriptional network of AR in PCa. Our work shows AR directly regulates a set of signature genes in the ER-to-Golgi protein vesicle-mediated transport pathway. The expression of these genes is required for maximum androgen-dependent ER-to-Golgi trafficking, cell growth, and survival. Our analyses also reveal the signature genes are associated with PCa progression and prognosis. Moreover, we find inhibition of the ER-to-Golgi transport process with a small molecule enhanced antiandrogen-mediated tumor suppression of hormone-sensitive and insensitive PCa. Finally, we demonstrate AR collaborates with CREB3L2 in mediating ER-to-Golgi trafficking in PCa. In summary, our findings uncover a critical role for dysregulation of ER-to-Golgi trafficking expression and function in PCa progression, provide detailed mechanistic insights for how AR tightly controls this process, and highlight the prospect of targeting the ER-to-Golgi pathway as a therapeutic strategy for advanced PCa.

Elevated Epstein-Barr virus (EBV) DNA load is common in lymphomas. However, it remains unclear whether the disparity in viral load and its prognostic value in lymphomas are correlated with Epstein-Barr encoding region (EBER) status. In this retrospective multicenter study, we collected the data of pretreatment whole blood EBV DNA (pre-EBV DNA) and EBER status and evaluated their disparity and prognostic values in lymphomas. A total of 454 lymphoma patients from December 2014 to August 2020 were retrospectively retrieved. Mann-Whitney U test, Kruskal-Wallis test and Bonferroni's adjustment were used to explore the disparity of EBV DNA and EBER status in lymphomas. Time-dependent receiver operating characteristic analysis and MaxStat analysis were used to determine optimal cutoff points of pre-EBV DNA load. Univariable and multivariable Cox proportional hazards models were established for the estimation of prognostic factors. The positive rate of EBV DNA in natural killer T-cell lymphoma (NKTL) patients was higher than that in diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and Hodgkin lymphoma (HL) patients, and the median positive pre-EBV copy number of NKTL was also higher than that of FL and DLBCL. EBV DNA could clearly distinguish the prognosis of DLBCL, NKTL, HL and peripheral T-cell lymphoma, and the integration of EBER status and EBV DNA could differentiate the prognosis of HL patients. Multivariable results revealed that pre-EBV DNA load had an effect on the prognosis of NKTL, FL and DLBCL. The status of pre-EBV DNA and EBER were disparate. Whole blood pre-EBV DNA predicted the prognosis of lymphomas, and the combination of EBV and EBER status could differentiate the prognosis of HL.

Sitting comfort is primarily determined by the cushioning capability of the seat foundation. Limited literature has been found related to the effects that different sized human buttocks had on the cushioning capability of the seat foundation. Moreover, there is no testing method specialized to measure the load-deformation behavior of foam cushions that imitates the sitting behavior between indenters with different sizes and seat support. This study investigated the effects of various indenter diameters (20 cm, 30 cm, 36 cm, 41 cm, 51 cm, and 58 cm), foam stiffness levels (high and low), and seat bases (spring versus solid flat panel) on the compressive load-deformation behavior of upholstered seat foundations. The load-deformation curves of all the tested foam-seat base combinations exhibited three typical regions, i.e., linear elasticity, plateau, and densification, when subjected to the loads applied through different indenter diameters. Statistical results indicated that the primary effects of the indenter diameter, foam stiffness level, and seat base had significant effects on the spring constants, which represented the slopes of lines in these three regions. In addition, a regression technique was proposed to derive power equations for the estimation of the spring constants of a seat foundation as a function of the indenter diameter, foam material stiffness, and seat base type.

Panaxatriol saponins (PTS) have a long history in the treatment of stroke. In our previous experiments, PTS has been found to alleviate ischemic stroke and play a role through regulating the inflammatory response, but the specific mechanism of its regulation is still unclear. Cell viability was determined by MTT assay. Expressions of polarization-related proteins CD16, CD68, ARG1 and CD206; inflammatory factors interleukin-1β (IL-1β); inducible nitric oxide synthase (iNOS); monocyte chemotactic protein 1(MCP-1) and cyclooxygenase-2 (COX-2); apoptosis-related proteins pro-caspase3; bax; caspase3 and bcl-2; and STAT3 and p-STAT3 were detected by western blot. ELISA was used to detect the expression of inflammatory-related factors in cells. The apoptosis rate was detected by flow cytometry. We found that the survival rate of oxygen sugar deprivation/reoxygenation (OGD/R) cells increased obviously after PTS treatment in a dose-dependent manner. PTS can promote M2 polarization of microglial cells (BV2) and inhibit inflammatory response of OGD/R cells, accompanied by decreased expression of inflammatory factors IL-1β, iNOS, MCP-1, and COX-2. PTS inhibited apoptosis of OGD/R cells and was accompanied by decreased expression of apoptotic proteins Bax and caspase3 and increased expression of Bcl-2. We also found that PTS activated STAT3 levels in BV2 cells. After the addition of STAT3 inhibitor Stattic, it was found that PTS could promote M2 polarization of BV2 cells by activating the STAT3 pathway, thus inhibiting cell inflammation and apoptosis. PTS promoted M2 polarization in microglia cells by activating the STAT3 pathway, thereby reducing cell inflammation and apoptosis after glucose/oxygen deprivation.

Objective: To observe the clinical effect of mesotherapy with nanochip for facial rejuvenation.Methods: 24 volunteers with aging skin were treated with a polycomponent formulation – NCTF® BOOST 135...

Background: BRCA1 plays critical roles in mammary gland development and mammary tumorigenesis. And loss of BRCA1 induces mammary tumors in a stochastic manner. These tumors present great heterogeneity at both intertumor and intratumor levels. Methods: To comprehensively elucidate the heterogeneity of BRCA1 deficient mammary tumors and the underlying mechanisms for tumor initiation and progression, we conducted bulk and single cell RNA sequencing (scRNA-seq) on both mammary gland cells and mammary tumor cells isolated from Brca1 knockout mice. Results: We found the BRCA1 deficient tumors could be classified into four subtypes with distinct molecular features and different sensitivities to anti-cancer drugs at the intertumor level. Whereas within the tumors, heterogeneous subgroups were classified mainly due to the different activities of cell proliferation, DNA damage response/repair and epithelial-to-mesenchymal transition (EMT). Besides, we reconstructed the BRCA1 related mammary tumorigenesis to uncover the transcriptomes alterations during this process via pseudo-temporal analysis of the scRNA-seq data. Furthermore, from candidate markers for BRCA1 mutant tumors, we discovered and validated one oncogene Mrc2, whose loss could reduce mammary tumor growth in vitro and in vivo. Conclusion: Our study provides a useful resource for better understanding of mammary tumorigenesis induced by BRCA1 deficiency.

The human genome is mostly transcribed, yielding a rich repository of noncoding transcripts that are involved in a myriad of biological processes including cancer. However, how many noncoding transcripts such as long noncoding RNAs (lncRNA) function in cancer is still unclear. This study identified a novel set of clinically relevant androgen-regulated lncRNAs in prostate cancer. Among this group, LINC00844 was demonstrated to be a direct androgen-regulated target that is actively transcribed in androgen receptor (AR)–dependent prostate cancer cells. The expression of LINC00844 is higher in normal prostate compared with malignant and metastatic prostate cancer clinical specimens, and patients with low expression had a poor prognosis and significantly increased biochemical recurrence, suggesting LINC00844 functions in suppressing tumor progression and metastasis. Indeed, in vitro loss-of-function studies revealed that LINC00844 prevents prostate cancer cell migration and invasion. Moreover, findings from gene expression profiling analysis indicated that LINC00844 functions in trans, affecting global androgen-regulated gene transcription. Mechanistic evidence reveals that LINC00844 is important in facilitating AR binding to the chromatin. Finally, LINC00844 mediates its phenotypic effects in part by activating the expression of NDRG1, a crucial cancer metastasis suppressor. Collectively, LINC00844 is a novel coregulator of AR that plays a central role in the androgen transcriptional network and the development and progression of prostate cancer. Implications: This study highlights the function of the lncRNA, LINC00844, in regulating global AR-regulated genes in prostate cancer by modulating AR binding to chromatin.

BACKGROUND Upper gastrointestinal bleeding (UGIB) is a common complication of acute ischemic stroke (AIS), but the effect of UGIB on the prognosis of middle-aged AIS patients is not clear. METHODS Patients with AIS admitted to our hospital from January 2011 to December 2015 were eligible to be included in this study. All included patients were divided into UGIB and non-UGIB groups. Some clinical characteristics were retrospectively collected. Primary outcomes were all-cause mortality within 1, 3, and 5 years, as well as the incidence of stroke recurrence. Cox proportional hazards regression analyses were used to determine the effect of UGIB on 5-year mortality and the incidence of stroke recurrence. Logistic regression was also used to identify the predictors of UGIB in AIS patients. RESULTS A total of 405 AIS patients were included in this study and then divided into UGIB and non-UGIB groups. The mean age of the UGIB group and non-UGIB group was 61.5±9.6 and 53.1±14.0 years, respectively (P

Background Neonatal meningitis is a severe infectious disease of the central nervous system with high morbidity and mortality. Ureaplasma parvum is extremely rare in neonatal central nervous system infection. Case presentation We herein report a case of U. parvum meningitis in a full-term neonate who presented with fever and seizure complicated with subdural hematoma. After hematoma evacuation, the seizure disappeared, though the fever remained. Cerebrospinal fluid (CSF) analysis showed inflammation with CSF pleocytosis (1135–1319 leukocytes/μl, mainly lymphocytes), elevated CSF protein levels (1.36–2.259 g/l) and decreased CSF glucose (0.45–1.21 mmol/l). However, no bacterial or viral pathogens in either CSF or blood were detected by routine culture or serology. Additionally, PCR for enteroviruses and herpes simplex virus was negative. Furthermore, the CSF findings did not improve with empirical antibiotics, and the baby experienced repeated fever. Thus, we performed metagenomic next-generation sequencing (mNGS) to identify the etiology of the infection. U. parvum was identified by mNGS in CSF samples and confirmed by culture incubation on mycoplasma identification medium. The patient’s condition improved after treatment with erythromycin for approximately 5 weeks. Conclusions Considering the difficulty of etiological diagnosis in neonatal U. parvum meningitis, mNGS might offer a new strategy for diagnosing neurological infections.

The pressure distribution is one of popular objective measurements for sitting comfort, but a few studies were found for the pressure distribution between subjects with different body mass index and office chair . The effects of sitting posture, body mass index, gender, and the types of office chair (adjustable and non-adjustable) on sitting pressure distribution were investigated in this study. 18 subjects with different body mass indexes (overweight, normal weight and under weight) completed five different sitting postures in the order of forward-watching screen, forward-writing, backward-typing, backward-bow one’s head, and backward-cross legged. The outcome demonstrated that the seat adjustable or not, the type of sitting posture has significant influence on the average pressure, maximum pressure gradient and pressure distribution uniformity. Gender and body mass index have significant effects on the circular pressure gradient. Results of sitting pressure distribution obtained in this research, could strengthen the particularity of the body shape consideration in the design of office chairs.

There are no licensed drugs for nonalcoholic fatty liver disease (NAFLD), and there is a lack of consensus on the best outcome measures for controlled trials. This systematic review aimed to evaluate the efficacy of GLP‐1 RAs in the management of NAFLD, the degree of heterogeneity in trial design and the robustness of conclusions drawn from these clinical trials. We searched publication databases and clinical trial registries through 2 November 2019 for clinical trials with NAFLD. We evaluated improvements in histological findings, noninvasive markers of hepatic steatosis, inflammation, and fibrosis, insulin resistance and anthropometric measures. Our final analysis included 24 clinical trials, comprising 6313 participants with a mean duration of 37 weeks. Four clinical trials, including RCT (n = 1), single‐arm studies (n = 2) and case series studies (n = 1), used biopsy‐confirmed liver histological change as their end‐points. The remaining studies (n = 20) used surrogate end‐points. GLP‐1 RAs were effective for the improvement in hepatic inflammation, hepatic steatosis and fibrosis. More importantly, GLP‐1 RAs showed promise in improving the histological features of NASH. In addition, 8 ongoing trials were identified. In this systematic review of published and ongoing clinical trials of the efficacy of GLP‐1RAs for NAFLD, we found that GLP‐1 RAs are effective for hepatic steatosis and inflammation, with the potential to reverse fibrosis. Further prospective studies of sufficient duration using histological end‐points are needed to fully assess the efficacy of GLP‐1 RAs in the management of NAFLD., This systematic review of published and ongoing clinical trials found that GLP‐1 RAs are effective for hepatic steatosis and inflammation, with the potential to reverse fibrosis. Further prospective studies of sufficient duration using histological end‐points are needed to fully assess the efficacy of GLP‐1 RAs in the management of NAFLD.

Early intervention with fecal microbiota transplantation (FMT) improves the growth performance and intestinal barrier function of piglets. Accelerating intestinal oxygen concentration is beneficial for symbiotic bacterial colonization. Saccharomyces boulardii (SB) is an aerobic fungus, which may contribute to the colonization of anaerobic symbiotic bacteria by competing for oxygen. Clostridium butyricum (CB) improves intestinal barrier function and performance, via regulating the gut microbiota composition of piglets. The objective of this study was to investigate the effect of early intervention with FMT combining CB and SB on growth performance, diarrhea, and intestinal barrier function in piglets. A total of 77 litters of neonatal piglets assigned to one of six treatments, which treated with antibiotics (AB), placebo (CON), and FMT (FMT), FMT-added CB (FMT+C), FMT-added SB (FMT+S), and FMT-added CB and SB (FMT+C+S), respectively. FMT+C+S treated piglets had higher body weight (BW) and average daily gain (ADG) both in weaning and finial period, and it significantly increased the levels of fecal mucin-2 (MUC2), fecal short-chain fatty acids (SCFAs), and relative abundance of fecal Lactobacillus spp., and Bifidobacterium genus. Moreover, early intervention with FMT+C+S reduced the diarrhea rate during the experiment. FMT+C+S also decreased the level of plasma diamine oxidase (DAO) and D-lactate (D-LA), and relative abundance of fecal E. coli during the suckling period. In summary, early intervention with FMT combining CB and SB improved the growth performance, intestinal barrier function, fecal SCFAs concentration, and fecal Lactobacillus and Bifidobacterium of piglets.

BACKGROUND Epithelial-mesenchymal transition (EMT) is an essential progress for tumor cell invasion to both epithelial and non-epithelial cancers, and zinc finger E-box-binding homeobox 1/2 (ZEB1/2) is a well-known promoter of EMT. In glioma cell lines, both ZEB1 and ZEB2 have been demonstrated to facilitate cancer cell proliferation and invasion with experiments in vitro. However, the clinical significance of ZEB1 and ZEB2 in glioblastoma (GBM) is still controversial. MATERIAL AND METHODS We detected the expression of ZEB1 and ZEB2 in 91 cases of GBM with immunohistochemistry and investigated the correlation between clinicopathological factors and ZEB family expression with Fisher test. By univariate analysis with Kaplan-Meier test, we explored the prognostic significance of ZEB1/2 expression and the clinicopathological factors in GBM. By multivariate analysis with the Cox regression model, we identified the independent prognostic factors in GBM. RESULTS The percentages of ZEB1 high expression and ZEB2 high expression were 31.9% (29/91) and 41.9% (36/91), respectively. High expression of ZEB2 was significantly associated with lower survival rate of GBM patients (P=0.001). ZEB2, lower KPS score (P=0.004), gross total resection (P

Hierarchical porous sludge-derived activated carbon coated on macroporous silicon carbide (SiC) foams substrate has been facilely fabricated via a simple one-step strategy by utilizing sludge as carbon source, and jointly using zinc chloride and hexadecanol as pore forming agents. The sludge-derived carbon has been confirmed to be hierarchical macro-meso-microporous structure based on detailed characterization by scanning electron microscopy (SEM), X-ray diffraction (XRD), Raman spectra and nitrogen adsorption-desorption measurement. The adsorption tests showed that the hierarchical porous sludge-derived activated carbon fabricated by one-step pore-forming (zinc chloride and hexadecanol microemulsion mixture) possesses excellent adsorption capacity (259.9mgg-1, breakthrough time reach 90min and saturation end-time up to 140min) of methyl mercaptan (CH3SH). The excellent adsorption performance can be attributed to the macroporous SiC foam skeleton and the mesopores channel formed by nonionic surfactant hexadecanol micelles, as well as the micropores activated by ZnCl2 as odor capture sites. The proposed pore-forming strategy paves an avenue for the sludge disposal and even the development of bio-derived materials.

Elevated Epstein-Barr virus (EBV) DNA load is common in lymphomas. However, it remains unclear whether the disparity in viral load and its prognostic value in lymphomas are correlated with EBER status. In this retrospective multicenter study, we collected the data of pretreatment whole blood EBV DNA (pre-EBV DNA) and EBER status and evaluated their disparity and prognostic values in lymphomas. A total of 454 lymphoma patients from December 2014 to August 2020 were retrospectively retrieved. Mann-Whitney U test, Kruskal-Wallis test, and Bonferroni's adjustment were used to explore the disparity of EBV DNA and EBER status in lymphomas. Time-dependent receiver operating characteristic analysis and MaxStat analysis were used to determine optimal cut-off points of pre-EBV DNA load. Univariable and multivariable Cox proportional hazards models were established for the estimation of prognostic factors. The positive rate of EBV-DNA in NKTL patients was higher than that in DLBCL, FL, and HL patients, and the median positive pre-EBV copy number of NKTL was also higher than that of FL and DLBCL. EBV-DNA could clearly distinguish the prognosis of DLBCL, NKTL, HL and PTCL, and the integration of EBER status and EBV DNA could differentiate the prognosis of HL patients. Multivariable results revealed that pre-EBV DNA load had an effect on the prognosis of NKTL, FL and DLBCL. The status of pre-EBV DNA and EBER were disparate. Whole blood pre-EBV DNA predicted the prognosis of lymphomas, and the integration of EBV and EBER status could differentiate the prognosis of HL Disclosures No relevant conflicts of interest to declare.

For most materials, the sign of Poisson's ratio does not change under tension and compression, i.e., it is positive or negative at the same time. However, this paper reports the design of a novel metamaterial consisting of rods and ropes whose cells have a total of four load-bearing modes. These load-bearing modes will switch with each other upon changing the external loading mode, causing them to exhibit a variety of peculiar properties. For example, a positive Poisson's ratio under tension and a negative Poisson's ratio under compression were achieved along the vertical direction. Secondly, the ratio of the tensile elastic modulus to the compressive elastic modulus of this material could be adjusted over a wide range of 0.1– 40, which depended on the stiffness of the rope and the angle of the rod. Theoretical and numerical analyses showed that the stiffness matrix of the designed metamaterial was asymmetric, which breaks the classical model in which the stiffness matrix of conventional materials is symmetric. The use of thin rods instead of ropes is also discussed, and a simplified analysis method is given. This material is expected to have applications in many fields, such as wave modulation, biomedical devices, etc.

The compression–torsion coupling metamaterials constructed by cells based on chiral mechanism of inclined rods with weak transverse constraints, display superior compression–torsion properties among the metamaterials reported previously. Aiming at metamaterials of this type, a general representative cell is extracted to reveal the relationship between the load and the deformation with considering the compression–torsion coupling effect. The stiffness matrix of the chiral 3D cell is derived based on Euler beam theory and applying dummy-load method, which is expressed as functions of the geometry parameters of cell structures and the mechanical properties of base material. The analytical predictions show good agreement with the numerical simulations. Results show that there exist optimal inclined angles of the rods corresponding to the maximal shear stiffness and the maximal compression–torsion coupling stiffness, respectively, which are both determined by the ratio of circular loop diameter to inclined rod length. This work provides guidelines for the design and analysis of compression–torsion coupling metamaterials, and opens a new avenue for theoretically analyzing the deformation coupling problem.

Auxetic materials exhibit many superior properties but drawback in low stiffness owe to the substantial porosity. Some narrow-ribs enhanced auxetic honeycombs have been designed for improving the in-plane stiffness. For these narrow-ribs enhanced auxetic structures, local buckling likely appears as the reinforcing walls are designed in low thickness for superior auxeticy. In this paper, a novel narrow-ribs enhanced auxetic honeycomb is designed by embedding rhombus into each cell of the normal re-entrant hexagonal honeycomb (NRHH). Analytical model is built to investigate the elastic behaviors of the new proposed honeycomb under uniaxial compression, in which the incremental method is firstly introduced for post-local-buckling analysis. Numerical simulations are carried out to verify the analytical results. It is interesting that bilinear elastic characteristic is found for the stress-strain and transverse strain-longitudinal strain curves of the new proposed honeycomb on account of the local buckling. Parameters studies are performed and the new proposed honeycomb is proved to exhibit superior mechanical properties compared to other narrow-ribs enhanced honeycombs. Significantly, the incremental method brought forward in the present paper for the local buckling analysis can be popularized to other honeycombs enhanced with narrow-ribs. Thus, the bilinear elastic characteristic is a general feature for these honeycombs.

The objective of the study was to investigate the correlation and consistency between nasopharyngoscopy (NP) and magnetic resonance imaging (MRI) in locating the obstruction planes in obstructive sleep apnea hypopnea syndrome (OSAHS) patients with different pathogenetic conditions. Anatomical examination of the upper airway was performed in OSAHS patients [including 32 mild cases (MI), 31 moderate cases (MO), and 30 severe cases (SE)] by NP and MRI. The differences between the three groups were analyzed to compare the correlation and consistency between the two examination methods. There were statistically significant differences in the collapse degree, cross-sectional area, left–right diameter, and anteroposterior diameter of the soft palate region, retroglossal region, and post-epiglottic region, as well as in the total thickness of the posterior epiglottic lateral wall. There was a positive correlation between the collapse degree and the cross-sectional area in Group MI, while a negative correlation was found in Group MO. There was a statistically significant difference in the kappa value of the posterior epiglottic obstruction plane of Group SE between the examination methods (kappa = 0.39, p = 0.007). Nasopharyngoscopy and MRI can depict soft tissue compliance and anatomical features of the upper airway in OSAHS patients, though they lack good correlation and consistency in locating the obstruction plane.

The RXR agonist (triphenyltin, TPT) and the RXR antagonist (UVI3003) both show teratogenicity and, unexpectedly, induce similar malformations in Xenopus tropicalis embryos. In the present study, we exposed X. tropicalis embryos to UVI3003 in seven specific developmental windows and identified changes in gene expression. We further measured the ability of UVI3003 to activate Xenopus RXRα (xRXRα) and PPARγ (xPPARγ) in vitro and in vivo. We found that UVI3003 activated xPPARγ either in Cos7 cells (in vitro) or Xenopus embryos (in vivo). UVI3003 did not significantly activate human or mouse PPARγ in vitro; therefore, the activation of Xenopus PPARγ by UVI3003 is novel. The ability of UVI3003 to activate xPPARγ explains why UVI3003 and TPT yield similar phenotypes in Xenopus embryos. Our results indicate that activating PPARγ leads to teratogenic effects in Xenopus embryos. More generally, we infer that chemicals known to specifically modulate mammalian nuclear hormone receptors cannot be assumed to have the same activity in non-mammalian species, such as Xenopus. Rather they must be tested for activity and specificity on receptors of the species in question to avoid making inappropriate conclusions.

In the present work, a new design of honeycomb is proposed by embedding the rhombic configuration into the normal re-entrant hexagonal honeycomb (NRHH), in order to enhance the honeycomb’s in-plane mechanical properties. Both theoretical analysis and numerical simulations are employed to calculate the in-plane mechanical properties of the new honeycomb under uniaxial compression, including Young’s modulus, Poisson’s ratio and critical buckling strength. The results show that the new honeycomb can maintain auxetic performance, while both the in-plane Young’s modulus and the critical buckling strength are significantly improved compared to the NRHH. Comparisons between the present design and other exiting enhanced periodic topologies are also carried out. With respect to them, the present design features superior performances. For these outstanding properties, this layout may provide a new concept for the optimization and design of auxetic materials.

Microplastic fibers (MFs) pollute aquatic habitats globally via sewage release, stormwater runoff, or atmospheric deposition. Of the synthetic MFs, polyester (PES) and polypropylene (PP) are the most common. Field studies show that fish ingest large quantities of MFs. However, few laboratory studies have addressed host responses, particularly at the organ and tissue levels. Adult Japanese medaka (Oryzias latipes), a laboratory model fish, were exposed to aqueous concentrations of PES or PP MFs (10,000 MFs/L) for 21 days. Medaka egested 1,367 ± 819 PES MFs (0.1 ± 0.04 mg) and 157 ± 105 PP MFs (1.4 ± 0.06 mg) per 24 hrs, with PP egestion increasing over time. Exposure did not result in changes in body condition, gonadosomatic- or hepatosomatic indices. PES exposure resulted in no reproductive changes, but females exposed to PP MFs produced more eggs over time. MF exposure did not affect embryonic mortality, development, or hatching. Scanning electron microscopy (SEM) of gills revealed denuding of epithelium on arches, fusion of primary lamellae, and increased mucus. Histologic sections revealed aneurysms in secondary lamellae, epithelial lifting, and swellings of inner opercular membrane that altered morphology of rostral most gill lamellae. SEM and histochemical analyses showed increased mucous cells and secretions on epithelium of foregut; however, overt abrasions with sloughing of cells were absent. For these reasons, increased focus at the tissue and cell levels proved necessary to appreciate toxicity associated with MFs.

Aberrant activation of signaling pathways is frequently observed and reported to be associated with the progression and poor prognosis of prostate cancer (PCa). We aimed to identify key biological processes regulated by androgen receptor (AR) using gene co-expression network from single cell resolution. The bimodal index was used to evaluate whether two subpopulations exist among the single cells. Gene expression among single cells revealed averaging pitfalls and bimodality pattern. Weighted gene co-expression network analysis (WGCNA) was used to identify modules of highly correlated genes. Twenty-nine gene modules were identified and AR-regulated modules were screened by significantly overlapping reported androgen induced differentially expressed genes. The biological function &ldquo, generation of precursor metabolites and energy&rdquo, was significantly enriched by AR-regulated modules with bimodality, presenting differential androgen response among subpopulations. Integrating with public ChIP-seq data, two genes FECH, and CROT has AR binding sites. Public in vitro studies also show that androgen regulates FECH and CROT. After receiving androgen deprivation therapy, patients lowly express FECH and CROT. Further survival analysis indicates that FECH/CROT signature can predict PCa recurrence. We reveal the heterogeneous function of &ldquo, upon androgen stimulation from the perspective of single cells. Inhibitors targeting this biological process will facilitate to prevent prostate cancer progression.

Dietary fibers with high water-binding capacity (WBC), swelling capacity (SC) and fermentability regulate food intake and intestinal microbiota. However, dietary fibers with such properties are generally rare or expensive. We evaluated SC, WBC, fermentability and bacterial shifts during in vitro fermentations of guar gum (GG), xanthan gum (XG) and the combined gum (CG) of XG and GG. SC and WBC were enhanced by the combination of GG and XG. Fermentation of CG showed similar Short chain fatty acids production and lower molecular weight compared with GG. Analyzing of fermentation kinetics by logistic-exponential model, initial fractional rate of degradation of CG were remarkable higher than GG. Microbiota analysis revealed that GG enriched Fusobacterium, Bacteriodes and Prevotella_9, and CG lead to promotion of Sphaerochaeta, Prevotella_9, Bacteroides and Christensenellaceae_R-7_group. These data suggest that combination of XG to GG changed hydration and fermentation characteristics of GG, and CG resulted in promotion of beneficial microbiota.

Struts with different thermal expansion coefficients are employed to design novel 3D chiral metamaterials, which interestingly show twist deformation under both temperature variation and uniaxial load. Analytical expressions on the twist angle of the proposed metamaterials are established to relate with geometry of cell structure and material properties of struts, showing good agreement with numerical simulations. Both theoretical analysis and numerical simulations suggest that the tensile-torsion and thermal-torsion coupling effects of the metamaterials can be tuned by tailoring cells’ geometric configuration and material selection. It is shown that the inclined rods’ angle and the rods’ stiffness play important roles in both the thermal-torsion and tensile-torsion coupling effects. Based on that, the conditions corresponding to maximum tensile-torsion and thermal-torsion coupling effects were determined, respectively. Besides, the thermal-torsion coupling effect is also proportional to the rods’ thermal expansion coefficients. Moreover, it is shown that the two coupling effects are strongly correlated to each other. The contour maps of the twist angle of the metamaterial are obtained under simultaneous temperature change and uniaxial load. The proposed metamaterial is expected to find applications in sensors, actuators and wave convertors, especially in environments of alternating temperature changes.

Deoxynivalenol (DON), a common mycotoxin, usually induces oxidative stress and intestinal injury of humans and animals. This study aims to investigate the protective effect of Gly-Pro-Ala (GPA) peptide, isolated from fish skin gelatin hydrolysate fraction 3 (FGSHF3), on alleviating the toxicity and oxidative stress induced by DON in the mice and IPEC-J2 cells. DON treatment decreases average daily gain and feeds intake, which causes enlargement of the liver and spleen. FGSHF3 (200 mg/kg) and GPA (200 mg/kg) treatment significantly increase average daily gain and inhibits enlargement of the liver and spleen. Furthermore, FGSHF3 and GPA treatment significantly alleviates intestinal injury and maintains tight junction in mice and IPEC-J2 cells. FGSHF3 and GPA treatment significantly inhibits ROS and MDA production and enhances antioxidant enzyme activity, such as CAT, SOD-1, GCLM, GCLC, and GSH-PX. Furthermore, FGSHF3 and GPA treatment promote Nrf2 migration from the cytoplasm to the nucleus, resulting in exerting antioxidant effects. And its effects are abolished after Nrf2 is knockdown by siRNA. Overall, our results suggest GPA peptide may be a promising candidate for the alleviation of DON-induced toxicity in humans and animals.

Dentin dysplasia type I (DDI) is an autosomal-dominant genetic disorder resulting from dentin defects. The molecular basis of DDI remains unclear. DDI exhibits unique characteristics with phenotypes featuring obliteration of pulp chambers and diminutive root, thus providing a useful model for understanding the genetics of tooth formation. Using a large Chinese family with 14 DDI patients, we mapped the gene locus responsible for DDI to 3p26.1-3p24.3 and further identified a missense mutation, c.353C>A (p.P118Q) in the SSUH2 gene on 3p26.1, which co-segregated with DDI. We showed that SSUH2 (p.P118Q) perturbed the structure and significantly reduced levels of mutant (MT) protein and mRNA compared with wild-type SSUH2. Furthermore, MT P141Q knock-in mice (+/- and -/-) had a unique partial obliteration of the pulp cavity and upregulation or downregulation of six major genes involved in odontogenesis: Dspp, Dmp1, Runx2, Pax9, Bmp2, and Dlx2. The phenotype of missing teeth was determined in zebrafish with morpholino gene knockdowns and rescued by injection of normal human mRNA. Taken together, our observations demonstrate that SSUH2 disrupts dental formation and that this novel gene, together with other odontogenesis genes, is involved in tooth development.

Copy number variations (CNVs) can cause many genetic disorders and the structure analysis of unknown CNVs is important for clinical diagnosis. The human α-globin gene cluster lies close to the telomere of the short arm on chromosome 16. Copy number variations of this region produce excessive or insufficient α-globin chains which imbalances the β-globin chains, resulting in thalassemia. However, these CNVs usually cannot be precisely defined by traditional methods. Here, we designed a technique strategy and applied it to identify two CNVs involving the α-globin gene cluster causing thalassemia in two Chinese families. A novel 282 kb duplication (αααα(282)) was identified in family A and a novel 235 kb deletion (--(235)) in family B. Proband A is a coinheritance of β(CD41-42) and αααα(282) and showed severe β-thalassemia intermedia phenotype. Proband B is a compound heterozygote of --(235)/α(CS)α genotype and was diagnosed with hemoglobin H disease. The clinical phenotypic features of the CNVs carriers were described, together with a complete picture of molecular structure of these rearrangements. Two CNVs are novel rearrangements in α-globin clusters and the αααα(282) is the first to identify the exact insert position of a duplication region from the telomere on chromosome 16. In a conclusion, successful identification and characterization of these two novel CNVs not only demonstrates the precision and effectiveness of our strategy in analyzing the structure of unknown CNVs, but also extended the spectrum of thalassemia and provide new examples for studying genomic recombination.

Growth factor receptor-bound protein-2 (Grb2) can act as the scaffold protein recruiting other molecules to the stimulated receptors. Grb2-associated binding protein 1 (Gab1) is involved in cell proliferation, and its expression may enhance the carcinogenesis and cancer progression. However, the function of Gab1 remains to be investigated. Epithelial ovarian cancer (EOC) is the most lethal malignancy in the female reproductive system with increasing incidence and unsatisfied overall survival (OS). We investigated the expression of Gab1 in EOC tissues and the correlations between Gab1 expression and the clinicopathological characteristics of patients with EOC using Spearman rank test. The staining results were evaluated based on both the percentage of Gab1-positive tumor cells and the staining intensity for Gab1 expression. Kaplan-Meier survival analysis and Cox proportional hazards analysis were used to compare the postoperative OS between EOC patients with high Gab1 expression and those with low Gab1 expression. The high expression of Gab1 was positively correlated with advanced FIGO stage and lymph node metastasis of EOC. Univariate analysis showed that advanced FIGO stage, pathological grade, lymph node metastasis or Gab1 expression were associated with poor OS. Moreover, multivariate analysis revealed that Gab1 expression could be an independent prognostic factor for the poor OS of EOC patients (P = 0.042). We propose that Gab1 expression is correlated with poor prognosis of EOC patients and may act as an independent prognostic indicator.

The pressure distribution between a seat and people is a very important index in the assessment of sitting discomfort for seat cushion. However, limited research has been found for the relationship between pressure distribution and anthropometric dimensions, especially for Body Mass Index (BMI) of users with different sizes. Effects of BMI ranges (underweight, normal and obese) and cushion hardness (medium, firm, extra firm and wood board) were the factors investigated in this study. The results indicated that the normal participant had a higher comfort degree than the obese and underweight participants. The obese participant preferred the extra firm foam cushion compared to normal participants who preferred the medium foam cushion.

The majority of the human genome is transcribed, yielding a rich repository of non-coding transcripts that are involved in a myriad of biological processes including cancer. However, how non-coding transcripts such as long non-coding RNAs (lncRNAs) function in prostate cancer is still unclear. In this study, we have identified a novel set of clinically relevant androgen-regulated lncRNAs in prostate cancer. Among this group, we showed LINC00844 is a direct androgen-regulated target that is actively transcribed in androgen receptor (AR)-dependent prostate cancer cells. The expression of LINC00844 is higher in normal prostate compared to malignant and metastatic prostate cancer samples and patients with low expression demonstrate poor prognosis and significantly increased biochemical recurrence, suggesting LINC00844 may function in suppressing tumor progression and metastasis. Indeed,in-vitroloss-of-function studies revealed that LINC00844 prevents prostate cancer cell migration and invasion. Moreover, findings from gene expression analysis indicated that LINC00844 functions intrans, affecting global androgen-regulated gene transcription. Mechanistically, we provide evidence to show LINC00844 is important in facilitating AR binding to the chromatin. Finally, we demonstrated LINC00844 mediates its phenotypic effects in part by activating the expression of NDRG1, a crucial cancer metastasis suppressor. Collectively, our findings suggest LINC00844 is a novel coregulator of AR that plays a central role in the androgen transcriptional network and the development and progression of prostate cancer.

No literature related to the study of sitting forces on chairs sat on by people who weighed over 136 kg was found. The Business Institutional Furniture Manufactures Association needs force data for development of performance test standards to test chairs for users who weigh up to 181 kg. 20 participants who weighed from 136 to 186 kg completed 6 tasks on an instrumented chair in the sequence of sitting down, remaining seated and rising. Effects of sitting motion, armrest use and seat cushion thickness on vertical sitting forces and centre-of-force were investigated. Results indicated hard sitting down yielded the highest sitting force of 213% in terms of participants' body weights. Armrest use affected sitting forces of normal sitting down, but not of rising and hard sitting down. Cushion thickness affected sitting forces of normal and hard sitting down and shifting, but not of rising, static seating or stretching backward situations. Practitioner Summary: Results of the sitting force and centre-of-force data obtained for this research can help furniture manufacturers develop new product performance test standards for creating reliable engineering design and manufacturing quality and durable products to meet a niche market need.

BACKGROUND Cytomegalovirus (CMV) infection has been shown to be related to severe or steroid-refractory ulcerative colitis (UC) flare-ups. The aim of this study was to evaluate the endoscopic and pathological characteristics of CMV colitis in patients with UC and to assess the predictive value of the endoscopic and pathological features of CMV colitis. METHODS A total of 50 consecutive UC patients with CMV infection who were admitted to Peking Union Medical College Hospital from 2010 to 2015 were enrolled in this study. RESULTS Twenty-five UC patients with CMV infection (50.0%) had concurrent CMV colitis. When the cutoff value was set at 1150 copies, the sensitivity and specificity of blood CMV DNAq polymerase chain reaction for predicting CMV colitis were 44.4% and 78.9%, respectively. A higher proportion of endoscopic punched-out ulcers, irregular ulcers, and cobblestone-like appearance were observed among the patients in the CMV colitis group than those in the non-CMV colitis group (52.0% versus 20.0%, 60.0% versus 16.0%, and 20.0% versus 0%, respectively, P < 0.05). The number of CMV inclusion bodies per high-power field was significantly higher in those with punch-out ulcerations (25.7% versus 60.0%, P < 0.05). A higher grade of pathological inflammation was observed in the CMV colitis group than in the control group (68.0% versus 44.0%). CONCLUSIONS Characteristic endoscopic features with punch-out ulcers and high CMV viremia load may be useful for predicting the presence of CMV colitis in histology. Punch-out ulcers were found to be associated with a higher number of inclusion bodies on histology, suggesting a role of targeted biopsy for endoscopist.

Objectives This study aimed to investigate differences in the influence of chin prominence and length on perception of facial aesthetics by Chinese dental clinicians, orthognathic patients, and dental students. Study Design Male and female silhouette lateral profiles were modified to obtain 28 facial profiles by altering chin prominence and length by 3 mm in the sagittal and vertical planes. Images were rated by 70 clinicians, 30 orthognathic patients, and 100 dental students on a 7-point Likert scale. Results Perceived attractiveness was highest when the male chin prominence (MCP) was −3 mm to 3 mm and the female chin prominence (FCP) was 3 mm. In contrast, male chin length (MCL) of 0 to 3 mm and female chin length (FCL) of 0 mm were considered the most attractive. In the sagittal and vertical profiles, MCP (−9 mm), FCP (−9 mm), FCL (−9 mm), and MCL (−9 mm) were ranked least attractive. Conclusions The overall aesthetic opinions of orthognathic patients, clinicians, and dental students are similar. The greater the retrusion or protrusion of the chin and the shorter or longer the chin length, the lower were the rates of facial aesthetics and the greater were the desire for surgery.

We exposed Xenopus tropicalis embryos to a selective antagonist of retinoid X receptor (UVI3003). UVI3003 induced multiple malformations at the concentrations of 200–1000 μg/L after 48 h exposure. The most prominent malformations affected brains, eyes, cement gland and fins. UVI3003 also induced variable and divergent malformations at 250–1500 μg/L after 0–24 and 24–48 h exposure. Microarray analysis showed that seven genes (rps15, serp2, fmr1, cyp2e1, lrrc9, ugtla6 and LOC100490188) were differentially regulated in all three treatment groups after 0–24 h exposure. The most significantly affected pathway was galactose metabolism. In 24–48 h exposure groups, 18 genes were differentially regulated, mainly comprising components of the PPAR signaling pathway. These results suggested that UVI3003 is teratogenic in amphibian embryos. Differential gene expression suggests that galactose metabolism and PPAR signaling pathways may provide underlying mechanistic detail accounting for the observed malformations.

Summary: Estrogen drives breast cancer (BCa) progression by directly activating estrogen receptor α (ERα). However, because of the stochastic nature of gene transcription, it is important to study the estrogen signaling pathway at the single-cell level to fully understand how ERα regulates transcription. Here, we performed single-cell transcriptome analysis on ERα-positive BCa cells following 17β-estradiol stimulation and reconstructed the dynamic estrogen-responsive transcriptional network from discrete time points into a pseudotemporal continuum. Notably, differentially expressed genes show an estrogen-stimulated metabolic switch that favors biosynthesis but reduces estrogen degradation. Moreover, folate-mediated one-carbon metabolism is reprogrammed through the mitochondrial folate pathway and polyamine and purine synthesis are upregulated coordinately. Finally, we show AZIN1 and PPAT are direct ERα targets that are essential for BCa cell survival and growth. In summary, our study highlights the dynamic transcriptional heterogeneity in ERα-positive BCa cells upon estrogen stimulation and uncovers a mechanism of estrogen-mediated metabolic switch. : Zhu et al. perform single-cell RNA-seq to reveal a dynamic transcriptional network in ERα+ breast cancer cells following estrogen stimulation and show that estrogen signaling promotes breast cancer cell survival and growth by mediating a metabolic switch in which folate-mediated one-carbon metabolism is reprogrammed via the mitochondrial folate pathway. Keywords: breast cancer, single-cell RNA sequencing, estrogen receptor α, metabolic switch

Agonists induce platelet activation or apoptosis with concomitant shedding of the platelet receptor glycoprotein Ibα (GPIbα) ectodomain in a disintegrin and metalloproteinase 17 (ADAM17)-dependent mechanism. Mitochondrial permeability transition pore (MPTP) plays a pivotal role in platelet activation or apoptosis. However, its impact on ADAM17-mediated GPIbα ectodomain shedding remains unclear. Here, we aimed to test the hypothesis that MPTP regulates ADAM17-dependent GPIbα ectodomain shedding. We showed that calcium ionophore A23187- or thrombin plus collagen-induced GPIbα ectodomain shedding was partially inhibited by a MPTP inhibitor, and a MPTP potentiator promoted A23187-induced GPIbα cleavage. Furthermore, A23187-induced elevation of mitochondrial Ca(2+) levels was blocked by the mitochondrial calcium uniporter (MCU) inhibitor Ru360 or treatment with the membrane-permeable Ca(2+) chelator BAPTA-AM. We also demonstrated that an increase in mitochondrial Ca(2+) levels triggered MPTP opening, as revealed by the examination of mitochondrial inner transmembrane potential depolarization. In addition, A23187 induced-mitochondrial reactive oxygen species (ROS) generation was blocked by the MPTP inhibitor or by treatment with the mitochondria-targeted ROS scavenger. Lastly, A23187-induced GPIbα shedding was partially blocked by inhibitors of either ROS or calpain, and was completely inhibited when platelets were exposed to both inhibitors. Therefore, these observations indicate that MPTP opening triggered mitochondrial ROS production, which plays an important role in regulating ADAM17-mediated shedding of the GPIbα ectodomain in A23187-treated platelets.

Limited research was found related to the study of back forces on chairs sat on by people who weighed over 136 kg. The Business Institutional Furniture Manufactures Association needs force data for development of performance test standards to test chairs for users who weigh up to 181 kg. 20 participants who weighed from 136 to 186 kg completed six tasks on an instrumented chair in the sequence of sitting down, remaining seated, and rising. Effects of sitting motion, armrest use, and seat cushion thickness on back forces and centre-of-force were investigated. Results indicated hard sitting down yielded the highest back force of 34.7 % in terms of participants’ body weights. Armrest use and cushion thickness affected back forces of normal sitting down, but not of rising, hard sitting down, and remaining seated.

To identify novel genes that mediate cellular sensitivity and resistance to 5-fluorouracil (5-FU), we performed a genome-wide genetic screening to identify altered susceptibility to 5-FU by Schizosaccharomyces pombe haploid nonessential gene deletion library containing 3004 deletion mutants. We identified 50 hypersensitive and 12 resistant mutants to this drug. Mutants sensitive or resistant to 5-FU were classified into various categories based on their putative functions. The largest group of the genes whose disruption renders cells altered susceptibility to 5-FU is involved in nucleic acid metabolism, but to our surprise, the second largest group is involved in membrane trafficking. In addition, several other membrane traffic mutants examined including gdi1-i11, ypt3-i5, Δryh1, Δric1, and Δaps1 exhibited hypersensitivity to 5-FU. Furthermore, we found that 5-FU in low concentration that generally do not affect cell growth altered the localization of Syb1, a secretory vesicle SNARE synaptobrevin which is cycled between the plasma membrane and the endocytic pathway. Notably, 5-FU at such low concentration also significantly inhibited the secretion of acid phosphatase. Altogether, our findings revealed the first evidence that 5-FU influences membrane trafficking as the potential underlying mechanism of the drug action.

Background Dentin dysplasia I (DDI) is a genetically heterogeneous autosomal-dominant disorder characterised by rootless teeth with abnormal pulpal morphology, the aetiology of which presents as genetically heterogeneous. Methods and results Using a cohort of a large Chinese family with 10 patients with DDI, we mapped to a 9.63 Mb candidate region for DDI on chromosome 18q21.2–q21.33. We then identified a mutation IVS7+46C>G which resulted in a novel donor splice site in intron 7 of the VPS4B gene with co-segregation of all 10 affected individuals in this family. The aberrant transcripts encompassing a new insert of 45 bp in size were detected in gingival cells from affected individuals. Protein structure prediction showed that a 15-amino acid insertion altered the ATP-binding cassette of VPS4B. The mutation resulted in significantly reduced expression of mRNA and protein and altered subcellular localisation of VPS4B, indicating a loss of function of VPS4B. Using human gingival fibroblasts, the VPS4B gene was found to act as an upstream transducer linked to Wnt/β-catenin signalling and regulating odontogenesis. Furthermore, knockdown of vps4b in zebrafish recapitulated the reduction of tooth size and absence of teeth similar to the tooth phenotype exhibited in DDI index cases, and the zebrafish mutant phenotype could be partially rescued by wild-type human VPS4B mRNA. We also observed that vps4b depletion in the zebrafish negatively regulates the expression of some major genes involved in odontogenesis. Conclusions This study identifies VPS4B as a disease-causing gene for DDI, which is one of the important contributors to tooth formation, through the Wnt/β-catenin signalling pathway.

Fibroblast growth factor receptor 4 (FGFR4) has been confirmed to be associated with the progression and prognosis of ovarian cancer, while the underlying mechanism has not been well elucidated and the clinical significance of its ligand, fibroblast growth factor 19 (FGF19), has not been explored. To study the clinical significance of FGF19 in advanced‑stage serous ovarian cancer, we detected the expression of FGF19 and FGFR4 by immunohistochemistry (IHC), evaluated the correlation between FGF19 and clinicopathological factors by Chi-square (χ2) test, and analyzed the association between FGF19, FGFR4 and the overall survival rate using the Kaplan‑Meier method. As a result, we demonstrated that high expression of FGF19 and FGFR4 both predicted unfavorable prognosis (P=0.033 and 0.018, respectively), whereas FGF19-FGFR4 double high expression was a more sensitive prognostic factor of advanced-stage serous ovarian cancer (P

Background Mutations in proline-rich transmembrane protein 2 (PRRT2) are a cause of paroxysmal kinesigenic dyskinesia (PKD). In this study, we investigated the PRRT2 gene mutation in a Chinese Han family with PKD and study the pathogenesis of the mutation with PRRT2 gene. Methods Peripheral venous blood was taken from the family members. Sanger sequencing was used for novel mutation sequencing. For the pathogenesis with the novel mutation was analyzed by bioinformatics, real-time PCR, subcellular localization and Western blot. Results The Sanger sequencing showed a novel mutation, c.186-187delGC, a deletion mutation, in exon 2 of the PRRT2 gene, the frameshift mutation generated a truncated protein that was stably expressed in transfected Human embryonic kidney (HEK) 293 cells. A subcellular localization assay in COS-7 cells with GFP-tagged protein showed nuclear localization for the mutant protein while the wild-type protein was localized in membranes. Co-transfection of HEK293 cells with wild-type and mutant expression plasmids cells did not influence mRNA or protein expression from the wild-type plasmid. Conclusions Our findings demonstrated that the c.186-187delGC mutation resulted in a truncated protein from the PRRT2 gene to involve in PKD pathogenesis with haploinsufficiency. The results extend the mutation spectrum of the PRRT2 gene and provide a new example for studying the pathogenesis of the mutated PRRT2 gene.

Objective: Inflammation of the small intestine may occur in type 2 diabetes. This study aimed to investigate whether ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) were altered in chronic inflammation of the small intestine of type 2 diabetic rats. Methods: Thirty-two male Sprague-Dawley rats were used. Eight rats in the control group were fed with regular chow, and 24 rats were fed a high-fat diet and injected with a single low dose of streptozotocin. All of the control rats and diabetic rats were bred for 10 months. Immunohistochemistry detected ABCA1 and ABCG1 in the small intestine in all the rats. Results: Hematoxylin-eosin staining showed chronic inflammation in the small intestine of the diabetic rats. Immunohistochemistry staining showed that alteration of ABCA1 and ABCG1 was different in the inflammatory and epithelial cells. Quantitative analysis showed that the overall expression of ABCA1 and ABCG1 increased in the diabetic rats compared to the control rats. Both ABCA1 and ABCG1 were enriched in the inflammatory cells of the small intestine in diabetic rats. In the epithelial cells, ABCA1, but not ABCG1, was detected in significantly more diabetic rats than control rats. Conclusion: Both ABCA1 and ABCG1 are enriched in chronic inflammation of the small intestine of type 2 diabetic rats. ABCA1, but not ABCG1, is activated in the intestinal epithelial cells of type 2 diabetic rats.

Xenopus tropicalis embryos were exposed for 48 hr to the mixtures of 5 μg Sn/L triphenyltin (TPT), which is a well-known endocrine disruptor, and 0.25--5 μg/L 9-cis retinoic acid (9c-RA), which is the natural ligand of retinoid X receptor. The phenotypes induced by combined exposure were more variable than those resulting from single exposure to either TPT or 9c-RA. The prominent phenotypes included underdeveloped head structures, abnormal eyes, narrow fins, enlarged protodaeum, etc. Especially, combined exposure induced unexpected notochord malformations, which ranged from small swellings of the surface of the tails to the extension and extrusion of notochord out of the posterior tails. Compared with the 5 μg Sn/L TPT-treated group, the index of fin deficiency was not affected, and the index of axis deficiency was significantly increased with increasing RA concentrations in the mixtures. Our results suggest that combined exposure to TPT and 9c-RA induced not only more variable phenotypes of malformations than exposure to single compound but also some new and unexpected phenotypes.