Globular adiponectin induces esophageal adenocarcinoma cell pyroptosis via the miR-378a-3p/UHRF1 axis.

BACKGROUND: Antiapoptosis is a major factor in the resistance of tumor cells to chemotherapy and radiotherapy. Thus, activation of cell pyroptosis may be an effective option to deal with antiapoptotic cancers such as esophageal adenocarcinoma (EAC). METHODS: Differential expression of ubiquitin-like versus PHD and ring finger structural domain 1 (UHRF1) in EAC and near normal tissues was analyzed, as well as the prognostic impact on survival in EAC. Also, the same study was done for globular adiponectin (gAD). Simultaneously, the mRNA expression of UHRF1 was observed in different EAC cell lines. Real time cellular analysis (RTCA) was used to detect cell proliferation, and flow cytometry and inverted fluorescence microscopy were used to detect pyroptosis. Biocredit analysis was conducted to observe the correlation between UHRF1 and key pyroptosis proteins. OD values and CCK8 assay were used to determine the effect of miR-378a-3p on EAC cells. Quantitative real-time polymerase chain reaction and Western blot were used to detect the correlation between UHRF1, gAD, and miR-378a-3p in EAC cells. Moreover, in vivo and in vitro experiments were performed to detect the relevant effects on tumor migration and invasion after inhibiting UHRF1 expression. RESULTS: UHRF1 was negatively correlated with the survival of patients with EAC, while miR-378a-3p showed the opposite effect. Additionally, gAD promoted EAC cell pyroptosis, upregulated miR-378a-3p, and significantly inhibited the proliferation of EAC cells. gAD directly reduced UHRF1 expression in EAC cells by upregulating miR-378a-3p. In cell migration and invasion assays, inhibition of UHRF1 expression significantly suppressed EAC cell metastasis. In animal experiments, we again demonstrated that gAD induced pyroptosis in EAC cells by inhibiting the expression of UHRF1. CONCLUSION: gAD-induced upregulation of miR-378a-3p significantly inhibited the proliferation of EAC by targeting UHRF1. Therefore, gAD may serve as an alternative therapy for chemotherapy- and radiation-refractory EAC or other cancers with the same mechanism of pyroptosis action.

Characterization and Developmental Expression Patterns of Four Hexamerin Genes in the Bumble Bee, Bombus terrestris (Hymenoptera: Apidae).

Hexamerins are members of the hemocyanin superfamily and play essential roles in providing amino acids and energy for the nonfeeding stages of insects. In this study, we cloned and analyzed the expression patterns of four hexamerin genes (hex 70a, hex 70b, hex 70c, and hex 110) at different worker development stages and queen diapause statuses in the bumble bee, Bombus terrestris. The results of this study showed that hex 110 has the longest open reading frame (ORF; 3,297 bp) compared to the ORFs of hex 70a (2,034 bp), hex 70b (2,067 bp), and hex 70c (2,055 bp). The putative translation product of Hex 70a, Hex 70b, Hex70c, and Hex 110 has 677, 688, 684, and 1,098aa with predicted molecular mass of 81.13, 79.69, 81.58, and 119 kDa. In the development stages of workers, the expression levels of hex 70a, hex 70b, and hex 70c increased gradually from the larval stage and exhibited high expression levels at the pink eyed and brown eyed pupae stage, whereas hex 110 exhibited the highest expression level at the larval period. Four hexamerin genes were highly expressed at the prediapause status of queen (P < 0.05), and compared to the eclosion queen, the lowest upregulation was 3.7-fold, and the highest upregulation was 1,742-fold. The expression levels of hex 70b, hex 70c, and hex 110 at diapause were significantly higher than those at postdiapause (P < 0.05). In conclusion, hexamerins may play important roles in queen diapause and metamorphosis of larval and pupal stages.

Chinese Sacbrood virus infection in Asian honey bees (Apis cerana cerana) and host immune responses to the virus infection.

Chinese Sacbrood virus (CSBV) is a positive-stranded RNAvirus that infects both the European honey bee (Apis mellifera) and the Asian honey bee (A. cerana). However, CSBV has much more devastating effects on Asian honey bees than on European honey bees, posing a serious threat to the agricultural and natural ecosystems that rely on A. cerana for pollination service. Using quantitative RT-PCR method, we conducted studies to examine the CSBV infection in Asian honey bee colonies and immune responses of individual bees in response to CSBV infection. Our study showed that CSBV could cause infection in different developmental stages of workers including eggs, larvae, pupae, newly emerged workers, and foraging workers. In addition, evaluating the tissue tropism and transmission of CSBV in infected bees showed that CSBV was detected in the ovaries, spermatheca, and feces of queens as well as semen of drones of the same colonies, suggesting an existence of vertical transmission of CSBV in Asian honey bees. Further, the detection of CSBV in colony food suggests that healthy bees could pick the infection by the virus-contaminated food, and therefore, a possible existence of a food-borne transmission pathway of CSBV in Asian bee colonies. The expression analysis of transcripts (defensin, abaecin, apidaecin, and hymenoptaecin) involving innate antiviral immune pathways showed that CSBV infection could induce significant immune responses in infected bees. However, the immune responses to CSBV infection varied among different development stages with eggs exhibiting the lowest level of immune expression and forager workers exhibiting the highest level of immune gene expression. The results obtained in the study yield important insights into the mechanisms underlying disease pathogenesis of CSBV infections in Asian honey bees and provide valuable information for a rational design of disease control measures.

Emotional social support and access to care among older people living with HIV in rural China.

OBJECTIVES: Globally, the number of older people living with HIV (PLH) is growing. Additionally, older PLH are facing particular challenges related to accessing health care. The objective of this study is to investigate the older PLH's access to care and its relationship to emotional and tangible social support. METHODS: A cross-sectional study was conducted among 225 PLH who were 50 years of age or older in Anhui, China. A computer-assisted personal interview was used to collect the participants' demographic characteristics, perceived health status, and access to care. The following two dimensions of social support were measured: emotional support and tangible support. The association between emotional/tangible support and access to care was calculated using Pearson's/point-biserial correlations and with multiple linear regression. RESULTS: Higher tangible support was reported by the participants who were married or living with a partner, those who had higher annual income levels, and those with better perceived health status. Emotional support was correlated with higher education, higher income, and better perceived health status. Multiple regression analyses showed that access to care was significantly associated with emotional support (ß = 0.2807, p < 0.0001) but not with tangible support (ß = -0.0183, p = 0.7922). CONCLUSIONS: The study findings point to the importance of providing emotional support for older PLH. It is suggested that emotional support should be provided for older PLH in addition to tangible assistance, in order to engage them in treatment and care.

Bioinformatics identify the role of chordin-like 1 in thyroid cancer.

The abnormal expression of chordin-like 1 (CHRDL1) is identified in many cancers, while the effect of CHRDL1 in thyroid cancer (THCA) remains unclear. The University of California Santa Cruz, Gene Expression Profiling Interactive Analysis, University of Alabama at Birmingham Cancer, and Gene Expression Omnibus database (GSE33570, GSE33630, and GSE60542) were used for determining the mRNA and methylation expression of CHRDL1 in tumor and normal tissues. Human Protein Atlas was used for exploring the protein expression level of CHRDL1. The genes correlated to CHRDL1 were assessed by cBioPortal database. The prognostic value of CHRDL1 was evaluated through Kaplan-Meier method, cox regression, and nomogram analysis. Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and gene set enrichment analysis were used for predicting potential function of CHRDL1. The relationship between CHRDL1 and immune cell infiltration was determined by Pearson method. The downregulated mRNA and protein expressions of CHRDL1 were identified in THCA through the analysis of data from The Cancer Genome Atlas, Gene Expression Omnibus, and Human Protein Atlas database. The survival analysis showed that the CHRDL1 expression significantly affected disease-free interval (DFI) and progression-free interval, and CHRDL1 was an independent predictor of DFI. Besides, we found that C-C motif chemokine ligand 21 could significantly affect DFI time when it was co-expressed with CHRDL1. Additionally, the function of CHRDL1 was enriched in cell migration, apoptosis, and immune cell receptor. The downregulated expression of CHRDL1 was observed in THCA and caused poor prognosis. CHRDL1 may be involved in signal pathway related to cancer development and immune response, which suggested it could be a potential biomarker.

Evaluation and identification of morphological characters suitable for delimitation of Taraxacum species distributed in northeastern China.

Taraxacum germplasm resources in northeastern China are not current and do not accurately reflect the actual distribution of the species. The objective of this study was to investigate the morphological traits of Taraxacum species distributed in northeastern China and identify those that will facilitate their classification in this region. Leaf, flower, and achene characteristics of 18 species were used for morphological classification. Scanning electron microscopy (SEM) was used to examine pollen morphology. Internal transcribed spacer (ITS) sequences were analyzed to determine sequence differences among the species and their utility in delimitation. Taxa were classified into groups based on their morphology. The ITS sequence analysis supported the taxon classification, but the genetic distances among the taxa did not reflect morphological differences. Phylogenetic analysis was used to divide the 18 species into three groups. Group I: T. coreanum (which has white flowers). Group Ⅱ: T. heterolepis, T. sinomongolicum, T. variegatum, T. asiaticum var. lonchophyllum, T. falcilobum, T. brassicaefolium, and T. erythropodium (outer involucre bracts, narrow membranous or nonmembranous). Group Ⅲ: T. formosanum, T. liaotungense, T. mongolicum, T. borealisinense, T. ohwianum, T. platypecidum, T. urbanum, T. antungense, T. asiaticum, and T. junpeianum (outer involucre bracts, broad membranous). The main taxonomic characteristics of Taraxacum floral organs and achene morphology.

Circular RNA NF1-419 Inhibits Proliferation and Induces Apoptosis by Regulating Lipid Metabolism in Astroglioma Cells.

BACKGROUND: Astroglioma is the most common primary tumor of the central nervous system. Currently, there is no effective treatment for astroglioma. In the present study, the extract (L3) from Ganoderma Lucidum (G. lucidum) was found to inhibit the growth of astroglioma U87 cells and change the expression of circular RNAs (circRNAs). One of these, including the circular NF1-419 (circNF1-419), was of interest because NF1 gene is a classic tumor suppressor gene. OBJECTIVES: The functional role of circ-NF1-419 in the inhibition of astroglioma cells remains unknown. This study focuses on the role of circNF1-419 in functional abnormalities of U87 astroglioma cells and aims to elaborate on its regulatory mechanism. METHODS: The circNF1-419 overexpressing U87 (U87-NF1-419) cells were constructed. We generated U87-NF1-419 to evaluate the role of circNF1-419 on cell cycle, apoptosis, proliferation, tumor growth and metabolic regulation. Finally, we used docking screening to identify compounds in G. lucidum extracts that target circ-419. RESULTS: U87-NF1-419 can promote cell apoptosis and regulate lipid metabolism through glycerophospholipid metabolism and retrograde endocannabinoid signaling. Further examinations revealed that the expression of metabolic regulators, such as L-type voltage-operated calcium channels (L-VOCC), phospholipase C-ß3 (PLCß3), Mucin1, cationic amino acid transporter 4 (CAT4), cationic amino acid transporter 1 (CAT1) and a kinase (PRKA) anchor protein 4 (AKAP4) was inhibited, while phosphatidylserine synthase 1 (PTDSS1) was enhanced in U87-NF1-419 cells. In vivo experiments showed that circNF1-419 inhibits tumor growth in BALB/C nude mice, and enhanced AKAP4 and PTDSS1 in tumor tissues. The virtual docking screening results supported that ganosporeric acid A, ganodermatriol, ganoderic acid B and α-D-Arabinofuranosyladenine in L3 could activate circNF1-419 in astroglioma treatment. CONCLUSION: This study indicated that circNF1-419 could be a therapeutic target for the clinical treatment of astroglioma. L3 from Ganoderma Lucidum (G. lucidum) could inhibit astroglioma growth by activating circNF1-419.

A case of human rabies with a long incubation period in Wuhan.

Rabies remains endemic in China and continues to pose a major threat to public health with a nearly 100 % case fatality rate in humans. We confirmed a case of human rabies in Wuhan, in May 2018. The patient had got a dog bite wound 3 years before symptoms of confusion, hydrophobia, and photophobia onset. On May 14, our laboratory confirmed that the patient was infected with a rabies virus that circulates in dogs in China and died on May 24, two weeks later after admission. Complete glycoprotein gene sequences determined for this isolate indicated the source of a RABV infection was dog-related RABV variants.

Vaccination with a potent DNA vaccine targeting B-cell epitopes of hGRP induces prophylactic and therapeutic antitumor activity in vivo.

Gastrin-releasing peptide (GRP), a bombesin-like peptide, is an autocrine or paracrine growth factor that can stimulate the growth of various cancer cells, making it an ideal target antigen to develop vaccines against cancer. In this study, we developed a novel DNA vaccine that encodes six tandem repeats of B-cell epitope GRP(18-27) (GRP6) flanked by HSP65 as carrier and four tandem repeats of mycobacterial HSP70(407-426) (M4) as helper T-cell epitopes for enhancement of immunogenicity. When intramuscularly immunized to mice, this anti-GRP DNA vaccine-induced GRP-specific antibody (Ab) responses that were at least 10-fold higher in magnitude compared with HSP65-GRP6 protein vaccine. Both prophylactic and therapeutic antitumor immunities induced by vaccination significantly suppressed the growth of GRP-dependent prostate carcinoma RM-1 in vivo and prolonged the survival of tumor-inoculated mice. Out results also showed that the immune sera with high titer of GRP-specific Abs effectively inhibited the growth of tumor in mice and dose dependently inhibited proliferation of cultured RM-1 cells in vitro, suggesting that the GRP neutralizing Ab is responsible for the protective and therapeutic antitumor activity of vaccination. These findings may be of great importance in the further exploration of the applications of growth factors identified in human in cancer therapy.

Hydration process and microstructure of magnesium potassium phosphate cement with nitrate solution.

Magnesium phosphate potassium cement (MKPC) can be potentially used for solidification/stabilization (S/S) treatment of hazardous wastes. The influence of inorganic salts on the hydration process and microstructure of cementitious materials must be considered, especially to assess the performance of the S/S treatment of wastes with a high nitrate content. Hence, in this study, the hydration process and microstructure of MKPC specimens were investigated, along with their variations in compressive strength setting time, pH, and conductivity. The pore structure, phases composition, and elemental composition of the specimens were investigated using the Brunauer-Emmett-Teller method, X-ray diffraction analysis, scanning electron microscopy, and energy-dispersive X-ray spectroscopy. The results showed that although the potassium nitrate (KNO3) solution did not affect the formation of struvite-K, it affected the crystallization degree of struvite-K, where its microstructure changed from dense, plate-like and prismatic crystals into loose, cluster-like crystals at higher amounts of nitrate. Furthermore, the addition of nitrate delayed the setting time and slowed the pH growth during the hydration process of the MKPC. The nitrate solution hindered the hydration process of the MKPC specimens and increased their porosity. When the amount of nitrate was less than 5 wt%, the effect of nitrate on the hydration and hardening of the MKPC was small. However, at higher amounts of nitrate, the nitrate ions had a negative effect on the compressive strength development of the MKPC and the hydration process was delayed.