A new basic burning raw material for simultaneous stabilization/solidification of PO43--P and F- in phosphogypsum.

Phosphogypsum (PG) contains a lot of soluble phosphate (PO43--P) and fluorine ion (F-), which seriously has hindered the sustainable development of the phosphorous chemical industry. In this study, a new burning raw material (BRM) as an intermediate product in the cement production process was used for PO43--P and F- stabilize in PG. The stabilizing mechanism of PO43--P and F- were investigated by Fourier Transform infrared spectroscopy (FT-IR), X-ray diffractometer (XRD), Scanning Electron Microscopy (SEM), X-ray fluorescence (XRF) and X-ray spectroscopy system (XPS). The effect of PG and BRM weight ratio, solid-to-liquid ratio, reaction time, and reaction temperature on the concentrations of PO43--P and F- were studied. The results showed that the concentration of F- in the PG leaching solution was 8.65 mg/L and the stabilizing efficiency of PO43--P was 99.78%, as well as the pH of the PG leaching solution was 8.12 when the weight ratio of PG and BRM was 100:2, and the solid to liquid ratio was 4:1, reacting for 24 h at the temperature of 30 â„ƒ. PO43--P and F- were mostly solidified as Ca5(PO4)3F, CaPO3(OH), Ca5(PO4)3(OH), Ca2P2O7·2H2O, CaSO4PO3(OH)·4H2O, CaF2, and CaFPO3·2H2O. Leaching test results indicated that the concentrations of PO43--P, F- and heavy metals were less than the integrated wastewater discharge standard (GB8978-1996). This study provides a new harmless treatment method for PG.

Analysis of the growth and development status of malnutrition and anemia in 352 children aged 0-3 years in Minhang community of Shanghai and evaluation of the effect after intervention.

The growth status of 352 malnourished and anemic children aged 0-3 years in Minhang District, Shanghai, were analyzed, and the effectiveness of health interventions was evaluated. The work focused on 352 malnourished and anemic children aged 0-3 years, summarized their health status by conducting two questionnaire surveys, and evaluated the effects of health interventions. The results revealed that the proportion of malnourished and anemic boys (57.10%) was slightly higher than that of girls (42.90%); and malnutrition-induced anemia accounted for 32.95% of the total number of children. The initial symptoms of malnourished children mainly manifested as below-normal height, weight loss, intellectual developmental delay and decreased muscle tone. Factors such as birth weight, number of infants, mode of delivery, preterm birth, feeding method, complementary feeding, medical history, and educational level of parents and primary caregivers had certain impacts on growth of children. Furthermore, the level of awareness of nutritional disorders knowledge was higher after the intervention compared to before the intervention. In conclusion, health education interventions for malnourished children can effectively improve their condition and enhance their overall health status, warranting widespread application and promotion.

High triiodothyronine levels induce myocardial hypertrophy via BAFF overexpression.

Activated B cells contribute to heart diseases, and inhibition of B-cell activating factor (BAFF) expression is an effective therapeutic target for heart diseases. Whether activated B cells participate in the development and progression of hyperthyroid heart disease, and what induces B cells activation in hyperthyroidism are unknown. The present study aimed to determine the roles of BAFF overexpression induced by high concentrations of triiodothyronine (T3) in the pathogenesis of hyperthyroid heart disease. Female C57BL/6J mice were subcutaneously injected with T3 for 6 weeks, and BAFF expression was inhibited using shRNA. Protein and mRNA expression of BAFF in mouse heart tissues evaluated via immunohistochemistry, western blotting and polymerase chain reaction (PCR). Proportions of B cells in mouse cardiac tissue lymphocytes were quantified via flow cytometry. Morphology and left ventricle function were assessed using pathological sections and echocardiography, respectively. Here, we demonstrate that compared with the control group, the proportion of myocardial B cells was larger in the T3 group; immunohistochemistry, western blotting and PCR analyses revealed increased protein and mRNA expression levels of TNF-α and BAFF in heart tissues of the T3 group. Compared with the normal controls group, in the T3 group, the diameter of myocardial cells and some echocardiographic values significantly increased and hypertrophy and structural disorder were noticeable. Our results revealed that elevated levels of circulating T3 can promote the expression of BAFF in myocardial cells and can lead to B-cell activation, an elevated inflammatory response and ventricular remodelling.

Baseline Sensitivity and Potential Resistance Mechanisms for Fusarium pseudograminearum to Fludioxonil.

Fusarium crown rot (FCR), which is caused by Fusarium pseudograminearum, is one of the most important diseases affecting wheat production in the Huanghuai wheat-growing region of China. Although the phenylpyrrole fungicide fludioxonil is known to have a broad-spectrum activity against a wide range of plant pathogens, including F. pseudograminearum, it has not yet been registered for the control of FCR in China, and further research is needed to assess the biological characteristics and molecular mechanisms associated with fludioxonil resistance, and especially the potential for highly resistant isolates to emerge. The current study demonstrated that the baseline fludioxonil sensitivity of 61 F. pseudograminearum isolates collected from the Henan province of China during the summers of 2019 to 2021 conformed to a unimodal distribution with a mean effective concentration for 50% inhibition (EC50) value of 0.021 ± 0.003 µg/ml, which indicated that none of the isolates exhibited natural resistance to fludioxonil. Nevertheless, four fludioxonil-resistant mutants were attained after repeated exposure to fludioxonil under laboratory conditions. All resistant mutants exhibited significantly lower growth rates on potato dextrose agar (PDA) and lower levels of sporulation and pathogenicity in wheat seedlings. In addition, the resistant mutants also exhibited less growth on PDA amended with either 0.5 M mannitol, 0.5 M glucose, 0.5 M MgCl2, or 0.5 M NaCl, which indicated that they had greater sensitivity to osmotic stress. Molecular analysis of the proposed fludioxonil target protein FpOs1 indicated that the predicted sequences of the resistant mutants contained none of the characteristic amino acid changes previously associated with fludioxonil resistance in other species. Further investigation via quantitative real-time PCR analysis revealed that expression of the FpOs1 gene was significantly altered in the resistant mutants in both the absence and presence of fludioxonil. Meanwhile, plate assays found evidence of cross-resistance between fludioxonil and cyprodinil, as well as with the triazole fungicides tebuconazole and difenoconazole, but not with other commonly used fungicides including prochloraz, fluazinam, and carbendazim. Taken together, these results provide new insights into the mechanism and biological characteristics associated with fludioxonil resistance in F. pseudograminearum and indicate that fludioxonil could provide effective and sustained control of FCR during wheat production.

Clinical features and diagnostic approaches for abdominal tuberculosis: five-year experience from a non-tuberculosis-designated hospital in China.

BACKGROUND AND PURPOSE: abdominal tuberculosis (TB) is a common form of extrapulmonary TB but it is still a diagnostic dilemma in clinical practice. This study aimed to highlight the clinical features and diagnostic approaches for abdominal TB. METHODS: seventy cases of diagnosed abdominal TB were retrospectively collected between August 1st, 2015 and June 30th, 2020. They were classified as peritoneal TB, lymph node TB, gastrointestinal TB, visceral TB or mixed TB. RESULTS: eighteen patients were diagnosed with peritoneal TB, nine with lymph node TB, five with gastrointestinal TB, two with visceral TB and 36 with mixed TB. More than 65 % of the patients had tuberculosis of other sites except the abdomen. The median diagnosis time was 60 days. Ascites (58.6 %), abdominal distension (48.6 %), weight loss (44.3 %) and fever (42.9 %) were the most common symptoms. The overall microbiological and histological detection rates were 70.0 % and 38.6 %, respectively. The non-ascite samples yielded a higher microbiological confirmation rate (63.6 %) than the total samples (40.8 %). Diagnosis was confirmed histologically in 18 patients (69.2 %). Forty-five cases (64.3 %) were clinically diagnosed. Invasive procedures such as surgery (6/7), percutaneous biopsy (7/7) and endoscopy in lymph node TB (4/5) had high confirmation rates. CONCLUSIONS: the diagnosis of abdominal TB should be reached by a combination of clinical, laboratory, radiological, microbiological and pathological findings.

Improved submucosal tunneling endoscopic resection with slant tunnel for submucosal tumors in proximal esophagus.

BACKGROUND: The improved submucosal tunneling endoscopic resection (STER) with slant tunnel was created by our group innovatively for submucosal tumors (SMTs) in the proximal esophagus. This study aimed to provide the preliminary results of the improved STER from our center. METHODS: The key step of the improved STER is establishing a slant tunnel instead of a vertical tunnel. After a longitudinal incision was made proximally in the inclined top to the tumor, a submucosal tunnel was established from the incision to the SMT slantingly. 28 patients undergoing STER with slant tunnel were enrolled in the retrospective study. Clinical results including en bloc resection, curative resection and complication were collected. RESULTS: All the submucous tumors located at proximal esophagus originated from muscularis propria were successfully resected by the innovative STER. Tumor size ranged from 18-43 mm, with 96.4% (27/28) en bloc resection rate and 92.9% (26/28) curative rate. Three patients suffered complication, 1 patient with mild pleural effusion and another 2 patients with fever for one day. All of the complications were cured by conservative treatment. CONCLUSIONS: STER with slant tunnel seems to provide an optional treatment for tumors in proximal esophagus.

Paternal origin of Tungusic-speaking populations: Insights from the updated phylogenetic tree of Y-chromosome haplogroup C2a-M86.

OBJECTIVES: Haplogroup C2a-M48 is the predominant paternal lineage of Tungusic-speaking populations, one of the largest population groups in Siberia. Up until now, the origins and dispersal of Tungusic-speaking populations have remained unclear. In this study, the demographic history of Tungusic-speaking populations was explored using the phylogenetic analysis of haplogroup C2a-M86, the major subbranch of C2a-M48. MATERIALS AND METHODS: In total, 18 newly generated Y chromosome sequences from C2a-M48 males and 20 previously available Y-chromosome sequences from this haplogroup were analyzed. A highly revised phylogenetic tree of haplogroup C2a-M86 with age estimates was reconstructed. Frequencies of this lineage in the literature were collected and a comprehensive analysis of this lineage in 13 022 individuals from 245 populations in Eurasia was performed. RESULTS: The distribution map of C2a-M48 indicated the most probable area of origin and diffusion route of this paternal lineage in North Eurasia. Most C2a-M86 samples from Tungusic-speaking populations belonged to the sublineage C2a-F5484, which emerged about 3300 years ago. We identified six unique sublineages corresponding to the Manchu, Evenks, Evens, Oroqen, and Daurpopulations; these sublineages diverged gradually over the past 1900 years. Notably, we observed a clear north-south dichotomous structure for sublineages derived from C2a-F5484, consistent with the internal north-south divergence of Tungusic languages and ethnic groups. CONCLUSIONS: We identified the important founding paternal haplogroup, C2a-F5484, for Tungusic-speaking populations as well as numerous unique subgroups of this haplogroup. We propose that the timeframe for the divergence of C2a-F5484 corresponds with the early differentiation of ancestral Tungusic-speaking populations.

Modifications to Expose Porta Hepatis for Laparoscopic Portoenterostomy Easier in Biliary Atresia.

BACKGROUND: Laparoscopic Kasai portoenterostomy (LKPE) is generally regarded to have a poorer outcome for surgical treatment of uncorrectable biliary atresia. We herein described our initial experience of some modifications to make LKPE easier in the treatment of type III biliary atresia (BA). METHODS: During the period July 2012-October 2016, a total of 25 infants with type III BA were treated with a modified LKPE technique. A percutaneous suture was introduced just below the xiphoid process to snare the round ligament and retract the liver; other percutaneous stay sutures were then introduced to the fundus and neck of the gallbladder to elevate the liver and expose the porta hepatis. In 15 cases, part of the hepatic lobus quadratus was removed laparoscopically to expose the porta hepatis. The two elastic rubber bands were put around the portal vein and hepatic artery, and the porta hepatis was exposed by stretching the two rubber bands laterally to facilitate laparoscopic portoenterostomy. RESULTS: Patients were divided into two groups according to their ages at operation: group I: age between 30 and 75 days (n = 18), and group II: age between 76 and 85 days (n = 8). There were no operative deaths, but two patients died of repeated cholangitis and liver failure. Blood loss during operation was minimal and no blood transfusions were required. Operating times varied from 210 to 270 min (mean 232.4 ± 19.0 min). Among the two groups, there were no differences in blood loss (P > 0.05), but there were differences in operating time (P < 0.05). All patients survived the surgery without any intraoperative complications, and the median follow-up time was 25.3 months. Total bilirubin dropped to normal in 18 patients with an additional 5 patients showing a significant overall drop after surgery. CONCLUSIONS: With the original concepts of Kasai portoenterostomy, perfect laparoscopic skills and some key modifications to expose the porta hepatis, our LKPE can be performed safely and successfully with improved outcome for infants with type III BA.

Effects of combined human parathyroid hormone (1-34) and menaquinone-4 treatment on the interface of hydroxyapatite-coated titanium implants in the femur of osteoporotic rats.

The objective of this study was to investigate the effects of human parathyroid hormone (1-34) (PTH1-34; PTH) plus menaquinone-4 (vitamin K2; MK) on the osseous integration of hydroxyapatite (HA)-coated implants in osteoporotic rats. Ovariectomized female Sprague-Dawley rats were used for the study. Twelve weeks after bilateral ovariectomy, HA-coated titanium implants were inserted bilaterally in the femoral medullary canal of the remaining 40 ovariectomized rats. All animals were then randomly assigned to four groups: Control, MK, PTH and PTH + MK. The rats from groups MK, PTH and PTH + MK received vitamin K2 (30 mg/kg/day), PTH1-34 (60 µg/kg, three times a week), or both for 12 weeks. Thereafter, serum levels of γ-carboxylated osteocalcin (Gla-OC) were quantitated by ELISA and the bilateral femurs of rats were harvested for evaluation. The combination of PTH and MK clearly increased the serum levels of Gla-OC (a specific marker for bone formation) compared to PTH or MK alone. The results of our study indicated that all treated groups had increased new bone formation around the surface of implants and increased push-out force compared to Control. In addition, PTH + MK treatment showed the strongest effects in histological, micro-computed tomography and biomechanical tests. In summary, our results confirm that treatment with PTH1-34 and MK together may have a therapeutic advantage over PTH or MK monotherapy on bone healing around HA-coated implants in osteoporotic rats.

[Effect of Ginkgo biloba extract (EGb50) on mitochondrial function in SH-SY5Y cells after hypoxia/reoxygenation injury].

Ischemic cerebrovascular disease and cerebral ischemia/reperfusion injury threaten the health of human being. We studied the protective effect of Ginkgo biloba extract 50 (EGb50) on the mitochondrial function in SH-SY5Y cells after hypoxia/reoxygenation (H/R) injury and explored its mechanisms, so as to provide new ideas for studies on the treatment for ischemic cerebrovascular disease. We established the H/R injury model in SH-SY5Y cells after administrating EGb50. Subsequently, the mitochondrial membrane potential and the concentration of intracellular Ca²âº were measured by flow cytometer. The levels of optic atrophy1 (Opa1) and dynamin-like protein 1 (Drp1) were evaluated by immunofluorescence and western blot. The results showed that the mitochondrial membrane potential was decreased and the level of intracellular Ca²âº was increased after H/R injury. Moreover, the expression of mitochondrial fusion protein Opa1 was decreased, while the expression of mitochondrial fission protein Drp1 was increased. However, EGb50 significantly increased the mitochondrial membrane potential and suppressed the level of intracellular Ca²âº. In addition, EGb50 increased the expression of Opa1 and decreased the expression of Drp1. The results demonstrated that EGb50 has a neuroprotective effect on SH-SY5Y cells after H/R injury, and could improve the energy metabolism and mitochondrial function. The underlying mechanisms may be associated with the regulation of mitochondrial fusion and fission, which provided data support for the treatment of ischemic cerebrovascular disease with EGb50.

The Effect of Functional Mandibular Shift on the Muscle Spindle Systems in Head-Neck Muscles and the Related Neurotransmitter Histamine.

The aim of this study is to explore the effects of abnormal occlusion and functional recovery caused by functional mandible deviation on the head and neck muscles and muscle spindle sensory-motor system by electrophysiological response and endogenous monoamine neurotransmitters' distribution in the nucleus of the spinal tract. Seven-week-old male Wistar rats were randomly divided into 7 groups: normal control group, 2W experimental control group, 2W functional mandible deviation group, 2W functional mandible deviation recovery group, 4W experimental control group, 4W functional mandible deviation group, 4W functional mandible deviation recovery group. Chewing muscles, digastric muscle, splenius, and trapezius muscle spindles electrophysiological response activities at the opening and closing state were recorded. And then the chewing muscles, digastric, splenius, trapezius, and neck trigeminal nucleus were taken for histidine decarboxylase (HDC) detection by high performance liquid chromatography (HPLC), immunofluorescence, and reverse-transcription polymerase chain reaction (RT-PCR). Histamine receptor proteins in the neck nucleus of the spinal tract were also examined by immunofluorescence and RT-PCR. Electromyography activity of chewing muscles, digastric, and splenius muscle was significantly asymmetric; the abnormal muscle electromyography activity was mainly detected at the ipsilateral side. After functional mandibular deviation, muscle sensitivity on the ipsilateral sides of the chewing muscle and splenius decreased, muscle excitement weakened, modulation depth decreased, and the muscle spindle afferent impulses of excitation transmission speed slowed down. Changes for digastric muscle electrical activity were contrary. The functions recovered at different extents after removing the deflector. However, trapezius in all the experimental groups and recovery groups exhibited bilateral symmetry electrophysiological responses, and no significant difference compared with the control group. After functional mandibular deviation, HDC protein and messenger ribonucleic acid (mRNA) levels on the ipsilateral sides of the chewing muscle and splenius increased significantly. HDC level changes for digastric muscle were contrary. After the removal of the mandibular position deflector, HDC protein and mRNA levels decreased on the ipsilateral sides of the chewing muscle and splenius while they increased in the digastric muscle. The difference of histamine decarboxylase content in the bilateral trapezius in each experimental group was small. After functional mandibular deviation, the temporomandibular joint mechanical receptors not only caused the fusimotor fiber hypoallergenic fatigue slow response on the ipsilateral sides of splenius, but also increased the injury neurotransmitter histamine release. The authors' results further support the opinion that the temporomandibular joint receptors may be involved in the mechanical theory of the head and neck muscles nervous system regulation.

PDCD1 strengthens the sensitivity of ovarian cancer to cisplatin chemotherapy by promoting apoptosis.

PURPOSE: The primary purpose of this study was to make clear the role of PDCD1 in the occurrence and progression of ovarian cancer, and explain its mechanism. METHODS: RT-PCR, westem blot, MTT and immunohistochemistry were used to detect the expression levels of PDCD1 mRNA and protein in human ovarian cancer cell lines (SKOV3, 3AO, CAOV3 and OVCAR3), human normal ovary, serous cystadenoma, and serous cystadenocarcinoma tissue. SKOV3, SKOV3-MOCK, and SKOV3-PDCD1 cells were subcutaneously injected into the armpit of nude mice to observe the effect of PDCD1 expression on tumorigenic ability. Cisplatin, carboplatin, cyclophosphamide, etoposide and paclitaxel were used in the experiments. RESULTS: PDCD1 was lowly expressed in SKOV3 and 3AO, moderately expressed in CAOV3, and highly expressed in OVCAR3. PDCD1 significantly inhibited the proliferation and clone formation ability of the ovarian carcinoma cell line SKOV3. In the SKOV3-PDCD1 group, the tumor formation rate decreased significantly and the tumor formation time prolonged significantly. The CAOV3 and OVCAR3 cells with high expression of PDCD1 were more sensitive to cisplatin. The SKOV3 and 3AO cells with low expression of PDCD1 were less sensitive to cisplatin. Compared with the SKOV3- MOCK control group, the apoptosis rate and the expression levels of the caspase-3/8 proteins activity increased significantly in the PDCD1 overexpression group. The expression levels of caspase-9 and Bax increased slightly. No significant changes were observed in the expression of Bcl-2. CONCLUSION: The expression of PDCD1 decreased significantly in human ovarian cancer. Overexpression of PDCD1 can inhibit the proliferation capacity of ovarian cancer. PDCD1 strengthens the sensitivity of ovarian cancer to cisplatin by promoting cisplatin-induced apoptosis.

Lipocalin 2 promotes the migration and invasion of esophageal squamous cell carcinoma cells through a novel positive feedback loop.

Lipocalin 2 (LCN2) is a poor prognostic factor in esophageal squamous cell carcinoma (ESCC), however its functional roles and molecular mechanisms of action remain to be clarified. Here, we described the functions and signaling pathways for LCN2 in ESCC. Overexpression of LCN2 in ESCC cells accelerated cell migration and invasion in vitro, and promoted lung metastasis in vivo. Blocking LCN2 expression inhibited its pro-oncogenic effect. Either overexpression of LCN2 or treatment with recombinant human LCN2 protein enhanced the activation of MEK/ERK pathway, which in turn increases endogenous LCN2 to increase MMP-9 activity. The decreased p-cofilin and increased p-ERM induced by pERK1/2 cause the cytoskeleton F-actin rearrangement and alter the behavior of ESCC cells mediated by LCN2. As a consequence, activation of MMP-9 and the rearrangement of F-actin throw light on the mechanisms for LCN2 in ESCC. These results imply that LCN2 promotes the migration and invasion of ESCC cells through a novel positive feedback loop.

The effects of combined human parathyroid hormone (1-34) and simvastatin treatment on the interface of hydroxyapatite-coated titanium rods implanted into osteopenic rats femurs.

The effect of human parathyroid hormone 1-34 (PTH) and simvastatin (SIM) alone could promote bone healing in osteoporotic implant fixation, but there are no reports about the combined use of PTH and SIM for promotion of bone healing around implant in osteoporotic settings. This study aims to investigate effects of PTH + SIM on implant stabilization in osteopenic rats. Fourteen weeks after chronically fed a low protein diet, osteopenic rats randomly received implants. Subsequently, the animals were randomly divided into four groups: Control, SIM, PTH and PTH + SIM. Then all rats from groups PTH, SIM and PTH + SIM received PTH (40 µg/kg, three times a week), SIM (25 mg/kg, daily), or both for 12 weeks. The results of our study indicated that all treatments promoted bone healing around implant compared to Control, but PTH + SIM treatment showed significantly stronger effects than PTH or SIM alone in histological, micro-CT, and biomechanical tests. The results indicated additive effects of PTH and SIM on implant fixation in osteoporotic rats.

Robust evidence for five new Graves' disease risk loci from a staged genome-wide association analysis.

Graves' disease (GD), characterized by autoantibodies targeting antigens specifically expressed in thyroid tissues causing hyperthyroidism, is triggered by a combination of genetic and environmental factors. However, only a few loci for GD risk were confirmed in the various ethnic groups, and additional genetic determinants have to be detected. In this study, we carried out a three-stage study in 9529 patients with GD and 9984 controls to identify new risk loci for GD and found genome-wide significant associations in the overall populations for five novel susceptibility loci: the GPR174-ITM2A at Xq21.1, C1QTNF6-RAC2 at 22q12.3-13.1, SLAMF6 at 1q23.2, ABO at 9q34.2 and an intergenic region harboring two non-coding RNAs at 14q32.2 and one previous indefinite locus, TG at 8q24.22 (Pcombined < 5 × 10(-8)). The genotypes of corresponding variants at 14q32.2 and 8q24.22 were correlated with the expression levels of C14orf64 and a TG transcript skipping exon 46, respectively. This study increased the number of GD loci with compelling evidence and indicated that non-coding RNAs might be potentially involved in the pathogenesis of GD.

miR-200b suppresses invasiveness and modulates the cytoskeletal and adhesive machinery in esophageal squamous cell carcinoma cells via targeting Kindlin-2.

To further our understanding of the pathobiology of esophageal squamous cell carcinoma (ESCC), we previously performed microRNA profiling that revealed downregulation of miR-200b in ESCC. Using quantitative real-time PCR applied to 88 patient samples, we confirmed that ESCC tumors expressed significantly lower levels of miR-200b compared with the respective adjacent benign tissues (P = 0.003). Importantly, downregulation of miR-200b significantly correlated with shortened survival (P = 0.025), lymph node metastasis (P = 0.002) and advanced clinical stage (P = 0.020) in ESCC patients. Quantitative mass spectrometry identified 57 putative miR-200b targets, including Kindlin-2, previously implicated in the regulation of tumor invasiveness and actin cytoskeleton in other cell types. Enforced expression of miR-200b mimic in ESCC cells led to a decrease of Kindlin-2 expression, whereas transfection of miR-200b inhibitor induced Kindlin-2 expression. Furthermore, transfection of miR-200b mimic or knockdown of Kindlin-2 in ESCC cells decreased cell protrusion and focal adhesion (FA) formation, reduced cell spreading and invasiveness/migration. Enforced expression of Kindlin-2 largely abrogated the inhibitory effects of miR-200b on ESCC cell invasiveness. Mechanistic studies revealed that Rho-family guanosine triphosphatases and FA kinase mediated the biological effects of the miR-200b-Kindlin-2 axis in ESCC cells. To conclude, loss of miR-200b, a frequent biochemical defect in ESCC, correlates with aggressive clinical features. The tumor suppressor effects of miR-200b may be due to its suppression of Kindlin-2, a novel target of miR-200b that modulates actin cytoskeleton, FA formation and the migratory/invasiveness properties of ESCC.

Identification of a novel lysyl oxidase-like 2 alternative splicing isoform, LOXL2 Δe13, in esophageal squamous cell carcinoma.

Lysyl oxidase-like 2 (LOXL2) participates in every stage of cancer progression and promotes invasion and metastasis. In this study, we identified a novel alternative splicing isoform of LOXL2, namely LOXL2 Δe13, which lacked exon 13. Deletion of exon 13 caused an open reading frame shift and produced a truncated protein. LOXL2 Δe13 was expressed ubiquitously in cell lines and tissues and was mainly localized to the cytoplasm. Although it showed impaired deamination enzymatic activity compared with full-length LOXL2, LOXL2 Δe13 promoted the cell mobility and invasion of esophageal squamous cell carcinoma (ESCC) cells to greater degrees. In further research on the mechanisms, gene expression profiling and signaling pathway analysis revealed that LOXL2 Δe13 induced the expression of MAPK8 without affecting the FAK, AKT, and ERK signaling pathways. RNAi-mediated knockdown of MAPK8 could block the cell migration promoted by LOXL2De13, but it had little effect on that of full-length LOXL2. Our data suggest that LOXL2 Δe13 modulates the effects of cancer cell migration and invasion through a different mechanism from that of full-length LOXL2 and that it may play a very important role in tumor carcinogenesis and progression.

Down-regulated desmocollin-2 promotes cell aggressiveness through redistributing adherens junctions and activating beta-catenin signalling in oesophageal squamous cell carcinoma.

In contrast to the well-recognized loss of adherens junctions in cancer progression, the role of desmosomal components in cancer development has not been well explored. We previously demonstrated that desmocollin-2 (DSC2), a desmosomal cadherin protein, is reduced in oesophageal squamous cell carcinoma (ESCC), and is associated with enhanced tumour metastasis and poor prognosis. Here, we report that restoration of DSC2 in ESCC cells impeded cell migration and invasion both in vitro and in vivo, whereas siRNA-mediated suppression of DSC2 expression increased cell motility. In E-cadherin-expressing ESCC cells, DSC2 restoration strengthened E-cadherin-mediated adherens junctions and promoted the localization of ß-catenin at these junctions, which indirectly inhibited ß-catenin-dependent transcription. These effects of DSC2 were not present in EC109 cells that lacked E-cadherin expression. ESCC patients with tumours that had reduced E-cadherin and negative DSC2 had poorer clinical outcomes than patients with tumours that lacked either E-cadherin or DSC2, implying that the invasive potential of ESCC cells was restricted by both DSC2 and E-cadherin-dependent junctions. Further studies revealed that DSC2 was a downstream target of miR-25. Enhanced miR-25 promoted ESCC cell invasiveness, whereas restoration of DSC2 abolished these effects. Collectively, our work suggests that miR-25-mediated down-regulation of DSC2 promotes ESCC cell aggressiveness through redistributing adherens junctions and activating beta-catenin signalling.

The polymorphism of ARNTL2 (BMAL2) gene rs2306074 C>T is associated with susceptibility of Alzheimer disease in Chinese population.

In the present study, we investigated whether polymorphism of ARNTL2 (BMAL2) gene rs2306074 T/C was associated with susceptibility of Alzheimer disease (AD) in Chinese population. A case-control method was employed in this study. 296 unrelated AD patients and 423 control subjects were recruited in current study. The prevalence of C carriers in BMAL2 gene rs2306074 T/C in AD patients was significantly higher than that of control subjects in both the whole sample and APOE ε 4 non-carriers (in the whole sample: χ (2) = 5.938, P = 0.012; in APOE ε 4 non-carriers: χ (2) = 9.048, P < 0.0001). In addition, both in the whole sample and APOE ε 4 non-carriers, prevalence of CC genotypes in BMAL2 gene rs2306074 of AD patients was also significantly higher than that in controls (in the whole sample: χ (2) = 5.126, P = 0.018; in APOE ε 4 non-carriers: χ (2) = 7.389, P = 0.023). However, there was no significant difference of prevalence of C carriers and CC genotypes in BMAL2 gene rs2306074 T/C between AD patients and control subjects among APOE ε 4 carriers (C carriers: χ (2) = 0.020, P = 0.900; CC genotypes: χ (2) = 0.017, P = 0.946). C carriers in BMAL2 gene rs2306074 T/C are associated with a high susceptibility of AD among APOE ε 4 non-carriers but not among APOE ε 4 carriers in Chinese population.