Serine/threonine-protein kinase D2-mediated phosphorylation of DSG2 threonine 730 promotes esophageal squamous cell carcinoma progression.

Desmoglein-2 (DSG2) is a transmembrane glycoprotein belonging to the desmosomal cadherin family, which mediates cell-cell junctions; regulates cell proliferation, migration, and invasion; and promotes tumor development and metastasis. We previously showed serum DSG2 to be a potential biomarker for the diagnosis of esophageal squamous cell carcinoma (ESCC), although the significance and underlying molecular mechanisms were not identified. Here, we found that DSG2 was increased in ESCC tissues compared with adjacent tissues. In addition, we demonstrated that DSG2 promoted ESCC cell migration and invasion. Furthermore, using interactome analysis, we identified serine/threonine-protein kinase D2 (PRKD2) as a novel DSG2 kinase that mediates the phosphorylation of DSG2 at threonine 730 (T730). Functionally, DSG2 promoted ESCC cell migration and invasion dependent on DSG2-T730 phosphorylation. Mechanistically, DSG2 T730 phosphorylation activated EGFR, Src, AKT, and ERK signaling pathways. In addition, DSG2 and PRKD2 were positively correlated with each other, and the overall survival time of ESCC patients with high DSG2 and PRKD2 was shorter than that of patients with low DSG2 and PRKD2 levels. In summary, PRKD2 is a novel DSG2 kinase, and PRKD2-mediated DSG2 T730 phosphorylation promotes ESCC progression. These findings may facilitate the development of future therapeutic agents that target DSG2 and DSG2 phosphorylation. © 2024 The Pathological Society of Great Britain and Ireland.

A Novel Multi-view Bi-clustering method for identifying abnormal Co-occurrence medical visit behaviors.

Abnormal co-occurrence medical visit behavior is a form of medical insurance fraud. Specifically, an organized gang of fraudsters hold multiple medical insurance cards and purchase similar drugs frequently at the same time and the same location in order to siphon off medical insurance funds. Conventional identification methods to identify such behaviors rely mainly on manual auditing, making it difficult to satisfy the needs of identifying the small number of fraudulent behaviors in the large-scale medical data. On the other hand, the existing single-view bi-clustering algorithms only consider the features of the time-location dimension while neglecting the similarities in prescriptions and neglecting the fact that fraudsters may belong to multiple gangs. Therefore, in this paper, we present a multi-view bi-clustering method for identifying abnormal co-occurrence medical visit behavioral patterns, which performs cluster analysis simultaneously on the large-scale, complex and diverse visiting record dimension and prescription dimension to identify bi-clusters with similar time-location features. The proposed method constructs a matrix view of patients and visit records as well as a matrix view of patients and prescriptions, while decomposing multiple data matrices into sparse row and column vectors to obtain a consistent patient population across views. Subsequently the proposed method identifies the corresponding abnormal co-occurrence medical visit behavior and may greatly facilitate the safe operations and the sustainability of medical insurance funds. The experimental results show that our proposed method leads to more efficient and more accurate identifications of abnormal co-occurrence medical visit behavior, demonstrating its high efficiency and effectiveness.

Safety and Efficacy of Oral Hydroxychloroquine in the Treatment of Ophthalmic Disease Associated with Sjögren's Syndrome.

Background: Dry eye disease is common among patients with primary Sjögren's syndrome (pSS). Hydroxychloroquine (HCQ), known for its immunomodulatory effects and minimal adverse effects, has emerged as a pivotal treatment option for pSS. Nonetheless, conflicting evidence exists regarding the therapeutic efficacy of HCQ in managing dry eye disease associated with pSS. Objectives: To evaluate the safety and efficacy of oral hydroxychloroquine in treating dry eye disease associated with pSS. Methods: A prospective randomized controlled study was conducted, enrolling pSS patients with moderate to severe dry eye disease. Participants were randomly assigned to an oral HCQ group and an observation group. Various scales (ESSDAI, ESSPRI, OSDI, and SPEED questionnaire score), dry eye-related tests (OSS score, TBUT, and Schirmer test I), ophthalmology-specific tests (BCVA, SD-OCT RT, field of view, latency and amplitudes for multifocal ERG ring 1 and ring 2), whole body protein levels (serum IgA, IgG, and IgM), and blood glucose were assessed before and after 12 months of treatment. Results: Pairwise comparison of the observed indicator baseline revealed no statistical significance (P > .05). After 12 months, the HCQ group exhibited notable improvements in ESSPRI, serum IgA, and Schirmer test I results compared to the control group (P < .05). Both groups demonstrated significant improvements in BCVA, OSDI, SPEED scores, and dry eye-associated examinations compared to baseline (P < .05). Serum IgG and IgM levels decreased in the HCQ group after 12 months of treatment, but without statistical significance (P > .05). None cases of HCQ retinopathy were reported during follow-up. Conclusions: Oral HCQ was demonstrated safety and efficacy in managing pSS-related dry eye disease. Treatment with Oral HCQ markedly reduced the ESSPRI score, improve patients' systemic dryness symptoms, and greatly decreased blood IgA levels. Combined with topical cyclosporin, HCQ improved Schirmer test I scores and alleviated ocular surface inflammation and dry eye signs and symptoms.

Pre-calving energy density and rumen protected lysine impacted blood metabolites and biomarkers of liver functions in dairy cows during the transition period.

Dairy cows usually face negative energy balance and disorders of normal organ function due to a mismatch between energy intake and energy demand. Negative energy balance directly affects liver function and blood metabolites because the liver is used as source of energy supply and a center of metabolic activity. This study was aimed to determine the effect of pre-calving energy density and rumen-protected lysine on blood metabolites and biomarkers of liver functions in the dairy cows during the transition period. Forty 3rd lactation Holstein cows going to enter their 4th lactation were randomly allocated to one of the four dietary treatments (high energy with rumen-protected lysine (HERPL) = 1.53NEL plus 40 g Lys, high energy without lysine (HECK) = 1.53NEL, low energy with rumen-protected lysine (LERPL) = 1.37NEL plus 40 g Lys, and low energy without lysine (LECK) = 1.37NEL arranged in a 2 × 2 factorial design. Blood samples were collected during the transition period, and concentrations of blood metabolites and biomarkers of liver function were measured. Interaction between pre-calving high-energy diet and rumen-protected lysine tended to increase plasma albumin, numerically increased glucose, decreased triglyceride, total bilirubin, and aspartate aminotransferase concentrations. The result revealed that pre-calving high-energy density increased insulin, albumin and decreased blood urea nitrogen and total bilirubin concentrations and substantial favor liver functions during the transition period.

First Report of Leaf Spot Caused by Phyllosticta capitalensis on Alpinia oxyphylla Miq. in China.

Alpinia oxyphylla Miq. is mainly distributed in Hainan, Guangdong and Guangxi provinces of China. Between July and August 2021, a leaf spot disease was observed in Ledong, Hainan Province, China (18°70'20.50″ N, 109°25'25.47″E) on A.oxyphylla. The incidence of infected leaves ranged from 8% to 10%, and the incidence rate of infected plants was about 50%. Symptoms appeared as primary yellow-brown withered spots on the diseased leaves, which further developed into irregular red-brown spots. The center of the lesions was gray-black, and the tissue was irregularly necrotic, ruptured or perforated, and there were yellow chlorotic halos around the edges of the lesions (Figure 1A). Tissues 5 mm in diameter were taken from the junction of diseased and healthy tissue for pathogen isolation, Successively, a total of 8 isolates were obtained from the affected leaves. Three single spore isolates (YZ-HN-001, YZ-HN-043 and YZ-HN-051) were obtained and confirmed to be identical based on morphological characteristics. Therefore, the representative isolate YZ-HN-001 was selected for morphological and molecular identification. On Potato Dextrose Agar(PDA), the colony was gray-white at first and gradually turned dark green to dark brown with lead gray on the back, growth was slow, and mycelium was short and dense (Figure 1B and Figure 1C). Pycnidia were epiphyllous, globose, brown (about 120-140 µm in diameter), and conidia were elliptical, colorless, single celled and smooth (8-12×4-7 µm) (Figure 1D). Molecular identification was performed by partially sequencing the internal transcribed spacer gene (ITS), 18S rRNA gene and the actin gene (ACT) by using the primers ITS1/ITS4 (White et al. 1990), EF4/Fungi5 (Khodaparase et al. 2005) and ACT-512F/ACT-783R (Carbone and Kohn. 1999). The sequences of the amplified fragments were deposited in GenBank, the ITS sequence (ON005130, 616 bp) showed 100% identity with Phyllosticta capitalensis strain CGMCC3.14345 (JN791605.1), the 18S rRNA sequence (ON005129, 541 bp) showed 99% identity with P. capitalensis isolate MUCC0029 (AB454185.1) and the ACT sequence (ON049348, 251 bp) showed 100% identity with P. capitalensis strain DZSN202005-2 (MW533248.1). A phylogenetic analysis was conducted in MEGA X using the neighbor-joining method and showed that isolate YZ-HN-001 clustered together with P. capitalensis (Figure 2). Based on the above morphological and molecular characteristics, the isolate was determined to be P. capitalensis. Pathogenicity tests were conducted in three replicates by inoculating surface-sterilized leaves of A. oxyphylla. The leaves were wounded and inoculated with colonized PDA plugs (5×5 mm) from 15-day-old cultures. Control leaves wounded in the same way and were inoculated with sterile PDA plugs (5×5 mm). Leaves were moisturized by spraying with sterile water every three days. After 20 days at room temperature (23 to 28℃), similar symptoms were observed in the inoculated leaves as in the field (Figure 1E), but no symptoms were observed on the control leaves (Figure 1F). The same P. capitalensis was reisolated in the inoculated leaves, confirming Koch's postulates. Phyllosticta capitalensis has been reported to cause leaf spots or black spots on various host plants around the world (Wikee et al. 2013), including on oil palm (Nasehi et al. 2020), tea plant (Cheng et al. 2019 ), and castor (Tang et al. 2020). Nevertheless, to our knowledge, this is the first report of leaf spot caused by P. capitalensis on A. oxyphylla worldwide.

The effect of curcumin supplementation on recovery following exercise-induced muscle damage and delayed-onset muscle soreness: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: curcumin consumption may have a protective effect against exercise-induced muscle damage (EIMD) through stabilization of the cell membrane via inhibition of free radical formation. Evidence supporting a protective role of curcumin after physical activity induced muscle injury in humans, however, it is inconsistent. METHODS: Medline, Scopus, and Google scholar were systematically searched up to May 2020. The Cochrane Collaboration tool for assessing the risk of bias was used for assessing the quality of studies. Random effects model, weighted mean difference (WMD), and 95% confidence interval (CI) were used for estimating the overall effect. Between-study heterogeneity was assessed using the chi-squared and I2 statistic. RESULTS: The results revealed a significant effect of curcumin supplementation on reducing creatine kinase (CK) (weighted mean difference [WMD] = -48.54 IU.L-1 ; 95% CI: -80.667, -16.420; p = .003) and muscle soreness index decrease (WMD = -0.476; 95% CI: -0.750, -0.202; p = .001). Moreover, a subgroup analysis resulted in a significant decrease in CK concentrations and muscle soreness index, according to follow-ups after exercise, dose of curcumin, duration of studies, exercise type, train status and study design. CONCLUSIONS: The current evidence revealed a efficacy of curcumin in reducing CK serum levels and muscle soreness index among adults. Therefore, curcumin may be known as a priority EIMD recovery agent in interventions.

The roles of miRNA, lncRNA and circRNA in the development of osteoporosis.

Osteoporosis is a common metabolic bone disease, influenced by genetic and environmental factors, that increases bone fragility and fracture risk and, therefore, has a serious adverse effect on the quality of life of patients. However, epigenetic mechanisms involved in the development of osteoporosis remain unclear. There is accumulating evidence that epigenetic modifications may represent mechanisms underlying the links of genetic and environmental factors with increased risk of osteoporosis and bone fracture. Some RNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have been shown to be epigenetic regulators with significant involvement in the control of gene expression, affecting multiple biological processes, including bone metabolism. This review summarizes the results of recent studies on the mechanisms of miRNA-, lncRNA-, and circRNA-mediated osteoporosis associated with osteoblasts and osteoclasts. Deeper insights into the roles of these three classes of RNA in osteoporosis could provide unique opportunities for developing novel diagnostic and therapeutic approaches to this disease.

Administration of alpha-lipoic acid could maintain bone mass and bone strength in senile female rats with alcohol consumption.

Previous studies have demonstrated the damaging effect of alcohol (ALH) consumption on bone tissue and bone metabolism. Alpha-lipoic acid (ALA) promotes osteoblast proliferation and inhibits osteoclast proliferation, and positively affects bone regeneration; however, reports about effects of ALA on bone loss for aged female rats with ALH consumption are limited. This study was designed to investigate the impact of treatment with ALA on bone loss for aged female rats with ALH consumption. In this study 30 female Sprague-Dawley rats (22 months old), weighing approximately 520 g, were incorporated. The animals were randomly divided into three groups: group CON, group ALH and group ALH + ALA and received saline, ALH, ALH plus ALA treatment until death at 16 weeks, respectively. The results of maintaining bone mass and bone strength in senile female rats with ALH consumption were evaluated by histology, microcomputerized tomography, gene expression analysis and biomechanical tests. Results from this study indicated that ALH + ALA had stronger effects on the prevention and treatment of osteoporosis in senile female rats with ALH consumption. The ALH + ALA produced stronger effects on the bone volume ratio (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N) and trabecular separation (Tb.Sp), BMD and strength of distal femurs, and regulation of osteogenesis and bone resorption-related gene expression. These results seem to indicate that ALA intervention prevents bone loss in senile female rats with ALH consumption.

[Absorption mechanism of dragon's blood phenolic extracts in Caco-2 cells].

The purpose of this study was to study the absorption characteristics of eight main components from dragon's blood phenolic extracts in Caco-2 cells based on the humancolon cancer cell Caco-2 model, and to clarify the oral absorption mechanism of such phenolic extracts. UPLC-MS/MS was used in this study to determine the content of 8 active ingredients including thevetiaflavone, 7,4'-dihydroxyflavone, 7,4'-dihydroxy-5-methoxyhomoisoflavanone, 7,4'-dihydroxyhomoisoflavanone, loureirin C, loureirin A, loureirin B and pterostilbene from dragon's blood phenolic extracts, and Caco-2 cells were used to investigate the effects of incubation time, concentration, temperature, P-gp inhibitor, MRP inhibitor, OCTN1 inhibitor and OCTN2 inhibitor on the absorption of each component. In addition, the transport experiment was conducted to measure the apparent permeability coefficient P_(app) and transport rate of the eight main components to predict the oral absorption mechanism of dragon's blood phenolic extracts. The experimental results showed that the cell uptake of the eight main components in dragon's blood phenolic extracts was time-dependent and concentration dependent, and the uptake of each component did not need to consume energy, which was consistent with the passive diffusion process. P-gp inhibitor, MRP inhibitor and OCTN1 inhibitor had no effect on the cell uptake of each component, only the addition of OCTN2 inhibitor significantly reduced the uptake of pterostilbene(P<0.05). In the transport results, the ER values of the outflow rates of the eight components were all less than 1.5. The above results show that the absorption mechanism of the eight components in Draconis resina phenolic extract may be passive diffusion, and pterostilbene may be the substrate of OCTN2.

Super-Enhancer-Driven Long Non-Coding RNA LINC01503, Regulated by TP63, Is Over-Expressed and Oncogenic in Squamous Cell Carcinoma.

BACKGROUND & AIMS: Long non-coding RNAs (lncRNAs) are expressed in tissue-specific pattern, but it is not clear how these are regulated. We aimed to identify squamous cell carcinoma (SCC)-specific lncRNAs and investigate mechanisms that control their expression and function. METHODS: We studied expression patterns and functions of 4 SCC-specific lncRNAs. We obtained 113 esophageal SCC (ESCC) and matched non-tumor esophageal tissues from a hospital in Shantou City, China, and performed quantitative reverse transcription polymerase chain reaction assays to measure expression levels of LINC01503. We collected clinical data from patients and compared expression levels with survival times. LINC01503 was knocked down using small interfering RNAs and oligonucleotides in TE7, TE5, and KYSE510 cell lines and overexpressed in KYSE30 cells. Cells were analyzed by chromatin immunoprecipitation sequencing, luciferase reporter assays, colony formation, migration and invasion, and mass spectrometry analyses. Cells were injected into nude mice and growth of xenograft tumors was measured. LINC01503 interaction with proteins was studied using fluorescence in situ hybridization, RNA pulldown, and RNA immunoprecipitation analyses. RESULTS: We identified a lncRNA, LINC01503, which is regulated by a super enhancer and is expressed at significantly higher levels in esophageal and head and neck SCCs than in non-tumor tissues. High levels in SCCs correlated with shorter survival times of patients. The transcription factor TP63 bound to the super enhancer at the LINC01503 locus and activated its transcription. Expression of LINC01503 in ESCC cell lines increased their proliferation, colony formation, migration, and invasion. Knockdown of LINC01503 in SCC cells reduced their proliferation, colony formation, migration, and invasion, and the growth of xenograft tumors in nude mice. Expression of LINC01503 in ESCC cell lines reduced ERK2 dephosphorylation by DUSP6, leading to activation of ERK signaling via MAPK. LINC01503 disrupted the interaction between EBP1 and the p85 subunit of PI3K, increasing AKT signaling. CONCLUSIONS: We identified an lncRNA, LINC01503, which is increased in SCC cells compared with non-tumor cells. Increased expression of LINC01503 promotes ESCC cell proliferation, migration, invasion, and growth of xenograft tumors. It might be developed as a biomarker of aggressive SCCs in patients.

De Novo Paternal FBN1 Mutation Detected in Embryos Before Implantation.

BACKGROUND Marfan syndrome (MFS) is an autosomal dominant disease caused by mutations in the Fibrillin (FBN)1 gene and characterized by disorders in the cardiovascular, skeletal, and visual systems. The diversity of mutations and phenotypic heterogeneity of MFS make prenatal molecular diagnoses difficult. In this study, we used pre-implantation genetic diagnosis (PGD) to identify the pathogenic mutation in a male patient with MFS and to determine whether his offspring would be free of the disease. MATERIAL AND METHODS The history and pedigree of the proband were analyzed. Mutation analysis was performed on the couple and immediate family members. The couple chose IVF treatment and 4 blastocysts were biopsied. PGD was carried out by targeted high-throughput sequencing of the FBN1 gene in the embryos, along with single-nucleotide polymorphism haplotyping. Sanger sequencing was used to confirm the causative mutation. RESULTS c.2647T>C (p.Trp883Arg) was identified as the de novo likely pathogenic mutation in the proband. Whole-genome amplification and sequencing of the 3 embryos revealed that they did not carry the mutation, and 1 blastocyst was transferred back to the uterus. The amniocentesis test result analyzed by Sanger sequencing confirmed the PGD. A premature but healthy infant free of heart malformations was born. CONCLUSIONS The de novo mutation c.2647T>C (p.Trp883Arg) in FBN1 was identified in a Chinese patient with MFS. Embryos without the mutation were identified by PGD and resulted in a successful pregnancy.

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.

Single-stage in situ suture repair of multiple-ligament knee injury: a retrospective study of 17 patients (18 knees).

BACKGROUND: Multiple-ligament injured knee (MLIK) is a rare but severe injury. Although the principles of MLIK management have progressed over the past 40 years, there is a paucity of high-quality evidence upon which to base the management of MLIK. Treatment strategies for MLIK are challenging for most orthopedic surgeons, and the optimal treatment remains controversial, especially with regard to repair vs. reconstruction of the ligaments. The aim of the present study was to observe clinical outcomes of single-stage in situ suture repair of knee dislocation with multiple-ligament injury using nonabsorbable suture material. METHODS: Consecutive patients with MLIK between 2002 and 2010 were included, for a total of 25 patients with knee dislocation. 17 patients (18 knees) with closed knee dislocation with a mean follow-up of 4.8 ± 1.3 years were retrospective analyzed. All patients were treated surgically with single-stage in situ suture repair for all injured ligaments and followed a standardized postoperative rehabilitation protocol. The VAS score, satisfactory score, total SF-36 score, Lysholm score, Tegner score, the Meyers functional rating and the ranges of motion and knee stability were used to evaluate outcomes. RESULTS: At final follow-up, mean visual analog scale score was 2.4 ± 0.9, patient satisfaction score was 8.0 ± 1.1, 36-item Short-Form Health Survey total score was 85.5 ± 10.4, and mean Lysholm score was 87.5 ± 7.7. There were significant differences between mean preinjury and postoperative Tegner activity scores (5.6 ± 1.4 and 3.4 ± 1.7, respectively; P < 0.01) and in mean range of motion between the injured and contralateral knees (112.5 ± 8.4° and 129.6 ± 10.3°, respectively; P < 0.01). At final follow-up, no patient demonstrated obvious ligamentous laxity, and only one patient was unable to return to work. Three patients had knee joint stiffness, two had wound problems (infection or fat liquefaction), and two had heterotopic bone formation. CONCLUSIONS: Single-stage in situ suture repair of injured ligaments confers advantages of reliable fixation and early exercise. It could be considered as an alternate and effective option in the dislocation knee with multiple-ligament injury.

[Research Progress in Mixed Lineage Kinase Domain-Like].

Necroptosis is a novel programmed cell death mechanism which is caspase independent. It is mediated by specific signaling via a death receptor ligation. Necroptosis usuaUy arises when the apoptotic Pathway is inhibited, and is characterized by a necrotic morphology. Recently many reports have revealed that necroptosis is precisely regulated by a cellular signaling pathway, like apoptosis. Receptor interaction protein kinase 1 and receptor interaction protein kinase 3 kinases are the key regulators of this alternative cell death mechanism. MLKL plays an important role in TNF-induced programmed necrosis pathway. In this paper physiological function and molecular mechanism were reviewed.

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.

Uterine myomas treated with microwave ablation: the agreement between ablation volumes obtained from contrast-enhanced sonography and enhanced MRI.

PURPOSE: This study explores the agreement between ablated uterine myoma volumes obtained from contrast-enhanced sonography and enhanced magnetic resonance imaging (MRI) after microwave ablation therapy. MATERIALS AND METHODS: Twenty uterine myomas in 18 patients (average size: 5.56 ± 1.26 cm) were successfully treated by microwave ablation. Contrast-enhanced sonography and enhanced MRI were performed within 7 days after the treatment. The ablation range of uterine myomas was observed and the ablation volume was calculated. By using the intraclass correlation coefficient (ICC) and Bland-Altman regression analysis, the agreement between ablated uterine myoma volumes obtained from contrast-enhanced sonography and enhanced MRI after microwave ablation therapy was analysed. RESULTS: The ablated volume ranged from 13.66 to 135.27 cm(3) after ablation, and the mean volume was 66.59 ± 35.71 cm(3) by using contrast-enhanced sonography. Respectively, the ablated volume ranged from 10.88 to 137.83 cm(3), and the mean volume was 66.81 ± 35.45 cm(3) by using enhanced MRI. The limits of agreement between the two methods were (-10.83 cm(3), 8.39 cm(3)), ICC was 0.991 (F = 209.61, P < 0.05), and 95% confidence interval is (0.976, 0.996). The results revealed a good agreement between the two examination methods of contrast-enhanced sonography and enhanced MRI. CONCLUSIONS: Contrast-enhanced sonography and enhanced MRI can be used interchangeably in observing the ablation range of uterine myomas treated with microwave ablation. Contrast-enhanced sonography can be used as a preferred non-invasive examination and for follow-up. Meanwhile, enhanced MRI can be used to comprehensively determine the relationships among uterine myomas, the entire uterus, and surrounding tissues.

[Infrared, Raman and density functional study of vibration spectra of 2, 3-dichloropyrazine].

Fourier transform infrared (FTIR) spectra of 2,3-dichloropyrazine in the region 400-4000 cm(-1) were measured under solid state condition using KBr pellets method and liquid state by the melting method, besides, a Fourier transform Raman (FT-Raman) spectra in region 600-4 000 cm(-1) was recorded. Then equilibrium geometry of 2,3-DCP was optimized, and based on this, the harmonic vibrational frequencies, infrared intensities and Raman activities were calculated using B3LYP method of the density function theory (DFT) in conjunction with 6-311++G(2df, 2pd) basis set, furthermore, a comprehensive anharmonic calculation was also been performed for obtaining more accurate vibrational frequencies using second-order perturbation theory treatment based on quadratic, cubic and quartic force constants. Infrared and Raman spectra were simulated corresponding to theory. Experimental FTIR and FT-Raman bands were compared with those positions of peaks obtained from anharmonic calculations and intensities or activities from harmonic carefully. Each vibrational band was assigned and interpreted in detail with help of potential energy distribution (PED) for the first time. In addition, it was shown that anharmonic results exactly reproduced to experimental data, improved the validity of prediction greatly in vibration frequencies, discrepancies between anharmonic and experimental results were limited to below 10 cm(-1) in most of vibrational bands, even if in the high energy regions, which have a poor performance for hanmonic calculation, and these differences would be decreased to lower than 19 cm(-1). It is extremely helpful for assigning and predicting vibrational spectra. Present conclusion can be expanded to others molecular systems.

Dislocation Does Not Seem To Be an Absolute Factor Effecting the Short- to Medium-Term Poor Prognosis of Patients with Acetabular Posterior Wall Fracture.

Dislocation is a complication of acetabular fractures involving the posterior wall, but whether dislocation is an absolute factor impacting the short- to medium-term prognosis of the hip joint remains controversial. This study aimed to compare the short- to medium-term clinical and radiological results among patients diagnosed with an acetabular fracture involving the posterior wall, with or without dislocation.Seventy-nine patients diagnosed with an acetabular fracture involving the posterior wall were retrospectively divided into posterior dislocation and non-dislocation groups. All fractures were open reduction + internal fixation with a plate screw combination through the single Kocher-Langenbeck approach. The short- to medium-term radiographic outcomes of follow-up were evaluated using the Matta radiologic grading system, while the clinical outcomes were evaluated using the modified Merle d'Aubigné-Postel evaluation system.The mean follow-up duration for all patients was 43.90 (range 24-75) months. Both groups achieved similar short- to medium-term clinical and radiographic results. There seems to be no significant differences between the two groups regarding the short- to medium-term assessment of clinical and radiographic results and the occurrence of postoperative complications (p > 0.05).In patients with acetabular fractures involving the posterior wall, hip dislocation is probably not an absolute determinant of a poor outcome. Even with early reduction, the short- to medium-term prognosis results appear similar to those of patients without dislocation.

Potential effects of different cell death inhibitors in protecting against ischemia-reperfusion injury in steatotic liver.

Liver ischemia-reperfusion injury (IRI) remains a common issue and with the increasing incidence of Nonalcoholic fatty liver disease (NAFLD), which are more sensitive to IRI, it is crucial to explore the possible strategy to alleviate the steatotic liver IRI. Several modes of cell death are involved in hepatocytes and immune cells during hepatic IRI, and the effects of different cell death inhibitors including apoptosis, necroptosis, pyroptosis, and ferroptosis in steatotic liver IRI have not been investigated. We established 70% IRI model on steatotic liver in mice. Apoptosis, necroptosis, pyroptosis and ferroptosis inhibitors were used to evaluate their effects on liver injury, inflammatory response, and immune cell infiltration. Immunofluorescence and immunohistochemical results demonstrated that there were apoptosis, necroptosis, pyroptosis, and ferroptosis in the progression of IRI in steatotic liver. All four types of cell death inhibitors showed protective effects, but ferroptosis inhibitor Fer-1 and pyroptosis inhibitor VX765 exerted better protective effects compared the apoptosis inhibitor Z-VAD and necroptosis inhibitor Nec-1. Further, we found that pyroptosis occurred mainly in macrophages and ferroptosis occured primarily in hepatocytes during steatotic liver IRI. Ferroptosis in heaptocytes and pyroptosis in macrophages are two major cell death types involved in steatotic liver IRI and inhibiting these cell death exerted good protective effects.