UBE2T promotes glioblastoma malignancy through ubiquitination-mediated degradation of RPL6.

Glioblastoma (GBM) is the most frequent and aggressive malignant glioma. Due to patients' poor prognosis, it is of great clinical significance to determine new targets that may improve GBM treatment. In the present study, we showed that ubiquitin (Ub)-conjugating enzyme E2T (UBE2T) was significantly overexpressed in GBM and could promote proliferation, invasion, and inhibit apoptosis of GBM cells. Mechanistically, UBE2T functioned as the Ub enzyme of ribosomal protein L6 (RPL6) and induced the ubiquitination and degradation of RPL6 in an E3 ligase-independent manner through direct modification by K48-linked polyubiquitination, thus contributing to the malignant progression of GBM cells. Furthermore, inhibiting the expression of RPL6 by UBE2T could not only reduce the expression of wild-type p53, but also enhance the gain-of-function of mutant p53. Moreover, knockdown of UBE2T in LN229 cells obviously suppressed tumor growth in LN229 xenograft mouse models. Collectively, our study demonstrated that UBE2T promotes GBM malignancy through ubiquitination-mediated degradation of RPL6 regardless of the p53 mutation status. It will provide new candidates for molecular biomarkers and therapeutic targets for clinical application in GBM.

[Spectral Study of LaCl3 in Aqueous Solutions].

In this study, the Raman and fluorescence spectra of LaCl3 solution were studied with theoretical calculation and spectroscopic experiments. Based on B3LYP method of density functional theory, with the 6-31G(D,P)+Def2-SV (P) based on the group level the lanthanum chloride solution of micro cluster structure is calculated. The results show that the micro cluster molecules tend to form a 9 coordination structure, which verifies the feasibility of the method. Theoretical and experimental Raman values are compared to the basic consistent. The addition of LaCl(3) leads to the increase of the peak intensity of the Raman spectra in the 300~600 cm-1 range, which may be caused by the superposition of the La-O vibration and the rocking peaks of O­H in aqueous solutions; In the 3 000~4 000 cm(-1) range, the peak of lanthanum chloride solution is narrow compared with water, which may be caused by the stretching vibration of O­H in lanthanum hydrate. Fluorescence emission spectra at 350 nm appear obvious new peak, the good linearity was obtained between the peak intensity and the concentrations, and a rapid method for the quantitative analysis of lanthanum chloride solution from the angle of the complex is also realized. On the same basis set level calculated fluorescence emission center of clusters, in the range of allowable error, the theoretical calculation and the experimental spectra are basically consistent, and the new peak of the experimental spectra are identified.

[[Zn-(CH3CH2OH)n]2+ Clusters Probed with Fluorescence Spectroscopy and Computation].

In this paper the cluster structures of [Zn-(CH3CH2OH)n]2+ have been investigated with spectroscopic experiment and theoretical calculation. According to the fluorescence spectroscopy experiments, the fluorescence peak of ethanol molecules was found between 275~330 nm. A new peak appeared between 350~380 nm after the metal ions (Zn2+) was added into ethanol solution due to the generation of new clusters of molecules, and the original fluorescence peak of ethanol molecules became weak owing to the destroyed structure of ethanol molecules induced by Zn2+. The cluster structures of Zn2+ in water solution were investigated by using different methods. By comparing the results, a more accurate and fast B3LYP method of DFT was found and applied to optimize the possible structures of [Zn-(CH3CH2OH)n]2+. The results suggested that the first solvation shell of the system is up to six ethanol molecules, and thermodynamic parameters also shows the six kinds of molecular clusters which are likely in the solution. Moreover compared the theoretical fluorescence spectroscopy with experimental fluorescence spectroscopy, new clusters [Zn-(CH3CH2OH)n]2+ have been generated, with [Zn-(CH3CH2OH)n]2+(n=1~3) as main constructions.

CPR++: Object Localization via Single Coarse Point Supervision.

Point-based object localization (POL), which pursues high-performance object sensing under low-cost data annotation, has attracted increased attention. However, the point annotation mode inevitably introduces semantic variance due to the inconsistency of annotated points. Existing POL heavily rely on strict annotation rules, which are difficult to define and apply, to handle the problem. In this study, we propose coarse point refinement (CPR), which to our best knowledge is the first attempt to alleviate semantic variance from an algorithmic perspective. CPR reduces the semantic variance by selecting a semantic centre point in a neighbourhood region to replace the initial annotated point. Furthermore, We design a sampling region estimation module to dynamically compute a sampling region for each object and use a cascaded structure to achieve end-to-end optimization. We further integrate a variance regularization into the structure to concentrate the predicted scores, yielding CPR++. We observe that CPR++ can obtain scale information and further reduce the semantic variance in a global region, thus guaranteeing high-performance object localization. Extensive experiments on four challenging datasets validate the effectiveness of both CPR and CPR++. We hope our work can inspire more research on designing algorithms rather than annotation rules to address the semantic variance problem in POL.

DECAF: An interpretable deep cascading framework for ICU mortality prediction.

Medical risk detection is an important topic and a challenging task to improve the performance of clinical practices in Intensive Care Units (ICU). Although many bio-statistical learning and deep learning approaches have provided patient-specific mortality predictions, these existing methods lack interpretability that is crucial to gain adequate insight on why such predictions would work. In this paper, we introduce cascading theory to model the physiological domino effect and provide a novel approach to dynamically simulate the deterioration of patients' conditions. We propose a general DEep CAscading Framework (DECAF) to predict the potential risks of all physiological functions at each clinical stage. Compared with other feature-based and/or score-based models, our approach has a range of desirable properties, such as being interpretable, applicable with multi prediction tasks, and learnable from medical common sense and/or clinical experience knowledge. Experiments on a medical dataset (MIMIC-III) of 21,828 ICU patients show that DECAF reaches up to 89.30 % on AUROC, which surpasses the best competing methods for mortality prediction.

Rethinking Sampling Strategies for Unsupervised Person Re-Identification.

Unsupervised person re-identification (re-ID) remains a challenging task. While extensive research has focused on the framework design and loss function, this paper shows that sampling strategy plays an equally important role. We analyze the reasons for the performance differences between various sampling strategies under the same framework and loss function. We suggest that deteriorated over-fitting is an important factor causing poor performance, and enhancing statistical stability can rectify this problem. Inspired by that, a simple yet effective approach is proposed, termed group sampling, which gathers samples from the same class into groups. The model is thereby trained using normalized group samples, which helps alleviate the negative impact of individual samples. Group sampling updates the pipeline of pseudo-label generation by guaranteeing that samples are more efficiently classified into the correct classes. It regulates the representation learning process, enhancing statistical stability for feature representation in a progressive fashion. Extensive experiments on Market-1501, DukeMTMC-reID and MSMT17 show that group sampling achieves performance comparable to state-of-the-art methods and outperforms the current techniques under purely camera-agnostic settings. Code has been available at https://github.com/ucas-vg/GroupSampling.

Identification of novel compound heterozygous variants in the DNAH1 gene of a Chinese family with left-right asymmetry disorder.

Most internal organs in humans and other vertebrates exhibit striking left-right asymmetry in position and structure. Variation of normal organ positioning results in left-right asymmetry disorders and presents as internal organ reversal or randomization. Up to date, at least 82 genes have been identified as the causative genetic factors of left-right asymmetry disorders. This study sought to discover potential pathogenic variants responsible for left-right asymmetry disorder present in a Han-Chinese family using whole exome sequencing combined with Sanger sequencing. Novel compound heterozygous variants, c.5690A>G (p.Asn1897Ser) and c.7759G>A (p.Val2587Met), in the dynein axonemal heavy chain 1 gene (DNAH1), were found in the proband and absent in unaffected family members. Conservation analysis has shown that the variants affect evolutionarily conserved residues, which may impact the tertiary structure of the DNAH1 protein. The novel compound heterozygous variants may potentially bear responsibility for left-right asymmetry disorder, which results from a perturbation of left-right axis coordination at the earliest embryonic development stages. This study broadens the variant spectrum of left-right asymmetry disorders and may be helpful for genetic counseling and healthcare management for the diagnosed individual, and promotes a greater understanding of the pathophysiology.

PercolationDF: A percolation-based medical diagnosis framework.

Goal: With the continuing shortage and unequal distribution of medical resources, our objective is to develop a general diagnosis framework that utilizes a smaller amount of electronic medical records (EMRs) to alleviate the problem that the data volume requirement of prevailing models is too vast for medical institutions to afford. Methods: The framework proposed contains network construction, network expansion, and disease diagnosis methods. In the first two stages above, the knowledge extracted from EMRs is utilized to build and expense an EMR-based medical knowledge network (EMKN) to model and represent the medical knowledge. Then, percolation theory is modified to diagnose EMKN. Result: Facing the lack of data, our framework outperforms naïve Bayes networks, neural networks and logistic regression, especially in the top-10 recall. Out of 207 test cases, 51.7% achieved 100% in the top-10 recall, 21% better than what was achieved in one of our previous studies. Conclusion: The experimental results show that the proposed framework may be useful for medical knowledge representation and diagnosis. The framework effectively alleviates the lack of data volume by inferring the knowledge modeled in EMKN. Significance: The proposed framework not only has applications for diagnosis but also may be extended to other domains to represent and model the knowledge and inference on the representation.

Vibration Response Analysis of the Tail Beam of Hydraulic Support Impacted by Coal Gangue Particles with Different Shapes.

The existing research on coal gangue identification based on vibration usually assumes that coal gangue particles are ideal shapes. To understand the vibration response difference in hydraulic support caused by coal and gangue with real shapes, this paper uses a three-dimensional (3D) scanning technology to determine the real shape of coal particles. The process of coal and gangue impacting the tail beam at different angles was simulated in the LS-DYNA software package, and the effects of shape parameters, velocity, and coal strength on the difference in vibration signals caused by the two were analyzed statistically. The conclusions are as follows: the vibrational response of the tail beam is concentrated mainly in the area between the ribs. The regularity of the velocity signal caused by gangue is better than the regularity of the velocity signal caused by coal, and the attenuation speed of the acceleration signal of gangue is slower than the attenuation speed of the acceleration signal of coal. The probability distributions of the velocity and acceleration responses were analyzed statistically, and the results show that the results from coal can be well fitted by a logarithmic normal function, and the standard deviations of velocity and acceleration are 0.05591 and 489.8, respectively. The gangue results are fitted by the gamma function and the Weibull function, and the standard deviations are 0.13531 and 737.9, respectively, showing that the fitting function has the potential to be used as the basis for coal gangue identification. The change in coal strength has little effect on the vibration response of the tail beam. With increasingly falling velocity, the vibration signal intensity of the tail beam increases, but the discrimination between coal and gangue weakens; therefore, measures should be taken to reduce the falling velocity of the rock mass. The research results of this paper can provide a reference for further study of coal gangue identification methods based on vibration.

Dynamic Response of Sandwich Tubes with Continuously Density-Graded Aluminum Foam Cores under Internal Explosion Load.

In this paper, the dynamic response of continually density-graded aluminum foam sandwich tubes under internal explosion load was studied. A 3D mesoscopic finite-element model of continually density-graded aluminum foam sandwich tubes was established by the 3D-Voronoi technology. The finite-element results were compared with the existing experimental results, and the rationality of the model was verified. The influences of the core density distribution, the core density gradient, and the core thickness on the blast resistance of the sandwich tubes were analyzed. The results showed that the blast resistance of the sandwich tube with the negative-gradient core is better than that of the sandwich tube with the uniform core. While the blast resistance of the sandwich tube with the positive-gradient core or the middle-hard-gradient core is worse than that of the sandwich tube with the uniform core. For the sandwich tube with the negative-gradient core, the core density gradient increased, and the blast resistance decreased. Increasing the thickness of the core can effectively decrease the deformation of the outer tube of the sandwich tube, but the specific energy absorption of both the whole sandwich tube and its core also decreases.

Identification of DNAH17 Variants in Han-Chinese Patients With Left-Right Asymmetry Disorders.

The formation of left-right asymmetry of the visceral organs is a conserved feature of the human body, and the asymmetry specification of structure and function is precisely orchestrated by multiple regulatory mechanisms. The abnormal results of organ positioning situs arise from defective cilia structure or function during embryogenesis in humans. In this study, we recruited two unrelated Han-Chinese families with left-right asymmetry disorders. The combination of whole-exome sequencing and Sanger sequencing identified two compound heterozygous variants: c.4109C>T and c.9776C>T, and c.612C>G and c.8764C>T in the dynein axonemal heavy chain 17 gene (DNAH17) in two probands with left-right asymmetry disorders. We report for the first time a possible association between DNAH17 gene variants and left-right asymmetry disorders, which is known as a causal gene for asthenozoospermia. Altogether, the findings of our study may enlarge the DNAH17 gene variant spectrum in human left-right asymmetry disorders, pave a way to illustrate the potential pathogenesis of ciliary/flagellar disorders, and provide supplementary explanation for genetic counseling.

MDK induces temozolomide resistance in glioblastoma by promoting cancer stem-like properties.

Glioblastoma (GBM) is the most frequently observed and aggressive type of high-grade malignant glioma. Temozolomide (TMZ) is the primary agent for GBM treatment. However, TMZ resistance remains a major challenge. In this study, we report that MDK is overexpressed in GBM, which leads to enhanced proliferation, apoptosis inhibition, increased invasion and TMZ resistance in GBM cells. It was also determined that MDK could significantly improve the stem-like properties of GBM cells. Mechanistically, MDK enhanced p-JNK through Notch1 and subsequently increased the expression of stemness markers, such as CD133 and Nanog, thereby promoting TMZ resistance. Finally, xenograft experiments and clinical sample analysis also demonstrated that MDK knockdown could significantly inhibit tumor growth in vivo, and the expression of MDK was positively correlated with Notch1, p-JNK and CD133. This study revealed that MDK induces TMZ resistance by improving the stem-like properties of GBM by upregulating the Notch1/p-JNK signaling pathway, which provides a possible target for therapeutic intervention of GBM, especially in TMZ-resistant GBM with high MDK expression.

Naturally occurring Girinimbine alkaloid inhibits the proliferation, migration, and invasion of human breast cancer cells via induction of apoptosis and inhibition of MEK/ERK and STAT3 signalling pathways.

The currently used anticancer drugs against breast cancer possess serious side effects, have limited efficacy, and often lead to recurrence of the malignancy. The main aim of this research was to investigate the anticancer potential of Girinimbine, a naturally occurring carbazole alkaloid, against ER-negative breast cancer cells (MDA-MB-453) along with its effects on cell migration and invasion, apoptosis, and MEK/ERK/STAT3 pathway. MTT assay was used to evaluate antiproliferative effects of Girinimbine while a clonogenic assay was used to study cell colony formation. Transwell migration and invasion assays were involved to study its effects on cell migration and invasion. Fluorescence microscopy using acridine orange/ethidium bromide was used to study apoptotic effects of girinimbine which was quantified by annexin v-FITC assay. Effects of girinimbine on MEK/ERK and STAT3 signalling pathways were evaluated by western blot assay. Results showed that girinimbine exhibited dose-dependent as well as time-dependent antiproliferative effects in MDA-MB-453 cells along with strongly inhibiting the cell colony potency of these cancerous cells. Girinimbine can inhibit both cancer cell migration as well as invasion. Girinimbine has induced potent chromatin condensation and nuclear fragmentation. The percentage of both early and late apoptotic cells increased significantly after girinimbine exposure. The anticancer effects of girinimbine were shown to be mediated via inhibition of the MEK/ERK as well as STAT3 signalling pathways. In conclusion, it may be proposed that girinimbine could be a promising anticancer agent against breast cancer, provided further in-depth studies are carried out.

Distribution of serotypes and virulence-associated genes in pathogenic Escherichia coli isolated from ducks.

The objective of the present study was to investigate the serotypes and virulence-associated genes of avian pathogenic Escherichia coli (APEC) isolated from duck colibacillosis cases. Two hundred and fifty-four APEC isolates from duck colibacillosis cases were serotyped and amplified for 12 known virulence-associated genes and the betA gene (encoding choline dehydrogenase) by polymerase chain reaction assays. One hundred and forty-three E. coli isolates from cloacal swabs of healthy ducks were also amplified for the same genes. A total of 53 O-serogroups were found in 254 APEC isolates, among which O93, O78 and O92 were predominant serogroups. Polymerase chain reaction results showed that Shiga-toxin-producing E. coli distributed in only 2.4% of ducks compared with 49.2% of the APEC isolates harbouring the irp2 gene, and 44.9% the fyuA gene, respectively. The ibeA gene was only present in 27 APEC isolates and was not found in healthy ducks. The rfaH gene was detected in 20.5% of APEC isolates, whereas 5.6% was found in healthy ducks. A total 79.5% of APEC isolates harboured the betA gene, which was significantly higher than in healthy ducks (16.1%), suggesting that betA may be associated with virulence.

microRNA-196a-5p inhibits testicular germ cell tumor progression via NR6A1/E-cadherin axis.

Testicular germ cell tumors (TGCTs) are a diverse group of neoplasms that are derived from dysfunctional fetal germ cells and can also present in extragonadal sites. The genetic drivers underlying malignant transformation of TGCTs have not been fully elucidated so far. The aim of the present study is to clarify the functional role and regulatory mechanism of miR-196a-5p in TGCTs. We demonstrated that miR-196a-5p was downregulated in TGCTs. It can inhibit the proliferation, migration, and invasion of testicular tumor cell lines including NT-2 and NCCIT through targeting the NR6A1 gene, which we proved its role in promotion of cell proliferation and repression of cellular junction and aggregation. Mechanistically, NR6A1 inhibited E-cadherin through binding with DR0 sites in the CDH1 gene promoter and recruiting methyltransferases Dnmt1. Further, NR6A1 promoted neuronal marker protein MAP2 expression in RA-induced neurodifferentiation of NT-2 cells and testicular tumor xenografts. Clinical histopathologically, NR6A1 was positively correlated with MAP2, and negatively correlated with E-cadherin in TGCTs. These findings revealed that the miR-196a-5p represses cell proliferation, migration, invasion, and tumor neurogenesis by inhibition of NR6A1/E-cadherin signaling axis, which may be a potential target for diagnosis and therapy of TGCTs.

Analysis of the Effect of Nine Consecutive Years' Intensive Management and Number of Times Achieving the Target Control on Endpoint Events in T2DM Patients in Sanlitun Community Health Service Center in Beijing.

OBJECTIVE: To investigate the effect of intensive management and achieving the target control more than 3 times on endpoint events during 9 consecutive years' annual assessment in type 2 diabetes (T2DM) patients in the Sanlitun Community Health Service Center in Beijing, including blood glucose, blood pressure, lipids profiles, and the joint target control. METHODS: In Beijing Community Diabetes Study (BCDS), 224 patients with T2DM from the Sanlitun Community Health Service Center were enrolled in 2008. All patients were randomly assigned to the intensive management group (n = 113) and the standard management group (n = 113) and the standard management group (. RESULTS: During the nine-year follow-up, the abscission number was 35 (14.29%), among which 14 (12.39%) was in the intensive management group and 21 (18.92%) was in the standard management group. The incidence of diabetic retinopathy (6 cases, 5.41%) and diabetic nephropathy (13 cases, 11.71%) in the standard management group was significantly higher than that in the intensive management group (1 case, 0.88%; 5 cases, 4.42%), respectively (P < 0.05). However, there were no significant differences on the other endpoint events between the two groups (P < 0.05). However, there were no significant differences on the other endpoint events between the two groups (P < 0.05). However, there were no significant differences on the other endpoint events between the two groups (P < 0.05). However, there were no significant differences on the other endpoint events between the two groups (P < 0.05). However, there were no significant differences on the other endpoint events between the two groups (. CONCLUSIONS: The intensive management can effectively reduce the occurrence of microvascular complications. The incidence of all-cause death and the other endpoint events decreased in T2DM patients who achieved the joint target control more than 3 times during the nine-year management, which improved survival time and life quality. This trial is registered with ChiCTR-TRC-13003978 and ChiCTR-OOC-15006090.

LMP1-positive extracellular vesicles promote radioresistance in nasopharyngeal carcinoma cells through P38 MAPK signaling.

Radioresistance has been one of the impediments to effective nasopharyngeal carcinoma (NPC) therapy in clinical settings. Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) is expressed in NPC and has potent effects on radioresistance. It has been detected in extracellular vesicles (EVs) or exosomes and shown to promote tumor proliferation and invasive potential. However, whether LMP1-positive EVs can confer radioresistance to cancer cells and the mechanism used to promote radioresistance need to be elucidated. In this study, the data showed that EVs derived from LMP1-positive NPC cells could induce recipient NPC cell proliferation and invasion and suppress apoptosis, especially promoting radioresistance. In addition, LMP1 could increase the secretion of LMP1-positive EVs. Furthermore, transmitted LMP1 subsequently performed its oncogenic functions through activating P38 MAPK signaling in recipient cells, and inhibiting P38 activity could efficaciously restore the sensitivity of NPC cells to ionizing radiation (IR). Finally, we found that LMP1-positive EVs could promote tumor growth and P38 inhibition eliminates this promoting effect in vivo, and EV formation is associated with a poor prognosis in NPC patients. These results showed that a few cells expressing LMP1 could enhance the radioresistance of NPC cells through potentially impacting the infected host and also modulating the tumor microenvironment.

[Detecting pathogenic Aeromonas hydrophila in fish by triplex PCR].

OBJECTIVE: To develop a rapid PCR method to detect pathogenic Aeromonas hydrophila in fish. METHODS: For multiple PCR, three pairs of primers were designed based on the conservative sequences of 16SrRNA genes, aerolysin (aer) gens and serine-protease (ahp) genes of Aeromonas hydrophila. By optimization of PCR conditions and estimation of specificity, sensitivity, detection rate, a triplex PCR assay was established. RESULTS: The assay had a high specificity detecting only pathogenic strains of Aeromonas hydrophila but not other irrelative bacteria. The assay had a high sensitivity with the detection limit as low as 100 fg, the detection rate of suspicious clinical samples by this assay was 81.8%, which was noticeably higher than that by bacterial isolation method (40.9%). The detection rate of mimic challenge samples by this assay was 87.5%, which was also noticeably higher than that by bacterial isolation method (67.5%). CONCLUSION: The simultaneous detection of 16SrRNA gene and two virulent genes in one PCR assay could avoid missed detection possibly caused by PCR with single virulent gene, and provided a useful tool for rapid diagnosis, large-scale quarantine, and epidemiological investigation of the pathogenic Aeromonas hydrophila.

[Raman active vibrations of aluminosilicates].

Raman spectra of aluminosilicate minerals, namely kyanite, andalusite, and sillimanite and K2O-Al2O3-SiO2 glasses were recorded. Four alumino-silicon tetrahedral model clusters were calculated by self-consistent (SCF) molecular orbital ab-ini-tio calculation of the quantum chem (QC) method. The result shows a decrease tendency in Raman frequencies in the 800-1200 cm(-1) frequency region with increase in four-coordinated Al content, which is assigned to the Si--Onb symmetry stretching vibrations. The Raman spectra in the 700-800 cm(-1) frequency region is attributed to Al-Onb symmetry stretching vibrations.

A novel substitution at the translation initiator codon (ATG-->ATC) of the lipoprotein lipase gene is mainly responsible for lipoprotein lipase deficiency in a patient with severe hypertriglyceridemia and recurrent pancreatitis.

A patient with severe hypertriglyceridemia and recurrent pancreatitis was found to have significantly decreased lipoprotein lipase (LPL) activity and normal apolipoprotein C-II concentration in post-heparin plasma. DNA analysis of the LPL gene revealed two mutations, one of which was a novel homozygous G-->C substitution, resulting in the conversion of a translation initiation codon methionine to isoleucine (LPL-1). The second was the previously reported heterozygous substitution of glutamic acid at residue 242 with lysine (LPL-242). In vitro expression of both mutations separately or in combination demonstrated that LPL-1 had approximately 3% protein mass and 2% activity, whereas LPL-242 had undetectable activity but normal mass. The combined mutation LPL-1-242 exhibited similar changes as for LPL-1, with markedly reduced mass, and for LPL-242, with undetectable activity. These results suggest that the homozygous initiator codon mutation rather than the heterozygous LPL-242 alteration was mainly responsible for the patient phenotypes.