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The mitogen-activated protein kinase (MAPK) cascades play important roles in various signaling transduction networks of biotic and abiotic stress responses. However, MAPK signaling pathways in cold-active yeast Rhodotorula mucilaginosa have not been reported comprehensively. In the present study, MAPK gene ( RmMAPK ) was first cloned and characterized from Antarctic sea ice yeast R. mucilaginosa AN5. The full length of the RmMAPK gene is 1086 bp and encodes a 361 amino acids protein with a predicted molecular mass of 40.9 kDa and a pI of 5.25. The RmMAPK contains 11 MAPK conserved subdomains and the phosphorylation motif TGY located in the activation loop of the kinase. Quantitative real-time PCR assay revealed that the expression of RmMAPK up-regulated rapidly and significantly when yeast cells were subjected to low temperature (4 °C), high salinity (120‰ NaCl) and heavy metal (2 mmol/L CuCl 2 ), which suggested that the RmMAPK might act as a key function in response to extreme stresses, such as low temperature, high salinity and heavy metal.

Stomach adenocarcinoma (STAD) is the major cancer worldwide with high morbidity and mortality rate. Late diagnosis and limited treatment options of STAD lead to disease progression, spread, and metastasis. Therefore, finding a new biomarker to diagnosis and treatment is very important for STAD in clinical practice.The clinical data, transcriptome data and CCLE data were downloaded from TCGA database and CCLE database, respectively. TIMER website, TISIDB website and CIBERSORT methodology were used to analyse immune infiltration. R software and R package were used to analyse gene difference expression, determine co-expression genes, conduct gene enrichment analyses, construct a prognostic signature and establish nomogram.MASP1 was decreased in STAD compared with normal tissue at the mRNA level (p0.001). The enrichment analysis showed that mismatch repair (MMR) was related to the MASP1 gene. Up-regulation of MAPS1 expression was positively associated with dendritic cells (p0.01), neutrophils (p0.05), macrophages (p0.001), CD4+ T cells (p0.001) and B cells (p0.05). A four-gene prognostic signature was determined based on MASP1-related immunomodulators. The prognostic signature was an independent prognostic predictor in STAD. Finally, we established a nomogram to forecast survival and the nomogram has a good prediction accuracy.In STAD, MASP1 is closely related to immunity. MASP1 has the potential to positively regulate the abundance of immune cells. The MASP1-related prognosis signature and nomogram can accurately predict the survival of patients with STAD. Therefore, MASP1 is likely to be a diagnosis and promising immunotherapy target spot in STAD clinical practice.

The COVID-19 pandemic is yet another reminder that the threat of infectious disease has never really gone away. As the cornerstone of preventing and controlling infectious diseases, effective surveillance and early warning are of great significance in understanding the outbreak and epidemic of specific infectious diseases and putting forward effective prevention and control measures. Therefore, we must continue strengthening the construction of infectious disease surveillance and early warning system. We reviewed the surveillance and early warning practices of infectious diseases in major countries and regions, then discussed the development direction in the field of surveillance and early warning of infectious diseases to provide the reference for strengthening the construction and capacity of infectious disease surveillance and early warning system in China.新型冠状病毒肺炎大流行再次警示人们，传染病威胁从未真正远去。有效的监测预警作为传染病防控的基石，对全面准确地认识特定传染病暴发流行、提出科学有效的防控策略和措施具有重要意义，因此须持续加强传染病监测预警体系建设。本文对世界主要国家和地区的传染病监测预警实践进行综述，探讨了传染病监测预警领域的发展方向，为进一步加强我国传染病监测预警体系建设与能力提升提供参考。.

Morphine tolerance is a classic, challenging clinical issue. However, the mechanism underlying this phenomenon remains poorly understood. Recently, studies have shown that ferroptosis correlates with drug resistance. Therefore, this study investigated whether spinal cord ferroptosis contributes to morphine tolerance. C57BL/6 mice were continuously subcutaneously injected with morphine, with or without the ferroptosis inhibitor liproxstatin-1. We found that chronic morphine exposure led to morphine antinociception tolerance, accompanied by loss of spinal cord neurons, increase in the levels of iron, malondialdehyde, and reactive oxygen species, and decreases in the levels of superoxide dismutase. Additionally, inflammatory response and mitochondrial shrinkage, processes that are involved in ferroptosis, were observed. Simultaneously, we found that 10 mg/kg of liproxstatin-1 could alleviate iron overload by balancing transferrin receptor protein 1/ferroportin expression and attenuate morphine tolerance by increasing glutathione peroxidase 4 levels, while reducing the levels of malondialdehyde and reactive oxygen species. It also downregulated the expression of extracellularly regulated protein kinases that had been induced by chronic morphine exposure. Our results indicate that spinal cord ferroptosis contributes to morphine tolerance, while liproxstatin-1 attenuates the development of morphine tolerance. These findings suggest that ferroptosis may be a potential therapeutic target for morphine tolerance.

本文报道一例外耳圆柱瘤病例，老年女性，主诉发现右外耳肿物12年，初步诊断为右外耳肿物，全身麻醉下行右侧外耳肿物切除术+游离全厚皮片移植术。术后病理报告为圆柱瘤，随访观察1年无复发。.

Zirconium alloys are basically used in the core structural components of a nuclear reactor. For further understanding mechanical behaviors of zirconium alloy, several alloys with various Nb content are investigated. Microstructure observation, Vickers hardness and mechanical stress-strain curves have been investigated and numerically extracted. Conclusions confirm that the precipitation content of the second phases in Zr-Sn-Nb-Fe-Cr alloys increases with the gradual increment of Nb content. When Nb content reaches to 1.2 wt.%, the excess Nb participates in the formation of second phase containing Nb, which increases the amount of second phases. Moreover, the increase of alloy strength and hardness is mainly attributed to the precipitation strengthening mechanism of second phases.

It is known that the expression of the deubiquitinating enzyme BRCA1-BRCA2-containing complex subunit 3 (BRCC3) and cyclin-dependent protein kinase 5 (Cdk5) is increased in Parkinson's disease (both are involved in neuroinflammatory response). However, the regulatory mechanism of Cdk5 on the post-translational modification of BRCC3 remains unclear. Here we studied whether Cdk5 phosphorylates BRCC3. Phosphorylation of BRCC3 by Cdk5 was predicted by GPS 5.0 software. His-BRCC3 plasmid was constructed by cloning the BRCC3 gene into pGEX-6P-1 vector, and then His-BRCC3 fusion protein was induced with isopropyl β-d-1-thiogalactopyranoside and purified using His-Tag affinity chromatography purification agarose. Phosphorylation of BRCC3 fusion protein by Cdk5 in vitro was detected by mass spectrometry and Western blotting. The results showed that multiple phosphorylation sites were predicted by GPS 5.0, and the His-BRCC3 fusion protein was successfully induced and purified. In vitro kinase assay, Western blotting, and mass spectrometry showed that Cdk5 can phosphorylate BRCC3. It has been demonstrated that protein kinase Cdk5 can phosphorylate the deubiquitinating enzyme BRCC3 in vitro, which provides new data for further study on the mechanism of neurodegeneration.

Chronic pain is a critical clinical problem with an increasing prevalence. However, there are limited effective prevention measures and treatments for chronic pain. Astrocytes are the most abundant glial cells in the central nervous system and play important roles in both physiological and pathological conditions. Over the past few decades, a growing body of evidence indicates that astrocytes are involved in the regulation of chronic pain. Recently, reactive astrocytes were further classified into A1 astrocytes and A2 astrocytes according to their functions. After nerve injury, A1 astrocytes can secrete neurotoxins that induce rapid death of neurons and oligodendrocytes, whereas A2 astrocytes promote neuronal survival and tissue repair. These findings can well explain the dual effects of reactive astrocytes in central nervous injury and diseases. In this review, we will summarise the (1) changes in the morphology and function of astrocytes after noxious stimulation and nerve injury, (2) molecular regulators and signalling mechanisms involved in the activation of astrocytes and chronic pain, (3) the role of spinal and cortical astrocyte activation in chronic pain, and (4) the roles of different subtypes of reactive astrocytes (A1 and A2 phenotypes) in nerve injury that is associated with chronic pain. This review provides updated information on the role of astrocytes in the regulation of chronic pain. In particular, we discuss recent findings about A1 and A2 subtypes of reactive astrocytes and make several suggestions for potential therapeutic targets for chronic pain.

Heavy metal pollution in Antarctica has far exceeded expectations. Antarctic yeast is widely present in polar marine environment. The mechanisms of metabolomics effect of heavy metal on polar yeast have not been reported previously. In this study, gas chromatography–mass spectrometry (GC–MS) wascarried out to performed the metabolite profiling analysis of Antarctic sea-ice yeast Rhodotorula mucilaginosa AN5 exposed to different cadmium (Cd) stresses of 5 mM (HM5), 10 mM (HM10) and 20 mM (HM20), respectively. Metabolic profile analysis showed that the composition and contents of cellular metabolites have been altered by cadmium. 93 different metabolites were identified altogether, among which 23, 58 and 81 different metabolites were found in HM5, HM10 and HM20 group respectively. MetaboAnalyst analysis showed that in HM5, HM10 and HM20 groups, 12, 24 and 31 metabolic pathways were involved in the stress of cadmium to R. mucilaginosa, respectively. By contrasting with Kyoto Encyclopedia of Genes and Genomes database, we discovered that exposure of yeast AN5 to Cd stress resulted in profound biochemical changes including amino acids, organic acids and saccharides. These results will supply a nonnegligible basis of studying the adaptive resistance mechanism of Antarctic yeast Rhodotorula mucilaginosa to heavy metal.

Glycogen Synthase Kinase-3β (GSK-3β) negatively regulates Wnt/β-catenin signaling pathway through degrading β-catenin protein. It plays an inhibitory role in various tumors, while the influence in the pathogenesis of renal carcinoma has not been elucidated. MicroRNA-155 (MiR-155) was found to be upregulated in renal carcinoma tissue. Bioinformatics analysis revealed the complementary binding site between miR-155 and 3'-UTR of GSK-3β. This study investigated the influence of miR-155 in regulating GSK-3β expression, Wnt/β-catenin signaling pathway activity, and renal carcinoma cell proliferation, invasion, and apoptosis.The targeted regulatory relationship between miR-155 and GSK-3β were tested by dual luciferase assay. Renal carcinoma tissue and benign renal tissue were collected to detect miR-155 and GSK-3β expressions. MiR-155, GSK-3β, and β-catenin levels were compared between HK-2 and 786-O cells. Renal carcinoma 786-O cells were cultured in vitro and divided into four groups, including miR-NC, anti-miR-155, pIRES2-blank, and pIRES2-GSK-3β groups. Cell apoptosis was evaluated by flow cytometry. Cell invasion was determined by transwell assay. Cell proliferation was assessed by EdU staining.MiR-155 targeted regulated GSK-3β expression. MiR-155 and β-catenin expressions were significantly increased, while GSK-3β level was significantly declined in renal carcinoma tissue compared with benign renal tissue. MiR-155 and β-catenin expressions were significantly elevated, whereas GSK-3β level was significantly downregulated in 786-O cells compared with HK-2 cells. Anti-miR-155 or pIRES2-GSK-3β transfection significantly up-regulated GSK-3β expression, attenuated β-catenin level, restrained cell proliferation and invasion, and enhanced cell apoptosis.MiR-155 promoted renal carcinoma pathogenesis. Inhibition of miR-155 increased GSK-3β expression, attenuated Wnt/β-catenin signaling pathway, weakened proliferation and invasion, and facilitated apoptosis in renal carcinoma cells.

Current gastric cancer staging systems overlook the anatomic extent of metastatic lymph nodes (AEMLNs). This study aimed to analyze the prognostic impact of AEMLNs on gastric cancer (GC).GC patients with metastatic lymph nodes (MLNs) undergoing curative surgery were retrospectively reviewed and assigned to perigastric (MLNs in station 1-6, PG) and extraperigastric group (7-12, with or without MLNs in PG area, EPG). Overall survival (OS), disease-free survival (DFS) and recurrence patterns were compared before and after 1:1 propensity score matching (PSM).662 patients were enrolled, 341 (51.5%) and 321 (48.5%) of whom were in the PG and EPG, respectively. After PSM (n = 195), EPG showed poorer 5-year OS (43.4% vs 54.5%, p = 0.014) and DFS (65.0% vs 73.4%, p = 0.068) than PG. EPG had higher incidence of peritoneal recurrence (PR) than PG (19.4% vs 7.4%, p = 0.002). Multivariate analysis identified AEMLNs as prognostic factor for OS [HR = 1.409, 95% confidence interval (CI) 1.062-1.868), DFS (HR = 1.600, 95% CI 1.059-2.416) and PR (HR = 3.708, 95% CI 1.685-8.160).The anatomic extent of metastatic lymph nodes has an independent prognostic role for GC. Including this element may improve the accuracy of current staging systems.

The H9N2 influenza virus has been frequently endemic in poultry, infected mammals and humans and has threatened public health. It is therefore imperative to understand the molecular mechanism enabling this virus to jump from avian to mammalian species. In this study, two H9N2 influenza viruses were isolated from the same region in eastern China but from different hosts; one was isolated from mink and named A/Mink/Shandong/WM01/2014(H9N2)(WM01), while the other was isolated from chicken and named A/Chicken/Shandong/LX830/2014(H9N2)(LX830). Sequencing and phylogenetic analysis showed that both H9N2 influenza viruses had similar genetic backgrounds. The results of infection in minks suggested that both viruses caused significant weight loss and pathological changes in the lungs. Mouse infection showed that LX830 was nonpathogenic in mice, but WM01 resulted in 25% mortality and pathological changes in the lungs, such as severe edema and diffused inflammation of the interalveolar septa. Comparison of the full genomes of both H9N2 influenza viruses showed 52-nucleotide-synonym mutations in 8 gene segments and 7-nucleotide-antonym mutations, resulting in 7 amino acid (AA) substitutions distributed in the PB1, PA, NA and M gene segments. None of these mutations did affect splicing of the M and NS gene segments at the nucleotide level or minor open reading frames (ORFs), such as PB1-F2 and PA-X. Phylogenetic analysis showed that both H9N2 influenza viruses belong to the prevalent epidemic genotype in Asia. Keywords: H9N2 influenza virus; chicken; minks; pathogenicity; phylogenetic.

By employing the glass fluxing technique in combination with cyclical superheating, the microstructural evolution of the undercooled Fe82B17Si1 alloy in the obtained undercooling range was studied. With increase in undercooling, a transition of cooling curves was detected from one recalescence to two recalescences, followed by one recalescence. The two types of cooling curves were fitted by the break equation and the Johnson–Mehl–Avrami–Kolmogorov model. Based on the cooling curves at different undercoolings, the recalescence rate was calculated by the multi-logistic growth model and the Boettinger–Coriel–Trivedi model. Both the recalescence features and the interface growth kinetics of the eutectic Fe82B17Si1 alloy were explored. The fitting results that were obtained using TEM (SAED), SEM and XRD were consistent with the changing rule of microstructures. Finally, the relationship between the microstructure and hardness was also investigated.

This study aims to investigate whether HOX transcript antisense RNA (HOTAIR) can participate in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) by regulating the Wnt/β-catenin pathway, thereby participating in the pathogenesis of osteoporosis.We detected the expression level of HOTAIR in 60 osteoporosis patients and 60 normal controls by Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Meanwhile, BMSCs derived from human or rats were subjected to determination of HOTAIR level. Subsequently, the effects of HOTAIR on osteogenic differentiation were evaluated by the activity of Alkaline Phosphatase (ALP), Alizarin Red S (ARS) staining, ALP staining and osteogenic-specific gene expression. The expression level of proteins related to the Wnt/β-catenin was determined by Western blot, and ALP activity was detected by ALP activity determination kit and alizarin red staining after knockdown or overexpression of HOTAIR, as well as the treatment of DKK1 or the Wnt pathway antagonist. Finally, osteoporosis model in rats was established by ovariectomy (OVX). We examined protein levels of HOTAIR, β-catenin, CyclinD, C-myc, and Runx2 in rat bone tissues. Bone morphology was observed in each group as well.The serum and BMSCs levels of HOTAIR in patients with osteoporosis were remarkably higher than that in normal people. Inhibition of HOTAIR induced increased ALP activity increased osteogenic marker genes and enhanced number of calcified nodules in BMSCs. However, the overexpression of HOTAIR exhibited the opposite effects. HOTAIR inhibited the expression level of Wnt/β-catenin pathway-related protein. Also, Wnt pathway antagonist DKK1 partially reversed the regulatory effects of HOTAIR on Wnt/β-catenin. DKK1 treatment markedly reduced the promotive effect of HOTAIR knockdown on ALP activity, ALP content and calcification ability of BMSCs. DKK1 administration in rats undergoing OVX showed worse bone morphology relative to controls. Protein levels of HOTAIR, β-catenin, CyclinD, C-myc and Runx2 remarkably downregulated in OVX rats administrated with DKK1.HOTAIR inhibits osteoblast differentiation of rat BMSCs. The underlying mechanism of which may be related to the mediation of Wnt/β-catenin pathway.

OBJECTIVE: Deep learning models, including recurrent neural network (RNN) and gated recurrent unit (GRU), were used to construct the clinical prognostic prediction models for peritoneal dialysis (PD) patients based on routine clinical data. The performance of the RNN and GRU were compared with logistic regression (LR), which is commonly used in medical researches. The possible underlining clinical implications based on the result from the GRU model were also investigated. METHODS: We used the clinical data from the PD center of Peking University Third Hospital as the data source. Both the baseline data at the beginning of dialysis, and the follow-up and prognostic data of the patients were used by the RNN and GRU prediction models. The hyper-parameters were tuned based on the 10-fold cross-validation. The risk prediction performance of each model was evaluated via area under the receiver ope-ration characteristic curve (AUROC), recall rate and F1-score on the testset. RESULTS: A total of 656 patients with the 261 occurrences of death were included in the experiment. The total number of all diagnostic records were 13 091. The results on the testset showed that the AUROC of the LR model, RNN mo-del, and GRU model was 0.701 4, 0.786 0, and 0.814 7, respectively. The predictive performances of the GRU and RNN models were significantly better than that of the LR model. The performances of the GRU and RNN models assessed by recall rate and F1-score were also significantly better than that of the LR model, in which the GRU model reached the best performance. In addition, the recall rates were different among different causes of death or by different prediction time windows. CONCLUSION: The recurrent neural network model, especially the GRU model, is more effective in predicting PD patients’ prognosis as compared with the LR model. This new model may be helpful for clinicians to provide timely intervention, thus improving the quality of care of PD.