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As the volume of data keeps growing rapidly, more and more servers are continuously added into data centers. The industry experience indicates that, in order to reduce the cost and energy consumption, data enter network (DCN) can be expanded by adding a small number of servers from time to time instead of adding a huge number of servers at a time. The DCN structures with incremental scalability can be expanded gradually while their topological properites are preserved. In order to improve the performance of the DCN, dual-centric DCN structures are proposed. However, the incremental scalabilities of the current dual-centric DCNs are not good. This paper proposes a new type of dual-centric data center network structure called GHDC (Generalized Hypercube Data Center network architecture), which is constructed by using commodity switches and multi-port servers. After analyzing the shortest distance between any two vertices, a routing algorithm is developed. To achieve incremental scalability, two incomplete GHDC structures are proposed. A small number of servers can be added into the incomplete GHDC structures while their topological properties are maintained. The analysis results show that GHDC significantly outperform FCell, FRectangle and FSquare in terms of the incremental scalability and robustness. The average through-put of GHDC is approximately equal to that of FSquare and highter than that of FCell and FRectangle by about 17.45% and 25.5%. Compared with the FCell, FRectangle and FSquare, GHDC reduces the cost andenergy consumption by about 10.84%, 22.85% and 29.55%, respectively.

Aberrantly elevated O-GlcNAcylation level is commonly observed in human cancer patients, and has been proposed as a potential therapeutic target. Speckle-type POZ protein (SPOP), an important substrate adaptor of cullin3-RING ubiquitin ligase, plays a key role in the initiation and development of various cancers. However, the regulatory mechanisms governing SPOP and its function during hepatocellular carcinoma (HCC) progression remain unclear. Here, we show that, in HCC, SPOP is highly O-GlcNAcylated by O-GlcNAc transferase (OGT) at Ser96. In normal liver cells, the SPOP protein mainly localizes in the cytoplasm and mediates the ubiquitination of the oncoprotein neurite outgrowth inhibitor-B (Nogo-B) (also known as reticulon 4 B) by recognizing its N-terminal SPOP-binding consensus (SBC) motifs. However, O-GlcNAcylation of SPOP at Ser96 increases the nuclear positioning of SPOP in hepatoma cells, alleviating the ubiquitination of the Nogo-B protein, thereby promoting HCC progression in vitro and in vivo. In addition, ablation of O-GlcNAcylation by an S96A mutation increased the cytoplasmic localization of SPOP, thereby inhibiting the Nogo-B/c-FLIP cascade and HCC progression. Our findings reveal a novel post-translational modification of SPOP and identify a novel SPOP substrate, Nogo-B, in HCC. Intervention with the hyper O-GlcNAcylation of SPOP may provide a novel strategy for HCC treatment.

Production of hydrogen fuel from sunlight and water, two of the most abundant natural resources on Earth, offers one of the most promising pathways for carbon neutrality

To explore the fitting effect of the ARIMA, GM(1,1), and RANSAC model in the changes of white blood cells (WBC) in benzene-exposed workers, and select the optimal model to predict the WBC count of workers. Among 350 employees in an aerospace process manufacturing enterprise in Nanjing, workers with 10 years of benzene exposure were selected, and used Excel software to organize the WBC data, and the ARIMA model and RANSAC model were established by R software, and the GM(1, 1) model was established by DPS software, and the magnitude of the mean absolute percentage error (MAPE) of fitting three models to WBC counts was compared. The MAPE based on the ARIMA(2,1,2) model is 6.78%, the MAPE based on the GM(1,1) model is 5.19%, and the MAPE based on the RANSAC model is 6.37%, so the GM( 1,1) model was more suitable for fitting the trend of WBC counts in benzene exposed workers in this study. The GM(1,1) model is suitable for fitting WBC counts in a small sample size and can provide a short-term prediction of WBC counts in benzene-exposed workers and provide basic information for occupational health risk assessment of workers.

As the most prevalent brain tumor, glioma is malignant with poor prognostic outcomes. As a result, it is of great importance to detect biomarkers for glioma diagnosis and prognosis. In this study, we determined grade-based characteristic gene clusters with gradual expression following grade change, including 1479 down- and 526 up-regulated genes. Combined interaction among proteins originating from these genes was analyzed, and hub genes were exhibited after GSEA enrichment, containing 12 and 11 genes which were correlated with prognostic outcomes, named as unfavorable and favorable gene sets, respectively. The GSVA score of each gene set was calculated and divided into high/low groups; we observed that cases in the low score group had better outcomes than the high score group based on the GSVA of the unfavorable set, while with favorable GSVA score, the low group had poorer outcomes than the high group. Eventually, we compared a variety of infiltrating immune cells between low/high GSVA subgroup, showing various immune cell types (B cell naive, activated mast cells, resting CD4 memory T cell, and so on) with opposite proportion. And interestingly, these cell types also accounted for a contrary percentage between unfavorable and favorable conditions. In conclusion, these two hub gene sets are of good importance as an evaluation system for clinical grade classification and prognosis prediction.

Peptide quantitative structure-activity relationships (pQSARs) have been widely applied to the statistical modeling and empirical prediction of peptide activity, property and feature. In the procedure, the peptide structure is characterized at sequence level using amino acid descriptors (AADs) and then correlated with observations by machine learning methods (MLMs), consequently resulting in a variety of quantitative regression models used to explain the structural factors that govern peptide activities, to generalize peptide properties of unknown from known samples, and to design new peptides with desired features. In this study, we developed a comprehensive platform, termed PepQSAR database, which is a systematic collection and decomposition of various data sources and abundant information regarding the pQSARs, including AADs, MLMs, data sets, peptide sequences, measured activities, model statistics, and literatures. The database also provides a comparison function for the various previously built pQSAR models reported by different groups via distinct approaches. The structured and searchable PepQSAR database is expected to provide a useful resource and powerful tool for the computational peptidology community, which is freely available at http://i.uestc.edu.cn/PQsarDB .

Application of microRNA-mediated mRNA expression in treatment of diverse cancers has been documented. The current study was explored to study the role of miR-217 in breast cancer (BC) progression and the related downstream factors. Clinical tissue samples, BC cell lines and the established xenograft models were prepared for ectopic expression and depletion experiments to discern the regulatory roles of miR-217-mediated NF1 in BC cell proliferation, metastasis and chemoresistance as well as tumorigenic ability of BC cells in nude mice. miR-217 was upregulated in BC, which was a predictor of poor prognosis of BC patients. NF1 could be targeted by miR-217. miR-217 promoted malignant characteristics of BC cells through enhancing ATF3-MMP13 interaction by inhibiting NF1. miR-217 repressed sensitivity against anti-cancer drugs by inducing autophagy of BC cells through the NF1/HSF1/ATG7 axis. Also, miR-217 could inhibit NF1 to facilitate tumorigenic ability of BC cells in vivo. Our study emphasized that miR-217 could potentially inhibit NF1 expression to activate the c-Jun, thus enhancing the expression and interaction of ATF3/MMP13 and promoting the malignant features of BC cells. Furthermore, miR-217 conferred chemoresistance on BC by enhancing BC cell autophagy, which was achieved by limiting NF1 expression to induce the HSF1/ATG7 pathway.

Purpose To evaluate the results of arthroscopic autologous iliac bone graft suspension fixation combined with the Remplissage procedure in the treatment of recurrent shoulder dislocation with bony Bankart lesions and joint hyperlaxity. Methods From 2018 to 2020, 22 patients with joint laxity underwent arthroscopic autologous iliac bone graft suspension fixation and Bankart repair combined with the Remplissage procedure due to recurrent shoulder dislocation. Clinical assessment included range of motion (forward flexion, abduction, 90° external rotation, conventional external rotation, adduction, and internal rotation), visual analog scale (VAS) score, Rowe score, University of California Los Angeles (UCLA) score, and Western Ontario Shoulder Instability Index (WOSI) score. Post-operatively, the healing of the bone graft was evaluated with computed tomography (CT) scanning. Results All 22 patients were followed up for a mean of 19.3 ± 4.1 months. CT imaging showed that the healing time of the bone graft was 6–8 weeks. The patient satisfaction rate was 100%, there were no cases of redislocation, all patients returned to their preinjury training state, and the fear test was negative. At the final follow-up, the UCLA, VAS, Rowe, and WOSI scores were 29.8 ± 2.1, 2.2 ± 0.8, 89.4 ± 4.2, and 482.3 ± 46.2, respectively (p Conclusion Arthroscopic autologous iliac bone graft suspension fixation and Bankart repair combined with the Remplissage procedure are effective in preventing recurrent instability with joint hyperlaxity. Furthermore, no patient had redislocation. Level of evidence IV.

It is widely acknowledged that diabetes leads to slow wound healing and ulceration, and severe serious diabetic foot ulceration may result in amputation. In recent years, much emphasis has been placed on exploring diabetic wound healing to protect patients from adverse events. We recently found interleukin-7 (IL-7), a growth factor for B-cells and T-cells, and its receptor was significantly upregulated in high glucose-induced fibroblasts and skin of diabetic mice. Moreover, IL-7 stimulated fibroblasts secreted ANGPTL4, which inhibited angiogenesis of endothelial cells resulting in delayed wound healing. In our previous study, fibroblasts, endothelial cells and keratinocytes were exposed to normal glucose (5.5 mM) or high glucose (30 mM) medium for 24 h, and RNA sequencing showed that IL-7 and IL-7R were significantly upregulated in fibroblasts. To remove the effect of high glucose and explore the influence of IL-7, exogenous rMuIL-7 used to treat normal mice led to delayed wound healing by inhibiting angiogenesis. Vitro experiments revealed that IL-7-induced fibroblasts inhibited endothelial cell proliferation, migration and angiogenesis. Further experiments showed that fibroblast angiopoietin-like-4 (ANGPTL4) secretion exhibited the inhibitory effect which was blocked by culture with the corresponding neutralizing antibody. Overall, our study revealed signaling pathways associated with diabetic wound healing and provided the foothold for further studies on delayed wound healing in this patient population. Graphical abstract Mechanism that high glucose activates IL-7-IL-7R-ANGPTL4 signal pathway in delayed wound healing. High glucose upregulates IL-7 and IL-7R in dermal fibroblasts. IL-7 stimulates dermal fibroblasts secreting Angptl4 which inhibits proliferation, migration and angiogenesis of endothelial cells in a paracrine way.

Background Ilex pubescens is an important traditional Chinese medicinal plant with many naturally occurring compounds and multiple pharmacological effects. However, the lack of reference genomic information has led to tardiness in molecular biology research and breeding programs of this plant. Results To obtain knowledge on the genomic information of I. pubescens, a genome survey was performed for the first time by next generation sequencing (NGS) together with genome size estimation using flow cytometry. The whole genome survey of I. pubescens generated 46.472 Gb of sequence data with approximately 82.2 × coverage. K-mer analysis indicated that I. pubescens has a small genome of approximately 553 Mb with 1.93% heterozygosity rate and 39.1% repeat rate. Meanwhile, the genome size was estimated to be 722 Mb using flow cytometry, which was possibly more precise for assessment of genome size than k-mer analysis. A total of 45.842 Gb clean reads were assembled into 808,938 scaffolds with a relatively short N50 of 760 bp. The average guanine and cytosine (GC) content was 37.52%. In total, 197,429 microsatellite motifs were detected with a frequency of 2.8 kb, among which mononucleotide motifs were the most abundant (up to 62.47% of the total microsatellite motifs), followed by dinucleotide and trinucleotide motifs. Conclusion In summary, the genome of I. pubescens is small but complex with a high level of heterozygosity. Even though not successfully applied for estimation of genome size due to its complex genome, the survey sequences will help to design whole genome sequencing strategies and provide genetic information support for resource protection, genetic diversity analysis, genetic improvement and artificial breeding of I. pubescens.

Achieving carbon neutrality in China before 2060 requires a radical energy transition. To identify the possible transition pathways of China’s energy system, this study presents a scenario-based assessment using the Low Emissions Analysis Platform (LEAP) model. China could peak the carbon dioxide (CO2) emissions before 2030 with current policies, while carbon neutrality entails a reduction of 7.8 Gt CO2 in emissions in 2060 and requires an energy system overhaul. The assessment of the relationship between the energy transition and energy return on investment (EROI) reveals that energy transition may decrease the EROI, which would trigger increased energy investment, energy demand, and emissions. Uncertainty analysis further shows that the slow renewable energy integration policies and carbon capture and storage (CCS) penetration pace could hinder the emission mitigation, and the possible fossil fuel shortage calls for a much rapid proliferation of wind and solar power. Results suggest a continuation of the current preferential policies for renewables and further research and development on deployment of CCS. The results also indicate the need for backup capacities to enhance the energy security during the transition.

The transient receptor potential vanilloid receptor 2 (TRPV2) has been found to participate in the pathogenesis of various types of cancers, however, its role(s) in the tumorigenesis of ESCC remain poorly understood.Western blotting and immunohistochemistry were performed to determine the expression profiles of TRPV2 in the ESCC patient tissues. A series of in vitro and in vivo experiments were conducted to reveal the role of TRPV2 in the tumorigenesis of ESCC.Our study first uncovered that the activation of TRPV2 by recurrent acute thermal stress (54 °C) or O1821 (20 μM) promoted cancerous behaviours in ESCC cells. The pro-angiogenic capacity of the ESCC cells was found to be enhanced profoundly and both tumour formation and metastasis that originated from the cells were substantially promoted in nude mouse models upon the activation of TRPV2. These effects were inhibited significantly by tranilast (120 μM) and abolished by TRPV2 knockout. Conversely, overexpression of TRPV2 could switch the cells to tumorigenesis upon activation of TRPV2. Mechanistically, the driving role of TRPV2 in the progression of ESCC is mainly regulated by the HSP70/27 and PI3K/Akt/mTOR signalling pathways.We revealed that TRPV2-PI3K/Akt/mTOR is a novel and promising target for the prevention and treatment of ESCC.

Guanxinshutong capsules (GXST) are usually used to treat acute myocardial infarction (AMI), and the clinical effect of GXST is significant. However, there have been only a few studies on the pharmacokinetics of GXST against AMI injury. The objective of this study was to investigate the pharmacokinetics of nine bioactive compounds of GXST in normal and AMI rats.In this work, a rat model of AMI was established by ligating the left anterior descending coronary artery. The pharmacokinetic parameters of nine bioactive compounds (gallic acid, danshensu, protocatechuic aldehyde, rosmarinic acid, salvianolic acid B and salvianolic acid A, dihydrotanshinone I, cryptotanshinone, and tanshinone IIA) in the plasma of AMI and normal rats were compared under the same dose of GXST by a LC-MS/MS method. Then, we selected P-glycoprotein (P-gp) and some representative cytochrome P450 enzymes (CYPs) for molecular docking to further analyze the interaction between these compounds.The pharmacokinetic studies showed that the area under the concentration-time curve (AUC) and maximum concentration (CThe results suggest that the pathological injury caused by AMI has a significant impact on the pharmacokinetic characteristics of some active compounds in GXST, which are conducive to providing a reference and promoting rational clinical drug use.

Purpose To predict the change of retinal sensitivity using optical coherence tomography (OCT) parameters in eyes with central serous chorioretinopathy (CSC). Methods Twenty-three eyes of 23 patients with CSC were enrolled. Retinal sensitivity was measured twice with a microperimetry in all examined eyes. OCT measurement was simultaneously conducted. The relationship between retinal sensitivities and the thicknesses of i) retinal nerve fiver layer + ganglion cell layer (RNFL+GCL), ii) inner nuclear layer (INL) iii) outer nuclear layer (ONL) and iV) serous retinal detachment height (SRDH) were investigated in a point-wise manner. We also investigated the association between the change of retinal sensitivity and OCT parameters at baseline. Results The mean age of participants was 49.8 ± 10.7 years. The mean SRDH was significantly lower (p