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Chia-Lin Wei, Yijun Ruan and colleagues used chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) to determine the CTCF-chromatin interactome in mouse embryonic stem cells. Mammalian genomes are viewed as functional organizations that orchestrate spatial and temporal gene regulation. CTCF, the most characterized insulator-binding protein, has been implicated as a key genome organizer. However, little is known about CTCF-associated higher-order chromatin structures at a global scale. Here we applied chromatin interaction analysis by paired-end tag (ChIA-PET) sequencing to elucidate the CTCF-chromatin interactome in pluripotent cells. From this analysis, we identified 1,480 cis - and 336 trans -interacting loci with high reproducibility and precision. Associating these chromatin interaction loci with their underlying epigenetic states, promoter activities, enhancer binding and nuclear lamina occupancy, we uncovered five distinct chromatin domains that suggest potential new models of CTCF function in chromatin organization and transcriptional control. Specifically, CTCF interactions demarcate chromatin-nuclear membrane attachments and influence proper gene expression through extensive cross-talk between promoters and regulatory elements. This highly complex nuclear organization offers insights toward the unifying principles that govern genome plasticity and function.

Nat. Genet. 43, 630–638 (2011); published online 19 June; corrected after print 11 July 2011 In the version of this article initially published, the accession codes section contained inaccuracies. The raw sequences and processed data generated from this study can be downloaded with accession number GSE28247.

Opioid anesthesia can modulate the impaired immune response and opioid-sparing anesthesia may preserve immune functions. This study was performed to assess the effects of opioid-free anesthesia (OFA) and opioid-based anesthesia (OA) on perioperative macrophages differentiation, cytokine changes, and perioperative complications in locally advanced GC (LAGC) patients. We used quality of recovery-15 (QoR-15) questionnaire scores and visual analog scale (VAS) scores to compare postoperative quality of recovery and pain level. In addition, the adverse reactions of patients in the two groups were compared. The perioperative serum level of inflammatory cytokines and the ratio of macrophage subtypes were detected. The OFA group had significantly longer extubation time and PACU stay, whereas the OA group had significantly higher rate of hypotension, higher doses of norepinephrine, higher PONV and dizziness rate, and delayed flatus passage time. The QoR-15 score on postoperative 24 h was significantly higher in OFA group than in OA group. At the end of or after the surgery, the OFA group had higher levels of interleukin (IL)-12, IL-1β, tumor necrosis factor (TNF)-α, CD68+CD163- macrophage rate, but lower levels of IL-10, transforming growth factor (TGF)-β, and CD68+CD163+ macrophage rate, indicating OFA attenuated perioperative immunosuppression by diminishing M2 and promoting M1 macrophage polarization. And the reversal tendency is more obvious in LAGC patients with neoadjuvant PD-1 inhibitor. The OFA may attenuate perioperative immunosuppression by diminishing M2 and promoting M1 macrophage polarization in LAGC patients with neoadjuvant PD-1 inhibitor. http://gcpgl.sysucc.org.cn, identifier 2022-FXY-001.

In the studies of intrusion detection/prevention systems (IDS/IPS) and network security situational awareness, malicious traffic detection has been given significantly more attention to prevent malicious traffic. Meanwhile, with the development of machine learning technology, an increasing number of algorithms and models have been employed for attack detection. Previous studies generally used common and typical machine learning models such as SVM, KNN, or a random forest. However, the bottleneck of these types of approaches is two-fold. The input of the model is constructed using the feature engineering method of artificially designed representation, which requires a substantial amounts expertise. Additionally, most detection methods ignore the temporal information between network packets in one micro-flow. In this paper, we regard malicious traffic detection as a classification task and propose a hybrid model that combines a recurrent neural network (RNN) with restricted Boltzmann machines (RBM) which take byte-level raw data as input without feature engineering. Specifically, distributed embedding is utilized to pre-process network data to make it more suitable for deep neural network models. Subsequently, an RBM model is used to extract the feature vectors of the network packets and an RNN model is used to extract the flow feature vector. Finally, the flow vectors are sent to the Softmax layer to obtain the detection result. Experiments based on the ISCX-2012 and DARPA-1998 published datasets show that our proposed RNN-RBM model has a greater detection accuracy, recall rate, and lower false alarm rate than most traditional machine learning models. This proves the effectiveness of the proposed RNN-RBM model in malicious traffic detection.

Despite the existing studies, the specific microbial factors that influence the occurrence and progression of breast cancer still remain unclear. Researchers have clarified the distinctive microbial profile related to ductal carcinoma, a common histological type of breast cancer, in order to identify tumor-specific microbes and their roles in tumorigenesis. With the tumor microbiome as the focus, the enrichment of Pseudoalteromonas elyakovii features accelerates the disease progression in patients with ductal carcinoma of the breast. This study reveals the initial role relationship and innovative findings between Pseudoalteromonas elyakovii and ductal carcinoma in the breast.

The complete mitochondrial genome and phylogenetic analysis for Leiognathus equula from the South China Sea was performed using shallow genome skimming. For accurate species identification and redescription, morphometric and meristic characters were examined and compared with previous descriptions. To facilitate the identification of species and to enable comparison with the mitochondrial genome phylogeny, molecular comparisons were conducted using three mitochondrial genes: large ribosomal RNA ( 16S rRNA), cytochrome c oxidase subunit 1 ( COX1 ), and NADH dehydrogenase ( ND5 ). The mitogenome (16 398 bp) comprised 38 mitochondrial genes, similar to most bony fishes: 13 protein-coding genes (PCGs), 2 rRNA and 22 transfer RNA genes, and 1 non-coding region. The complete mitogenome comprised 30.7% A, 24.2% T, 15.0% G, and 30.1% C. The A+T content (54.9%) was higher than the G+C content (45.1%). All PCGs started with the typical ATG codon, except COX1 , which started with GTG. Seven PCGs ended with incomplete stop codons (TA or T). The Ka/Ks ratios of all PCGs were < 1, indicating purifying selection. The phylogenies of Leiognathidae, both based on the amino acid sequences of the 13 PCGs and the single genes 16S RNA and COX1 , were monophyletic with high nodal support (> 75%). L. brevirostris (NC 026232) is believed to be a Nuchequula species, whereas L. ruconius (NC 057225) is not classified under Leiognathus in the NCBI database. The phylogenetic trees divided the Leiognathidae family into three clades. The mitogenome phylogeny suggested that the Leiognathidae and Chaetodontidae clades are sister groups. These findings provide important genetic data for population genetics research and a phylogenetic analysis of Leiognathidae.

The complete mitochondrial genome and phylogenetic analysis for from the South China Sea was performed using shallow genome skimming. For accurate species identification and redescription, morphometric and meristic characters were examined and compared with previous descriptions. To facilitate the identification of species and to enable comparison with the mitochondrial genome phylogeny, molecular comparisons were conducted using three mitochondrial genes: large ribosomal RNA ( rRNA), cytochrome c oxidase subunit 1 ( ), and NADH dehydrogenase ( ). The mitogenome (16 398 bp) comprised 38 mitochondrial genes, similar to most bony fishes: 13 protein-coding genes (PCGs), 2 rRNA and 22 transfer RNA genes, and 1 non-coding region. The complete mitogenome comprised 30.7% A, 24.2% T, 15.0% G, and 30.1% C. The A+T content (54.9%) was higher than the G+C content (45.1%). All PCGs started with the typical ATG codon, except , which started with GTG. Seven PCGs ended with incomplete stop codons (TA or T). The Ka/Ks ratios of all PCGs were < 1, indicating purifying selection. The phylogenies of Leiognathidae, both based on the amino acid sequences of the 13 PCGs and the single genes RNA and , were monophyletic with high nodal support (> 75%). (NC 026232) is believed to be a species, whereas (NC 057225) is not classified under in the NCBI database. The phylogenetic trees divided the Leiognathidae family into three clades. The mitogenome phylogeny suggested that the Leiognathidae and Chaetodontidae clades are sister groups. These findings provide important genetic data for population genetics research and a phylogenetic analysis of Leiognathidae.

Introduction This trial aimed to compare the efficacy and safety between biosimilar QL1207 and the reference aflibercept for the treatment of neovascular age-related macular degeneration (nAMD). Methods This randomized, double-blind, phase 3 trial was conducted at 35 centers in China. Patients aged ≥ 50 years old with untreated subfoveal choroidal neovascularization secondary to nAMD and best-corrected visual acuity (BCVA) letter score of 73–34 were eligible. Patients were randomly assigned to receive intravitreous injections of QL1207 or aflibercept 2 mg (0.05 ml) in the study eye every 4 weeks for the first 3 months, followed by 2 mg every 8 weeks until week 48, stratified by baseline BCVA ≥ or < 45 letters. The primary endpoint was BCVA change from baseline at week 12. The equivalence margin was ± 5 letters. The safety, immunogenicity, pharmacokinetics (PK), and plasma vascular endothelial growth factor (VEGF) concentration were also evaluated. Results A total of 366 patients were enrolled (QL1207 group, n  = 185; aflibercept group, n  = 181) from Aug 2019 to Jan 2022 with comparable baseline characteristics. The least-squares mean difference in BCVA changes was − 1.1 letters (95% confidence interval − 3.0 to 0.7; P  = 0.2275) between the two groups, within the equivalence margin. The incidences of treatment-emergent adverse events (TEAE; QL1207: 71.4% [132/185] vs. aflibercept: 71.8% [130/181]) and serious TEAE (QL1207: 14.1% [26] vs. aflibercept: 12.7% [23]) appeared comparable between treatment groups, and no new safety signal was found. Anti-drug antibody, PK profiles, and VEGF concentration were similar between the two groups. Conclusions QL1207 has equivalent efficacy to aflibercept for nAMD with similar safety profiles. It could be used as an alternative anti-VEGF agent for clinical practice. Trial Registration ClinicalTrials.gov: NCT05345236 (retrospectively registered on April 25, 2022); National Medical Products Administration of China: CTR20190937 (May 20, 2019).

With the rapid development of underground engineering construction such as hydropower projects, mines, tunnels, etc., underground hydrodynamic-related problems have become a more prominent challenge. In view of the shortcomings of the current hydrodynamic grouting materials, a systematic analysis for the preparation, performance, and water-blocking reinforcement mechanism of a new nano-composite cement-based dynamic water grouting material was carried out by a comprehensive approach of theoretical analysis, laboratory test, field test, and microscopic study. Utilizing the “synergistic hydration” effect produced by compounding ordinary Portland cement and sulfoaluminate cement, aimed at the harmonization of rheological and solidification characteristics of grouting material, a new nano-composite cement-based grouting material (NCC) was developed by mixing with water-reducing agent (JC), early strength agent (VT), nano-materials (SiO2), and cellulose (QC). The properties of the NCC, such as rheology, fluidity, pumpability, setting time, compressive strength, and anti-scour performance were carefully examined by laboratory tests. The NCC product was successfully field tested. Finally, an integrated analysis of X-ray diffraction and scanning electron microscopy was used to investigate the mechanism of water-blocking reinforcement, and consequently, it led to a water-blocking reinforcement process model of nano-composite cement slurry. The research result, i.e., NCC product, provided a new solution to effectively resolve the problem of gushing water disaster in the management of underground engineering construction.

There is significant variability with respect to the prognosis of nonmetastatic clear cell renal cell carcinoma (ccRCC) patients with venous tumor thrombus (VTT). By applying multiregion whole‐exome sequencing on normal‐tumor‐thrombus‐metastasis quadruples from 33 ccRCC patients, we showed that metastases were mainly seeded by VTT (81.8%) rather than primary tumors (PTs). A total of 706 nonmetastatic ccRCC patients with VTT from three independent cohorts were included in this study. C‐index analysis revealed that pathological grading of VTT outperformed other indicators in risk assessment (OS: 0.663 versus 0.501–0.610, 0.667 versus 0.544–0.651, and 0.719 versus 0.511–0.700 for Training, China‐Validation, and Poland‐Validation cohorts, respectively). We constructed a risk predicting model, TT‐GPS score, based on four independent variables: VTT height, VTT grading, perinephric fat invasion, and sarcomatoid differentiation in PT. The TT‐GPS score displayed better discriminatory ability (OS, c‐index: 0.706–0.840, AUC: 0.788–0.874; DFS, c‐index: 0.691–0.717, AUC: 0.771–0.789) than previously reported models in risk assessment. In conclusion, we identified for the first‐time pathological grading of VTT as an unheeded prognostic factor. By incorporating VTT grading, the TT‐GPS score is a promising prognostic tool in predicting the survival of nonmetastatic ccRCC patients with VTT. Inspired by the metastasis‐seeding potential of VTT in ccRCC, we identified for the first time that pathological grading of VTT could serve as an unheeded prognostic factor. By incorporating VTT grading, TT‐GPS score was constructed, displaying superior discriminatory ability for risk stratification in nonmetastatic ccRCC patients with VTT. This study highlights the significance of introducing VTT grading or TT‐GPS score into routine pathological reports to improve the efficacy of risk assessment.