Inflammatory response is essential to host defense and repair, and requires tight regulation as excessive and constant inflammatory response is deleterious. We recently identified that one of the ...general but key mechanisms for inflammatory gene transcription regulation is controlled by the formation of super enhancers mediated by NF-κB, and bromodomain and extraterminal (BET) proteins.
Given that microRNA transcription shares a similar mechanism to mRNA, we assume that the inflammatory microRNAs transcription could be NF-κB and BET bromodomain dependent. In the present study, we confirmed that inflammatory stimuli changed human umbilical vein endothelial cells (HUVEC) microRNA profile. Among these microRNAs, miR-146a and miR-155, two well-established inflammatory microRNAs, are both downregulated at transcriptional level by NF-κB and BET bromodomain inhibition. To pursue this mechanism, we analyzed the ChIP-seq data and found that NF-κB, BRD4 and RNA POL II were rapidly distributed at the upstream regions of miR-146a and miR-155, and more importantly mediated the formation of the super enhancers that drive miR-146a and miR-155 transcription. These microRNAs transcription driven by super enhancers in turn downregulate both in vitro and in vivo canonical inflammatory genes expression through targeting inflammatory mediators. This novel finding demonstrated how the host self-regulates inflammatory genes expression at both transcriptional and post-transcriptional level to ensure the appropriate level of the host inflammatory response.
•BET proteins and NF-κB regulate miR-146a/miR-155 expression at transcriptional level.•BET proteins and NF-κB direct super enhancers formation at miR-146a/miR-155 gene loci•Super enhancers selectively regulate a subset of microRNAs transcription.•The microRNAs driven by super enhancers in turn regulate inflammatory genes expression.
The process of liquid radial reflux interference during jet penetration in a liquid-filled composite structure is divided in this study into three stages: bottom plate reflection interference, ...side-wall reflection interference, and side-wall secondary reflection interference. The calculation model of the velocity interval of the disturbed jet and the residual penetration depth of the jet has been established through theoretical analysis. Results show that the liquid-filled composite structure can interfere with the high-speed section of the shaped charge jet. The accuracy of the theoretical analysis in this paper has been verified through numerical simulation, X-ray, and depth-of-penetration experiments. Among the results, those of the X-ray experiment show that the liquid-filled composite structure has interference on the tip of the shaped charge jet, which provides a possibility for the application of the liquid-filled composite structure to ammunition safety and other extreme cases.
Early prediction of the lithium-ion (Li-ion) battery degradation trajectory is of great importance to arrange the maintenance of battery energy storage systems (BESSs). Although extensive data driven ...methods have achieved a super good performance in state of health (SOH) and remaining useful life (RUL) prediction, the nonlinear characteristics of the Li-ion battery degradation trajectory still prevent an accurate prediction once very limited cycling data known in advance. To solve this issue, this paper proposes an empirical-informed model for the degradation trajectory prediction with only few data from the Li-ion battery's early cycling stage, which integrates the experience based knowledge to train the data driven model. A novel experience based model is proposed to describe the battery degradation curve, which further guides the training procedure of the long-short term memory (LSTM) network. In addition, XGBoost is selected to use a perceptually important point (PIP) based feature for providing the reference capacities. In this way, the proposed method can implement an end-to-end early prediction of the battery trajectory using only partial charging voltage as the input. The performance of the proposed method is verified on three datasets.
Small nucleolar RNAs (snoRNAs) play a crucial role during colorectal cancer (CRC) development. The study of SNORA71A is few, and its role in CRC is unknown. This study focused on screening abnormal ...snoRNAs in CRC and exploring the role of key snoRNA in CRC. The expression pattern of snoRNAs in 3 CRC and 3 normal colon tissues was detected via small RNA sequencing. The six candidate snoRNAs were identified by quantitative PCR (qPCR). Subsequently, the expression level of SNORA71A was further verified through the Cancer Genome Atlas (TCGA) data analysis and qPCR. The CCK8 and transwell assays were used to detect the functional role of SNORA71A in CRC cells. The integrated analysis of snoRNA expression profile indicated that a total 107 snoRNAs were significantly differentially expressed (DE) in CRC tissues compared with normal tissues, including 45 upregulated and 62 downregulated snoRNAs. Bioinformatics analysis revealed that the DE snoRNAs were mainly implicated in “detection of chemical stimulus involved in sensory perception of smell” and “sensory perception of smell” in the biological process. The DE snoRNAs were preferentially enriched in “olfactory transduction” and “glycosphingolipid biosynthesis-ganglio series pathway.” The expression of SNORA71A was upregulated in CRC tissues and cells. SNORA71A expression showed statistically significant correlations with TNM stage (P=0.0196) and lymph node metastasis (P=0.0189) and can serve as biomarkers for CRC. Importantly, SNORA71A significantly facilitated the CRC cell proliferation, migration, and invasion. Our findings indicate that SNORA71A screened by sequencing acted as an oncogene and promoted proliferation, migration, and invasion ability of CRC cells.
To study the ability of shaped charges to penetrate typical ship targets, two shaped charges with the same diameter of 200 mm but different configurations are designed to generate two forms of ...jetting projectile charge (JPC). Based on the protective structure of typical ship targets, static penetration tests are performed using the two types of a shaped charge with copper liner and 10-layer spaced targets with a total span of 16 m which is made in 921A steel. Numerical simulations under the same working conditions are also carried out. It is found that the simulation results of the penetration depth and the number of layers of target perforated by the JPC are much greater than the experimental results. In fact, the JPC breaks up when moving to a certain distance, and the JPC segments after breakup have a transverse drift velocity, causing the segment to deviate from the original penetrating channel. The influence of drift velocity after JPC fracture cannot be considered in numerical simulation, resulting in significant differences between numerical simulation and experimental results. Thus, this paper proposed a segment-based numerical simulation method and analyzed the penetration process of JPC fragments after JPC fracture. Combined with experimental results, the radial motion after JPC fracture and the final distribution of penetration holes can be well revealed. It is found that the penetration depth and the number of layers of target perforated by the JPC depend on the tip velocity of each segment and the jet length.
By using the density functional theory, we find that organometallic multidecker sandwich clusters V2n+1Cp2n+2, V n (FeCp2) n+1 (Cp = cyclopentadienyl), and V2n Ant n+1 (Ant = anthracene) may have ...linear structures, and their total magnetic moments generally increase with the cluster size. The one-dimensional (VCp)∞, (VBzVCp)∞ (Bz = benzene), and (V2Ant)∞ wires are predicted to be ferromagnetic half-metals, while the one-dimensional (VCpFeCp)∞ wire is a ferromagnetic semiconductor. The spin transportation calculations show that the finite V2n+1Cp2n+2 and V n (FeCp2) n+1 sandwich clusters coupled to gold electrodes are nearly perfect spin-filters.
Purpose
The purpose of this study was to compare the post-operative radiographic and clinical outcomes of less invasive plate fixation versus screw fixation of displaced intra-articular calcaneus ...fractures (DIACFs) via sinus tarsi approach.
Methods
A total of 165 consecutive DIACFs that underwent open reduction internal fixation via sinus tarsi approach from 2013 to 2018 were reviewed at least a two year follow-up. The methods of fixation were divided into two groups: less invasive plate fixation versus screw fixation of calcaneus fracture (59 vs 106, respectively). The radiographic outcomes including pre- and post-operative Bohler’s and Gissane’s angles were evaluated. The post-operative function was evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score, the Olerud and Molander Scale and the Visual Analogue Scale (VAS). The complications, the rates of implant removal and cost were also compared.
Results
The average follow-up was 44.2 months in the plate groups and 47.9 months in the screw groups (
P
> 0.05). There was no significant difference in the Bohler’s angle and Gissane’s angle between the plate group and screw group during the pre-operation and the last follow-up. There was no significant difference in the final AOFAS score, Olerud and Molander score and VAS score between the two groups (
P
> 0.05). The total incidence of complications was 6.7% in the plate group and 6.6% in the screw group (
P
> 0.05). The rates of implant removal and total cost during the hospitalization in the plate group were significantly higher compared with screws group (
P
< 0.05).
Conclusion
The less invasive plate fixation versus screw fixation of DIACFs via sinus tarsi approach contributed comparable quality of reduction, complications and post-operative functional outcomes. The less invasive plate technique was significantly higher in terms of implant costs and the rate of implant removal.
Relationships between forest cover and streamflow have been studied worldwide, but only a few studies have examined how gradual changes in forest structure and species composition due to logging and ...climate change affect watershed water yield (Q) and flow regimes. In this study, we analyzed long-term (45 years) hydrologic, climate and forest dynamics data from the subboreal Tahe watershed in northeastern China. Our purpose was to evaluate the effects of forest logging and regeneration on changes in forest biomass and species and to quantify the subsequent impact on mean annual streamflow and flow regime under a changing climate. The study watershed was dominated by old-growth larch (Larix gmelinii Rupr.) during the 1970s, but gradually transformed into young deciduous larch mixed with deciduous broad-leaved birch (Betula platyphylla Sukaczev) during the 2010s. During the same period, the watershed experienced climate change with a significant increase in air temperature of 0.028 ℃/year. We applied eight sensitivity-based techniques to separate the effects of climate change on water yield from those due to forest changes. We used flow duration curves (FDCs) to characterize flow regimes by dividing the study into four key periods based on the proportional change of larch and birch trees. We found that the mean annual streamflow decreased by 10 mm (−16 mm attributed to forest change and +6 mm to climate change) between the 1984–1994 period and the 2006–2016 period when the proportion of birch increased by 20% with a similar total forest volume in the later period. The mean annual streamflow increased from 216 mm to 270 mm (+35.5 mm due to forest change vs +17.7 mm due to climate change) when forest volume decreased by 18.7% (17 m3/ha) between the 1970s and 1984–1994. Water yield changed only slightly (3.5 mm) when forest volume increased by 8.7% (6 m3/ha) from 2000 to 2011. In addition, the magnitude of high flow and low flow increased following deforestation and a shift in species composition from a period (1984–1994) with 70% larch with 30% birch to a later period (2006–2016) with 50% larch with 50% birch. Both high flow and low flow decreased coinciding with a reforestation period (2006–2016). Our results highlight complex interactions among climate, forest structure, total biomass, and plant diversity (trees species composition) in influencing watershed hydrology. Further study is needed to examine the effects of ecohydrological processes such as evapotranspiration in larch and birch forests on hydrologic changes across multiple scales.
Pyrotinib, an irreversible pan-ErbB inhibitor, has been approved for treating HER2-positive advanced breast cancer in China. We conducted a nationwide, prospective observational study to examine the ...real-world data of pyrotinib-based therapy in this population. Patients from 61 sites across China were included. Pyrotinib-based regimens were prescribed at local physician's discretion. Demographics, treatment patterns, prognosis and safety were evaluated. The primary outcome was real-world progression-free survival (rwPFS). Of 1129 patients, pyrotinib-based therapy was prescribed as first-, second- and third- or later-line treatment in 437 (38.7%), 476 (42.2%) and 216 (19.1%) patients, respectively. Median rwPFS (mrwPFS) was 14.3 (95% CI, 13.3-15.2) months in the total population, with the longest mrwPFS of 17.8 (95% CI, 15.2-24.9) months in the first-line setting, followed by 14.4 (95% CI, 12.9-15.3) months in the second-line setting. Patients with third- or later-line treatment also achieved a mrwPFS of 9.3 (95% CI, 8.4-11.8) months. Patients with trastuzumab- or trastuzumab-pertuzumab-treated disease achieved a mrwPFS of 14.3 and 13.6 months, respectively. Dual HER2 blockade with pyrotinib plus trastuzumab showed a mrwPFS of 16.2 months in the total population, with data not mature in the first-line setting. For patients with baseline brain metastases, the mrwPFS was 11.7 months. The most common adverse event was diarrhea (any grade, 73.5%; grade ≥ 3, 15.3%). In real world, pyrotinib-based therapy shows promising effectiveness in the first-, as well as second- and later-line treatment, with acceptable tolerability. Further investigations regarding front-line use or novel combinations of pyrotinib might facilitate to maximize its anti-tumor potential.
The coating of polyurea elastomers on walls is a hotspot in the protection field. This work combines a numerical simulation with experimental validation to examine the blast resistance after coating ...a polyurea elastomer on a 370 mm wall under a contact explosion. Firstly, the failure limit, failure mode, and failure mechanism of the 370 mm unreinforced wall under different strength loads are studied. In the case of the contact explosion, the increase in size of the 370 mm wall blasting pit gradually stops after the dose is increased to more than 1 kg. Thereafter, the energy of the explosive load wis released by splashing wall fragments as well as by the deflection and movement of the wall. Spraying double-sided polyurea reinforcement on the wall can effectively improve the resistance to damages caused by exposure to explosive loads and can inhibit the damage to the surrounding personnel and equipment caused by flying structural debris. When the polyurea thickness on the front surface is 6 mm, the optimal thickness of the back surface should be 2 mm.
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