The Nucleocapsid Protein (NP) of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is not only the core structural protein required for viral packaging, but also participates in the ...regulation of viral replication, and its post‐translational modifications such as phosphorylation have been shown to be an important strategy for regulating virus proliferation. Our previous work identified NP could be ubiquitinated, as confirmed by two independent studies. But the function of NP ubiquitination is currently unknown. In this study, we first pinpointed TRIM6 as the E3 ubiquitin ligase responsible for NP ubiquitination, binding to NP's CTD via its RING and B‐box‐CCD domains. TRIM6 promotes the K29‐typed polyubiquitination of NP at K102, K347, and K361 residues, increasing its binding to viral genomic RNA. Consistently, functional experiments such as the use of the reverse genetic tool trVLP model and gene knockout of TRIM6 further confirmed that blocking the ubiquitination of NP by TRIM6 significantly inhibited the proliferation of SARS‐CoV‐2. Notably, the NP of coronavirus is relatively conserved, and the NP of SARS‐CoV can also be ubiquitinated by TRIM6, indicating that NP could be a broad‐spectrum anti‐coronavirus target. These findings shed light on the intricate interaction between SARS‐CoV‐2 and the host, potentially opening new opportunities for COVID‐19 therapeutic development.
We conducted petrographic, geochemical, and new U-Pb laser ablation inductively coupled mass spectrometry analyses of detrital zircons in the sandstone samples from the important Mengqiguer ...sandstone-type uranium deposit located in the Yili basin of the Xishanyao Formation. This formation (Shuixigou Group) is a major uranium-bearing target stratum in the basin. The main purpose of our investigations was to determine the provenance of the host sand units that has remained unclear to date. Our petrographic results suggested that the host sandstone is texturally and chemically immature, indicating superior physicochemical conditions for later uranium mineralisation. The major and trace element data of the detrital sandstone samples point towards the upper continental crust, and the chondrite-normalised rare earth element (REE) plots show enriched light REE and relatively flat heavy-REE distribution, with a negative Eu anomaly. The characteristics of the REEs and the trace elements point to felsic rocks as the provenance of the target strata with a continental arc tectonic setting. The detrital zircons indicate an age span of ∼235-∼2327 Ma, with major age populations of ∼300-∼500 Ma. The increasing amount of zircon grains from the Late Devonian to the Early Carboniferous coinciding with the age of volcanic magmatic activities of the Wusun and Nalati mountains indicates that the rocks formed under the Tianshan collisional orogeny and the subsequent extensional environment.
MicroRNA-101 (miR-101) expression is negatively associated with tumor growth and blood vessel formation in several solid epithelial cancers. However, the role of miR-101 in human breast cancer ...remains elusive.
MiR-101 was significantly decreased in different subtypes of human breast cancer tissues compared with that in adjacent normal breast tissues (P<0.01). Up-regulation of miR-101 inhibited cell proliferation, migration and invasion, and promoted cell apoptosis in ER alpha-positive and ER alpha-negative breast cancer cells and normal breast cells. Down-regulation of miR-101 displayed opposite effects on cell growth and metastasis. Further investigation revealed a significant inverse correlation between the expression of miR-101 and Stathmin1 (Stmn1), and miR-101 could bind to the 3'-untranslated region (UTR) of Stmn1 to inhibit Stmn1 translation. The inhibition of cell growth and metastasis induced by up-regulation of miR-101 was partially restored by overexpression of Stmn1. Knockdown of Stmn1 attenuates the down-regulation of miR-101-mediated enhancement of cell growth and metastasis. More importantly, in vivo analysis found that Stmn1 mRNA and protein level in different subtypes of human breast cancer tissues, contrary to the down-regulation of miR-101, were significantly elevated.
This study demonstrates that down-regulation of miR-101 in different subtypes of human breast cancer tissues is linked to the increase of cellular proliferation and invasiveness via targeting Stmn1, which highlights novel regulatory mechanism in breast cancer and may provide valuable clues for the future clinical diagnosis of breast cancer.
Deep convolutional neural networks (CNNs) have achieved tremendous successes but tend to suffer from high computation costs mainly due to heavy over-parameterization, resulting in the difficulty of ...directly applying them to the ever-growing application demands based on low-end edge devices with strong power restriction and real-time inference requirement. Recently, there has much research attention devoted to compressing the network via pruning to address this issue. Most of the existing methods rely on some hand-designed pruning rules, which suffer from several limitations. Firstly, manually designed rules are only applicable to limited application scenarios, which can hardly generalize well in a broader scope. And these rules are typically designed based on human experience and via trial and error, and thus highly subjective. Then, channels of different layers in a network may have diverse distributions, which means the same pruning rule is not appropriate for each layer. To address these limitations, we propose a novel channel pruning scheme, in which the task-irrelevant channels are removed in a task-driven manner. Specifically, an adaptively differentiable search module is proposed to find the best pruning rule automatically for different layers in CNNs under sparsity constraints. Besides, we employed knowledge distillation to alleviate the excessive performance loss. Once the training process is finished, a compact network will be obtained by removing channels based on layer-wise pruning rules. We have evaluated the proposed method on some well-known benchmark datasets including CIFAR, MNIST, and ImageNet in comparison to several state-of-the-art pruning methods. Experimental results demonstrate the superiority of our method over the compared ones in terms of both parameters and FLOPs reduction.
Purpose
To compare the clinical outcomes between patients that underwent transjugular intrahepatic portosystemic shunt (TIPS) via the left and right portal veins (PVs).
Materials and methods
All ...relevant studies in the Pubmed, Embase, and Cochrane Library databases published as of June 2020 were identified by searching, after which RevMan v5.3 was used to conduct the present meta-analysis. Relevant endpoint data were extracted from each study, related to postoperative hepatic encephalopathy (HE) rates, TIPS dysfunction, re-bleeding, and mortality.
Results
A total of eight studies were identified as being relevant for inclusion in this meta-analysis. These studies included 2592 total patients suffering from liver cirrhosis that underwent TIPS treatment via the left (
n
= 1500) or right (
n
= 1092) PVs. Rates of postoperative HE were significantly lower in the left PV group relative to the right PV group (5.7% vs. 18.1%, OR 0.19;
P
< 0.00001), as were rates of TIPS dysfunction (8.1% vs. 16.5%, OR 0.41;
P
< 0.00001). In contrast, the rates of re-bleeding did not differ significantly between these groups (12.0% vs. 14.9%, OR 0.76;
P
= 0.11), nor did mortality rates (30.9% vs. 31.0%, OR 0.85,
P
= 0.22). We did not detect any significant heterogeneity among included studies for any analyzed endpoints, nor was any risk of publication bias pertaining to these studies detected through the use of funnel plots.
Conclusions
TIPS conducted via the left PV was associated with decreased rates of postoperative HE and TIPS dysfunction relative to TIPS conducted via the right PV.
A high maternal triglyceride (mTG) level during early pregnancy is linked to adverse pregnancy outcomes, but the use of specific interventions has been met with limited success. A retrospective ...cohort study was designed to investigate the impact of gestational weight gain (GWG) on the relationship between high levels of mTG and adverse pregnancy outcomes in normal early pregnancy body mass index (BMI) women. The patients included 39,665 women with normal BMI who had a singleton pregnancy and underwent serum lipids screening during early pregnancy. The main outcomes were adverse pregnancy outcomes, including gestational hypertension, preeclampsia, gestational diabetes, cesarean delivery, preterm birth, and large or small size for gestational age (LGA or SGA) at birth. As a result, the high mTG (≥2.05mM) group had increased risks for gestational hypertension ((Adjusted odds ratio (AOR), 1.80; 95% CI, 1.46 to 2.24)), preeclampsia (1.70; 1.38 to 2.11), gestational diabetes (2.50; 2.26 to 2.76), cesarean delivery (1.22; 1.13 to 1.32), preterm birth (1.42, 1.21 to 1.66), and LGA (1.49, 1.33 to 1.68) compared to the low mTG group, after adjustment for potential confounding factors. Additionally, the risks of any adverse outcome were higher in each GWG subgroup among women with high mTG than those in the low mTG group. High mTG augmented risks of gestational hypertension, preeclampsia, preterm birth, and LGA among women with 50th or greater percentile of GWG. Interestingly, among women who gained less than the 50th percentile of GWG subgroups, there was no relationship between high mTG level and risks for those pregnancy outcomes when compared to low mTG women. Therefore, weight control and staying below 50th centile of the suggested GWG according to gestational age can diminish the increased risks of adverse pregnancy outcomes caused by high mTG during early pregnancy.
Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa. To develop these comprehensive guidelines ...for the diagnosis and management of NPC, the Chinese Society of Clinical Oncology (CSCO) arranged a multi‐disciplinary team comprising of experts from all sub‐specialties of NPC to write, discuss, and revise the guidelines. Based on the findings of evidence‐based medicine in China and abroad, domestic experts have iteratively developed these guidelines to provide proper management of NPC. Overall, the guidelines describe the screening, clinical and pathological diagnosis, staging and risk assessment, therapies, and follow‐up of NPC, which aim to improve the management of NPC.
Nasopharyngeal carcinoma (NPC) is the most common head and neck cancer in Southeast Asia. Because local recurrence and distant metastasis are still the main causes of NPC treatment failure, it is ...urgent to identify new tumor markers and therapeutic targets for advanced NPC.
RNA sequencing (RNA-seq) was applied to look for interchromosome translocation in NPC. PCR, FISH, and immunoprecipitation were used to examine the fusion gene expression at RNA, DNA, and protein levels in NPC biopsies. MTT assay, colony formation assay, sphere formation assay, co-immunoprecipitation, chromatin immunoprecipitation assay, and
chemoresistance assay were applied to explore the function of
in NPC.
We demonstrated that
was present in 10.03% (35/349) primary NPC biopsies and 10.7% (9/84) in head and neck cancer (HNC) samples. RARS-MAD1L1 overexpression increased cell proliferation, colony formation, and tumorigenicity
, and the silencing of endogenous RARS-MAD1L1 reduced cancer cell growth and colony formation
In addition, RARS-MAD1L1 increased the side population (SP) ratio and induced chemo- and radioresistance. Furthermore RARS-MAD1L1 interacted with AIMP2, which resulted in activation of FUBP1/c-Myc pathway. The silencing of FUBP1 or the administration of a c-Myc inhibitor abrogated the cancer stem cell (CSC)-like characteristics induced by RARS-MAD1L1. The expression of c-Myc and ABCG2 was higher in
-positive HNC samples than in negative samples.
Our findings indicate that RARS-MAD1L1 might contribute to tumorigenesis, CSC-like properties, and therapeutic resistance, at least in part, through the FUBP1/c-Myc axis, implying that
might serve as an attractive target for therapeutic intervention for NPC.
.
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