SH3 and multiple ankyrin repeat domains 1 (SHANK1) is a scaffold protein, plays an important role in the normal function of neuron system. It has recently been shown to be a potential oncogene. In ...the present study, we report that the expression of SHANK1 is upregulated in non-small cell lung cancer (NSCLC), and is correlated with clinic pathological characteristics of NSCLC. Moreover, SHANK1 overexpression enhances the proliferation, migration and invasion of NSCLC cells. Mouse cell-derived xenograft model also confirmed the effects of SHANK1 on tumor growth in vivo. Furthermore, we found that SHANK1 increases the protein degradation of Klotho (KL), an important tumor suppressor, through ubiquitination-dependent pathway. In particular, we report discovery of KL as a SHANK1-interacting protein that acts as a new substate of the E3 ubiquitin ligase MDM2. SHANK1 can form a complex with KL and MDM2 and enhance the interaction between KL and MDM2. Our findings reveal an important oncogenic role and mechanism of SHANK1, suggesting SHANK1 can be a potential therapeutic target in NSCLC.
Identifying plant, fungal, and animal ingredients in a specific mixture remains challenging during the limitation of PCR amplification and low specificity of traditional methods. Genomic DNA was ...extracted from mock and pharmaceutical samples. Four type of DNA barcodes were generated from shotgun sequencing dataset with the help of a local bioinformatic pipeline. Taxa of each barcode was assigned by blast to TCM-BOL, BOLD, and GenBank. Traditional methods including microscopy, thin layer chromatography (TLC), and high-performance liquid chromatography (HPLC) were carried out according to Chinese pharmacopoeia. On average, 6.8 Gb shotgun reads were sequenced from genomic DNA of each sample. Then, 97, 11, 10, 14, and one operational taxonomic unit (OTU) were generated for ITS2, psbA-trnH, rbcL, matK, and COI, respectively. All the labeled ingredients including eight plant, one fungal, and one animal species were successfully detected in both the mock and pharmaceutical samples, in which Chebulae Fructus, Poria, and Fritilariae Thunbergia Bulbus were identified via mapping reads to organelle genomes. In addition, four unlabeled plant species were detected from pharmaceutical samples, while 30 genera of fungi, such as Schwanniomyces, Diaporthe, Fusarium were detected from mock and pharmaceutical samples. Furthermore, the microscopic, TLC, and HPLC analysis were all in accordance with the standards stipulated by Chinese Pharmacopoeia. This study indicated that shotgun metabarcoding could simultaneously identified plant, fungal, and animal ingredients in herbal products, which has the ability to serve as a valuable complement to traditional methods.
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Global per capita meat consumption continues to rise, especially pork. Meat quality is influenced by the content of intramuscular fat (IMF) as a key factor. The longissimus dorsi muscle of Dahe pigs ...(DHM, IMF: 7.98% + or - 1.96%) and Dahe black pigs (DHBM, IMF: 3.30% + or - 0.64%) was studied to explore cellular heterogeneity and differentially expressed genes (DEGs) associated with IMF deposition using single-nucleus RNA sequencing (snRNA-seq). The lipid composition was then analyzed using non-targeted lipidomics. A total of seven cell subpopulations were identified, including myocytes, fibroblast/fibro/adipogenic progenitors (FAPs), satellite cells, endothelial cells, macrophages, pericytes, and adipocytes. Among them, FAPs and adipocytes were more focused because they could be associated with lipid deposition. 1623 DEGs in the FAPs subpopulation of DHBM were up-regulated compared with DHM, while 1535 were down-regulated. These DEGs enriched in the glycolysis/gluconeogenesis pathway. 109 DEGs were up-regulated and 806 were down-regulated in the adipocyte subpopulation of DHBM compared with DHM, which were mainly enriched in the PPAR signaling pathway and fatty acid (FA) biosynthesis. The expression level of PPARG, ABP4, LEP, and ACSL1 genes in DHM was higher than that in DHBM. Lipidomics reveals porcine lipid composition characteristics of muscle tissue. A total of 41 lipid classes and 2699 lipid species were identified in DHM and DHBM groups. The top ten relative peak areas of lipid classes in DHM and DHBM were triglyceride (TG), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), diglyceride (DG), cardiolipin (CL), ceramides (Cer), Simple Glc series (Hex1Cer), sphingomyelin (phSM), and phosphatidylinositol (PI). The relative peak areas of 35 lipid species in DHM were lower than DHBM, and 28 lipid species that were higher. There was a significant increase in the TG fatty acyl chains C6:0, C17:0, and C11:4, and a significant decrease in C16:0, C18:1, C18:2, and C22:4 in DHBM (p < 0.05). C16:0 FA may downregulate the expression level of PPARG gene, which leads to the downregulation of fat metabolism-related genes such as ACSL, PLIN2, and FABP4 in DHBM compared with DHM. This may be the reason that the lipid deposition ability of Dahe pigs is stronger than that of Dahe black pigs, which need further investigation.
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This study aimed to investigate RING-Finger Protein 6 (RNF6) expression in esophageal squamous cell carcinoma (ESCC) cells and whether it affects cell proliferation, invasion, and migration by ...regulating the TGF-β1/c-Myb pathway.
TCGA database was used to analyze RNF6 expression in normal tissues and esophageal cancer tissues. Kaplan-Meier method was used to examine the correlation between RNF6 expression and patient prognosis. SiRNA interference vector and RNF6 overexpression plasmid were constructed, and RNF6 was transfected into Eca-109 and KYSE-150 esophageal cancer cell line.
scratch assay and Transwell assay were conducted to investigate the effects of RNF6 on the migration and invasion of Eca-109 and KYSE-150 cells. RT-PCR detected the expression of Snail, E-cadherin, and N-cadherin, and TUNEL detected the apoptosis of cells.
RNF6 up-regulation promoted the progression of esophageal cancer and predicted poor prognosis. RNF6 also enhanced the migration and invasion of ESCC cells
. RNF6 silencing inhibited the migration and invasion of ESCC cells. TGF-β inhibitors reversed the oncogenic effects of RNF6. RNF6 regulated the migration and invasion of ESCC cells by activating the TGF-β pathway. RNF6/TGF-β1 promoted esophageal cancer progression through c-Myb.
RNF6 promotes the proliferation, invasion, and migration of ESCC cells possibly by activating the TGF-β1/c-Myb pathway and affects the progression of ESCC.
Lung cancer has one of the highest morbidity and mortality rates in the world. Frailty is common in many countries and is a major cause of premature functional decline and premature death in older ...adults, and may affect the treatment and prognosis of lung cancer patients. To investigate the predictive value of frailty at diagnosis on all-cause mortality in lung cancer patients, this study retrospectively collected and analysed clinical information on lung cancer patients from 2015-2018. A total of 1667 patients with primary lung cancer were finally included in this study. The median follow-up time of patients was 650 (493, 1001.5) days. A total of 297(17.8%) patients had FI-LAB(the frailty index based on laboratory test) status of frail at the moment of diagnosis and the all-cause mortality rate for all patients was 61.1% (1018/1667). In a univariate model, we found a higher total all-cause mortality risk in frail patients (frail vs. robust, HR(hazard ratio) = 1.616, 95% CI(confidence interval) = 1.349,1.936), after balancing other variables combined into model 1 to model 6. The results were analyzed visually using ROC(Receiver operating characteristic) curves with nomogram and the AUC values ranged from 0.866-0.874. The final inclusion of age, TNM stage, CCI(Charlson comorbidity index) score, surgery history and chemotherapy into a multifactorial model balanced the predictive power of frailty grading on all-cause mortality. The study showed that for lung cancer patients, the higher the level of frailty at diagnosis, the higher the risk of all-cause mortality. In the context of widespread electronic medical records in hospitals, it is convenient and feasible to use FI-LAB to assess the prognosis of lung cancer patients.
Functionalization of amide bond via the cleavage of a non-carbonyl, C-N σ bond remains under-investigated. In this work, a transition-metal-free single-electron transfer reaction has been developed ...for the C-N σ bond cleavage of
-acylazetidines using the electride derived from sodium dispersions and 15-crown-5. Of note, less strained cyclic amides and acyclic amides are stable under the reaction conditions, which features the excellent chemoselectivity of the reaction. This method is amenable to a range of unhindered and sterically encumbered azetidinyl amides.
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Short-term load dispatching (STLD) for a hydropower plant with multiple turbines in one tunnel (HPMTT) refers to determining when to startup or shutdown the units of different tunnels and scheduling ...the online units of each tunnel to obtain optimal load dispatch while simultaneously meeting the hydraulic and electric system constraints. Modeling and solving the STLD for a HPMTT is extremely difficult due to mutual interference between units and complications of the hydraulic head calculation. Considering the complexity of the hydraulic connections between multiple power units in one tunnel, a two-phase decomposition approach for subproblems of unit-commit (UC) and optimal load dispatch (OLD) is described and a two-stage model (TSM) is adopted in this paper. In the first stage, an on/off model for the units considering duration constraints is established, and the on/off status of the units and tunnels is determined using a heuristic searching method and a progressive optimal algorithm. In the second stage, a load distribution model is established and solved using dynamic programming for optimal load distribution under the premise of the on/off status of the tunnel and units in the first stage. The proposed method is verified using the load distribution problem for the Tianshengqiao-II reservoir (TSQII) in dry season under different typical load rates. The results meet the practical operation requirements and demonstrate the practicability of the proposed method.
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ABSTRACT Long-term inflow forecasting is extremely important for reasonable dispatch schedules of hydropower stations and efficient utilization plans of water resources. In this paper, a novel ...forecast framework, meteorological data long short-term memory neural network (M-LSTM), which uses the meteorological dataset as input and adopts LSTM, is proposed for monthly inflow forecasting. First, the meteorological dataset, which provides more effective information for runoff prediction, is obtained by inverse distance weighting (IDW). Second, the maximal information coefficient (MIC) can adequately measure the degree of correlation between meteorological data and inflow; therefore, the MIC can distinguish key attributes from massive meteorological data and further reduce the computational burden. Last, LSTM is chosen as the prediction method due to its powerful nonlinear predictive capability, which can couple historical inflow records and meteorological data to forecast inflow. The Xiaowan hydropower station is selected as the case study. To evaluate the effectiveness of the M-LSTM for runoff prediction, several methods including LSTM, meteorological data backpropagation neural network (M-BPNN), meteorological data support vector regression (M-SVR) are employed for comparison with the M-LSTM and six evaluation criteria are used to compare its performance. Results revealed that M-LSTM outperforms other test methods in developing the long-term prediction method.
Frailty is associated with poor prognosis in a wide range of illnesses. However, its prognostic implications for older patients with community-acquired pneumonia (CAP) are not adequately addressed.
...In this study, patients were classified into 3 groups according to the frailty index based on standard laboratory tests (FI-Lab) score: robust (FI-Lab < 0.2), pre-frail (FI-Lab 0.2-0.35), and frail (FI-Lab ≥ 0.35). The relationships between frailty and all-cause mortality and short-term clinical outcomes (length of stay, duration of antibiotic therapy, in-hospital mortality) were examined.
Finally, 1164 patients were included, the median age was 75 years (interquartile range: 69, 82), and 438 patients (37.6%) were women. According to FI-Lab, 261(22.4%), 395(33.9%), and 508(43.6%) were robust, pre-frail, and frail. After adjustment for confounding variables, frailty was independently associated with prolonged antibiotic treatment (p = 0.037); pre-frailty and frailty were independently associated with longer inpatient days (p < 0.05 for both). The risk of in-hospital mortality was independently increased in frail patients (HR = 5.01, 95% CI = 1.51-16.57, p = 0.008) but not pre-frail patients (HR = 2.87, 95% CI = 0.86-9.63, p = 0.088) compared to robust patients. During a median follow-up of 33.9 months (interquartile range: 32.8 to 35.1 months), 408 (35.1%) patients died, of whom 29 (7.1%) were robust, 112 (27.5%) were pre-frail, and 267 (65.9%) were frail. Compared to robust patients, frail and pre-frail were significantly associated with increased risk for all-cause death (HR = 4.29, 95%CI: 1.78-10.35 and HR = 2.42 95%CI: 1.01-5.82, respectively).
Frailty is common among older patients with CAP and is strongly associated with increased mortality, longer length of stay, and duration of antibiotics. A routine frail assessment at the admission of elderly patients with CAP is necessary as the first step for appropriate multidisciplinary interventions.
Host genetics and environment participate in the shaping of gut microbiota. Diannan small ear pigs and Diqing Tibetan pigs are excellent native pig breeds in China and live in different environments. ...However, the gut microbiota of Diannan small ear pigs and Diqing Tibetan pigs were still rarely understood. Therefore, this study aimed to analyze the composition characteristics of gut microbiota and metabolites in Diannan small ear pigs and Diqing Tibetan pigs.
Fresh feces of 6 pigs were randomly collected from 20 4-month-old Diannan small ear pigs (DA group) and 20 4-month-old Diqing Tibetan pigs (TA group) for high-throughput 16S rRNA sequencing and liquid chromatography-mass spectrometry (LC-MS) non-targeted metabolome analysis.
The results revealed that Firmicutes and Bacteroidetes were the dominant phyla in the two groups. Chao1 and ACE indices differed substantially between DA and TA groups. Compared with the DA group, the relative abundance of Prevotellaceae, and
was significantly enriched in the TA group, while the relative abundance of Lachnospiraceae,
, and
was significantly reduced. Cholecalciferol, 5-dehydroepisterol, stigmasterol, adrenic acid, and docosahexaenoic acid were significantly enriched in DA group, which was involved in the steroid biosynthesis and biosynthesis of unsaturated fatty acids. 3-phenylpropanoic acid, L-tyrosine, phedrine, rhizoctin B, and rhizoctin D were significantly enriched in TA group, which was involved in the phenylalanine metabolism and phosphonate and phosphinate metabolism.
We found that significant differences in gut microbiota composition and metabolite between Diannan small ear pigs and Diqing Tibetan pigs, which provide a theoretical basis for exploring the relationship between gut microbiota and pig breeds.
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