Next-generation sequencing (NGS) has drastically enhanced human cancer research, but diverse sequencing strategies, complicated open-source software, and the identification of massive numbers of ...mutations have limited the clinical application of NGS. Here, we first presented GPyFlow, a lightweight tool that flexibly customizes, executes, and shares workflows. We then introduced DIVIS, a customizable pipeline based on GPyFlow that integrates read preprocessing, alignment, variant detection, and annotation of whole-genome sequencing, whole-exome sequencing, and gene-panel sequencing. By default, DIVIS screens variants from multiple callers and generates a standard variant-detection format list containing caller evidence for each sample, which is compatible with advanced analyses. Lastly, DIVIS generates a statistical report, including command lines, parameters, quality-control indicators, and mutation summary. DIVIS substantially facilitates complex cancer genome sequencing analyses by means of a single powerful and easy-to-use command. The DIVIS code is freely available at
https://github.com/niu-lab/DIVIS
, and the docker image can be downloaded from
https://hub.docker.com/repository/docker/sunshinerain/divis
.
The development of high-precision optogenetics in deep tissue is limited due to the strong optical scattering induced by biological tissue. Although various wavefront shaping techniques have been ...developed to compensate the scattering, it is still a challenge to non-invasively characterize the dynamic scattered optical wavefront inside the living tissue. Here, we present a non-invasive scattering compensation system with fast multidither coherent optical adaptive technique (fCOAT), which allows the rapid wavefront correction and stable focusing in dynamic scattering medium. We achieve subcellular-resolution focusing through 500-μm-thickness brain slices, or even three pieces overlapped mouse skulls after just one iteration with a 589 nm CW laser. Further, focusing through dynamic scattering medium such as live rat ear is also successfully achieved. The formed focus can maintain longer than 60 s, which satisfies the requirements of stable optogenetics manipulation. Moreover, the focus size is adjustable from subcellular level to tens of microns to freely match the various manipulation targets. With the specially designed fCOAT system, we successfully achieve single-cellular optogenetic manipulation through the brain tissue, with a stimulation efficiency enhancement up to 300% compared with that of the speckle.
Cough is one of the most common complications following intravenous administration of sufentanil during anesthesia induction. The study aimed to investigate the protective effect of alfentanil, ...afentanyl derivative with short onset time and short duration, in reducing sufentanil-induced cough.
Eighty patients that scheduled for thyroid surgery under general anesthesia were randomly divided into the alfentanil group and normal saline group, with 40 cases per group. Patients in the alfentanil group received intravenous administration of 2 μg/kg alfentanil prior to sufentanil injection during general anesthesia induction, while the same dose of normal saline was administered in the normal saline group. The outcomes measures included the incidence and severity of cough and common side effects of opioids following the administration of sufentanil during the induction of general anesthesia, intraoperative hemodynamics parameters and major adverse events during anesthesia recovery period.
The incidence of cough within one minute after the injection of sufentanil during anesthesia induction was 40% in the normal saline group, and the pretreatment of alfentanil significantly reduced the incidence of sufentanil-induced cough to 5% (p < 0.05). Correspondingly, the patients in the alfentanil group had decreased severity of sufentanil-induced cough compared with the normal saline group (p < 0.05). No significant differences in the incidences of common side effects of opioids (dizziness, nausea and vomiting, chest tightness and respiratory depression) within one minute after sufentanil injection were found (p > 0.05). Furthermore, there were no significant differences between the two groups in intraoperative hemodynamic parameters, extubation time, or the incidences of emergence agitation, respiratory depression, delayed recovery from anesthesia and postoperative nausea and vomiting during Postanesthesia Care Unit stay (p > 0.05).
Pretreatment with low-dose alfentanil (2 μg/kg) effectively and safely reduced both the incidence and severity of sufentanil-induced cough during anesthesia induction.
Chinese Clinical Trial Registry (identifier: ChiCTR2300069286).
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•EGCG was transformed from a bioactive ingredient to a bioactive drug carrier.•The lipid solubility, stability, and bioactivity of EGCG were improved.•The tough issue of targeted ...delivery of water-soluble EGCG was improved.•Co-loading and delivering of EGCG and PTX were achieved without inert carrier.•This strategy exhibited a synergistic effect in the treatment of breast tumors.
Epigallocatechin gallate (EGCG) has attracted the increasing attention of many researchers, especially in the field of tumor therapy. However, EGCG has poor fat solubility, low stability, low bioavailability, and a high effective dose in vivo. Traditional drug delivery methods are difficult to deliver the water-soluble EGCG efficiently and in high doses to tumor sites. To address these issues, a new type of strategy has been tried in this study to transform EGCG from a “Bioactive natural ingredient” into a “Bioactive drug carrier”. Briefly, the EGCG was modified with a fat-soluble 9-fluorene methoxy carbonyl (Fmoc) motif, and the obtained EGCG-Fmoc showed a considerable improvement in lipid solubility and stability. Interestingly, EGCG-Fmoc obtained the characteristic of self-assembly in water, making it easier to take up by tumor cells. Furthermore, the self-assembled nanocomplex exhibited paclitaxel encapsulation performance and could achieve the dual delivery of EGCG and paclitaxel.
The extremely low bioavailability of oral paclitaxel (PTX) mainly due to the complicated gastrointestinal environment, the obstruction of intestinal mucus layer and epithelium barrier. Thus, it is of ...great significance to construct a coordinative delivery system which can overcome multiple intestinal physicochemical obstacles simultaneously. In this work, a high-density PEGylation-based glycocholic acid-decorated micelles (PTX@GNPs) was constructed by a novel polymer, 9-Fluorenylmethoxycarbonyl-polyethylene glycocholic acid (Fmoc-PEG-GCA). The Fmoc motif in this polymer could encapsulate PTX via π‒π stacking to form the core of micelles, and the low molecular weight and non-long hydrophobic chain of Fmoc ensures the high-density of PEG. Based on this versatile and flexible carriers, PTX@GNPs possess mucus trapping escape ability due to the flexible PEG, and excellent intestine epithelium targeting attributed to the high affinity of GCA with apical sodium-dependent bile acid transporter. The in vitro and in vivo results showed that this oral micelle could enhance oral bioavailability of PTX, and exhibited similar antitumor efficacy to Taxol injection via intravenous route. In addition, oral PTX@GNPs administered with lower dosage within shorter interval could increase in vivo retention time of PTX, which supposed to remodel immune microenvironment and enhance oral chemotherapy efficacy by synergistic effect.
A novel high-density PEGylation-based glycocholic acid-decorated micelles was constructed, which has the advantage of synergistically enhanced mucus penetration and intestinal epithelium transport, and can achieve sequential oral delivery of paclitaxel. Display omitted
Abstract
Ferroptosis, with iron-dependent and ROS-dependent, is a novel type of cell death in a variety of diseases and some studies confirmed that ferroptosis-related lncRNAs are involved in the ...occurrence and development of several cancers. However, the ferroptosis-related lncRNA in the role of gliomas is unclear. Here, we constructed a prognostic scoring model of ferroptosis-related lncRNAs in gliomas. Data were downloaded from the Chinese glioma genome atlas (CGGA), the cancer genome atlas, and FerrDb database. In this study, we found 1051 lncRNAs associated with ferroptosis by Spearman's rank correlation analysis in CGGA653, and 547 lncRNAs were related to prognosis in gliomas. Subsequently, we identified 9 ferroptosis-related signatures (AC010729.2, AC062021.1, FAM225B, FAM66C, HOXA-AS2, LINC00662, LINC00665, MIR497HG, and TMEM72-AS1) by least absolute shrinkage and selection operator and Cox proportional hazards model. Next, all glioma patients were divided into high- and low-risk groups based on the median risk score based on these signatures, and the low-risk group had better prognosis significantly than the high-risk group by Kaplan-Meier curve. Moreover, the risk score can predict survival status with high sensitivity and specificity by receiver operating characteristic curve (area under the curve at 1, 3, 5 years: 0.791, 0.84, 0.856, respectively). In addition, some pathways (cell cycle, p53 signaling pathway, apoptosis, and oxidative phosphorylation) significantly enriched in KEGG enrichment pathway, and a nomogram was constructed by integrating some independent prognostic clinicopathological features to predict the overall survival in gliomas (C-index: 0.786). In summary, these 9 ferroptosis-related signatures have potential prognostic value and could be crucial factors for treating malignant gliomas.
With the continuous development of economy and society, power demand forecasting has become an important task of the power industry. Accurate power demand forecasting can promote the operation and ...development of the power supply industry. However, since power consumption is affected by a number of factors, it is difficult to accurately predict the power demand data. With the accumulation of data in the power industry, machine learning technology has shown great potential in power demand forecasting. In this study, gradient boosting decision tree (GBDT), extreme gradient boosting (XGBoost) and light gradient boosting machine (LightGBM) are integrated by stacking to build an XLG-LR fusion model to predict power demand. Firstly, preprocessing was carried out on 13 months of electricity and meteorological data. Next, the hyperparameters of each model were adjusted and optimized. Secondly, based on the optimal hyperparameter configuration, a prediction model was built using the training set (70% of the data). Finally, the test set (30% of the data) was used to evaluate the performance of each model. Mean absolute error (MAE), root mean square error (RMSE), mean absolute percentage error (MAPE), and goodness-of-fit coefficient (R^2) were utilized to analyze each model at different lengths of time, including their seasonal, weekly, and monthly forecast effect. Furthermore, the proposed fusion model was compared with other neural network models such as the GRU, LSTM and TCN models. The results showed that the XLG-LR model achieved the best prediction results at different time lengths, and at the same time consumed the least time compared to the neural network model. This method can provide a more reliable reference for the operation and dispatch of power enterprises and future power construction and planning.
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•Twenty new (10S)-10,12-disubstituted aloperines were designed and synthesized.•Compound 3i showed a moderate activity against SARS-CoV-2 variant EG.5.1.•3i inhibited TMPRSS2 protease ...activity to exhibit anti-HCoV-OC43 effect.•3i could directly target an allosteric site of host TMPRSS2, rather than catalytic center.•The combination of 3i and MPV exerted an additive effect against HCoV-OC43.
By inducing steric activation of the 10CH bond with a 12-acyl group to form a key imine oxime intermediate, 20 novel (10S)-10,12-disubstituted aloperine derivatives were successfully synthesized and assessed for their antiviral efficacy against HCoV-OC43. Of them, compound 3i exhibited the moderate activities against HCoV-OC43, as well as against the SARS-CoV-2 variant EG.5.1 with the comparable EC50 values of 4.7 and 4.1 μM. A mechanism study revealed that it inhibited the protease activity of host TMPRSS2 by binding to an allosteric site, rather than the known catalytic center, different from that of camostat. Also, the combination of compound 3i and molnupiravir, as an RdRp inhibitor, showed an additive antiviral effect against HCoV-OC43. The results provide a new binding mode and lead compound for targeting TMPRSS2, with an advantage in combating broad-spectrum coronavirus.
Tibial tuberosity–trochlear groove distance(TT-TG) is a measurement to assist in the diagnosis and treatment of patellar instability, however it still has some limitations. Our study was to modify ...the accepted measurement method and seek a more reliable and standardized method.
The data of 65 healthy controls and 49 patients with bilateral patellar instability from 2010 to 2016 were collected and analyzed by CT. The TT-TG, tibial maximal mediolateral axis (MML), and their ratio i.e., the modified-TT-TG (M-TT-TG) were compared between the two groups.
The MML (71.9±12.0 vs. 71.3±10.9) was not significantly different between the two groups (P>0.05). However, the TT-TG(18.1±6.0 vs. 13.1±2.9) and M-TT-TG (0.25±0.08 vs. 0.19±0.04) were significantly different between the two groups (P<0.05). A TT-TG of >15mm was found in 24.5% of healthy controls and 71.5% of patients. The healthy controls with a TT-TG of >15mm were compared with the patients; although no significant difference was found in the TT-TG (16.8±1.5 vs. 18.1±6.0), the healthy controls had a significantly larger MML (76.9±12.7 vs. 71.9±10.9) and significantly smaller M-TT-TG (0.22±0.04 vs. 0.25±0.08). A total of 53.1% of patients but only 6.9% of healthy controls had an M-TT-TG of >0.25.
The M-TT-TG is a more reliable and standardized way to measure the effect of the TT-TG with the goal of reducing the false-positive rate associated with the standard measurement technique. The normal M-TT-TG ranges from 0.11 to 0.25, with an M-TT-TG of >0.25 being associated with patellofemoral malalignment.
III.
Seventeen C20-
-alkyl/benzyl oxime derivatives were synthesized by a concise and effective method. Most of these derivatives showed tens to several hundred nanomolar IC
values against HT-29 ...colorectal, HGC-27 gastric and MDA-MB-231 breast cancer cells, whose antiproliferative activity is 15-240 fold better than that of salinomycin. The C20-oxime etherified derivatives can coordinate potassium ions, and further adjust the cytosolic Ca
concentrations in HT-29 cells. The significant improvement of the potency should be attributed to the better ion binding and transport ability of the modified derivatives. In addition, the C20-
-alkyl/benzyl oxime derivatives showed much better selectivity indexes (SI) than salinomycin, indicating that they present lower neurotoxic risk.
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