Resistance to chemotherapy is a major challenge for the treatment of patients with colorectal cancer (CRC). Previous studies have found that microRNAs (miRNAs) play key roles in drug resistance; ...however, the role of miRNA‐373‐3p (miR‐375‐3p) in CRC remains unclear. The current study aimed to explore the potential function of miR‐375‐3p in 5‐fluorouracil (5‐FU) resistance. MicroRNA‐375‐3p was found to be widely downregulated in human CRC cell lines and tissues and to promote the sensitivity of CRC cells to 5‐FU by inducing colon cancer cell apoptosis and cycle arrest and by inhibiting cell growth, migration, and invasion in vitro. Thymidylate synthase (TYMS) was found to be a direct target of miR‐375‐3p, and TYMS knockdown exerted similar effects as miR‐375‐3p overexpression on the CRC cellular response to 5‐FU. Lipid‐coated calcium carbonate nanoparticles (NPs) were designed to cotransport 5‐FU and miR‐375‐3p into cells efficiently and rapidly and to release the drugs in a weakly acidic tumor microenvironment. The therapeutic effect of combined miR‐375 + 5‐FU/NPs was significantly higher than that of the individual treatments in mouse s.c. xenografts derived from HCT116 cells. Our results suggest that restoring miR‐375‐3p levels could be a future novel therapeutic strategy to enhance chemosensitivity to 5‐FU.
Resistance to chemotherapy is a major challenge for the treatment of patients with colorectal cancer (CRC). Our results suggest that the restoration of microRNA‐375‐3p levels could be a future novel therapeutic strategy to modulate and enhance chemosensitivity to 5‐fluorouracil treatment in CRC.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
AbstractRC shear walls are commonly used as lateral load-resisting elements in seismic regions, and the estimation of their shear strengths can become simultaneously design-critical and complex when ...they have so-called squat geometries, i.e., height-to-length ratios less than two. This paper presents a study on the training and interpretation of an advanced machine-learning model that strategically combines two algorithms for the said purpose. To train the model, a comprehensive shear strength database of 434 samples of squat RC walls is utilized. First, the eXtreme Gradient Boosting (XGBoost) algorithm is used to establish a predictive model for estimating the shear strength, wherein 70% and 30% of the data are respectively used for training and validation. This effort resulted in an approximately 97% validation accuracy, which well exceeds current mechanics-based/semiempirical models. Second, the SHapley Additive exPlanations (SHAP) algorithm is used to estimate the relative importance of the factors affecting XGBoost’s shear strength estimates. This step thus enabled physical and quantitative interpretations of the input-output dependencies, which are nominally hidden in conventional machine-learning approaches. Through this setup, several squat wall attributes are identified as being critical in shear strength estimates.
Dysregulated prefrontal control over amygdala is engaged in the pathogenesis of psychiatric diseases including depression and anxiety disorders. Here we show that, in a rodent anxiety model induced ...by chronic restraint stress (CRS), the dysregulation occurs in basolateral amygdala projection neurons receiving mono-directional inputs from dorsomedial prefrontal cortex (dmPFC→BLA PNs) rather than those reciprocally connected with dmPFC (dmPFC↔BLA PNs). Specifically, CRS shifts the dmPFC-driven excitatory-inhibitory balance towards excitation in the former, but not latter population. Such specificity is preferential to connections made by dmPFC, caused by enhanced presynaptic glutamate release, and highly correlated with the increased anxiety-like behavior in stressed mice. Importantly, low-frequency optogenetic stimulation of dmPFC afferents in BLA normalizes the enhanced prefrontal glutamate release onto dmPFC→BLA PNs and lastingly attenuates CRS-induced increase of anxiety-like behavior. Our findings thus reveal a target cell-based dysregulation of mPFC-to-amygdala transmission for stress-induced anxiety.
We report an asymptomatic child who was positive for a coronavirus by reverse transcription PCR in a stool specimen 17 days after the last virus exposure. The child was virus positive in stool ...specimens for at least an additional 9 days. Respiratory tract specimens were negative by reverse transcription PCR.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Ethylene/polar monomer coordination copolymerization offers an attractive way of making functionalized polyolefins. However, ethylene copolymerization with industrially relevant short chain length ...alkenoic acid remain a big challenge. Here we report the efficient direct copolymerization of ethylene with vinyl acetic acid by tetranuclear nickel complexes. The protic monomer can be extended to acrylic acid, allylacetic acid, ω-alkenoic acid, allyl alcohol, and homoallyl alcohol. Based on X-ray analysis of precatalysts, control experiments, solvent-assisted electrospray ionization-mass spectrometry detection of key catalytic intermediates, and density functional theory studies, we propose a possible mechanistic scenario that involves a distinctive vinyl acetic acid enchainment enabled by Ni···Ni synergistic effects. Inspired by the mechanistic insights, binuclear nickel catalysts are designed and proved much more efficient for the copolymerization of ethylene with vinyl acetic acid or acrylic acid, achieving the highest turnover frequencies so far for both ethylene and polar monomers simultaneously.
•The ensemble machine learning is adopted to predict the shear strength of RC deep beams.•The model has a very high accuracy and also verified with mechanical-driven models.•Feature importance and ...partial dependence analysis are used to interpret the model predictions.
This paper presents a practical yet comprehensive implementation of the ensemble methods for prediction of the shear strength for reinforced concrete deep beams with/without web reinforcements. The fundamentals of the background of the ensemble machine learning methods are firstly introduced, and four typical ensemble machine learnning models such as random forest, adoptive boosting, gradient boosting regression tree and extreme gradient boosting are utlized in this study to obtain the predictive model. Then the implementation procedure using these methods to train a predictive model is given in details. The input data is split into training and testing sets, the 10-fold cross validation is used to evaluate the model performance, the grid search method is used to find the hyper-parameters, and the feature importance and partial dependence analysis are adopted as the interpretation of the model outputs. To use the ensemble methods to predict the shear strength of reinforced concrete deep beams, in total 271 test data was collected for training the models. The models all achieve good capacity in predicting the shear strength, and demonstrate superior performance over traditional machine learnning methods. Meanwhile, the classical mechanics-driven shear models are also employed as comparisons. The sensitivity of the key factors in ensemble models is analyzed and the importances of the input variables are obtained. It is shown that the ensemble machine learnning models are significantly superior to mechanics-driven models in both predicting accuracy and discrepancy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Space charge transfer of heterostructures driven by the work‐function‐induced built‐in field can regulate the electronic structure of catalysts and boost the catalytic activity. Herein, an epitaxial ...heterojunction catalyst of CoO/Mo2C with interfacial electron redistribution induced by work functions (WFs) is constructed for overall water splitting via a novel top‐down strategy. Theoretical simulations and experimental results unveil that the WFs‐induced built‐in field facilitates the electron transfer from CoO to Mo2C through the formed “Co─C─Mo” bond at the interface of CoO/Mo2C, achieving interfacial electron redistribution, further optimizing the Gibbs free energy of primitive reaction step and then accelerating kinetics of hydrogen evolution reaction (HER). As expected, the CoO/Mo2C with interfacial effects exhibits excellent HER catalytic activity with only needing the overpotential of 107 mV to achieve 10 mA cm−2 and stability for a 60‐h continuous catalyzing. Besides, the assembled CoO/Mo2C behaves the outstanding performance toward overall water splitting (1.58 V for 10 mA cm−2). This work provides a novel possibility of designing materials based on interfacial effects arising from the built‐in field for application in other fields.
Heterostructure CoO/Mo2C catalysts are designed and developed via a novel top‐down strategy for overall water splitting in alkaline electrolytes, where electron transfer from CoO to Mo2C at the interface driven by built‐in field induced by the work function optimizes the adsorption energy of the reaction intermediate and enhances the catalytic activity.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
N6‐methyladenosine (m6A) is a well‐known modification of RNA. However, as a key m6A methyltransferase, METTL16 has not been thoroughly studied in gastric cancer (GC). Here, the biological role of ...METTL16 in GC and its underlying mechanism was studied. Immunohistochemistry was used to detect the expression of METTL16 and relationship between METTL16 level and prognosis of GC was analysed. CCK8, colony formation assay, EdU assay and xenograft mouse model were used to study the effect of METTL16. Regulatory mechanism of METTL16 in the progression of GC was studied through flow cytometry analysis, RNA degradation assay, methyltransferase inhibition assay, RT‐qPCR and Western blotting. METTL16 was highly expressed in GC cells and tissues and was associated with prognosis. In vitro and in vivo experiments confirmed that METTL16 promoted proliferation of GC cells and tumour growth. Furthermore, down‐regulation of METTL16 inhibited proliferation by G1/S blocking. Significantly, we identified cyclin D1 as a downstream effector of METTL16. Knock‐down METTL16 decreased the overall level of m6A and the stability of cyclin D1 mRNA in GC cells. Meanwhile, inhibition of methyltransferase activity reduced the level of cyclin D1. METTL16‐mediated m6A methylation promotes proliferation of GC cells through enhancing cyclin D1 expression.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
To determine the dynamic changes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in respiratory and fecal specimens in children with coronavirus disease 2019 (COVID-19).
From ...January 17, 2020 to February 23, 2020, three paediatric cases of COVID-19 were reported in Qingdao, Shandong Province, China. Epidemiological, clinical, laboratory, and radiological characteristics and treatment data were collected. Patients were followed up to March 10, 2020, and dynamic profiles of nucleic acid testing results in throat swabs and fecal specimens were closely monitored.
Clearance of SARS-CoV-2 in respiratory tract occurred within two weeks after abatement of fever, whereas viral RNA remained detectable in stools of pediatric patients for longer than 4 weeks. Two children had fecal SARS-CoV-2 undetectable 20 days after throat swabs showing negative, while that of another child lagged behind for 8 days.
SARS-CoV-2 may exist in children's gastrointestinal tract for a longer time than respiratory system. Persistent shedding of SARS-CoV-2 in stools of infected children raises the possibility that the virus might be transmitted through contaminated fomites. Massive efforts should be made at all levels to prevent spreading of the infection among children after reopening of kindergartens and schools.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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