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INTRODUCTION To investigate the neuroprotective effect and mechanism of DL-3-n-butylphthalide (NBP) on the brain-derived neurotrophic factor (BDNF)/tyrosine kinase B (TrkB) and its downstream signalling pathway after cerebral ischemia/reperfusion injury (CIRI) in rats. MATERIAL AND METHODS The middle cerebral artery occlusion/reperfusion (MCAO/R) model was used. Reperfusion was performed 2 h after ischemia, and 20 mg/kg of NBP was intraperitoneally injected. Neurological defect score and pathological changes were performed. Apoptotic cells were detected using in situ end-labelling with TUNEL. The expression of BDNF and TrkB proteins was measured by Western blot and immunohistochemical staining. BDNF mRNA, TrkB mRNA, protein kinase B (AKT) mRNA and caspase-3 mRNA expression were measured using real-time polymerase chain reaction (qPCR). RESULTS After 24 h of reperfusion, the neurological defect score and the percentage of apoptotic cells in the ischemia/reperfusion group (I/R group) were higher than those in the ischemia/reperfusion + drug group (I/R + d group). The positive expressions of BDNF and TrkB mRNA and protein in the I/R + d group were obviously higher than those in the I/R group (p < 0.05). After intervention with the TrkB receptor inhibitor (K252a), the expression levels of BDNF and TrkB and AKT mRNA were significantly decreased in the ischemia/reperfusion + drug + TrkB receptor inhibitor group (I/R + d + R group) compared with the I/R + d group, however the caspase-3 mRNA expression level showed the reverse trend. The expressions of BDNF, TrkB and p-Akt proteins in the I/R + d group were remarkably higher than those in the I/R group at each time point, and reached the peak at 24 hours after reperfusion, which were earlier than that in the I/R group. CONCLUSIONS Butylphthalide represents a neuroprotective effect after CIRI in rats and used within 24 h of early onset contributes to better prognosis. The underlying mechanism may be related to reducing the apoptosis of nerve cells through BDNF/TrkB signalling pathway.

The Hedgehog (HH) signaling pathway plays important roles in gastrointestinal carcinogenesis and the gastrointestinal tumor microenvironment (TME). Aberrant HH signaling activation may accelerate the growth of gastrointestinal tumors and lead to tumor immune tolerance and drug resistance. The interaction between HH signaling and the TME is intimately involved in these processes, for example, tumor growth, tumor immune tolerance, inflammation, and drug resistance. Evidence indicates that inflammatory factors in the TME, such as interleukin 6 (IL-6) and interferon-γ (IFN-γ), macrophages, and T cell-dependent immune responses, play a vital role in tumor growth by affecting the HH signaling pathway. Moreover, inhibition of proliferating cancer-associated fibroblasts (CAFs) and inflammatory factors can normalize the TME by suppressing HH signaling. Furthermore, aberrant HH signaling activation is favorable to both the proliferation of cancer stem cells (CSCs) and the drug resistance of gastrointestinal tumors. This review discusses the current understanding of the role and mechanism of aberrant HH signaling activation in gastrointestinal carcinogenesis, the gastrointestinal TME, tumor immune tolerance and drug resistance and highlights the underlying therapeutic opportunities., Graphical abstract Hedgehog pathway (HH) is one of the most important modulators of gastrointestinal cancer. This review concludes the role of HH pathway in gastrointestinal carcinogenesis as well as the development of tumor microenvironment, which indicates the mechanisms of immune tolerance and drug resistance in gastrointestinal cancers and highlights the potential therapeutics.Image 1

Successful deep learning critically depends on the representation of the learned objects. Recent state-of-the-art pharmaceutical deep learning models successfully exploit graph-based de novo learning of molecular representations. Nonetheless, the combined potential of human expert knowledge of molecular representations and convolution neural networks has not been adequately explored for enhanced learning of pharmaceutical properties. Here we show that broader exploration of human-knowledge-based molecular representations enables more enhanced deep learning of pharmaceutical properties. By broad learning of 1,456 molecular descriptors and 16,204 fingerprint features of 8,506,205 molecules, a new feature-generation method MolMap was developed for mapping these molecular descriptors and fingerprint features into robust two-dimensional feature maps. Convolution-neural-network-based MolMapNet models were constructed for out-of-the-box deep learning of pharmaceutical properties, which outperformed the graph-based and other established models on most of the 26 pharmaceutically relevant benchmark datasets and a novel dataset. The MolMapNet learned important features that are consistent with the literature-reported molecular features. While deep learning models have allowed the extraction of fingerprints from the structural description of molecules, they can miss information that is present in the molecular descriptors that chemists use. Shen and colleagues present a method to combine both sources of information into two-dimensional fingerprint maps, which can be used in a wide variety of pharmaceutical tasks to predict the properties of drugs.

Surgical techniques for repair of rectovaginal fistula (RVF) have been continually developed, but the ideal procedure remains unclear. Endoscopic repair is a novel and minimally invasive technique for RVF repair with increasing reporting.To review the current applications and preliminary outcomes of this technique for RVF repair, aiming to give surgeons an alternative in clinical practice.Available articles were searched according to the search strategy. And the sample size, fistula etiology, fistula type, endoscopic repair approaches, operative time and hospital stay, follow-up period, complication and life quality assessment were selected for recording and further analysis.A total of 11 articles were eventually identified, involving 71 patients with RVFs who had undergone endoscopic repair. The principal causes of RVFs were surgery (In conclusion, endoscopic repair of RVF is novel, minimally invasive and promising with acceptable preliminary effectiveness. Given its unique advantages, endoscopic repair can be an alternative technique for surgeons.

An adsorbent ZO (oxidized ZIF-8-derived carbon) was prepared on the ZIF-8-derived carbon (ZC) by Hummer's method. The removal rate and adsorption amount of Pb2+ was measured on different molar ratio of 2-Hmim to 2, 2 '-bipyridine in ZO, including 1:1 (1:1 ZO) and 1:2 (1:2 ZO). The adsorption experiments show that the best condition to adsorb Pb2+ in Pb2+ solution for 1:1 ZO is adsorbent dosage of 20 mg, adsorption time of 16 h, initial Pb2+concentration of 15 mg/L, and pH = 3; that for 1:2 ZO is adsorbent dosage of 15 mg, adsorption time of 18 h, initial Pb2+ concentration of 15 mg/L, and pH = 4. The adsorption data fits the quasi-second-order kinetics and the Langmuir adsorption model. The competitive adsorption results show that 1:1 ZO and 1:2 ZO have a superior selectivity for Pb2+ competing with Cu2+ and Fe2+.This study shows 1:2 ZO is more helpful for the removal of Pb2+ than 1:1 ZO.

To identify the important genes that affect the phenotypic differences between the Landrace and Debao pigs, especially the differences in metabolism and muscle growth. Differentially expressed genes of psoas major were detected by mRNA transcriptome sequencing in Landrace and Debao pigs. By extracting the total RNA of the psoas major muscle of the Landrace pig and the Debao pig, purifying the mRNA, constructing the cDNA library, conducting transcriptome sequencing, and then through the sequencing quality evaluation, we know that the sequencing quality of this study is relatively high. A total of 17,943 genes were detected in all samples, including 17,870 known genes and 73 new genes. Defined genes with |log2FC| greater than 2 and Q-value less than 0.001, and screened them as significantly differentially expressed genes. A total of 1661 differentially expressed genes were screened from the samples of Landrace pigs and Debao pigs, among which 1255 genes were differentially up-regulated and 406 genes were differentially down-regulated. Through differential gene analysis, it is concluded that these genes are mainly involved in metabolic regulation, muscle and fat development and other processes, especially some important functional genes such as MAPK14, FOS, SIRT1, KRAS, EGR1, CDNNB1, etc. To sum up, this study used transcriptome sequencing method, and then selected differentially expressed genes between Landrace pigs and Debao pigs through data analysis, and finally screened out important genes affecting phenotypic differences, which provided genetic support for breeding better breeds in the future.

The ultimate goal of neurosurgery is to remove the lesion to the greatest extent while retaining neurological function. The preservation of motor function, sensory function, especially language function is of great significance to patients. So preoperative and intraoperative functional mapping has important guidance for surgery. The current invasive method⁃intraoperative direct electrical stimulation (DES) is still the "gold standard" for language mapping and lateralization, while non⁃invasive method such as functional magnetic resonance (fMRI), diffusion tensor imaging (DTI), magnetoencephalography (MEG) and navigated transcranial magnetic stimulation (nTMS) are easy to operate and can be used for preoperative positioning, postoperative follow⁃up and review. Multimodal functional assessment can improve the accuracy of preoperative language mapping. This article intends to review the positioning methods of language function areas and compare the advantages and disadvantages of various methods. DOI:10.3969/j.issn.1672⁃6731.2020.11.003

Xenobiotic and host active substances interact with gut microbiota to influence human health and therapeutics. Dietary, pharmaceutical, herbal and environmental substances are modified by microbiota with altered bioavailabilities, bioactivities and toxic effects. Xenobiotics also affect microbiota with health implications. Knowledge of these microbiota and active substance interactions is important for understanding microbiota-regulated functions and therapeutics. Established microbiota databases provide useful information about the microbiota-disease associations, diet and drug interventions, and microbiota modulation of drugs. However, there is insufficient information on the active substances modified by microbiota and the abundance of gut bacteria in humans. Only ∼7% drugs are covered by the established databases. To complement these databases, we developed MASI, Microbiota—Active Substance Interactions database, for providing the information about the microbiota alteration of various substances, substance alteration of microbiota, and the abundance of gut bacteria in humans. These include 1,051 pharmaceutical, 103 dietary, 119 herbal, 46 probiotic, 142 environmental substances interacting with 806 microbiota species linked to 56 diseases and 784 microbiota–disease associations. MASI covers 11 215 bacteria-pharmaceutical, 914 bacteria-herbal, 309 bacteria-dietary, 753 bacteria-environmental substance interactions and the abundance profiles of 259 bacteria species in 3465 patients and 5334 healthy individuals. MASI is freely accessible at http://www.aiddlab.com/MASI.

Cancers resist targeted therapeutics by drug-escape signaling. Multitarget drugs co-targeting cancer and drug-escape mediators (DEMs) are clinically advantageous. DEM coverage may be expanded by drug combinations. This work evaluated to what extent the kinase DEMs (KDEMs) can be optimally co-targeted by drug combinations based on target promiscuities of individual drugs. We focused on 41 approved and 28 clinical trial small molecule kinase inhibitor drugs with available experimental kinome and clinical pharmacokinetic data. From the kinome inhibitory profiles of these drugs, drug combinations were assembled for optimally co-targeting an established cancer target (EGFR, HER2, ABL1, or MEK1) and 9-16 target-associated KDEMs at comparable potency levels as that against the cancer target. Each set of two-, three-, and four-drug combinations co-target 36-71%, 44-89%, 50-88%, and 27-55% KDEMs of EGFR, HER2, ABL1, and MEK1, respectively, compared with the 36, 33, 38, and 18% KDEMs maximally co-targeted by an existing drug or drug combination approved or clinically tested for the respective cancer. Some co-targeted KDEMs are not covered by any existing drug or drug combination. Our work suggested that novel drug combinations may be constructed for optimally co-targeting cancer and drug escape by the exploitation of drug target promiscuities.

Ti3AlC2 bulk ceramics were prepared via aqueous gelcasting followed by C-rich and Al-rich pressureless sintering. The optimized pH value, zeta potential, dispersant content, and solid loading content were determined to be 10, 72.6 mV, 1.6 wt%, and 52 vol%, respectively. Impurities at ppm level containing in the flowing argon could cause severe decomposition of gelcasted bulk Ti3AlC2, forming whiskers of Al2OC and Al4O4C and floccule of AlN. C-rich pressureless sintering resulted in the delamination of a duplex layer of Ti(CO) and Ti3(AlO)Cx-Ti(O,C). The channels formed after debinding facilitated the outward diffusion of Al and the inward diffusion of O and C, and thereby promoting the decomposition of C-rich sintered Ti3AlC2. The combined effect of the unclosed channels and the porous reaction Ti3(AlO)Cx-Ti(O,C) layer brought a catastrophic reduction in the density and mechanical properties of the C-rich sintered Ti3AlC2 ceramic. While the Al-rich pressureless sintering system isolated C, CO and N2 and supplied a closed Al-rich atmosphere, thereby suppressing the decomposition reactions and promoting the sintering densification and ultimately leading to the superior in mechanical properties. The density, hardness, flexural strength and fracture toughness of the Al-rich sintered ceramic reaches 4.13 g/cm3, 4.36 GPa, 345 MPa, 4.79 MPa m1/2, respectively.

Treatment and recycling of radioactive waste are major challenges for the nuclear energy sector. Pertechnetate anions, 99TcO4−, occur in nuclear waste and are formed mainly during nuclear fission. 99TcO4− is a very hazardous contaminant due to its long half-life and high solubility and mobility in water. The effective capture of 99Tc contamination at legacy nuclear sites remains a serious and unsolved environmental issue. In this work, 99TcO4−/ReO4− was adsorbed by compressible graphene–chitosan sponges with grafted tertiary amine groups. Moreover, the hydrophobic branched chains strongly reduced the interference of competitive anions during adsorption. Results show that 99TcO4−/ReO4− can be effectively removed even under highly acidic conditions and in the presence of competing anions. More than 98% of 99TcO4−/ReO4− was removed using simulated nuclear wastes.

Objective To summarize the clinical, pathological and genetic features of 10 patients with late ⁃ onset mitochondrial encephalomyopathy with lactic acidosis and stroke ⁃ like episodes (MELAS). Methods and Results The clinical data of 10 patients with late ⁃ onset MELAS were retrospectively analyzed from January 2007 to December 2018. Muscle biopsy was performed in 8 cases. Polymerase chain reaction ⁃ fragment length polymorphism (PCR⁃RFLP) analysis and whole sequencing of mitochondrial DNA (mtDNA) were used to screen mtDNA mutations, and the mutation load of m.3243A > G in blood was detected by pyrophosphate sequencing. The onset age of the first stroke ⁃like episodes were 40-67 years old in all patients. The main manifestations included epilepsy, aphasia, headache, dementia, mental disorder, limb paralysis and visual impairment. Past history revealed 5 cases with diabetes mellitus, 6 with deafness, 3 with hypertension and 2 with stroke. Six patients had a family history of maternally inherited diabetic mellitus, and 2 had a family history of MELAS. Laboratory examination revealed 6 cases with hyperlipidemia, 6 with carotid atherosclerosis, 1 with stenosis of right internal carotid artery and middle cerebral artery. Brain MRI showed cortex lesions involving one or more lobes in all patients, and 4 cases also had multiple infarctions in brainstem and basal ganglia. Muscle biopsy demonstrated ragged red fiber (RRF) and strongly succinate dehydrogenase ⁃ stained vessels (SSVs) in all of 8 patients except one. Genetic analysis identified 9 cases with m.3243A > G, and 1 with m.10191T > C mutation. The blood mutation load of m.3243A > G was 9%-33% in 7 cases. Conclusions The clinical phenotype of patients with late ⁃ onset MELAS was not significantly different from that of typical patients. However, the age of onset in late ⁃ onset MELAS was late, and it could be complicated with a variety of cerebrovascular risk factors and atherosclerosis. The hotspot mutation of this group of late ⁃ onset MELAS patients was m.3243A > G, but the mutation rate in blood was low. DOI：10.3969/j.issn.1672⁃6731.2020.03.015

An aligned carbon-nanotube array has been identified as an ideal candidate for super-capacitor devices due to its high specific surface, regular pore structures and highly efficient ion transfer paths. However, poor mechanical strength and super hydrophobicity greatly impede its applications in the manipulation of the energy storage device. In this paper, we fabricate a robust flexible solid-state supercapacitor (FSC) device by using a silk fibroin incorporated 3D aligned carbon nanotube array (CNTA) composite matrix. We thoroughly investigate the effect of a silk fibroin scaffold as well as its carbonization product on the electrochemical properties of the composite devices. Compared with pure CNTA-based FSC devices, the mechanical strength as well as hydrophilicity of the CNTA@silk fibroin (CNTA@SF) composites are greatly enhanced. Meanwhile there is neither damage of the aligned structure of CNTA nor sacrifice of the volumetric capacitance of the device. Additionally, further carbonization of the CNTA@SF composites can generate a pyridine-type nitrogen doped CNTA (CNTA@C) hybrid thus further enhancing the electrochemical capacitance while still maintaining the original flexibility and hydrophilicity. The charge transfer resistance (Rct) of the CNTA@C-based device decreases about 40% (from 3 Ω to 1.8 Ω) and the volumetric specific capacitance increases to about 60% higher (from 126.8 mF cm−3 to 197.4 mF cm−3) compared with the initial. Meanwhile, excellent cyclic stability (2.9 mA cm−3, 10 000 cycles with a loss of less than 1%), good rate performance (from 0.58–5.8 mA cm−3, volumetric specific capacitance Cv retention stays at around 80%) as well as high energy density of 0.018 mW h cm−3 (with the power density of 0.46 mW cm−3) were successfully derived. Our approach thus reveals a new kind of robust 3D platform based on a carbon nanotube array and silk fibroin which has great potential for the design of biocompatible FSC devices as well as implantable electronics in the future.

In this study, the formation energies and electronic properties of six native defects as well as H impurities in wurtzite (wz) CdSe are systematically investigated using hybrid density functional calculations. It is shown that native defects, including antisite CdSe and interstitial Cdi, may be sources of the unintentional n-type conductivity in CdSe under Se-poor conditions; meanwhile, the vacancy defect VSe is not a good donor. However, when the common H impurity is considered, it is suggested that both the substitutional impurity HSe and the interstitial impurity Hi are the dominant and effective origins of the unintentional n-type conductivity in Se-poor conditions. However, unintentional p-type conductivity in CdSe is challenging to form regardless of the growth conditions. Moreover, hybrid functional calculations of the electronic structures show that the six native point defects and the extrinsic impurities Hi and HSe will cause more or fewer changes in the band gap. Among all considered defects and impurities, it is found that only the interstitial defect Cdi introduces impurity levels into the band gap. In particular, the present hybrid functional calculations theoretically affirm that the vacancy defect VCd in CdSe can induce a 2 μB magnetic moment; however, other native defects will not introduce any magnetic moment.

Sperm are specialized cells that require adenosine triphosphate (ATP) to support their function. Maintaining sperm energy homeostasis in vitro is vitally important to improve the efficacy of boar sperm preservation. Metformin can activate 5′-AMP-activated protein kinase (AMPK) to improve metabolic flexibility and maintain energy homeostasis. Thus, the aim of the present study was to investigate whether metformin can improve boar sperm quality through AMPK mediation of energy metabolism. Sperm motility parameters, membrane integrity, acrosome integrity, mitochondrial membrane potential (ΔΨm), ATP content, glucose uptake, and lactate efflux were analyzed. Localization and expression levels of AMPK and phospho-Thr172-AMPK (p-AMPK) were also detected by immunofluorescence and western blotting. We found that metformin treatment significantly increased sperm motility parameters, ΔΨm, and ATP content during storage at 17 °C. Moreover, results showed that AMPK was localized at the acrosomal region, connecting piece, and midpiece of sperm and p-AMPK was distributed at the post-acrosomal region, connecting piece, and midpiece. When sperm were incubated with metformin for 4 h at 37 °C, sperm motility parameters, ΔΨm, ATP content, p-AMPK, glucose uptake, and lactate efflux all significantly increased, whereas the addition of Compound C treatment, an inhibitor of AMPK, counteracted these positive effects. Together, our results suggest that metformin promotes AMPK activation, which contributes to the maintenance of energy hemostasis and mitochondrial activity, thereby maintaining boar sperm functionality and improving the efficacy of semen preservation.

Rationale: Interleukin 22 (IL-22) is an epithelial survival cytokine that is at present being explored as therapeutic agents for acute and chronic liver injury. However, its molecular basis of protective activities remains poorly understood. Methods: Here we demonstrate that IL-22 inhibits the deteriorating metabolic states induced by stimuli in hepatocytes. Utilizing cell biological, molecular, and biochemical approaches, we provide evidence that IL-22 promotes oxidative phosphorylation (OXPHOS) and glycolysis and regulates the metabolic reprogramming related transcriptional responses. Results: IL-22 controls metabolic regulators and enzymes activity through the induction of AMP-activated protein kinase (AMPK), AKT and mammalian target of rapamycin (mTOR), thereby ameliorating mitochondrial dysfunction. The upstream effector lncRNA H19 also participates in the controlling of these metabolic processes in hepatocytes. Importantly, amelioration of liver injury by IL-22 through activation of metabolism relevant signaling and regulation of mitochondrial function are further demonstrated in cisplatin-induced liver injury and steatohepatitis. Conclusions: Collectively, our results reveal a novel mechanism underscoring the regulation of metabolic profiles of hepatocytes by IL-22 during liver injury, which might provide useful insights from the bench to the clinic in treating and preventing liver diseases.

Background Patent ductus arteriosus (PDA) can close on its own during childhood. Patent ductus arteriosus with left pulmonary artery (LPA) occlusion is rare. Here, we describe possible aetiologies of this condition and treatment strategies based on recent guidelines. Case summary A 35-year-old man experienced shortness of breath for 20 years. Physical examination revealed pitting oedema, digital clubbing, and bi-phasic murmur along the left sternal border at the 2nd and 3rd intercostal space. Congenital heart disease was suspected. Echocardiography revealed a severely dilated pulmonary trunk and PDA; however, the LPA was not visible. The patient has undergone PDA ligation surgery >30 years ago, which may have caused accidental LPA ligation; however, extreme elevation of pulmonary pressure led to increased difficulties in performing LPA reconstruction and PDA division. Therefore, pulmonary arterial hypertension (PAH) initial combination therapy with parenteral prostanoids was prescribed. The patient’s condition improved gradually. Discussion Inadvertent ligation of the LPA instead of PDA is a rare and usually fatal complication during ductal ligation. Patients who survive this catastrophic complication usually develop the progressive pulmonary vascular disease with increased pulmonary pressure and impaired lung parenchyma resulting in right heart and respiratory failure. Early and regular follow-up with cardiac imaging studies is important to diagnose this complication. Reconstruction of the ligated LPA and PDA late in the disease course is difficult due to the development of pulmonary arterial hypertension. Initial PAH combination therapy may be valuable for relieving the patients’ symptoms at that stage. Heart and lung transplantation can also be considered in suitable patients.

Omics-based biomedical learning frequently relies on data of high-dimensions (up to thousands) and low-sample sizes (dozens to hundreds), which challenges efficient deep learning (DL) algorithms, particularly for low-sample omics investigations. Here, an unsupervised novel feature aggregation tool AggMap was developed to Aggregate and Map omics features into multi-channel 2D spatial-correlated image-like feature maps (Fmaps) based on their intrinsic correlations. AggMap exhibits strong feature reconstruction capabilities on a randomized benchmark dataset, outperforming existing methods. With AggMap multi-channel Fmaps as inputs, newly-developed multi-channel DL AggMapNet models outperformed the state-of-the-art machine learning models on 18 low-sample omics benchmark tasks. AggMapNet exhibited better robustness in learning noisy data and disease classification. The AggMapNet explainable module Simply-explainer identified key metabolites and proteins for COVID-19 detections and severity predictions. The unsupervised AggMap algorithm of good feature restructuring abilities combined with supervised explainable AggMapNet architecture establish a pipeline for enhanced learning and interpretability of low-sample omics data.

The sources, sizes, components, and toxicological responses of particulate matter (PM) have demonstrated remarkable spatiotemporal variability. However, associations between components, sources, and toxicological effects in different-sized PM remain unclear. The purposes of this study were to 1) determine the sources of PM chemical components, 2) investigate the associations between components and toxicology of PM from Guangzhou high air pollution season. We collected size-segregated PM samples (PM

BackgroundThis study compared the survival outcomes of different surgical approaches to determine the optimal approach for gastric cardia adenocarcinoma (GCA) and aimed to standardize the surgical treatment guidelines for GCA.MethodsA total of 7103 patients with GCA were enrolled from our previously established gastric cardia and esophageal carcinoma databases. In our database, when the epicenter of the tumor was at or within 2 cm distally from the esophagogastric junction, the adenocarcinoma was considered to originate from the cardia and was considered a Siewert type 2 cancer. The main criteria for the enrolled patients included treatment with radical surgery, no radio- or chemotherapy before the operation, and detailed clinicopathological information. Follow-up was mainly performed by telephone or through home interviews. According to the medical records, the surgical approaches included transthoracic, thoracoabdominal, and transabdominal approaches. Kaplan–Meier and Cox proportional hazards regression models were applied to correlate the surgical approach with survival in patients with GCA.ResultsThere were marked differences in age and tumor stage among the patients who underwent the three surgical approaches (P P P P ConclusionThoracoabdominal approach and transabdominal approach were shown to be poor prognostic factors. Patients with (locally advanced) GCA may benefit from the transthoracic approach. Further prospective randomized clinical trials are necessary.

Background An increase in the incidence of central venous catheter (CVC)-associated deep venous thrombosis (CADVT) has been reported in pediatric patients over the past decade. At the same time, current screening guidelines for venous thromboembolism risk have low sensitivity for CADVT in hospitalized children. This study utilized a multimodal deep learning model to predict CADVT before it occurs. Methods Children who were admitted to intensive care units (ICUs) between December 2015 and December 2018 and with CVC placement at least 3 days were included. The variables analyzed included demographic characteristics, clinical conditions, laboratory test results, vital signs and medications. A multimodal deep learning (MMDL) model that can handle temporal data using long short-term memory (LSTM) and gated recurrent units (GRUs) was proposed for this prediction task. Four benchmark machine learning models, logistic regression (LR), random forest (RF), gradient boosting decision tree (GBDT) and a published cutting edge MMDL, were used to compare and evaluate the models with a fivefold cross-validation approach. Accuracy, recall, area under the ROC curve (AUC), and average precision (AP) were used to evaluate the discrimination of each model at three time points (24 h, 48 h and 72 h) before CADVT occurred. Brier score and Spiegelhalter’s z test were used measure the calibration of these prediction models. Results A total of 1830 patients were included in this study, and approximately 15% developed CADVT. In the CADVT prediction task, the model proposed in this paper significantly outperforms both traditional machine learning models and existing multimodal deep learning models at all 3 time points. It achieved 77% accuracy and 90% recall at 24 h before CADVT was discovered. It can be used to accurately predict the occurrence of CADVT 72 h in advance with an accuracy of greater than 75%, a recall of more than 87%, and an AUC value of 0.82. Conclusion In this study, a machine learning method was successfully established to predict CADVT in advance. These findings demonstrate that artificial intelligence (AI) could provide measures for thromboprophylaxis in a pediatric intensive care setting.

To better understand the corrosion and corrosion products behavior in the primary circuit of lead-bismuth eutectic (LBE) coolant reactor, the concentration distribution of soluble impurities and the transport of solid particles are investigated through the finite-element method. An axisymmetric model of the primary circuit of an LBE reactor was constructed to accelerate the calculation of the thermal hydraulic filed of the circuit. The saturation concentration of solute Fe, Cr and Ni in LBE coolant are identified through the equilibrium of their oxides and PbO, and the very different saturation concentrations of Fe/Cr/Ni in LBE will lead to significant element-selective corrosion. The migration of solid oxide particles in the primary circuit is also investigated by the Euler–Lagrange tracing model. The simulation shows that driving force for the movement of particles &gt, 100 μm is buoyancy, which lets particles float on a free surface, while particles &lt, 10 μm tend to suspend in coolant. However, the behavior of particles also depends on the formation position, the particles formed above the core have a high possibility of re-entering in the core.

BACKGROUND Gastric cardia adenocarcinoma (GCA), which has been classified as type II adenocarcinoma of the esophagogastric junction in western countries, is of similar geographic distribution with esophageal squamous cell carcinoma in China, and even referred as "sister cancer" by Chinese oncologists. The molecular mechanism for GCA is largely unknown. Recent studies have shown that decreased expression of E-cadherin is associated with the invasion and metastasis of multiple cancers. However, the E-cadherin expression has not been well characterized in gastric cardia carcinogenesis and its effect on GCA prognosis. AIM To characterize E-cadherin expression in normal gastric cardia mucosa, dysplasia and GCA tissues, and its influence on prognosis for GCA. METHODS A total of 4561 patients with GCA were enrolled from our previously established GCA and esophageal cancer databases. The enrollment criteria included radical surgery for GCA, but without any radio- or chemo-therapy before operation. The GCA tissue from 4561 patients and matched adjacent normal epithelial tissue (n = 208) and dysplasia lesions (n = 156) were collected, and processed as tissue microarray for immunohistochemistry. The clinicopathological characteristics were retrieved from the medical records in hospital and follow-up was carried out through letter, telephone or home interview. E-cadherin protein expression was determined by two step immunohistochemistry. Kaplan–Meier and Cox regression analyses were used to correlate E-cadherin protein expression with survival of GCA patients. RESULTS Of the 4561 GCA patients, there were 3607 males with a mean age of 61.6 ± 8.8 and 954 females with a mean age of 61.9 ± 8.6 years, respectively. With the lesions progressed from normal gastric cardia mucosa to dysplasia and GCA, the positive immunostaining rates for E-cadherin decreased significantly from 100% to 93.0% and 84.1%, respectively (R2 = 0.9948). Furthermore, E-cadherin positive immunostaining rate was significantly higher in patients at early stage (0 and I) than in those at late stage (II and III) (92.7% vs 83.7%, P = 0.001). E-cadherin positive expression rate was significantly associated with degree of differentiation (P = 0.001) and invasion depth (P < 0.001). Multivariate analysis showed that the GCA patients with positive E-cadherin immunostaining had better survival than those with negative (P = 0.026). It was noteworthy that E-cadherin positive expression rate was similar in patients with positive and negative lymph node metastasis. However, in patients with negative lymph node metastasis, those with positive expression of E-cadherin had better survival than those with negative expression (P = 0.036). Similarly, in patients with late stage GCA, those with positive expression of E-cadherin had better survival than those with negative expression (P = 0.011). CONCLUSION E-cadherin expression may be involved in gastric cardia carcinogenesis and low expression of E-cadherin may be a promising early biomarker and overall survival predictor for GCA.

Oxygen measurement and control system is critical for minimizing corrosion in nuclear systems. Oxygen measurement and control tools use lead-bismuth eutectic (LBE) and pure lead as a coolant or as ...

In this study, pure HfO2 and Pr6O11-HfO2 coatings were prepared by atmospheric plasma spraying. The chemical compositions, morphologies, infrared radiation performances and thermal resistances of the coatings were characterized. The results showed that doping Pr6O11 could effectively improve the infrared emittance of the HfO2 coating. The HfO2 coating doping with 10 wt. % Pr6O11 exhibited the highest infrared emittance, which was 0.859 at room temperature and 0.883 at 1600 °C, correspondingly. This was mainly attributed to the oxygen vacancies, which created by the substitution of Hf4+ by Pr3+, could introduce localized energy states within the HfO2 band gap and increase the lattice distortion, producing lower symmetry vibrations. In addition, the Pr6O11-HfO2 infrared radiation coating possessed high tensile adhesive strength and good thermal resistance, which could withstand a high temperature treatment at 1700 °C for at least 50 h without exfoliation, and there was only a slight reduction in emittance.

Lung adenocarcinoma (LUAD), which comprises over 50% of all cases of non-small-cell lung cancer, has a poor prognosis and requires novel therapeutic approaches. The sonic Hedgehog (Shh) pathway, which plays a crucial role in differentiation, proliferation, and survival of cancer cells, is likely to be activated in LUADs, suggesting the Shh pathway as a potential therapeutic target for LUAD treatment. In this study, we reported that vismodegib, an inhibitor of the Shh pathway, only elicited minor antitumor efficacy in A549 and NCI-H1975 LUAD cells as well as in the xenograft tumors, with overexpressed GLI2 and increased autophagic activity. The aberrant autophagy in LUAD cells was further confirmed by the three main stages of autophagic flux, including the formation of autophagosomes, the fusion of autophagosomes with lysosomes, and degradation of autophagosomes in lysosomes. Furthermore, inhibition of autophagy by siRNA against ATG5 or ATG7 rescued the sensitivity of A549 and NCI-H1975 LUAD cells to vismodegib in vitro. Meanwhile, administration of the pharmaceutical inhibitor of autophagy, chloroquine, contributed to the enhanced anti-LUAD efficacy of vismodegib in vivo, probably through overproduction of ROS, acceleration of apoptosis, and suppression of GLI2 in LUAD tissues. In summary, our research revealed that downregulating autophagy facilitated the anti-LUAD efficacy of the Shh pathway suppression, thus highlighting a potential approach for LUAD therapy via simultaneously targeting the Shh signaling and autophagy pathway.

In this study, the REO-HfO2 (REO = Tb4O7, Gd2O3 and Sm2O3) coatings and pure HfO2 coatings were prepared by atmospheric plasma spraying. The chemical compositions, morphologies, infrared radiation performance and thermal resistances of the coatings were systematically investigated. The experimental results showed that the Tb4O7-HfO2, Gd2O3-HfO2, Sm2O3-HfO2 and pure HfO2 coatings had infrared emissivity values of 0.863, 0.852, 0.854 and 0.621, respectively, at room temperature. Based on the phase analysis, the higher infrared emissivity of the REO-HfO2 coatings could be attributed to the fact that the newly formed RE2Hf2O7 (RE = Tb, Gd and Sm) phase, which had a defective fluorite-type structure, and the RE3+ ions enhanced the lattice absorption and electron absorption. Additionally, the Tb4O7-HfO2 coating exhibited a relatively higher infrared emissivity than those of the Gd2O3-HfO2 and Sm2O3-HfO2 coating over the wavelength range of 1–15 μm, which was due to the relatively higher vibrational frequency of the Tb O bond in RE2Hf2O7 (RE = Tb, Gd and Sm) and the transformation of Tb3+ into Tb4+ in the Tb4O7-HfO2 system. In addition, the REO-HfO2 ceramic coatings exhibited excellent thermal resistance, which could withstand high-temperature treatment at 1600 °C for at least 50 h without undergoing a phase change and exfoliation, and the infrared emissivity at different temperatures hardly changed after thermal treatment.

Resting two-dimensional speckle tracking echocardiography (2D-STE) identified right ventricular (RV) systolic function were reported to predict exercise capacity in pulmonary hypertension (PH) patients, but little attention had been payed to 2D-STE detected RV diastolic function. Therefore, we aim to elucidate and compare the relations between 2D-STE identified RV diastolic/systolic functions and peak oxygen consumption (PVO2) determined by cardiopulmonary exercise testing (CPET) in pre-capillary PH. 2D-STE was performed in 66 pre-capillary PH patients and 28 healthy controls. Linear correlation and multivariate regression analyses were performed to evaluate and compare the relations between RV 2D-STE parameters and PVO2. Receiver operating characteristic curves were used to compare the predictive value of 2D-STE parameters in predicting the cut-off—PVO2 − 0.65/s had a 88.2% sensibility and 82.2% specificity to predict PVO2

Objective To observe the influence of nape acupuncture therapy on swallowing function of patients with cerebral infarction. Methods Eighty patients with dysphagia after cerebral infarction were recruited and randomly allocated to the nape acupuncture group and the control group, 40 each group. Both groups were given general medicine therapy and swallowing functional training, while the nape acupuncture group was given nape acupuncture based on the control group, and fiberoptic nasopharyngoscopy was used for the swallowing function before and after treatment. Rosenbek Penetration-Aspiration Scale (PAS) score of 5ml pudding food, 5ml and 10ml liquid food, and the scores for bedside water-swallowing test and standardized swallowing assessment (SSA) were obtained. Before and after treatment, the differences between the two groups were identified respectively. Results After treatment, the scores of SSA and PAS of swallowing of 3 kinds of food in both groups were significantly improved compared with those before treatment (P

In the paper, the structures, pressure-induced structural transitions (from cubic to hexagonal), lattice dynamics and the possible transition mechanisms for rare earth dihydrides REH2 and trihydrides REH3 (RE = Sm, Gd, Tb, Dy, Ho, and Tm) are investigated comparatively and systematically using first-principles calculations. The transition pressures from the cubic CaF2-type structure to the hexagonal REB2-type structure for REH2 (RE = Sm, Gd, Tb, Dy, Ho, Tm) and the transition pressures from the cubic BiF3-type structure to the hexagonal LaF3-type structure for REH3 (RE = Sm, Gd, Tb, Dy, Tm) are predicted reasonably. It is concluded that the two kinds of structural phase transitions are not sensitive to RE 4f electrons. In the two kinds of structural phase transitions under pressure, we note that the ‘‘2.1 A rule’’ (the purposed minimum H H distance for the stable metal hydirde at 0 K and 0 GPa) doesn't work. While lattice dynamics show that the dynamical stable pressure ranges for the cubic REH2 (RE = Sm Gd, Tb, Dy, Ho, Tm) are about in 0–52, 0–60, 0–70,0-87, 0–94 and 0–108 GPa, respectively. Ones of the cubic REH3 (RE = Sm, Gd, Tb, Dy, Tm) are around 17–147, 31–182, 13–200, 16–224 and 14–280 GPa, respectively. In contrast to the corresponding structural transition pressure as well as the lattice dynamics of the hexagonal structure under high pressure, the phonon modes softening behaviors under pressure might be responsible for the pressure-induced structural phase transition in the cubic REH2, but not in the cubic REH3.

In this study, MoSi2/SiC coating with high infrared emissivity was fabricated by atmospheric plasma spray (APS) method, in view of the potential application in high temperature energy-saving area. The phase composition, microstructure, infrared emissivity and thermal shock resistance of the obtained coating were characterized. Compared with MoSi2 coating, the MoSi2/SiC coating exhibited a higher emissivity of 0.908 at 1400 °C, owing to the smaller band gap energy and the distortion of Mo4.8Si3C0.6. Moreover, high thermal shock resistance was validated, as no emissivity degradation or obvious spalling of coating was found and only a few microcracks could be observed in the surface after 50 thermal cycles with water-quenching from 1300 °C to 25 °C.

Materials that are capable of adapting their properties dynamically to an external stimulus are called stimuli-responsive or “smart materials” [...]

Background An increase in the incidence of central venous catheter (CVC)-related thrombosis (CRT) has been reported in pediatric intensive care patients over the past decade. Risk factors for the development of CRT are not well understood, especially in children. The study objective was to identify potential clinical risk factors associated with CRT with novel fusion machine learning models. Methods Patients aged 0–18 who were admitted to intensive care units from December 2015 to December 2018 and underwent at least one CVC placement were included. Two fusion model approaches (stacking and blending) were used to build a better performance model based on three widely used machine learning models (logistic regression, random forest and gradient boosting decision tree). High-impact risk factors were identified based on their contribution in both fusion artificial intelligence models. Results A total of 478 factors of 3871 patients and 3927 lines were used to build fusion models, one of which achieved quite satisfactory performance (AUC = 0.82, recall = 0.85, accuracy = 0.65) in 5-fold cross validation. A total of 11 risk factors were identified based on their independent contributions to the two fusion models. Some risk factors, such as D-dimer, thrombin time, blood acid-base balance-related factors, dehydrating agents, lymphocytes and basophils were identified or confirmed to play an important role in CRT in children. Conclusions The fusion model, which achieves better performance in CRT prediction, can better understand the risk factors for CRT and provide potential biomarkers and measures for thromboprophylaxis in pediatric intensive care settings.

An open-frame aluminophosphate, K[(Zn

Background Pulmonary hypertension (PH) is defined as a mean pulmonary arterial pressure (PAP) ≥25 mm Hg measured by right heart catheterization. However, the upper limit of a normal mean PAP is 20 mm Hg. There is a gap between the upper limit of normal and the threshold for diagnosing PH. Therefore, we aimed to investigate whether individuals with a mildly elevated PAP, defined as 20 mm Hg < mean PAP Methods and Results We reviewed studies evaluating the risk of progression to PH and/or mortality in individuals with a mildly elevated PAP versus those with a normal PAP. The mean PAP value of each participant was confirmed by right heart catheterization. We reviewed 1213 studies and 8 fulfilled our inclusion criteria. Our results indicated that individuals with a mildly elevated PAP were 1.81 to 2.45 times more likely to progress to PH than individuals with a normal PAP. There was a statistically significant difference in mortality between the mildly elevated PAP and normal PAP groups (hazard ratio, 2.48; 95% CI, 1.69–3.64). We also pooled survival probabilities in each arm to obtain a summary survival curve for each group, and the pooled survival rates in the mildly elevated PAP group were numerically lower than those in the normal PAP group. Conclusions Our study revealed that individuals with a mildly elevated PAP were at an increased risk of progression to PH and mortality than those with a normal PAP.

Kidney damage initiates the deteriorating metabolic states in tubule cells that lead to the development of end‐stage renal disease (ESTD). Interleukin‐22 (IL‐22) is an effective therapeutic antidote for kidney injury via promoting kidney recovery, but little is known about the underlying molecular mechanisms. Here, we first provide evidence that IL‐22 attenuates kidney injury via metabolic reprogramming of renal tubular epithelial cells (TECs). Specifically, our data suggest that IL‐22 regulates mitochondrial function and glycolysis in damaged TECs. Further observations indicate that IL‐22 alleviates the accumulation of mitochondrial reactive oxygen species (ROS) and dysfunctional mitochondria via the induction of AMPK/AKT signaling and PFBFK3 activities. In mice, amelioration of kidney injury and necrosis and improvement of kidney functions via regulation of these metabolism relevant signaling and mitochondrial fitness of recombinant IL‐22 are certificated in cisplatin‐induced kidney damage and diabetic nephropathy (DN) animal models. Taken together, our findings unravel new mechanistic insights into protective effects of IL‐22 on kidneys and highlight the therapeutic opportunities of IL‐22 and the involved metabolic regulators in various kidney diseases., IL‐22 attenuates kidney injury via metabolic reprogramming of renal TECs, regulates mitochondrial function and glycolysis in damaged TECs, and alleviates the accumulation of mitochondrial ROS and dysfunctional mitochondria via the induction of AMPK/AKT and PFBFK3 activities. Ameliorating kidney injury of IL‐22 via regulation of metabolism relevant signaling is certificated in cisplatin‐induced kidney damage and diabetic nephropathy animal models.