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Autosomal-recessive mutations inSPEG(striated muscle preferentially expressed protein kinase) have been linked to centronuclear myopathy. Loss of SPEG is associated with defective triad formation, abnormal excitation-contraction coupling, and calcium mishandling in skeletal muscles. To elucidate the underlying molecular pathways, we have utilized multi-omics tools and analysis to obtain a comprehensive view of the complex biological processes. We identified that SPEG interacts with myospryn complex proteins (CMYA5, FSD2, RyR1), and SPEG deficiency results in myospryn complex abnormalities. In addition, transcriptional and protein profiles of SPEG-deficient muscle revealed defective mitochondrial function including aberrant accumulation of enlarged mitochondria on electron microscopy. Furthermore, SPEG regulates RyR1 phosphorylation at S2902, and its loss affects JPH2 phosphorylation at multiple sites. On analyzing the transcriptome, the most dysregulated pathways affected by SPEG deficiency included extracellular matrix-receptor interaction and peroxisome proliferator-activated receptors signaling, which may be due to defective triad and mitochondrial abnormalities. In summary, we have elucidated the critical role of SPEG in triad as it works closely with myospryn complex, phosphorylates JPH2 and RyR1, and demonstrated that its deficiency is associated with mitochondrial abnormalities. This study emphasizes the importance of using multi-omics techniques to comprehensively analyze the molecular anomalies of rare diseases.SynopsisWe have previously linked mutations inSPEG(striated preferentially expressed protein) with a recessive form of centronuclear myopathy and/or dilated cardiomyopathy and have characterized a striated muscle-specific SPEG-deficient mouse model that recapitulates human disease with disruption of the triad structure and calcium homeostasis in skeletal muscles. In this study, we applied multi-omics approaches (interactomic, proteomic, phosphoproteomic, and transcriptomic analyses) in the skeletal muscles of SPEG-deficient mice to assess the underlying pathways associated with the pathological and molecular abnormalities.SPEG interacts with myospryn complex proteins (CMYA5, FSD2, RyR1), and its deficiency results in myospryn complex abnormalities.SPEG regulates RyR1 phosphorylation at S2902, and its loss affects JPH2 phosphorylation at multiple sites.SPEGα and SPEGβ have different interacting partners suggestive of differential function.Transcriptome analysis indicates dysregulated pathways of ECM-receptor interaction and peroxisome proliferator-activated receptor signaling.Mitochondrial defects on the transcriptome, proteome, and electron microscopy, may be a consequence of defective calcium signaling.

Zinc-ion batteries (ZIBs), in particular quasi-solid-state ZIBs, occupy a crucial position in the field of energy storage devices owing to the superiorities of abundant zinc reserve, low cost, high safety and high theoretical capacity of zinc anode. However, as divalent Zn2+ ions experience strong electrostatic interactions when intercalating into the cathode materials, which poses challenges to the structural stability and higher demand in Zn2+ ions diffusion kinetics of the cathode materials. Here, a microwave-assisted hydrothermal method is adopted to prepare pre-potassiated hydrated vanadium pentoxide (K0.52V2O5•0.29H2O, abbreviated as KHVO) cathode material, in which the potassium ions pre-inserted into the interlayers can act as “pillars” to stabilize the lamellar structure, and crystal water can act as “lubricant” to improve the diffusion efficiency of Zn2+ ions. Consequently, the KHVO displays high electrochemical properties with high capacity (∼ 300 mAh/g), superior rate capability (69 mAh/g at 5 A/g) and ultralong cycling performance (>1500 cycles at 2 A/g) in quasi-solid-state ZIBs. These superior Zn storage properties result from the large diffusion coefficient and highly stable and reversible Zn2+ (de)intercalation reaction of KHVO.

The electrochemical kinetics of vanadium diphosphide is regulated by the phosphorus–carbon covalent bond to boost the sodium storage performance.

Given the abundant natural reserves of potassium and its similar properties to lithium, potassium-ion batteries (KIBs) are expected to be an emerging energy storage system to replace lithium-ion batteries (LIBs). Here, to overcome the sluggish diffusion kinetics and structure collapse of the anode in current KIBs, copper tetrathiovanadate (Cu3VS4) nanoparticles uniformly loaded in carbon nanofibers (CVS/CNF) are designed as a new anode for KIBs through electrospinning and subsequent carbonization/sulfidation treatment. Benefiting from the highly conductive Cu species and CNF network, an outstanding charge transfer kinetics is achieved in CVS/CNF composites. Meanwhile, the nanosized CVS particles and robust CNF networks are believed to be beneficial for enhanced structural stability during potassium insertion, and thus endow the composite anode with an excellent long-term capability. The CVS/CNF composite anode displays a high capacity (486 mA h g−1 at 0.1 A g−1), great rate feature (162 mA h g−1 at 6 A g−1) and outstanding cycling performance (193 mA h g−1 after 2000 cycles at 1 A g−1), which are superior to those of most of the reported transition metal sulfide anodes.

Background: Malnutrition is associated with poor prognosis and prevalent in gastric cancer patients. However, there is no standardized method for evaluating malnutrition; the Global Leadership Initiative on Malnutrition (GLIM) aimed to establish a standard criteria for evaluating malnutrition. However, the cutoff point for muscle reduction remains unclear, and its clinical value has not yet been verified. Hence, we aimed to examine the relationship between combinations of different muscle measurement indices and the survival of gastric cancer patients to determine the accurate method for diagnosing sarcopenia, establish the standard GLIM criteria, and explore its clinical value. Methods: This multicenter and observational cohort study included 1,406 gastric cancer patients. The accurate prediction combination was determined using the cutoff point for muscle loss by predicting the survival risk according to the GLIM criteria established using a combination of muscle mass indicators. Least absolute shrinkage and selection operator regression analysis was used to screen the independent risk factors for survival with the construction of a Cox regression model. The R software was used to establish the nomogram of individual survival prediction and to verify the clinical significance of malnutrition diagnosed based on the GLIM criteria. Results: The risk ratio of patients with malnutrition based on the leg circumference and weight-corrected grip strength was the highest (hazard ratio [HR]=2.159, 95% confidence interval [CI]=1.800, 2.588 in severely malnourished patients). Malnutrition occurred in 54.5% of patients diagnosed with gastric cancer based on the GLIM criteria. Malnutrition is an independent risk factor for unfavorable survival in gastric cancer patients; its nomogram model can accurately predict the survival of gastric cancer. Conclusion: Muscle loss is one of the components of the GLIM criteria and is determined by measuring the leg circumference and weight-corrected grip strength. The GLIM criteria are effective in diagnosing malnutrition and predicting the survival in gastric cancer patients.

This paper mainly studies the numerical simulation of the force process of the runner blades in the transient process of the pump-turbine. In this paper, dynamic simulation technology is used to ca...

A challenging issue in the field of the automatic recognition of emotion from speech is the efficient modelling of long temporal contexts. Moreover, when incorporating long-term temporal dependencies between features, recurrent neural network (RNN) architectures are typically employed by default. In this work, we aim to present an efficient deep neural network architecture incorporating Connectionist Temporal Classification (CTC) loss for discrete speech emotion recognition (SER). Moreover, we also demonstrate the existence of further opportunities to improve SER performance by exploiting the properties of convolutional neural networks (CNNs) when modelling contextual information. Our proposed model uses parallel convolutional layers (PCN) integrated with Squeeze-and-Excitation Network (SEnet), a system herein denoted as PCNSE, to extract relationships from 3D spectrograms across timesteps and frequencies; here, we use the log-Mel spectrogram with deltas and delta-deltas as input. In addition, a self-attention Residual Dilated Network (SADRN) with CTC is employed as a classification block for SER. To the best of the authors' knowledge, this is the first time that such a hybrid architecture has been employed for discrete SER. We further demonstrate the effectiveness of our proposed approach on the Interactive Emotional Dyadic Motion Capture (IEMOCAP) and FAU-Aibo Emotion corpus (FAU-AEC). Our experimental results reveal that the proposed method is well-suited to the task of discrete SER, achieving a weighted accuracy (WA) of 73.1% and an unweighted accuracy (UA) of 66.3% on IEMOCAP, as well as a UA of 41.1% on the FAU-AEC dataset.

Physiological studies have illustrated that speech can be used as a biomarker to analyze the severity of depression and different frequency bands of the speech spectrum contribute unequally for depression detection. To this end, we propose a Time-Frequency Attention (TFA) component and combine it with the Squeeze-and-Excitation (SE) component to form our Time-Frequency Channel Attention (TFCA) block for emphasizing those discriminative timestamps, frequency bands and channels. In addition, considering the time-frequency attributes of the data, a Time-Frequency Channel Vectorization (TFCV) block is proposed to vectorize the tensor. Furthermore, we merge the proposed blocks (i.e., TFCA and TFCV blocks) and the two blocks (i.e., Dense block and Transition Layer) of the DenseNet into a unified architecture to form our Time-Frequency Channel Attention and Vectorization (TFCAV) network. In this way, to predict the depression level of an individual, we firstly introduce the sphere embedding normalization method to preprocess the long-term logarithmic amplitude spectrum for maintaining the time-frequency attributes and divide it into segments. Then, these segments are input into the TFCAV network to obtain the depression scores. Finally, the average of scores is taken as the result corresponding to the long-term spectrum. Our method is validated on two challenging databases, i.e., AVEC2013 and AVEC2014 depression databases. The experimental performance illustrates the superiority of the proposed network over some previous methods.

The abundant natural resources and low cost benefits of zinc-ion batteries (ZIBs) and potassium-ion batteries (KIBs) offer a better alternative to lithium-ion batteries (LIBs). Nevertheless, the large radius of K+ and high charge density of Zn2+ lead to sluggish electrochemical kinetics and the development of appropriate electrode materials for KIBs and ZIBs is therefore very important. Herein, hierarchical K-doped brookite vanadium dioxide (K–VO2(B)) spheres prepared via a simple microwave-assisted hydrothermal approach are proposed. K–VO2(B) as an anode material for PIBs shows enhanced electrochemical performance in terms of high capacity (∼420 mA h g−1), exceptional rate capability and long-term cycling performance (500 cycles). For ZIBs, it also achieves a high capacity of 350 mA h g−1 at 500 mA g−1 and 122 mA h g−1 at an extremely high rate of 50 A g−1. The outstanding PIB and ZIB performance of the K–VO2(B) is mainly benefitted from the improved ion diffusion coefficients after K-doping and the occurrence of inherently stable (de)intercalation reactions.

Striated preferentially expressed gene (SPEG), a member of the myosin light chain kinase family, is localized at the level of triad surrounding myofibrils in skeletal muscles. In humans, SPEG mutations are associated with centronuclear myopathy and cardiomyopathy. Using a striated muscle-specific Speg-knockout (KO) mouse model, we have previously shown that SPEG is critical for triad maintenance and calcium handling. Here, we further examined the molecular function of SPEG and characterized the effects of SPEG deficiency on triad and focal adhesion proteins. We used yeast two-hybrid assay, and identified desmin, an intermediate filament protein, to interact with SPEG and confirmed this interaction by co-immunoprecipitation. Using domain-mapping assay, we defined that Ig-like and fibronectin III domains of SPEG interact with rod domain of desmin. In skeletal muscles, SPEG depletion leads to desmin aggregates in vivo and a shift in desmin equilibrium from soluble to insoluble fraction. We also profiled the expression and localization of triadic proteins in Speg-KO mice using western blot and immunofluorescence. The amount of RyR1 and triadin were markedly reduced, whereas DHPRα1, SERCA1 and triadin were abnormally accumulated in discrete areas of Speg-KO myofibers. In addition, Speg-KO muscles exhibited internalized vinculin and β1 integrin, both of which are critical components of the focal adhesion complex. Further, β1 integrin was abnormally accumulated in early endosomes of Speg-KO myofibers. These results demonstrate that SPEG-deficient skeletal muscles exhibit several pathological features similar to those seen in MTM1 deficiency. Defects of shared cellular pathways may underlie these structural and functional abnormalities in both types of diseases.

Centronuclear myopathies (CNMs) are a subtype of congenital myopathies characterized by skeletal muscle weakness and an increase in the number of central myonuclei. SPEG (striated preferentially expressed protein kinase) has been identified as the sixth gene associated with CNM, and it has been shown that striated muscle-specific Speg-knockout (KO) mice have defective triad formation, abnormal excitation-contraction coupling, and calcium mishandling. The impact of SPEG deficiency on the survival and function of myogenic cells remains to be deciphered. In this study, the authors examined the overall population, proliferation, and differentiation of myogenic cells obtained from striated muscle-specific Speg-KO mice and compared them with wild-type (WT) controls. SPEG-deficient skeletal muscles contained fewer myogenic cells, which on further study demonstrated reduced proliferation and delayed differentiation compared with those from WT muscles. Regenerative response to skeletal muscle injury in Speg-KO mice was compared with that of WT mice, leading to the identification of similar abnormalities including fewer satellite cells, fewer dividing cells, and an increase in apoptotic cells in KO mice. Overall, these results reveal specific abnormalities in myogenic cell number and behavior associated with SPEG deficiency. Similar satellite cell defects have been reported in mouse models of MTM1- and DNM2-associated CNM, suggestive of shared underlying pathways.

Background This research aimed at exploring the mechanisms of alterations of metabolites and pathways in T2D from the perspective of metabolomics and transcriptomics, as well as uncovering novel drug candidate for T2D treatment. Methods Metabolites in human plasma from 42 T2D patients and 45 non‐diabetic volunteers were detected by liquid chromatography‐mass spectrometer (LC‐MS). Microarray dataset of the transcriptome was obtained from Gene Expression Omnibus (GEO) database. Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to conduct pathway enrichment analysis. Connectivity Map (CMap) was employed to select potential drugs for T2D therapy. In vivo assay was performed to verify above findings. The protein expression levels of ME1, ME2 and MDH1 were detected by Western blot to determine the status of NAD/NADH cofactor system. Results In our study, differentially expressed metabolites were selected out between healthy samples and T2D samples with selection criteria P value 2, including N‐acetylglutamate and Malate. Genes set enrichment analysis (GSEA) revealed that 34 pathways were significantly enriched in T2D. Based on CMap analysis and animal experiments, Atractyloside was identified as a potential novel drug for T2D treatment via targeting ME1, ME2 and MDH1 and regulating the NAD/NADH cofactor system. Conclusion The present research revealed differentially expressed metabolites and genes, as well as significantly altered pathways in T2D via an integration of metabolomics, transcriptomics and CMap analysis. It was also demonstrated that comprehensive analysis based on metabolomics and transcriptomics was an effective approach for identification and verification of metabolic biomarkers and alternated pathways.

The discovery of novel electrode materials promises to unleash a number of technological advances in lithium-ion batteries. V2O5 is recognized as a high-performance cathode that capitalizes on the rich redox chemistry of vanadium to store lithium. To unlock the full potential of V2O5, nanotechnology solution and rational electrode design are used to imbue V2O5 with high energy and power density by addressing some of their intrinsic disadvantages in macroscopic crystal form. Here, we demonstrate a facile and environmental-friendly method to prepare nanorods-constructed 3D porous V2O5 architectures (3D-V2O5) in large-scale. The 3D porous architecture is found to be responsible for the enhanced charge transfer kinetics and Li-ion diffusion rate of the 3D-V2O5 electrode. As the result, the 3D-V2O5 surpasses the conventional bulk V2O5 by showing enhanced discharge capacity and rate capability (delivering 154 and 127 mAh g−1 at 15 and 20 C, respectively).

Striated preferentially expressed protein kinase (SPEG), a myosin light chain kinase, is mutated in centronuclear myopathy (CNM) and/or dilated cardiomyopathy. No precise therapies are available for this disorder, and gene replacement therapy is not a feasible option due to the large size of SPEG. We evaluated the potential of dynamin-2 (DNM2) reduction as a potential therapeutic strategy because it has been shown to revert muscle phenotypes in mouse models of CNM caused by MTM1, DNM2, and BIN1 mutations. We determined that SPEG-β interacted with DNM2, and SPEG deficiency caused an increase in DNM2 levels. The DNM2 reduction strategy in Speg-KO mice was associated with an increase in life span, body weight, and motor performance. Additionally, it normalized the distribution of triadic proteins, triad ultrastructure, and triad number and restored phosphatidylinositol-3-phosphate levels in SPEG-deficient skeletal muscles. Although DNM2 reduction rescued the myopathy phenotype, it did not improve cardiac dysfunction, indicating a differential tissue-specific function. Combining DNM2 reduction with other strategies may be needed to target both the cardiac and skeletal defects associated with SPEG deficiency. DNM2 reduction should be explored as a therapeutic strategy against other genetic myopathies (and dystrophies) associated with a high level of DNM2.

Objective — To observe the effects of ropivacaine combined with ketorolac transverse abdominis plane (TAP) block on postoperative analgesia in patients undergoing gynecological laparoscopic surgery. Methods — 90 ASAⅠorⅡpatients, aged 18-65 years and weighting 40-80 kg, scheduled for gynecological laparoscopic surgery were recruited and divided into three groups using random number table:ropivacaine combined with ketorolac 15 mg/side for TAP block (KR group), ropivacaine for TAP block and 30 mg preoperatively intravenous ketorolac (KIVR group) and ropivacaine for TAP block alone (R group) with 30 patients in each group. Intraoperative opioid consumption, Bruggrmann comfort scale (BCS) scores at 2h (T1), 4h (T2), 8h (T3), 12h (T4), 16h (T5), 24h (T6) after surgery were recorded. Adverse reactions such as nausea and vomiting, respiratory depression, local anesthetic poisoning, gastrointestinal bleeding, and complications related to TAP block operation were recorded. Results — The total consumpsion of sufentanil was higher in the R group than that in the KIVR group and KR group (P < 0.05). The total dosage of remifentanil in R group was higher than that in KR group (P < 0.05). The BCS scores of the three groups at T3, T4, T5 and T6 were lower in R group than that in KR group (P < 0.05) while R Group was lower than KIVR group at T3 and T4 (P < 0.05), and KIVR group was lower than KR group at T5 and T6. There was no statistically differences in BCS score between the three groups at T1 and T2 (P > 0.05). No statistical differences in the incidence of adverse reactions among all groups were observed. Conclusion — Ropivacaine combined with ketolorac transverse abdominisplane block reduced the intraoperative opioid consumption, improved postoperative comfort score and do not increased the incidence of adverse reactions in gynecological laparoscopic surgery.

Recent clinical cohort studies have highlighted that there is a three-fold greater SARS-Cov-2 infection risk in cancer patients, and overall mortality in individuals with tumours is increased by 41% with respect to general COVID-19 patients. Thus, access to therapeutics and intensive care is compromised for people with both diseases (comorbidity) and there is risk of delayed access to diagnosis. This comorbidity has resulted in extensive burden on the treatment of patients and health care system across the globe; moreover, mortality of hospitalized patients with comorbidity is reported to be 30% higher than for individuals affected by either disease. In this data-driven review, we aim specifically to address drug discoveries and clinical data of cancer management during the COVID-19 pandemic. The review will extensively address the treatment of COVID-19/cancer comorbidity; treatment protocols and new drug discoveries, including the description of drugs currently available in clinical settings; demographic features; and COVID-19 outcomes in cancer patients worldwide.

Reported herein is the design, synthesis, and pharmacologic evaluation of a class of TRPV1 antagonists constructed on 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole as A-region and triazole as B-region. The SAR analysis indicated that 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole analogues displayed excellent antagonism of hTRPV1 activation by capsaicin and showed better potency compared to the corresponding dihydroindole analogues. Optimization of this design led to the eventual identification of 2-((1-(2-(trifluoromethyl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole (6g), a potent TRPV1 antagonist. In vitro, using cells expressing recombinant human TRPV1 channels, 6g displayed potent antagonism activated by capsaicin (IC50 = 0.075 μM) and only partially blocked acid activation of TRPV1. In vivo, 6g exhibited good efficacy in capsaicin-induced and heat-induced pain models and had almost no hyperthermia side-effect. Furthermore, pharmacokinetic studies revealed that compound 6g had a superior oral exposure after oral administration in rats. To understand its binding interactions with the receptor, the docking study of 6g was performed in rTRPV1 model and showed an excellent fit to the binding site. On the basis of its superior profiles, 6g could be considered as the lead candidate for the further development of antinociceptive drugs.

Recently, diverse kinase inhibitors were reported having interaction with BRD4. It provided a strategy for developing a new structural framework for the next-generation BRD4-selective inhibitors. Starting from PLK1 kinase inhibitor BI-2536, we designed 18 compounds by modifying dihydropteridine core. Compound 23 showed potent BRD4 inhibitory activities with IC50 of 79 nM and no inhibitory activities for PLK1. Cell antiproliferation assay was performed and potent inhibitory activity against MV4;11 with IC50 of 1.53 μM. Cell apoptosis and western blotting indicated compound 23 induced apoptosis by down-regulating c-Myc. These novel selective BRD4 inhibitors provided new lead compounds for further drug development.

Non-immune hydrops fetalis (NIHF) is a complex condition with a high mortality and morbidity rate. Here we report the etiology and outcome of 1004 fetuses with NIHF, in a large single Maternal and Children’s hospital of Southern China, since the year of 2009 to 2016. Among these 1004 fetuses with NIHF, the etiology was identified prenatally in 722 of them (72%). The most common ones were hematologic diseases and chromosomal abnormalities. There were eight spontaneous abortions, 18 intrauterine fetal demise, 672 pregnancy terminations and 87 were lost to follow-up. 219 of the 1004 fetuses were live-born and the overall survival rate was 21.8% at this point. After birth 16 perinatal or early neonatal deaths were encountered and five lost to follow-up. Of the remaining 198 newborns, 153 thrived without apparent morbidity. The most significant factors associated with mortality were prematurity and low birthweight. In conclusion, we described the largest report of underlying causes and outcome of NIHF in Southern China. Etiologies were identified for 72% of 1004 fetuses with NIHF. And two poor prognostic factors for survival are preterm birth at less than 36.5 weeks and birthweight lower than 2575 g respectively.

We synthesized PEG-TPP as carrier to encapsulate paclitaxel (PTX) in the form of micelles to overcome its water-solubility problem. PTX-loaded micelles possess a-week stability and appropriate particle size (152.1 ± 1.2 nm) which is beneficial for enhanced permeability and retention (EPR) effect. Strong pH dependence of PTX releasing from micelles is verified by in vitro release study. At cellular level, PTX-loaded micelles can target mitochondria effectively which may results a better cytotoxicity of micelles (especially IC50 = 0.123 ± 0.035 μmol/L of micelles and 0.298 ± 0.067 μmol/L of PTX alone on MCF-7 cells). The fluorescence distributions of both isolated and sliced organs show that the micelles can effectively target tumors. Moreover, we further prove the enhanced therapeutic effects of micelles in tumor-bearing mice comparing with PTX alone. The results show that the biodegradable drug delivery system prepared by PEG-TPP can overcome the poor solubility of paclitaxel and improve its tumor targeting and antitumor activity.

Background Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder. Although most patients present with isolated CH, some patients present with CH and extra-thyroidal congenital malformations (ECMs), for which less is known about the underlying genetics. The aim of this study was to investigate the genetic mechanisms in patients with CH and ECMs using chromosomal microarray (CMA) and whole exome sequencing (WES). Methods Peripheral venous blood samples were collected from 16 patients with CH and ECMs. Genomic DNA was extracted from peripheral blood leukocytes. CMA and WES were performed to detect copy number and single nucleotide variants. Results CMA identified clinically significant copy number variants in 7 patients consistent with their phenotypes. For 6 of them, the genotype and phenotype suggested a syndromic diagnosis, and the remaining patient carried a pathogenic microdeletion and microduplication including GLIS3. WES analysis identified 9 different variants in 7 additional patients. The variants included 2 known mutations (c.1096C>T (p.Arg366Trp) in KCNQ1 and c.848C>A (p.Pro283Gln) in NKX2-5) and 7 novel variants: one nonsense mutation (c.4330C>T (p.Arg1444*) in ASXL3), one frameshift mutation (c.1253_1259delACTCTGG (p.Asp418fs) in TG), three missense variants (c.1472C>T (p.Thr491Ile) in TG, c.4604A>G (p.Asp1535Gly) in TG, and c.2139G>T (p.Glu713Asp) in DUOX2, and two splice site variants (c.944-1G>C and c.3693 + 1G>T) in DUOX2. Conclusions We report the first genetic study of CH patients with ECMs using CMA and WES. Overall, our detection rate for pathogenic and possibly pathogenic variants was 87.5% (14/16). We report 7 novel variants, expanding the mutational spectrum of TG, DUOX2, and ASXL3.

In order to study the influence of the change of the guide vane airfoil on the flow characteristics in the draft tube of a reversible hydraulic turbine, a reversible hydraulic turbine was used as the object of study, and the effect of the change on the flow pattern, energy loss, and pressure pulsation in the draft tube area was studied based on the SST k-ω turbulence model. The results show that under low flow conditions, the modified movable guide vane directly affects the direction and speed of water entering the draft tube, reduces the density of vortex in the draft tube area, reduces the impact on the near wall of the draft tube during the rotation of the vortex belt, and improves the stability of the unit operation. The turbulent energy comparison graph shows that the energy loss in the bent elbow section and the diffusion section of the draft tube is reduced, and the energy return coefficient of the draft tube is improved by calculating that the energy recovery level of the draft tube is improved under different operating conditions. A comparative analysis of the pressure pulsation in the draft tube area before and after the modification in combination with the development of the vortex belt shows that the modified movable guide vane effectively reduces the vibration intensity in the draft tube area and improves the stable operation threshold of the unit.

Background Nemaline myopathy 8 is a severe autosomal recessive muscle disorder characterized by fetal akinesia or hypokinesia, contractures, fractures, respiratory failure and swallowing difficulties apparent at birth. Methods An affected dizygotic twin pair from a non‐consanguineous Chinese family presented with severe asphyxia, lethargy and no response to stimuli. The dysmorphic features included prominent nasal bridge, telecanthus, excessive hip abduction, limb edema, absent palmar and sole creases, acromelia, bilateral clubfoot, appendicular hypertonia and cryptorchidism. Both infants died in the first week of life. Whole‐exome sequencing was used to identify the causative gene. Results Whole‐exome sequencing identified a recurrent missense variant c.1516A>C and a novel splice‐acceptor variant c.1153‐1G>C in KLHL40 gene in both siblings. We estimated the disease incidence in Southern Chinese population to be 2.47/100,000 based on the cumulative allele frequency of pathogenic and likely pathogenic variants in our internal database. Conclusion Our study expanded the mutation spectrum of KLHL40 and the condition could have been underdiagnosed before. We identified a recurrent missense variant c.1516A>C and provided evidence further supporting the founder effect of this variant in Southern Chinese population. Given the severity of the condition and the relative high incidence, this not‐so‐rare disorder should be included in expanded carrier screening panel for Chinese population., Two male babies with nemaline myopathy‐8 also showed appendicular hypertonia exome sequencing identified a recurrent missense variant and a novel splice‐acceptor variant in KLHL40 Four additional novel pathogenic variants of KLHL40 were identified and it is speculated that nemaline myopathy‐8 is not‐so‐rare in Chinese population.

To study the evolution principle of the coherent structure in the low flow rate runaway condition, the pump-turbine of the certain pumped storage power plant is employed. The transient dynamic stress of the runner has been numerically simulated and examined in this study, in order that can probe the mechanism of channel vortices acting on the blade and the evolution of their coherent structure in the runner. Based on the Realizable k-ε turbulent model, the unsteady flow of the whole pump-turbine channels is calculated. Results show that the flow in the runner channels presents with the turbulence state, and with many different scales vortices. These vortices structures are mainly distributed in the inlet region of the blade, the area of the blade trailing edge and the middle section of the runner channels. These vortex structures affect the distribution of the blade pressure load. Moreover, vortices structure at the inlet of the runner depends on the change of the attack angle. In the flow region formed at the outlet of the blade near the suction surface and the runner cone, the blade has a limited effect to the fluid, thus the vortex structure depends on the Coriolis force and the centrifugal force joint action.

The pain after thoracic surgery is often moderate to severe. Perioperative analgesia has always been one of the research hotspots of thoracic anesthesia. The patients were prepared before operation according to the routine, and the fasting time was performed according to the fasting guidelines before anesthesia for adult surgery. After entering the operating room, first establish an infusion channel in the vein of the upper limb, and routinely use a monitor to monitor the basic vital signs. Puncture the right internal jugular vein and place the tube under ultrasound; Under local anesthesia, the radial artery was punctured and catheterized, and the catheter was connected with the transducer to monitor the invasive blood pressure. All patients in group P used the puncture method through the lateral approach. Use the same method on the opposite side. The plane was measured by acupuncture. If there was hypoesthesia, the effect of block was determined, and the spinal nerve block segments after plane fixation were recorded. The complications related to puncture (such as pneumothorax, hemothorax, local anesthetic poisoning, etc.), operation time, extubation time, propofol, remifentanil and the use of cisatracurium during maintenance were recorded. Among all patients, the patients with ID ≥ 2 in TPVB group and Gen group were 14.1% and 18.8% respectively, and the difference was not statistically significant (P > 0.05). Thoracic paravertebral block combined with general anesthesia is beneficial to reduce perioperative complications, incidence rate and mortality, and improve postoperative outcome.

In this paper, we propose Inverse Adversarial Training (IAT) algorithm for training neural dialogue systems to avoid generic responses and model dialogue history better. In contrast to standard adversarial training algorithms, IAT encourages the model to be sensitive to the perturbation in the dialogue history and therefore learning from perturbations. By giving higher rewards for responses whose output probability reduces more significantly when dialogue history is perturbed, the model is encouraged to generate more diverse and consistent responses. By penalizing the model when generating the same response given perturbed dialogue history, the model is forced to better capture dialogue history and generate more informative responses. Experimental results on two benchmark datasets show that our approach can better model dialogue history and generate more diverse and consistent responses. In addition, we point out a problem of the widely used maximum mutual information (MMI) based methods for improving the diversity of dialogue response generation models and demonstrate it empirically., Comment: ACL 2021

Most of text emotion recognition methods are mainly based on the combination of simple word embedding and single network model, which cannot effectively capture the semantic emotional relationship in the sentence. To address this issue, we propose a neural network architecture called AMINN (Attention-Based Multi-Information Neural Network). We apply the attention mechanism to dynamically integrate the semantic emotional information to obtain key emotional information. The proposed method consists of pre-trained word embedding with fine-tuned training, two subnetworks and attention mechanism to capture the semantic emotional information in the text. The CNN sub-network captures the local semantic emotional information of the text, the BiLSTM subnetwork captures the contextual semantic emotional information of the text. The attention mechanism is used to fuse these two subnetworks. We conduct experiments on both Chinese(nlpcc2014) and English(SST) datasets to evaluate the effectiveness of our methods. Experimental results show that the proposed model is better than all baseline methods and is not limited by language. It pushes the recognition accuracy of single sentence positive/negative classification from 79% to 86%, and the f1 value reaches the highest value of 0.78. The recognition performance of fine-grained sentiment labels was also improved by 9.6%. These experimental results prove the superiority of our model.

Highlights 3D flower-like architecture assembled by NH4V4O10 nanobelts (3D-NVO) was fabricated.The Zn2+ ion was intercalated into NVO cathode within the interlayer region (NH4V4O10 ↔ ZnxNH4V4O10).The 3D-NVO cathode could deliver a large reversible capacity of 485 mAh g−1 at a current density of 100 mA g−1 for zinc-ion battery. Electronic supplementary material The online version of this article (10.1007/s40820-020-0401-y) contains supplementary material, which is available to authorized users., Given the advantages of being abundant in resources, environmental benign and highly safe, rechargeable zinc-ion batteries (ZIBs) enter the global spotlight for their potential utilization in large-scale energy storage. Despite their preliminary success, zinc-ion storage that is able to deliver capacity > 400 mAh g−1 remains a great challenge. Here, we demonstrate the viability of NH4V4O10 (NVO) as high-capacity cathode that breaks through the bottleneck of ZIBs in limited capacity. The first-principles calculations reveal that layered NVO is a good host to provide fast Zn2+ ions diffusion channel along its [010] direction in the interlayer space. On the other hand, to further enhance Zn2+ ion intercalation kinetics and long-term cycling stability, a three-dimensional (3D) flower-like architecture that is self-assembled by NVO nanobelts (3D-NVO) is rationally designed and fabricated through a microwave-assisted hydrothermal method. As a result, such 3D-NVO cathode possesses high capacity (485 mAh g−1) and superior long-term cycling performance (3000 times) at 10 A g−1 (~ 50 s to full discharge/charge). Additionally, based on the excellent 3D-NVO cathode, a quasi-solid-state ZIB with capacity of 378 mAh g−1 is developed. Electronic supplementary material The online version of this article (10.1007/s40820-020-0401-y) contains supplementary material, which is available to authorized users.

N-(4-Tert-butylphenyl)-4-(3-chloropyridin-2-yl) piperazine-1-carboxamide (BCTC) is a potent and extensively studied urea-based TRPV1 antagonist. Although BCTC was effective in alleviating chronic pain in rats, it showed obvious hyperthermia side-effect and unsatisfactory pharmacokinetic profile, therefore, it was not developed further. In order to enrich the structural types of urea-based TRPV1 antagonists, two series of novel analogs, in which the pyridine ring of BCTC was replaced with a mildly basic pyrimidine ring or 1,2,3,4-tetrahydro-β-carboline scaffold, were designed and synthesized. Advancing the structure-activity relationship of these two series led to the discovery of N-(4-methoxyphenyl)-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indole-2-carboxamide (7o), with an improved pharmacological and tolerability profile compared with the lead compound BCTC.

Bromodomain-containing protein 4 (BRD4) is a key epigenetic regulator in cancer, and inhibitors targeting BRD4 exhibit great anticancer activity. By replacing the methyltriazole ring of the BRD4 inhibitor I-BET-762 with an N-methylthiazolidone heterocyclic ring, fifteen novel BRD4 inhibitors were designed and synthesized. Compound 13f had a hydrophobic acetylcyclopentanyl side chain, showing the most potent BRD4 inhibitory activity in the BRD4-BD1 inhibition assay (IC50 value of 110 nM), it also significantly suppressed the proliferation of MV-4-11 cells with high BRD4 level (IC50 value of 0.42 μM). Furthermore, the potent apoptosis-promoting and G0/G1 cycle-arresting activity of compound 13f were indicated by flow cytometry. As the downstream-protein of BRD4, c-Myc was in significantly low expression by compound 13f treatment in a dose-dependent manner. All the findings supported that this novel compound 13f provided a perspective for developing effective BRD4 inhibitors.

An increase in internal pressure of a Roto-Jet pump is due to combined action of its impeller and rotating casing. Internal pressure of the pump chamber was determined according to outlet pressure of the impeller, and the influence of the rotary casing effect was ignored. To study the combined action mechanism of the rotating casing effect and impeller structure on the Roto-Jet pump, we used the open test bed of the Roto-Jet pump and four model pumps with impellers of different structures as research objects. We also conducted a comprehensive experimental study on the coupling mechanism between the rotating casing effect and impeller structure. Numerical calculation was performed to avoid the assumption of isotropic eddy viscosity, Reynolds stress linear pressure-strain model is selected, and the numerical calculation results are compared with the experimental results to verify its credibility. The results show that the rotating casing effect has multiple functions to reduce the friction loss of the disc, improve the pressure distribution inside the rotating casing, and increase the pump head. All scheme, pressure, and velocity fluctuations occur in the upstream and wake regions of the collecting pipe and the energy loss is concentrated in the upstream region. The difference in velocity distribution inside the collecting pipe is small and negligible. As long as the impeller and rotating casing continue to rotate synchronously, the liquid shear velocity at the same coordinate position of each scheme remains unchanged, and the liquid rotation angular velocity in the rotating casing is approximately 75% of the rotating casing which conforms to the rigid motion law. In the same scheme, the coefficient of uneven velocity inside the rotating casing gradually increases along the radial direction. The closer to the axis, the faster is the decrease of the peak tangential velocity and the velocity tends to be uniform. The size, shape, and position of the vortex core inside the rotating casing change constantly with various schemes. The distribution of vortex cores varies under each scheme. The front cover and rotating casing have a serious effect on the vortex core. The extremely poor analysis of the test results shows that the performance of the Roto-Jet pump is better when the closed impeller is rotated in synchronisation with the rotating casing. The advantages and disadvantages of each blade type can be determined according to the situation. The research results can exhibit the influence mechanism of the Roto-Jet pump shell effect. Selection of an impeller structure provides a reference.

Fact verification models have enjoyed a fast advancement in the last two years with the development of pre-trained language models like BERT and the release of large scale datasets such as FEVER. However, the challenging problem of fake news detection has not benefited from the improvement of fact verification models, which is closely related to fake news detection. In this paper, we propose a simple yet effective approach to connect the dots between fact verification and fake news detection. Our approach first employs a text summarization model pre-trained on news corpora to summarize the long news article into a short claim. Then we use a fact verification model pre-trained on the FEVER dataset to detect whether the input news article is real or fake. Our approach makes use of the recent success of fact verification models and enables zero-shot fake news detection, alleviating the need of large-scale training data to train fake news detection models. Experimental results on FakenewsNet, a benchmark dataset for fake news detection, demonstrate the effectiveness of our proposed approach., Comment: Accepted to COLING 2020

Multiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder of fatty acid, amino acid, and choline metabolism caused by mutations in EFTA, EFTB, or ETFDH. Many MADD patients are responsive to treatment with riboflavin, termed riboflavin-responsive MADD (RR-MADD). Here, we report three novel mutations and one previously reported mutation in ETFDH in four RR-MADD patients who presented at various ages, and characterize the corresponding changes in ETF-QO protein structure. Clinicians should consider MADD in the differential diagnosis when patients present with muscle weakness and biochemical abnormalities. Gene testing plays a critical role in confirming the diagnosis of MADD, and may not only prevent patients from invasive testing, but also allow timely initiation of riboflavin treatment. The novel variants in ETFDH and the corresponding clinical features reported here enrich the allelic heterogeneity of RR-MADD and provide insight into genotype-phenotype relationships. Keywords: Multiple acyl-CoA dehydrogenase deficiency, Glutaric aciduria II, ETFDH, ETF-QO, Riboflavin

A new series of derivatives of 3-(7-chloro-5-(2-fluorophenyl)-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)propanoic acid were designed and synthesized as analgesic modulating for Transient receptor potential vanilloid 1. They were investigated for TRPV1 antagonistic activity in vitro, analgesic activity and sedative activity in vivo and aqueous solubility. Preliminary studies identified 3-(7-chloro-5-(2-fluorophenyl)-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-N,N-dimethylpropanamide(Compound 11), as a potent analgesic modulating for TRPV1 with potent activity and good aqueous solubility.

SLC25A46 (solute carrier family 25 member 46) mutations have been linked to various neurological diseases with recessive inheritance, including Leigh syndrome, optic atrophy, and lethal congenital pontocerebellar hypoplasia. SLC25A46 is expressed in the outer membrane of mitochondria, where it plays a critical role in mitochondrial dynamics. A deceased 7-month-old female infant was suspected to have Leigh syndrome. Clinical exome sequencing was non-diagnostic, but research reanalysis of the sequencing data identified two novel variants in SLC25A46: a missense (c.1039C>T, p.Arg347Cys; NM_138773, hg19) and a donor splice region variant (c.283+5G>A) in intron 1. Both variants were predicted to be damaging. Sanger sequencing of cDNA detected a single missense allele in the patient compared to control, and the SLC25A46 transcript levels were also reduced due to the splice region variant. Additionally, Western blot analysis of whole-cell lysate showed a decrease of SLC25A46 expression in proband fibroblasts, relative to control cells. Further, analysis of mitochondrial morphology revealed evidence of increased fragmentation of the mitochondrial network in proband fibroblasts, compared to control cells. Collectively, our findings suggest that these novel variants in SLC24A46, the donor splice one and the missense variant, are the cause of the neurological phenotype in this proband.

ARHGAP42 encodes Rho GTPase activating protein 42 that belongs to a member of the GTPase Regulator Associated with Focal Adhesion Kinase (GRAF) family. ARHGAP42 is involved in blood pressure control by regulating vascular tone. Despite these findings, disorders of human variants in the coding part of ARHGAP42 have not been reported. Here, we describe an 8-year-old girl with childhood interstitial lung disease (chILD), systemic hypertension, and immunological findings who carries a homozygous stop-gain variant (c.469G>T, p.(Glu157Ter)) in the ARHGAP42 gene. The family history is notable for both parents with hypertension. Histopathological examination of the proband lung biopsy showed increased mural smooth muscle in small airways and alveolar septa, and concentric medial hypertrophy in pulmonary arteries. ARHGAP42 stop-gain variant in the proband leads to exon 5 skipping, and reduced ARHGAP42 levels, which was associated with enhanced RhoA and Cdc42 expression. This is the first report linking a homozygous stop-gain variant in ARHGAP42 with a chILD disorder, systemic hypertension, and immunological findings in human patient. Evidence of smooth muscle hypertrophy on lung biopsy and an increase in RhoA/ROCK signaling in patient cells suggests the potential mechanistic link between ARHGAP42 deficiency and the development of chILD disorder., Author summary Childhood interstitial lung disease (chILD) is a heterogeneous group of rare disorders characterized by diffuse pulmonary infiltrates, respiratory signs and symptoms, and impaired gas exchange. These disorders are complex to diagnose and are associated with substantial morbidity and mortality. Although pathogenic variants in a number of genes have been described to cause chILD, these known genetic etiologies explain only a minority of the cases and there are additional genes yet to be identified. We have identified an 8-year-old girl with chILD, systemic hypertension, and immune abnormalities who carries a homozygous stop-gain variant in the ARHGAP42 gene. Functional studies demonstrate that this stop-gain variant leads to exon 5 skipping and reduced levels of ARHGAP42 protein. We also show enhanced RhoA expression and its activity in the patient’s lymphoblastoid cell lines. ARHGAP42 is involved in regulation of blood pressure and its deficiency causes hypertension in murine models and human adults. This is the first report to link a homozygous stop-gain variant in ARHGAP42 with a chILD disorder, systemic hypertension, and immunological findings in a pediatric patient. Identification of additional chILD patients carrying ARHGAP42 mutations will better define its role in chILD.

Background The incidence of congenital hypothyroidism (CH) differs significantly among different ethnicities and regions, and early differentiation of transient CH is important to avoid unnecessary prolonged treatment with L-T4. Objective To investigate the incidence of CH based on the newborn screening program in Guangxi Zhuang Autonomous Region, China, and to analyze the predictors that might allow for an early differentiation between permanent (P) and transient (T) CH. Design and methods Data from newborn screening program over a seven-year period (January 2009 to January 2016) at Guangxi Maternal and Child Health Hospital are analyzed. Blood samples were collected on filter paper between 3 and 7 days after birth, and TSH level was measured by time-resolved fluorescence assay. Individuals with increased TSH (TSH ≥ 8 IU/L) levels detected by newborn screening were recalled for further evaluation. Serum TSH, FT3 and FT4 were determined by electrochemiluminescence assay using venous blood samples. Diagnosis of CH is based on elevated TSH levels (>10 IU/L) and decreased FT4 levels (4 levels were diagnosed as hyperthyrotropinemia. Permanent or transient CH was determined by using the results of thyroid function tests after temporary withdrawal of L-T4 therapy at approximately 2–3 years of age. Results Among 1,238,340 infants in the newborn screening program, 14,443 individuals were recalled for reevaluation (re-call rate 1.18%), 911 and 731 individuals were subsequently determined to have hyperthyrotropinemia and CH respectively; thus, a prevalence of 1:1359 and 1:1694 for hyperthyrotropinemia and CH. Of the 731 patients with CH, 161 patients were diagnosed with permanent CH (PCH), and 159 patients were diagnosed with transient CH (TCH), the other 411 patients are too young to determine their subtypes. Patients with PCH required an increasing dose of L-T4 during the first few years, whereas patients with TCH required a decreased dose of L-T4. The TSH levels at diagnosis and the dose of L-T4 used were significantly higher in PCH cases than in transient cases. The FT4 levels at diagnosis were significantly lower in PCH cases than in TCH cases. The TSH levels at diagnosis, FT4 levels at diagnosis and L-T4 doses at 90 days were evaluated as predictors for differentiating PCH and TCH, and their accuracy at their respective optimal cutoffs were determined to be 60.6%, 66.7% and 93.9%, respectively. Conclusions The CH incidence in Guangxi Zhuang Autonomous Region is slightly higher (1:1694) compared to the worldwide levels (1/2000–1/4000). The PCH and TCH ratio is close to 1; thus, the estimated PCH incidence is 1/3388, which is similar to reported worldwide average incidence (1/3000). The L-T4 dose required at 90 days (>30 μg/day) has the highest predictive value for PCH. Earlier differentiation of PCH and TCH helps to determine appropriate treatment course.

Background Gene variants have been reported to be associated with congenital hypothyroidism (CH), the purpose of this study was to analyze the mutation spectrum and prevalence of 12 known causative genes ( TSHR , PAX8 , NKX2 . 1 , NKX2 . 5 , FOXE1 , DUOX2 , TG , TPO , GLIS3 , NIS , SLC26A4 and DEHAL1 ) in CH in China. Methods Peripheral venous blood samples were collected from the patients. Genomic DNA was extracted from peripheral blood leukocytes. All exons and their exon-intron boundary sequences of the 12 known CH associated genes in 66 CH patients were screened by next-generation sequencing (NGS). Results NGS analysis of 12 known CH associated genes revealed that 32 patients (32/66, 48.5%) were detected to have at least one potentially functional variant. 21, 9, 1, 1, 1 and 1 patients were found to have potential pathogenic variants in DUOX2 , TG , PAX8 , SLC26A4 , TSHR and TPO genes, respectively. Novel variants included one DUOX2 and one TPO missense variants of unknown significance (VUS). Conclusion Our study expands the mutation spectrum of DUOX2 and TPO genes. 48.5% CH patients had at least one potential pathogenic variant. We found relatively high frequency of DUOX2 (31.8%) and TG (13.6%) mutations in our cohort.

People are taking up antioxidants in their daily diet and being exposed to a potential diesel exhaust particles (DEP)-containing environment. Thus it is important to study in vitro cellular responses when cells are exposed to DEP with or without antioxidant treatment. The investigation of DEP and resveratrol (RES) on cellular biophysical and biochemical changes is needed to better understand the mechanisms of DEP and RES in mammalian cells. A combination of two non-invasive techniques (atomic force microscopy, AFM, and Raman spectroscopy, RM) and multimodal tools were applied to evaluate the biophysical, biochemical alterations and cytokine, membrane potential and cell cycle of cells with or without RES pretreatment to different times of DEP exposure. AFM results indicated that RES protected cells from DEP-induced damage to cytoskeleton and cell architectures, and noted that RES treatments also attenuated DEP-induced alterations in cell elasticity and surface adhesion force over DEP incubation time. RM monitored the changes in characteristic Raman peak intensities of DNA and protein over the DEP exposure time for both RES and non-RES treated groups. The cytokine and chemokine changes quantified by Multiplex ELISA revealed that the inflammatory responses were enhanced with the increase in DEP exposure time and that RES enhanced the expression levels of cytokine and chemokine. This work demonstrated that significant biophysical and biochemical changes in cells might be relevant to early pathological changes induced by DEP damage. Copyright © 2016 John Wiley & Sons, Ltd.

Exenatide is known as the first marketed GLP-1 agonist for antidiabetic treatment, but it need twice injection a day because of its fast clearance. This work aims to prolong the half-life of exenatide by modified with novel lipid chain. Four optimized exenatide analogs named as Cys12-Exenatide (1-39)-NH2, Cys40-Exenatide (1-39)-NH2, Cys12-Tyr22-Gln24-Glu28-Arg35-Exenatide (1-39)-NH2 and Tyr22-Gln24-Glu28-Arg35-Cys40-Exenatide (1-39)-NH2 were selected and applied for conjugation. Then a series of evaluations including GLP-1R activation assay were conducted, conjugation C2 was selected for further investigation. Glucoregulatory and insulin secretion assay and hypoglycemic duration test were accessed and showed that C2 was capable of comparable insulinotropic activities and glucose-lowering abilities with those of liraglutide and exenatide. Cell protective effects in INS-1 cells confirmed that C2 had relatively protection effects. Meanwhile, once daily injection of C2 to STZ-induced diabetic mice achieved long-term beneficial effects on glucose tolerance, body weight and blood chemistry. Acute feeding studies were evaluated in DIO mice. These results suggested that C2 is a promising agent for further investigation of its potential to treat diabetes patients with obese.

Diesel exhaust particles (DEPs) are major air pollutants that lead to numerous human disorders, especially pulmonary diseases, partly through the induction of oxidative stress. Resveratrol is a polyphenol that ameliorates the production of reactive oxygen species (ROS) and delays aging-related processes. Herein we studied the cytoprotective effect of resveratrol on DEP-exposed human lung cells in a factorial experimental design. This work investigates biophysical features including cellular compositions and biomechanical properties, which were measured at the single-cell level using confocal Raman microspectroscopy (RM) and atomic force microscopy (AFM), respectively. Principal component analysis (PCA), hierarchical cluster analysis (HCA) and partial least square regression (PLS) analysis were applied to analyze Raman spectra with and without resveratrol protection. The health status of individual cells could be effectively predicted using an index derived from characteristic Raman spectral peak (e.g., 1006 cm−1) based on PLS model. AFM measurements indicated that cellular adhesion force was greatly reduced, while Young’s modulus was highly elevated in resveratrol treated DEP-exposed cells. Anti-oxidant resveratrol reduced DEP-induced ROS production and suppressed releases of several cytokines and chemokines. These findings suggest resveratrol may enhance resistance of human lung cells (e.g., SAEC) to air pollutants (e.g. DEPs).

Multidrug resistance (MDR) refers to the cross-resistance of cancer cells to one drug, accompanied by other drugs with different mechanisms and structures, which is one of the main obstacles of clinical chemotherapy. Overexpression of P-glycoprotein (P-gp) was an extensively studied cause of MDR. Therefore, inhibiting P-gp have become an important strategy to reverse MDR. In this study, two series of triazole-tetrahydroisoquinoline-core P-gp inhibitors were designed and synthesized. Among them, compound I-5 had a remarkable reversal activity of MDR activity and the preliminary mechanism study was also carried out. All the results proved that compound I-5 was considered as a promising P-gp-mediated MDR reversal candidate.

This paper is based on four terminal measuring way of measuring buoy battery internal resistance, in the case of certain current injection frequency and amplitude, by means of the voltage response signal acquisition on both ends of the battery, using the phase-locked amplifier technology, to extract useful signal amplification. Details the battery internal resistance monitoring system based on PSoC4 the design ideas and implementation of internal resistance of the high precision measurement process. The measured data in the Modbus protocol under the first machine.

To explore the genetic basis and pregnancy outcome of fetuses with urinary system anomalies.Ultrasonographic features, genetic testing and pregnancy outcomes of 337 fetuses with urinary system anomalies identified by prenatal ultrasonograhy were collected for analysis.Ultrasonographic features of the fetuses were mainly characterized by hydronephrosis or hydronephrosis, polycystic kidney disease, and renal dysplasia. Thirty four fetuses (10.1%) were found to harbor a genetic defect, including 14 numerical chromosomal disorders, 10 structural chromosomal aberrations, and 10 pathogenic copy number variations (CNVs). In 31 cases, the parents elected induced labor. For the 303 fetuses with negative findings, 142 were born by spontaneous delivery or Caesarean section, 48 cases underwent induced labor, 1 case had miscarriage, and the remaining 112 cases had unknown or missed pregnancy outcomes.Hydronephrosis or hydronephrosis, polycystic kidney disease, and renal dysplasia are the most common findings among fetuses with urinary system anomalies. Approximately 10.1% of such fetuses are positive by genetic testing.