Search

The stability of grid-connected inverters is very sensitive to varying grid impedance, especially in the weak grid condition. In this paper, based on the Lyapunov method and with the micro-grid impedance identification, an active damping adaptive control strategy is proposed to guarantee local asymptotic stability for an LCL inverter system. First, using the backstepping design and taking the state variable errors as new variables, an appropriate Lyapunov function is constructed, so that the asymptotic stability control law can be obtained. Then, with this asymptotic stability controller, taking the varying impedance into account, an adaptive controller is developed using the Lyapunov direct method. Hence, the controller presented here can assure asymptotic stability, the system performance can also be improved instantly according to the adaptive control, and the expected stability and performance can also be achieved. Finally, the feasibility of the proposed control strategy was verified via a simulation and an experiment.

This paper presents a supply-insensitive low-power quadrature local oscillation (LO) generator based on the current-reused voltage-controlled oscillator (VCO) and divide-by-two frequency divider (FD). By utilizing the mutual power-supply rejection (M-PSR) technique, a voltage regulator is embedded into the FD to provide a supply-insensitive voltage for VCO. Meanwhile, the feedback loop provides a supply-insensitive current and time constant compensation for FD. The M-PSR technique does not require extra voltage headroom, thus the proposed quadrature LO generator can work under the supply of 0.9 V. A prototype of the proposed quadrature LO generator is implemented in a 28-nm CMOS process. Measurement results indicate that the LO generator achieves a phase noise of −110.5 dBc/Hz@1MHz at the carrier of 5.9 GHz and the power consumption is 1.8 mW. This work has a competitive figure of merit in supply sensitivity or in area (FOMss or FOMa respectively) among the state-of-the-art works.

Bloodstream infections (BSIs) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) are potentially life-threatening and an urgent threat to public health. The present study aims to clarify the characteristics of carbapenemase-encoding and virulent plasmids, and their interactions with the host bacterium. A total of 425 Kp isolates were collected from the blood of BSI patients from nine Chinese hospitals, between 2005 and 2019. Integrated epidemiological and genomic data showed that ST11 and ST307 Kp isolates were associated with nosocomial outbreak and transmission. Comparative analysis of 147 Kp genomes and 39 completely assembled chromosomes revealed extensive interruption of acrR by ISKpn26 in all Kp carbapenemase-2 (KPC-2)-producing ST11 Kp isolates, leading to activation of the AcrAB-Tolc multidrug efflux pump and a subsequent reduction in susceptibility to the last-resort antibiotic tigecycline and six other antibiotics. We described 29 KPC-2 plasmids showing diverse structures, two virulence plasmids in two KPC-2-producing Kp, and two novel multidrug-resistant (MDR)-virulent plasmids. This study revealed a multifactorial impact of KPC-2 plasmid on Kp, which may be associated with nosocomial dissemination of MDR isolates.

Photocatalytic technology, with features of wide applicability, mild reaction conditions and sunlight availability, satisfies the requirements of “green chemistry”. As the star photoanode material for photoelectrochemical catalysis, WO3 has a suitable band gap of 2.8 eV and a strong oxidation capacity, as well as displaying great potential in organic wastewater degradation. However, its performance is usually hindered by competition with water oxidation to generate peroxides, rapid charge complexation caused by surface defect sites, and so on. Herein, WO3 films modified with cobalt–phosphate (Co-Pi/WO3) film were prepared and involved in photocatalytic organic wastewater degradation. A degradation rate constant of 0.63311 h−1 was obtained for Co-Pi/WO3, which was much higher than that of WO3, 10.23 times that of direct photocatalysis (DP) and 23.99 times that of electrocatalysis (EC). After three cycles of degradation, the film can maintain a relatively good level of stability and a degradation efficiency of 93.79%.

The formation and development of chloroplasts play a vital role in the breeding of high-yield rice (Oryza sativa L.). Porphobilinogen deaminases (PBGDs) act in the early stage of chlorophyll and heme biosynthesis. However, the role of PBGDs in chloroplast development and chlorophyll production remains elusive in rice. Here, we identified the spotted leaf 42 (spl42) mutant, which exhibited a reddish-brown spotted leaf phenotype. The mutant showed a significantly lower chlorophyll content, abnormal thylakoid morphology, and elevated activities of reactive oxygen species (ROS)-scavenging enzymes. Consistently, multiple genes related to chloroplast development and chlorophyll biosynthesis were significantly down-regulated, whereas many genes involved in leaf senescence, ROS production, and defense responses were upregulated in the spl42 mutant. Map-based cloning revealed that SPL42 encodes a PBGD. A C-to-T base substitution occurred in spl42, resulting in an amino acid change and significantly reduced PBGD enzyme activity. SPL42 targets to the chloroplast and interacts with the multiple organelle RNA editing factors (MORFs) OsMORF8-1 and OsMORF8-2 to affect RNA editing. The identification and characterization of spl42 helps in elucidating the molecular mechanisms associated with chlorophyll synthesis and RNA editing in rice.

After the official launch of China’s unified carbon market, the potential for carbon emission reduction is huge. The pilot regional markets urgently need to be connected with the national carbon market to form a regional synergy and linkage mechanism and further promote the development of a unified carbon market. Spillover effects can be used to analyze the interaction between multiple markets. In this context, this study focuses on the overall spillover relationship among regional carbon trading markets. Using the VAR-GARCH-BEKK model and social network analysis (SNA), this study empirically analyzes the mean spillover effect and volatility spillover effect of regional carbon markets, and it establishes a spillover network between markets. The results show that the spillover effect of China’s regional carbon markets is widespread. Among them, the mean spillover effect is weak, and the impact period is short;. The volatility spillover effect is strong and has various directions; the spillover network connection between regional carbon markets is strong, but the spillover intensity is weak. Spillover effects will spread to the overall carbon market through information spillover paths and risk spillover paths. The stronger spillover effect and the stronger linkage between markets can bring more resource integration and unified supervision. Finally, we put forward policy recommendations, such as improving the carbon market mechanism and enhancing the maturity of carbon market development, increasing the participation and activity of the carbon market to encourage more participants to join the carbon market, improving the institutional system of the carbon market, and effectively supervising the process of information and risk spillover between carbon markets.

Abstract Understanding the role of climate changes and geography as drivers of population divergence and speciation is a long‐standing goal of evolutionary biology and can inform conservation. In this study, we used restriction site‐associated DNA sequencing (RAD‐seq) to evaluate genetic diversity, population structure, and infer demographic history of the endangered tree, Phoebe zhennan which is distributed around the Sichuan Basin. Genomic patterns revealed two distinct clusters, each largely confined to the West and East. Despite sympatry of the two genomic clusters at some sites, individuals show little or no evidence of genomic introgression. Demographic modeling supported an initial divergence time between the West and East lineages at ~15.08 Ma with further diversification within the West lineage at ~7.12 Ma. These times largely coincide with the two independent intensifications of the East Asian monsoon that were initiated during the middle (Langhian) and late Miocene (Messinian), respectively. These results suggest that the Miocene intensification phases of the East Asian monsoon played a pivotal role in shaping the current landscape‐level patterns of genetic diversity within P. zhennan, as has been found for the interspecific divergence of other subtropical Chinese plants. Based on isolation‐by‐distance and species distribution modeling, we hypothesize that P. zhennan followed a ring diversification which was facilitated by the Sichuan Basin acting as barrier to gene flow. In situ and ex situ conservation management plans should consider the results obtained in this study to help secure the future of this beautiful and culturally significant endangered tree.

Neonatal hypoxic-ischemic brain damage (HIBD) often results in various neurological deficits. Among them, a common, yet often neglected, symptom is circadian rhythm disorders. Previous studies revealed that the occurrence of cysts in the pineal gland, an organ known to regulate circadian rhythm, is associated with circadian problems in children with HIBD. However, the underlying mechanisms of pineal dependent dysfunctions post HIBD remain largely elusive. Here, by performing 10x single cell RNA sequencing, we firstly molecularly identified distinct pineal cell types and explored their transcriptome changes at single cell level at 24 and 72 h post neonatal HIBD. Bioinformatic analysis of cell prioritization showed that both subtypes of pinealocytes, the predominant component of the pineal gland, were mostly affected. We then went further to investigate how distinct pineal cell types responded to neonatal HIBD. Within pinealocytes, we revealed a molecularly defined β to α subtype conversion induced by neonatal HIBD. Within astrocytes, we discovered that all three subtypes responded to neonatal HIBD, with differential expression of reactive astrocytes markers. Two subtypes of microglia cells were both activated by HIBD, marked by up-regulation of Ccl3. Notably, microglia cells showed substantial reduction at 72 h post HIBD. Further investigation revealed that pyroptosis preferentially occurred in pineal microglia through NLRP3-Caspase-1-GSDMD signaling pathway. Taken together, our results delineated temporal changes of molecular and cellular events occurring in the pineal gland following neonatal HIBD. By revealing pyroptosis in the pineal gland, our study also provided potential therapeutic targets for preventing extravasation of pineal pathology and thus improving circadian rhythm dysfunction in neonates with HIBD.

Objective: We introduced meta-analysis and trial sequential analysis (TSA) into the evidence-based evaluation of the efficacy of the Mongolian medicine formula Gurigumu for liver diseases as an evidence-based medicine approach to identify the problems in the modernization process of Mongolian medicine. Methods: Randomized controlled trials of Gurigumu formulae for liver diseases were collected from several bibliographic databases by combining subject words and free words. The Cochrane Collaboration Network Bias Risk Assessment Tool was used to evaluate the quality of the studies included in the analysis. RevMan software (version 5.3) was used to evaluate the total effective rate; other outcome indicators including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), and triglyceride (TG) levels underwent meta-analysis and subgroup analysis before and after treatment. TSA was used for the sequential analysis of total efficiency to verify the stability of the results. Results: Fifteen randomized controlled trials involving 1188 patients were included in the analysis. The results of the meta-analysis showed that the Gurigumu formulae had potential effects for liver disease in the total effective rate, ALT, AST, TG, and TC. Further, the total effective rate was were found to be stable via TSA verification. Conclusion: This study determined the potential impact of Gurigumu formulae on liver diseases. Through the process of evidence-based research, key problems in the experimental design of Mongolian medicine and in the clinical methods were identified. The results introduce a new direction for the construction and improvement of a modern Mongolian medical system.

An image-based gradation calculation method considering crushed stone morphology is proposed in this paper. Eight kinds of crushed stones are prepared to figure out the effect of the particle shape on the gradation. All particles are pictured, and the photos are processed to obtain particle shape indices by using the image-based method. A minimum Feret diameter analysis method is used, which can reflect the influence of the particle shape. Then, the paper proposes a developed overall regularity to describe the morphology of particles, which is calculated by the weight of three shape indices: aspect ratio, convexity, and sphericity. The developed overall regularity is applied on gradation curve equations to provide an image-based gradation calculation method. And the provided method is validated to well fit the actual case. Furthermore, the method is also applied on two examples of gradation designation and the result proves to be feasible and practicable.

Since impacts of rail transit on urban industries and space most obviously appear in metro station areas, correlations between the spatial distribution of producer services and urban built environment in metro station areas are studied in Xi’an, China. At first, the scope determining methods of a metro station area were separately proposed for both single-line station and multiline transfer station based on their construction and transportation modes. Then, when the producer services were divided into 6 categories of business, POI numbers of enterprises of each category in metro station areas were collected and weighted to calculate the distribution intensity for categories. Finally, on condition that the urban built environment of a metro station area included job and residence space, outdoor activity space, and municipal road space, correlation performances between the distribution intensity of categories and indexes representing 3 space elements of the built environment were calculated through second-order partial correlation analysis, while the corresponding mechanisms of correlations were explained too. The main conclusions of this paper indicate that there are significant positive correlations between the distribution intensity and the diversity index of job and residence space for most categories, whereas significant negative correlations between it and the openness index of outdoor activity space for most categories. Moreover, positive but weak correlations were appeared between the distribution intensity and the street network density index of municipal road space only for categories of intermediary consulting and leasing.

In this paper, we completely characterize the reducing subspaces for Tφa on weighted Hardy space ℋω2D2 under three assumptions on ω, where φa=zk+az¯l, k,l∈ℕ2, k≠l, and a∈0,1. It is shown that the coefficient a∈0,1 does not affect the reducing subspaces for Tφa. We also prove that, for every δ>0, weighted Dirichlet space Dδ2D2 is a weighted Hardy space which satisfies these assumptions. As an application, we describe the reducing subspaces for Tφa on Dδ2D2 and get the structure of commutant algebra V∗Tφa.

In order to improve the high-temperature deformation resistance and creep resistance of TiAl-based alloys, cold crucible directional solidification (CCDS) technology was employed. A β-type TiAl-based alloy with the nominal composition of Ti44Al6Nb1Cr2V was prepared using the optimized CCDS parameters of 45 kW input power and 0.5 mm·min-1 solidification rate. Thermo-compression testing was utilized to evaluate the hightemperature deformation resistance and creep resistance of the CCDS Ti44Al6Nb1Cr2V alloy. Results show that the CCDS Ti44Al6Nb1Cr2V alloy billets contain aligned columnar grains and a high percentage of small-angle lamellae. Thermo-compression testing results in the radial direction of the CCDS alloy show a much higher peak stress than other reported results in similar conditions. The much higher hardening exponent and deformation activation energy are obtained, corresponding to the excellent high-temperature deformation resistance and creep resistance, which are because of the hard-oriented grains, weaker stress-strain coordination capability of lamella structure and relatively more hysteretic dynamic recrystallization. Thermo-compression testing results in the longitudinal direction of the CCDS Ti44Al6Nb1Cr2V alloy show the much higher peak stress than that in the radial direction, indicating the better high-temperature deformation resistance and creep resistance attributed to the hard-oriented lamellae in this condition.

Abstract Background Listeriosis is a rare but severe foodborne infectious disease. Perinatal listeriosis is often associated with septicemia, central nervous system (CNS) infection, and serious adverse pregnancy outcomes (miscarriage and neonate death). Here we report the characteristics and outcomes of perinatal listeriosis cases treated over 6 years at Beijing Obstetrics and Gynecology Hospital (BOGH), the largest maternity hospital in China. Methods We retrospectively reviewed the records of laboratory-confirmed, pregnancy-associated listeriosis cases treated from January 1, 2013 to December 31, 2018. The clinical manifestations, laboratory results, perinatal complications and outcomes (post-natal follow-up of 6 months) were investigated. Results In BOGH, 12 perinatal listeriosis cases were diagnosed based on Listeria monocytogenes positive culture, including 10 single pregnancies and 2 twin pregnancies. The corresponding incidence of pregnancy-associated listeriosis was 13.7/100,000 deliveries. Among those cases, four pregnant women and four newborns had septicemia, and two of the neonates with septicemia also suffered CNS infection. All the maternal patients recovered. Two inevitable miscarriages and four fetal stillbirths occurred. Of the eight delivered newborns, six survived, and two died within 2 days from birth. None of the survivors had neurological sequelae during a 6-month follow-up. The overall feto-neonatal fatality rate was 57.1%; notably, this rate was 100% for infections occurring during the second trimester of pregnancy and only 14.3% for those occurring in the third trimester. Conclusions Perinatal listeriosis is associated with high feto-neonatal mortality, and thus, a public health concern. Additional large-scale studies are needed to strengthen the epidemiological understanding of listeriosis in China.

Abstract Background A prompt diagnosis of HIE remains a challenge clinically. This study aimed to identify potential biomarkers of neonatal hypoxic-ischemic encephalopathy (HIE) via a novel proteomic approach, the isobaric tags for absolute and relative quantification (iTRAQ) method. Methods Blood samples were collected from neonates with mild (n = 4), moderate (n = 4), or severe (n = 4) HIE who were admitted to the neonatal intensive care unit of Children’s Hospital of Soochow University between Oct 2015 and Oct 2017. iTRAQ was performed in HIE patients and healthy controls (n = 4). Bioinformatics analyses including Gene Ontology and KEGG pathway enrichment analysis were performed to evaluate the potential features and capabilities of the identified differentially expressed proteins. Results A total of 51 commonly differentially expressed proteins were identified among the comparisons between mild, moderate, and severe HIE as well as healthy controls. Haptoglobin (HP) and S100A8 were most significantly up-regulated in patients with HIE and further validated via real-time PCR and western blotting. The differentially expressed proteins represented multiple biological processes, cellular components and molecular functions and were markedly enriched in complement and coagulation cascades. Conclusions HP and S100A8 may serve as a potential biomarker for neonatal HIE and reflects the severity of HIE. The complement and coagulation cascades play crucial roles in the development of neonatal HIE.

Underground seismic exploration is a technical assurance for the geological transparency of the mining face. However, seismic exploration with explosive seismic source has shortcomings such as acquisition difficulties and serious safety hazards. Besides, dynamic detection of the mining face with explosive source is challenging. To this end, the study proposes a supercritical CO2 source based on the underground seismic geological condition of the roadway. The phase change blasting mechanism of the supercritical source was revealed, and the equivalent energy of the source was calculated. Additionally, a field test was also carried out. The results show that the seismic signals of the CO2 source have clear P-waves, S-waves, and channel waves; the signal excited by the source has strong energy and rich frequency bands; the signal-to-noise ratio of single CO2 source is high; and the attenuation images of transmitted channel wave excited by the source shows high resolution and the result is consistent with field validation data. CO2 source can be used as a new source of underground in-seam seismic exploration and it also helps in reducing the dependence of explosive seismic source. Besides, the study can achieve early warnings of dynamic geological disasters in the working face and has the advantages of high efficiency, safe, low cost, and environmentally friendly. Keywords: Seismic exploration, Seismic source, CO2 source, Spectrum, Transmitted channel wave

Abstract The autosomal recessive form of primary microcephaly (MCPH) is a rare disorder characterized by microcephaly with variable degree of intellectual disability. WDR62 has been reported as the second causative gene of MCPH2. West syndrome is a severe epilepsy syndrome composed of the triad of spasms, hypsarrhythmia, and mental retardation. There are limited clinical reports regarding WDR62 mutation and West syndrome. Here we report a boy who was identified with WDR62 mutation and was followed up from age 3 months to 5 months and 14 days. He had the first seizure as the classic epileptic spasm at the age of 3 months. Psychomotor retardation was noted before the seizure occurred. The head circumference was 38.5 cm (SD 2.6) when he was 4 months old, no dysmorphic facial features were observed. He couldn’t support his head steadily or turn over. He was able to laugh when tricked by the parents, but couldn’t track the sound and light. At the early stage, the electroencephalogram showed multifocal discharges, which evolved into hypsarrhythmia one month later, and brain MRI showed developmental malformation of cerebral gyrus. Two heterozygous mutations were identified in WDR62 by whole exome sequencing c.1535G > A, p.R512Q and c.2618dupT, p.K874Qfs*40. The patient was administrated with oral sodium valproate, nitrazepam, intramuscular adrenocorticotropic hormone for 2 weeks, and followed by prednisone, levetiracetam, topiramate and vigabatrin. However, there was no significant improvement on the seizure control after these treatments. According to the genetic report and clinical manifestation, we speculated that the WDR62 compound heterozygous mutation is responsible for the serious clinical phenotype.

Abstract Background Necrotizing enterocolitis (NEC) is the leading cause of death among preterm infants born at

An efficient intracavity-frequency-doubled singly resonant optical parametric oscillator (SR-OPO), pumped by a high-maturity 532 nm laser, tunable in the yellow wavelength region is demonstrated. An elaborate V-shaped idler cavity design is employed for a potassium titanyl phosphate (KTP) OPO nonlinear crystal to achieve a 5.06 W idler output at 1151.2 nm at a 10 kHz pulse repetition frequency. Using a second KTP crystal to intracavity frequency double the circulating idler wave, a 2.37 W yellow output at 575.6 nm is generated. High optical conversion efficiency (25.4% and 11.2%), 0.5 nm spectral linewidth, and 32 ns pulse duration of the 575.6 nm yellow output are achieved.

A highly-efficient tunable 1.6 μm MgO:PPLN-OPO, which we believe to be the first one pumped by a diode-end-pumped Raman laser, is demonstrated. A good beam-quality of actively Q-switched Nd:YVO4/YVO4 Raman laser at 1176 nm and a good mode matching of the whole system resulted in a high-performance OPO. The highest Raman-to-signal conversion efficiency was 49.5% at 1638.8 nm when the incident Raman power was 2 W. The maximum output power of 3.2 W at 1663.5 nm with the pulse-width of 2.85 ns was obtained pumped by 7.57-W Raman laser. Meanwhile, the linewidth was less than 0.3 nm and a high beam quality with M2 factor of 1.92 was obtained.

An actively Q-switched all-solid-state YVO4 Raman laser, which used a 885-nm side-pumped Nd:YAG laser as the fundamental wavelength and delivered yellow output, is demonstrated. An in-band pump scheme is adopted to mitigate the thermal effects in the laser crystal and a Z-shaped laser cavity is used to compensate thermal lensing further. By intracavity frequency doubling of the Stokes wave with KTP crystal, 13.7-W yellow output at a wavelength of 588 nm, with a pulse repletion frequency of 10 kHz, was obtained under a diode pump power of 233 W. Additionally, single-pulse energy was 1.37 mJ with the pulse-width of 12.5 ns, corresponding to a peak power of 110 kW.

We present results of numerical simulations on the photoelectron momentum distributions of the p-orbital electrons of neon atoms ionized by a pair of time-delayed and oppositely circularly polarized intense laser pulses. Deploying the strong-field theory, we can readily produce vortex-shaped momentum distributions. Similarity and disparity in the vortex patterns between the neon and hydrogen atoms are observed. The optical Stark effect is found to induce distortions in the vortex momentum distributions, which are quantitatively described by introducing several physical quantities. Among these quantities, the autocorrelation parameter turns out to be the most sensitive probe for extremely weak Stark effect. The nonlinear phase induced by the optical Stark effect deciphers the distortions of the vortex momentum distributions.

In recent years, with the development of machine learning, especially after the rise of deep learning, time series clustering has been proven to effectively provide useful information in cloud computing and big data. However, many modern clustering algorithms are difficult to mine the complex features of time series, which is important for further analysis. Convolutional neural network provides powerful feature extraction capabilities and has excellent performance in classification tasks, but it is hard to be applied to clustering. Therefore, a similarity measurement method based on convolutional neural networks is proposed. This algorithm converts the number of output changes of the convolutional neural network in the same direction into the similarity of time series, so that the convolutional neural network can mine unlabeled data features in the clustering process. Especially by preferentially collecting a small amount of high similarity data to create labels, a classification algorithm based on the convolutional neural network can be used to assist clustering. The effectiveness of the proposed algorithm is proved by extensive experiments on the UCR time series datasets, and the experimental results show that its superior performance than other leading methods. Compared with other clustering algorithms based on deep networks, the proposed algorithm can output intermediate variables, and visually explain the principle of the algorithm. The application of financial stock linkage analysis provides an auxiliary mechanism for investment decision-making.

Transient receptor potential melastatin 2 (TRPM2) is an important ion channel that represents a potential target for treating injury caused by cerebral ischemia. However, it is unclear whether reducing TRPM2 expression can help repair cerebral injury, and if so what the mechanism underlying this process involves. This study investigated the protective effect of reducing TRPM2 expression on pheochromocytoma (PC12) cells injured by oxygen-glucose deprivation (OGD). PC12 cells were transfected with plasmid encoding TRPM2 shRNAS, then subjected to OGD by incubation in glucose-free medium under hypoxic conditions for 8 hours, after which the cells were allowed to reoxygenate for 24 hours. Apoptotic cells, mitochondrial membrane potentials, reactive oxygen species levels, and cellular calcium levels were detected using flow cytometry. The relative expression of C-X-C motif chemokine ligand 2 (CXCL2), NACHT, LRR, and PYD domain–containing protein 3 (NALP3), and caspase-1 were detected using fluorescence-based quantitative reverse transcription-polymerase chain reaction and western blotting. The rates of apoptosis, mitochondrial membrane potentials, reactive oxygen species levels, and cellular calcium levels in the TRPM2-shRNA + OGD group were lower than those observed in the OGD group. Taken together, these results suggest that TRPM2 knockdown reduces OGD-induced neuronal injury, potentially by inhibiting apoptosis and reducing oxidative stress levels, mitochondrial membrane potentials, intracellular calcium concentrations, and NLRP3 inflammasome activation.

Traditional Chinese Medicine (TCM) has been shown to be efficacious in treating leukemia for thousands of years. It has been shown that Shen Qi Sha Bai Decoction (SQSBD) has been extensively used in the treatment of acute myeloid leukemia (AML). However, the mechanism of SQSBD in treating AML remains unclear. In this study, we employed network pharmacology to analyze the potential active components and elucidate molecular mechanism of SQSBD in treating AML. A total of 268 active components were identified from SQSBD, among which 9 key components (Quercetin, luteolin, kaempferol, licochalcone A, formononetin, wogonin, β-sitosterol, oroxylin A, naringenin, and baicalein) were hit by the 6 hub targets (CDK1, MAPK1, JUN, PCNA, HSB1, STAT3) associated with leukemia. Molecular docking showed that two core active components, quercetin and licochalcone A, exhibited the highest component-like properties (DL), and could bind well to CDK1 and MAPK1 protein. The experimental validation of these two components showed that quercetin inhibited cell growth through CDK1 dephosphorylation-mediated cell cycle arrest at G2/M phase in human AML U937 and HL60 cells, and licochalcone A induced cell differentiation in these leukemia cells via activation of MAPK1 and upregulation of CD11b. All these results indicate that SQSBD is effective in the treatment of AML, and quercetin and licochalcone A are the major candidate compounds for AML treatment.

Hookworm is one type of soil-transmitted helminth, which could exert an anti-inflammatory effect in human or animal host, which provides a beneficial possibility for the discovery of inflammatory-related disease interventions. The identification of hookworm-derived anti-inflammatory molecules is urgently needed for future translational research. The emergence of metabolomics has become a powerful approach to comprehensively characterize metabolic alterations in recent times. Herein, excretory and secretory products (ESPs) were collected from cultured adult worm, while small intestinal contents were obtained from Nippostrongylus brasiliensis (N. brasiliensis, Nb)-infected mice. Through ultra-high-performance liquid chromatography coupled with mass spectrometry (UHPLC-MS) platform, metabolomics analysis was used to explore the identification of anti-inflammatory molecules. Out of 45 differential metabolites that were discovered from ESPs, 10 of them showed potential anti-inflammatory properties, which could be subclassed into amino acids, furanocoumarins, linear diarylheptanoids, gamma butyrolactones, and alpha-keto acids. In terms of intestinal contents that were derived from N. brasiliensis-infected mice, 14 out of 301 differential metabolites were discovered to demonstrate anti-inflammatory effects, with possible subclassification into amino acids, benzylisoquinolines, quaternary ammonium salts, pyrimidines, pregnane steroids, purines, biphenyls, and glycerophosphocholines. Furthermore, nine of the differential metabolites appeared both in ESPs and infected intestinal contents, wherein four were proven to show anti-inflammation properties, namely, L-glutamine, glutamine (Gln), pyruvate, and alanine-Gln (Ala-Gln). In summary, we have provided a method for the identification and analysis of parasite-derived molecules with potential anti-inflammatory properties in the present study. This array of anti-inflammatory metabolites could provide clues for future evaluation and translational study of these anti-inflammatory molecules.

Mangrove-derived endophytes are rich in bioactive secondary metabolites with a variety of biological activities. Recently, a fungus Pseudofusicoccum sp. J003 was first isolated by our research group from mangrove species Sonneratia apetala Buch.-Ham. The subsequent chemical investigation of the methanol extract of the culture broth of this strain has led to the isolation of a new sesquiterpenoid named acorenone C (1), two alkaloids (2–3), four phenolic compounds (4–7), and four steroid derivatives (8–11). The new structure of 1 was established by extensive spectroscopic analysis, including 1D, 2D NMR spectroscopy, and HRESIMS. Its absolute configuration was elucidated by experimental ECD and ECD calculation. The in vitro AChE inhibitory, anti-inflammatory, and cytotoxic activities of the selected compounds were evaluated. The results showed that compound 1 showed mild AChE inhibitory activity, with an inhibition rate of 23.34% at the concentration of 50 μM. Compound 9 exerted a significant inhibitory effect against nitric oxide (NO) production in LPS-stimulated RAW 264.7 mouse macrophages, with an inhibition rate of 72.89% at the concentration of 25 μM, better than that of positive control L-NMMA. Compound 9 also displayed obvious inhibition effects on the growth of two human tumor cell lines, HL-60 and SW480 (inhibition rates 98.68 ± 0.97% and 60.40 ± 4.51%, respectively). The antimicrobial activities of the compounds (1–11) against Escherichia coli, Bacillus subtilis, Staphylococcus aureus, and Pseudomonas aeruginosa were also tested; however, none of them showed antimicrobial activities.

An efficient MgO: PPLN singly resonant optical parametric oscillator (SROPO) pumped by a Nd: YVO4/YVO4 2nd-Stokes Raman laser at 1313 nm was demonstrated. The maximum conversion efficiency of 54.8% was obtained at the pump power of 1.16 W, which was higher than that of the OPO pumped by 1st-Stokes Raman laser at 1176 nm, due to the better beam quality, narrower line width and pulse width of the 2nd-Stokes Raman laser. The maximum output power of 1.57 W at 1855.5 nm with the pulse repetition frequency (PRF) of 40 kHz was achieved under the pump power of 4 W. The corresponding conversion efficiency was 39.7%, with the pulse width of 2.53 ns, linewidth of 0.45 nm, and M2 of 1.87. Meanwhile, with the crystal period ranging from 27.91 to 29.98 μm, the tuning range of signal wave was 1778.6–1861.8 nm.

Toxoplasma gondii, an opportunistic protozoan, infects one-third of people worldwide and could lead to serious outcomes in immunodeficient or immunocompromised populations. The present study aimed to investigate the prevalence and risk factors for T. gondii infection among high-risk populations in Jiangsu Province, eastern China. We conducted a cross-sectional survey among 4 categories of populations in 13 prefectures including HIV/AIDS patients, livestock breeding/processing (B/P) staff, pregnant women, and cancer patients. We detected specific immunoglobulin G and M (IgG and IgM) levels for each participant using enzyme-linked immunosorbent assay (ELISA) and asked to complete a questionnaire for each participant that covered sociodemographic information as well as the basic knowledge of attitudes toward and the practices for the prevention of toxoplasmosis. A total of 5231 participants distributed across 13 prefecture-level cities was surveyed, including 2455 males and 2776 females. Total seropositivity rate in each population category was as follows: 9.08% (HIV/AIDS patients), 11.65% (livestock B/P staff), 5.50% (pregnant women), and 12.89% (cancer patients). We detected IgM positivity in HIV/AIDS patients (0.47%, 6/1289), livestock B/P staff (0.08%, 1/1330), and cancer patients (0.46%, 6/1303) but not in pregnant women. Further, we detected IgM+IgG positivity only in cancer patients (0.31%, 4/1303). The seropositivity rate for pregnant women was significantly lower, while cancer patients were significantly higher. Higher educational levels were associated with lower seropositivity rates for T. gondii infection. High seropositivity rates were associated with long period of HIV infection among HIV/AIDS patients, frequent contact with livestock among livestock breeding/processing staff and male older patients among cancer patients, respectively. Analysis of practices across all participants showed that frequent contact with pets in everyday life or using the same cutting board for both raw and cooked foods leads to higher seropositivity rates. Therefore, we obtained the seroprevalence and risk factors of toxoplasmosis among high-risk populations in Jiangsu Province which could provide evidence for the implementation of control measures in the near future.

Due to the lack of places to employ communication infrastructures, there are many coverage blind zones in maritime communication networks. Benefiting from the high flexibility and maneuverability, unmanned aerial vehicles (UAVs) have been proposed as a promising method to provide broadband maritime coverage for these blind zones. In this paper, a multi-UAV-enabled maritime communication model is proposed, where UAVs are deployed to provide the transmission service for maritime users. To improve the performance of the maritime communication systems, an optimization problem is formulated to maximize the minimum average throughput among all users by jointly optimizing the user association, power allocation, and UAV trajectory. To derive the solutions with a low computational complexity, we decompose this problem into three subproblems, namely user association optimization, power allocation optimization, and UAV trajectory optimization. Then, a joint iterative algorithm is developed to achieve the solutions based on the successive convex approximation and interior-point methods. Extensive simulation results validate the effectiveness of the proposed algorithm and demonstrate that UAVs can be used to enhance the maritime coverage.

Atherosclerosis (AS) is a dominant and growing cause of death and disability worldwide that involves inflammation from its inception to the emergence of complications. Studies have demonstrated that intervention with helminth infections or derived products could modulate the host immune response and effectively prevent or mitigate the onset and progression of inflammation-related diseases. Therefore, to understand the molecular mechanisms underlying the development of atherosclerosis, we intervened in ApoE-/- mice maintained on a high-fat diet with Nippostrongylus brasiliensis (N. brasiliensis) infection and immunized with its derived products. We found that N. brasiliensis infection and its derived proteins had suitable protective effects both in the initial and progressive stages of atherosclerosis, effectively reducing aortic arch plaque areas and liver lipid contents and downregulating serum LDL levels, which may be associated with the significant upregulation of serum anti-inflammatory cytokines (IL-10 and IL-4) and the down-regulation of proinflammatory cytokines (TNF-α and IFN-γ) in the serum. In conclusion, these data highlighted the effective regulatory role of N. brasiliensis and its derived proteins in the development and progression of atherosclerosis. This could provide a promising new avenue for the prevention and treatment of atherosclerosis.

To date, immune checkpoint inhibitors have been successively approved and widely used in clinical cancer treatments, however, the overall response rates are very low and almost all cancer patients eventually progressed to drug resistance, this is mainly due to the intricate tumor microenvironment and immune escape mechanisms of cancer cells. One of the main key mechanisms leading to the evasion of immune attack is the presence of the immunosuppressive microenvironment within tumors. Recently, several studies illustrated that triggering receptor expressed on myeloid cells-2 (TREM2), a transmembrane receptor of the immunoglobulin superfamily, was a crucial pathology-induced immune signaling hub, and it played a vital negative role in antitumor immunity, such as inhibiting the proliferation of T cells. Here, we reviewed the recent advances in the study of TREM2, especially focused on its regulation of tumor-related immune signaling pathways and its role as a novel target in cancer immunotherapy.

Purpose: This study aimed to describe the clinical and laboratory characteristics and the parameters of the respiratory mechanics of mechanically ventilated patients with confirmed COVID-19 pneumonia and to clarify the risk or protective factors for weaning failure.Methods: Patients diagnosed with COVID-19 pneumonia were selected from the special intensive care unit (ICU) of the Sino-French New City Branch of Tong Ji Hospital, Wuhan, and treated by the National Medical Team Work. They were divided into successful weaning (SW) group (N = 15) and unsuccessful weaning (USW) group (N = 18) according to the prognosis. Information of these patients was analyzed.Results: There were 33 patients included in this study. Patients in the USW group were associated with a poor outcome; the 28-day mortality rate was higher than in the SW group (86.7 vs. 16.7% p < 0.001). By comparison, we found that the initial plateau pressure (Pplat) and driving pressure (DP) of the USW group were higher and that compliance was lower than that of the SW group, but there was no difference between positive end-expiratory pressure (PEEP), partial pressure of carbon dioxide (PCO2), and the ratio of partial pressure arterial oxygen and fraction of inspired oxygen (P/F ratio). Comparing the worst respiratory mechanics parameters of the two groups, the results of the Pplat, DP, compliance, and PEEP were the same as the initial data. The PCO2 of the USW group was higher, while the P/F ratio was lower. A logistic regression analysis suggested that higher Pplat might be an independent risk factor and that higher compliance and lower DP might be protective factors for weaning failure of invasive mechanically ventilated patients with COVID-19 pneumonia.Conclusions: Patients with USW were associated with a poor outcome, higher Pplat might be a risk factor, and a higher compliance and a lower DP might be protective factors for the weaning failure of ventilated COVID-19 patients. Mechanical ventilation settings will affect the patient's prognosis.

Purpose: A phenotype of COVID-19 ARDS patients with extremely low compliance and refractory hypercapnia was found in our ICU. In the context of limited number of ECMO machines, feasibility of a low-flow extracorporeal carbon dioxide removal (ECCO2R) based on the renal replacement therapy (RRT) platform in these patients was assessed.Methods: Single-center, prospective study. Refractory hypercapnia patients with COVID-19-associated ARDS were included and divided into the adjusted group and unadjusted group according to the level of PaCO2 after the application of the ECCO2R system. Ventilation parameters [tidal volume (VT), respiratory rate, and PEEP], platform pressure (Pplat) and driving pressure (DP), respiratory system compliance, arterial blood gases, and ECCO2R system characteristics were collected.Results: Twelve patients with refractory hypercapnia were enrolled, and the PaCO2 was 64.5 [56-88.75] mmHg. In the adjusted group, VT was significantly reduced from 5.90 ± 0.16 to 5.08 ± 0.43 ml/kg PBW; DP and Pplat were also significantly reduced from 23.5 ± 2.72 mmHg and 29.88 ± 3.04 mmHg to 18.5 ± 2.62 mmHg and 24.75 ± 3.41 mmHg, respectively. In the unadjusted group, PaCO2 decreased from 94 [86.25, 100.3] mmHg to 80 [67.50, 85.25] mmHg but with no significant difference, and the DP and Pplat were not decreased after weighing the pros and cons.Conclusions: A low-flow ECCO2R system based on the RRT platform enabled CO2 removal and could also decrease the DP and Pplat significantly, which provided a new way to treat these COVID-19 ARDS patients with refractory hypercapnia and extremely low compliance.Clinical Trial Registration:https://www.clinicaltrials.gov/, identifier NCT04340414.

As a tunable optical material, LiNbO3 crystal has attracted broad interest in the last several decades. Despite wide applications in optical band as electrooptic modulators or piezoelectric sensors, the tunability of LiNbO3 in terahertz band is very limited, which restrains its performance as practical devices. Here we experimentally and theoretically demonstrate the dielectric permittivity spectrum of an integrated LiNbO3 interdigitated electrode meta-structure by terahertz time-domain spectroscopy ranging from 0.4 to 1.5 THz at room temperature. Under external electrical and optical fields pump, a considerable tuning of absorption coefficient of the sample can be achieved, which rendered a modulation of transmission amplitude reaching up to 13.3%. The observations are attributed to the strong absorption of ionized carriers induced by electrical and optical excitation. Our design appreciably modulates the dielectric property of unpatterned LiNbO3 crystals by the application of a metal interdigital electrode on the surface, and provides a reference for potential applications on tunable photonic devices in terahertz range.

BackgroundMental syndromes such as anxiety and depression are common comorbidities in patients with chronic insomnia disorder (CID). The locus coeruleus noradrenergic (LC-NE) system is considered to be crucial for modulation of emotion and sleep/wake cycle. LC-NE system is also a critical mediator of the stress-induced anxiety. However, whether the LC-NE system contributes to the underlying mechanism linking insomnia and these comorbidities remain unclear. This study aimed to investigate the LC-NE system alterations in patients with insomnia and its relationship with depression and anxiety symptoms.Materials and MethodsSeventy patients with CID and 63 matched good sleep control (GSC) subjects were recruited and underwent resting-state functional MRI scan. LC-NE functional network was constructed by using seed-based functional connectivity (FC) analysis. The alterations in LC-NE FC network in patients with CID and their clinical significance was explored.ResultsCompared with GSC group, the CID group showed decreased left LC-NE FC in the left inferior frontal gyrus, while they had increased LC-NE FC in the left supramarginal gyrus and the left middle occipital gyrus (MOG). For the right LC-NE FC network, decreased FC was found in left dorsal anterior cingulate cortex (dACC). Interesting, the increased LC-NE FC was located in sensory cortex, while decreased LC-NE FC was located in frontal control cortex. In addition, the FC between the left LC and left MOG was associated with the duration of the disease, while abnormal FC between right LC and left dACC was associated with the anxiety scores in patients with CID.ConclusionThe present study found abnormal LC-NE functional network in patients with CID, and the altered LC-NE function in dACC was associated with anxiety symptoms in CID. The present study substantially extended our understanding of the neuropathological basis of CID and provided the potential treatment target for CID patients who also had anxiety.

Cancer stem cells (CSCs) contribute to the cancer initiation, metastasis and drug resistance in non-small cell lung cancer (NSCLC). Herein, we identified a miR-221/222 cluster as a novel regulator of CSCs in NSCLC. Targeted overexpression or knockdown of miR-221/222 in NSCLC cells revealed the essential roles of miR-221/222 in regulation of lung cancer cell proliferation, mammosphere formation, subpopulation of CD133+ CSCs and the expression of stemness genes including OCT4, NANOG and h-TERT. The in vivo animal study showed that overexpression of miR-221/222 significantly enhanced the capacity of lung cancer cells to develop tumor and grow faster, indicating the importance of miR-221/222 in tumorigenesis and tumor growth. Mechanistically, Reck was found to be a key direct target gene of miR-221/222 in NSCLC. Overexpression of miR-221/222 significantly suppressed Reck expression, activated Notch1 signaling and increased the level of NICD. As an activated form of Notch1, NICD leads to enhanced stemness in NSCLC cells. In addition, knockdown of Reck by siRNA not only mimicked miR-221/222 effects, but also demonstrated involvement of Reck in the miR-221/222-induced activation of Notch1 signaling, verifying the essential roles of the miR-221/222-Reck-Notch1 axis in regulating stemness of NSCLC cells. These findings uncover a novel mechanism by which lung CSCs are significantly manipulated by miR-221/222, and provide a potential therapeutic target for the treatment of NSCLC.

Ischemic cardiac disease is the leading cause of morbidity and mortality in the world. Despite the great efforts and progress in cardiac research, the current treatment of cardiac ischemia reperfusion injury (I/RI) is still far from being satisfactory. This study was performed to investigate the role of long non-coding RNA (lncRNA) H19 in regulating myocardial I/RI. We found that H19 expression was downregulated in the I/R hearts of mice and cardiomyocytes treated with H2O2. Overexpression of H19 alleviated myocardial I/RI of mice and cardiomyocyte injury induced by H2O2. We found that H19 functioned as a competing endogenous RNA of miR-877-3p, which decreased the expression of miR-877-3p through the base-pairing mechanism. In parallel, miR-877-3p was upregulated in H2O2-treated cardiomyocytes and mouse ischemia reperfusion (I/R) hearts. miR-877-3p exacerbated myocardial I/RI and cardiomyocyte apoptosis. We further established Bcl-2 as a downstream target of miR-877-3p. miR-877-3p inhibited the mRNA and protein expression of Bcl-2. Furthermore, H19 decreased the Bcl-2/Bax ratio at mRNA and protein levels, cytochrome c release, and activation of caspase-9 and caspase-3 in myocardial I/RI mice, which were canceled by miR-877-3p. In summary, the H19/miR-877-3p/Bcl-2 pathway is involved in regulation of mitochondrial apoptosis during myocardial I/RI, which provided new insight into molecular mechanisms underlying regulation of myocardial I/RI. Keywords: myocardial ischemia reperfusion injury, I/RI, lncRNA H19, miR-877-3p, Bcl-2, mitochondrial apoptosis

Abstract Objective The aim of this study was to investigate the effect of oral lactulose for pediatric patients with complicated appendicitis, who underwent appendectomy. Background Oral lactulose was widely used for gastrointestinal function regulation. However, clinical benefit for oral lactulose regarding its effects on recent postoperative gastrointestinal (GI) recovery and long term adhesive small bowel obstruction (ASBO) incidence, especially in the postoperative pediatric population has not yet defined. Methods A total of 525 pediatric patients with complicated appendicitis underwent appendectomy were retrospectively reviewed. Among them, 317 cases were subjected to oral lactulose management and 208 patients without, served as control. Propensity score 1:1 matching was carried out to adjust for any potential baseline variables. In 189 paired patients, clinical outcomes, including gastrointestinal recovery variables, incidence of ABSO, as well as adverse events, were compared according to the oral lactulose administration or not. Results Patients who received oral lactulose administration achieved early gastrointestinal function recovery, including, first bowel movement (Risk ratio [RR], 1.34; 95% confidence interval [CI] 1.02–2.63, p = 0.005) and first solid feeding (RR, 1.26; 95% CI, 1.01–1.92, p = 0.012). A lower occurrence of ASBO (OR, 0.47; 95% CI, 0.25–0.87; p = 0.011) and lower constipation (Odds ratio [OR], 0.25; 95% CI, 0.13–0.46; p

Abstract Similarity queries, including range queries and k nearest neighbor (kNN) queries, in metric spaces have applications in many areas such as multimedia retrieval, computational biology and location-based services. With the growing volumes of data, a distributed method is required. In this paper, we propose an Asynchronous Metric Distributed System (AMDS), to support efficient metric similarity queries in the distributed environment. AMDS uniformly partitions the data with the pivot-mapping technique to ensure the load balancing, and employs publish/subscribe communication model to asynchronous process large scale of queries. The employment of asynchronous processing model also improves robustness and efficiency of AMDS. In addition, we develop efficient similarity search algorithms using AMDS. Extensive experiments using real and synthetic data demonstrate the performance of metric similarity queries using AMDS. Moreover, the AMDS scales sublinearly with the growing data size.

Abstract Background To compare neurocognitive functioning of Type 1 diabetic mellitus (T1DM) and healthy adults, and explore risk factors of cognitive dysfunction of T1DM patients, especially the association between cognitive impairment and diabetic peripheral neuropathy (DPN). Methods Seventy T1DM (age: 32.17 ± 9.57 yr., duration: 8.99 ± 7.02 yr) patients and 48 healthy volunteers were included. All subjects received evaluation of MMSE and MoCA scales. Cognitive function of T1DM patients was evaluated in different cognitive domains. Risk factors affecting cognitive function were further explored. Results Three patients with educational level ≤ 6-year were excluded from final analysis. Scores of both MMSE (28.4 ± 1.7 vs. 29.1 ± 1.0, P = 0.005) and MoCA scales (25.9 ± 2.7 vs.27.1 ± 2.4, P = 0.017) in T1DM group were lower than that in control group. For MMSE scale, scores of orientation (9.60 ± 0.79 vs.9.87 ± 0.39, P

Abstract Rock burst is a catastrophic dynamic disaster caused by sudden failure and instability of coal, loading paths play an important role in the failure of coal, the coal failure process is associated with charge exception information. Hence, violent coal failure mechanics and time–frequency domain distribution of charge signal such as rock burst under different loading paths should be studied in-depth. In this paper, grade and cyclic loading test were carried out for coal with impact tendency samples produced by blocks cored from 800 depth in Xiaoqing coal mine of the Tiefa coal group in northeast China. Theory discussion was carried out for the result of stress and strain, frequency-spectra analysis was conducted for the wavelet charge data, figures showing the evolution mechanism of mechanical properties and the relationship of time–frequency domain amplitude of charge signals in coal with different loading paths and stage were obtained. The failure process and characteristics of coal under different loading paths were summarized. It found that the loading path changed the manner of energy accelerate–release, there were more plastic strain generation in coal under cyclic loading than that under grade loading, the former was more likely to cause greater damage and failure, then the strength of coal under cyclic loading is generally lower than that under grade loading, an energy conversion mechanical model of stress, damage and deformation was developed and explained the effect of the loading path. Charge signal was primarily distributed in the strengthening and peak stages, where there was a high amplitude pulse at each stress drop. The charge pulse was a type of low frequency signal with a primary frequency distribution range of 1 –100 Hz. Discussion on the charge generating mechanism from the perspective of friction slip, it demonstrated that the charge obtained during the coal failure process directly to stress loaded on and damage, the result verified it better. We propose that the research results in this study could be efficiently applied to daily mining activities, to provide an early warning and effectively avoid rock burst disaster.

In this paper, we report the results of numerical simulation on vortex-shaped photoelectron momentum spectra of the hydrogen atom irradiated by a pair of time-delayed circularly polarized ultrashort pulses. Spectral alterations including broadening, splitting, and fusion are observed with stronger pulse intensity deploying the quantum wave-packet theory. These alterations of the dynamic interference structure are further investigated to stem from the ac Stark effect, by making the local approximation for an analytical ansatz. In addition, for evaluating the ac Stark effect on the hydrogen atom quantitatively, we propose a nonlinear-curve-fitting algorithm of the ground-state population for extracting the complex Stark coefficient, which we define. We find that the ac Stark effect can be well characterized by the complex coefficient, as supported by the overall agreement between the momentum spectra obtained from the wave-packet theory and the local approximation ansatz. The present research may shed further light on Stark effect in laser atom interactions.

Disruption of normal barrier function is a fundamental factor in the pathogenesis of inflammatory bowel disease, and intestinal stem cell (ISC) transplantation may be an optional treatment for patients. However, it is complicated and inefficient to isolate ISCs from the intestine, which hampers its wide application in clinic. We developed a two-step protocol in which mesenchymal stem cells (MSCs) were first induced into Sox17- or Foxa2-positive definitive endoderm cells by activin A treatment and then into Lgr5-positive ISC-like cells by miR-17 and FGF2 treatment. Furthermore, these Lgr5-positive cells could differentiate into enterocyte-like cells following induction with EGF. The results from an in vivo experiment showed that the MSC-derived Lgr5-positive cells were able to protect against dextran sulfate sodium-induced colitis. Taken together, our work might provide a new source of autologous ISCs. Keywords: mesenchymal stem cells, differentiation, intestinal stem cells

Cancer stem cells (CSCs) are believed to be the main source of cancer relapse and metastasis. PIWI-interacting small non-coding RNAs (piRNAs) have been recently recognized to be relevant to cancer biology. Whether and how piRNAs regulate human CSCs remain unknown. Herein, upregulation of piR-823 was identified in tested luminal breast cancer cells, especially in the luminal subtype of breast CSCs. Enforced expression or targeted knockdown of piR-823 demonstrated its oncogenic function in regulating cell proliferation and colony formation in MCF-7 and T-47D breast cancer cells. In addition, piR-823 induced ALDH (+) breast CSC subpopulation promoted the expression of stem cell markers including OCT4, SOX2, KLF4, NANOG, and hTERT, and increased mammosphere formation. Tail vein injection of magnetic nanoparticles carrying anti-piR-823 into the mammary gland of tumor-burdened mice significantly inhibited tumor growth in vivo. DNA methyltransferases (DNMTs) including DNMT1, DNMT3A, and DNMT3B were demonstrated to be the downstream genes of piR-823, which regulate gene expression by maintaining DNA methylation. piR-823 increased the expression of DNMTs, promoted DNA methylation of gene adenomatous polyposis coli (APC), thereby activating Wnt signaling and inducing cancer cell stemness in the luminal subtype of breast cancer cells. The current study not only revealed a novel mechanism through which piRNAs contribute to tumorigenesis in breast cancer by regulating CSCs, but also provided a therapeutic strategy using non-coding genomes in the suppression of human breast cancer.

Colon cancer ranks as the third most common malignancy in the world. Combination chemotherapy, resorting to electrospun fibrous technology, has been considered as a promising strategy to exert synergistic effects in colon cancer treatment. Herein, we manufactured various pluronic F127 (PF127)-modified electrospun fibrous meshes with different weight ratios of camptothecin (CPT) and curcumin (CUR). The fluorescence characterization of the obtained PF127-CPT-meshes, PF127-CUR-meshes, and PF127-CPT/CUR-meshes (2:1) showed that CPT and CUR were evenly distributed within individual fibers of these meshes. Drug release experiments revealed that both types of drugs could be released from fibrous meshes simultaneously and sustainably. Importantly, these meshes exhibited strong in vitro anti-colon cancer activities, compared with the control meshes without drugs. Moreover, the combination index values of the PF127-CPT/CUR-meshes (CPT/CUR weight ratio = 5:1, 3:1, or 2:1) were

In this study, a hybrid method combining extreme learning machine (ELM) and particle swarm optimization (PSO) is proposed to forecast train arrival delays that can be used for later delay management and timetable optimization. First, nine characteristics (e.g., buffer time, the train number, and station code) associated with train arrival delays are chosen and analyzed using extra trees classifier. Next, an ELM with one hidden layer is developed to predict train arrival delays by considering these characteristics mentioned before as input features. Furthermore, the PSO algorithm is chosen to optimize the hyperparameter of the ELM compared to Bayesian optimization and genetic algorithm solving the arduousness problem of manual regulating. Finally, a case is studied to confirm the advantage of the proposed model. Contrasted to four baseline models (k-nearest neighbor, categorical boosting, Lasso, and gradient boosting decision tree) across different metrics, the proposed model is demonstrated to be proficient and achieve the highest prediction accuracy. In addition, through a detailed analysis of the prediction error, it is found that our model possesses good robustness and correctness.

Inappropriate mechanical ventilation may induce hemodynamic alterations through cardiopulmonary interactions. The aim of this study was to explore the relationship between airway pressure and central venous pressure during the first 72 h of mechanical ventilation and its relevance to patient outcomes. We conducted a retrospective study of the Department of Critical Care Medicine of Peking Union Medical College Hospital and a secondary analysis of the MIMIC-III clinical database. The relationship between the ranges of driving pressure and central venous pressure during the first 72 h and their associations with prognosis were investigated. Data from 2790 patients were analyzed. Wide range of driving airway pressure (odds ratio, 1.0681; 95% CI, 1.0415–1.0953; p

Neuroblastoma (NB) is one of the most common solid tumors in childhood. To date, targeting MYCN, a well-established driver gene in high-risk neuroblastoma, is still challenging. In recent years, inhibition of bromodomain and extra terminal (BET) proteins shows great potential in multiple of Myc-driven tumors. ARV-825 is a novel BET inhibitor using proteolysis-targeting chimera (PROTAC) technology which degrades target proteins by the proteasome. In this study, we investigated the effect of ARV-825 in neuroblastoma in vitro and in vivo. Our results showed that ARV-825 treatment robustly induced proliferative suppression, cell cycle arrest, and apoptosis in NB cells. Moreover, ARV-825 efficiently depleted BET protein expression, subsequently repressing the expression of MYCN or c-Myc. In the NB xenograft model, ARV-825 profoundly reduced tumor growth and led to the downregulation of BRD4 and MYCN expression in mice. Taken together, these findings provide evidence that PROTAC BET inhibitor is an efficient way to achieve MYCN/c-Myc manipulation, and ARV-825 can be used as a potential therapeutic strategy for the treatment of neuroblastoma.

Laser pulses can be utilized to induce intermediate states of phase change materials between amorphous and crystalline phases, making phase change materials attractive and applicable for multi-level storage applications. In this paper, intermediate states of Ge2Sb2Te5 thin films induced via employing a nanosecond multi-pulse laser with different energy and pulse duration were performed by Raman spectroscopy, reflection measurement and thermal simulations. Upon laser-crystallized Ge2Sb2Te5 films, optical functions change drastically, leading to distinguishable reflectivity contrasts of intermediate states between amorphous and crystalline phases due to different crystallinity. The changes in optical intensity for laser-crystallized Ge2Sb2Te5 are also accompanied by micro-structure evolution, since high-energy and longer pulses result in higher-level intermediate states (corresponding to high reflection intensity) and largely contribute to the formation of stronger Raman peaks. By employing thermal analysis, we further demonstrated that the variations of both laser fluence and pulse duration play decisive roles in the degree of crystallinity of Ge2Sb2Te5 films. Laser fluence is mainly responsible for the variations in crystallization temperature, while the varying pulse duration has a great impact on the crystallization time. The present study offers a deeper understanding of the crystallization characteristic of phase change material Ge2Sb2Te5.