Search

53BP1 is a well-established DNA damage repair factor that has recently emerged to critically regulate gene expression for tumor suppression and neural development. However, its precise function and regulatory mechanisms remain unclear. Here, we showed that phosphorylation of 53BP1 at serine 25 by ATM is required for neural progenitor cell proliferation and neuronal differentiation in cortical brain organoids. Dynamic phosphorylation of 53BP1-serine 25 controls 53BP1 target genes governing neuronal differentiation and function, cellular response to stress, and apoptosis. Mechanistically, ATM and RNF168 govern 53BP1's binding to gene loci to directly affect gene regulation, especially at genes for neuronal differentiation and maturation. 53BP1 serine 25 phosphorylation effectively impedes its binding to bivalent or H3K27me3-occupied promoters, especially at genes regulating H3K4 methylation, neuronal functions, and cell proliferation. Beyond 53BP1, ATM-dependent phosphorylation displays wide-ranging effects, regulating factors in neuronal differentiation, cytoskeleton, p53 regulation, as well as key signaling pathways such as ATM, BDNF, and WNT during cortical organoid differentiation. Together, our data suggest that the interplay between 53BP1 and ATM orchestrates essential genetic programs for cell morphogenesis, tissue organization, and developmental pathways crucial for human cortical development. 53BP1 is a DNA damage repair factor that regulates gene expression for tumor suppression and neural development, but its precise regulatory mechanisms are unclear. This study shows that phosphorylation of 53BP1 by ATM kinase is crucial for modulating genetic programs in neural progenitors and cortical organoids. [ABSTRACT FROM AUTHOR]

This paper presents a numerical study on the yield resistance and ultimate resistance of steel beam with random corrosion damage. The corrosion is considered by introducing random cylindrical pits to the intact steel beam, in which the thickness of the beam, both at the section and along the length of the beam is reduced. Altogether 240 corroded beams are numerically studied, wherein the effects of corrosion ratio, corrosion diameter, corrosion depth and corrosion location on the yield resistance and ultimate resistance of steel beam are considered. It is found that for global corrosion scenario, when the corrosion ratio is 4.76%, 9.26%, 13.37%, 18.25%, 22.36%, and 25.76%, due to the random nature of corrosion, the reduction factors of ultimate resistance of steel beam range from 0.9–0.92, 0.81–0.86, 0.77–0.8, 0.71–0.76, 0.64–0.67, and 0.58–0.64, respectively. Moreover, when corrosion distributes only at the bottom flange or top flange of steel beam, the adverse effects of bottom flange corrosion and top flange corrosion on the resistance of steel beam are the same. The corrosion diameter and corrosion depth have limited effects on the resistance of steel beam. The relationship between the reduction factors for the yield resistance and ultimate resistance with the corrosion ratio of the beam is proposed. It is found that for the global corrosion case, the reduction factors of the yield resistance and ultimate resistance of the beam are linearly and negatively correlated with the corrosion ratio. For each 10% increase in the corrosion ratio, the reduction factor of yield resistance and ultimate resistance decrease by 18.9% and 15.1%, respectively. The resistances of the corroded beam with random corrosion pits and uniform corrosion are also compared. The results suggest that by using uniform corrosion model, the resistance of the corroded steel beam will be significantly overestimated. When the corrosion ratio is about 14%, the overestimation on the ultimate resistance of steel beam by using uniform corrosion model is more than 10%. [ABSTRACT FROM AUTHOR]

This study investigates the effects of forest aging on ectomycorrhizal (EcM) fungal community and foraging behavior and their interactions with plant–soil attributes. We explored EcM fungal communities and hyphal exploration types via rDNA sequencing and investigated their associations with plant–soil traits by comparing younger (~120 years) and older (~250 years) temperate forest stands in Northeast China. The results revealed increases in the EcM fungal richness and abundance with forest aging, paralleled by plant–soil feedback shifting from explorative to conservative nutrient use strategies. In the younger stands, Tomentella species were prevalent and showed positive correlations with nutrient availability in both the soil and leaves, alongside rapid increases in woody productivity. However, the older stands were marked by the dominance of the genera Inocybe, Hymenogaster, and Otidea which were significantly and positively correlated with soil nutrient contents and plant structural attributes such as the community-weighted mean height and standing biomass. Notably, the ratios of longer-to-shorter distance EcM fungal exploration types tended to decrease along with forest aging. Our findings underscore the integral role of EcM fungi in the aging processes of temperate forests, highlighting the EcM symbiont-mediated mechanisms adapting to nutrient scarcity and promoting sustainability in plant–soil consortia. [ABSTRACT FROM AUTHOR]

An experimental study of the ultralow-cycle fatigue of iron-based shape memory alloy (Fe-SMA) in triaxial stress states was conducted. Monotonic tensile tests of specimens with different geometries were carried out to investigate monotonic mechanical properties of Fe-SMA under various triaxial stress states in terms of stress triaxiality and Lode angle, followed by ultralow cyclic tests (cycles <100) which were carried out to study the ultralow-cycle fatigue of Fe-SMA under various loading systems at triaxial stress states. Fe-SMA had nonlinear combined hardening under cyclic loading. A parameter identification method based on an optimization-based algorithm was established to calibrate the constitutive model of Fe-SMA. The initiation and propagation of cracks in the fracture process were different for Fe-SMA under monotonic and cyclic loading. The influences of stress triaxiality and Lode angle on the fracture ductility of Fe-SMA were investigated. An ultralow cyclic fracture criterion, the cyclic Bai–Wierzbicki (CBW) criterion, was established based on the accumulation of ductile damage and the attenuation of ductile damage threshold. The applicability of the calibrated constitutive model and the proposed fracture criterion was validated by simulating the ultralow-cycle fatigue and fracture failures of Fe-SMA. [ABSTRACT FROM AUTHOR]

Coronavirus disease-2019 (COVID-19) has now entered its third year as a worldwide pandemic. Unlike the Unites States, over 90% of patients have used traditional Chinese medicine (TCM) in China combined with conventional western medicine. The present minireview/commentary summarizes the experiences of TCM in the treatment of COVID-19 combined with conventional western medicine, lessons from the United States and some additional insights. COVID-19 falls into the category of "dampness−toxin plague" and is divided into five stages: mild stage, moderate stage, severe stage, critical stage, and recovery stage. Clinical trials conducted in China have suggested that TCM treatment plays a significant role in alleviating clinical symptoms, decreasing the time of hospitalization, reducing the overall fatality rate, and providing other beneficial outcomes when combined with conventional western medicine. To date, TCM is not widely used in the American hospital system. Only one TCM clinical trial to treat mild to moderate COVID-19 has been registered with ClinicalTrials.gov. A suggestion of dialogues among associated parties is proposed. TCM has been used as part of an integrative medicine treatment paradigm combined with conventional western medicine for COVID-19 in China. As registered clinical trials combining conventional western medicine with TCM continue to be produced and show positive benefits, the possibilities for TCM integration into treatment protocols for COVID-19 will become more of a possibility in the United States. [ABSTRACT FROM AUTHOR]

Context: Several small studies have suggested that the gut microbiome might influence osteoporosis, but there is little evidence from human metabolomics studies to explain this association. Objective: This study examined the association of gut microbiome dysbiosis with osteoporosis and explored the potential pathways through which this association occurs using fecal and serum metabolomics. Methods: We analyzed the composition of the gut microbiota by 16S rRNA profiling and bone mineral density using dual-energy X-ray absorptiometry in 1776 community-based adults. Targeted metabolomics in feces (15 categories) and serum (12 categories) were further analyzed in 971 participants using ultra-high-performance liquid chromatography coupled to tandem mass spectrometry. Results: This study showed that osteoporosis was related to the beta diversity, taxonomy, and functional composition of the gut microbiota. The relative abundance of Actinobacillus, Blautia, Oscillospira, Bacteroides, and Phascolarctobacterium was positively associated with osteoporosis. However, Veillonellaceae other, Collinsella, and Ruminococcaceae other were inversely associated with the presence of osteoporosis. The association between microbiota biomarkers and osteoporosis was related to levels of peptidases and transcription machinery in microbial function. Fecal and serum metabolomics analyses suggested that tyrosine and tryptophan metabolism and valine, leucine, and isoleucine degradation were significantly linked to the identified microbiota biomarkers and to osteoporosis, respectively. Conclusion: This large population-based study provided robust evidence connecting gut dysbiosis, fecal metabolomics, and serum metabolomics with osteoporosis. Our results suggest that gut dysbiosis and amino acid metabolism could be targets for intervention in osteoporosis. [ABSTRACT FROM AUTHOR]

Recent years have witnessed the emergence of worldwide megalopolises and the accompanying public safety events, making urban safety a top priority in modern urban management. Among various threats, dangerous goods such as gas and hazardous chemicals transported through cities have bred repeated tragedies and become the deadly "bomb" we sleep with every day. While tremendous research efforts have been devoted to dealing with dangerous goods transportation (DGT) issues, further study is still in great need to quantify this problem and explore its intrinsic dynamics from a big data perspective. In this article, we present a novel system called DGeye, to feature a fusion between DGT trajectory data and residential population data for dangers perception and prediction. Specifically, DGeye first develops a probabilistic graphical model-based approach to mine spatio-temporally adjacent risk patterns from population-aware risk trajectories. Then, DGeye builds the novel causality network among risk patterns for risk pain-point identification, risk source attribution, and online risky state prediction. Experiments on both Beijing and Tianjin cities demonstrate the effectiveness of DGeye in real-life DGT risk management. As a case in point, our report powered by DGeye successfully drove the government to lay down gas pipelines for the famous Guijie food street in Beijing. [ABSTRACT FROM AUTHOR]

This study proposes a new fabrication of fresh perovskite-based Zr-Ca catalysts. The catalytic behaviors of the bifunctional catalysts prepared by the co-precipitation method were examined during ozonation of m-cresol, a model organic pollutant. The catalysts outperformed the other tested catalysts in the catalytic ozonation of pollutants. The catalytic activity was favored by an aging temperature of 140°C and a calcination temperature in the 700°C–900°C range. The samples were characterized by X-ray diffraction, scanning electron microscopy, and high-resolution transmission electron microscopy. The most active catalysts were composed of two phases, CaZrO3 and ZrO2. From X-ray photoelectron spectroscopy and in situ Fourier transform infrared studies, we inferred the nature of the active sites and a possible reaction mechanism. The mechanism was suggested as a non-radical mechanism. [ABSTRACT FROM AUTHOR]

Employer Brand Evaluation (EBE) is to understand an employer's unique characteristics to identify competitive edges. Traditional approaches rely heavily on employers' financial information, including financial reports and filings submitted to the Securities and Exchange Commission (SEC), which may not be readily available for private companies. Fortunately, online recruitment services provide a variety of employers' information from their employees' online ratings and comments, which enables EBE from an employee's perspective. To this end, in this article, we propose a method named Company Profiling-based Collaborative Topic Regression (CPCTR) to collaboratively model both textual (i.e., reviews) and numerical information (i.e., salaries and ratings) for learning latent structural patterns of employer brands. With identified patterns, we can effectively conduct both qualitative opinion analysis and quantitative salary benchmarking. Moreover, a Gaussian processes-based extension, GPCTR, is proposed to capture the complex correlation among heterogeneous information. Extensive experiments are conducted on three real-world datasets to validate the effectiveness and generalizability of our methods in real-life applications. The results clearly show that our methods outperform state-of-the-art baselines and enable a comprehensive understanding of EBE. [ABSTRACT FROM AUTHOR]

A non-dipper pattern of high blood pressure is associated with increased risk of organ damage and cardiovascular disease in patients with hypertension. The aim of the study was to evaluate the left ventricular (LV) remodeling and function and arterial stiffness in a dipper/non-dipper pattern of high blood pressure in patients with hypertension. A total of 183 hypertensive patients with no history of adverse cardiovascular events were divided into two groups based on 24 hours ambulatory blood pressure monitoring (ABPM): 66 patients with a dipper pattern and 117 patients with non-dipper pattern. Detailed transthoracic echocardiogram was performed and analyzed with advance speckle tracking 3-orthogonal direction strain analysis to assess LV systolic function and tissue Doppler-derived E/E' for LV diastolic function assessment. Cardio ankle vascular index (CAVI) was used to evaluate arterial stiffness. Compared with patients with dipper hypertension, those with non-dipper hypertension had increased LV mass index, higher prevalence of eccentric and concentric LV hypertrophy, more impaired LV diastolic and systolic function and peripheral arterial stiffness. Multivariable analysis revealed that a non-dipper pattern was independently associated with LV systolic dysfunction evaluated by speckle tracking-derived strain analysis. In conclusion, a non-dipper pattern of hypertension is an independent risk factor for LV systolic dysfunction. Treatment that could reverse this non-dipper pattern may reduce cardiac damage in these patients. [ABSTRACT FROM AUTHOR]

BPI is a pluripotent protein located in neutrophils and tissue that likely plays a vital role in host defense against GNB (gram-negative bacteria) and their endotoxin by means of its antibiotic and endotoxin neutralizing and disposing functions. BPI has several biological functions in mammals such as human, bovine, pig and rabbit, it also has major influence in the natural defense of the animal body. In this paper, by comparative study on BPI gene expression in various tissues between Rongchang pig and Landrace, we confirmed the expression of pig BPI gene in various tissues to determine the difference expression of antibacterial related gene among indigenous breed (Rongchang pig) and artificially cultivated breed (Landrace), The Rongchang pig (0 day old, 28 day old, 120 day old) and Landrace BPI (0 day old, 28 day old, 120 day old) gene were expressed in normal liver, heart, lung, kidney, spleen and small intestine. The results showed that: The expression level of BPI in lung of Rongchang pig was relatively higher level compared to that in heart, liver, kidney, spleen and small intestine. The expression level of BPI in liver of Landrace was relatively higher level compared to that in heart, lung, kidney, spleen and small intestine. Real-time fluorescence quantitative PCR analysis revealed that the native breed (Rongchang pig) has a better resistance to disease than Landrace. When Rongchang pig and Landrace were 0 day old, the expression level of BPI of Rongchang pig was higher than Landrace in heart, liver, spleen, kidney, small intestine, lower than Landrace in lung. When Rongchang pig and Landrace were 28 day old, the expression level of BPI of Rongchang pig was higher than Landrace in spleen (p<0.05), kidney (p<0.05), small intestine (p<0.05); lower than Landrace in lung, heart, liver. When Rongchang pig and Landrace were 120 day old, the expression level of BPI of Rongchang pig was higher than Landrace in spleen, lung (p<0.05), kidney (p<0.05), small intestine (p<0.05); lower than Landrace in heart, liver. The research trials showed that the expression of BPI gene increased with its increasing age in different growth stages. Ages and tissues are the main factors that influence the gene expression significantly. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) comprises nerve and motor function disorders that may be caused by a variety of damaging factors and is challenging to treat. The aim of the present study was to investigate the regenerative effects of neural stem cell (NSC) transplantation combined with intraperitoneal injection of erythropoietin (EPO) on cross-sectional SCI in rats. A model of SCI was induced in 40 adult Wistar rats via the complete transection of the 10th thoracic vertebra (T10). The rats were allocated at random into 4 groups: Control, NSC, EPO and NSC + EPO groups (n=10 per group). Morphological alterations associated with axonal regeneration were detected using neurofilament (NF)-200 immunohistochemistry and immunofluorescence staining after 8 weeks. Basso, Beattie and Bresnahan (BBB) scoring was used to evaluate the recovery of hindlimb function. A total of 5 rats died following surgery, including 2 control rats and 1 rat each in the EPO, NSC and NSC + EPO groups. NSCs labeled with bromodeoxyuridine were observed to have survived and migrated in the spinal cord tissue after 8 weeks. Significant histomorphological differences were observed in the NSC and NSC + EPO groups compared with the EPO and control groups. Furthermore, the rats of the NSC + EPO group exhibited significantly enhanced axonal regeneration in the SCI area compared with the NSC group rats. The rats of the NSC and NSC + EPO groups exhibited significantly improved BBB scores compared with the EPO and control group rats at 7 days after treatment (P<0.05). In addition, the BBB scores of the NSC + EPO group were significantly improved compared with those of the three other groups at 7 days after surgery (P<0.05). Therefore, the results of the present study suggest that NSC transplantation combined with intraperitoneal injection of EPO may benefit the survival and regeneration of injured axons, and accelerate the repair of injured spinal cord tissue, thus facilitating the functional recovery of hindlimb locomotor function in rats. [ABSTRACT FROM AUTHOR]

For the steel truss, the strain energy value under normal applying load is defined as the structure performance parameter. The work value of external force of the single bar is defined as the demand of damaged scenario. Structural vulnerability index is proposed in this paper based on the above two parameters. The importance coefficient of member is acquired by the strain energy coefficient according to single failure bar. The vulnerability index of different failure scenarios is compared to determine the important bar and weak path. The effects of different load distributions on the vulnerability coefficient of truss system are discussed and investigated. [ABSTRACT FROM AUTHOR]

Histones are the main structural components of the nucleosome, hence targets of many regulatory proteins that mediate processes involving changes in chromatin. The functional outcome of many pathways is “written” in the histones in the form of post-translational modifications that determine the final gene expression readout. As a result, modifications, alone or in combination, are important determinants of chromatin states. Histone modifications are accomplished by the addition of different chemical groups such as methyl, acetyl and phosphate. Thus, identifying and characterizing these modifications and the proteins related to them is the initial step to understanding the mechanisms of gene regulation and in the future may even provide tools for breeding programs. Several studies over the past years have contributed to increase our knowledge of epigenetic gene regulation in model organisms like Arabidopsis, yet this field remains relatively unexplored in crops. In this study we identified and initially characterized histones H3 and H4 in the monocot crop sugarcane. We discovered a number of histone genes by searching the sugarcane ESTs database. The proteins encoded correspond to canonical histones, and their variants. We also purified bulk histones and used them to map post-translational modifications in the histones H3 and H4 using mass spectrometry. Several modifications conserved in other plants, and also novel modified residues, were identified. In particular, we report O-acetylation of serine, threonine and tyrosine, a recently identified modification conserved in several eukaryotes. Additionally, the sub-nuclear localization of some well-studied modifications (i.e., H3K4me3, H3K9me2, H3K27me3, H3K9ac, H3T3ph) is described and compared to other plant species. To our knowledge, this is the first report of histones H3 and H4 as well as their post-translational modifications in sugarcane, and will provide a starting point for the study of chromatin regulation in this crop. [ABSTRACT FROM AUTHOR]

Prolonged use of glucocorticoids (GCs) for the treatment of chronic inflammatory and autoimmune diseases commonly exerts various side-effects, including impairment of skeletal development. However, the effect of GCs on chondrocytes, which play a key role in skeletal development, has been rarely reported. In the present study, autophagy was induced in the ATDC5 chondrocyte cell line following treatment with dexamethasone (Dex) at doses of 1-100 μM, and that this effect can be inhibited by RU486, a GC antagonist. Autophagy induced by the highest Dex dose (100 μM) was associated with a reduction in ATDC5 cell viability. We conclude that high doses of GC can reduce ATDC5 chondrocyte cell viability by inducing autophagy. [ABSTRACT FROM AUTHOR]

Phenotypic assays of hepatitis B virus (HBV) play an important role in research related to the problem of drug resistance that emerges during long-term nucleot(s)ide therapy in patients with chronic hepatitis B. Most of the phenotypic assay systems that are available currently rely on the transfection of recombinant replication-competent HBV DNA into hepatoma cell lines. Cloning clinical HBV isolates using conventional digestion-and-ligation techniques to generate replication-competent recombinants can be very difficult because of the sequence heterogeneity and unique structure of the HBV genome. In this study, a new strategy for constructing an HBV 1.1× recombinant was developed. The core of this strategy is the 'fragment substitution reaction' (FSR). FSR allows PCR fragments to be cloned without digestion or ligation, providing a new tool for cloning fragments or genomes amplified from serum HBV DNA, and therefore making the assay of HBV phenotypes more convenient. Using this strategy, a phenotypic assay was performed on an HBV strain carrying an rtS246T variant isolated from a patient with chronic hepatitis B that was only responsive partially to entecavir therapy. The results indicated that this strain is sensitive to entecavir in vitro. J. Med. Virol. 84:34-43, 2011. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Mycoplasma hyopneumoniae is an important pathogen of pigs causing enzootic pneumonia of swine. The pathogen remains largely enigmatic as far as the host-pathogen interactions are concerned. In the present study, the protein profiles of two strains of M. hyopneumoniae were compared by two-dimensional gel electrophoresis and mass spectrometry. The results indicate that the major adhesin P97, the 50-kDa protein derived from P159 adhesin, and the 43-kDa cleavage product of P102 are expressed at much higher levels in the pathogenic strain 232. In contrast, the avirulent strain J switches its focus to metabolism and expresses more glyceraldehyde 3-phosphate dehydrogenase in gluconeogenesis and lactate dehydrogenase, pyruvate dehydrogenase, and phosphate acetyltransferase in the pyruvate metabolism pathway. We speculate that the avirulent strain may have developed better capabilities to cope with the rich environment during repeated inoculations. Simultaneously, the capability to infect host cells may become less important so that the adhesion-related protein genes are down-regulated. [ABSTRACT FROM AUTHOR]

Skeletal muscle atrophy is a debilitating condition that occurs with aging and disease, but the underlying mechanisms are incompletely understood. Previous work determined that common transcriptional changes occur in muscle during atrophy induced by different stimuli. However, whether this holds true at the proteome level remains largely unexplored. Here, we find that, contrary to this earlier model, distinct atrophic stimuli (corticosteroids, cancer cachexia, and aging) induce largely different mRNA and protein changes during muscle atrophy in mice. Moreover, there is widespread transcriptome-proteome disconnect. Consequently, atrophy markers (atrogenes) identified in earlier microarray-based studies do not emerge from proteomics as generally induced by atrophy. Rather, we identify proteins that are distinctly modulated by different types of atrophy (herein defined as "atroproteins") such as the myokine CCN1/Cyr61, which regulates myofiber type switching during sarcopenia. Altogether, these integrated analyses indicate that different catabolic stimuli induce muscle atrophy via largely distinct mechanisms. [Display omitted] • Deep-coverage proteomics reveal molecular changes responsible for muscle wasting • Different catabolic stimuli induce muscle atrophy via largely distinct mechanisms • Transcriptome-proteome disconnect occurs during muscle wasting • Atroproteins are proteins modulated by atrophic stimuli Skeletal muscle wasting is caused by many catabolic stimuli, which were thought to act via shared mechanisms. Hunt et al. now show that distinct catabolic stimuli induce muscle wasting via largely different molecular changes. The authors identify atrophy-associated proteins ("atroproteins") that may represent diagnostic biomarkers and/or therapeutic targets. [ABSTRACT FROM AUTHOR]

A new uniform shallow trenches termination (ST²) with field plate for high-voltage VDMOS transistor is proposed in this Letter. In ST² structure, the electric field near the source is decreased and the depletion region is extended by the field plate, besides, many electric field peaks are introduced in shallow trenches under the field plate and the average electric field strength is increased, both improve the characteristic of the breakdown voltage (BV). Simulation results show the BV of ST² VDMOS is 706 V with a termination length Ld = 132 µm, which reaches 97% of that of the parallel-plane junction, and the influence of the edge curvature effect is almost entirely eliminated. The ST² structure is compatible with conventional CMOS process with only one additional mask and its fabrication is low-cost. [ABSTRACT FROM AUTHOR]

A stacked lateral double-diffused metal–oxide–semiconductor field-effect transistor (LDMOS) with enhanced depletion effect by surface substrate is proposed (ST-LDMOS), which is compatible with the traditional CMOS processes. The new stacked structure is characterized by double substrates and surface dielectric trenches (SDT). The drift region is separated by the P-buried layer to form two vertically parallel devices. The doping concentration of the drift region is increased benefiting from the enhanced auxiliary depletion effect of the double substrates, leading to a lower specific on-resistance (Ron,sp). Multiple electric field peaks appear at the corners of the SDT, which improves the lateral electric field distribution and the breakdown voltage (BV). Compared to a conventional LDMOS (C-LDMOS), the BV in the ST-LDMOS increases from 259 V to 459 V, an improvement of 77.22%. The Ron,sp decreases from 39.62 mΩ·cm2 to 23.24 mΩ·cm2 and the Baliga’s figure of merit (FOM) of is 9.07 MW/cm2. [ABSTRACT FROM AUTHOR]