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The loading resistance of slip critical steel connection is determined by the slip factor between faying surfaces and pretension force in bolts. The shot-blasting treatment is a commonly used and simple type of surface treatments. In order to avoid the risk of rusting of shot-blasted surfaces which threatens the structure safety, shot-blasted surfaces are generally coated with aluminum or zinc-based product. In this study, the slip factors of high strength steels (Q550, Q690 and Q890) with inorganic zinc-rich coating are investigated. Two values of coating thickness (60 μ m and 80 μ m) are selected and the influence of thickness of coating on slip factor is studied. Based on classical friction mechanism theory, compared with slip factor of shot-blasted surface, the decreasing of slip factor of surface with inorganic zinc-rich coating is analyzed. Moreover, the coating thickness effect on slip factor is also investigated. Because the difference between the measured slip displacement at 5 min (short-term tests) and 3 h (long-term tests) exceed 2 μ m , corresponding creep tests are carried out to evaluate long-term effects. Based on tests results, the recommended values of slip factor of high strength steel surface with inorganic zinc-rich coating is 0.30. • Slip factors of HSSs with inorganic zinc-rich coating are tested. • Steel strength effect on slip factor of steel surface with coating can be ignored. • Creep tests are carried out to study the long-term effect on slip resistance. • Suggested slip factors of HSS surface with inorganic zinc-rich coating are given. [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]

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]

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]

Aiming at studying the impact of different payment methods on M&A performance, this paper conducts empirical research using panel data of 2009--2013 Shanghai and Shenzhen A-share Market. The results show that, the difference of payment terms does not have a significant impact on the M&A performance in the overall regression. Further grouping regression shows that, for enterprises of mature industry, if they use cash payment terms in the M&A activity, their shareholders’ earning power is significantly lower than other enterprises, but the profitability is significantly lower, and if they use stock payment terms in the M&A activity, their operating capacity is significantly higher than other companies; for enterprises of growing industry, whether they use cash payment terms or not has no significant impact on the M&A performance, and if they use stock payment terms, the profitability is significantly higher than other enterprises; for enterprises of recession industry, the difference of payment methods does not affect the M&A performance.

The poor stiffness and strength of traditional U-shaped dampers is an issue that is addressed in the present work by the development of a new form of T-section metallic damper, termed as the TSMD. Theoretical and experimental studies are carried out to evaluate the seismic performances of TSMD. Based on the principle of virtual work and Castigliano's second theorem, theoretical formulas of yield strength and initial stiffness of TSMD are derived and verified. Stiffness, strength and energy dissipation capacity of TSMD are significantly higher than those of the U-shaped damper with the same size of flange. A finite element model which can capture the cyclic responses and fracture failures of TSMD is established. Based on the numerical simulation and parametric study, the effects of geometrical dimensions and material properties on the seismic performances of TSMD are quantified. The mechanical characteristics of the damper are significantly affected by the web width, height, flange width, and thickness of the T-section of TSMD. Shape memory alloy-made TSMD shows stronger strength hardening and fracture resistance capacities than traditional steel-made TSMD and decreases damper residual displacement after cyclic loading. This study aims to provide valuable insights into the behavior and potential applications of the TSMD. • A new form of T-section metallic damper (TSMD) was proposed. • Theoretical formulas of yield strength and stiffness of TSMD are derived. • The cyclic responses and fracture failures of TSMD were studied. [ABSTRACT FROM AUTHOR]

Wavecatcher (inward-turning) intake flows, at design Mach 12, are investigated numerically, to display the effect of wall temperature on flow structures and intake performance. Hypersonic experiments on shock wave/boundary layer interaction are used to validate the Spalart-Allmaras turbulence model for reproducing the features of hypersonic flow. Simulations of hypersonic intake flow are performed at different wall temperatures, including isothermal Tw = 300 K, Tw = 1000 K, Tw = 2000 K, and the adiabatic case. The shock structures, impinging shock positions, surface streamlines, and the development of internal streamwise vortices are discussed. The mass-averaged performance of intake flow shows that, when the wall temperature changes from Tw = 300 K to adiabatic, the mass capture coefficient decreases from 0.991 to 0.933, the total pressure recovery decreases from 0.200 to 0.083, while exit section Mach number decreases from 4.478 to 3.514. The results suggest that the osculating design method of wavecatcher intake design can successfully be extended to Mach 12, while capturing all airflow at isothermal wall conditions.

Aegilops umbellulata (UU) is a wheat wild relative that has potential use in the genetic improvement of wheat. In this study, 46 Ae. umbellulata accessions were investigated for stripe rust resistance, heading date (HD), and the contents of iron (Fe), zinc (Zn), and seed gluten proteins. Forty-two of the accessions were classified as resistant to stripe rust, while the other four accessions were classified as susceptible to stripe rust in four environments. The average HD of Ae. umbellulata was significantly longer than that of three common wheat cultivars (180.9 d vs. 137.0 d), with the exception of PI226500 (138.9 d). The Ae. umbellulata accessions also showed high variability in Fe (69.74–348.09 mg kg–1) and Zn (49.83–101.65 mg kg–1) contents. Three accessions (viz., PI542362, PI542363, and PI554399) showed relatively higher Fe (230.96–348.09 mg kg–1) and Zn (92.46–101.65 mg kg–1) contents than the others. The Fe content of Ae. umbellulata was similar to those of Ae. comosa and Ae. markgrafii but higher than those of Ae. tauschii and common wheat. Aegilops umbellulata showed a higher Zn content than Ae. tauschii, Ae. comosa, and common wheat, but a lower content than Ae. markgrafii. Furthermore, Ae. umbellulata had the highest proportion of γ-gliadin among all the species investigated (Ae. umbellulata vs. other species=mean 72.11% vs. 49.37%; range: 55.33–86.99% vs. 29.60–67.91%). These results demonstrated that Ae. umbellulata exhibits great diversity in the investigated traits, so it can provide a potential gene pool for the genetic improvement of these traits in wheat.

Abstract Background To investigate different responses to a high-fat/cholesterol diet and uncover their underlying genetic factors between C57BL/6J (B6) and DBA/2J (D2) inbred mice. Methods B6 and D2 mice were fed a high-fat/cholesterol diet for a series of time-points. Serum and bile lipid profiles, bile acid yields, hepatic apoptosis, gallstones and atherosclerosis formation were measured. Furthermore, a whole genome microarray was performed to screen hepatic genes expression profile. Quantitative real-time PCR, western blot and TUNEL assay were conducted to validate microarray data. Results After fed the high-fat/cholesterol diet, serum and bile total cholesterol, serum cholesterol esters, HDL cholesterol and Non-HDL cholesterol levels were altered in B6 but not significantly changed in D2; meanwhile, biliary bile acid was decreased in B6 but increased in D2. At the same time, hepatic apoptosis, gallstones and atherosclerotic lesions occurred in B6 but not in D2. The hepatic microarray analysis revealed distinctly different genes expression patterns between B6 and D2 mice. Their functional pathway groups included lipid metabolism, oxidative stress, immune/inflammation response and apoptosis. Quantitative real time PCR, TUNEL assay and western-blot results were consistent with microarray analysis. Conclusion Different genes expression patterns between B6 and D2 mice might provide a genetic basis for their distinctive responses to a high-fat/cholesterol diet, and give us an opportunity to identify novel pharmaceutical targets in related diseases in the future.

The fire resistance of beam-to-column connections affects the safety of clad racks under fire conditions. However, existing research lacks studies on the behavior of these special connections at high temperatures. This study investigates the fire resistance of clad rack beam-to-column bolted connections (CRBCs). Firstly, single cantilever tests of CRBCs at temperatures of 20 °C, 300 °C, 400 °C, 500 °C, 600 °C, and 700 °C are carried out. The failure modes of the CRBCs at 600 °C and below are identical to that at ambient temperature, while the failure mode at 700 °C is different. The stiffness and strength of the CRBCs decrease with the increasing temperature. Subsequently, an FE model considering the high-temperature metal fracture is established, which can accurately simulate the typical failure mechanisms and satisfactorily predict the full range moment-rotation behavior of CRBCs. Furthermore, parametric analyses are conducted to investigate the influences of related parameters on the failure mechanism, initial rotational stiffness, and flexural capacity of CRBCs. Finally, theoretical models based on the component method are established for calculating the initial rotational stiffness and flexural capacity of CRBCs at high temperatures, respectively. The comparison of the theoretical model, experimental results, and numerical results indicates that the theoretical model can accurately calculate the mechanical properties of CRBCs at high temperatures. The findings of this study can provide a reference for the analysis and design of the fire resistance of clad rack structures. • High-temperature flexural tests were conducted on CRBCs. • Failure modes and moment-rotation curves of CRBCs at 6 temperatures were obtained. • FE model considering metal fracture can simulate the experiment well. • Theoretical model for estimating mechanical properties of CRBCs is proposed. [ABSTRACT FROM AUTHOR]

Due to the huge property difference between high strength structural (HSS) steels and mild steels after welding, mechanical behavior and failure mode of fillet welded joints of HSS steels should be studied further. Numerical simulations can provide increased insight into this topic. This paper concerns finite element simulations of component tests of two types transverse fillet welded joints of HSS steels: lap-welded transverse fillet welds and cruciform type transverse fillet welds. In order to investigate the influences of triaxial stress states on fracture ductility of weld metals, a series of tests on specimens with various initial geometries are carried out. By comparing three typical uncoupled fracture models (stress triaxiality-dependent ductile fracture model (VGM), Lode angle-dependent ductile fracture model (MSSM) and combination of stress triaxiality and Lode angle ductile fracture model (BWM)), BWM gives precious prediction of ductile fracture of weld metals. The behaviors in terms of load-displacement and failure modes of transverse fillet welds are all well captured by the numerical simulations with calibrated ductile fracture models. Specifically, the location of fracture initiation and propagation of cracks obtained from simulations are both identical with real responses. [Display omitted] • Effects of triaxial stress states on fracture ductility of weld metals are studied. • An uncoupled ductile fracture model for weld metals is adopted and calibrated. • Mechanical behavior of transverse fillet welded joints are simulated. [ABSTRACT FROM AUTHOR]

Abstract Background Little is known about the inter-relationship among fruit and vegetable intake, gut microbiota and metabolites, and type 2 diabetes (T2D) in human prospective cohort study. The aim of the present study was to investigate the prospective association of fruit and vegetable intake with human gut microbiota and to examine the relationship between fruit and vegetable-related gut microbiota and their related metabolites with type 2 diabetes (T2D) risk. Methods This study included 1879 middle-age elderly Chinese adults from Guangzhou Nutrition and Health Study (GNHS). Baseline dietary information was collected using a validated food frequency questionnaire (2008–2013). Fecal samples were collected at follow-up (2015–2019) and analyzed for 16S rRNA sequencing and targeted fecal metabolomics. Blood samples were collected and analyzed for glucose, insulin, and glycated hemoglobin. We used multivariable linear regression and logistic regression models to investigate the prospective associations of fruit and vegetable intake with gut microbiota and the association of the identified gut microbiota (fruit/vegetable-microbiota index) and their related fecal metabolites with T2D risk, respectively. Replications were performed in an independent cohort involving 6626 participants. Results In the GNHS, dietary fruit intake, but not vegetable, was prospectively associated with gut microbiota diversity and composition. The fruit-microbiota index (FMI, created from 31 identified microbial features) was positively associated with fruit intake (p

Background: Little is known about the interplay among dairy intake, gut microbiota and cardiometabolic health in human prospective cohort studies. Methods: The present study included 1780 participants from the Guangzhou Nutrition and Health Study. We examined the prospective association between habitual dairy consumption (total dairy, milk, yogurt) and gut microbial composition using linear regression after adjusting for socio-demographic, lifestyle and dietary factors. The cross-sectional association of dairy-associated microbial features with cardiometabolic risk factors was examined with a linear regression model, adjusting for potential confounders. Serum metabolomic profiles were analyzed by partial correlation analysis. Findings: There was a significant overall difference in gut microbial community structure (β-diversity) comparing the highest with the lowest category for each of total dairy, milk and yogurt (P < 0.05). We observed that dairy-associated microbes and α-diversity indices were inversely associated with blood triglycerides, while positively associated with high-density lipoprotein cholesterol. A follow-up metabolomics analysis revealed the association of targeted serum metabolites with dairy-microbial features and cardiometabolic traits. Specifically, 2-hydroxy-3-methylbutyric acid, 2-hydroxybutyric acid and L-alanine were inversely associated with dairy-microbial score, while positively associated with triglycerides (FDR-corrected P < 0.1). Interpretation: Dairy consumption is associated with the gut microbial composition and a higher α-diversity, which provides new insights into the understanding of dairy-gut microbiota interactions and their relationship with cardiometabolic health. Funding: This work was supported by the National Natural Science Foundation of China, Zhejiang Ten-thousand Talents Program, Westlake University and the 5010 Program for Clinical Researches of the Sun Yat-sen University.

To research the mechanical properties and low cycle fatigue performance of Q355B structural steel and Q355GNHB weathering steel, this study performs monotonic and cyclic tests on the base metal, welded metal and heat-affected zone (HAZ) of Q355GNHB welded connections and Q355B. The monotone and cyclic constitutive model parameters are calibrated using the true stress-strain relationship and the Chaboche hybrid strengthening model, and their accuracy is verified by ABAQUS. To streamline the calibration process, a simplified calibration method is established for the Chaboche combined hardening model. Compared to the traditional calibration method, the proposed method uses the stress-strain data obtained from the monotonic tests. The applicability of the calibrated model is verified by simulating the tests via ABAQUS. The research results show that both Q355B structural steel and Q355GNHB weathering steel have excellent bearing capacity and plastic deformation capacity. The Q355GNHB weathering steel has better ductility, while the Q355B structural steel has higher bearing capacity and stronger strength reserve capacity. The strength of Q355GNHB varies according to different zones: the yield strength of the base metal material is the lowest, while the tensile strength and the plastic deformation capacity of the welded metal material is the lowest. Besides, the Chaboche combined hardening model and simplified combined hardening model can capture the cyclic fatigue performance of Q355B and Q355GNHB steel. The research results provide effective data support for the in-depth study of the constitutive relations and mechanical properties of weathering steel materials and the accurate simulation of the properties of weathering steel structures. • Real stress-strain relationships of 30 stainless steel specimens are obtained. • Base metal, welded metal and the heat-affected zone of Q355GNHB are considered. • A simplified calibration method of cyclic constitutive model is built for Q355GNHB. • The applicability of the calibrated model is verified by ABAQUS. [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]

Trypanosome histone N-terminal sequences are very divergent from the other eukaryotes, although they are still decorated by post-translational modifications (PTMs). Here, we used a highly robust workflow to analyze histone PTMs in the parasite Trypanosoma cruzi using mass spectrometry-based (MS-based) data-independent acquisition (DIA). We adapted the workflow for the analysis of the parasite's histone sequences by modifying the software EpiProfile 2.0, improving peptide and PTM quantification accuracy. This workflow could now be applied to the study of 141 T. cruzi modified histone peptides, which we used to investigate the dynamics of histone PTMs along the metacyclogenesis and the life cycle of T. cruzi. Global levels of histone acetylation and methylation fluctuates along metacyclogenesis, however most critical differences were observed between parasite life forms. More than 66 histone PTM changes were detected. Strikingly, the histone PTM pattern of metacyclic trypomastigotes is more similar to epimastigotes than to cellular trypomastigotes. Finally, we highlighted changes at the H4 N-terminus and at H3K76 discussing their impact on the trypanosome biology. Altogether, we have optimized a workflow easily applicable to the analysis of histone PTMs in T. cruzi and generated a dataset that may shed lights on the role of chromatin modifications in this parasite. Trypanosomes are unicellular parasites that have divergent histone sequences, no chromosome condensation and a peculiar genome/gene regulation. Genes are transcribed from divergent polycistronic regions and post-transcriptional gene regulation play major role on the establishment of transcripts and protein levels. In this regard, the fact that their histones are decorated with multiple PTMs raises interesting questions about their role. Besides, this digenetic organism must adapt to different environments changing its metabolism accordingly. As metabolism and epigenetics are closely related, the study of histone PTMs in trypanosomes may enlighten this strikingly, and not yet fully understood, interplay. From a biomedical perspective, the comprehensive study of molecular mechanisms associated to the metacyclogenesis process is essential to create better strategies for controlling Chagas disease. • T. cruzi histone PTMs can now be easily evaluated using an optimized workflow of MS-based DIA acquisition together with modification at EpiProfile platform. • New PTMs were described including multiple methylations at H3K4, a key PTM associated with transcription activation in higher eukaryotes. • Transient PTM changes are a common feature during all steps of metacyclogenesis. • Histone PTM pattern of metacyclic trypomastigotes is more similar to epimastigotes than to cellular trypomastigotes. [ABSTRACT FROM AUTHOR]

• Tests of six types of specimens of high strength steels are conducted. • The von Mises yield function is no longer applicable well for HSS. • The plasticity model of HSS should considers the effect of Lode angle. • A new yield function with consideration of Lode angle effect of HSS is proposed. The high strength steel (HSS) with a nominal yield stress not less than 460 N/mm2 has been increasingly used in engineering structures. An accurate yield criterion which describes the elastoplastic behavior of high strength steels under complex stress states, is significant for the analysis and design of high strength steel structures. For ductile metal materials, the most generally used the von Mises yield criterion neglects the effects of stress triaxiality and Lode angle on the metal plasticity. However, due to the reduce ductility with the increase in strength, such yield criterion may not applicable to HSSs. In the present paper, the tests of six types of specimens are carried out to evaluate effects of stress triaxiality and Lode angle on the plastic behavior of HSSs (Q550, Q690 and Q890). The applicability of von Mises yield criterion is examined firstly using experimental results and finite element analyses. It demonstrates that an appropriate yield function of HSSs should consider effects of the Lode angle while the influence of stress triaxiality is negligible. Based on the experimental and numerical results, a yield function for HSSs is proposed, to essentially simulate the elastoplastic behavior of high strength steel under complex stress states. [ABSTRACT FROM AUTHOR]

• Despite single-cell antileukemic activity, DOT1L and EZH2 (PRC2) inhibition is not consistently synergistic in KMT2A- rearranged cell lines. • PRC2 does not control one of its best validated canonical targets, the HOXA cluster, in KMT2A -rearranged leukemias. • DOT1L and EZH2 oppose each other on ribosomal genes. • DOT1L inhibition affects protein translation in KMT2A -rearranged leukemias via transcriptional effects on ribosomal genes. • DOT1L inhibition is synergistic with the protein translation inhibitor homoharringtonine. Inhibition of the H3K79 histone methyltransferase DOT1L has exhibited encouraging preclinical and early clinical activity in KMT2A (MLL) -rearranged leukemia, supporting the development of combinatorial therapies. Here, we investigated two novel combinations: dual inhibition of the histone methyltransferases DOT1L and EZH2, and the combination with a protein synthesis inhibitor. EZH2 is the catalytic subunit in the polycomb repressive complex 2 (PRC2), and inhibition of EZH2 has been reported to have preclinical activity in KMT2A - r leukemia. When combined with DOT1L inhibition, however, we observed both synergistic and antagonistic effects. Interestingly, antagonistic effects were not due to PRC2-mediated de-repression of HOXA9. HOXA cluster genes are key canonical targets of both KMT2A and the PRC2 complex. The independence of the HOXA cluster from PRC2 repression in KMT2A-r leukemia thus affords important insights into leukemia biology. Further studies revealed that EZH2 inhibition counteracted the effect of DOT1L inhibition on ribosomal gene expression. We thus identified a previously unrecognized role of DOT1L in regulating protein production. Decreased translation was one of the earliest effects measurable after DOT1L inhibition and specific to KMT2A -rearranged cell lines. H3K79me2 chromatin immunoprecipitation sequencing patterns over ribosomal genes were similar to those of the canonical KMT2A-fusion target genes in primary AML patient samples. The effects of DOT1L inhibition on ribosomal gene expression prompted us to evaluate the combination of EPZ5676 with a protein translation inhibitor. EPZ5676 was synergistic with the protein translation inhibitor homoharringtonine (omacetaxine), supporting further preclinical/clinical development of this combination. In summary, we discovered a novel epigenetic regulation of a metabolic process—protein synthesis—that plays a role in leukemogenesis and affords a combinatorial therapeutic opportunity. [ABSTRACT FROM AUTHOR]

DNA methyltransferases (Dnmts) comprise a family of proteins which involved in the establishment and maintenance of DNA methylation patterns. In pig, the molecular characterization and tissue expression profile of Dnmt gene family are not clear. To solve this problem, reverse transcriptase PCR and rapid amplification of cDNA ends were used to clone the sequences of the porcine Dnmt2 and Dnmt3b genes. Furthermore, the mRNA expression profiles of Dnmt1, Dnmt2, Dnmt3a and Dnmt3b genes from 54 adult tissues and 2 entire fetuses of Rongchang pig were analyzed by quantitative real-time PCR (qRT-PCR). As a result, the lengths of porcine Dnmt2 and Dnmt3b gene cDNAs were 1 227 and 2 559 bp with cytosine-C5 specific DNA methylase domain, respectively. The four Dnmt genes were highly expressed in longissimus dorsi muscle (P

Saturated fatty acids with different chain lengths have different biological activities, but little is known about very-long-chain saturated fatty acids (VLCSFAs). This study investigated the associations between the circulating VLCSFAs and cardiovascular health. This community-based cohort study included 2198 adults without carotid artery plaques (CAPs) at baseline. The percentage of baseline erythrocyte VLCSFA (arachidic acid (C20:0), behenic acid (C22:0), and lignoceric acid (C24:0)) was measured by gas chromatography. The presence of CAPs was determined at baseline and every 3 years thereafter by ultrasound examination. A meta-analysis was conducted to summarize the pooled associations between circulating VLCSFAs and the risk of cardiovascular diseases (CVDs). During a median of 7.2 years of follow-up, 573 women (35.1%) and 281 men (49.6%) were identified as CAP incident cases. VLCSFAs were inversely related with CAP risk in women (all p-trend

• Ultra-low cycle fatigue life of steel rod energy dissipaters is accurately predicted. • Constitutive model considering strain amplitude effect is incorporated in FE model. • Ductile fracture model is calibrated and validated against experiments. • Fatigue failure mechanism of steel rod dissipaters is scrutinized. • Configuration of steel rod energy dissipater is improved. • Key factors in predicting fatigue life of steel rod energy dissipaters are clarified. In recent decades, various bar-typed miniature energy dissipaters with buckling restrained mechanisms have been proposed for seismic mitigation of engineering structures. The recently proposed assembled steel rod energy dissipater (ASRED), incorporating equally divided tubes as filler components, have shown plump hysteretic loops and remarkable fatigue performance. For such miniature dissipaters with varied dimensions, its ultra-low-cycle fatigue (ULCF) life is correlated with the geometrical dimensions. However, no research concerning this issue has been found. To enable the fracture prediction of ASREDs under various loading situations, numerical models integrated with the ductile fracture model were established in this paper. A newly proposed constitutive model and the famous combined hardening model were both employed in the numerical models to comparatively investigate the key factors affecting the accuracy of the fracture prediction. Moreover, the possible influence of Lode angle was also investigated by employing two different ductile fracture models, namely, the cyclic Bai-Wierzbicki model (CBWM) and the cyclic void growth model (CVGM). Seven specimens with different lengths and loading protocols were simulated, and the results show that the strain amplitude distributes unevenly in the ASRED and increases cycle by cycle at the fixed ends, which leads to the necking-induced failure mode. Using the fracture model of CBWM, numerical simulations that considers the influence of strain amplitude could successfully predict the fracture of all specimens. The dissipaters behaved approximately in an axially loaded state throughout the entire fatigue life, therefore the influence of the Lode angle was negligible, and the fracture predictions given by the CVGM are same with that by the CBWM. Based on a comprehensive analysis of the extended numerical investigations, an improved configuration for ASRED is proposed. [ABSTRACT FROM AUTHOR]

Database search is the dominant approach in high-throughput proteomic analysis. However, the interpretation rate of MS/MS spectra is very low in such a restricted mode, which is mainly due to unexpected modifications and irregular digestion types. In this study, we developed a new algorithm called Alioth, to be integrated into the search engine of pFind, for fast and accurate unrestricted database search on high-resolution MS/MS data. An ion index is constructed for both peptide precursors and fragment ions, by which arbitrary digestions and a single site of any modifications and mutations can be searched efficiently. A new re-ranking algorithm is used to distinguish the correct peptide-spectrum matches from random ones. The algorithm is tested on several HCD datasets and the interpretation rate of MS/MS spectra using Alioth is as high as 60%–80%. Peptides from semi- and non-specific digestions, as well as those with unexpected modifications or mutations, can be effectively identified using Alioth and confidently validated using other search engines. The average processing speed of Alioth is 5–10 times faster than some other unrestricted search engines and is comparable to or even faster than the restricted search algorithms tested.This article is part of a Special Issue entitled: Computational Proteomics. [ABSTRACT FROM AUTHOR]

Arterial ischemia and hemorrhage are associated with bevacizumab, an inhibitor of vascular endothelial growth factor that is widely used to treat many types of cancers. As specific types of arterial ischemia and hemorrhage, cerebrovascular events such as central nervous system (CNS) ischemic events and CNS hemorrhage are serious adverse events. However, increased cerebrovascular events have not been uniformly reported by previous studies. New randomized controlled trials (RCTs) have been reported in recent years and we therefore conducted an up-to-date meta-analysis of RCTs to fully characterize the risk of cerebrovascular events with bevacizumab. We searched the databases of PubMed, Web of Science, and the American Society of Clinical Oncology conferences to identify relevant clinical trials up to February 2014. Eligible studies included prospective RCTs that directly compared patients with cancer treated with and without bevacizumab. A total of 12,917 patients from 17 RCTs were included in our analysis. Patients treated with bevacizumab had a significantly increased risk of cerebrovascular events compared with patients treated with control medication, with a relative risk of 3.28 (95% CI, 1.97-5.48). The risks of CNS ischemic events and CNS hemorrhage were increased compared with control, with RRs of 3.22 (95% CI, 1.71-6.07) and 3.09 (95% CI, 1.36-6.99), respectively. Risk varied with the bevacizumab dose, with RRs of 3.97 (95% CI, 2.15-7.36) and 1.96 (95% CI, 0.76-5.06) at 5 and 2.5 mg/kg/week, respectively. Higher risks were observed in patients with metastatic colorectal cancer (RR, 6.42; 95% CI, 1.76-35.57), and no significant risk was observed in other types of tumors. In conclusion, the addition of bevacizumab significantly increased the risk of cerebrovascular events compared with controls, including CNS ischemic events and CNS hemorrhage. The risk may vary with bevacizumab dose and tumor type.

This paper numerically studies the anti-collapse behavior of the modular steel building (MSB) in the scenario of interior module removal and corner module removal. The vertical displacement, lateral displacement and internal force of a six-storey MSB in a sudden module loss are studied. The reasonability by using rigid body assumption in collapse analysis of the MSB is examined. A refined fracture model of the steel is incorporated into ABAQUS via user subroutine, in which the effects of both stress triaxiality and Lode angle on the fracture ductility of the steel are considered. In the pushover analyses, the effects of the horizontal connection, opening of the wall panel and thickness of the wall panel on the collapse resistance and failure mode of the MSB are studied. The dynamic amplification factor (DAF) of the MSB at the collapse limit state is also obtained. It is found that the rigid body assumption may significantly underestimate the displacement and maximum shear force in the horizontal connection of the MSB. Two types of failure modes of the structure are observed, namely, connection failure-induced collapse and module unit failure-induced collapse. Among the studied parameters, the effect of the opening size of the wall panel on the behavior of the structure is the most significant. In the scenario of the interior module removal and corner module removal, the DAFs of the structure at the collapse limit state range from 1.20–1.29 and 1.27–1.50, respectively. • Anti-collapse behavior of modular steel building (MSB) was studied. • The reasonability of rigid body assumption in collapse analysis of MSB was studied. • Effects of connection and wall panel on collapse resistance of MSB were studied. • Dynamic amplification factor of the MSB at the collapse limit state was obtained. [ABSTRACT FROM AUTHOR]

• Improved test methodology for connection with bolt pre-tension was presented. • Full-range distribution of triaxial stress field near bolt hole was analyzed. • Proportions of friction force and bearing force were investigated. • A trade-off between ultimate resistance and bearing resistance was discovered. • Comparisons with current codes were presented. Bolt pre-tension is regularly used in the practical case of bearing-type connection. Due to confinement of lap plates, complicate triaxial stress field can be observed near bolt hole, which may affect bearing behavior of the whole connection. Currently, investigations on the related issues are limited. To fill this research gap, this paper presents a combined experimental and numerical study on high strength steel single-bolt connections with bolt pre-tension. Results reveal several meaningful recognitions on the bearing behavior of connection with bolt pre-tension. Firstly, the effect of bolt pre-tension on the final tearout failure mode is negligible. Secondly, distribution of triaxial stress field initiates with a circular pattern and gradually shrinks to a localized pattern between shear fracture lines at ultimate resistance of the connection. Thirdly, out-plane confinement will limit the piling-up of plate material in front of bolt, which will reduce the related bearing resistance. However, increasing bolt grade is still beneficial to the whole connection due to a trade-off between ultimate resistance of the connection and related bearing resistance. Comparison with current code is further conducted. It is found that current Eurocode3 has adequate design safety for connection with bolt pre-tension while extra safety is needed for current AISC 360-16. [ABSTRACT FROM AUTHOR]

• Seismic performance of Q690D steel H-section beam-column bending about weak axis is experimentally studied. • Finite element model incorporated with ductile damage for Q690 high strength steel beam-column is established and verified. • Parametric study on Q690 high strength steel beam-column is conducted using numerical simulation results. Recently structural members fabricated of high strength constructional steels in civil and building engineering has been widely explored. However, their usage in earthquake zones is still restricted by seismic standards worldwide due to its poor ductility. In order to attain potential seismic application, this paper conducted five cyclic lateral loading experiments on H-shaped beam-columns fabricated of Q690D high strength structural steel. The tested members were cyclically bent about the weak axis. It was recognized that the low-fatigue fracture of edge fiber around bottom cross-section was the main failure mode. Besides, the hysteretic curves, cyclic backbones and energy dissipation characteristics were thoroughly discussed. The ultimate inter-storey drift was greater than the limitation of 1/50. All tested beam-columns exhibit favorable cyclic deformability and energy dissipated ability. To further study the influence of several factors, a series of FEA simulations were performed through verified numerical models. Ductile damage behaviors and advanced cyclic constitutive relationships were considered to improve the simulation performance. The influences of plate component slenderness and axial load ratio on seismic performance of steel beam-columns were thoroughly discussed. It is concluded that there exist interdependence characteristics between different influential factors on seismic performance. [ABSTRACT FROM AUTHOR]

• Full-scale corner-supported modular building was tested and simulated. • Stages of connection behavior in transfer of vertical load was analyzed. • Full-range variation of bolt pre-tension force in the bolt group was revealed. • Tolerance of splice connection for extreme initial imperfections was studied. • A transitional initial imperfection for modular building was found. Splice connection, comprised of splice plates and slip-critical high strength bolts, is an efficient and convenient connecting technique for modular buildings. Previous investigations on this splice connection were mainly conducted based on tests of substructures, which may not reveal the real connection behavior in the whole modular building. To fill this research gap, this paper presents a comprehensive research on a full-scale corner-supported modular building assembled with splice connections. Behavior of the splice connection during the transfer of vertical load in the full-scale modular building is analyzed in details with combined experimental and numerical techniques. Test results showed that no unfavorable phenomenon was caused by the proposed splice connection before the global buckling of the module column. Based on the validated numerical model, a three-stage behavior during the entire loading process is found for the splice connection. The involvement of splice connection in the transfer of vertical load is negligible in the first stage while the splice connection provides sufficient constraint for the second-order moment at the bottom of module column in the second stage. The localized deformation and obvious formation of gap are found in the third stage. However, the analysis on the full-range bolt pre-tension force of the bolt group indicates that the origin of such negative phenomenon is located after the global buckling, which will not affect design on the vertical-load transfer performance of the module column. The sensitivity of connection behavior to the values of initial imperfections are also investigated by the parametric study. It is found that the proposed splice connection has a satisfactory tolerance for extreme initial imperfections. A transitional initial imperfection is further proposed, which may be used as an important reference for the practical control on the initial imperfection. [ABSTRACT FROM AUTHOR]

• Multi-bolt high strength steel connections in tandem were tested and simulated. • Full-range load-distribution pattern were analyzed. • Bearing behavior of an individual bolt among the bolt group was investigated. • A nonlinear ultimate bearing resistance model was proposed. • Suggestions related to current design codes were given. This paper presents an experimental and numerical investigation on the bearing behavior of multi-bolt high strength steel connections in single bolt line. Three grades of high strength steel with nominal yield stress of 550 MPa, 690 MPa and 890 MPa were used to fabricate thirty lap connections with two or three bolts. It is found that the deformation capability of high strength steel plate near bolt hole is sufficient to meet the deformation demand of compatibility in multi-bolt connection even with an intended bolt hole misalignment of 2 mm for M24 high strength bolt. The comparison with Eurocode3 and AISC 360-16 is conducted. When no partial or safety factors are considered, the original formulae of Eurocode3 already has sufficient safety while AISC 360-16 gives unsafe predictions. Numerical models were established and verified by test results. With the obtained results, the full-range distribution of internal load among different bolts can be divided into four stages. Features for each stage are summarized and the effect of bolt hole misalignment on the distribution pattern is evaluated. Numerical analysis results indicate that, behavior of an individual bolt in multi-bolt connection may be influenced by surrounding bolts. The formation of critical yielding band between different bolts may explain this influence. Based on the experimental and numerical analyses, this paper proposed a new ultimate bearing resistance model for multi-bolt connections. The proposed model is capable of describing the nonlinearity in the ultimate bearing resistance of multi-bolt connection and achieves improved predicting accuracy compared to classical models. [ABSTRACT FROM AUTHOR]

It has been well-recognized that high strength steels possess worse ductility and deformability compared to normal strength steels, leading to greater risk of low-cycle failure. In addition, high strength steels generally exhibit prominent cyclic softening behavior rather than cyclic hardening behavior. These characteristics should be properly implemented into finite element model to gain exclusive numerical simulation on cyclic behavior of high strength steel beam columns. In this paper, finite element models which not only consider the initial imperfection but also incorporate the ductile fracture behavior as well as cyclic softening behavior were established and used to simulate cyclic loading experiments on high strength steel beam-columns bending about strong axis. The simulation results including hysteretic curves and failure modes both provide good agreement with experimental results, verifying the capability of finite element models proposed. Accordingly, a parametric study was conducted to investigate the effects of axial load ratio, flange width-to-thickness ratio and web height-to-thickness ratio on cyclic behaviors of Q690 high strength steel beam-columns. It can be concluded that the increase in flange width-to-thickness ratio and axial load ratio will change the damage mechanism and consequently present different cyclic deterioration characteristics. Furthermore, the increase in flange and web slenderness and axial load ratio results in decrease in deformability and sectional plasticity development ability. • Finite element model for simulating cyclic behavior of Q690 high strength steel beam-columns was established. • Finite element model was verified using experimental results. • Parametric study on effects of axial load ratio and plate slenderness ratio on cyclic behavior was conducted. [ABSTRACT FROM AUTHOR]

Histone acetyltransferases KAT2A and KAT2B are paralogs highly expressed in the intestinal epithelium, but their functions are not well understood. In this study, double knockout of murine Kat2 genes in the intestinal epithelium was lethal, resulting in robust activation of interferon signaling and interferon-associated phenotypes including the loss of intestinal stem cells. Use of pharmacological agents and sterile organoid cultures indicated a cell-intrinsic double-stranded RNA trigger for interferon signaling. Acetyl-proteomics and sequencing of immunoprecipitated double-stranded RNA were used to interrogate the mechanism behind this response, which identified mitochondria-encoded double-stranded RNA as the source of intrinsic interferon signaling. Kat2a and Kat2b therefore play an essential role in regulating mitochondrial functions and maintaining intestinal health.

Gene expression is tightly controlled during animal development to allow the formation of specialized cell types. Our understanding of how animals evolved this exquisite regulatory control remains elusive, but evidence suggests that changes in chromatin-based mechanisms may have contributed. To investigate this possibility, here we examine chromatin-based gene regulatory features in the closest relatives of animals, choanoflagellates. Using Salpingoeca rosetta as a model system, we examined chromatin accessibility and histone modifications at the genome scale and compared these features to gene expression. We first observed that accessible regions of chromatin are primarily associated with gene promoters and found no evidence of distal gene regulatory elements resembling the enhancers that animals deploy to regulate developmental gene expression. Remarkably, a histone modification deposited by polycomb repressive complex 2, histone H3 lysine 27 trimethylation (H3K27me3), appeared to function similarly in S. rosetta to its role in animals, because this modification decorated genes with cell type-specific expression. Additionally, H3K27me3 marked transposons, retaining what appears to be an ancestral role in regulating these elements. We further uncovered a putative new bivalent chromatin state at cell type-specific genes that consists of H3K27me3 and histone H3 lysine 4 mono-methylation (H3K4me1). Together, our discoveries support the scenario that gene-associated histone modification states that underpin development emerged before the evolution of animal multicellularity.

The limited availability of cytokines in solid tumours hinders maintenance of the antitumour activity of chimeric antigen receptor (CAR) T cells. Cytokine receptor signalling pathways in CAR T cells can be activated by transgenic expression or injection of cytokines in the tumour, or by engineering the activation of cognate cytokine receptors. However, these strategies are constrained by toxicity arising from the activation of bystander cells, by the suboptimal biodistribution of the cytokines and by downregulation of the cognate receptor. Here we show that replacement of the extracellular domains of heterodimeric cytokine receptors in T cells with two leucine zipper motifs provides optimal Janus kinase/signal transducer and activator of transcription signalling. Such chimeric cytokine receptors, which can be generated for common γ-chain receptors, interleukin-10 and -12 receptors, enabled T cells to survive cytokine starvation without induction of autonomous cell growth, and augmented the effector function of CAR T cells in vitro in the setting of chronic antigen exposure and in human tumour xenografts in mice. As a modular design, leucine zippers can be used to generate constitutively active cytokine receptors in effector immune cells., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

We investigated species composition and community structure of a typical Quercus variabilis natural secondary forest in the northern foothills of the Qinling Mountains, within the dynamic monitoring plot of deciduous broad-leaved forest at the Louguantai experimental forest farm in Zhouzhi County, Shaanxi Province. The results showed that there were 3162 individual woody plants with diameter at breast height ≥1 cm in the plot, which were belonged to 42 species, 36 genera, and 25 families. The community genus's areal type was dominated by the temperate component, which accounted for 44.4%, and followed by the tropical component. The community was dominated by several tree species. The top three species with respect to importance value were Q. variabilis , Pinus tabuliformis , and Quercus aliena , with the sum of their importance value being 64.7%. The average DBH of all woody plants was 7.58 cm. The distribution of all individuals and dominant species in the tree layer was approximately normal, with more medium-size individuals. The community structure was stable. The community was poorly renewed, with a trend of population decline. Biodiversity indices varied considerably among different plots, being lower than those of subtropical broad-leaved evergreen forests. There was a significant correlation between community species distribution and environmental factors. Soil and topography explained 42.4% of the variation in community distribution. Altitude and soil alkali hydrolysable nitrogen had a significant effect on community distribution. Altitude, soil total phosphorus, and organic matter content significantly affected the species diversity of Q. variabilis communities. The stronger adaptability of Q. variabilis populations allowed them to become dominant in low-nutrient environments, which limited species diversity in the community.

Background: Mass spectrometry (MS)-based proteomic analysis of posttranslational modifications (PTMs) usually requires the pre-enrichment of modified proteins or peptides. However, recent ultra-deep whole proteome profiling generates millions of spectra in a single experiment, leaving many unassigned spectra, some of which may be derived from PTM peptides., Methods: Here we present JUMPptm, an integrative computational pipeline, to extract PTMs from unenriched whole proteome. JUMPptm combines the advantages of JUMP, MSFragger and Comet search engines, and includes de novo tags, customized database search and peptide filtering, which iteratively analyzes each PTM by a multi-stage strategy to improve sensitivity and specificity., Results: We applied JUMPptm to the deep brain proteome of Alzheimer's disease (AD), and identified 34,954 unique peptides with phosphorylation, methylation, acetylation, ubiquitination, and others. The phosphorylated peptides were validated by enriched phosphoproteome from the same sample. TMT-based quantification revealed 482 PTM peptides dysregulated at different stages during AD progression. For example, the acetylation of numerous mitochondrial proteins is significantly decreased in AD. A total of 60 PTM sites are found in the pan-PTM map of the Tau protein., Conclusion: The JUMPptm program is an effective tool for pan-PTM analysis and the resulting AD pan-PTM profile serves as a valuable resource for AD research., (© 2022 Wiley-VCH GmbH.)

Recent proteome and transcriptome profiling of Alzheimer's disease (AD) brains reveals RNA splicing dysfunction and U1 small nuclear ribonucleoprotein (snRNP) pathology containing U1-70K and its N-terminal 40-KDa fragment (N40K). Here we present a causative role of U1 snRNP dysfunction to neurodegeneration in primary neurons and transgenic mice (N40K-Tg), in which N40K expression exerts a dominant-negative effect to downregulate full-length U1-70K. N40K-Tg recapitulates N40K insolubility, erroneous splicing events, neuronal degeneration and cognitive impairment. Specifically, N40K-Tg shows the reduction of GABAergic synapse components (e.g., the GABA receptor subunit of GABRA2), and concomitant postsynaptic hyperexcitability that is rescued by a GABA receptor agonist. Crossing of N40K-Tg and the 5xFAD amyloidosis model indicates that the RNA splicing defect synergizes with the amyloid cascade to remodel the brain transcriptome and proteome, deregulate synaptic proteins, and accelerate cognitive decline. Thus, our results support the contribution of U1 snRNP-mediated splicing dysfunction to AD pathogenesis.

Forest is the main component of terrestrial ecosystems that harbors about 40% of the existing species on the earth. As a vital component of biodiversity, phyllosphere microbes in the canopy play a critical and unique role in maintaining plant health, improving host resistance, and influencing global biogeochemical cycle. However, the studies on the community structure of phyllosphere fungi in natural forests are scarce as compared to that on rhizosphere microbes. Consequently, we know litter about how phyllosphere fungi associates with leaf traits. In this study, we analyzed fungal community composition of canopy leaves of six dominant tree species ( i.e ., Pinus koraiensis , Tilia amurensis , Quercus mongolica , Acer mono , Fraxinus mandshurica , and Ulmus japonica ), in a broad-leaved Korean pine forest of Changbai Mountain Nature Reserve in Jilin Province, using high-throughput sequencing. We compared the differences of phyllosphere fungal community structure and functional groups of different dominant tree species. Moreover, 14 key leaf functional traits of their host trees were measured to investigate the relationships between fungal community composition and leaf functional traits. We found that the dominant phyla and class of phyllosphere fungi were Ascomycota and Basidiomycota, and Dothideomycetes and Taphrinomycetes, respectively. Results of LEfSe analysis indicated that all the tree species except Ulmus japonica had significant biomarkers, such as the Eurotiomycetes of Pinus koraiensis and the Ascomycetes of Quercus mongolica . The main functional groups of phyllosphere fungi were pathotroph. The results of redundancy and envfit analysis showed that functional traits related to plant nutrient acquisition as well as resistance to diseases and pests were the main factors influencing the community structure of phyllosphere fungi.

Histone variants, such as histone H3.3, replace canonical histones within the nucleosome to alter chromatin accessibility and gene expression. Although the biological roles of selected histone post-translational modifications (PTMs) have been extensively characterized, the potential differences in the function of a given PTM on different histone variants is almost always elusive. By applying proteomics and genomics techniques, we investigate the role of lysine 27 tri-methylation specifically on the histone variant H3.3 (H3.3K27me3) in the context of mouse embryonic stem cell pluripotency and differentiation as a model system for development. We demonstrate that while the steady state overall levels of methylation on both H3K27 and H3.3K27 decrease during differentiation, methylation dynamics studies indicate that methylation on H3.3K27 is maintained more than on H3K27. Using a custom-made antibody, we identify a unique enrichment of H3.3K27me3 at lineage-specific genes, such as olfactory receptor genes, and at binding motifs for the transcription factors FOXJ2/3. REST, a predicted FOXJ2/3 target that acts as a transcriptional repressor of terminal neuronal genes, was identified with H3.3K27me3 at its promoter region. H3.3K27A mutant cells confirmed an upregulation of FOXJ2/3 targets upon the loss of methylation at H3.3K27. Thus, while canonical H3K27me3 has been characterized to regulate the expression of transcription factors that play a general role in differentiation, our work suggests H3.3K27me3 is essential for regulating distinct terminal differentiation genes. This work highlights the importance of understanding the effects of PTMs not only on canonical histones but also on specific histone variants, as they may exhibit distinct roles.

Although somatic mutations in Histone 3.3 (H3.3) are well-studied drivers of oncogenesis, the role of germline mutations remains unreported. We analyze 46 patients bearing de novo germline mutations in histone 3 family 3A ( H3F3A ) or H3F3B with progressive neurologic dysfunction and congenital anomalies without malignancies. Molecular modeling of all 37 variants demonstrated clear disruptions in interactions with DNA, other histones, and histone chaperone proteins. Patient histone posttranslational modifications (PTMs) analysis revealed notably aberrant local PTM patterns distinct from the somatic lysine mutations that cause global PTM dysregulation. RNA sequencing on patient cells demonstrated up-regulated gene expression related to mitosis and cell division, and cellular assays confirmed an increased proliferative capacity. A zebrafish model showed craniofacial anomalies and a defect in Foxd3-derived glia. These data suggest that the mechanism of germline mutations are distinct from cancer-associated somatic histone mutations but may converge on control of cell proliferation., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Objective: To investigate the clinical features and outcome of neonatal acute respiratory distress syndrome (ARDS) in southwest Hubei, China., Methods: According to the Montreux definition of neonatal ARDS, a retrospective clinical epidemiological investigation was performed on the medical data of neonates with ARDS who were admitted to Department of Neonatology/Pediatrics in 17 level 2 or level 3 hospitals in southwest Hubei from January to December, 2017., Results: A total of 7 150 neonates were admitted to the 17 hospitals in southwest Hubei during 2017 and 66 (0.92%) were diagnosed with ARDS. Among the 66 neonates with ARDS, 23 (35%) had mild ARDS, 28 (42%) had moderate ARDS, and 15 (23%) had severe ARDS. The main primary diseases for neonatal ARDS were perinatal asphyxia in 23 neonates (35%), pneumonia in 18 neonates (27%), sepsis in 12 neonates (18%), and meconium aspiration syndrome in 10 neonates (15%). Among the 66 neonates with ARDS, 10 neonates (15%) were born to the mothers with an age of ≥35 years, 30 neonates (45%) suffered from intrauterine distress, 32 neonates (49%) had a 1-minute Apgar score of 0 to 7 points, 24 neonates (36%) had abnormal fetal heart monitoring results, and 21 neonates (32%) experienced meconium staining of amniotic fluid. Intraventricular hemorrhage was the most common comorbidity (12 neonates), followed by neonatal shock (9 neonates) and patent ductus arteriosus (8 neonates). All 66 neonates with ARDS were treated with mechanical ventilation in addition to the treatment for primary diseases. Among the 66 neonates with ARDS, 10 died, with a mortality rate of 15% (10/66), and 56 neonates were improved or cured, with a survival rate of 85% (56/66)., Conclusions: Neonatal ARDS in southwest Hubei is mostly mild or moderate. Perinatal asphyxia and infection may be the main causes of neonatal ARDS in this area. Intraventricular hemorrhage is the most common comorbidity. Neonates with ARDS tend to have a high survival rate after multimodality treatment.

We examined the effects of nitrogen, soil microbe and their interactions on biomass allocation, growth and photosynthesis of Fraxinus mandschurica, a typical tree species in Changbai Mountain, through outdoor control experiments. In June 2017, an experiment with two-factor randomized block design was carried out. There were four treatments: control (F), nitrogen addition (FN), sterilization (FS), sterilization and nitrogen addition (FSN), six repetitive blocks, three repetitions per block, including 18 repetitions of each treatment. In mid-August 2018, we measured photosynthetic parameters and then harvested seedlings to measure biomass and growth parameters in September. The results showed that compared with F, FN significantly increased total biomass by 14%, basal diameter by 9%, chlorophyll content, net photosynthetic rate (P n ), stomatal conduc-tance (g s ), transpiration rate (T r ) by 75%, 318%, 231%, 227% respectively. FS significantly increased total biomass by 13%, basal diameter by 9% and chlorophyll content, P n , g s and T r increased by 34%, 213%, 120% and 115%, respectively. FSN increased total biomass by 23%, basal diameter by 14%, chlorophyll content, P n , g s and T r increased by 81%, 672%, 312% and 273%, respectively. Nitrogen, soil microbe and their interactions had significant effects on biomass, growth and photosynthesis of F. mandschurica seedlings. Soil microbe would regulate the response of F. mandschurica seedlings to nitrogen.

Seeds are the basis for forest regeneration. To examine the composition and spatio-temporal dynamics of seed rains, a total of 150 seed traps of 0.5 m 2 were installed in a 25 hm 2 broad-leaved Korean pine (Pinus koraiensis) mixed forest plot in Changbai Mountains. With a total of 252 collections from May 2006 to September 2017, we collected 764299 mature and immature seeds which were belonged to 27 species, 17 genera, and 12 families. More than 90% of all collected seeds (704231 seeds) were from 13 canopy species. Seeds of four tree species, including Tilia amurensis, Fraxinus mandschurica, Acer mono, and Acer pseudo-sieboldianum could be collected every year from each trap. Mast-seeding was found in every canopy layer, but it happened one to two years earlier in the overstorey layer than midstorey and understorey layer. Almost all species produced seeds in autumn, with considerable spatiotemporal variation. Generally, the spatial variation of seeds was larger than temporal variation. Compared with annual variation coefficient of seeds in tropical forest of the Barro Colorado Island (BCI) and subtropical evergreen forest in the Gutianshan, annual variation coefficient of seeds in Changbai Mountains was higher, which supported the hypothesis that annual variation in seed rains would be lower in the tropics than that in higher latitudes.