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Abstract Fluxes in human copper levels recently garnered attention for roles in cellular signaling, including affecting levels of the signaling molecule cyclic adenosine monophosphate. We herein apply an unbiased temporal evaluation of the signaling and whole genome transcriptional activities modulated by copper level fluctuations to identify potential copper sensor proteins responsible for driving these activities. We find that fluctuations in physiologically relevant copper levels modulate EGFR signal transduction and activation of the transcription factor CREB. Both intracellular and extracellular assays support Cu1+ inhibition of the EGFR phosphatase PTPN2 (and potentially PTPN1)–via ligation to the PTPN2 active site cysteine side chain–as the underlying mechanism. We additionally show i) copper supplementation drives weak transcriptional repression of the copper importer CTR1 and ii) CREB activity is inversely correlated with CTR1 expression. In summary, our study reveals PTPN2 as a physiological copper sensor and defines a regulatory mechanism linking feedback control of copper stimulated EGFR/CREB signaling and CTR1 expression.

Abstract Cis-regulatory elements (CREs) are pivotal in orchestrating gene expression throughout diverse biological systems. Accurate identification and in-depth characterization of functional CREs are crucial for decoding gene regulation networks during cellular processes. In this study, we develop Kethoxal-Assisted Single-stranded DNA Assay for Transposase-Accessible Chromatin with Sequencing (KAS-ATAC-seq) to quantitatively analyze the transcriptional activity of CREs. A main advantage of KAS-ATAC-seq lies in its precise measurement of ssDNA levels within both proximal and distal ATAC-seq peaks, enabling the identification of transcriptional regulatory sequences. This feature is particularly adept at defining Single-Stranded Transcribing Enhancers (SSTEs). SSTEs are highly enriched with nascent RNAs and specific transcription factors (TFs) binding sites that define cellular identity. Moreover, KAS-ATAC-seq provides a detailed characterization and functional implications of various SSTE subtypes. Our analysis of CREs during mouse neural differentiation demonstrates that KAS-ATAC-seq can effectively identify immediate-early activated CREs in response to retinoic acid (RA) treatment. Our findings indicate that KAS-ATAC-seq provides more precise annotation of functional CREs in transcription. Future applications of KAS-ATAC-seq would help elucidate the intricate dynamics of gene regulation in diverse biological processes.

Abstract Do motor patterns of object lifting movements change as a result of ageing? Here we propose a methodology for the characterization of these motor patterns across individuals of different age groups. Specifically, we employ a bimanual grasp-lift-replace protocol with younger and older adults and combine measurements of muscle activity with grip and load forces to provide a window into the motor strategies supporting effective object lifts. We introduce a tensor decomposition to identify patterns of muscle activity and grip-load force ratios while also characterizing their temporal profiles and relative activation across object weights and participants of different age groups. We then probe age-induced changes in these components. A classification analysis reveals three motor components that are differentially recruited between the two age groups. Linear regression analyses further show that advanced age and poorer manual dexterity can be predicted by the coupled activation of forearm and hand muscles which is associated with high levels of grip force. Our findings suggest that ageing may induce stronger muscle couplings in distal aspects of the upper limbs, and a less economic grasping strategy to overcome age-related decline in manual dexterity.

Abstract N 6-methyladenosine (m6A) plays critical roles in regulating mRNA metabolism. However, comprehensive m6A methylomes in different plant tissues with single-base precision have yet to be reported. Here, we present transcriptome-wide m6A maps at single-base resolution in different tissues of rice and Arabidopsis using m6A-SAC-seq. Our analysis uncovers a total of 205,691 m6A sites distributed across 22,574 genes in rice, and 188,282 m6A sites across 19,984 genes in Arabidopsis. The evolutionarily conserved m6A sites in rice and Arabidopsis ortholog gene pairs are involved in controlling tissue development, photosynthesis and stress response. We observe an overall mRNA stabilization effect by 3’ UTR m6A sites in certain plant tissues. Like in mammals, a positive correlation between the m6A level and the length of internal exons is also observed in plant mRNA, except for the last exon. Our data suggest an active m6A deposition process occurring near the stop codon in plant mRNA. In addition, the MTA-installed plant mRNA m6A sites correlate with both translation promotion and translation suppression, depicting a more complicated regulatory picture. Our results therefore provide in-depth resources for relating single-base resolution m6A sites with functions in plants and uncover a suppression-activation model controlling m6A biogenesis across species.

Although the data-driven static voltage stability problems have been widely studied, most of the classical algorithms focus more on improving the accuracy of the system prediction, ignoring the error classification errors generated during the prediction process. Furthermore, current research ignores the utilization of data-driven voltage stability assessment of energy storage systems. Therefore, this paper proposes a static voltage stability assessment method for photovoltaic energy storage systems based on considering the error classification constraint algorithm using Neyman-Pearson umbrella algorithms. Firstly, the Spearman Correlation Coefficient is employed in the feature selection phase. Secondly, an updated voltage stability assessment (VSA) model is proposed. Compared with the existing data-driven prediction of system static voltage stability in the literature, it can realize voltage stability assessment more quickly. Furthermore, on the basis of rapid voltage stability assessment, the umbrella NP classifier can also effectively limit the first-class error and attenuate the effect of error classification by mirroring the control of the number of cycle splits and the type I classification error threshold. Finally, the simulation and experimental results show that the effectiveness and robustness of the scheme proposed in this paper in grid-connected photovoltaic energy farms.

Abstract Background The cumulative effect of postpartum weight retention from each pregnancy in a woman’s life may contribute to her risk of ultimately developing type 2 diabetes and cardiovascular disease. However, there is limited direct evidence supporting this hypothesis. Thus, we sought to characterize the impact of postpartum weight retention on the trajectories of cardiovascular risk factors over the first 5-years after pregnancy. Methods In this prospective observational cohort study, 330 women (mean age 35.7 ± 4.3 years, mean pre-pregnancy body mass index 25.2 ± 4.8 kg/m2, 50.9% primiparous) underwent serial cardiometabolic characterization (anthropometry, blood pressure, lipids, oral glucose tolerance test, insulin sensitivity/resistance (Matsuda index, HOMA-IR), C-reactive protein (CRP), adiponectin) at 1-year, 3-years, and 5-years postpartum. Based on the magnitude of weight change between pre-pregnancy and 5-years postpartum, they were stratified into the following 3 groups: weight loss (n = 100), weight gain 0–6% (n = 110), and weight gain ≥ 6% (n = 120). Results At 1-year postpartum, cardiovascular risk factors did not differ between the groups. However, an adverse risk factor profile progressively emerged in the weight retention groups at 3- and 5-years. Indeed, after covariate adjustment, there was stepwise worsening (from the weight loss group to weight gain 0–6% to weight gain ≥ 6% group) of the following cardiovascular risk factors at 5-years: triglycerides (p = 0.001), HDL (p = 0.02), LDL (p = 0.01), apolipoprotein-B (p = 0.003), Matsuda index (p

The small-signal stability of high voltage direct current (HVDC)-connected wind farms (WFs) is a challenging issue in modern power systems. The relative stability, i.e., the stability margin, of such a typical multiple-input multiple-output (MIMO) system is quite difficult to be quantified. This paper evaluates the relative stability of HVDC-connected WFs using a new stability index based on the ν-gap metric. We first develop a MIMO model represented by a transfer function matrix of the HVDC-connected WFs. Then, a new stability index, i.e., the robust stability margin, based on the ν-gap metric is proposed to quantify the relative stability of such a MIMO system. Finally, we propose a method to compute the stable region of control parameters based on the corresponding stability criterion of ν-gap metric. Case studies are given to demonstrate the effectiveness of the proposed method.

This study presents the first column-averaged dry-air mole fractions of carbon dioxide (XCO2), methane (XCH4) and carbon monoxide (XCO) in the coal mine aggregation area in Shanxi, China, using two portable Fourier transform infrared spectrometers (EM27/SUNs), in the framework of the Collaborative Carbon Column Observing Network (COCCON). The measurements, collected over two months, were analyzed. Significant daily variations were observed, particularly in XCH4, which highlight the impact of coal mining emissions as a major CH4 source in the region. This study also compares COCCON XCO with measurements from the TROPOspheric Monitoring Instrument (TROPOMI) onboard the Sentinel-5P satellite, revealing good agreement, with a mean bias of 7.15 ± 9.49 ppb. Additionally, comparisons were made between COCCON XCO2 and XCH4 data and analytical data from the Copernicus Atmosphere Monitoring Service (CAMS). The mean biases between COCCON and CAMS were −6.43 ± 1.75 ppm for XCO2 and 15.40 ± 31.60 ppb for XCH4. The findings affirm the stability and accuracy of the COCCON instruments for validating satellite observations and detecting local greenhouse gas sources. Operating COCCON spectrometers in coal mining areas offers valuable insights into emissions from these high-impact sources.

During the later reproductive period of rice growth, the chlorophyll in the leaves degraded, accompanied by the nitrogen (N) transportation from leaves to panicle, resulting in a change in leaf color from green to yellow. This study aimed to investigate the effects of exogenous N supply on leaf color-changing, N accumulation, N transportation, and N loss of indica-japonica hybrid rice during the grain-filling stage. Two indica-japonica hybrid rice cultivars, Chunyou 167 (CY167) and Chunyou 927 (CY927), which exhibited significant differences in leaf color-changing during the grain-filling stage, were selected as materials for field experiment and hydroponic experiment with low, medium, and high N treatments (LN, MN, and HN). The dynamic changes in SPAD value from heading to maturity were measured and fitted with quadratic function to extract leaf color-changing parameters; labeled 15N was used as N source after heading to trace the source of N in the panicle and the remobilization of vegetative organ N. The results showed that 67.37–72.38% of the panicle N was transported from vegetative organs, the N transport efficiency was the upper three leaves > lower leaves > stem, and about 3.1–35.0% of the transported N was lost via volatilization. The effects of exogenous N concentration on N harvest index, N dry matter/grain production efficiency, N reuse efficiency, and N loss were closely related to leaf color-changing parameters. In MN and HN treatment, the N loss was negatively correlated with the onset time of leaf color-changing (T0) and the final leaf color index (CIf), but positively correlated with the leaf color-changing rate (Rmean). Increasing the supply of exogenous N increased T0 and CIf, but decreased Rmean, N transport/reuse efficiency, N harvest index, and N dry matter/grain production efficiency. Compared to the cultivar CY167 with normal leaf color-changing, the “stay-green” cultivar CY927 had higher T0, CIf, and lower Rmean, resulting in less N volatilization loss, lower N harvest index and N transport efficiency, while higher N reuse efficiency. In conclusion, the exogenous N supply affects leaf color by influencing the transportation and reuse of leaf N during the grain-filling stage.

Summary: The N6-methyladenosine (m6A) RNA modification is an important regulator of gene expression. m6A is deposited by a methyltransferase complex that includes methyltransferase-like 3 (METTL3) and methyltransferase-like 14 (METTL14). High levels of METTL3/METTL14 drive the growth of many types of adult cancer, and METTL3/METTL14 inhibitors are emerging as new anticancer agents. However, little is known about the m6A epitranscriptome or the role of the METTL3/METTL14 complex in neuroblastoma, a common pediatric cancer. Here, we show that METTL3 knockdown or pharmacologic inhibition with the small molecule STM2457 leads to reduced neuroblastoma cell proliferation and increased differentiation. These changes in neuroblastoma phenotype are associated with decreased m6A deposition on transcripts involved in nervous system development and neuronal differentiation, with increased stability of target mRNAs. In preclinical studies, STM2457 treatment suppresses the growth of neuroblastoma tumors in vivo. Together, these results support the potential of METTL3/METTL14 complex inhibition as a therapeutic strategy against neuroblastoma.

Abstract The TMEM63 family proteins (A, B, and C), calcium-permeable channels in animals that are preferentially activated by hypo-osmolality, have been implicated in various physiological functions. Deficiency of these channels would cause many diseases including hearing loss. However, their structures and physiological roles are not yet well understood. In this study, we determine the cryo-electron microscopy (cryo-EM) structure of the mouse TMEM63C at 3.56 Å, and revealed structural differences compared to TMEM63A, TMEM63B, and the plant orthologues OSCAs. Further structural guided mutagenesis and calcium imaging demonstrated the important roles of the coupling of TM0 and TM6 in channel activity. Additionally, we confirm that TMEM63C exists primarily as a monomer under physiological conditions, in contrast, TMEM63B is a mix of monomer and dimer in cells, suggesting that oligomerization is a regulatory mechanism for TMEM63 proteins.

Soil texture affects rice nutrient uptake and yield formation by influencing soil structure, microbial activity, and soil nutrient supply capacity. Analyzing the relationship between soil texture, nutrient content, and rice agronomic traits is of great significance for precise and efficient fertilizer application. The tillage layer (0–20 cm) of 31 paddy fields in China’s main rice-producing areas was collected to perform rice pot experiments, and soil texture characteristics, physicochemical properties, microbial-related indicators, and rice agronomic traits were measured and analyzed. The results showed that these soils could be classified into four types of soil texture: loamy sandy soil, sandy loam soil, silty loam soil, and silty soil. Analysis of variance showed that the available nitrogen (AN), available potassium (AK), and available phosphorus (AP) contents were the highest in silty loam, silty, and sandy loam soils, respectively, and silt loamy soil had the highest CEC. Principal component analysis (PCA) also showed that soil physicochemical properties can be distinguished to a certain extent according to soil texture types. For the relationship of soil texture parameters and soil physicochemical properties, soil organic matter (OM), total nitrogen (TN), AN, ammonium nitrogen (NH4+-N), and microbial carbon (MBC) contents were positively correlated with soil clay content, AK was positively correlated with silt content, and soil phosphorus status was significantly related to pH. Mantel’s test revealed significant correlations between rice N, P, and K nutrient status, dry matter accumulation, and yield, and soil available nutrient content, MBC, pH, and soil texture parameters. Structural equation modeling (SEM) indicated that sand affected soil available nutrients by regulating pH, while clay can positively influence soil available nutrients by affecting soil organic matter mineralization and microbial activity, thus influencing nutrient absorption and yield formation in rice. Overall, in rice production, the silty and silty loam paddy soil with fine texture and higher clay content facilitates the mineralization of soil organic matter and the activity of soil microbes, resulting in more available soil nutrients, which benefits the rice absorption and accumulation of nutrients. Furthermore, a higher content of clay also promotes the distribution of dry matter to the panicle, thereby promoting rice yield formation.

ObjectivesThis paper aims to evaluate the impact resistance of Ti80 alloy under low-velocity impact loads using a numerical study of the dynamic response.MethodsFirst, the finite element software Abaqus/Explicit is used to establish a finite element model of a Ti80 alloy plate under low-velocity impact load. Second, the rationality of the material parameters and reliability of the finite element model are verified through a comparison with the experimental results. Finally, the effects of the impactor shape, yield strength and fracture energy on the dynamic response of the Ti80 alloy plate under low-velocity impact load are discussed on the basis of the finite element model.ResultsThe numerical results agree well with the experimental results in their dynamic response and deformation/failure modes. Under low-velocity impact load, damage initializes on the backside of the Ti80 alloy plate due to excessive tensile deformation. The hole expansion effect of the conical impactor causes serious plugging damage to the Ti80 alloy plate. The peak impact force, peak displacement of the impactor and energy absorbtion exhibit an approximately linear relationship to the yield strength. The fracture energy has a significant effect on the deformation/failure mode of the Ti80 alloy plate. Compared to the yield strength, the energy absorbtion is less sensitive to the fracture energy.ConclusionsThe results can provide references for the impact resistance design of Ti80 alloy structures.

ABSTRACTBackground: Elucidating epigenetic mechanisms could provide new biomarkers for disease diagnosis and prognosis. Technological advances allow genome-wide profiling of 5-hydroxymethylcytosines (5hmC) in liquid biopsies. 5hmC-Seal followed by NGS is a highly sensitive technique for 5hmC biomarker discovery in cfDNA. Currently, 5hmC Seal is optimized for EDTA blood collection. We asked whether heparin was compatible with 5hmC Seal as many clinical and biobanked samples are stored in heparin.Methods: We obtained 60 samples in EDTA matched to 60 samples in heparin from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Samples were comprised of 30 controls and 30 individuals who were later diagnosed with colon cancer. We profiled genome-wide 5hmC in cfDNA using 5hmC-Seal assay followed by NGS. The 5hmC profiling data from samples collected in EDTA were systematically compared to those in heparin across various genomic features.Results: cfDNA isolation and library construction appeared comparable in heparin vs. EDTA. Typical genomic distribution patterns of 5hmC, including gene bodies and enhancer markers, were comparable in heparin vs. EDTA. 5hmC analysis of cases and controls yielded highly correlated differential features suggesting that both anticoagulants were compatible with 5hmC Seal assay.Conclusions: While not currently recommended for the 5hmC-Seal protocol, blood samples stored in heparin were successfully used to generate analysable and biologically relevant genome-wide 5hmC profiling. Our findings are the first to support opportunities to expand the biospecimen resource to heparin samples for 5hmC Seal and perhaps other PCR-based technologies in epigenetic research.

Abstract Objective Basal insulin glargine has a neutral effect on cardiovascular risk in type 2 diabetes (T2DM). In practice, basal insulin is often paired with a glucagon-like peptide-1 receptor agonist (GLP1-RA) or meal insulin; however, the cardiovascular implications of these combinations have not been fully elucidated. In this context, we sought to evaluate the vascular function effects of adding the GLP1-RA exenatide or meal insulin lispro to basal glargine therapy in early T2DM. Methods In this 20-week trial, adults with T2DM of

Abstract Virtual synchronization control can be applied to DC/DC converter for enhanced inertia support by imitating the rotor dynamics of the synchronous generator (SG). However, efficient power sharing and robust operation ability cannot be guaranteed in a multiple parallel‐operated DC/DC converters system. This paper proposes the hierarchical control scheme to achieve higher efficiency and superior anti‐disturbance ability for multiple DC/DC converters with virtual synchronization‐based control. The primary control layer enables proportional power sharing by using improved virtual synchronization control for each DC/DC converter, which aims at eliminating the influence of line parameter mismatch among converters. The secondary control layer deals with DC voltage stability improvement through the extended disturbance‐observer‐based backstepping control with the consideration of external power fluctuation on the whole system. Two control levels are integrated as the hierarchical control architecture to realize different control objectives in different time scales, while only neighbouring communications and DC voltage information are needed among the system. Simulations on PSCAD/EMTDC are conducted and show that the load power is accurately and proportionally shared, while system oscillations are eliminated with the extended disturbance‐observer‐based backstepping control, which validates the advantages of the proposed hierarchical control scheme.

Abstract In clinical research, weight measurement in first trimester is often treated as a surrogate for pre-pregnancy weight. The validity of this critical assumption, however, is uncertain. Thus, we sought to prospectively evaluate the relationship between pre-gravid weight and first trimester weight. In this prospective preconception observational cohort study, 474 newly-married women in Liuyang, China, underwent pre-gravid evaluation at median 17.7 weeks before a singleton pregnancy, during which they had weight measurement in first trimester. The relationship between pre-gravid and first trimester weight was assessed by Bland–Altman analysis, Concordance Correlation Coefficient, and Pearson correlation. Mean pre-gravid weight was 49.8 ± 6.4 kg and mean weight in first trimester was 51.1 ± 7.0 kg. The Concordance Correlation Coefficient between pre-gravid and first trimester weight was 0.76 (95% limits of agreement: 0.72–0.80) and Pearson correlation was r = 0.78 (p

Combining a GLP-1 receptor agonist, to increase endogenous beta cell function, with exogenous insulin is a possible therapeutic option for the treatment of type 2 diabetes. Here, the authors show adding exenatide to basal insulin in early type 2 diabetes does not further enhance underlying pancreatic beta-cell function or the capacity to achieve diabetes remission, but may yield on-treatment glycemic benefits.

Background: Acute respiratory distress syndrome (ARDS) could account for a considerable proportion of neonatal death, while the genetic etiology and pathophysiology of neonatal ARDS remain elusive. In this case-control study, 515 neonates were enrolled in the China Neonatal Genomes Project (CNGP, NCT03931707) from August 2016 to June 2021, including 196 ARDS and 319 non-ARDS matched by sex, gestational age, birth weight, perinatal asphyxia, pneumonia, sepsis, and necrotizing enterocolitis. Clinical exome sequencing was used to detect genetic variants. Collapsing analyses together with permutation tests were used to identify ARDS risk genes enriched for rare variants in ARDS samples. In silico functional interaction analysis and expression pattern studies at different stages of lung development were used to investigate the biological functions of the risk genes. Results: Collapsing analyses identified that rare variants were significantly abundant in the genes associated with the precursor of the lamellar body and there were eight predicted risk genes with strong confidence (P

High-voltage direct current (HVDC) technology based on Line Commutated Converter (LCC) is widely used in modern power systems due to its numerous benefits. However, as a typical power electronic device, LCC-HVDC has caused significant changes in the dynamic behavior of modern power systems due to largely replaced conventional power supplies in power systems. The interactions among sending-terminal and receiving-terminal system become stronger and have caused some stability issues, but the mechanism behind this has yet to be fully revealed. In order to analyze the interactions among sending-terminal and receiving-terminal system of LCC-HVDC, a small-signal model of modular HSS modeling is proposed based on Harmonic State Space (HSS) theory. Comparison of time-domain response with detailed switching model shows that the proposed can well reflect the dynamic behavior of the detailed switching model. Based on the model, the influence of controller’s parameters on system stability is analyzed, as well as the dynamic interactions of LCC-HVDC among sending-terminal and receiving-terminal system are investigated. Analytical results demonstrate that there exists interactions among sending-terminal and receiving-terminal system which have an influence on the stability of the system.

Abstract Background/Objective Previous studies have consistently demonstrated that maternal weight status both before and during pregnancy is associated with infant birthweight. However, a fundamental limitation across this literature remains that previous studies have not evaluated the concomitant impact of paternal weight at conception, owing to the paucity of studies in which fathers were assessed prior to pregnancy. Thus, we established a cohort of preconception couples to prospectively evaluate the associations of maternal and paternal weight prior to pregnancy with infant birthweight at delivery. Methods In this prospective observational cohort study, 1292 newly-married women and their partners in Liuyang, China, were assessed at median of 23.3 weeks before a singleton pregnancy, thereby enabling concomitant assessment of preconception maternal and paternal body mass index (BMI) in relation to infant birthweight. Results Mean birthweight was 3294 ± 450 g with 147 neonates (11.4%) born large-for-gestational-age (LGA) and 94 (7.3%) small-for-gestational-age (SGA). After adjustment for maternal and paternal factors prior to conception (age, education, smoking, BMI, household income), length of gestation, total gestational weight gain, gestational diabetes, preeclampsia, and infant sex, it was noted that infant birthweight increased by 42.2 g (95% CI 29.5–54.8; p

ABSTRACT Upon influenza A virus (IAV) infection, the IAV progeny ribonucleoprotein complex, with a defective viral genome, is sensed by DNA-dependent activator of interferon-regulatory factor (DAI). DAI initiates the recruitment of an array of proteins to form a multiprotein platform (PANoptosome), which triggers apoptosis, necroptosis, and pyroptosis during IAV infection. However, the mechanisms mediating the assembly of the PANoptosome are unclear. Here, we identified a scaffold protein, sperm-associated antigen 9 (SPAG9), which could interact with DAI to promote cell death during IAV infection. We further demonstrated that the cell death enhanced by SPAG9 was achieved through the DAI/SPAG9/c-Jun N-terminal kinase (JNK) axis, which could promote IAV-induced DAI-mediated cell death, including apoptosis, necroptosis, and pyroptosis. Our data further showed that the DAI/SPAG9/JNK signaling pathway enhanced the interactions among receptor-interacting serine/threonine kinase 1 (RIPK1), RIPK3, and DAI, thereby promoting IAV-induced PANoptosome formation. Overall, our study for the first time revealed a feed-forward circuit signaling pathway that enhanced IAV-induced DAI-mediated cell death, provided insights into the molecular mechanisms of cell death, and established therapeutic targets to address infectious and inflammatory diseases. IMPORTANCE Upon influenza A virus (IAV) infection, DAI is activated, recruits downstream proteins to assemble a multiprotein platform (PANoptosome), and then triggers cell death. Until now, the protein composition and assembly mechanism of the PANoptosome during IAV infection had not been elucidated. Using proximity labeling and mass spectrometry technology, we identified SPAG9 as a novel component of the PANoptosome and confirmed that SPAG9 promotes IAV-induced cell death by enhancing the interaction among RIPK1, RIPK3, and DAI. Our study will broaden the knowledge of the molecular mechanisms of cell death.

Background: Women with a history of certain adverse outcomes in pregnancy (preterm birth, delivery of a small-for-gestational age [SGA] infant, preeclampsia, and gestational diabetes mellitus [GDM]) have an elevated lifetime prevalence of metabolic syndrome (MetS) and cardiovascular disease, compared with their peers. However, it is not known if MetS precedes the index pregnancy in young, nulliparous women who experience these antepartum outcomes. Thus, we sought to evaluate the relationship between pregravid cardiovascular risk factor profile and these pregnancy outcomes in low-risk women. Methods: In this prospective preconception cohort study, 1183 newly married women underwent systematic assessment of cardiovascular risk factors (anthropometry, blood pressure, lipids, glucose) at median 24.7 weeks before pregnancy, whereupon they were followed for the outcomes of preterm birth, SGA delivery, preeclampsia, and GDM. Results: Women who had pregravid MetS (harmonized definition) (n?=?49) were more likely to have a Caesarean delivery than their peers (61.4% vs. 38.6%, p?=?0.003). However, they did not have a higher incidence of preterm delivery, SGA, preeclampsia, or GDM. Similarly, women who had at least one of these adverse pregnancy outcomes (n?=?141) did not have a higher prevalence of MetS or any of its component disorders before pregnancy. Indeed, before pregnancy, there were no significant differences between these women and their peers in waist circumference, body mass index, blood pressure, fasting glucose, triglycerides, low-density-lipoprotein, or high-density-lipoprotein cholesterol. Conclusions: The adverse cardiovascular risk factor profile that is seen in women with a history of preterm birth, SGA, preeclampsia, or GDM does not necessarily manifest before their pregnancy.

Environmental conditions greatly affect the growth of rice. To investigate the geographic differences in yield formation of single-season high-yielding hybrid rice in southern China, experiments were conducted in 2017 and 2018 in the upper and middle–ower reaches of the Yangtze River with 10–30 main locally planted high-yielding hybrid cultivars used as materials. Compared with rice planted in the middle–lower reaches of the Yangtze River, rice planted in the upper reaches has a longer tillering duration, higher accumulated temperature (≥10°C) during tillering period, but lower accumulated temperature and solar radiation from initial booting to maturity. Yield traits comparison between the upper and the middle–lower reaches of Yangtze River showed that the former had 48.1% more panicles per unit area while the latter had 46.4% more grains per panicle; the rice yield in the former was positively correlated with the seed setting rate and the dry matter accumulation before heading, while the latter was positively correlated with grains per panicle and dry matter accumulation from booting to maturity. Comparison of the same variety Tianyouhuazhan planted in different regions showed there was a significant positive correlation between panicle number and the duration of and accumulated temperature during the tillering period (r=0.982**, r=0.993**, respectively), and between grains per panicle and accumulated solar radiation during booting period (r=0.952*). In the upper reaches of the Yangtze River, more than 90% of cultivars with an yield of greater than 11 t ha–1 had an effective panicle number of 250–340 m–2, and there was a significant negative correlation between seed setting rate and grains per panicle; therefore, the high-yielding rice production in these regions with a long effective tillering period (>40 d) should choose varieties with moderate grains per panicle, adopt crop managements such as good fertilizer and water measures during vegetative growth period to ensure a certain number of effective panicles, and to increase the dry matter accumulation before heading. While in regions with a short effective tillering period (

Recently, with the fast development of renewable energy, various power-electronic-based devices have been widely incorporated in power systems, and controller saturation limiters have been broadly utilized, such as in voltage-source converter. It has been well recognized that these saturation limiters make sustained oscillations possible. To study the impact of saturation limiters, by considering the dynamical response of double saturation limiters in both the d-axis and q-axis of the alternating current control, this paper establishes single-input-single-output models for two novel phenomena including the double-clipped oscillation and single-clipped oscillation, based on the describing function. Then the describing-function-based Nyquist criterion is used to obtain the amplitude and frequency of the sustained oscillations. The model accuracy is verified by the electromagnetic transient simulation, and the influences of control parameters are extensively studied. All these findings clearly demonstrate that the saturation limiters play an active role in sustained oscillations in power-electronic-based power systems.

The recent blackout in UK indicates that the adequacy of flexible resources is a significant factor for the stability of bulk energy system under the high integration of renewable energy. This paper proposes a planning model that incorporates various flexible resources into uncertain energy system and hence optimizes the unites' capacity and dispatch schedule. Based on Bash Game theory, the optimization capacity and dispatch schedule problems are formulated accordingly. Without setting the capacity configuration variable, the model initiatively considers the stochastic nature of RE at the planning stage. To simplify the complexity of the planning model, the problem is relaxation decoupled into two convex sub-issues, which achieves dramatic improvements in solution time. The novel model has been simulated both under IEEE-39 system and IEEE-118 system and hence the model's performance has been tested. Under the proposed model, the energy system can operate in a secure, economic and optimal state. Results demonstrate the effectiveness of the proposed method in applying to the future energy system.

Thermally assisted surface hardening techniques have led to a surge in research efforts and industrial applications, with emphasis on strengthening of metallic materials with high work hardening, high strength and/or poor deformability. This paper reviews the development of common thermally assisted surface hardening techniques, including warm shot peening, warm laser shock peening, and thermally assisted ultrasonic surface hardening. The development and working principle for each of the techniques are discussed. The enhanced mechanical properties and corresponding mechanisms are reviewed in detail. As compared with conventional surface hardening techniques, thermally assisted surface hardening techniques with optimum processing temperatures can further increase the surface and subsurface hardness, thickness of the hardening layer, fatigue life, and wear resistance of mechanical components. The improvements are attributed to the unique microstructures fabricated by the synergistic effects of thermal energy and high-strain-rate plastic deformation. Thermal energy can soften the materials, allowing plastic deformation to produce higher magnitude and deeper region of work hardening. More interestingly, the thermomechanical treatment can also induce dynamic strain aging and dynamic precipitation in some metallic alloys, which leads to precipitation strengthening and enhanced stability of dislocations and compressive residual stress. The coupled thermal-dynamic effect enables a broader design space for alloy hardening. Lastly, future research directions of thermally assisted surface hardening techniques are discussed.

Summary: Hypotonic stress causes the activation of swelling-activated nonselective cation channels (NSCCs), which leads to Ca2+-dependent regulatory volume decrease (RVD) and adaptive maintenance of the cell volume; however, the molecular identities of the osmosensitive NSCCs remain unclear. Here, we identified TMEM63B as an osmosensitive NSCC activated by hypotonic stress. TMEM63B is enriched in the inner ear sensory hair cells. Genetic deletion of TMEM63B results in necroptosis of outer hair cells (OHCs) and progressive hearing loss. Mechanistically, the TMEM63B channel mediates hypo-osmolarity-induced Ca2+ influx, which activates Ca2+-dependent K+ channels required for the maintenance of OHC morphology. These findings demonstrate that TMEM63B is an osmosensor of the mammalian inner ear and the long-sought cation channel mediating Ca2+-dependent RVD.

ObjectivesThe sex ratio at birth (proportion of boys to girls) generally shows slight male preponderance but may decrease in response to societal stressors. Discrete adverse events such as terrorist attacks and disasters typically lead to a temporary decline in the sex ratio 3–5 months later, followed by resolution over around 5 months thereafter. We hypothesised that the unexpected outcome of the 2016 US presidential election may have been a societal stressor for liberal-leaning populations and thereby precipitated such an effect on the sex ratio in Canada.DesignEcological study.SettingAdministrative data for Ontario (Canada’s most populous province).ParticipantsAll births in Ontario from April 2010 to Oct 2017 inclusive (n=1 079 758).Primary and secondary outcome measuresWe determined the sex ratio at birth in Ontario for each month from April 2010 to October 2017 and performed segmented regression analysis to evaluate the seasonally adjusted sex ratio for the following three time periods: before the November 2016 election; after the election to before the anticipated impact; and from anticipated impact to 5 months thereafter.ResultsIn the 12 months following the election, the lowest sex ratio occurred in March 2017 (4 months post election). Compared with the preceding months, the sex ratio was lower in the 5 months from March to July 2017 (p=0.02) during which time it was rising (p=0.01), reflecting recovery from the nadir. Both effects were seen in liberal-leaning regions of Ontario (lower sex ratio (p=0.006) and recovery (p=0.002) in March–July 2017) but not in conservative-leaning areas (p=0.12 and p=0.49, respectively).ConclusionThe 2016 US presidential election preceded a temporary reduction in the sex ratio at birth in Canada, with the time course of changes therein matching the characteristic pattern of a discrete societal stressor.

Abstract Background Gestational diabetes (GDM) and milder gestational impaired glucose tolerance (GIGT) identify women at risk of developing type 2 diabetes and cardiovascular disease later in life. Accordingly, the postpartum years after gestational dysglycemia can provide insight into early events in the natural history of these disorders. We thus sought to prospectively evaluate the relationship between gestational glucose tolerance and emerging cardiometabolic biomarkers [adiponectin, chemerin, retinol-binding protein-4 (RBP-4), C-reactive protein (CRP), plasminogen activator inhibitor-1 (PAI-1)] at both 1- and 3-years postpartum in a cohort reflecting the full spectrum of gestational dysglycemia (from normal to GIGT to GDM). Methods Three-hundred-and-thirty-nine women completed a glucose challenge test (GCT) and oral glucose tolerance test (OGTT) in pregnancy, which identified 4 gestational glucose tolerance groups: GDM (n = 105); GIGT (n = 59); abnormal GCT with normal OGTT (n = 99); and normal GCT with normal OGTT (n = 76). At 1- and 3-years postpartum, the women underwent repeat OGTT with measurement of biomarkers (adiponectin/chemerin/RBP-4/CRP/PAI-1). Results Serum adiponectin was lower in women with GDM and GIGT at both 1-year and 3-years (both P ≤ 0.002), whereas chemerin, RBP-4, CRP and PAI-1 showed no differences across the 4 groups. Importantly, the change in PAI-1 between 1- and 3-years progressively increased from the normal GCT group to the abnormal GCT group to GIGT to GDM (P = 0.03). Indeed, both GDM (t = 2.98, P = 0.003) and GIGT (t = 2.14, P = 0.03) independently predicted an increase in PAI-1 from 1- to 3-years postpartum. Conclusions Hypoadiponectinemia and rising PAI-1 over time are early features of the cardiometabolic biomarker profile of women with recent gestational dysglycemia.

The investigation of real-time dynamic behavior evaluation in the active distribution networks (ADNs) is a challenging task, and it has great importance due to the emerging trend of distributed generations, electric vehicles, and flexible loads integration. The advent of new elements influences the dynamic behavior of the electric distribution networks and increases the assessment complexity. However, the proper implementation of low-cost phasor measurement units (PMUs) together with the development of power system applications offer tremendous benefits. Therefore, this paper proposes a PMU-based multi-dimensional dynamic index approach for real-time dynamic behavior evaluation of ADNs. The proposed evaluation model follows the assessment principles of accuracy, integrity, practicability, and adaptability. Additionally, we introduced low-cost PMUs in the assessment model and implemented them for real-time and high-precision monitoring of dynamic behaviors in the entire distribution network. Finally, a complete model called the real-time dynamic characteristics evaluation system is presented and applied to the ADN. It is pertinent to mention that our proposed evaluation methodology does not rely on the network topology or line parameters of the distribution network since only the phasor measurements of node voltage and line current are involved in the dynamic index system. Thus, the presented methodology is well adaptive to different operation states of ADN despite frequent topology changes. The validation of the proposed approach was verified by conducting simulations on the modified IEEE 123-node distribution network. The obtained results verify the effectiveness and relevance of the proposed model for the real-time dynamic behavior evaluation of ADNs.

Electric power distribution networks plays a significant role in providing continuous electrical energy to different categories of customers. In the context of the present advancements, future load expansion in the active distribution networks (ADNs) poses the key challenge of planning to be derived as a multi-stage optimization task, including the optimal expansion planning scheme optimization (EPSO). The planning scheme optimization is a multi-attribute decision-making issue with high complexity and solving difficulty, especially when it involves a large-scale planning zone. This paper proposes a novel approach of a multi-year planning scheme for the effective solution of the EPSO problem in large planning zones. The proposed approach comprises three key parts, where the first part covers two essential aspects, i.e., (i) suggesting a project condition set that considers the elements directly related to a group of specific conditions and requirements (collectively referred to as conditions) to ADN planning projects; and (ii) Developing a condition scoring system to evaluate planning projects. The second part of our proposed scheme is a quantization method of correlativity among projects based on two new concepts: contribution index (CI) and dependence index (DI). Finally, considering the multi-year rolling optimization, a detailed mathematical model of condition evaluation and spatiotemporal optimization sequencing of ADN planning projects is developed, where the evaluation and optimization are updated annually. The proposed model has been successfully validated on a practical distribution network located in Xiantao, China. The investigated case study and comparisons verify the various advantages, suitability, and effectiveness of the proposed planning scheme, consequently saving more than 10% of the investment compared with the existing implemented scheme.

Background The 1‐hour glucose challenge test (GCT) is routinely performed in pregnancy to screen for gestational diabetes mellitus. Remarkably, it has recently emerged that the GCT can also predict a woman's future risk of cardiovascular disease, although the mechanistic basis of this relationship is unclear. In this context we hypothesized that a higher GCT may identify women with an otherwise unrecognized adverse cardiovascular phenotype. Thus, we sought to evaluate the relationship between the antepartum GCT and subsequent postpartum cardiovascular risk factor profile. Methods and Results In this study 503 women completed a screening GCT in late second trimester and then underwent cardiometabolic characterization at 3 months postpartum, whereupon traditional (blood pressure, glucose, lipids) and nontraditional (apolipoprotein B, C‐reactive protein, adiponectin) cardiovascular risk factors were compared across GCT tertiles. At 3 months postpartum, each of the following risk factors progressively worsened from the lowest to middle to highest GCT tertile: fasting glucose (P=0.0002), 2‐hour glucose (P

Using either electropulsing (EP) or surface severe plastic deformation (SSPD) to process metallic glasses can improve their plasticity, however, the moderate improvement in plasticity does not warrant a commercial usage. This work, for the first time, demonstrates the integration of electropulsing and surface severe plastic deformation is much more effective in improving the plasticity of metallic glasses than EP or SSPD treatment alone, opening a new avenue towards an unprecedented combination of strength and plasticity in metallic glasses. It is found that SSPD can generate microstructure heterogeneity featured by a mixture of matrix and plastically displaced regions with increased atomic volume. When applying EP and SSPD simultaneously, a synergistic effect occurs to produce a hybrid network with excess free volume and nanocrystals uniformly embedded in amorphous matrix. Molecular dynamics simulation and fracture surface analysis further reveal that the hybrid network is able to effectively reduce shear band localization, and therefore delay the fracture of metallic glasses. Keywords: Structure heterogeneity, Electropulsing-assisted surface severe plastic deformation, Nanocrystals, Free volume, Metallic glass, Plasticity

Endophilin A1 is a member of the N-BAR domain-containing endophilin A protein family that is involved in membrane dynamics and trafficking. At the presynaptic terminal, endophilin As participate in synaptic vesicle recycling and autophagosome formation. By gene knockout studies, here we report that postsynaptic endophilin A1 functions in synaptic plasticity. Ablation of endophilin A1 in the hippocampal CA1 region of mature mouse brain impairs long-term spatial and contextual fear memory. Its loss in CA1 neurons postsynaptic of the Schaffer collateral pathway causes impairment in their AMPA-type glutamate receptor-mediated synaptic transmission and long-term potentiation. In KO neurons, defects in the structural and functional plasticity of dendritic spines can be rescued by overexpression of endophilin A1 but not A2 or A3. Further, endophilin A1 promotes actin polymerization in dendritic spines during synaptic potentiation. These findings reveal a physiological role of endophilin A1 distinct from that of other endophilin As at the postsynaptic site.

A virtual power plant takes advantage of interactive communication and energy management systems to optimize and coordinate the dispatch of distributed generation, interruptible loads, energy storage systems and battery switch stations, so as to integrate them as an entity to exchange energy with the power market. This paper studies the optimal dispatch strategy of a virtual power plant, based on a unified electricity market combining day-ahead trading with real-time trading. The operation models of interruptible loads, energy storage systems and battery switch stations are specifically described in the paper. The virtual power plant applies an optimal dispatch strategy to earn the maximal expected profit under some fluctuating parameters, including market price, retail price and load demand. The presented model is a nonlinear mixed-integer programming with inter-temporal constraints and is solved by the fruit fly algorithm.

This paper presents a hierarchical multi-stage scheduling scheme for the AC/DC hybrid active distribution network (ADN). The load regulation center (LRC) is considered in the developed scheduling strategy, as well as the AC and DC sub-network operators. They are taken to be different stakeholders. To coordinate the interests of all stakeholders, a two-level optimization model is established. The flexible loads are dispatched by LRC in the upper-level optimization model, the objective of which is minimizing the loss of the entire distribution network. The lower-level optimization is divided into two sub-optimal models, and they are carried out to minimize the operating costs of the AC/DC sub-network operators respectively. This two-level model avoids the difficulty of solving multi-objective optimization and can clarify the role of various stakeholders in the system scheduling. To solve the model effectively, a discrete wind-driven optimization (DWDO) algorithm is proposed. Then, considering the combination of the proposed DWDO algorithm and the YALMIP toolbox, a hierarchical optimization algorithm (HOA) is developed. The HOA can obtain the overall optimization result of the system through the iterative optimization of the upper and lower levels. Finally, the simulation results verify the effectiveness of the proposed scheduling scheme.