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Several amino acids can stimulate milk synthesis in mammary epithelial cells (MECs), however, the regulatory role of isoleucine (Ile) and underlying molecular mechanism remain poorly understood. In this study, we aimed to evaluate the regulatory effects of Ile on milk protein and fat synthesis in MECs and reveal the mediation mechanism of Brahma-related gene 1 (BRG1) on this regulation. Ile dose-dependently affected milk protein and fat synthesis, mTOR phosphorylation, SREBP-1c expression and maturation, and BRG1 protein expression in bovine MECs. PI3K inhibition by LY294002 treatment blocked the stimulation of Ile on BRG1 expression. BRG1 knockdown and gene activation experiments showed that it mediated the stimulation of Ile on milk protein and fat synthesis, mTOR phosphorylation, and SREBP-1c expression and maturation in MECs. ChIP-PCR analysis detected that BRG1 bound to the promoters of mTOR and SREBP-1c, and ChIP-qPCR further detected that these binding were increased by Ile stimulation. In addition, BRG1 positively regulated the binding of H3K27ac to these two promoters, while it negatively affected the binding of H3K27me3 to these promoters. BRG1 knockdown blocked the stimulation of Ile on these two gene expression. The expression of BRG1 was higher in mouse mammary gland in the lactating period, compared with that in the puberty or dry period. Taken together, these experimental data reveal that Ile stimulates milk protein and fat synthesis in MECs via the PI3K-BRG1-mTOR/SREBP-1c pathway.
Many waterflooding oil fields, injecting water into an oil-bearing reservoir for pressure maintenance, are in their middle to late stages of development. To explore the geological conditions and improve oilfield recovery of the most important well group of the Hu 136 block, located on the border areas of three provinces (Henan, Shandong, and Hebei), Zhongyuan Oilfield, Sinopec, central China, a 14C cross-well tracer monitoring technology was developed and applied in monitoring the development status and recognize the heterogeneity of oil reservoirs. The tracer response in the production well was tracked, and the water drive speed, swept volume of the injection fluid were obtained. Finally, the reservoir heterogeneity characteristics, such as the dilution coefficient, porosity, permeability, and average pore-throat radius, were fitted according to the mathematical model of the heterogeneous multi-layer inter-well theory. The 14C-AMS technique developed in this work is expected to be a potential analytical method for evaluating underground reservoir characteristics and providing crucial scientific guidance for the mid to late oil field recovery process.
Developmental signals and environmental stresses regulate carbon distribution in the vegetative and reproductive organs of plants and affect seed yield. Cleistogenes songorica is a xerophytic grass with great potential application value in ecological restoration. However, how carbohydrate transport and distribution during grain filling affect the seed yield of C. songorica under water stress is not clear. The present study showed that the soluble sugar and starch contents of cleistogamous (CL) spikes and chasmogamous (CH) spikes were significantly higher at the milk stage, which was attributed to a significantly higher seed number and seed yield per spike under water stress conditions than under well-watered conditions (P < 0.01). RNA-seq data revealed a total of 54,525 differentially expressed genes (DEGs) under water stress conditions, but only 3744 DEGs were shared among all comparison groups. Weighted gene co-expression network analysis showed that the transport and distribution of carbohydrates were regulated by ABA-responsive genes (CsABA8OX1_1, CsABA8OX1_2, CsABA8OX2_1, CsABA8OX2_2, CsNCED3, CsNCED1_1, CsNCED1_2 and CsNCED4_1) and sugar transport and starch synthesis genes (CsSUS1, CsSUS2, CsSUS3, CsAGP1, CsAGP4, CsAGP5, CsSSS1 and CsSBE5) under water stress conditions. These genes jointly regulated carbohydrate remobilization in sources (stems, leaves and sheaths) to promote grain filling and improve seed yield. The present study helped to clarify the phenotypic, metabolic and transcriptional response mechanisms of vegetative organs, such as stems and leaves, and reproductive organs, such as CL spikes and CH spikes, to promote carbohydrate redistribution under water stress, and it provides theoretical guidance for improving seed yields.
Nicotine 2,6-dihydroxybenzoate is a nicotine salt that can be used as the nicotine source in tobacco products. X-ray powder diffraction data, unit-cell parameters, and space group for nicotine 2,6-dihydroxybenzoate, C10H15N2⋅C7H5O4, are reported [a = 7.726(8) Å, b = 11.724(3) Å, c = 9.437(1) Å, α = 90°, β = 109.081(3)°, γ = 90°, unit-cell volume V = 802.902 Å3, Z = 2, ρcal = 1.309 g cm−3, and space group P21] at room temperature. All measured lines were indexed and were consistent with the P21 space group.
Land fiscalization in China is a local development strategy intended to tilt the distribution of interests disproportionately toward local officials. We propose that the degree of power concentration among provincial Chinese leaders affects their need for support from lower-level bureaucrats. The more that power is dispersed among provincial leaders, the more they are incentivized to dispense benefits to local officials. To test this hypothesis, we used provincial-year panel data spanning 2003–2012 to examine how power concentration among provincial leaders affected land fiscalization within their jurisdictions. The empirical results robustly supported the hypothesis.
To explore whether embryo culture with melatonin (MT) can improve the embryonic development and clinical outcome of patients with repeated cycles after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) failure, immature oocytes from controlled ovarian superovulation cycles were collected for in vitro maturation (IVM) and ICSI. The obtained embryos were cultured in 0, 10–11, 10–9, 10–7 and 10–5 M MT medium respectively, and 10–9 M was screened out as the optimal concentration. Subsequently, 140 patients who underwent failed IVF/ICSI cycles received 140 cycles of embryo culture in vitro with a medium containing 10–9 M MT, these 140 MT culture cycles were designated as the experimental group (10–9 M group), and the control group was the previous failed cycles of patients (0 M group). The results showed that the fertilization, cleavage, high-quality embryo, blastocyst, and high-quality blastocyst rates of the 10–9 M group were significantly higher than those of the 0 M group (P < 0.01; P < 0.01; P < 0.0001; P < 0.0001; P < 0.0001). To date, in total, 50 vitrified-warmed cycle transfers have been performed in the 10–9 M group and the implantation rate, biochemical pregnancy rate and clinical pregnancy rate were significantly higher than those in the 0 M group (all P < 0.0001). Two healthy infants were delivered successfully and the other 18 women who achieved clinical pregnancy also had good examination indexes. Therefore the application of 10–9 M MT to embryo cultures in vitro improved embryonic development in patients with repeated cycles after failed IVF/ICSI cycles and had good clinical outcomes.
Temperature strongly impacts the rates of physiological and biochemical processes, which in turn can determine the survival and population size of insects. At low temperatures performance is limited, however, cold tolerance and performance at low temperature can be improved after short- or long-term acclimation in many insect species. To understand mechanisms underlying acclimation, we sequenced and compared the transcriptome of the blowfly Chrysomya megacephala under rapid cold hardening (RCH) and long-term cold acclimation (LCA) conditions. The RCH response was dominated by genes related to immune response, spliceosome, and protein processing in endoplasmic reticulum with up-regulation during recovery from RCH. In contrast, LCA was associated with genes related to carbohydrate metabolism and cytoskeleton branching and stabilizing. Meanwhile, mRNA levels of genes related to glycerophospholipid metabolism, and some heat shock proteins (Hsps) were collectively up-regulated by both RCH and LCA. There were more genes and pathway adjustments associated with LCA than RCH. Overall, the transcriptome data provide basic information of molecular mechanisms underpinning the RCH and LCA response. The partly independent molecular responses to RCH and LCA suggest that several avenues for manipulating cold performance exist and RCH might be more effective as it only triggers fewer genes and affects the general metabolisms less. These observations provide some appropriate methods to improve cold tolerance of C. megacephala, and hold promise for developing an extended use of mass-reared C. megacephala with better cold performance as a pollinator of crops at low temperatures.
Long-term care given to disabled older adults takes many forms, with each impacting life satisfaction through different ways. Drawing data from the 2011–2018 China Health and Retirement Longitudinal Survey, this article explores the effects of various care types on life satisfaction, with a particular focus on disabled older persons. Estimates derived from a fixed effects model with propensity score matching show that compared with formal care, informal care has significant positive effects on life satisfaction for disabled older adults. In addition, informal care has its greatest positive effect on life satisfaction on those who are mildly disabled, men and rural residents compared to their counterparts, while formal care addresses the needs of individuals with severe disability. We find that the main channels of effect occur through reduced loneliness and unhappiness, increased participation in social activities and improved physical health. This work contributes to the existing literature by demonstrating how various care types affect life satisfaction in China where filial piety, the central pillar of the Confucian ethics, is one of the common shared values among residents. These findings highlight the benefits derived from policies that promote and support the provision of informal care for older individuals. Moreover, there is a pressing need to buttress the formal care provision as a supplement to support severely disabled older adults in China.
When a manipulator captures its target by a visual servo system, uncertainties can arise because of mechanical system and visual sensors exist error. This paper proposes an intelligent method to predict the successful rate for a manipulator to capture its target with motion and sensor errors. Because the mapping between the joint space of the manipulator and the Cartesian space at the end of the manipulator is nonlinear, when there is a bounded error of the manipulator’s joint, the error range of the end motion is constantly changing with the different joint positions. And at the same time, the visual servo camera will also measure the target from different positions and postures, so as to produce measurement results with different error ranges. The unknown time-varying error property not only greatly affects the stability of the closed-loop control but also causes the capture failure. The purpose of this paper is to estimate the success probability of different capture trajectories by establishing the nondeterministic model of manipulator control system. First, a system model including motion subsystem and feedback subsystem was established with system error described by Gaussian probability. And then Bayesian estimation was introduced into the system model to estimate the executing state of the predefined trajectory. Linear least quadratic regulators (LQR) control is used to simulate the input correction in the closed-loop control between motion subsystem and feedback subsystem. At last, the successful probability of capturing the target is established by the Gaussian distribution at the end point of the trajectory with geometric relationship calculation between tolerance range and error distribution. The effectiveness and practicability of the proposed method are proved by simulation and experiment.
Gut microbiome and dietary patterns have been suggested to be associated with depression/anxiety. However, limited effort has been made to explore the effects of possible interactions between diet and microbiome on the risks of depression and anxiety.
Using the latest genome-wide association studies findings in gut microbiome and dietary habits, polygenic risk scores (PRSs) analysis of gut microbiome and dietary habits was conducted in the UK Biobank cohort. Logistic/linear regression models were applied for evaluating the associations for gut microbiome-PRS, dietary habits-PRS, and their interactions with depression/anxiety status and Patient Health Questionnaire (PHQ-9)/Generalized Anxiety Disorder-7 (GAD-7) score by R software.
We observed 51 common diet–gut microbiome interactions shared by both PHQ score and depression status, such as overall beef intake × genus Sporobacter [hurdle binary (HB)] (PPHQ = 7.88 × 10−4, Pdepression status = 5.86 × 10−4); carbohydrate × genus Lactococcus (HB) (PPHQ = 0.0295, Pdepression status = 0.0150). We detected 41 common diet–gut microbiome interactions shared by GAD score and anxiety status, such as sugar × genus Parasutterella (rank normal transformed) (PGAD = 5.15 × 10−3, Panxiety status = 0.0347); tablespoons of raw vegetables per day × family Coriobacteriaceae (HB) (PGAD = 6.02 × 10−4, Panxiety status = 0.0345). Some common significant interactions shared by depression and anxiety were identified, such as overall beef intake × genus Sporobacter (HB).
Our study results expanded our understanding of how to comprehensively consider the relationships for dietary habits–gut microbiome interactions with depression and anxiety.
The optimization of laser pulse shapes is of great importance and a major challenge for laser direct-drive implosions. In this paper, we propose an efficient intelligent method to perform laser pulse optimization via hydrodynamic simulations guided by the genetic algorithm and random forest algorithm. Compared to manual optimizations, the machine-learning guided method is able to efficiently improve the areal density by a factor of 63% and reduce the in-flight-aspect ratio by a factor of 30% at the same time. A relationship between the maximum areal density and ion temperature is also achieved by the analysis of the big simulation dataset. This design method has been successfully demonstrated by the 2021 summer double-cone ignition experiments conducted at the SG-II upgrade laser facility and has great prospects for the design of other inertial fusion experiments.
Taurine (Tau) has many profound physiological functions, but its role and molecular mechanism in muscle cells are still not fully understood. In this study, we investigated the role and underlying molecular mechanism of Tau on protein synthesis and proliferation of C2C12 myoblast cells. Cells were treated with Tau (0, 60, 120, 180 and 240 μM) for 24 h. Tau dose-dependently promoted protein synthesis, cell proliferation, mechanistic target of rapamycin protein (mTOR) phosphorylation and also AT-rich interaction domain 4B (ARID4B) expression, with the best stimulatory effects at 120 μM. LY 294002 treatment showed that Tau promoted ARID4B expression in a phosphoinositide 3-kinase (PI3K)-dependent manner. ARID4B knockdown (by small interfering RNA transfection for 24 h) prevented Tau from stimulating protein synthesis and cell proliferation, whereas ARID4B gene activation (using the CRISPR/dCas9 technology) had stimulatory effects. ARID4B knockdown abolished Tau signalling to mRNA expression and protein phosphorylation of mTOR, whereas ARID4B gene activation had stimulatory effects. Chromatin immunoprecipitation (ChIP)-PCR identified that all of ARID4B, H3K27ac and H3K27me3 bound to the −4368 to –4591 bp site in the mTOR promoter, and ChIP-quantitative PCR (qPCR) further detected that Tau stimulated ARID4B binding to this site. ARID4B knockdown or gene activation did not affect H3K27me3 binding to the mTOR promoter but decreased or increased H3K27ac binding, respectively. Furthermore, ARID4B knockdown abolished the stimulation of Tau on H3K27ac binding to the mTOR promoter. In summary, these data uncover that Tau promotes protein synthesis and proliferation of C2C12 myoblast cells through the PI3K-ARID4B-mTOR pathway, providing a deep understanding of how Tau regulates anabolism in muscle cells.
Previous studies have demonstrated structural and functional changes of the hippocampus in patients with major depressive disorder (MDD). However, no studies have analyzed the dynamic functional connectivity (dFC) of hippocampal subregions in melancholic MDD. We aimed to reveal the patterns for dFC variability in hippocampus subregions – including the bilateral rostral and caudal areas and its associations with cognitive impairment in melancholic MDD.
Forty-two treatment-naive MDD patients with melancholic features and 55 demographically matched healthy controls were included. The sliding-window analysis was used to evaluate whole-brain dFC for each hippocampal subregions seed. We assessed between-group differences in the dFC variability values of each hippocampal subregion in the whole brain and cognitive performance on the MATRICS Consensus Cognitive Battery (MCCB). Finally, association analysis was conducted to investigate their relationships.
Patients with melancholic MDD showed decreased dFC variability between the left rostral hippocampus and left anterior lobe of cerebellum compared with healthy controls (voxel p < 0.005, cluster p < 0.0125, GRF corrected), and poorer cognitive scores in working memory, verbal learning, visual learning, and social cognition (all p < 0.05). Association analysis showed that working memory was positively correlated with the dFC variability values of the left rostral hippocampus-left anterior lobe of the cerebellum (r = 0.338, p = 0.029) in melancholic MDD.
These findings confirmed the distinct dynamic functional pathway of hippocampal subregions in patients with melancholic MDD, and suggested that the dysfunction of hippocampus-cerebellum connectivity may be underlying the neural substrate of working memory impairment in melancholic MDD.
Laser–plasma accelerators (LPAs) have great potential to realize a compact X-ray free-electron laser (FEL), which is limited by the beam properties currently. Two-color high-intensity X-ray FEL provides a powerful tool for probing ultrafast dynamic systems. In this paper, we present a simple and feasible method to generate a two-color X-ray FEL pulse based on an LPA beam. In this scheme, time-dependent mismatch along the bunch is generated and manipulated by the designed lattice system, enabling FEL lasing at different wavelength within two undulator sections. The time separation between the two pulses can be precisely adjusted by varying the time-delay chicane. Numerical simulations show that two-color soft X-ray FELs with gigawatt-level peak power and femtosecond duration can be generated, which confirm the validity and feasibility of the scheme.
The Middle Miocene Climatic Optimum is known for abrupt events during the global cooling trend of the past 20 Ma. Its identification in the Tibetan Plateau can help explain the cause of the critical Middle Miocene climate transition in Central Asia. In this study, fine-grained mixed sediments widely distributed in the Miocene Qaidam Lake in the northern Tibetan Plateau were used as a sensitive indicator for palaeoclimate. Their geochemical characteristics were investigated, together with an analysis of 2600 m long successive gamma-ray logging data from the whole JS2 drillcore, to understand the mid-Miocene climate transition in the Tibetan Plateau. By comparing the gamma-ray curve of the mixed sediments with global temperature, the Middle Miocene Climatic Optimum event can be easily identified. Further, the detailed petrological features and geochemical data of lacustrine fine-grained mixed sediments from a 400 m drillcore show oxidizing, high-sedimentation rate and brackish-saline water conditions in a semi-arid climate during the Middle Miocene period, demonstrating a dryer climate in the Qaidam Basin than in the monsoon-sensitive regions in Central Asia. These fine-grained mixed sediments have recorded climate drying before 15.3 Ma that represents a climatic transition within the Middle Miocene Climatic Optimum; increasing carbonate-rich mixed sediments, decreasing algal limestone layers and decreasing lacustrine organic matter are indicators of this transition. Regional tectonic events include the retreat of the Paratethys from Central Asia at ∼15 Ma and the synchronous tectonic reorganization of the Altyn-Tagh fault system and the northeastern Tibetan Plateau. We find that global climate change is the primary factor affecting the overall characteristics and changes of the Neogene climate in the Qaidam Basin, including the occurrence of the Middle Miocene Climatic Optimum and the cooling and drying tendency, while the regional events are a secondary factor.
Peanut shell plays key roles in protecting the seed from diseases and pest infestation but also in the processing of peanut and is an important byproduct of peanut production. Most studies on peanut shell have focused on the utilization of its chemical applications, but the genetic basis of shell-related traits is largely unknown. A panel of 320 peanut (Arachis hypogaea) accessions including var. hypogaea, var. vulgaris, var. fastigiata and var. hirsuta was used to study the genetic basis of two physical and five microstructure-related traits in peanut shell. Significant phenotypic differences were revealed among the accessions of var. hypogaea, var. hirsuta, var. vulgaris and var. fastigiata for mechanical strength, thickness, three sclerenchymatous layer projections and main cell shape of the sclerenchymatous layer. We identified 10 significant single nucleotide polymorphisms (SNPs) through genome-wide association study (P < 5.0 × 10−6) combining the shell-related traits and high-quality SNPs. In total, 192 genes were located in physical proximity to the significantly associated SNPs, and 11 candidate genes were predicted related to their potential contribution to the development and structure of the peanut shell. All SNPs were detected on the B genome demonstrating the biased contribution of the B genome for the phenotypical make-up of peanut. Exploring the newly identified candidate genes will provide insight into the molecular pathways that regulate peanut shell-related traits and provide valuable information for molecular marker-assisted breeding of an improved peanut shell.
The rice water weevil, Lissorhoptrus oryzophilus Kuschel (Coleoptera: Curculionidae), is a destructive pest that causes damage to rice crops worldwide. The olfactory system is critical for host or mate location by weevils, but only limited information about the molecular mechanism of olfaction-related behaviour has been reported in this insect. In this study, we conducted SMRT-seq transcriptome analysis and obtained 54,378 transcripts, 38,706 of which were annotated. Based on these annotations, we identified 40 candidate chemosensory genes, including 31 odorant-binding proteins (OBPs), six chemosensory proteins (CSPs) and three sensory neuron membrane proteins (SNMPs). Phylogenetic analysis showed that LoryOBPs, LoryCSPs and LorySNMPs were distributed in various clades. The results of tissue expression patterns indicated that LoryOBPs were highly abundant in the antennae, whereas LoryCSPs were highly abundant not only in the antennae but also in the abdomen, head and wings. Our findings substantially expand the gene database of L. oryzophilus and may serve as a basis for identifying novel targets to disrupt key olfactory genes, potentially providing an eco-friendly strategy to control this pest in the future.
High dietary fiber intake has been associated with a lower risk of diabetes, but the association of dietary fiber with prediabetes is only speculative, especially in China, where the supportive data from prospective studies is lacking. This study aimed to examine the association between dietary fiber intake and risk of incident prediabetes among Chinese adults. We performed a prospective analysis in 18,085 participants of the TCLSIH cohort study who were free of diabetes, prediabetes, cancer, and cardiovascular disease at baseline. Dietary data were collected using a validated 100-item food frequency questionnaire. Prediabetes was defined based on the American Diabetes Association diagnostic criteria. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During 63,175 person-years of follow-up, 4,139 cases of incident prediabetes occurred. The multivariable HRs (95% CIs) of prediabetes for the highest versus lowest quartiles were 0.85 (0.75, 0.98) (P for trend =0.02) for total dietary fiber, 0.84 (0.74, 0.95) (P for trend <0.01) for soluble fiber, and 1.05 (0.93, 1.19) (P for trend =0.38) for insoluble fiber. Fiber from fruits, but not from cereals, beans, and vegetables was inversely associated with prediabetes. Our results indicate that intakes of total dietary fiber, soluble fiber, and fiber derived from fruit sources were associated with a lower risk of prediabetes.