Search

Drug-induced liver injury (DILI) is the main cause of failure in drug development and postapproval withdrawal. Although toxicogenomic techniques provide an unprecedented opportunity for mechanistic assessment and biomarker discovery, they are not suitable for the screening of large numbers of exploratory compounds in early drug discovery. Using a comprehensive analysis of toxicogenomics (TGx) data, we aimed to find DILI-relevant transcription factors (TFs) that could be incorporated into a reporter gene assay system. Gene set enrichment analysis (GSEA) of the Open TG-GATEs dataset highlighted 4 DILI-relevant TFs, including CREB, NRF2, ELK-1, and E2F. Using ten drugs with already assigned idiosyncratic toxicity (IDT) risks, reporter gene assays were conducted in HepG2 cells in the presence of the S9 mix. There were weak correlations between NRF2 activity and IDT risk, whereas strong correlations were observed between CREB activity and IDT risk. In addition, CREB activation associated with 3 Withdrawn/Black box Warning drugs was reversed by pretreatment with a PKA inhibitor. Collectively, we suggest that CREB might be a sensitive biomarker for DILI prediction, and its response to stress induced by high-risk drugs might be primarily regulated by the PKA/CREB signaling pathway.

Manganese ion (MnPeripheral blood Mn analysis of the patients was performed using inductively coupled plasma atomic emission spectroscopy (ICP-AES). A coculture model of dendritic cells (DCs)/macrophages, CD8The content of Mn in patients' peripheral blood was negatively related to the progression of OLK. MnMn

With the large-scale application of LiFePO

Lime mud (i.e., micrite) is a major component of carbonate deposits. Various mechanisms (biotic versus abiotic) have been proposed for the formation of lime mud in Earth’s history. However, the detailed role that microbes play in the nucleation and subsequent precipitation of micrites remains to be resolved. Herein we undertook a detailed geobiological characterization of laminated lime mudstone from the Middle Triassic Guanling Formation in Yunnan Province, southwestern China. Morphological features, together with previous geobiological investigations, suggest that the laminated lime mudstones represent the former presence of microbial mats. These lime mudstones consist mainly of calcite, dolomite and quartz, with clay minerals and pyrites as subordinate components. In particular, micro-analysis shows copious nano-globules (65–878 nm) and capsule-shaped nano-rods in laminations. These low-Mg calcite nano-globule aggregates are closely associated with mucilaginous biofilms resembling extracellular polymeric substances (EPS). Nano-sized globules coalesce to form semi-euhedral micrite crystals. We suggest that a decaying hydrolytic destruction of the EPS by microbial communities within microbial mat leads to the precipitation of the nano-globules by enhancing alkalinity in local micro-environment. As an intermediate, these nano-globules further aggregate to form micrite crystals possibly through a dissolution-reprecipitation process.

Circulating tumor cells (CTCs), as a type of tumor, have attracted wide attention because of their characteristics of shedding from the primary tumor and spreading to other tissues and organs through peripheral blood. The circulating tumor DNA (ctDNA), the DNA released by CTCs and other tumor cells into the peripheral blood, was considered as a promising detection substance for clinical application. By utilizing the biocompatibility of red blood cells to realize the attachment of tetrahedral DNA (TDN), as well as the specific target recognition ability of TDN to enable efficient recognition of targets, a biocompatible electrochemical biosensor for effective and rapid detection of ctDNA was developed using methylene blue (MB) as the signal probe. The current signal and the logarithm of ctDNA concentration were linearly correlated in the range from 1 fM to 100 pM with the detection limit of 0.66 fM. With high specificity, the TDN-based biosensor can detect ctDNA efficiently in the real biological environment such as serum, which provided a potential opportunity for the early clinical diagnosis.

Hydrological connectivity is an essential indicator of wetland pattern and functional stability. The reduction of connectivity usually means the degradation of wetland ecological function, internal energy flow, and nutrient cycle disturbance. Taking Hanshiqiao wetland as a case, we used Morphological Spatial Pattern Analysis (MSPA) with the Connectivity Index (IIC, Integral Index of Connectivity; PC, Probability of Connectivity) to analyze the change in hydrological connectivity of Hanshiqiao Wetland from both spatial and temporal aspects. The results showed that the hydrological connectivity of Hanshiqiao Wetland significantly improved with the implementation of the wetland restoration project. According to the changes in MSPA function types, the spatial morphological evolution of Hanshiqiao Wetland can be divided into two stages: the recovery stage and the stable stage. In the restoration stage, the area of the core wetland gradually increased, and many croplands and islet wetlands were transformed into the core wetland. The area of the core wetland recovered from 33 hm2 in 2005 to 119 hm2 in 2020. However, during the stable period, the landscape pattern of Hanshiqiao Wetland did not change significantly, and the hydrological connectivity of the wetland was mainly affected by water resource supply. In general, during the restoration period of Hanshiqiao Wetland, the changes in core wetlands played a leading role in the hydrological connectivity of Hanshiqiao Wetland. In the stable period, the main factors affecting the hydrological connectivity of Hanshiqiao Wetland are upstream recharge water, land-use change, and climate change. However, with climate warming and population surge, upstream water supply gradually decreases, and Hanshiqiao Wetland faces an increasingly severe water resource crisis. Therefore, to maintain the hydrological connectivity of Hanshiqiao Wetland, it is necessary to increase the artificial ecological water supply. The combined MSPA model and grey relational analysis method can better reveal the evolution characteristics and driving mechanism of wetland hydrological connectivity, which can provide a methodological reference for other wetland-related research.

Using panel data from mainland China, this study incorporates uncertainty, information seeking, and social support into the goal disruption theoretical model to examine the indirect influence of goal disruption on psychological disequilibrium through uncertainty and the moderating roles of information seeking and social support in this relationship. The results demonstrate that goal disruption causes uncertainty and then leads to psychological disequilibrium. Information seeking can reduce uncertainty and social support can attenuate psychological disequilibrium as well. Limitations and further directions are discussed.

Neuroinflammation is the important pathological feature of Alzheimer's disease (AD). Legumain, a lysosomal cysteine protease, plays an important role in neuroinflammation during ischemic stroke and depressive disorder. Legumain is involved in AD process through cleaving APP; however, it is unclear if legumain can possibly modulate neuroinflammation without cleaving APP in AD. Thus, we established a mouse model of AD by single intracerebroventricular injections of Aβ1-42 in legumain knockout (KO) mice. The behavioral tests showed that legumain-KO effectively ameliorated cognitive impairment induced by Aβ1-42. Moreover, legumain deprivation significantly improves the synaptic plasticity damages in Aβ1-42-treated mice. Moreover, legumain-KO considerably inhibited the activation of microglia and reduced the expression of inflammatory cytokines in the hippocampus of Aβ1-42-treated mice. Interestingly, we found that legumain-KO inhibited TLR4/MyD88/NF-κB pathway, which was activated by Aβ1-42 in the hippocampus. In conclusion, our results suggested that legumain-KO reduced the level of neuroinflammation that was associated with inhibiting TLR4/MyD88/NF-κB pathways, thereby improving the hippocampal synaptic plasticity and reducing the cognitive impairments in Aβ1-42-treated mice. Legumain knockout blocked microglia activation by inhibiting TLR4/MyD88/NF-κB signaling pathways, and further reduced inflammatory cytokine expression. As a result, legumain knockout alleviated synaptic damage and cognitive impairment induced by Aβ1--42.

We propose and demonstrate the effectual generation and control of nonparaxial self-accelerating beams by using UV-resin pendant droplets. We show that the geometrical shape of the hanging droplets formed as a result of the interplay between surface tension and gravity offers a natural curvature enabling the generation of nonparaxial self-accelerating beams. By simply adjusting the tilt angle of the surface where the droplets reside, a passing light beam is set to propagate along different curved trajectories, bending into large angles with non-diffracting features superior to a conventional Airy beam. Such self-accelerating beams are directly traced experimentally through the scattered light in yeast-cell suspensions, along with extensive ray tracing and numerical simulations. Furthermore, by modifying the shape of uncured pendant resin droplets in real time, we showcase the dynamical trajectory control of the self-accelerating beams. Our scheme and experimental method may be adopted for droplet-based shaping of other waves such as microfluidic jets and surface acoustic waves., Comment: 8 pages, 8 figures, research article

We demonstrate generation and dynamical control of self-accelerating beams simply using tilted UV-resin pendant-droplets. The curved trajectories of such large-angle self-bending beams are directly observed through scattering of yeast-cell suspensions, in excellent agreement with simulations.

We reported that over-expression of MST1 induced the impairment of spatial memory via disturbing neural oscillation patterns in mice. Meanwhile, the P-MST1 is increased in the hippocampus after chronic unpredictable mild stress (CUMS). However, it is unclear if MST1 knockdown protects against stress-induced memory deficits via modulating neural activities. In the study, a CUMS mouse model was established and an intrahippocampal injection of AAV-shMST1 was used to knockdown MST1 in the hippocampus. The data showed that there were memory deficits with over-expressed P-MST1 level in CUMS mice. However, MST1 knockdown can significantly prevent the damages of CUMS-induced working memory and synaptic plasticity via regulating neural oscillation patterns. It suggests that MST1 down-regulation effectively protected against stress-induced behavioral dysfunctions. Moreover, as a more convenient way, neural oscillation analysis could provide some assistance for the auxiliary diagnosis and treatment of depression.

Alzheimer's disease (AD) is the most prevalent form of dementia in the old adult and characterized by progressive cognitive decline and neuronal damage. The mammalian Ste20-like kinase1/2 (MST1/2) is a core component in Hippo signaling, which regulates neural stem cell proliferation, neuronal death and neuroinflammation. However, whether MST1/2 is involved in the occurrence and development of AD remains unknown. In this study we reported that the activity of MST1 was increased with Aβ accumulation in the hippocampus of 5xFAD mice. Overexpression of MST1 induced AD-like phenotype in normal mice and accelerated cognitive decline, synaptic plasticity damage and neuronal apoptosis in 2-month-old 5xFAD mice, but did not significantly affect Aβ levels. Mechanistically, MST1 associated with p53 and promoted neuronal apoptosis by phosphorylation and activation of p53, while p53 knockout largely reversed MST1-induced AD-like cognitive deficits. Importantly, either genetic knockdown or chemical inactivation of MST1 could significantly improve cognitive deficits and neuronal apoptosis in 7-month-old 5xFAD mice. Our results support the idea that MST1-mediated neuronal apoptosis is an essential mechanism of cognitive deficits and neuronal loss for AD, and manipulating the MST1 activity as a potential strategy will shed light on clinical treatment for AD or other diseases caused by neuronal injury.

Citrobacter koseri (C. koseri) is an opportunistic pathogen that can cause a variety of diseases. Although the mortality rate of C. koseri infections is high, there is a paucity of clinical information. Furthermore, the genomic features of this species are poorly understood. Herein, we present a patient with endogenous endophthalmitis secondary to septicemia, and collected a C. koseri isolate, CKNJ, from the blood of the patient. Whole genome sequencing revealed that CKNJ harbors no plasmids and codes for 67 putative virulence factors. Whole genome single nucleotide polymorphism-based phylogenetic analysis revealed that the CKNJ strain was close to strains with the same isolation sites. Compared to the other sequenced C. koseri chromosomes, CKNJ contains several strain-variable regions, including one prophage and 2 large genomic islands. Sequencing of the first complete genome of a clinical strain from China should reinforce our understanding of the genomic features and pathogenicity of this invasive infection-causing C. koseri with clinical significance.

The rapid rise of China on the global stage has promoted a widely held concern about the country’s political intention behind its expanding overseas economic activities. This paper attempts to shed new light on this old question: Is the abundance of natural resources in Africa the primary motivation for Chinese economic engagement in the continent? To this end, we investigate the nexus of China’s direct investment in 54 African countries and its international trade with the region between 2003 and 2014 to estimate how and to which extent Chinese investment affects its trade with the continent. This empirical task is facilitated using a transaction-level trade database from Chinese customs, which allows us to trace the trade records by product, destination, and exporting firm. Our empirical results support the trade-promoting effect of China’s foreign direct investment in the region, and this effect is found to be more significant for China’s exports of consumption and processed goods to the continent than for China’s imports of primary goods from this same region. Furthermore, we do not find systematic evidence that these investment activities lead to more primary goods being imported by Chinese state-owned enterprises. While these findings do not rule out the existence of resource-seeking motivation, they cast doubt on that being a primary driving force behind Chinese investment in Africa.

This paper is aimed at purifying and identifying selenium (Se)-containing antioxidative peptides from Se-enriched soybean peptides (SSP). In this work, the SSP was separated into five fractions (F1 to F5). Fraction F4, displaying the highest antioxidative activity, was further separated, and sub-fractions F4-1 to F4-5 were selected for antioxidative activity evaluation using 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2-azino-bis-(3-ethylbenzo-thiazoline-6-sulphonic acid)diammonium salt (ABTS), and OH− radical scavenging assays. The Se-containing antioxidative peptides with sequence Ser–SeC–Ala–His–Lys (SSeCAHK) were identified in sub-fraction F4-1 and chemically synthesized. This Se-containing pentapeptide showed a preventive effect against hydrogen peroxide (H2O2)-induced oxidative stress in HepG2 cells. Pretreating the cells for 2 h with SSeCAHK (0.13–0.50 mg mL−1) induced strong intracellular, reactive oxygen species (ROS) scavenging activity while preventing a decrease in reduced glutathione (GSH) and an increase in malondialdehyde (MDA). Therefore, SSeCAHK treatment improved H2O2-induced oxidative stress in HepG2 cells, demonstrating the significant potential of SSeCAHK as a natural antioxidative functional material for dietary supplementation.

Skeletal muscle is an important and complex organ with multiple biological functions in humans and animals. Proliferation and differentiation of myoblasts are the key steps during the development of skeletal muscle. MicroRNA (miRNA) is a class of 21-nucleotide noncoding RNAs regulating gene expression by combining with the 3'-untranslated region of target messenger RNA. Many studies in recent years have suggested that miRNAs play a critical role in myogenesis. Through high-throughput sequencing, we found that miR-323-3p showed significant changes in the longissimus dorsi muscle of Rongchang pigs in different age groups. In this study, we discovered that overexpression of miR-323-3p repressed myoblast proliferation and promoted differentiation, whereas the inhibitor of miR-323-3p displayed the opposite results. Furthermore, we predicted Smad2 as the target gene of miR-323-3p and found that miR-323-3p directly modulated the expression level of Smad2. Then luciferase reporter assays verified that Smad2 was a target gene of miR-323-3p during the differentiation of myoblasts. These findings reveal that miR-323-3p is a positive regulator of myogenesis by targeting Smad2. This provides a novel mechanism of miRNAs in myogenesis.

We reconstruct the apparatus architecture of the gondollelid conodont Nicoraella kockeli based on fused clusters from the early Middle Triassic (middle Anisian, Pelsonian) of Luoping County, east Yunnan Province, southwest China. These materials were characterized non-invasively using Synchrotron X-Ray Tomographic Microscopy and the ensuing data analysed using computed tomography, allowing us to infer the composition, homologies and architectural arrangement of elements within the apparatus. Much of the original three-dimensional architecture of the apparatus is preserved and our apparatus reconstruction is the best characterized of any taxon within the superfamily Gondolelloidea. This allows us to test architectural models for gondolelloids and prioniodinins, more generally, as well as the functional interpretations based upon them. In particular, we reject a recent functional interpretation of the conodont feeding apparatus which was based on a biomechanically-optimised inference of apparatus architecture in a close gondolelloid relative of Nicoraella. Nevertheless, our architectural model provides a foundation for future functional interpretations of gondolleloids and prioniodinins, more generally.

Background Athletic performances are complex traits with heritability of ~66%. Dynamic balance is one of the most important athletic performances, and there has been little studies for it in sports genomics. The candidate PPARD gene was reported to be able to affect muscle development for balance predisposition and influence the athletic performance including skiing triumph in the Caucasian population. This study aims to investigate whether the PPARD gene is a susceptibility gene for dynamic balance performance in Han Chinese children. Results A total 2244 children were recruited and their balance beam performances were measured. Five polymorphisms in the PPARD gene were genotyped through the MassARRAY Sequenom platform. Rs2016520 exerted significant association with dynamic balance performance (minor allele C, P = 0.015, Pcorrected < 0.05) and was affirmed in a meta-analysis by combining previously reported Caucasian cohorts (OR = 1.57, 95% CI = [1.30, 1.91], P < 10 -5) . Another polymorphism, rs2267668, was also significantly associated with dynamic balance performance (minor allele G, P = 0.015, Pcorrected < 0.05). In the dichotomous study, 321 cases (61% boys and 39% girls) and 370 controls (49% boys and 51% girls) in our samples were selected as representatives, and the thresholds were the mean velocity (0.737 m/s) ± standard deviation (0.264 m/s), in which rs2016520-C and rs2267668-G still remained significant (CI =1.41 [1.11~1.79], P = 0.004, Pcorrected < 0.016; CI =1.45 [1.14~1.86], P = 0.002, Pcorrected < 0.016). In different genders, consistent OR direction was observed for each variant. Conclusions Our results suggested that the PPARD gene is associated with dynamic balance performance of human being, and further studies to reveal its etiology is strongly suggested. Electronic supplementary material The online version of this article (10.1186/s41065-019-0092-x) contains supplementary material, which is available to authorized users.

This paper took cherry wine lees as the main raw material, and used three extraction methods (ultrasound-assisted enzymatic method, microwave extraction method, condensation reflux extraction method) to extract anthocyanin. The result showed that the extraction number of anthocyanins by ultrasonic-assisted enzymatic method was the highest. On the basis of single factor experiment, the response surface method was used for optimization. The impacts of experimental factors on extraction amount were successively the enzymolysis time, enzymolysis temperature, pH value, ultrasonic power, amount of enzyme added and solid-liquid ratio. Through polynomial regression analysis, the regression model of anthocyanin extraction rate was established, and according to the actual production condition, the following optimal process parameters were determined: enzyme addition: 1.5%; solid-liquid ratio: 1:32; pH value: 4.30; enzymolysis temperature: 54 °C; enzymolysis time: 55 min, and the ultrasonic power: 300 W. Under this condition, the extraction amount of anthocyanin from Cherry Wine lees was 4.19 mg/g.

Trace fossils have proven useful for studying the timing and process of biotic recovery after the Permian-Triassic Mass Extinction (PTME). Recovery stages are defined by comparing successive ichnoassemblages from the latest Permian to the early Middle Triassic. Lower Triassic trace fossils have been explored in some detail, but those of the lower Middle Triassic are less well known. Here, well-preserved fossil materials from the Luoping Biota from Yunnan Province, South China suggest that a fully recovered shallow-marine ecosystem was re-established by the early Middle Triassic. Trace fossil assemblages of the Luoping Biota are characterized by high ichnodiversity, with 14 ichnogenera in the shallow-marine environment of an intra-carbonate platform basin, and nine ichnogenera in the subtidal environment. Such moderate to high ichnodiversity, together with a marked increase in burrow sizes and the common occurrence of key ichnotaxa (e.g. Rhizocorallium and Thalassinoides), suggests that the ichnofauna had reached recovery stage four. In contrast, non-turbiditic strata of the offshore setting record only three ichnogenera, with bioturbation indices never exceeding one. Periodic anoxia in bottom waters was presumably the main control for such a protracted trace fossil recovery in an offshore setting, which otherwise aided the fine preservation of body fossils of the Luoping Biota. Furthermore, event sedimentation (turbidite deposits) in the offshore setting incorporated moderate ichnodiversity and moderate to high bioturbation indices, both interpreted as a result of short-term colonization by transported infaunal animals from proximal settings. The occurrence of variable crustacean traces (e.g. Sinusichnus, Spongeliomorpha, and Thalassinoides) at Luoping and the locomotion traces of marine reptiles, together with abundant fishes and fossil decapods, highlights the value of trace fossils in ecosystem reconstruction after the PTME.

A new troodontid (LH PV39) recovered from the Upper Cretaceous Wulansuhai Formation, Inner Mongolia, China, is described, highlighting the dorsoventrally compressed sacral centra. The completely fused neurocentral junctions indicate that LH PV39 had reached adulthood at the time of death, but its size is nevertheless 20% smaller than that of the sympatric Philovenator, demonstrating that it is the second small-bodied troodontid recovered from the Wulansuhai Formation. Phylogenetic analyses scoring LH PV39 using different strategies and performed with different algorithms unambiguously recovered it as a troodontid. While the parsimony-based analysis scoring LH PV39 as an independent OTU with all of its available characteristics included recovered it as a basal troodontid, the Bayesian analysis suggests a closer relationship of LH PV39 to Almas and an unnamed troodontid from Ukhaa Tolgod, Mongolia (MPC-D100/1126+D100/3500). Body size analysis confirmed a single trend of gigantism throughout the evolution of troodontids, and suggests that the Late Cretaceous troodontids evolved in two directions: (i) several size-independent characteristics evolved while retaining the small sizes that are typical of the Early Cretaceous relatives, resulting in the Late Cretaceous small-bodied troodontids; and (ii) size-dependent characteristics (e.g., the elongation of the rostrum) evolved accompanying the size increase, resulting in large-bodied derived troodontids. The mosaic features of the Late Cretaceous small-bodied troodontids place them intermediate between their Early Cretaceous basal relatives and the Late Cretaceous large-bodied taxa in a well-resolved phylogeny, which is crucial for understanding the size and morphological evolution of troodontids.

Microgravity, as a part of the stress of space flight, has several negative effects on cognitive functions. Repetitive transcranial magnetic stimulation (rTMS), as a novel non-invasive technique, could be an effective approach to alleviated cognitive decline, applied in both preclinical and clinical studies. Neural oscillations and their interactions are involved in cognitive functions and support the communication of neural information. The neural oscillation could be a window from which we may understand what happens in the brain. The current study aimed to explore if 15 Hz rTMS plays a neural modulation role in a mouse model of hindlimb unloading. We hypothezed that rTMS can improve the cognitive and neural oscillatory deficits induced by hindlimb unloading via maintaining the balance between glutamatergic and GABAergic systems. Our data show that rTMS can significantly alleviate behavior deficits, modulate theta oscillation, improve the disturbed power distribution of theta oscillation and the decreased strength of Cross-Frequency Coupling in the dentate gyrus region, and effectively mitigated the blocked communication of neural information in the perforant pathway (PP)-dentate gyrus (DG) neural pathway in Hu mice. Furthermore, biochemical analysis using high-performance liquid chromatography and Western blot assay confirmed that rTMS increases the low expression of glutamate (Glu) and N-Methyl d-Aspartate receptor subtype 2B (NR2B) and decreases the high expression of γ-aminobutyric acid (GABA), 67 KDa isoform of glutamate decarboxylase (GAD67), and GABA type A receptor subunit alpha1 (GABAARα1) in the hippocampus of Hu mice. Taken together, the results suggest that rTMS plays a significant neural modulation role in the hippocampal neural activity disorders induced by Hu, which possibly depends on rTMS maintaining the balance of glutamatergic and gamma-aminobutyric acidergic (GABAergic) systems.

With the emergence of tools for extracting CSI data from commercial WiFi devices, CSI-based device-free activity recognition technology has developed rapidly and has been widely used in security monitoring, smart home, medical monitoring, and other fields. However, the existing CSI-based activity recognition algorithms need a large number of training samples to obtain the ideal recognition accuracy. To solve the problem, an attention-based bidirectional LSTM method using multidimensional features (called MF-ABLSTM method) is proposed. In this method, the signal preprocessing and continuous wavelet transform algorithms are used to construct time-frequency matrix, the sample entropy is used to characterize the statistical feature of CSI amplitudes, the energy difference at a fixed time interval is used to characterize the time-domain feature of activities, and the energy distribution of different frequency components is used to characterize the frequency-domain feature of activities. By expanding the training samples with the proposed tensor prediction algorithm, the accurate activity recognition can be realized with only a few samples. A large number of experiments verify the good performance of MF-ABLSTM method.

In boreal regions, the frequency of forest fires is increasing. In this study, thermogravimetric analysis was used to analyze the pyrolysis kinetics of dead surface combustibles in different forest types within the Daxing’an Mountains, China. The results show that the combustible material load of forest types, the Larix forest (LG) is relatively high. Base on the E of kinetic parameters, the LG, and Quercus forest (QM) forest types had relatively high combustibility values and comprehensive combustibility values for 1-, 10-, and 100-h time lags. According to the obtained P values, the pyrolysis of dead surface fuels with 1-, 10-, and 100-h time lags is relatively difficult in the Larix / Betula mixed forest (L-B) and QM forest types. Therefore, mixed forests of the LG, L-B, and QM tree species can be established as fire-resistant forests to establish a fire barrier, reduce the combustibility of forest stands, and reduce the possibility of forest fires.

In the process of China's energy system revolution, integrated energy system is the key way to solve low utilization rate of fossil energy and renewable energy consumption. This paper studies the operation characteristics of the core equipment and the utilization process of renewable energy, and establishes the energy supply scheme of the integrated energy system based on the gas-fired combined cooling, heating and power system. A double-layer optimization method for the capacity configuration with consideration of operation strategy of the integrated energy system is proposed to solve the optimized problem. Firstly, a comprehensive energy system with CCHP as the core and considering renewable energy access is proposed. The energy coupling relationship and operation characteristics of various equipment are analyzed. Secondly, The operation characteristics of the equipment are analyzed, and the constraints of the optimization model are constructed. The optimization objectives are investment operation and maintenance, renewable energy consumption, resource consumption and so on. The genetic algorithm combined with the mixed integer linear programming solver is used to verify the economy and environmental protection of the conventional integrated energy system considering the energy storage device and renewable energy consumption.

MicroRNA (miRNA) is a type of highly conserved nucleotide sequence composed of 18 to 25 nucleotides, which can specifically bind to the 3'-noncoding regions of mRNA, and then play a negative regulatory role in degrading mRNA or inhibiting translation. Long non-coding RNA (lncRNA) is a type of nucleotide sequence that exceeds 200 nucleotides in length and cannot encode proteins or can only encode protein peptides. It regulates gene expression at the levels of epigenetic, transcriptional and post-transcriptional. As an important energy storage organ, fat plays an important role in regulating the energy balance of animals, and is closely related to meat production traits such as meat production and meat quality. And the disorder of fat function can lead to hyperlipidemia, type 2 diabetes and a series of cardiovascular diseases, so the molecular regulation mechanism of animal fat deposition has attracted more attention. In recent years, more and more studies have found that miRNA and lncRNA play a crucial role in animal fat deposition. We review here the current research progresses in the role of miRNA and lncRNA in animal fat deposition, to provide theoretical guidance and new ideas for further revealing the molecular regulation mechanism of animal fat deposition.微小RNA (MicroRNA，miRNA) 是一类由18–25 个核苷酸组成的高度保守的核苷酸序列，它可以特异性结合信使RNA (mRNA) 的3′-非编码区域，进而发挥降解mRNA 或阻遏mRNA 翻译的负调控作用。长链非编码RNA (Long non-coding RNA，lncRNA) 是一类长度超过200 个核苷酸、不能编码蛋白质或只能编码蛋白质微肽的核苷酸序列，它可以在表观遗传、转录水平和转录后水平调控基因表达。脂肪作为一种重要的储能物质，在调节动物体能量平衡过程中发挥着重要的作用，并与动物产肉量、肉品质等产肉性状密切相关。而脂肪功能的紊乱可导致高血脂、Ⅱ型糖尿病以及一系列心血管疾病发生，因此动物脂肪沉积的分子调控机制备受人们关注。近年来，越来越多的研究发现miRNA 和lncRNA 在动物脂肪沉积中发挥重要作用。文中就现阶段miRNA 和lncRNA在动物脂肪沉积中的研究进展进行综述，以期为进一步揭示动物脂肪沉积的分子调控机制提供理论指导和新思路。.

Neuroinflammation is the important pathological feature of Alzheimer's disease (AD). Legumain, a lysosomal cysteine protease, plays an important role in neuroinflammation during ischemic stroke and depressive disorder. Legumain is involved in AD process through cleaving APP; however, it is unclear if legumain can possibly modulate neuroinflammation without cleaving APP in AD. Thus, we established a mouse model of AD by single intracerebroventricular injections of Aβ

Network pharmacology is an approach that uses bioinformatics to predict and identify multiple drug targets and interactions in disease. Here, we applied network pharmacology to investigate the potential mechanisms of action of triptolide, an active component in the traditional Chinese medicine Tripterygium wilfordii Hook F, in colorectal cancer (CRC). We first searched public databases for genes and proteins known to be associated with CRC, as well as those predicted to be targets of triptolide, and then used Ingenuity Pathway Analysis (IPA) to identify enriched gene pathways and networks. Networks and pathways that overlapped between CRC-associated proteins and triptolide target proteins were then used to predict candidate protein targets of triptolide in CRC. The following proteins were found to be expressed in both CRC-associated networks and triptolide target networks: JUN, FOS, CASP3, BCL2, IFNG, and VEGFA. Docking studies suggested that triptolide can fit in the binding pocket of the four top candidate triptolide target proteins (CASP3, BCL2, VEGFA and IFNG). The overlapping pathways were activation of neuroinflammation signaling, glucocorticoid receptor signaling, T helper (Th) cell differentiation, Th1/Th2 activation, and colorectal cancer metastasis signaling. These results show that network pharmacology can be used to generate hypotheses about how triptolide exerts therapeutic effects in CRC. Network pharmacology may be a useful method for characterizing multi-target drugs in complex diseases.

To reduce dependence on petroleum, the biosynthesis of important chemicals from simple substrates using industrial microorganisms has attracted increased attention. Metabolic engineering of Saccharomyces cerevisiae offers a sustainable and flexible alternative for the production of various chemicals. As a key metabolic intermediate, malonyl-CoA is a precursor for many useful compounds. However, the productivity of malonyl-CoA derivatives is restricted by the low cellular level of malonyl-CoA and enzymatic performance. In this review, we focused on how to increase the intracellular malonyl-CoA level and summarize the recent advances in different metabolic engineering strategies for directing intracellular malonyl-CoA to the desired malonyl-CoA derivatives, including strengthening the malonyl-CoA supply, reducing malonyl-CoA consumption, and precisely controlling the intracellular malonyl-CoA level. These strategies provided new insights for further improving the synthesis of malonyl-CoA derivatives in microorganisms.

A new small-bodied troodontid (LH PV39) recovered from the Upper Cretaceous Wulansuhai Formation, Suhongtu, Inner Mongolia, China, is described. The new specimen preserves six postaxial cervical vertebrae, five completely fused sacral and four posterior caudal vertebrae in addition to two manual unguals. The completely fused neurocentral junctions indicate that a skeletally mature individual of the same species of LH PV39 would be smaller than Philovenator and comparable in body size to a skeletal mature individual of Almas. The extremely dorsoventrally compressed sacral centra and neural canal, and the middle three sacral centra that are shorter and wider than the first and the last one distinguishing LH PV39 from other known troodontids. A series of phylogenetic analyses were conducted using modified published matrices. By coding LH PV39 in different strategies, the troodontid affinity of LH PV39 is confirmed and it was recovered as the sister taxon of either Mei and Sinovenator (LH PV39 scored as a separate OTU) or Linhevenator (incorporating LH PV39 into Philovenator) in the best resolved coelurosaurian interrelationships. The referral of LH PV39 to Philovenator does not seriously alter the phylogenetic position of Philovenator nor the interrelationships of troodontids. This new finding confirms that the small and large sized troodontids are coexisted in the Gobi Desert of the Mongolia Plateau until the end of Cretaceous.

Unmanned Aerial Vehicle (UAV) is playing a gradually enhanced role in fields of recon and information acquisition, however restricted departure condition of fixed wing aircrafts, take-off preparation time of multirotor aircrafts etc. have limited its further applications. This research aims to combine advantage of hovering and self-deployable departure to reconcile the shortcomings, meanwhile adapts to drone swarm trend. A catapulted self-deployable quadrotor is designed using 3D modelling software, and later a compatible self-deployable control algorithm is developed using STM32F103 microcontroller, along with its circuitry. Eventually, a prototype of the design is 3D printed, assembled and tested. This design shows merits of easy to carry, low requirements for take-off conditions and good hovering performance and is compatible for multi-UAVs cooperation tendency.

The secular change in 87Sr/86Sr ratio of the Mesozoic recorded the highest value above 0.7083 in Early–Middle Triassic boundary, i.e., the Triassic maximum, suggesting that a major reform in oceanography occurred after the end-Permian mass extinction. We have detected correlative highest 87Sr/86Sr value from the Triassic carbonate, including our data. The stratigraphic horizon of the maximum was constrained to the Olenekian–Anisian boundary (OAB) (247.2 Ma), by conodont. As the oceanic data represent the global average, the present study confirmed the chemostratigraphical utility of the “Triassic maximum” of 87Sr/86Sr ratio in global correlation. After the sharp rise throughout Early Triassic since the end-Permian mass extinction, a remarkable turnover of seawater-87Sr/86Sr values appeared in the OAB. A major global change likely appeared in the OAB to change the Sr-isotope balance in seawater from a continental flux-dominated to a mantle flux-dominated regime. The sharp turning point in 87Sr/86Sr values likely has recorded the timing of the biological influence on the environment.

The rachises of extant feathers, composed of dense cortex and spongy internal medulla, are flexible and light, yet stiff enough to withstand the load required for flight, among other functions. Incomplete knowledge of early feathers prevents a full understanding of how cylindrical rachises have evolved. Bizarre feathers with unusually wide and flattened rachises, known as "rachis-dominated feathers" (RDFs), have been observed in fossil nonavian and avian theropods. Newly discovered RDFs embedded in early Late Cretaceous Burmese ambers (about 99 million year ago) suggest the unusually wide and flattened rachises mainly consist of a dorsal cortex, lacking a medulla and a ventral cortex. Coupled with findings on extant feather morphogenesis, known fossil RDFs were categorized into three morphotypes based on their rachidial configurations. For each morphotype, potential developmental scenarios were depicted by referring to the rachidial development in chickens, and relative stiffness of each morphotype was estimated through functional simulations. The results suggest rachises of RDFs are developmentally equivalent to a variety of immature stages of cylindrical rachises. Similar rachidial morphotypes documented in extant penguins suggest that the RDFs are not unique to Mesozoic theropods, although they are likely to have evolved independently in extant penguins.

The ACTN3 gene locates on 11q13-q14 and encodes the α-actinin-3 protein, which is only expressed in human skeletal muscle and influenced muscle function and metabolism. The previous studies reported that SNP rs1815739 is associated with elite power athletes’ performance. In this study, we investigated the association between five SNPs within the ACTN3 gene and Chinese children physical fitness. We recruited 2244 Han Chinese children participants, and measured their 25-m run, stand broad jump, 10-m shuttle run, handgrip, BMI (calculated by weight and height) data. SNPs rs1671064, rs2275998, rs2290463, rs10791881, and rs1815739 of ACTN3 gene were genotyped and analyzed in five physical fitness data. QTL analysis on genotype and physical fitness data was carried out in all samples. Furthermore, a dichotomous division of samples into an overweight group (543) and a normal group (1701) was used for an association study of overweight. In the QTL analysis, we found rs2290463 was significantly associated with stand broad jump (corrected P value = 0.009, beta = 2.692). After added age and gender as covariates in the regression test, the association became more significant (P value = 5.80 × 10− 5, corrected P value = 4.06 × 10− 4); when we used BMI as a covariate, the association still existed (P value = 4.65 × 10− 4, corrected P value = 0.001). In the association study of overweight, rs2275998 was found to be significant (OR, 95% CI = 0.733 [0.6–0.895]; Pallele = 0.011, Pgenotype = 0.024) after the Bonferroni correction, and the association did not change much after a further correction for gender, age, and stand broad jump performance. Our results showed that common variants in ACTN3 are significantly associated with both stand broad jump performance and overweight in Han Chinese children.

The Luoping Biota discovered from the early Middle Triassic (Anisian) Guanling Formation of southwestern China represents a fully recovered shallow marine ecosystem, marking the end point of Early Triassic biotic recovery following the end-Permian mass extinction. Contemporaneously preserved are prolific trace fossils, which offer good opportunities to understand the palaeoecology of marine invertebrates from a fully recovered shallow marine ecosystem. Here we present a newly discovered sinuous branching burrow from the fossil-bearing unit in Member Ⅱ of the Guanling Formation. Several features, including the horizontal regular sinuous nature, the branching pattern, typical H-junction, and the small wavelength/amplitude ratio of these sinuous structures within the burrow systems justify assignment of these traces as Sinusichnus sinuosus, a trace possibly produced by decapod crustaceans. Close association of S. sinuosus with Rhizocorallium commune suggests a deposit-feeding strategy of these trace makers. The newly reported Anisian material from the Guan-ling Formation in Luoping represents first report of Sinusichnus from South China. The global record of Sinusichnus occurrence suggests that these burrows might have an older history than Early Middle Triassic.

A new helminthomorph millipede,Sinosoma luopingensenew genus new species, from the Triassic Luoping biota of China, has 39 body segments, metazonites with lateral swellings that bear a pair of posterolateral pits (?insertion pits for spine bases), and sternites that are unfused to the pleurotergites. This millipede shares a number of characters with nematophoran diplopods, but lacks the prominent dorsal suture characteristic of that order. Other “millipede” material from the biota is more problematic. Millipedes are a rare part of the Luoping biota, which is composed mainly of marine and near-shore organisms. Occurrences of fossil millipedes are exceedingly rare in Triassic rocks worldwide, comprising specimens from Europe, Asia, and Africa, and consisting of juliform millipedes and millipedes that are either nematophorans or forms very similar to nematophorans.

Copious microtubular structures are reported, for the first time, from the coprolites of early Middle Triassic Guanling Formation in Luoping, Yunnan Province, southwestern China. Multiple salient characteristics of these microtubes, including curved to coiled grooves with longitudinal striations, angular turns, cross-cuttings, and a terminal rounded pitting at one end of a groove, support their strong affinities with ambient inclusion trails (AITs) that are more commonly found in pre-Ediacaran sedimentary rocks. These newly found microtubular structures are here interpreted to represent the youngest occurrence of AITs in the geological record. A review of all AITs and similar microtubular structures reveals their common occurrences in Ediacaran phosphorite and Phanerozoic phosphatized fossil substrate. Similar to the AITs found from the post-Ediacaran strata, the AITs from the Luoping coprolites are also preserved in a phosphatized substrate. We suggest that a microbial-induced process might have contributed to the phosphogenesis of faeces and AITs formation. This process is interpreted to have involved the precipitation of phosphate minerals by microbial communities, and the movement of pyrite through and within phosphatized substrate gel driven by fluid pressure. This new interpretive model differs from the existing scenario invoked to explain the formation mechanism of pre-Ediacaran AITs, in which pyrite propulsion is thought to be more likely driven by metamorphism-induced fluid pressure. We thus hypothesize that the transformation in AITs' formative substrate, from chert to phosphate, as well as their formation mechanism, might have been triggered by a significant change in ocean biogeochemistry linked to a phosphogenic event in the Neoproterozoic.

Among the characters of caenagnathid oviraptorosaurians, the lateral occlusal grooves and ridges on the occlusal surface of the jaw bones often receive special attention. Recent studies demonstrated that ontogenetic edentulism is present in caenagnathids, and therefore the lateral occlusal grooves and ridges are vestigial alveoli and interdental septa, respectively. In the present paper, the dentary structures of caenagnathids were reevaluated based on CT images of Caenagnathiasia sp. IVPP V20377. Several previously unknown features including crateriform vestigial alveoli, the morphology of the dentary interior hollow space, and the paired blind tubes beneath the dentary symphyseal shelf are recognized. Current lines of evidence suggest different jaw bone morphologies are likely produced by various tooth reduction patterns, which indicates ontogenetic dietary shift, if once presented in caenagnathids and Sapeornis, may have been different from the condition seen in Limusaurus. The 3D images of dentary interior spaces suggest that while tooth reduction progresses, the empty alveoli are partially modified into structures accommodating blood vessels that nourish the rhamphotheca, probably representing a functional compensation for the insufficient blood supply in toothed jaw bones.