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Abstract Korla pear has a unique taste and aroma and is a breeding parent of numerous pear varieties. It is susceptible to Valsa mali var. pyri, which invades bark wounded by freezing injury. Its genetic relationships have not been fully defined and could offer insight into the mechanism for freezing tolerance and disease resistance. We generated a high-quality, chromosome-level genome assembly for Korla pear via the Illumina and PacBio circular consensus sequencing (CCS) platforms and high-throughput chromosome conformation capture (Hi-C). The Korla pear genome is ~ 496.63 Mb, and 99.18% of it is assembled to 17 chromosomes. Collinearity and phylogenetic analyses indicated that Korla might be derived from Pyrus pyrifolia and that it diverged ~ 3.9-4.6 Mya. During domestication, seven late embryogenesis abundant (LEA), two dehydrin (DHN), and 54 disease resistance genes were lost from Korla pear compared with P. betulifolia. Moreover, 21 LEA and 31 disease resistance genes were common to the Korla pear and P. betulifolia genomes but were upregulated under overwintering only in P. betulifolia because key cis elements were missing in Korla pear. Gene deletion and downregulation during domestication reduced freezing tolerance and disease resistance in Korla pear. These results could facilitate the breeding of novel pear varieties with high biotic and abiotic stress resistance.

Abstract Background Quercetin is a flavonol compound widely distributed in plants that possesses diverse biological properties, including antioxidative, anti-inflammatory, anticancer, neuroprotective and senescent cell-clearing activities. It has been shown to effectively alleviate neurodegenerative diseases and enhance cognitive functions in various models. The immune system has been implicated in the regulation of brain function and cognitive abilities. However, it remains unclear whether quercetin enhances cognitive functions by interacting with the immune system. Results In this study, middle-aged female mice were administered quercetin via tail vein injection. Quercetin increased the proportion of NK cells, without affecting T or B cells, and improved cognitive performance. Depletion of NK cells significantly reduces cognitive ability in mice. RNA-seq analysis revealed that quercetin modulated the RNA profile of hippocampal tissues in aging animals towards a more youthful state. In vitro, quercetin significantly inhibited the differentiation of Lin−CD117+ hematopoietic stem cells into NK cells. Furthermore, quercetin promoted the proportion and maturation of NK cells by binding to the MYH9 protein. Conclusions In summary, our findings suggest that quercetin promotes the proportion and maturation of NK cells by binding to the MYH9 protein, thereby improving cognitive performance in middle-aged mice. Graphical abstract

Abstract Creatine kinases are essential for maintaining cellular energy balance by facilitating the reversible transfer of a phosphoryl group from ATP to creatine, however, their role in mitochondrial ATP production remains unknown. This study shows creatine kinases, including CKMT1A, CKMT1B, and CKB, are highly expressed in cells relying on the mitochondrial F1F0 ATP synthase for survival. Interestingly, silencing CKB, but not CKMT1A or CKMT1B, leads to a loss of sensitivity to the inhibition of F1F0 ATP synthase in these cells. Mechanistically, CKB promotes mitochondrial ATP but reduces glycolytic ATP production by suppressing mitochondrial calcium (mCa2+) levels, thereby preventing the activation of mitochondrial permeability transition pore (mPTP) and ensuring efficient mitochondrial ATP generation. Further, CKB achieves this regulation by suppressing mCa2+ levels through the inhibition of AKT activity. Notably, the CKB‐AKT signaling axis boosts mitochondrial ATP production in cancer cells growing in a mouse tumor model. Moreover, this study also uncovers a decline in CKB expression in peripheral blood mononuclear cells with aging, accompanied by an increase in AKT signaling in these cells. These findings thus shed light on a novel signaling pathway involving CKB that directly regulates mitochondrial ATP production, potentially playing a role in both pathological and physiological conditions.

Abstract Background Mesenchymal stem cells (MSCs) hold a great promise for cell-based therapy in the field of regenerative medicine. In this study, we aimed to evaluate the safety and efficacy of intravenous infusion of human umbilical cord-derived MSCs (HUC-MSCs) in patients with aging frailty. Methods In this randomized, double-blind, placebo-controlled trial, participants diagnosed with aging frailty were randomly assigned to receive intravenous administrations of HUC-MSCs or placebo. All of serious adverse events and AEs were monitored to evaluate the safety of treatment during the 6-month follow-up. The primary efficacy endpoint was alteration of physical component scores (PCS) of SF-36 qualities of life at 6 months. The secondary outcomes including physical performance tests and pro-inflammatory cytokines, were also observed and compared at each follow-up visits. All evaluations were performed at 1 week, 1, 2, 3 and 6 months following the first intravenous infusion of HUC-MSCs. Results In the MSCs group, significant improvements in PCS of SF-36 were observed from first post-treatment visit and sustained throughout the follow-up period, with greater changes compared to the placebo group (p = 0.042). EQ-VAS scores of MSCs group improved significantly at 2 month (p = 0.023) and continued until the end of the 6-month visit (p = 0.002) in comparison to the placebo group. The timed up and go (TUG) physical performance test revealed significant group difference and showed continual enhancements over 6 months (p

The lack of reliable negative samples is an important factor limiting the quality of machine learning-based debris flow susceptibility mapping (DFSM). The purpose of this paper is to propose multiple negative-sample acquisition strategies for DFSM considering different sample representation forms. The sample representation forms mainly include a single grid, multi-grid, and watershed unit, and the negative-sample acquisition strategies are based on support vector machine (SVM), spy technique, and isolation forest (IF) methods, respectively. These three strategies can assign a value to all the samples based on different assumptions, and reliable, negative samples can be generated from samples with values below a predefined threshold. Combining different sample representation forms with negative sample acquisition strategies, nine datasets were then involved in random forest (RF) modeling. The receiver operating characteristic (ROC) curves and related statistical results were used to evaluate the models. The results show that the strategy based on the spy technique is suitable for multiple datasets, while the IF-based strategy is well-adapted to the watershed unit datasets. This study can provide more options for improving the quality of datasets in DFSM, which can further improve the performance of machine learning models.

Abstract Background Metformin, a type 2 diabetes treatment, improves the cognitive function of aged mice; however, whether the protective effects of metformin on cognitive function in aged mice are associated with the gut microbiome is poorly understood. Although some studies suggest that the gut microbe composition influences cognitive function and that manipulating the gut microbiota might protect against age-related cognitive dysfunction, there is no direct evidence to validate that the gut microbiota mediates the effect of metformin on cognitive improvement. Results In this study, we show that the gut microbiota is altered by metformin, which is necessary for protection against ageing-associated cognitive function declines in aged mice. Mice treated with antibiotics did not exhibit metformin-mediated cognitive function protection. Moreover, treatment with Akkermansia muciniphila, which is enriched by metformin, improved cognitive function in aged mice. Mechanistically, A. muciniphila decreased pro-inflammatory-associated pathways, particularly that of the pro-inflammatory cytokine interleukin (IL)-6, in both the peripheral blood and hippocampal profiles, which was correlated with cognitive function improvement. An IL-6 antibody protected cognitive function, and an IL-6 recombinant protein abolished the protective effect of A. muciniphila on cognitive function in aged mice. Conclusion This study reveals that A. muciniphila, which is mediated in the gut microbiota by metformin, modulates inflammation-related pathways in the host and improves cognitive function in aged mice by reducing the pro-inflammatory cytokine IL-6. Video Abstract Graphical Abstract

Flight control law parameters should be designed to provide a sufficient stability margin for closed-loop aircraft while ensuring command tracking accuracy. The singular perturbation margin (SPM) and generalized gain margin (GGM), which are generalizations of the classical phase margin (PM) and gain margin (GM), respectively, from a linear time-invariant system to a nonlinear time-varying system, can be used to quantitatively characterize the maximum singular perturbation and regular perturbation allowed to maintain system stability. In this paper, the sliding mode flight control structure and the design parameters of the sliding mode control law are first introduced for an oblique wing aircraft (OWA), the SPM-gauge and GGM-gauge are added to this closed-loop aircraft model, and the analytical expressions of the SPM and GGM are derived with respect to the control law parameters. Second, the stability margin design requirements of closed-loop aircraft in flight control system design specifications are converted into limitations on the SPM and GGM to determine the value range of the flight control law parameters. Then, with the goal of reducing the sum of the approaching time and sliding time, the parameter value combination is selected within the control law parameter range that meets the stability margin requirements, thus forming a flight control law design method for OWA during the wing skewing process. Finally, the designed control law parameters are applied to a sample OWA, and the stability margin of closed-loop aircraft during the wing skewing process is verified.

ABSTRACTThe gut-joint axis, one of the mechanisms that mediates the onset and progression of joint and related diseases through gut microbiota, and shows the potential as therapeutic target. A variety of drugs exert therapeutic effects on rheumatoid arthritis (RA) through the gut-joint axis. However, the anti-inflammatory and immunomodulatory effect of novel photobiomodulatory therapy (PBMT) on RA need further validation and the involvement of gut-joint axis in this process remains unknown. The present study demonstrated the beneficial effects of PBMT on RA, where we found the restoration of gut microbiota homeostasis, and the related key pathways and metabolites after PBMT. We also discovered that the therapeutic effects of PBMT on RA mainly through the gut-joint axis, in which the amino acid metabolites (Alanine and N-acetyl aspartate) play the key role and rely on the activity of metabolic enzymes in the target organs. Together, the results prove that the metabolites of amino acid from gut microbiota mediate the regulation effect on the gut-joint axis and the therapeutic effect on rheumatoid arthritis of PBMT.

Bacterial nicotinamidase/pyrazinamidase PncA increases host nicotinamide adenine dinucleotide (NAD+) levels and ameliorates diet-induced non-alcoholic fatty liver disease (NAFLD) in mice.

Abstract Background Glycyrrhizic acid (GA), a saponin compound often used as a flavoring agent, can elicit anti-inflammatory and anti-tumor effects, and alleviate aging. However, the specific mechanism by which GA alters immune cell populations to produce these beneficial effects is currently unclear. Results In this study, we systematically analyzed single-cell sequencing data of peripheral blood mononuclear cells from young mice, aged mice, and GA-treated aged mice. Our in vivo results show that GA reduced senescence-induced increases in macrophages and neutrophils, and increased numbers of lymphoid lineage subpopulations specifically reduced by senescence. In vitro, GA significantly promoted differentiation of Lin−CD117+ hematopoietic stem cells toward lymphoid lineages, especially CD8+ T cells. Moreover, GA inhibited differentiation of CD4+ T cells and myeloid (CD11b+) cells by binding to S100 calcium-binding protein 8 (S100A8) protein. Overexpression of S100A8 in Lin− CD117+ hematopoietic stem cells enhanced cognition in aged mice and the immune reconstitution of severely immunodeficient B-NDG (NOD.CB17-Prkdcscid/l2rgtm1/Bcgen) mice. Conclusions Collectively, GA exerts anti-aging effects by binding to S100A8 to remodel the immune system of aged mice.

The upset state is an unexpected flight state, which is characterized by an unintentional deviation from normal operating parameters. It is difficult for the pilot to recover the aircraft from the upset state accurately and quickly. In this paper, an upset recovery strategy and pilot assistance system (PAS) based on reinforcement learning is proposed. The man–machine closed-loop system was established and the upset state, such as a high angle of attack and large attitude angle, was induced. The upset recovery problem was transformed into a sequential decision problem, and the Markov decision model of upset recovery was established by taking the deflection change of the control surface as the action. The proximal policy optimization (PPO) algorithm was selected for the strategy training. The adaptive pilot model and the reinforcement learning method proposed in this paper were used to make the aircraft recover from the upset state. Based on the correspondence between the flight state, the recovery method, and the recovery result, the aircraft upset recovery safety envelopes were formed, and the four-level upset recovery PAS with alarm warning, coordinated control, and autonomous recovery modes was constructed. The results of the digital virtual flight simulation and ground flight test show that compared with a traditional single pilot, the aircraft upset recovery strategy, the upset recovery safety envelopes, and the PAS established in this study could reduce the handling burden of the pilot and improve the success rate and effect of upset recovery. This research has certain theoretical reference values for flight safety and pilot training.

This paper introduces a facile solution route to fabricate MoTe2 grain nano-domains for hybrid polymer heterojunction solar cells and photodetectors. Fabricated MoTe2 structures were investigated using Raman and XRD, and surface morphologies characterized using FE-SEM and TEM. We subsequently assembled a non-fullerene polymer heterojunction device using the PBDB-T:ITIC active layer for ITO/HTL/active-layer/LiF/Al architype solar cells and photodetectors. We also investigated effects from different MoTe2 nanostructure proportions embedded in the PBDB-T:ITIC polymer matrix as active layers to assemble solar cell and photodetector devices. Maximum power conversion efficiency ≈8.94% with improved carrier mobility ≈9.23 × 10−4 cm2 V−1 s−1 was achieved for 10 vol% MoTe2 nanostructure inclusion with PBDB-T:ITIC active layer. A fabricated photodetector using 10 vol%-MoTe2@PBDB-T:ITIC film achieved maximum detectivity ≈2.62 × 1010 Jones with 0.706 A W−1 responsivity at 755 μW cm−2 light density under 656 nm laser source. The proposed facile approach to fabricate 2D MoTe2 atomic layer infusion with polymer heterojunction offers a credible mechanism to progress interfacial characteristics for future organic semiconducting devices.

Background The pain induced by postoperative dressing changes adversely influence recovery and quality of life. In this study, we try to evaluate the pain alleviation effect of virtual reality (VR) distraction during postoperative dressing changes of patients who received surgical drainage of perianal abscess. Methods This was a prospective, randomized clinical trial. A total of 172 patients with perianal abscess were randomly assigned into control (only analgesics) and VR groups (VR distraction + analgesics). The pain and physiological measurements of all patients were collected before, during, and after the first dressing change following surgery. The difference in pain intensity and physiological parameters measurement between control and VR group was analyzed. Results The baseline characteristics of VR and control group were comparable (all P > 0.05). There was no significant difference in mean pain scores prior to and after dressing change between groups (both P > 0.05). Mean pain scores of 5, 10, 15, and 20 min measuring points during the first dressing change were significantly lower in the VR group compared with the control group (all P

In numerical analysis, the pile equivalent calculation method plays a key role in foundation pit calculation results. However, the effect and mechanism of different pile equivalent calculation methods in the foundation pit has remained unclear. To solve this question, based on FLAC3D, four pile equivalent calculation methods were introduced into a typical pile–anchor pit. This research was carried out from the perspective of soil displacement and stress, special points’ stress paths, and the plastic zone. The results revealed that there was a remarkable influence on the calculation results for different pile equivalent calculation methods. Specifically, compared with structural pile elements, displacements near the pile were smaller in solid pile element mode. Moreover, with the increase in excavation depth, stress concentration appeared in the solid pile element mode. The solid support pile with the interface, compared to that without the interface, had less displacement but more stress concentration around the pile, which led the special points’ stress paths around the solid pile to become irregular. Regarding the structural pile elements, it is suggested that both modeling approaches had a similar effect. These findings could help to provide a deeper insight into pile–anchor foundation pit numerical analysis.

Using a nonlinear pilot-induced oscillation prediction method based on digital virtual flight simulation calculations, digital experiments on predicting lateral-directional nonlinear pilot-induced oscillations due to landing configuration switching of fly-by-wire civil aircraft with different closed-loop dynamic characteristics are carried out. It is proposed that the lateral-directional pilot-induced oscillations due to the landing configuration switch can be evaluated using the changes in dynamic characteristic parameters before and after the configuration switch. The quantitative boundaries of the dynamic characteristic parameters of an example aircraft are determined, and a criterion suggestion is formed to predict the lateral-directional nonlinear pilot-induced oscillations due to landing configuration switching. This study provides a reference for the optimal design of the lateral-directional flight control law of fly-by-wire aircraft during the approach stage and provides suggestions for the formulation of evaluation criteria for other nonlinear pilot-induced oscillation phenomena.

Abstract The canals are essential for agricultural irrigation, shipping and industry as important hydraulic infrastructure. In the seasonal freeze regions, the water conveyance canals are damaged due to the effects of freeze–thaw cycles. The freeze depth of soil in the water transfer canal varies considerably due to changes in temperature and water content. This paper compared the relationship of freeze depth, temperature and water content by field tests and numerical calculation methods by incorporating phase change. The results from present study showed that the decrease in temperature causes the water in the soil to freeze, the ice front migrated downwards, and the water in soil below ice front gradually migrated towards the ice front resulting in a large difference in water content of the soil before and after freezing. The Polyurethane insulation board + Concrete board slope structure (PC) as an insulation slope structure was proposed in this paper to mitigate the effect of freezing and thawing on the water conveyance canals. The freeze depth decreased significantly under the protective effect. In addition, this paper compared the anti-frost effect of different thicknesses of polyurethane insulation boards, and the results provided a reference for the anti-frost design of water conveyance canals.

Sarcopenia, a disorder characterized by age-related muscle loss and reduced muscle strength, is associated with decreased individual independence and quality of life, as well as a high risk of death. Skeletal muscle houses a normally mitotically quiescent population of adult stem cells called muscle satellite cells (MuSCs) that are responsible for muscle maintenance, growth, repair, and regeneration throughout the life cycle. Patients with sarcopenia are often exhibit dysregulation of MuSCs homeostasis. In this review, we focus on the etiology, assessment, and treatment of sarcopenia. We also discuss phenotypic and regulatory mechanisms of MuSC quiescence, activation, and aging states, as well as the controversy between MuSC depletion and sarcopenia. Finally, we give a multi-dimensional treatment strategy for sarcopenia based on improving MuSC function.

This paper presents a monolithic microwave integrated circuit (MMIC) low noise amplifier (LNA) that is compatible with n257 (26.5–29.5 GHz) and n258 (24.25–27.5 GHz) frequency bands for fifth-generation mobile communications system (5G) and millimeter-wave radar. The total circuit size of the LNA is 2.5 × 1.5 mm2. To guarantee a trade-off between noise figure (NF) and small signal gain, the transmission lines are connected to the source of gallium nitride (GaN)-on-SiC high electron mobility transistors (HEMT) by analyzing the nonlinear small signal equivalent circuit. A series of stability enhancement measures including source degeneration, an RC series network, and RF choke are put forward to enhance the stability of designed LNA. The designed GaN-based MMIC LNA adopts hybrid-matching networks (MNs) with co-design strategy to realize low NF and broadband characteristics across 5G n257 and n258 frequency band. Due to the different priorities of these hybrid-MNs, distinguished design strategies are employed to benefit small signal gain, input-output return loss, and NF performance. In order to meet the testing conditions of MMIC, an impeccable system for measuring small has been built to ensure the accuracy of the measured results. According to the measured results for small signal, the three-stage MMIC LNA has a linear gain of 18.2–20.3 dB and an NF of 2.5–3.1 dB with an input–output return loss better than 10 dB in the whole n257 and n258 frequency bands.

When considering the robust control of fixed-wing Unmanned Aerial Vehicles (UAVs), a conflict often arises between addressing nonlinearity and meeting fast-solving requirements. In existing studies, the less nonlinear robust control methods have shown significant improvements that parallel computing and dimensionality reduction techniques in real-time applications. In this paper, a nonlinear fast Tube-based Robust Compensation Control (TRCC) for fixed-wing UAVs is proposed to satisfy robustness and fast-solving requirements. Firstly, a solving method for discrete trajectory tubes was proposed to facilitate fast parallel computation. Subsequently, a TRCC algorithm was developed that minimized the trajectory tube to enhance robustness. Additionally, considering the characteristics of fixed-wing UAVs, dimensionality reduction techniques such as decoupling and stepwise approaches are proposed, and a fast TRCC algorithm that incorporates the control reuse method is presented. Finally, simulations verify that the proposed fast TRCC effectively enhances the robustness of UAVs during tracking tasks while satisfying the requirements for fast solving.

Glycyrrhiza uralensis contains many secondary metabolites with a wide range of pharmacological activities. Drought stress acts as a positive regulator to stimulate the production of medicinal active component in G. uralensis, however, the underlying mechanism remains unclear. The aim of this work is to investigate the accumulation and regulatory mechanism of pharmaceutical active ingredients in G. uralensis under drought stress. The materials of the aerial and underground parts of G. uralensis seedlings treated by 10% PEG6000 for 0, 2, 6, 12, and 24 h were used for RNA sequencing and determination of phytohormones and pharmaceutical active ingredients. PEG6000, ibuprofen (IBU), and jasmonic acid (JA) were utilized to treat G. uralensis seedlings for content detection and gene expression analysis. The results showed that, the contents of glycyrrhizic acid, glycyrrhetinic acid, and flavonoids (licochalcone A, glabridin, liquiritigenin, isoliquiritigenin, and liquiritin) were significantly accumulated in G. uralensis underground parts under drought stress. Kyoto Encyclopedia of Genes and Genomes analysis of the transcriptome data of drought-treated G. uralensis indicated that up-regulated differentially expressed genes (UDEGs) involved in glycyrrhizic acid synthesis in the underground parts and flavonoids synthesis in both aerial and underground parts were significantly enriched. Interestingly, the UDEGs participating in jasmonic acid (JA) signal transduction in both aerial and underground parts were discovered. In addition, JA content in both aerial and underground parts under drought stress showed the most significantly accumulated. And drought stress stimulated the contents of JA, glycyrrhizic acid, and flavonoids, coupled with the induced expressions of genes regulating the synthesis and transduction pathway. Moreover, In PEG6000- and JA-treated G. uralensis, significant accumulations of glycyrrhizic acid and flavonoids, and induced expressions of corresponding genes in these pathways, were observed, while, these increases were significantly blocked by JA signaling inhibitor IBU. JA content and expression levels of genes related to JA biosynthesis and signal transduction were also significantly increased by PEG treatment. Our study concludes that drought stress might promote the accumulation of pharmaceutical active ingredients via JA-mediated signaling pathway, and lay a foundation for improving the medicinal component of G. uralensis through genetic engineering technology.

Alternative splicing (AS) is a post-transcriptional regulatory mechanism that increases protein diversity. There is growing evidence that AS plays an important role in regulating plant stress responses. However, the mechanism by which AS coordinates with transcriptional regulation to regulate the drought response in Glycyrrhiza uralensis remains unclear. In this study, we performed a genome-wide analysis of AS events in G. uralensis at different time points under drought stress using a high-throughput RNA sequencing approach. We detected 2,479 and 2,764 AS events in the aerial parts (AP) and underground parts (UP), respectively, of drought-stressed G. uralensis. Of these, last exon AS and exon skipping were the main types of AS. Overall, 2,653 genes undergoing significant AS regulation were identified from the AP and UP of G. uralensis exposed to drought for 2, 6, 12, and 24 h. Gene Ontology analyses indicated that AS plays an important role in the regulation of nitrogen and protein metabolism in the drought response of G. uralensis. Notably, the spliceosomal pathway and basal transcription factor pathway were significantly enriched with differentially spliced genes under drought stress. Genes related to splicing regulators in the AP and UP of G. uralensis responded to drought stress and underwent AS under drought conditions. In summary, our data suggest that drought-responsive AS directly and indirectly regulates the drought response of G. uralensis. Further in-depth studies on the functions and mechanisms of AS during abiotic stresses will provide new strategies for improving plant stress resistance.

Abstract Background Epilepsy is a group of neurological disorders characterized by recurrent epileptic seizures. Epilepsy is affected by many factors, approximately 20–30% of cases are caused by acquired conditions, but in the remaining cases, genetic factors play an important role. Early establishment of a specific diagnosis is important to treat and manage this disease. Methods In this study, we have recruited 43 epileptic encephalopathy patients and the molecular genetic analysis of those children was performed by whole-exome sequencing (WES). Results Fourteen patients (32.6%, 14/43) had positive genetic diagnoses, including fifteen mutations in fourteen genes. The overall diagnostic yield was 32.6%. A total of 9 patients were diagnosed as pathogenic mutations, including 4 variants had been reported as pathogenic previously and 6 novel variants that had not been reported previously. Therefore, WES heralds promise as a tool for clinical diagnosis of patients with genetic disease. Conclusion Early establishment of a specific diagnosis, on the one hand, is necessary for providing an accurate prognosis and recurrence risk as well as optimizing management and treatment options. On the other hand, to unveil the genetic architecture of epilepsy, it is of vital importance to investigate the phenotypic and genetic complexity of epilepsy.

Abstract Background Cell-free fetal DNA (cffDNA) has opened up new approaches for non-invasive prenatal testing (NIPT), and it is often used as the second-tier test for high-risk pregnant women in detecting trisomy (T) 21, T18, and T13 after serum biochemistry screening. This study aims to discuss the clinical performance of NIPT as an alternative first-tier screening test for pregnant women in detecting T21, T18, T13, and sex chromosome aneuploidies (SCAs) in China. Methods A total of 42,924 samples were recruited. The cell-free plasma DNA was directly sequenced. Each of the chromosome aneuploidies of PPV was analyzed. A total of 22 placental samples were acquired, including 14 FP and 8 TP samples. The placental verification of FP NIPT results was performed. Results Among 42,924 samples, 281 (0.65%) positive cases, including 87 of T21, 31 of T18, 22 of T13, and 141 of SCAs were detected. For the detection of T21, the positive predictive value (PPV) was 78.46%, for trisomy 18, 62.96%, for trisomy 13, 10.00%, for SCAs, 47.22% in the total samples. For trisomy 21, the PPV was 86.67%, for trisomy 18, 80.00%, for trisomy 13, 20.00%, for SCAs, 56.52% in advanced maternal age (AMA) women. The PPV of T21 increased with age. For T18, the PPV showed an overall upward trend. For T13 and SCAs, PPV was raised first and then lowered. Placental verification of false positive (FP) NIPT results confirmed confined placental mosaicism(CPM) was the reason for false positives. Conclusions This study represents the first time that NIPT has been used as a first-tier screening test for fetal aneuploidies in a pilot city with large clinical samples in China. We propose that NIPT could replace serum biochemistry screening as a first-tier test.

ABSTRACT Oral antibiotics remain the therapy of choice for severe bacterial infections; however, antibiotic use disrupts the intestinal microbiota, increasing the risk of colonization by intestinal pathogens. Currently, our understanding of antibiotic-mediated disturbances of the microbiota remains at the level of bacterial families or specific species, and little is known about the effect of antibiotics on potentially beneficial and pathogenic bacteria under the conditions of gut microbiota dysbiosis. Additionally, the question of whether the effects of antibiotics on the gut microbiota are temporary or permanent is controversial. In this study, we used 16S rRNA gene sequencing to evaluate the short- and long-term effects of ampicillin, vancomycin, metronidazole, and neomycin on the murine intestinal microbiota. We found that the changes in the intestinal microbiota reflected the antibiotics’ mechanisms of action and that dysbiosis of the intestinal microbiota led to competition between different bacterial communities. In particular, an increase in Enterococcus, which accompanies a decrease in probiotics-related genera such as Lactobacillus, is commonly seen across antibiotic treatments. In addition, we found that these oral antibiotics had long-term negative effects on the intestinal microbiota and promoted the development of antibiotic-resistant bacterial strains. These results indicate that ampicillin, vancomycin, metronidazole, and neomycin have long-term negative effects and can cause irreversible changes in the diversity of the intestinal microbiota, thereby increasing the risk of host disease. IMPORTANCE The intestinal microbiota is a dynamic community of hundreds of millions of microorganisms that play important roles in human health. However, treatment with antibiotics can disrupt the delicate balance of this community, leading to deleterious effects on the host such as inflammation and enhanced susceptibility to infection. To date, most studies of the effects of antibiotic treatment on the microbiota have focused on specific intestinal pathogens and bacterial families. However, few studies have investigated the effects of antibiotic treatment on the relative abundance of probiotic bacteria, pathogenic bacteria, and opportunistic bacterial pathogens in the gut.

The current research into decision-making strategies for air combat focuses on the performance of algorithms, while the selection of actions is often ignored, and the actions are often fixed in amplitude and limited in number in order to improve the convergence efficiency, making the strategy unable to give full play to the maneuverability of the aircraft. In this paper, a decision-making strategy for close-range air combat based on reinforcement learning with variable-scale actions is proposed; the actions are the variable-scale virtual pursuit angles and speeds. Firstly, a trajectory prediction method consisting of a real-time prediction, correction, and judgment of errors is proposed. The back propagation (BP) neural network and the long and short term memory (LSTM) neural network are used as base prediction network and correction prediction network, respectively. Secondly, the past, current, and future positions of the target aircraft are used as virtual pursuit points, and they are converted into virtual pursuit angles as the track angle commands using angle guidance law. Then, the proximity policy optimization (PPO) algorithm is applied to train the agent. The simulation results show that the attacking aircraft that uses the strategy proposed in this paper has a higher win rate during air combat and the attacking aircraft’s maneuverability is fully utilized.

Traditional pathological diagnoses and clinical methods are insufficient to accurately predict the prognosis of lung adenocarcinoma (LUAD). Epithelial-mesenchymal transition (EMT) process is closely related to tumor cell migration. However, the prognostic value of EMT-related genes in LUAD is still unclear. In this study, we collected bulk RNA-sequencing (RNA-seq) and microarray data of LUAD patients from public databases and identified different expressed EMT-related genes in tumor and normal tissues. Then, we used the least absolute shrinkage and selection operator Cox regression model to develop a multigene signature in the cancer genome atlas (TCGA) cohort and validated the model in the OncoSG (Singapore Oncology Data Portal) cohort as well as other datasets. Finally, we constructed a 12-gene signature to divide LUAD patients into high-risk and low-risk groups of overall survival (OS), which has a better stability and accuracy in predicating the OS of patients compared with some other published signatures of LUAD. In addition, evaluation of the risk model using the time-related receiver operating characteristic (ROC) curve confirmed the predictive ability of the model. Functional analysis showed that these genes are related to immunity. CD8 T cell and CD4 T cell types were significantly negatively correlated with the risk score in the analysis of immune infiltration. In general, our model provides useful information that may help clinicians better predict the prognosis of LUAD patients and provides potential targets for immunotherapy of LUAD.

The wind tunnel virtual flight test realizes the dynamic semi-free flight of the model in the wind tunnel through the deflections of the control surface and uses the test data to identify the aerodynamic derivatives. The difference in dynamics between the wind tunnel virtual flight and the free flight leads to discrepancies between the identification and theoretical results. To solve the problems, a step-by-step identification and correction method for aerodynamic derivatives is established based on the difference between the equations of motion of wind tunnel virtual flight and free flight to identify and correct the lift, drag derivatives, pitch moment derivatives, and velocity derivatives, respectively. To establish an aerodynamic parameter identification model, the flight dynamics equation is expressed as a decoupled form of the free flight force and the influence of the test support frame force on the model’s motions through linearization. To ensure the identification accuracy of each aerodynamic derivative, an excitation signal design method based on amplitude–frequency characteristic analysis is proposed. The longitudinal aerodynamic parameter identification results of a blended-wing-body aircraft show that identification results with higher accuracy can be obtained by adopting the proposed identification and correction method.

Abstract Background Trisomy 8 mosaicism has a wide phenotypic variability, ranging from mild dysmorphic features to severe malformations. This report concluded a female pregnant woman with trisomy 8 mosaicism, and carefully cytogenetic diagnoses were performed to give her prenatal diagnostic information. This report also provides more knowledge about trisomy 8 mosaicism and the prenatal diagnostic for clinicians. Case presentation In this present study, we reported one case of pregnancy woman with trisomy 8 mosaicism. Noninvasive prenatal testing prompted an abnormal Z-score, but further three dimension color ultrasound result suggested a single live fetus with no abnormality. The phenotypic of the pregnant woman was normal. Based on our results, there were no abnormal initial myeloid cells (

Abstract Background The underlying physiological mechanisms associated with aging are still complex and unclear. As a very important tissue of human body, the circulatory system also plays a very important role in the process of aging. In this study, we use the isobaric tags for relative and absolute quantification (iTRAQ) method to identify differentially expressed proteins in plasma for humans and monkeys between young and aged. Western blotting and behavioral experiment in mice were performed to validate the expression of the candidate protein. Results Between the young / the old humans and the young / the old monkeys 74 and 69 proteins were found to be differently expressed, respectively. For the human samples, these included 38 up-regulated proteins and 36 down-regulated proteins (a fold change ≥1.3 or ≤ 0.667, p value ≤0.05).For the monkey samples, 51 up-regulated proteins and 18 down-regulated proteins (a fold change ≥1.3 or ≤ 0.667, p value ≤0.05). KEGG pathway analysis revealed that phagosome, focal adhesion, ECM-receptor interaction and PI3K/AKT signaling pathway were the most common pathways involved in aging. We found only IGFBP4 protein that existed in up-regulated proteins in aged both for human and monkey. In addition, the differential expression of IGFBP4 was validated by western blot analysis and IGFBP4 treatment mimicked aging-related cognitive dysfunction in mice. Conclusions This first, the integrated proteomics for the plasma protein of human and monkey reveal one protein-IGFBP4, which was validated by western blotting and behavioral analysis can promote the process of aging. And, iTRAQ analysis showed that proteolytic systems, and inflammatory responses plays an important role in the process of aging. These findings provide a basis for better understanding of the underlying mechanisms involved in aging.

Abstract Background Lung cancer is the second most common cancer with an extremely poor overall survival rate. Post-transcriptional regulation of gene expression play many important roles in human cancer, and one of the potential mechanisms underlying this is alternative mRNA maturation at its 3′ untranslated regions (3′-UTRs). Methods Cancer tissues and paired adjacent normal lung tissues from 26 patients diagnosed with non-small cell lung cancer (NSCLC) were analyzed by in vitro transcription-sequencing alternative polyadenylation sites (IVT-SAPAS). 41,773,101 reads in average were obtained from each paired sample. A potential regulation of Cleavage Stimulation Factor Subunit 2 (CSTF2) on 3′UTR length of genes was tested in H460 cells. Results 1439 (10.26%) genes showed up-regulated expression and 1364 (9.72%) genes showed down-regulated expression in lung cancer tissue versus normal lung tissue, and shorten 3′UTR in cancer tissue was detected in cancer tissues collected from 96.2% (25/26) patients, indicating lung cancer tend to have shortened 3′UTRs of these identified genes. KEGG analysis showed 1855 genes with shorten 3′UTR were enriched in mTOR signaling, ubiquitin mediated proteolysis and RNA degradation. Knocking down CSTF2 expression in H460 cells results in 3′UTR elongation of genes that was identified to be with shortened length in cancer tissues. Conclusion Alternative polyadenylation (APA) site-switching of 3′UTRs is prevalent in NSCLC, and CSTF2 may serve as an oncogene regulates the 3′UTR length of cancer related genes in NSCLC.

Abstract Background Pregnancy complications could lead to maternal and fetal morbidity and mortality. Early diagnosing and managing complications have been associated with good outcomes. The placenta was an important organ for development of pregnancy complications. Thus, non-invasive prenatal testing technologies could detect genetic variations, such as aneuploidies and sub-chromosomal copy number variations, reflecting defective placenta by maternal plasma cffDNAs. Maternal cffDNAs had been proved to derive from trophoblast cells of placenta. Results In order to find out the relationship between genetic variations and pregnancy complications, we reviewed NIPT results for subchromosomal copy number variations in a cohort of 3890 pregnancies without complications and 441 pregnancies with pregnancy complications including gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), preterm prelabor rupture of membranes (PPROM) and placenta implantation abnormalities (PIA). For GDMs, we identified three CNV regions containing some members of alpha- and beta-defensins, such as DEFA1, DEFA3, DEFB1. For PIHs, we found three duplication and one deletion region including Pcdhα, Pcdhβ, and Pcdhγ, known as protocadherins, which were complicated by hypertensive disorders. For PPROMs and PIAs, we identified one and two CNV regions, respectively. SFTPA2, SFTPD and SFTPA1, belonging to surfactant protein, was considered to moderated the inflammatory activation within the fetal extra-embryonic compartment, associated to duration of preterm prelabor rupture of fetal membranes, while MEF2C and TM6SF1 could be involved in trophoblast invasion and differentiation. Conclusions Our findings gave a clue to correlation between genetic variations of maternal cell-free DNAs and pregnancy complications.

Abstract Background Noninvasive prenatal screening (NIPS) based on cell-free fetal DNA (cffDNA) has rapidly been applied into clinic. However, the reliability of this method largely depends on the concentration of cffDNA in the maternal plasma. The chance of test failure results or false negative results would increase when cffDNA fraction is low. In this study, we set out to develop a method to enrich the cffDNA for NIPS based on the size difference between cell-free DNA (cfDNA) of fetal origin and maternal origin, and to evaluate whether the new NIPS method can improve the test quality. Methods We utilized 10,000 previous NIPS data to optimize a size-selection strategy for enrichment. Then, we retrospectively performed our new NIPS method with cffDNA enrichment on the 1415 NIPS samples, including 1404 routine cases and 11 false negative cases, and compared the results to the original NIPS results. Results The 10,000 NIPS data revealed the fetal fraction in short cfDNA fragments (

Abstract Background Noninvasive prenatal testing (NIPT) for fetal aneuploidies by scanning cell-free fetal DNA in maternal plasma is rapidly becoming a first-tier aneuploidy screening test in clinical practices. With the development of whole-genome sequencing technology, small subchromosomal deletions and duplications that could not be detected by conventional karyotyping are now able to be detected with NIPT technology. Methods In the present study, we examined 8141 single pregnancies with NIPT to calculate the positive predictive values of each of the chromosome aneuploidies and the subchromosomal microdeletions and microduplications. Results We confirmed that the positive predictive values (PPV) for trisomy 13, trisomy 18, trisomy 21, and sex chromosome aneuploidy were 14.28%, 60%, 80%, and 45.83%, respectively. At the same time, we also found 51 (0.63%) positive cases for chromosomal microdeletions or microduplications but only 13 (36.11%) true-positive cases. These results indicate that NIPT for trisomy 21 detection had the highest accuracy, while accuracy was low for chromosomal microdeletion and microduplications. Conclusions Therefore, it is very important to improve the specificity, accuracy, and sensitivity of NIPT technology for the detection of subchromosomal microdeletions and microduplications.

Debris flow susceptibility mapping (DFSM), which has proven to be one of the most effective tools for risk management, faces a variety of problems. To realize the rational use of debris flow sample resources and improve the modeling efficiency, a unified model based on transfer learning was established for cross-regional DFSM. First, samples with 10 features collected from two debris flow-prone areas were separately used to perform factor prediction ability analysis (FPAA) based on the information gain ratio (IGR) method and then develop traditional machine learning models based on random forests (RF). Secondly, two feature matrices representing different areas were projected into a common latent feature space to obtain two new feature matrices. Then, the samples with new features were used together for FPAA and developing a unified machine learning model. Finally, the performance of the models was obtained and compared based on the area under curves (AUC) and some statistical results. All the conditioning factors played different roles in debris flow prediction in the two study areas, based on which two traditional models and a unified model were established. The unified model based on feature transferring realized efficient cross-regional modeling, solved the unconvincing problem of limited sample modeling, and enabled more accurate identification of some debris flow samples.

BackgroundThe ABO blood group system is clinically important in kidney transplantation, but ABO genotyping fails to attract sufficient attention in some countries and regions. We identified one case of early graft dysfunction due to an ABO genotype mismatch. Here, we performed ABO genotyping in blood samples, analyzed grouping discrepancies, and investigated the weak A subgroup frequency in kidney transplantation candidates.MethodsBlood samples from 302 uremic patients with grouping discrepancies and 356 uremic patients with type A blood were analyzed using standard serologic serotyping techniques. The ABO genotypes and alleles were analyzed by polymerase chain reaction sequence-specific primer (PCR-SSP) and sequence-based typing (PCR-SBT).ResultsAll 302 uremic patients with grouping discrepancies carried weak ABO subgroup alleles and 77.48% carried irregular ABO antibodies. The discrepancy rate between serotyping and genotyping was 42.38%, and the mismatching rate of donor selection according to serotype reached 88.74%. And 2.53% of 356 uremic patients with type A blood were determined to be in the weak A subgroup, which was a higher percentage than that observed in the healthy Chinese population (0.53%) by serological screening, but much lower than that observed in Caucasians (20%).ConclusionWe revealed the high risk of blood type misjudgment and genetically ABO-mismatched transplantation if serological test was performed only in blood-group typing. Improved precision of ABO genotyping is crucial for successful kidney transplantation and reasonable organ allocation.

Glycyrrhizic acid (GA) is the substance with the highest content of triterpenoid saponins that can be extracted from licorice, and has anti-inflammatory, neuroprotective, and anticancer functions, among others. The aim of this study was to investigate the protective effect of GA on cognitive decline in middle-aged mice and explore its mechanisms. We injected GA by the tail vein of C57BL/6 mice and measured their cognitive levels using the Morris water maze. The Morris water maze results demonstrated that GA improved learning and memory abilities in middle-aged mice. Furthermore, the RNA-sequencing and flow cytometric analyses revealed that GA could increase T and B cells. We then confirmed the relationship between cognition and the immune system in the immune-deficient B-NDG mouse model. Our results suggest that GA improves cognition in aging mice by regulating T/B cell proliferation.

Pancreatic cancer is among the most aggressive malignancies associated with chronic inflammation. Moreover, cellular immunity can be inhibited by inflammation induced by nucleotide-binding domain, leucine-rich family, pyrin-containing 3 (NLRP3) inflammasome. Accordingly, NLRP3 inhibition combining cytokine-induced killer (CIK) cells may improve antitumor efficacy. 3,4-Methylenedioxy-β-nitrostyrene (MNS) was selected as a specific NLRP3 inflammasome inhibitor. Western blot was used to evaluate the NLRP3 inflammasome expression in pancreatic cancer cell lines SW1990 and PANC-1. The impact of NLRP3 inhibition on migration, invasiveness, and proliferation of pancreatic cancer cells was analyzed through wound healing assay, Transwell assay, and Cell Counting Kit-8 (CCK-8) assay, respectively. The combining antitumor effect in vivo of CIK and NLRP3 inhibition was evaluated in a subcutaneous human pancreatic cancer BALB/c nude mouse model. Western blot analysis showed significant expression of NLRP3 inflammasome in human pancreatic cancer lines SW1990 and PANC-1, and MNS did significantly inhibit the expression of NLRP3 inflammasome in cell lines. Moreover, NLRP3 inhibition could significantly decrease the migration, invasiveness, and proliferation of pancreatic cancer cells. In vivo experiments showed that combination treatment with MNS and CIK cells had the greatest antitumor effect among the four treatment groups including control, MNS, and CIK. Combination treatment with NLRP3 inflammasome inhibition and CIK cells showed greater antitumor efficacy through inflammation inhibition and immunity restoration.

We expand the renewable technology model palette and present a validated high resolution hydro power time series model for energy systems analysis. Among the weather-based renewables, hydroelectricity shows unique storage-like flexibility, which is particularly important given the high variability of wind and solar power. Often limited by data availability or computational performance, a high resolution, globally applicable and validated hydro power time series model has not been available. For a demonstration, we focus on 41 Chinese reservoir-based hydro stations as a demo, determine their upstream basin areas, estimate their inflow based on gridded surface runoff data and validate their daily inflow time series in terms of both flow volume and potential power generation. Furthermore, we showcase an application of these time series with hydro cascades in energy system long term investment planning. Our method's novelty lies in: • it is based on highly resolved spatial-temporal datasets; • both data and algorithms used here are globally applicable; • it includes a hydro cascade model that can be integrated into energy system simulations. Keywords: Hydro power, Reanalysis, Energy systems, China

In this paper, we investigate the characteristics of the colorless polyimide (CPI) film-based flexible organic X-ray detector. The CPI film can be applied to various applications, because it shows excellent visible light transmittance by removing the yellow color of polyimide (PI) film, which has the advantage of physical and chemical stability. In addition, the deformation curvature of the CPI substrate according to temperature showed similar characteristics to that of the glass substrate. For the organic active layer of the proposed detector, PBDB-T was fixed as a donor, and PC71BM and ITIC were used as acceptors. To evaluate the mechanical stability of the flexible detector, the degradation sensitivity was measured as bending curvature and bending cycle. The sensitivity of the detector with ITIC acceptor showed a 46.82% higher result than PC71BM acceptor on bending curvature (R = 10); and at the same curvature, when the bending cycle was 500 times, a 135.85% higher result than PC71BM acceptor.

Landslides cause huge damage to social economy and human beings every year. Landslide susceptibility mapping (LSM) occupies an important position in land use and risk management. This study is to investigate a hybrid model which makes full use of the advantage of supervised learning model (SLM) and unsupervised learning model (ULM). Firstly, ten continuous variables were used to develop a ULM which consisted of factor analysis (FA) and k-means cluster for a preliminary landslide susceptibility map. Secondly, 351 landslides with “1” label were collected and the same number of non-landslide samples with “0” label were selected from the very low susceptibility area in the preliminary map, constituting a new priori condition for a SLM, and thirteen factors were used for the modeling of gradient boosting decision tree (GBDT) which represented for SLM. Finally, the performance of different models was verified using related indexes. The results showed that the performance of the pretreated GBDT model was improved with sensitivity, specificity, accuracy and the area under the curve (AUC) values of 88.60%, 92.59%, 90.60% and 0.976, respectively. It can be concluded that a pretreated model with strong robustness can be constructed by increasing the purity of samples.

Cholesterol 7α-hydroxylase (CYP7A1) plays a critical role in control of bile acid and cholesterol homeostasis. Bile acids activate farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5) to regulate lipid, glucose, and energy metabolism. However, the role of bile acids in hepatic inflammation and fibrosis remains unclear. In this study, we showed that adenovirus-mediated overexpression of Cyp7a1 ameliorated lipopolysaccharide (LPS)-induced inflammatory cell infiltration and pro-inflammatory cytokine production in WT and TGR5-deficient (Tgr5−/−) mice, but not in FXR-deficient (Fxr−/−) mice, suggesting that bile acid signaling through FXR protects against hepatic inflammation. Nuclear factor κ light-chain enhancer of activated B cells (NF-κB)-luciferase reporter assay showed that FXR agonists significantly inhibited TNF-α-induced NF-κB activity. Furthermore, chromatin immunoprecipitation and mammalian two-hybrid assays showed that ligand-activated FXR interacted with NF-κB and blocked recruitment of steroid receptor coactivator-1 to cytokine promoter and resulted in inhibition of NF-κB activity. Methionine/choline-deficient (MCD) diet increased hepatic inflammation, free cholesterol, oxidative stress, apoptosis, and fibrosis in CYP7A1-deficient (Cyp7a1−/−) mice compared with WT mice. Remarkably, adenovirus-mediated overexpression of Cyp7a1 effectively reduced hepatic free cholesterol and oxidative stress and reversed hepatic inflammation and fibrosis in MCD diet-fed Cyp7a1−/− mice. Current studies suggest that increased Cyp7a1 expression and bile acid synthesis ameliorate hepatic inflammation through activation of FXR, whereas reduced bile acid synthesis aggravates MCD diet-induced hepatic inflammation and fibrosis. Maintaining bile acid and cholesterol homeostasis is important for protecting against liver injury and nonalcoholic fatty liver disease.

In this study, we investigated the characteristics of an organic-inorganic hybrid indirect-type X-ray detector with a CH3NH3PbI3 (MAPbI3) perovskite active layer. A layer with a thickness of 192 nm annealed at 100 °C showed higher absorption, higher crystallinity, and lower surface roughness than did perovskite layers made under different conditions. In the indirect X-ray detector, a scintillator coupled with the detector to convert X-ray photons to visible photons, and the converted photons were absorbed by the active layer to generate charge carriers. The detector with the optimized MAPbI3 (192 nm thick and 100 °C annealing condition) active layer was coupled with a CsI(Tl) scintillator which consisted of 400 μm thick CsI and 0.5 mm thick Al, and achieved the highest sensitivity, i.e., 2.84 mA/Gy·cm2. In addition, the highest short-circuit current density (JSC), i.e., 18.78 mA/cm2, and the highest mobility, i.e., 2.83 × 10−4 cm2/V·s, were obtained from the same detector without the CsI(Tl) scintillator.

In this paper, we studied the optimized conditions for adding inorganic quantum dots (QD) to the P3HT:PC70BM organic active layer to increase the sensitivity of the indirect X-ray detector. Commonly used QDs are composed of hazardous substances with environmental problems, so indium phosphide (InP) QDs were selected as the electron acceptor in this experiment. Among the three different sizes of InP QDs (4, 8, and 12 nm in diameter), the detector with 4 nm InP QDs showed the highest sensitivity, of 2.01 mA/Gy·cm2. To further improve the sensitivity, the QDs were fixed to 4 nm in diameter and then the amount of QDs added to the organic active layer was changed from 0 to 5 mg. The highest sensitivity, of 2.26 mA/Gy·cm2, was obtained from the detector with a P3HT:PC70BM:InP QDs (1 mg) active layer. In addition, the highest mobility, of 1.69 × 10−5 cm2/V·s, was obtained from the same detector. Compared to the detector with the pristine P3HT:PC70BM active layer, the detector with a P3HT:PC70BM:InP QDs (1 mg) active layer had sensitivity that was 61.87% higher. The cut-off frequency of the P3HT:PC70BM detector was 21.54 kHz, and that of the P3HT:PC70BM:InP QDs (1 mg) detector was 26.33 kHz, which was improved by 22.24%.

The existence of only natural brown and green cotton fibers (BCF and GCF, respectively), as well as poor fiber quality, limits the use of naturally colored cotton (Gossypium hirsutum L.). A better understanding of fiber pigment regulation is needed to surmount these obstacles. In this work, transcriptome analysis and quantitative reverse transcription PCR revealed that 13 and 9 phenylpropanoid (metabolic) pathway genes were enriched during pigment synthesis, while the differential expression of phenylpropanoid (metabolic) and flavonoid metabolic pathway genes occurred among BCF, GCF, and white cotton fibers (WCF). Silencing the chalcone flavanone isomerase gene in a BCF line resulted in three fiber phenotypes among offspring of the RNAi lines: BCF, almost WCF, and GCF. The lines with almost WCF suppressed chalcone flavanone isomerase, while the lines with GCF highly expressed the glucosyl transferase (3GT) gene. Overexpression of the Gh3GT or Arabidopsis thaliana 3GT gene in BCF lines resulted in GCF. Additionally, the phenylpropanoid and flavonoid metabolites of BCF and GCF were significantly higher than those of WCF as assessed by a metabolomics analysis. Thus, the flavonoid biosynthetic pathway controls both brown and green pigmentation processes. Like natural colored fibers, the transgenic colored fibers were weaker and shorter than WCF. This study shows the potential of flavonoid pathway modifications to alter cotton fibers’ color and quality.

Mobile crowd sensing (MCS) systems usually attract numerous participants with widely varying sensing costs and interest preferences to perform tasks, where accurate task assignment plays an indispensable role and also faces many challenges (e.g., how to simplify the complicated task assignment process and improve matching accuracy between tasks and participants, while guaranteeing submitted data credibility). To overcome these challenges, we propose a service benefit aware multi-task assignment (SBAMA) strategy in this paper. Firstly, service benefits of participants are modeled based on their task difficulty, task history, sensing capacity, and sensing positivity to meet differentiated requirements of various task types. Subsequently, users are then clustered by enhanced fuzzy clustering method. Finally, a gradient descent algorithm is designed to match task types to participants achieving the maximum service benefit. Simulation results verify that the proposed task assignment strategy not only effectively reduces matching complexity but also improves task completion rate.

Complex chromosome rearrangements (CCRs), which are rather rare in the whole population, may be associated with aberrant phenotypes. Next-generation sequencing (NGS) and conventional techniques, could be used to reveal specific CCRs for better genetic counseling. We report the CCRs of a girl and her mother, which were identified using a combination of NGS and conventional techniques including G-banding, fluorescence in situ hybridization (FISH) and PCR. The girl demonstrated CCRs involving chromosomes 3 and 8, while the CCRs of her mother involved chromosomes 3, 5, 8, 11 and 15. HumanCytoSNP-12 Chip analysis identified a 35.4 Mb duplication on chromosome 15q21.3-q26.2 in the proband and a 1.6 Mb microdeletion at chromosome 15q21.3 in her mother. The proband inherited the rearranged chromosomes 3 and 8 from her mother, and the duplicated region on chromosome 15 of the proband was inherited from the mother. Approximately one hundred genes were identified in the 15q21.3-q26.2 duplicated region of the proband. In particular, TPM1, SMAD6, SMAD3, and HCN4 may be associated with her heart defects, and HEXA, KIF7, and IDH2 are responsible for her developmental and mental retardation. In addition, we suggest that a microdeletion on the 15q21.3 region of the mother, which involved TCF2, TCF12, ADMA10 and AQP9, might be associated with mental retardation. We delineate the precise structures of the derivative chromosomes, chromosome duplication origin and possible molecular mechanisms for aberrant phenotypes by combining NGS data with conventional techniques.

Yu-ping-feng-san (YPFS) is a Chinese medical formula that is used clinically for allergic diseases and characterized by reducing allergy relapse. Our previous studies demonstrated that YPFS efficiently inhibited T helper 2 cytokines in allergic inflammation. The underlying mechanisms of action of YPFS and its effective components remain unclear. In this study, it was shown that YPFS significantly inhibited production of thymic stromal lymphopoietin (TSLP), an epithelial cell-derived initiative factor in allergic inflammation, in vitro and in vivo. A method of human bronchial epithelial cell (16HBE) binding combined with HPLC-MS (named 16HBE-HPLC-MS) was established to explore potential active components of YPFS. The following five components bound to 16HBE cells: calycosin-7-glucoside, ononin, claycosin, sec-o-glucosylhamaudol and formononetin. Serum from YPFS-treated mice was analyzed and three major components were detected claycosin, formononetin and cimifugin. Among these, claycosin and formononetin were detected by 16HBE-HPLC-MS and in the serum of YPFS-treated mice. Claycosin and formononetin decreased the level of TSLP markedly at the initial stage of allergic inflammation in vivo. Nuclear factor (NF)-κB, a key transcription factor in TSLP production, was also inhibited by claycosin and formononetin, either in terms of transcriptional activation or its nuclear translocation in vitro. Allergic inflammation was reduced by claycosin and formononetin when they are administered only at the initial stage in a murine model of atopic contact dermatitis. Thus, epithelial cell binding combined with HPLC-MS is a valid method for screening active components from complex mixtures of Chinese medicine. It was demonstrated that the compounds screened from YPFS significantly attenuated allergic inflammation probably by reducing TSLP production via regulating NF-κB activation.

Clonorchis sinensis (C. sinensis), an important food-borne parasite that inhabits the intrahepatic bile duct and causes clonorchiasis, is of interest to both the public health field and the scientific research community. To learn more about the migration, parasitism and pathogenesis of C. sinensis at the molecular level, the present study developed an upgraded genomic assembly and annotation by sequencing paired-end and mate-paired libraries. We also performed transcriptome sequence analyses on multiple C. sinensis tissues (sucker, muscle, ovary and testis). Genes encoding molecules involved in responses to stimuli and muscle-related development were abundantly expressed in the oral sucker. Compared with other species, genes encoding molecules that facilitate the recognition and transport of cholesterol were observed in high copy numbers in the genome and were highly expressed in the oral sucker. Genes encoding transporters for fatty acids, glucose, amino acids and oxygen were also highly expressed, along with other molecules involved in metabolizing these substrates. All genes involved in energy metabolism pathways, including the β-oxidation of fatty acids, the citrate cycle, oxidative phosphorylation, and fumarate reduction, were expressed in the adults. Finally, we also provide valuable insights into the mechanism underlying the process of pathogenesis by characterizing the secretome of C. sinensis. The characterization and elaborate analysis of the upgraded genome and the tissue transcriptomes not only form a detailed and fundamental C. sinensis resource but also provide novel insights into the physiology and pathogenesis of C. sinensis. We anticipate that this work will aid the development of innovative strategies for the prevention and control of clonorchiasis.

The p38 MAPK signaling pathway plays a pivotal role in inflammation. Targeting p38 MAPK may be a potential strategy for the treatment of inflammatory diseases. In the present study, we show that a novel chromone derivative, DCO-6, significantly reduced lipopolysaccharide (LPS)-induced production of nitric oxide, IL-1β and IL-6, decreased the levels of iNOS, IL-1β and IL-6 mRNA expression in both RAW264.7 cells and mouse primary peritoneal macrophages, and inhibited LPS-induced activation of p38 MAPK but not of JNK, ERK. Moreover, DCO-6 specifically inhibited TLR4-dependent p38 activation without directly inhibiting its kinase activity. LPS-induced production of intracellular reactive oxygen species (ROS) was remarkably impaired by DCO-6, which disrupted the formation of the TRAF6-ASK1 complex. Administering DCO-6 significantly protected mice from LPS-induced septic shock in parallel with the inhibition of p38 activation and ROS production. Our results indicate that DCO-6 showed anti-inflammatory properties through inhibition of ROS-dependent activation of TRAF6-ASK1-p38 pathway. Blockade of the upstream events required for p38 MAPK action by DCO-6 may provide a new therapeutic option in the treatment of inflammatory diseases.