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Abstract Background Fleas, considered to be the main transmission vectors of Bartonella, are highly prevalent and show great diversity. To date, no investigations have focused on Bartonella vectors in Southeast China. The aim of this study was to investigate the epidemiological and molecular characteristics of Bartonella in fleas in Southeast China. Methods From 2016 to 2022, flea samples (n = 1119) were collected from 863 rodent individuals in seven inland and coastal cities in Southeast China. Flea species, region, gender, host species and habitat were recorded. The DNA samples from each individual flea were screened by real-time PCR for the Bartonella ssrA gene. All positive samples were confirmed by PCR based on the presence of the gltA gene and sequenced. The factors associated with Bartonella infection were analyzed by the Chi-square test and Fisher's exact test. ANOVA and the t-test were used to compare Bartonella DNA load. Results Bartonella DNA was detected in 26.2% (293/1119) of the flea samples, including in 27.1% (284/1047) of Xenopsylla cheopis samples, 13.2% (5/38) of Monopsyllus anisus samples, 8.3% (2/24) of Leptopsylla segnis samples and 20.0% (2/10) of other fleas (Nosopsyllus nicanus, Ctenocephalides felis, Stivalius klossi bispiniformis and Neopsylla dispar fukienensis). There was a significant difference in the prevalence of Bartonella among flea species, sex, hosts, regions and habitats. Five species of Bartonella fleas were identified based on sequencing and phylogenetic analyses targeting the gltA gene: B. tribocorum, B. queenslandensis, B. elizabethae, B. rochalimae and B. coopersplainsensis. Conclusions There is a high prevalence and diversity of Bartonella infection in the seven species of fleas collected in Southeast China. The detection of zoonotic Bartonella species in this study, including B. tribocorum, B. elizabethae and B. rochalimae, raises public health concerns. Graphical Abstract

Abstract The lasso peptide microcin Y (MccY) effectively inhibits various serotypes of Salmonella in vitro, but the antibacterial effect against S. Pullorum in poultry is still unclear. This study was the first to evaluate the safety and anti-S. Pullorum infection of MccY in specific pathogen-free (SPF) chicks. The safety test showed that the body weight, IgA and IgM levels of serum, and cecal microbiota structure of 3 groups of chicks orally administrated with different doses of MccY (5 mg/kg, 10 mg/kg, 20 mg/kg) for 14 days were not significantly different from those of the control group. Then, the chicks were randomized into 3 groups for the experiment of anti-S. Pullorum infection: (I) negative control group (NC), (II) S. Pullorum-challenged group (SP, 5 × 108 CFU/bird), (III) MccY-treated group (MccY, 20 mg/kg). The results indicated that compared to the SP group, treatment of MccY increased body weight and average daily gain (P

The operation of the grid-connected inverter (GCI) in weak grid conditions presents a risk of instability due to the presence of high grid impedance and the negative impedance effect of the phase-locked loop (PLL). In response to this issue, this paper introduces an impedance remodeling control strategy for the GCI utilizing the inertia-damping phase-locked loop (ID-PLL). Firstly, the proposed ID-PLL exhibits certain inertia and damping properties in comparison to the traditional PLL (T-PLL), resulting in an enhanced phase margin of the GCI system's equivalent output impedance. Consequently, the adaptation range of the grid impedance increases from 12mH (SCR = 3.00) to 24mH (SCR = 1.37). Next, from the perspective of impedance analysis, this study remodels the PLL impedance and inverter control loop impedance, further improving the amplitude and phase margin of the system's output impedance. As a result, the adaptation range of the grid impedance extends to 33mH (SCR = 1.00), and the transition of grid-connected currents becomes smooth and free of overshoot. Finally, the effectiveness of the proposed control strategy is validated through theoretical analysis and experimental verification.

Abstract This study introduces PDMotion, a mobile application comprising 11 digital tests, including those adapted from the MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III and novel assessments, for remote Parkinson's Disease (PD) motor symptoms evaluation. Employing machine learning techniques on data from 50 PD patients and 29 healthy controls, PDMotion achieves accuracies of 0.878 for PD status prediction and 0.715 for severity assessment. A post-hoc explanation model is employed to assess the importance of features and tasks in diagnosis and severity evaluation. Notably, novel tasks that are not adapted from MDS-UPDRS Part III like the circle drawing, coordination test, and alternative tapping test are found to be highly important, suggesting digital assessments for PD can go beyond digitizing existing tests. The alternative tapping test emerges as the most significant task. Using its features alone achieves prediction accuracies comparable to the full task set, underscoring its potential as an independent screening tool. This study addresses a notable research gap by digitalizing a wide array of tests, including novel ones, and conducting a comparative analysis of their feature and task importance. These insights provide guidance for task selection and future development in PD mobile assessments, a field previously lacking such comparative studies.

Background/Aims There may be many predictors of anticoagulation-related gastrointestinal bleeding (GIB), but until now, systematic reviews and assessments of the certainty of the evidence have not been published. We conducted a systematic review to identify all risk factors for anticoagulant-associated GIB to inform risk prediction in the management of anticoagulation-related GIB. Methods A systematic review and meta-analysis were conducted to search PubMed, EMBASE, Web of Science, and Cochrane Library databases (from inception through January 21, 2022) using the following search terms: anticoagulants, heparin, warfarin, dabigatran, rivaroxaban, apixaban, DOACs, gastrointestinal hemorrhage, risk factors. According to inclusion and exclusion criteria, studies of risk factors for anticoagulation-related GIB were identified. Risk factors for anticoagulant-associated GIB were used as the outcome index of this review. Results We included 34 studies in our analysis. For anticoagulant-associated GIB, moderate-certainty evidence showed a probable association with older age, kidney disease, concomitant use of aspirin, concomitant use of the antiplatelet agent, heart failure, myocardial infarction, hematochezia, renal failure, coronary artery disease, helicobacter pylori infection, social risk factors, alcohol use, smoking, anemia, history of sleep apnea, chronic obstructive pulmonary disease, international normalized ratio (INR), obesity et al. Some of these factors are not included in current GIB risk prediction models. such as anemia, co-administration of gemfibrozil, co-administration of verapamil or diltiazem, INR, heart failure, myocardial infarction, etc. Conclusions The study found that anemia, co-administration of gemfibrozil, co-administration of verapamil or diltiazem, INR, heart failure, myocardial infarction et al. were associated with anticoagulation-related GIB, and these factors were not in the existing prediction models. This study informs risk prediction for anticoagulant-associated GIB, it also informs guidelines for GIB prevention and future research.

Urban green infrastructure (GI) addresses human social development issues and challenges through urban green space ecosystem services. However, the ecosystem service functions of suburban cropland, especially regulating services and cultural services, have been seriously underestimated. The distribution of green spaces and suburban cropland varies in different regions of China, as well as their potential development methods. This article examines the potential of integrating suburban cropland into urban green infrastructure, offering a perspective on nature-based solutions in China. We divided the suburban cropland in China into three parts: peri‑suburban, mid-suburban, and outer-suburban by the concept of 15-minute living circle based on different travel modes of people. Based on statistical yearbook data, satellite remote sensing images and the fragstats 4.2 programme, a quantitative analysis was conducted on the spatial distribution, landscape pattern and social development of suburban farmland and green space in four cities. Then, the potential for improving the exposure level of suburban cropland after incorporating suburban cropland into urban green infrastructure was quantified and compared. Finally, we explored the potential development of the three kinds of suburban cropland as green infrastructure based on the concept of NbS. We found the spatial pattern of cropland and green space in the mid-suburban is greatly affected by regional geographical conditions, the green exposure level, i.e., green space availability indicators, in Beijing, Shanghai, Guangzhou, and Xi'an increased by 83 %, 300 %, 24 %, and 612 %, respectively, after incorporating suburban cropland into urban green infrastructure. The potential development models for suburban cropland should be based on NbS and China's national conditions: peri‑suburban cropland should be fully utilized for cultural and social functions, the mid-suburban cropland should focus on multifunctional utilization of cropland, and the outer-suburban is prioritized for ecological functions. Our study provides scientific insights for deep exploration of the functions of suburban cropland in China.

Nature-based Solutions (NbS) is a concept aims to address challenges related to human well-being, including human health, socio-economic development, and ecological security on both national and global scales. This concept was proposed against the backdrop of global climate change, ecological crises affecting humanity, and threats to sustainable development and it has been increasingly recognized and applied internationally over the past decade. The principle of NbS is reciprocity between humans and ecosystems, which is completely in line with the goals, systems, practices, and concepts guiding China's construction of ecological civilization. This paper clarifies concepts, evaluation criteria, and comprehensive benefits related to NbS, to trace the connection between NbS and both traditional and contemporary ecological civilization principles in China. By drawing valuable experience from NbS practices in China, it will focus on proposing policy and implementation suggestions to address challenges currently faced in NbS applications in China. This research will promote the research and practice of nature-based solutions in China. Meanwhile, provide novel perspectives and technologies for urban ecological design as well as sustainable development.

The Paleogene sandstone reservoir of Huizhou Sag is an important target for deep exploration in the Pearl River Mouth Basin, South China Sea. Because of the intense volcanic activity, it had a significant impact on the development of reservoirs, making it hard to predict. The diagenetic process of volcanogenic sediment and their influence of the reservoir have been studied by petrographic analysis, X-ray diffraction and scanning electron microscopy (SEM). Four types of volcanogenic sediment were identified: volcanic dust (

Although the discrete element method (DEM) has been used to simulate soil-subsoiler interactions, the degree of soil heterogeneity along the depth profile has not been well documented. Models of a layered soil structure were developed using the DEM, and they were a heterogeneous soil model (HeS Model) with seven layers, a semi-heterogeneous soil model (SHeS Model) with three layers, and a homogeneous soil model (HoS Model) with one layer. The models simulated the soil dynamic behavior resulting from a subsoiler travelling at speeds from 2 to 6 km h−1. Simulations were compared with field measurements. Results showed that soil particles flow in front of the subsoiler formed three distinguished zones: “pushing”, “rising”, and “passive” zones, with the “pushing” zone having the highest particle velocities. Compared with the measurements, the overall relative errors of the simulated soil disturbance widths (W) within the range of working speed from 2 to 6 km h−1 were below 20 % for all three models. Whereas the overall relative errors of the simulated soil surface flatness (F) were larger than 20 % for all three models. These suggest that all three models are suitable for predicting W, but not for predicting F, if a 20 % relative error was used as the judging criterion. The overall relative errors of the simulated elevated soil area (A) were 11.1 %, 18.8 %, and 25.7 % for the HeS, SHeS, and HoS Models, respectively, which suggest that HeS Model had the highest accuracy in predicting A. This study provides critical information for determining the degree of soil heterogeneity in simulations of the dynamics of soil-subsoiler interaction.

ABSTRACT Non-typhoidal salmonellae-induced zoonotic intestinal bleeding infections are a crucial threat to public health worldwide, and the development of new medications is required to prevent and treat non-typhoid Salmonella (NTS) infections. MccY, a class of lasso peptide, is effective in biological sterilization against Salmonella and Shigella. In this study, the therapeutic effect of MccY on S. Typhimurium-infected BALB/c mice has been discussed. specific pathogen free (SPF) mice were infected with the ST53 strain with bacterial loads of 106 and 103 CFU/mL, respectively, and then treated with 9.92 mg/kg BW MccY. Results revealed that MccY significantly reduced mouse mortality by 20%–40% and effectively alleviated weight loss and diarrhea. The integrity of the intestinal structure was protected, and the expression of TNF-α, IL-6, IL-10, and IL-18 was inhibited. Particularly, MccY exerted multiple effects on gut microbiota ecology, including direct elimination of Salmonella, showing promise in limiting infection to the gut level and thereby halting the transmission of NTS. MccY indirectly inhibited other opportunistic pathogens and partially restored the microbiota, promoting an increase in Bacteroidetes, Lactobacillus, Muribaculum, and Clostridium. Consequently, this work provides an understanding of the link between host infection and therapeutic application of MccY. IMPORTANCE Diseases caused by Enterobacteriaceae multidrug-resistant strains have become increasingly difficult to manage. It is necessary to verify the new antibacterial drug MccY effect on non-typhoid Salmonella infection in mice since it is regarded as a promising microcin. The results demonstrated that MccY has a potential therapeutic application value in the protection against Salmonella-induced intestinal damage and alleviating related intestinal dysbiosis and metabolic disorders. MccY could be a promising candidate as an antimicrobial or anti-inflammatory agent for treating infectious diseases.

Introduction: The construction of digital governance of national land space depends greatly on the development of a digital model for robust control of water and ecological space. However, how changes to the urban-water coupling relationships affect the resilience control of water ecological space is rarely reported.Methods: The evolution characteristics of urban and water space in the study area from 2000 to 2020 and the correlation between them are analyzed based on the grid analysis using InVEST and Moran’I methods. Based on the theory of human-environment interaction territorial system to provide a theoretical framework to explain the urban and water space. We used digital to construct an resilience control framework in the Dongting Lake area based on the correlation between the urban and water space.Results: The results show that: 1) From 2000 to 2020, the geographical evolution of towns and cities in the research area displayed obvious spatial variation in intensity, indicating a process of expansion and change. The regional and temporal fluctuations of the water conservation function are significant. The mountainous areas in the east, south, and northwest are where the high values of the water conservation function are primarily found. These regions have more vegetation, which increases the water conservation function. 2) According to the results of local binary spatial autocorrelation analysis, it can be seen that from 2000 to 2020, the high-high agglomeration of town space and water-related is mainly distributed in Linxiang City, Yueyang County, Miluo City, Li County, and Yiyang City, and the low-low agglomeration is mainly distributed in Dongting Lake, Datong Lake, and along the Yangtze River. 3) Based on how urban spatial evolution affects water ecological space, we construct a theoretical framework of urban-water coupling and establish a digital model of water ecological space resilience control in the Dongting Lake area from four perspectives: threshold, visualization, dynamics, and intelligence.

Measurements of rice physical traits, such as length, width, and percentage of filled/unfilled grains, are essential steps of rice breeding. A new approach for measuring the physical traits of rice grains for breeding purposes was presented in this study, utilizing image processing techniques. Backlight photography was used to capture a grayscale image of a group of rice grains, which was then analyzed using a clustering algorithm to differentiate between filled and unfilled grains based on their grayscale values. The impact of backlight intensity on the accuracy of the method was also investigated. The results show that the proposed method has excellent accuracy and high efficiency. The mean absolute percentage error of the method was 0.24% and 1.36% in calculating the total number of grain particles and distinguishing the number of filled grains, respectively. The grain size was also measured with a little margin of error. The mean absolute percentage error of grain length measurement was 1.11%, while the measurement error of grain width was 4.03%. The method was found to be highly accurate, non-destructive, and cost-effective when compared to conventional methods, making it a promising approach for characterizing physical traits for crop breeding.

Abstract Background Thrombolysis-related intracranial hemorrhage has a high mortality rate, and many factors can cause intracranial hemorrhage. Until now, systematic reviews and assessments of the certainty of the evidence have not been updated. Aim We conducted a systematic review to identify risk factors for thrombolysis-related intracranial hemorrhage. Method The protocol for this systematic review was prospectively registered with PROSPERO (CRD42022316160). All English studies that met the inclusion criteria published before January 2022 were obtained from PubMed, EMBASE, Web of Science, and Cochrane Library. Two researchers independently screened articles, extracted data, and evaluated the quality and evidence of the included studies. Risk factors for intracranial hemorrhage were used as the outcome index of this review. Random or fixed-effect models were used in statistical methods. Results Of 6083 citations, we included 105 studies in our analysis. For intracranial hemorrhage, moderate-certainty evidence showed a probable association with age, National Institutes of Health stroke scale, leukoaraiosis, hypertension, atrial fibrillation, diabetes, total cholesterol, proteinuria, fibrinogen levels, creatinine, homocysteine, early infarct signs, antiplatelet therapy and anticoagulant therapy; In addition, we found low-certainty evidence that there may be little to no association between risk of intracranial hemorrhage and weight, sex, platelet count, uric acid, albumin and white matter hyperintensity. Leukoaraiosis, cardiovascular disease, total cholesterol, white blood cell count, proteinuria, fibrinogen levels, creatinine, homocysteine and early CT hypodensities are not included in most intracranial hemorrhage risk assessment models. Conclusion This study informs risk prediction for thrombolysis-related intracranial hemorrhage, it also informs guidelines for intracranial hemorrhage prevention and future research.

The territorial spatial planning in the new era strengthens the control of different functional spaces and emphasizes integrated and coordinated development of each functional space. Therefore, it is important to monitor the “structure-function” characteristics of water-ecological space based on the context of territorial spatial planning and develop a management and control framework. Based on land use and social statistics, and with the help of ArcGIS analysis, this paper examined the structure and function of the water-ecological space in the Dongting Lake study for 2010, 2015, and 2020, generating a control framework and proposing key initiatives. The main results are as follows: 1) The overall scale of the water ecological space in the Dongting Lake study is over 7,300 km2. Water bodies had the largest share, followed by coastal terrestrial areas, while the land-water ecotone was the smallest. There was a small decrease in the water ecological space during the study period. Yueyang had the largest overall scale of water ecological space, while Linli had the smallest. 2) The comprehensive function of water ecological space in the Dongting Lake study was about 0.4000, increasing somewhat during the study period. Among the units, the comprehensive function value was highest in Yuanjiang City, while Jincheng City had the lowest. 3) From the structural elements of water ecological space, scientific planning of functional zoning of water ecological space should be carried out and combined with the delineation of “three zones and three lines.” Key initiatives such as multi-scale and multi-level planning and control, use control and access restrictions, determination of water ecological space ownership, pollution control and accountability, and comprehensive water ecological treatment and restoration should be promoted.

The Rio Muni Basin is a hotspot for deep-water oil exploration in West Africa. The discovery of thirteen oil and gas fields, including Ceiba, Akom 1, and Oveng, proves the basin’s excellent exploration prospects, but only limited research has thus far been carried out there. The recent new drilling indicates that there are organic matter-rich fine-grained sedimentary rocks in the Albian and Cenomanian–Turonian stages of the Cretaceous strata. However, the depositional models of organic-rich, fine-grained sedimentary rocks are not clear. The main objectives of this study are as follows: (1) to identify the lithofacies characteristics of fine-grained sedimentary rocks in the Albian–Turonian stages of the Rio Muni Basin; and (2) to establish a depositional model for organic-rich fine-grained sediments. In this study, the mineralogical characteristics of Albian–Turonian fine-grained were determined by means of X-ray diffraction (XRD) analysis, scanning electron microscopy (SEM), and thin section analysis. In addition, the integration of mineralogical features with the total organic carbon (TOC) content allows for the recognition of three distinct lithofacies: (1) siliceous-clayey rock, (2) terrigenous clastic mixed fine-grained rock, and (3) lime-mixed fine-grained rock. Based on the evolutionary history of the passive continental margin basins in West Africa and the lithofacies characteristics, the deposition mode of organic-rich fine-grained sedimentary rocks in the Albian–Turonian stages was reconstructed by combining geochemical features with the characteristics of framboidal pyrite. The depositional models for the Albian stage are “continental margin–restricted sea–marine algae–source rocks” with the development of organic-rich fine-grained sedimentary rocks. The depositional models for the Cenomanian–Turonian stage are “continental margin–semiopen sea–mixed-source rocks”. The Albian and Cenomanian–Turonian organic-rich fine-grained sedimentary rocks represent two different deposition modes with restricted sea and semiopen sea conditions. The sedimentary characteristics in the study area during the two periods were both inherited and notably different.

Two novel nitrogen-rich heterocyclic energetic compounds, 5-amino-3-azido-4-nitro-1H-pyrazole (3) and 5,5′-diazido-4,4′-dinitro-1H,1′H-2,2′-biimidazole(6), featuring ortho azido/nitro groups were designed and synthesized by reactions of diazonium salts with sodium azide. In addition, treatment of diazonium salts with a mixture of hydrazine monohydrate and sodium nitrite in acetic acid also gave the same products 3 and 6 in high yields. Both structures of the products were characterized by 1H NMR, 13C NMR, IR and elemental analysis, as well as single-crystal X-ray diffraction. Furthermore, their physicochemical and energetic properties were studied.

Klinefelter syndrome (KS, 47XXY) is a disorder characterized by sex chromosomal aneuploidy, which may lead to changes in epigenetic regulations of gene expression. To define epigenetic architectures in 47XXY, we annotated DNA methylation in euploid males (46XY) and females (46XX), and 47XXY individuals using whole genome bisulfite sequencing (WGBS) and integrated chromatin accessbilty, and detected abnormal hypermethylation in 47XXY. Furthermore, we detected altered chromatin accessibility in 47XXY, in particular in chromosome X, using Assay for Transposase-Accessible Chromatin sequencing (ATAC-seq) in cultured amniotic cells. Our results construct the whole genome-wide DNA methylation map in 47XXY, and provide new insights into the early epigenomic dysregulation resulting from an extra chromosome X in 47XXY.

To initiate its development into a plant, a small dark-grown seedling (prior to its emergence from the ground) must penetrate through the growth media. The path that the seedling takes during this journey has yet to be explained. As such, we conducted non-destructive tests using CT scans to observe the growth of dark-grown seedlings in soil over time; we also developed a model to simulate the dynamics of an emerging seedling, and to examine effects of various growth medium conditions, including Lunar soil. It was previously postulated that, with gravitropism in a terrestrial growth medium, a dark-grown seedling would grow directly upright. However, our CT scan results showed that dark-grown soybean seedlings departed from the vertical path in soil, as far as a lateral distance of approximately 10 mm. The phenomenon of the non-straight path was also demonstrated by the model results. Through simulations, we found that an emerging seedling naturally weaves through the particles of growth medium, in search for the path of least resistance. As a result, the seedling ends up travelling a longer distance. Compared with a seedling that was artificially forced to take a straight path in a growth media, the seedling taking the natural path encountered significantly lower resistances (20% lower) from the growth medium, while travelled 12% longer distance during the emergence process. A seedling encountered a much higher impedance in Lunar soil. Our results suggest that taking the path of least resistance, in addition to shaping and orientating itself for mechanical advantage, are strategies evolved by plant species that have contributed to its vast success. An understanding of plant behavior and survival strategies on Earth lay the foundation for future research in agriculture in novel environments, including on celestial bodies.

Urban vitality is an important reflection of a city’s development potential and urban quality. This study used exploratory spatio-temporal big data such as social media check-ins to portray the spatio-temporal evolution of urban vitality at the subdistrict scale in Changsha, a city in central China, from 2013 to 2021, finding that urban vitality in Changsha exhibited central agglomeration and outward circling expansion over time, and then we used Geodetector and spatial regression analyses to explain the interactive effects and spatio-temporal heterogeneity of the spatial elements of subdistrict form, subdistrict function, and subdistrict economy on urban vitality. The results show the following: (1) The subdistrict form and subdistrict function dimensions had a significant effect on urban vitality, and the effect of the economic dimension of the subdistrict was not significant. (2) The interaction effect of the density of entertainment and leisure facilities and the density of business office facilities in subdistrict function was the dominant factor in the change of urban vitality. (3) Under the spatio-temporal effect, land use diversity and park facility density had the strongest positive effect on urban vitality; road density and shopping facility density had the weakest effect. The study aimed to provide a reference for the optimization and allocation of spatial elements of subdistricts in sustainable urban development and urban renewal, in order to achieve the purpose of urban vitality creation and enhancement.

ABSTRACT Salmonella bacteria pose a significant threat to animal husbandry and human health due to their virulence and multidrug resistance. The lasso peptide MccY is a recently discovered antimicrobial peptide that acts against various serotypes of Salmonella. In this study, we further explore the resistance mechanism and activity of MccY. Mutants of Ton system genes, including tonB, exbB, and exbD, in Salmonella enterica subsp. enterica serovar Typhimurium were constructed, and the MICs to MccY exhibited significant increases in these deletion mutants compared to the MIC of the parent strain. Subsequently, MccY resistance was quantitatively analyzed, and these mutants also showed greatly reduced rates of killing, even with a high concentration of MccY. In addition, a minimal medium with low iron environment enhanced the sensitivity of these mutants to MccY. Measurements of a series of physiological indicators, including iron utilization, biofilm formation, and motility, demonstrated that MccY may decrease the virulence of S. Typhimurium. Transcriptomic analysis showed that iron utilization, biofilm formation, flagellar assembly, and virulence-related genes were downregulated to varying degrees when S. Typhimurium was treated with MccY. In conclusion, deletion of Ton system genes resulted in resistance to MccY and the susceptibility of these mutants to MccY was increased and differed under a low-iron condition. This lasso peptide can alter multiple physiological properties of S. Typhimurium. Our study will contribute to improve the knowledge and understanding of the mechanism of MccY resistance in Salmonella strains. IMPORTANCE The resistance of Salmonella to traditional antibiotics remains a serious challenge. Novel anti-Salmonella drugs are urgently needed to address the looming crisis. The newly identified antimicrobial peptide MccY shows broad prospects for development and application because of its obvious antagonistic effect on various serotypes of Salmonella. However, our previous study showed that the peptide could confer resistance to Salmonella by disrupting the receptor gene fhuA. In this study, we further explored the potential resistance mechanism of MccY and demonstrated the importance of the Salmonella Ton complex for MccY transport. Disruption in Ton system genes resulted in S. Typhimurium resistance to this peptide, and MccY could alter multiple bacterial physiological properties. In summary, this study further explored the resistance mechanism and antibacterial effect of MccY in S. Typhimurium and provided a scientific basis for its development and application.

BackgroundEffective multicomponent interventions in the community targeted at preventing frailty in at-risk older adults can promote healthy ageing. However, there is a lack of studies exploring the effectiveness of technology-enabled autonomous multi-domain community-based interventions for frailty. We developed a novel end-to-end System for Assessment and Intervention of Frailty (SAIF) with exercise, nutrition, and polypharmacy components. This pilot study aimed to explore SAIF’s effectiveness in improving frailty status, physical performance and strength, and its usability in pre-frail older adults.Materials and methodsThis is a single arm 8-week pilot study in 20 community-dwelling older adults who were pre-frail, defined using the Clinical Frailty Scale (CFS) as CFS 3 + (CFS 3 and FRAIL positive) or CFS 4. For outcomes, we assessed frailty status using the modified Fried Frailty Phenotype (FFP) and CFS; physical performance using Short Physical Performance Battery (SPPB); and Hand Grip Strength (HGS) at baseline and 8-week. User experience was explored using the System Usability Scale (SUS), interest-enjoyment subscale of the Intrinsic Motivation Inventory and open-ended questions. We analyzed effectiveness using repeated-measures tests on pre-post scores, and usability using a convergent mixed-method approach via thematic analysis of open-ended responses and descriptive statistics of usability/interest-enjoyment scales.ResultsSixteen participants (71.8 ± 5.5 years) completed the 8-week study. There was a significant improvement in FFP score (−0.5, p < 0.05, effect size, r = 0.43), but not CFS (−1.0, p = 0.10, r = 0.29). Five (31.3%) improved in frailty status for both FFP and CFS. SPPB (+1.0, p < 0.05, r = 0.42) and HGS (+3.5, p < 0.05, r = 0.45) showed significant improvements. Three themes were identified: “Difficulty in module navigation” (barriers for SAIF interaction); “User engagement by gamification” (facilitators that encourage participation); and “Perceived benefits to physical health” (subjective improvements in physical well-being), which corroborated with SUS (68/100) and interest-enjoyment (3.9/5.0) scores. Taken together, user experience results cohere with the Senior Technology Acceptance and Adoption Model.ConclusionOur pilot study provides preliminary evidence of the effectiveness of SAIF in improving frailty status, physical performance and strength of pre-frail older adults, and offers user experience insights to plan the follow-up large-scale randomized controlled trial.

Abstract Proper development of the mammalian cerebral cortex relies on precise gene expression regulation, which is controlled by genetic, epigenetic, and epitranscriptomic factors. Here we generate RNA demethylase Fto and methyltransferase Mettl3 cortical-specific conditional knockout mice, and detect severe brain defects caused by Mettl3 deletion but not Fto knockout. Transcriptomic profiles using RNA sequencing indicate that knockout of Mettl3 causes a more dramatic alteration on gene transcription than that of Fto. Interestingly, we conduct ribosome profiling sequencing, and find that knockout of Mettl3 leads to a more severe disruption of translational regulation of mRNAs than deletion of Fto and results in altered translation of crucial genes in cortical radial glial cells and intermediate progenitors. Moreover, Mettl3 deletion causes elevated translation of a significant number of mRNAs, in particular major components in m6A methylation. Our findings indicate distinct functions of Mettl3 and Fto in brain development, and uncover a profound role of Mettl3 in regulating translation of major mRNAs that control proper cortical development.

Urban green space (UGS) is essential for sustainable urbanization and human well-being. The utilization status of UGS is closely related to the provision of ecosystem services for urban residents. Limitations on data availability, however, have led to the absence of a comprehensive approach for evaluating the actual utilization status of UGS at a large scale. Furthermore, differences in actual UGS utilization between intra-urban and peri-urban areas have not received enough attention. This study used big data analysis by combining point of interest (POI) and land use and cover change (LUCC) to quantify the spatial patterns of UGS utilization, and to evaluate the actual utilization status of UGS in 366 cities on the Chinese mainland. We also explored the differences in the actual utilization of UGS in intra-urban and peri-urban areas. The results showed that 94.01% of UGS resources in China had not been utilized. There was a clear pattern of spatial mismatch between the stock and the actual utilization of UGS, especially in the northwestern region indicated by the Hu Huanyong Line. The actual utilization rate of UGS was closely related to the regional development level. There was a certain mismatch between the actual utilization and stock of intraurban green space (IUGS). The hot spots of the actual utilization rate of IUGS were in Yunnan, Guizhou, and Sichuan Provinces in southwestern China. The differences in UGS actual utilization rates between IUGS and peri-urban green space (PUGS) were small in eastern China, but large in southwestern and northwestern China. The actual utilization rate of IUGS in most Chinese cities was significantly larger than that of PUGS, indicating that PUGS were not well utilized. Our results provide scientific support for urban and regional planners in targeting specific areas for UGS design and development, and in optimizing future UGS planning in China.

The study of soil–plant–machine interaction (SPMI) examines the system dynamics at the interface of soil, machine, and plant materials, primarily consisting of soil–machine, soil–plant, and plant–machine interactions. A thorough understanding of the mechanisms and behaviors of SPMI systems is of paramount importance to optimal design and operation of high-performance agricultural machinery. The discrete element method (DEM) is a promising numerical method that can simulate dynamic behaviors of particle systems at micro levels of individual particles and at macro levels of bulk material. This paper presents a comprehensive review of the fundamental studies and applications of DEM in SPMI systems, which is of general interest to machinery systems and computational methods communities. Important concepts of DEM including working principles, calibration methods, and implementation are introduced first to help readers gain a basic understanding of the emerging numerical method. The fundamental aspects of DEM modeling including the study of contact model and model parameters are surveyed. An extensive review of the applications of DEM in tillage, seeding, planting, fertilizing, and harvesting operations is presented. Relevant methodologies used and major findings of the literature review are synthesized to serve as references for similar research. The future scope of coupling DEM with other computational methods and virtual rapid prototyping and their applications in agriculture is narrated. Finally, challenges such as computational efficiency and uncertainty in modeling are highlighted. We conclude that DEM is an effective method for simulating soil and plant dynamics in SPMI systems related to the field of agriculture and food production. However, there are still some aspects that need to be examined in the future.

A cost-effective harvesting method and equipment for small-scale farms is essential to ensure the viability and sustainability of their operations. This study aims to retrofit and test a pull-type combine harvester for effective and efficient operations in small grains. A 1960s-era functional combine harvester was retrofitted with a stripper header rotor in place of the sickle bar cutting system to increase the harvesting capacity. Preliminary field testing found that the original header auger and feeder house could not handle the changed crop composition at an increased capacity and did not properly convey the grain from the auger to the feeder house and onto the threshing system. Therefore, redesign modifications were conducted for the auger and feeder house to help increase the efficiency and capacity required to use the stripper header. Various design concepts were proposed, analyzed, and prototyped in this study. The machine performance of the material-conveying efficiency of the wheat-material-other-than-grain mixture was evaluated at various material throughput rates. The results showed that the auger shim and feeder house paddle redesign increased the efficiency from 80.68% to 98.56%, as compared to the original machine configuration. The cost-effective and high-performance pull-type combine harvester proposed in this study has a high potential in solving the bottleneck problem of local production of small grains by small-scale farming operations.

Abstract Background Soft tissue sarcomas (STS) has a high rate of early metastasis. In this study, we aimed to uncover the potential metastasis mechanisms and related signaling pathways in STS with differentially expressed genes and tumor-infiltrating cells. Methods RNA-sequencing (RNA-seq) of 261 STS samples downloaded from the Cancer Genome Atlas (TCGA) database were used to identify metastasis-related differentially expressed immune genes and transcription factors (TFs), whose relationship was constructed by Pearson correlation analysis. Metastasis-related prediction model was established based on the most significant immune genes. CIBERSORT algorithm was performed to identify significant immune cells co-expressed with key immune genes. The GSVA and GSEA were performed to identify prognosis-related KEGG pathways. Ultimately, we used the Pearson correlation analysis to explore the relationship among immune genes, immune cells, and KEGG pathways. Additionally, key genes and regulatory mechanisms were validated by single-cell RNA sequencing and ChIP sequencing data. Results A total of 204 immune genes and 12 TFs, were identified. The prediction model achieved a satisfactory effectiveness in distant metastasis with the Area Under Curve (AUC) of 0.808. LTB was significantly correlated with PAX5 (P

Abstract High amount of corn (Zea mays L.) residue left in the field interferes with seeding operations, which hinders the viability of conservation agriculture. Vertical tillage is a promising practice in dealing with heavy crop residue, but its effectiveness largely depends on the design and use of tillage machines. In this study, three vertical tillage discs with different shapes, namely notched, plain, and rippled, were tested in a soil bin at two different working depths, shallow (63.5 mm) and deep (127 mm). Corn residues were spread on top of the soil as surface residue. soil cutting forces, soil displacement, and residue mixing with soil, as well as residue cutting were measured. The results showed that the working depth had a stronger effect on the performance of discs as compared to the disc type. No difference in residue cutting was found between the treatments. The deep working depth resulted in 5.1% higher residue mixing, 53.4% greater soil cutting forces, and 34.9% larger soil displacements, as compared to the shallow depth. The rippled disc resulted in the largest soil displacements with the greatest demand in soil cutting forces. Overall, the rippled disc was the most aggressive among the three discs with regard to the performance indicators measured. The results suggested that varying working depth would be an effective approach in changing the soil dynamics and residue cutting performance of the discs for vertical tillage.

The sedimentary facies, architecture, and depositional mechanism of deltaic systems have been one of the global research hotspots in recent decades; however, the detailed distribution, sedimentary evolution, source rock potential, and major control factors of the coal-bearing shallow-water delta are still unclear. A typical shallow-water braided delta with coal-bearing source rocks developed in the Middle–Late Triassic Mungaroo Formation of the North Carnarvon Basin, which can be a good study area for an analysis of coal-bearing source rocks. In this study, the sedimentary facies, distribution and evolution, and coal-bearing source rock features of the Triassic strata were analyzed based on the integrated study of wireline logs, drilled cores, thin sections, seismic facies and attributes, and geochemical data. A range of shallow-water delta sedimentary facies was identified, including the proximal delta plain channel/interdistributary bay, distal delta plain channel/interdistributary bay, and the delta front. The coal-bearing shallow-water delta system of the Middle–Late Triassic Mungaroo Formation was characterized by the largest scale delta system with relatively broad proximal and distal delta plains and relatively narrow delta front subfacies. The scale of the delta system showed a trend of increasing from the Early Triassic Locker Shale to the Middle–Late Triassic Mungaroo Formation and then decreasing to the Late Triassic Brigadier Formation. The distal delta plain subfacies of the Mungaroo Formation should have the highest potential coal-bearing source rock, and the proximal delta plain also can be a favorable target for source rock evaluation. The major control factors of the coal-bearing source rocks of the Mungaroo shallow-water delta mainly included the Triassic megamonsoon climate, the topographic features, eustatic changes, and provenance supply. The proximal and distal delta plains of the shallow-water delta system with thin coal seams, carbonaceous mudstone, and dark mudstone lithologies’ association could be a favorable source rock exploration facies for the next stage of natural gas field exploration.

Trisomy 18, commonly known as Edwards syndrome, is the second most common autosomal trisomy among live born neonates. Multiple tissues including cardiac, abdominal, and nervous systems are affected by an extra chromosome 18. To delineate the complexity of anomalies of trisomy 18, we analyzed cultured amniotic fluid cells from two euploid and three trisomy 18 samples using single-cell transcriptomics. We identified 6 cell groups, which function in development of major tissues such as kidney, vasculature and smooth muscle, and display significant alterations in gene expression as detected by single-cell RNA-sequencing. Moreover, we demonstrated significant gene expression changes in previously proposed trisomy 18 critical regions, and identified three new regions such as 18p11.32, 18q11 and 18q21.32, which are likely associated with trisomy 18 phenotypes. Our results indicate complexity of trisomy 18 at the gene expression level and reveal genetic reasoning of diverse phenotypes in trisomy 18 patients.

Skin cutaneous melanoma (SKCM) is a type of highly invasive cancer originated from melanocytes. It is reported that aberrant alternative splicing (AS) plays an important role in the neoplasia and metastasis of many types of cancer. Therefore, we investigated whether ASEs of pre-RNA have such an influence on the prognosis of SKCM and the related mechanism of ASEs in SKCM. The RNA-seq data and ASEs data for SKCM patients were obtained from the TCGA and TCGASpliceSeq database. The univariate Cox regression revealed 1265 overall survival-related splicing events (OS-SEs). Screened by Lasso regression, 4 OS-SEs were identified and used to construct an effective prediction model (AUC: .904), whose risk score was proved to be an independent prognostic factor. Furthermore, Kruskal–Wallis test and Mann–Whitney–Wilcoxon test showed that an aberrant splicing type of aminoacyl tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2) regulated by CDC-like kinase 1 (CLK1) was associated with the metastasis and stage of SKCM. Besides, the overlapped signal pathway for AIMP2 was galactose metabolism identified by the co-expression analysis. External database validation also confirmed that AIMP2, CLK1, and the galactose metabolism were associated with the metastasis and stage of SKCM patients. ChIP-seq and ATAC-seq methods further confirmed the transcription regulation of CLK1, AIMP2, and other key genes, whose cellular expression was detected by Single Cell Sequencing. In conclusion, we proposed that CLK1-regulated AIMP2-78704-ES might play a critical role in the tumorigenesis and metastasis of SKCM via galactose metabolism. Besides, we established an effective model with MTMR14-63114-ES, URI1-48867-ES, BATF2-16724-AP, and MED22-88025-AP to predict the metastasis and prognosis of SKCM patients.

Abstract Background The prevalence of central obesity is constantly increasing, and visceral fat is associated with increased production of inflammatory factors and metabolic risk factors. Lutein might retard the development of metabolic disease through its antioxidant and anti-inflammatory properties. Furthermore, epidemiological studies have associated higher dietary intake and serum levels of lutein with decreased adiposity. However, few randomised controlled trials have shown the effects of lutein supplementation on inflammatory biomarkers and metabolic risk factors, especially in adults with central obesity. Methods This study will be conducted as a double-blind, parallel placebo-controlled clinical trial in which 120 people who have central obesity, are 18 to 60 years old and are willing to provide informed consent will be randomly assigned to the intervention or placebo group in a 1:1 ratio according to sex, age and waist circumference. The intervention group will receive 10 mg daily lutein supplementation for 12 weeks to explore the effect of lutein supplementation on serum lutein, glycaemic and lipid profiles, inflammatory factors and body composition. Two populations (intention-to-treat population and per-protocol population) will be used in the data analyses. Discussion Our findings from this trial will contribute to the knowledge of the association between lutein supplementation and inflammatory biomarkers and metabolic risk factors in people with central obesity and will offer a possibility for the prevention of inflammatory diseases. Trial registration Chinese Clinical Trial Registry: ChiCTR1800018098. Registered on 30 August 2018.

Abstract In eddy current testing, the law of attenuation of eddy current (EC) is of great concern. In conductive half space under the excitation of uniform magnetic field, the EC density decreases exponentially in the depth direction. However, in conductor with finite thickness tested by coil, the distribution of EC in the depth direction is more complicated. This paper studies the characteristics of EC attenuation in metallic plate of finite thickness. Simulation results show that there is an EC reflection at the bottom of plate, which changes the law of EC attenuation. A new concept, namely the equivalent attenuation coefficient, is proposed to quantify the speed of EC attenuation. The characteristics of EC attenuation are utilized to explain the nonmonotonic relation between coil voltage and plate thickness. Procedure of selecting frequency is discussed. Thereafter, measurement of plate thickness is carried out and accurate result is obtained.

Urban green space (UGS) is essential to the improvement of human well-being and health, and the inequity of UGS supply has received widespread concern. The urban green space availability (UGSA) can effectively evaluate UGS supply. However, the UGSA under different daily transportation patterns has not received enough attention, as well as the potential of UGS that is not available by transportation patterns. Meanwhile, the inequity of UGS supply between cities with different economic development levels at the regional or national scale is still unclear. So, we constructed seven UGS indicators to represent the UGS supply: UGSA considering four kinds of daily transportation patterns (UGSA0.5 km, UGSA2.5 km, UGSA10km, and UGSA30km), the potential of UGS (PUGS), the proportion of PUGS (PPUGS), and stock of UGS indicator (SUGS). The spatial patterns of availability, potential, and stock of UGS in 366 cities on the Chinese mainland in 2015 were captured. Then, the concentration curve and concentration index (CI) were applied to describe the inequity of UGS supply between the cities. Finally, we used correlation analysis, regression analysis, and GeoDetector techniques to explore the driving factors of the spatial pattern of availability and potential of UGS. The results showed that: (1) The SUGS, PUGS, and PPUGS were lower in the southeastern region indicated by the Hu Huanyong Line than that in the northwestern region. Only 44.11% of China's UGS were available through the daily transportation patterns. The spatial patterns of the four UGSA were similar, while the UGSA30km’s hot spots appeared in Southwest China. (2) Less developed cities occupied more SUGS, PUGS, and PPUGS. With the increase of buffer radius, the equity of UGSA among cities was gradually improved, while developed cities always possessed more UGSA. (3) With the increase of buffer radius, the dominant driving factors of UGSA indicators gradually changed from social economy and infrastructure variables to physical geography variables. Our study provides new evidence for a comprehensive understanding of UGSA, and the results of UGS supply and its inequity will contribute to sustainable UGS development in targeting cities or regions in China.

Background: Achieving urban sustainability is the ultimate destination of urban development. City rankings as one of the sustainability assessment tools have received increasing attention from the scientific community. However, few study assesses Chinese cities’ sustainability performance using the big data of existing city rankings. Aim: This study aims to assess Chinese cities’ sustainability performances based on the outcomes of the existing internet big data of city rankings. Methods: The outcomes of city rankings were used as the raw dataset. The “sustainability” of city rankings, city’s appearance frequency, and its ranking place were comprehensively considered during evaluation processes. By considering the above factors, the scores of different cities were calculated in terms of overall sustainability and domain sustainability. Furthermore, the GeoDetector was applied to explore the association between social-economic and overall ranking scores as well as the interrelation among TBL dimensions. Results: Chinese cities’ sustainability performance was extremely uneven in spatial distribution. In terms of overall and domain sustainability, well-performing cities were aggregated in the Beijing-Tianjin-Hebei, the Yangtze River Delta, and the Pearl River Delta metropolitan regions. The top ten sustainable cities were Hangzhou, Beijing, Shenzhen, Guangzhou, Zhuhai, Hong Kong, Tianjin, Suzhou, and Xiamen. Most cities did not reach good coordination among the TBL dimensions, instead of developing well in one or two aspects. The results also revealed that current city rankings eyeing more economic and social development, while considering less environmental dimension. Moreover, TBL dimensions mutually reinforce each other in sustainable city construction. The environmental pillar played a critical role and interacting with other dimensions significantly enhanced urban sustainability. Conclusion: The outcomes of existing city rankings can be used as a new resource to evaluate cities’ sustainability performance. Current city rankings in China are not systematically considered in terms of TBL dimensions. Cities should enhance the coordination among TBL pillars, and increase the attention on environmental dimension. More empirical studies involving big data of city rankings will contribute to a new perspective to promote the practice of sustainable urbanization in China.

BackgroundBreastfeeding is essential for maintaining the health of mothers and babies. Breastfeeding can reduce the infection rate and mortality in newborns, and can reduce the chances of overweight and obesity in children and adolescents. For mothers, a longer duration of breastfeeding can reduce the risk of breast cancer, ovarian cancer, and type 2 diabetes. Although breastfeeding has many benefits, the global breastfeeding rate is low. With the progress of time, the popularity of mobile devices has increased rapidly, and interventions based on mobile health (mHealth) may have the potential to facilitate the improvement of the breastfeeding status. ObjectiveThe main objective of this study was to analyze the existing evidence to determine whether mHealth-based interventions can improve the status of breastfeeding. MethodsWe systematically searched multiple electronic databases (PubMed, Web of Science, The Cochrane Library, Embase, CNKI, WanFang, and Vip ) to identify eligible studies published from 1966 to October 29, 2020. Included studies were randomized controlled trials (RCTs) studying the influence of mHealth on breastfeeding. The Cochrane Collaboration Risk of Bias tool was used to examine the risk of publication bias. RevMan 5.3 was used to analyze the data. ResultsA total of 15 RCTs with a total sample size of 4366 participates met the inclusion criteria. Compared with usual care, interventions based on mHealth significantly increased the postpartum exclusive breastfeeding rate (odds ratio [OR] 3.18, 95% CI 2.20-4.59; P

BackgroundBone is the most common metastatic site of Breast invasive carcinoma (BRCA). In this study, the bone metastasis-specific regulation network of BRCA was constructed based on prognostic stemness-related signatures (PSRSs), their upstream transcription factors (TFs) and downstream pathways.MethodsClinical information and RNA-seq data of 1,080 primary BRCA samples (1,048 samples without bone metastasis and 32 samples with bone metastasis) were downloaded from The Cancer Genome Atlas (TCGA). The edgeR method was performed to identify differential expressed genes (DEGs). Next, mRNA stemness index (mRNAsi) was calculated by one-class logistic regression (OCLR). To analyze DEGs by classification, similar genes were integrated into the same module by weighted gene co-expression network analysis (WGCNA). Then, univariate and multivariate Cox proportional hazard regression were applied to find the PSRSs. Furthermore, PSRSs, 318 TFs obtained from Cistrome database and 50 hallmark pathways quantified by GSVA were integrated into co-expression analysis. Significant co-expression patterns were used to construct the bone metastasis-specific regulation network. Finally, spatial single-cell RNA-seq and chromatin immunoprecipitation sequence (ChIP-seq) data and multi-omics databases were applied to validate the key scientific hypothesis in the regulation network. Additionally, Connectivity Map (CMap) was utilized to select the potential inhibitors of bone metastasis-specific regulation network in BRCA.ResultsBased on edgeR and WGCNA method, 43 PSRSs were identified. In the bone metastasis-specific regulation network, MAF positively regulated CD248 (R = 0.435, P < 0.001), and hallmark apical junction was the potential pathway of CD248 (R = 0.353, P < 0.001). This regulatory pattern was supported by spatial single-cell RNA sequence, ChIP-seq data and multi-omics online databases. Additionally, alexidine was identified as the possible inhibitor for bone metastasis of BRCA by CMap analysis.ConclusionPSRSs played important roles in bone metastasis of BRCA, and the prognostic model based on PSRSs showed good performance. Especially, we proposed that CD248 was the most significant PSRS, which was positively regulated by MAF, influenced bone metastasis via apical junction pathway. And this axis might be inhibited by alexidine, which providing a potential treatment strategy for bone metastasis of BRCA.

Source-to-sink (S2S) systems have represented a major area of research in recent years; however, few modern S2S system analyses have been applied to typical dryland uplifts/mountains. A modern lacustrine sedimentary system is widely developed in the Great Lakes Basin of western Mongolia, and the Jargalant Nuruu in the Mongolian Altai is a suitable natural laboratory for modern dryland S2S system analysis. In this study, the multi-order S2S system of the Jargalant Nuruu was applied based on a digital elevation model (DEM) and Google Earth database analysis. The Jargalant Nuruu system is subdivided into three second-order sub-S2S systems of the eastern, western, and southern parts (S2S-E, S2S-W, and S2S-S, respectively) and 35 third-order sub-S2S systems (E1–E18, W1–W9, and S1–S8) according to the slope gradients, altitude, and hydrographic net of the Jargalant Nuruu recognized by DEM data, integrated with the quantitative recognition of the topographic drainage divide and structural patterns of the uplift margin. The three second-order S2S systems correspond to three various S2S system coupling models. The S2S-E is characterized by a steep slope gradient system (average 15.61°) with small-scale dominantly alluvial fan deposits (average 4.56 km2). S2S-W is represented by a gentle slope gradient system (average 10.24°) with large-scale dominated fan-shaped lobes (average 30.04 km2). S2S-S, in contrast, is a transformation zone system with transitional features between the two former types. Four major potential controlling factors for the difference in sub-S2S systems are summarized here, including tectonic activity, bedrock properties in the source area, morphology from source to sink, and climatic conditions. The landforms, sedimentary characteristics, and their differences in these sub-S2S systems are the result of the comprehensive influence and control of these multiple factors. This case study could serve as a useful reference for characterizing the sedimentary features of a modern or even ancient S2S system in other regions.

Abstract The mammalian central nervous system (CNS) is one of the most complex systems, with thousands of cell types and subtypes with distinct and unique morphology and gene expression profiles. Based on classic histological methods and conventional cellular and molecular approaches, single cell sequencing is becoming a powerful tool to uncover the complexity of the CNS. In this review, we summarize the principle of single cell sequencing and highlight its use for studying the development of neural stem cells, neural progenitors, and distinct neurons. By revealing transcriptomes in each individual cell using single cell sequencing, we are now able to dissect the cellular heterogeneity of a hundred billion cells in the CNS and comprehensively investigate mechanisms of brain development and function at the cellular and molecular levels.

Background: Kidney renal clear cell carcinoma (KIRC) is the malignancy originated from the renal epithelium, with a high rate of distant metastasis. Aberrant alternative splicing (AS) of pre-mRNA are widely reported to be involved in the tumorigenesis and metastasis of multiple cancers. The aim of this study is to explore the mechanism of alternative splicing events (ASEs) underlying tumorigenesis and metastasis of KIRC.Methods: RNA-seq of 537 KIRC samples downloaded from the TCGA database and ASEs data from the TCGASpliceSeq database were used to identify ASEs in patients with KIRC. The univariate and Lasso regression analysis were used to screen the most significant overall survival-related ASEs (OS-SEs). Based on those, the OS-SEs model was proposed. The interaction network of OS-SEs and splicing factors (SFs) with absolute value of correlation coefficient value >0.750 was constructed by Pearson correlation analysis. The OS-SEs significantly related to distant metastasis and clinical stage were identified by non-parametric test, and those were also integrated into co-expression analysis with prognosis-related Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways identified by Gene Set Variation Analysis (GSVA). ASEs with significance were selected for multiple online database validation.Results: A total of prognostic 6,081 overall survival-related ASEs (OS-SEs) were identified by univariate Cox regression analysis and a prediction model was constructed based on 5 OS-SEs screened by Lasso regression with the Area Under Curve of 0.788. Its risk score was also illustrated to be an independent predictor, which the good reliability of the model. Among 390 identified candidate SFs, DExD-Box Helicase 39B (DDX39B) was significantly correlated with OS and metastasis. After external database validation, Retained Intron of Ras Homolog Family Member T2 (RHOT2) and T-Cell Immune Regulator 1 (TCIRG1) were identified. In the co-expression analysis, overlapped co-expression signal pathways for RHOT2 and TCIRG1 were sphingolipid metabolism and N-glycan biosynthesis.Conclusions: Based on the results of comprehensive bioinformatic analysis, we proposed that aberrant DDX39B regulated RHOT2-32938-RI and TCIRG1-17288-RI might be associated with the tumorigenesis, metastasis, and poor prognosis of KIRC via sphingolipid metabolism or N-glycan biosynthesis pathway.

Purpose – Poor medication adherence leads to high hospital admission rate and heavy amount of health-care cost. To cope with this problem, various electronic pillboxes have been proposed to improve the medication adherence rate. However, most of the existing electronic pillboxes use time-based reminders which may often lead to ineffective reminding if the reminders are triggered at inopportune moments, e.g. user is sleeping or eating. Design/methodology/approach – In this paper, the authors propose an AI-empowered context-aware smart pillbox system. The pillbox system collects real-time sensor data from a smart home environment and analyzes the user’s contextual information through a computational abstract argumentation-based activity classifier. Findings – Based on user’s different contextual states, the smart pillbox will generate reminders at appropriate time and on appropriate devices. Originality/value – This paper presents a novel context-aware smart pillbox system that uses argumentation-based activity recognition and reminder generation.

Purpose – This paper aims to adapt and computerize the Trail Making Test (TMT) to support long-term self-assessment of cognitive abilities. Design/methodology/approach – The authors propose a divide-and-combine (DAC) approach for generating different instances of TMT that can be used in repeated assessments with nearly no discernible practice effects. In the DAC approach, partial trails are generated separately in different layers and then combined to form a complete TMT trail. Findings – The proposed approach was implemented in a computerized test application called iTMT. A pilot study was conducted to evaluate iTMT. The results show that the instances of TMT generated by the DAC approach had an adequate level of difficulty. iTMT also achieved a stronger construct validity, higher test–retest reliability and significantly reduced practice effects than existing computerized tests. Originality/value – The preliminary results suggest that iTMT is suitable for long-term monitoring of cognitive abilities. By supporting self-assessment, iTMT also can help to crowdsource the assessment processes, which need to be administered by healthcare professionals conventionally, to the patients themselves.

Background/Aims: As a malignant and melanocytic tumor, cutaneous melanoma is the devastating skin tumor with high rates of recurrence and metastasis. Bone is the common metastatic location, and bone metastasis may result in pathologic fracture, neurologic damage, and severe bone pain. Although metastatic melanoma was reported to get benefits from immunotherapy, molecular mechanisms and immune microenviroment underlying the melanoma bone metastasis and prognostic factors are still unknown.Methods: Gene expression profiling of 112 samples, including 104 primary melanomas and 8 bone metastatic melanomas from The Cancer Genome Atlas database, was assayed to construct a ceRNA network associated with bone metastases. Besides, we detected the fraction of 22 immune cell types in melanoma via the algorithm of “cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT).” Based on the significant ceRNAs or immune cells, we constructed nomograms to predict the prognosis of patients with melanoma. Ultimately, correlation analysis was implemented to discover the relationship between the significant ceRNA and immune cells to reveal the potential signaling pathways.Results: We constructed a ceRNA network based on the interaction among 8 pairs of long noncoding RNA–microRNA and 15 pairs of microRNA–mRNA. CIBERSORT and ceRNA integration analysis discovered that AL118506.1 has both significant prognostic value (P = 0.002) and high correlation with T follicular helper cells (P = 0.033). Meanwhile, T cells CD8 and macrophages M2 were negatively correlated (P < 0.001). Moreover, we constructed two satisfactory nomograms (area under curve of 3-year survival: 0.899; 5-year survival: 0.885; and concordance index: 0.780) with significant ceRNAs or immune cells, to predict the prognosis of patients.Conclusions: In this study, we suggest that bone metastasis in melanoma might be related to AL118506.1 and its role in regulating thrombospondin 2 and T follicular helper cells. Two nomograms were constructed to predict the prognosis of patients with melanoma and demonstrated their value in improving the personalized management.