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Eddy current sensors have been widely used in the field of micro- and nano-measurements. The detection circuit is a key part of eddy current sensors. In particular, the electrical parameters in the signal conversion circuit have an important effect on the measurement performance. It is necessary to study the effect of the electrical parameters on the measurement performance and propose an optimization method. In this study, a simulation model of the eddy current sensor is established by coupling a magnetic field and a circuit field. The circuits include the LC parallel resonance, the AC bridge, and three combination circuits of the LC resonant and AC bridge. The output voltage variation with the thickness of copper film is calculated, and the effect of the electrical parameters on sensitivity Ki is obtained. In the LC parallel resonant circuit, it' is revealed that K1 is maximum when the parallel capacitance CP is equal to the resonant capacitance C0. An optimization method of adjusting resistance RS in different thickness intervals is proposed. In the AC bridge circuit, it' is revealed that there exists an optimal RS, which makes K2 maximum. In three combination circuits, K3, K4, and K5 are the maximum when the capacitances (C1, C2, and C3) reach the resonant capacitance C0. In addition, the sensitivity of each combination circuit is improved compared with that of the AC bridge. The relevant analysis results are further verified by a series of experiments. According to the calculation results and the experimental analysis, the optimization method for electrical parameters is further proposed. [ABSTRACT FROM AUTHOR]

Peatlands are some of the largest carbon reservoirs in terrestrial ecosystems and play a key role in the global carbon cycle. Understanding peatland development, carbon accumulation processes, and the peatland response to varying forcing factors over different temporal and spatial scales helps reveal the underlying processes and general patterns of these ecosystems. To assess the role of climate and local conditions in peatland development, the basal samples from 23 peat cores and three well dated long peat cores were used to explore peatland initiation, lateral expansion, and carbon accumulation rate in the Baijianghe peatland located in the Changbai Mountains, Northeast China. Our results reveal that the Baijianghe peatland was initiated from forest conditions at 7.9 cal. kyr BP and then expanded laterally by paludification. The rapid expansion between 5 and 4 cal. kyr BP likely resulted from high precipitation and gentle topography. The mean carbon accumulation rates of the three long peat cores were 36.3, 39.1 and 48.4 g C m−2 yr−1, respectively, which are higher than rates from the northern peatlands. Both climate and local conditions have exerted an important influence on carbon accumulation rates in the Baijianghe peatland since the middle Holocene. The carbon accumulation patterns between 5 and 1.5 cal. kyr BP were probably linked to local conditions rather than climatic settings, including topography, hydrological conditions, and plant composition. The consistently decreasing carbon accumulation rate values at all locations within the BJH peatland over the last 1.5 cal. kyr BP suggests that climate is the primary control. This study highlights the varying primary controls on the process of peatland development and reveals the important role of local conditions in carbon accumulation. [ABSTRACT FROM AUTHOR]

• The Dongfanghong peatland originated in 1011 cal. CE post Millennium Eruption, expanding laterally through paludification. • The carbon accumulation averaged 118 g C/m2/yr, ranging from 38 to 374 g C/m2/yr. • Climate mainly governed multi-centennial carbon accumulation rates. • Hydrological conditions regulated both lateral expansion and carbon accumulation. Peatlands are terrestrial ecosystems with high carbon sequestration efficiency, providing critical feedback on climate change. It is crucial to understand how peatland development and carbon accumulation respond to various factors to reveal the future direction of carbon reservoirs under changing climatic conditions. To assess the impact of climate and hydrological conditions on the development and carbon accumulation of peatlands, 15 peat core samples were analyzed to examine the processes of lateral expansion in the Dongfanghong (DFH) peatland, a minerotrophic fen located in the Changbai Mountains of northeast China. Accelerator Mass Spectrometry 14C, total organic carbon, dry bulk density, testate amoebae, δ13C of α-cellulose in Carex spp. and plant macrofossil analyses were conducted on a high-resolution peat core. The proxies were used to calculate carbon accumulation rate (CAR) and reconstruct water table depth as well as surface moisture and vegetation development of the DFH peatland. Our findings indicated that the DFH peatland was initiated at 1011 cal. CE and experienced paludification during the last millennium. The expansion of the DFH peatland was primarily determined by hydrological conditions rather than climatic factors such as total solar irradiance and regional temperature. The rapid expansion between 1500 and 1700 cal. CE was likely resulted from relatively low precipitation and a decrease in water table/surface moisture. CAR generally correlated with total solar irradiance, regional temperature, and precipitation, suggesting that climate may be crucial for CAR in DFH peatlands over multi-centennial timescales. However, the increased CAR under relatively dry conditions suggested that the CAR were regulated by hydrological conditions over a centennial timescale. This study highlighted the important roles of climate and hydrological conditions in the lateral expansion and CAR of the peatland in minerotrophic fen and that there may be a threshold for hydrology during the process of peatland development and carbon accumulation. [ABSTRACT FROM AUTHOR]

Northwest China (NW China) falls within Arid Central Asia (ACA) and has a climate dominated by westerly winds, a fragile ecosystem, and a high sensitivity to climate change. Paleoenvironmental reconstructions of this region can assist in understanding the general processes contributing to environmental variation in such arid areas. This study examined a dated sedimentary core containing both peat and lacustrine deposits obtained from the shore of the Bosten Lake, NW China. The study aimed to reconstruct paleoenvironmental variations over the last 3,000 years and to explore the possible drivers of peatland development over the last millennium. An examination of grain size and δ13C was conducted to investigate lake level variation. The results showed that the lake level of the Bosten Lake declined gradually between 2,905 and 480 cal yr BP and increased thereafter, consistent with other records of the Bosten Lake. At a centennial timescale, the lake level was high under a wet climate during the Dark Age Cold Period (DACP), whereas it decreased significantly during the Medieval Warm Period (MWP). The inferred "cold and wet" and "warm and dry" patterns indicated climatic characteristics of a "westerlies-dominated climatic regime". In addition, the persistent decreasing lake level during the MWP resulted in Phragmites peatland initiation and development along the shores of the Bosten Lake. [ABSTRACT FROM AUTHOR]

Inspired by gecko's adhesive feet, a wheeled wall climbing robot is designed in this paper with the synchronized gears and belt system acting as the wheels by considering both motion efficiency and adhesive capability. Adhesion of wheels is obtained by the bio-inspired adhesive material wrapping on the outer surface of wheels. A ducted fan mounted on the back of the robot supplies thrust force for the adhesive material to generate normal and shear adhesion force whilemoving on vertical surfaces. Experimental verification of robot climbing on vertical flat surface was carried out. The stability and the effect of structure design parameters were analyzed. [ABSTRACT FROM AUTHOR]

With the advent of the big data era, the need to combine multiple individual data sets to draw causal effects arises naturally in many medical and biological applications. Especially each data set cannot measure enough confounders to infer the causal effect of an exposure on an outcome. In this article, we extend the method proposed by a previous study to causal data fusion of more than two data sets without external validation and to a more general (continuous or discrete) exposure and outcome. Theoretically, we obtain the condition for identifiability of exposure effects using multiple individual data sources for the continuous or discrete exposure and outcome. The simulation results show that our proposed causal data fusion method has unbiased causal effect estimate and higher precision than traditional regression, meta‐analysis and statistical matching methods. We further apply our method to study the causal effect of BMI on glucose level in individuals with diabetes by combining two data sets. Our method is essential for causal data fusion and provides important insights into the ongoing discourse on the empirical analysis of merging multiple individual data sources. [ABSTRACT FROM AUTHOR]

[Display omitted] • Depth to water table (DWT) predominantly determined mire plant assemblages. • The mire plant assemblages - based transfer function was developed. • The MAT model has a strong predictive power. • Reconstructed DWT s were comparable to those from testate amoebae. Quantitative relationships between mire plant assemblages and environmental variables have been investigated widely in Europe and North America, but hitherto insufficiently addressed in the East Asian monsoon region. In this study, the plant assemblages of 274 plots along hydrological gradients in five peatlands from the Changbai Mountains region, Northeast China were investigated during the growing seasons (from May to October) from 2014 to 2016. Seven environmental variables of surface water including depth to water table (DWT), pH, electrical conductivity (EC), total nitrogen (TN), total phosphorus (TP), calcium (Ca) and magnesium (Mg) were measured. Canonical correspondence analysis (CCA) indicated that DWT was the principal environmental variable determining the plant assemblages. A transfer function for inferring DWT based on plant assemblages was developed and refined using four models. The transfer function was shown to have strong predictive power following thorough statistical and ecological tests. When the plant assemblages-based transfer function was applied to a 41 cm peat sequence from Laobaishan bog in the Changbai Mountains region, the reconstructed DWTs were essentially consistent, in the trend and vital details of mire surface wetness, with those inferred from a testate amoebae-transfer function, which has been verified to be robust for reconstructing water table in peatlands in the same region. This study suggests that the mire plant assemblages-based transfer function has great potential for quantitative reconstruction of past mire surface wetness, and allows for further research into palaeoclimatology, palaeohydrology and palaeoecology in the East Asian monsoon region using multi-proxy methods. [ABSTRACT FROM AUTHOR]

Deep marine carbonate paleokarst reservoirs have large hydrocarbon reserves in Tarim Basin, NW China. Geological modeling and characterization are critical to the development of such reservoirs. However, reliable 3D modeling of paleokarst is a challenging task due to their multi-scale, multi-type, highly discrete, and complex spatial distribution characteristics. Here we show the detailed workflow of paleokarst classification, modeling, and characterization methods according to multi-disciplinary data and karst genesis. First, the paleokarst is classified into large-scale karst caves, small-scale dissolved pores, and multi-scale fractures, and the large-scale caves are divided into weathered crust caves, subsurface river system, and fault-controlled caves according to their genesis. Then, in order to obtain an accurate representation of the 3D external shape and internal architecture of such reservoirs, a classified modeling approach for converting seismic attributes to geological objects based on geostatistics and karst theory is proposed. Combined seismic wave impedance inversion with frequency-divided attribute can quantitatively characterize large-scale caves. Collaborative sequential simulation method is used for small-scale dissolved pores simulation. Multi-scale discrete fracture networks are characterized by several methods, including manual interpretation, ant tracing, and stochastic simulation. Finally, a fusion principle and technique for different type of caves, pores, and fractures based on the karst genesis is developed. The proposed technology has been applied to the 3D geological modeling and quantitative characterization of TH80 Block in Tahe Oilfield, and the reliability of model is verified by 3 new drilling wells. The results show that the strong heterogeneity of study area is characterized effectively, and the 3D model finely describes the spatial distribution and petro-physical properties of different reservoir groups. The reserve size and composition are calculated and refined based on the model. The remaining oil distribution is clarified after model applies to reservoir numerical simulation, which lays reliable geological foundation for further adjustment of development plan. [ABSTRACT FROM AUTHOR]

Background: The relative contributions of genetic and environmental factors versus unavoidable stochastic risk factors to the variation in cancer risk among tissues have become a widely-discussed topic. Some claim that the stochastic effects of DNA replication are mainly responsible, others believe that cancer risk is heavily affected by environmental and hereditary factors. Some of these studies made evidence from the correlation analysis between the lifetime number of stem cell divisions within each tissue and tissue-specific lifetime cancer risk. However, they did not consider the measurement error in the estimated number of stem cell divisions, which is caused by the exposure to different levels of genetic and environmental factors. This will obscure the authentic contribution of environmental or inherited factors.Methods: In this study, we proposed two distinct modeling strategies, which integrate the measurement error model with the prevailing model of carcinogenesis to quantitatively evaluate the contribution of hereditary and environmental factors to cancer development. Then, we applied the proposed strategies to cancer data from 423 registries in 68 different countries (global-wide), 125 registries across China (national-wide of China), and 139 counties in Shandong province (Shandong provincial, China), respectively.Results: The results suggest that the contribution of genetic and environmental factors is at least 92% to the variation in cancer risk among 17 tissues. Moreover, mutations occurring in progenitor cells and differentiated cells are less likely to be accumulated enough for cancer to occur, and the carcinogenesis is more likely to originate from stem cells. Except for medulloblastoma, the contribution of genetic and environmental factors to the risk of other 16 organ-specific cancers are all more than 60%.Conclusions: This work provides additional evidence that genetic and environmental factors play leading roles in cancer development. Therefore, the identification of modifiable environmental and hereditary risk factors for each cancer is highly recommended, and primary prevention in early life-course should be the major focus of cancer prevention. [ABSTRACT FROM AUTHOR]

Peatlands are one of the most significant carbon reservoirs in the terrestrial ecosystem. Understanding past peatland carbon accumulation processes and their responses to varying external and internal forcing factors would help reveal the general development patterns of peatland ecosystems and provide useful insights into projecting the fate of carbon reservoirs into the future. In this paper, the basal ages of 17 peat cores were used to explore the lateral expansion processes of the Laolike peatland, northeast China. Two cores were selected to calculate carbon accumulation rates (CAR) and reconstruct moisture/precipitation records based on δ13C and grain size analyses. The basal ages show that the peatland was initiated at 12.1 cal kyr BP, then laterally expanded with its fastest rate occurring during the early Holocene, and reached its largest area around 6 cal kyr BP. The time-weighted mean CAR in the Laolike peatland ranged from 31.1 to 52.9 g C/m2/yr (with an average of 42 g C/m2/yr) during the Holocene. The peatland experienced a high CAR of 52.5 g C/m2/yr from 11.7 to 5 cal kyr BP, followed by a low CAR of 35.1 g C/m2/yr after 5 cal kyr BP. Both lateral expansion and vertical accretion are consistent with the summer insolation, climate seasonality, and the strength of the East Asia summer monsoon (EASM) over multi-millennium timescales, where the CAR correlated well with δ13C and grain size, implying moisture/precipitation might be the primary factors controlling carbon accumulation over millennium timescales. Local conditions, such as topography and hydrology, also played an important role in the process of peatland initiation and lateral expansion, as well as the discrepant CAR within the peatland. This study reveals the roles of climate and local conditions in peatland initiation, expansion, and CAR during the Holocene. In addition, we provide a window for a better understanding of the driving factors of peatland development in the temperate zones of the Northern Hemisphere. • Climate conditions are the primary control on the lateral expansion and vertical accretion of Laolike peatland over multi-millennium timescales. • Moisture/precipitation affects carbon accumulation of Laolike peatland over millennium timescales. • Local conditions play an important role in the lateral expansion and the internal differences of carbon accumulation rate. [ABSTRACT FROM AUTHOR]

Causal discovery is a powerful tool to disclose underlying structures by analyzing purely observational data. Genetic variants can provide useful complementary information for structure learning. Recently, Mendelian randomization (MR) studies have provided abundant marginal causal relationships of traits. Here, we propose a causal network pruning algorithm MRSL (MR-based structure learning algorithm) based on these marginal causal relationships. MRSL combines the graph theory with multivariable MR to learn the conditional causal structure using only genome-wide association analyses (GWAS) summary statistics. Specifically, MRSL utilizes topological sorting to improve the precision of structure learning. It proposes MR-separation instead of d-separation and three candidates of sufficient separating set for MR-separation. The results of simulations revealed that MRSL had up to 2-fold higher F1 score and 100 times faster computing time than other eight competitive methods. Furthermore, we applied MRSL to 26 biomarkers and 44 International Classification of Diseases 10 (ICD10)-defined diseases using GWAS summary data from UK Biobank. The results cover most of the expected causal links that have biological interpretations and several new links supported by clinical case reports or previous observational literatures. [ABSTRACT FROM AUTHOR]

[Display omitted] • Soil bacterial richness and communities differed with altitude and vegetation type. • Soil bacterial richness was mainly controlled by MAAT and MAP. • Soil C/P and MAP were the most important regulators of soil bacterial community. • Soil pH significantly affected bacterial diversity and community but to a less extent. • Soil SMC and C-limitation of microbial metabolism are important regulators of soil SOC. Peatlands are crucial carbon (C) sinks, and the combined activities of soil bacteria and soil abiotic properties play an essential role in regulating the C cycle. However, mountain peatlands are particularly vulnerable to global change, which could lead to a change from C sink to source. Understanding how variations in soil bacterial communities and diversity along an altitude gradient affect C storage through changes in enzyme stoichiometry ratios is essential. To address this issue, this study collected soil samples from six peatlands at different altitudes in the Changbai Mountains, China, which were dominated by either sedge or shrub/ Sphagnum species. The study examined a range of soil physical and chemical properties, quantified bacterial community diversity and structure, and assessed enzyme stoichiometry. The results indicated that bacterial communities varied with altitude and vegetation, with bacterial α-diversity (richness) being higher at lower altitudes and in sedge-dominated peatlands. Mean annual air temperature (MAAT) and mean annual precipitation (MAP) were the primary drivers of bacterial diversity, and soil bacterial community composition was significantly influenced by soil carbon/phosphorus (C/P) ratio and MAP. On the other hand, soil pH had only minor effected in mountain peatlands. Path analysis emphasized the greater importance of soil moisture and microbial C limitations than bacterial richness and community on soil organic carbon (SOC) in mountain peatlands. The study also suggested that increasing bacterial richness and relative abundances of rare phyla could increase soil C concentration in peatlands. Overall, this study provided valuable insights into the regulation of C cycling in mountain peatlands and could help mitigate global climate change. [ABSTRACT FROM AUTHOR]

Background: The timings of reproductive life events have been examined to be associated with various psychiatric disorders. However, studies have not considered the causal pathways from reproductive behaviors to different psychiatric disorders. This study aimed to investigate the nature of the relationships between five reproductive behaviors and twelve psychiatric disorders. Methods: Firstly, we calculated genetic correlations between reproductive factors and psychiatric disorders. Then two-sample Mendelian randomization (MR) was conducted to estimate the causal associations among five reproductive behaviors, and these reproductive behaviors on twelve psychiatric disorders, using genome-wide association study (GWAS) summary data from genetic consortia. Multivariable MR was then applied to evaluate the direct effect of reproductive behaviors on these psychiatric disorders whilst accounting for other reproductive factors at different life periods. Results: Univariable MR analyses provide evidence that age at menarche, age at first sexual intercourse and age at first birth have effects on one (depression), seven (anxiety disorder, ADHD, bipolar disorder, bipolar disorder II, depression, PTSD and schizophrenia) and three psychiatric disorders (ADHD, depression and PTSD) (based on p<7.14×10-4), respectively. However, after performing multivariable MR, only age at first sexual intercourse has direct effects on five psychiatric disorders (Depression, Attention deficit or hyperactivity disorder, Bipolar disorder, Posttraumatic stress disorder and schizophrenia) when accounting for other reproductive behaviors with significant effects in univariable analyses. Conclusion: Our findings suggest that reproductive behaviors predominantly exert their detrimental effects on psychiatric disorders and age at first sexual intercourse has direct effects on psychiatric disorders. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) have changed the treatment pattern of advanced and metastatic NSCLC. A series of ICI based therapies have emerged in the first-line treatment field, but the comparative efficacy was unclear. Method: We searched multiple databases and abstracts of major conference proceedings up to Apri1, 2022 for phase III randomised trials of advanced driver-gene wild type NSCLC patients receiving first-line therapy. Outcomes analyzed included progression free survival (PFS), overall survival (OS), and et al. Results: Thirty-two double-blind RCTs were included, involving 18,656 patients assigned to 22 ICI-based first-line regimens. A series of ICI regiments (including ICI plus chemotherapy), ICI monotherapy, doublet ICIs, doublet ICIs plus chemotherapy) emerged, and showed significant PFS and OS benefit than chemotherapy and chemotherapy + bevacizumab (BEV) for advanced wild-type NSCLC. In comprehensive terms of PFS, chemoimmunotherapy (CIT) were significantly more effective than ICI monotherapy and doublet ICIs. In terms of OS for patients with non-squamous NSCLC, pembrolizumab containing CIT was associated with a median rank of the best regimens, and followed by Atezolizumab+BEV based CIT; while for OS in patients with squamous NSCLC, Cemiplimab and sintilimab based CIT were the most effective regimens. For more than 2 years follow-up, the atezolizumab, pembrolizumab, nivolumab and durvalumab containing ICI therapy all provide a durable long-term OS benefit over chemotherapy and BEV + chemotherapy. Conclusions: The findings of the present NMA represent the most comprehensive evidence, which might suggest or provide basis for first-line ICI therapy decision for advanced NSCLC patients without oncogenic driver mutations. [ABSTRACT FROM AUTHOR]

Whether nitrogen (N) availability will limit plant growth and removal of atmospheric CO2 by the terrestrial biosphere this century is controversial. Studies have suggested that N could progressively limit plant growth, as trees and soils accumulate N in slowly cycling biomass pools in response to increases in carbon sequestration. However, a question remains over whether longer‐term (decadal to century) feedbacks between climate, CO2 and plant N uptake could emerge to reduce ecosystem‐level N limitations. The symbioses between plants and microbes can help plants to acquire N from the soil or from the atmosphere via biological N2 fixation—the pathway through which N can be rapidly brought into ecosystems and thereby partially or completely alleviate N limitation on plant productivity. Here we present measurements of plant N isotope composition (δ15N) in a peat core that dates to 15,000 cal. year BP to ascertain ecosystem‐level N cycling responses to rising atmospheric CO2 concentrations. We find that pre‐industrial increases in global atmospheric CO2 concentrations corresponded with a decrease in the δ15N of both Sphagnum moss and Ericaceae when constrained for climatic factors. A modern experiment demonstrates that the δ15N of Sphagnum decreases with increasing N2‐fixation rates. These findings suggest that plant‐microbe symbioses that facilitate N acquisition are, over the long term, enhanced under rising atmospheric CO2 concentrations, highlighting an ecosystem‐level feedback mechanism whereby N constraints on terrestrial carbon storage can be overcome. [ABSTRACT FROM AUTHOR]

• Warmer water injection, oscillating tides, and MAR operations collectively affect the efficiency and sustainability of MAR. • Warmer water injection reduces freshwater storage and recovery, as well as extracted water quality. • Starting extraction with a receding tide could extend the duration of extracting water with lower saline concentration. • Intermittent injection-extraction operation could mitigate the efficiency decrease caused by the warmer water injection. • This study provides insights into water management in artificial island with extensive industrial activities. Storing and utilizing freshwater in coastal aquifers with managed aquifer recharge (MAR) presents significant challenges, particularly in small island settings where seawater intrusion is a major source of groundwater salinization. Existing studies usually evaluate density-dependent flow under isothermal condition, which neglects the potential impact of temperature on fluid density. To fill the knowledge gap, we performed both laboratory experiments and numerical modeling to investigate the impact of warmer water injection on freshwater storage and extracted water quality for island aquifer. It is found that warmer water (70 °C) injection compromise the "barrier effect" achieved by normal water injection, resulting in a reduced ability to prevent coastal seawater intrusion by, creating an upward hydraulic gradient beneath the injection well. In addition, warm water injection result in a 5 % decrease in freshwater storage capacity for island aquifer. However, by employing a combination of receding tide cycles and intermittent injection-extraction operations, the duration of lowered saline concentration within the extracted water can be extended by approximately 10 % with an 11 % reduction in the overall extracted saline concentration. This study provides valuable insights into the influence of warmer water injection on coastal aquifer quality. The findings from both the laboratory experiments and numerical simulations enhance the understanding of thermal density-dependent dynamics of coastal aquifers, offering valuable guidance for effective freshwater storage and usage in island settings. [ABSTRACT FROM AUTHOR]

Causal mediation analysis investigates the mechanism linking exposure and outcome. Dealing with the impact of unobserved confounders among exposure, mediator and outcome is an issue of great concern. Moreover, when multiple mediators exist, this causal pathway intertwines with other causal pathways, rendering it difficult to estimate the path-specific effects. In this study, we propose a method (PSE-MR) to identify and estimate path-specific effects of an exposure (e.g. education) on an outcome (e.g. osteoarthritis risk) through multiple causally ordered and non-ordered mediators (e.g. body mass index and pack-years of smoking) using summarized genetic data, when the sequential ignorability assumption is violated. Specifically, PSE-MR requires a specific rank condition in which the number of instrumental variables is larger than the number of mediators. Furthermore, we illustrate the utility of PSE-MR by providing guidance for practitioners and exploring the mediation effects of body mass index and pack-years of smoking in the causal pathways from education to osteoarthritis risk. Additionally, the results of simulation reveal that the causal estimates of path-specific effects are almost unbiased with good coverage and Type I error properties. Also, we summarize the least number of instrumental variables for the specific number of mediators to achieve 80% power. [ABSTRACT FROM AUTHOR]

Nonrandom selection in one-sample Mendelian Randomization (MR) results in biased estimates and inflated type I error rates only when the selection effects are sufficiently large. In two-sample MR, the different selection mechanisms in two samples may more seriously affect the causal effect estimation. Firstly, we propose sufficient conditions for causal effect invariance under different selection mechanisms using two-sample MR methods. In the simulation study, we consider 49 possible selection mechanisms in two-sample MR, which depend on genetic variants (G), exposures (X), outcomes (Y) and their combination. We further compare eight pleiotropy-robust methods under different selection mechanisms. Results of simulation reveal that nonrandom selection in sample II has a larger influence on biases and type I error rates than those in sample I. Furthermore, selections depending on X+Y, G+Y, or G+X+Y in sample II lead to larger biases than other selection mechanisms. Notably, when selection depends on Y, bias of causal estimation for non-zero causal effect is larger than that for null causal effect. Especially, the mode based estimate has the largest standard errors among the eight methods. In the absence of pleiotropy, selections depending on Y or G in sample II show nearly unbiased causal effect estimations when the casual effect is null. In the scenarios of balanced pleiotropy, all eight MR methods, especially MR-Egger, demonstrate large biases because the nonrandom selections result in the violation of the Instrument Strength Independent of Direct Effect (InSIDE) assumption. When directional pleiotropy exists, nonrandom selections have a severe impact on the eight MR methods. Application demonstrates that the nonrandom selection in sample II (coronary heart disease patients) can magnify the causal effect estimation of obesity on HbA1c levels. In conclusion, nonrandom selection in two-sample MR exacerbates the bias of causal effect estimation for pleiotropy-robust MR methods. Author summary: It is well known that nonrandom selection in one-sample Mendelian Randomization (MR) can result in biased estimates and inflated type I error rates. Actually, two-sample MR analyses are more prone to be affected by nonrandom selection than one-sample MR analyses, because two samples for genome-wide association studies (GWAS) may be selected each under different mechanisms from the source population. Summary-level genetic association statistics in two-sample MR may be derived from different study designs such as case-control, case-only and cohort studies, which further inevitably affect the causal effect estimation of exposure on outcome. In this study, we firstly propose a theorem for causal effect invariance under different selection mechanisms. In the simulation, we design 49 combinations of nonrandom selection mechanisms in sample I and sample II, which are widespread in practical applications. The simulation results reveal that the selection mechanisms in sample II have a larger influence on biases and type I error rates than those in sample I. As an illustrative example, we find the nonrandom selection in sample II (coronary heart disease patients) can magnify the causal effect estimation of obesity on the HbA1c levels. [ABSTRACT FROM AUTHOR]

Aims: Morinda officinalis oligosaccharides (MOOs), a traditional Chinese medicine, have been used to treat mild and moderate depressive episodes. In this study, we investigated whether MOOs can ameliorate depressive‐like behaviors in post‐stroke depression (PSD) rats and further explored its mechanism by suppressing microglial NLRP3 inflammasome activation to inhibit hippocampal inflammation. Methods: Behavioral tests were performed to evaluate the effect of MOOs on depressive‐like behaviors in PSD rats. The effects of MOOs on the expression of IL‐18, IL‐1β, and nucleotide‐binding domain leucine‐rich repeat (NLR) family pyrin domain containing 3 (NLRP3) inflammasome were measured in both PSD rats and lipopolysaccharide (LPS) and adenosine triphosphate (ATP) stimulated primary rat microglia by reverse transcription polymerase chain reaction (RT‐PCR), immunofluorescence and Western blot analysis. Adeno‐associated virus (AAV) was injected into the hippocampus to regulate NLRP3 inflammasome expression. The detailed molecular mechanism underlying the effects of MOOs was analyzed by Western blot and immunofluorescence. Results: MOOs can alleviate depressive‐like behaviors in PSD rats. PSD rats showed increased expression of IL‐18, IL‐1β, and NLRP3 inflammasome in the ischemic hippocampus, while MOOs reversed the elevation. NLRP3 downregulation ameliorated depressive‐like behaviors and hippocampal inflammation response in PSD rats, while NLRP3 upregulation inhibited the effect of MOOs on depressive‐like behaviors and hippocampal inflammation response in PSD rats. Moreover, we found that NLRP3 was mainly expressed on microglia. In vitro, MOOs effectively inhibited the expression of IL‐18, IL‐1β, and NLRP3 inflammasome in LPS + ATP treated primary rat microglia. We also showed that modulation of NLRP3 inflammasome by MOOs was associated with the IκB/NF‐κB p65 signaling pathway. Conclusion: Overall, our study reveals the antidepressive effect of MOOs on PSD rats through modulation of microglial NLRP3 inflammasome. We also provide a novel insight into hippocampal inflammation response in PSD pathology and put forward NLRP3 inflammasome as a potential therapeutic target for PSD. [ABSTRACT FROM AUTHOR]

Background: Genetic correlations, causalities and pathways between large-scale complex exposures and ovarian and breast cancers need systematic exploration. Methods: Mendelian randomisation (MR) and genetic correlation (GC) were used to identify causal biomarkers from 95 cancer-related exposures for risk of breast cancer [BC: oestrogen receptor-positive (ER + BC) and oestrogen receptor-negative (ER − BC) subtypes] and ovarian cancer [OC: high-grade serous (HGSOC), low-grade serous, invasive mucinous (IMOC), endometrioid (EOC) and clear cell (CCOC) subtypes]. Results: Of 31 identified robust risk factors, 16 were new causal biomarkers for BC and OC. Body mass index (BMI), body fat mass (BFM), comparative body size at age 10 (CBS-10), waist circumference (WC) and education attainment were shared risk factors for overall BC and OC. Childhood obesity, BMI, CBS-10, WC, schizophrenia and age at menopause were significantly associated with ER + BC and ER − BC. Omega-6:omega-3 fatty acids, body fat-free mass and basal metabolic rate were positively associated with CCOC and EOC; BFM, linoleic acid, omega-6 fatty acids, CBS-10 and birth weight were significantly associated with IMOC; and body fat percentage, BFM and adiponectin were significantly associated with HGSOC. Both GC and MR identified 13 shared factors. Factors were stratified into five priority levels, and visual causal networks were constructed for future interventions. Conclusions: With analysis of large-scale exposures for breast and ovarian cancers, causalities, genetic correlations, shared or specific factors, risk factor priority and causal pathways and networks were identified. [ABSTRACT FROM AUTHOR]

Background: Genetic correlations, causalities and pathways between large-scale complex exposures and ovarian and breast cancers need systematic exploration.Methods: Mendelian randomisation (MR) and genetic correlation (GC) were used to identify causal biomarkers from 95 cancer-related exposures for risk of breast cancer [BC: oestrogen receptor-positive (ER + BC) and oestrogen receptor-negative (ER - BC) subtypes] and ovarian cancer [OC: high-grade serous (HGSOC), low-grade serous, invasive mucinous (IMOC), endometrioid (EOC) and clear cell (CCOC) subtypes].Results: Of 31 identified robust risk factors, 16 were new causal biomarkers for BC and OC. Body mass index (BMI), body fat mass (BFM), comparative body size at age 10 (CBS-10), waist circumference (WC) and education attainment were shared risk factors for overall BC and OC. Childhood obesity, BMI, CBS-10, WC, schizophrenia and age at menopause were significantly associated with ER + BC and ER - BC. Omega-6:omega-3 fatty acids, body fat-free mass and basal metabolic rate were positively associated with CCOC and EOC; BFM, linoleic acid, omega-6 fatty acids, CBS-10 and birth weight were significantly associated with IMOC; and body fat percentage, BFM and adiponectin were significantly associated with HGSOC. Both GC and MR identified 13 shared factors. Factors were stratified into five priority levels, and visual causal networks were constructed for future interventions.Conclusions: With analysis of large-scale exposures for breast and ovarian cancers, causalities, genetic correlations, shared or specific factors, risk factor priority and causal pathways and networks were identified. [ABSTRACT FROM AUTHOR]

Although observational studies have shown an association between sex hormone-binding globulin (SHBG), testosterone (T) and cardiovascular diseases (CVD), controversy remains. In this study, we aim to explore the causal effects of SHBG and T on Coronary heart disease (CHD). We used univariable, network and multivariable mendelian randomization (MR) analysis to investigate the causal effect of SHBG and T on CHD. We performed inverse variance weighted (IVW) MR as the primary analysis, with the robustness of this approach further tested by other methods in sensitivity analysis. The SHBG and T were collected from the UK Biobank data, about 180,000 men aged 40 to 69 years. CHD was collected from CARDIoGRAMplusC4D 1000 Genomes-based GWAS, which was a meta-analysis including 48 studies and involving 60,801 CHD cases and 123,504 controls. Using univariable MR-IVW, the results suggested that a one standard deviation (SD) increase in SHBG, the risk of CHD decreased by approximately 14% (OR (95% CI): 0.86(0.76,0.97)), and that a SD increase in total testosterone (TT), the risk also decreased, approximately 8% (OR (95% CI): 0.92(0.85,0.99)). Multivariable MR showed that both SHBG and TT had no direct causal effect with CHD (a SD increase in SHBG: OR (95% CI):0.75(0.57,1.00), P = 0.053; a SD increase in TT: OR (95% CI): 1.05(0.90,1.22), P = 0.53). In the network MR analysis, the results suggested that TT might act as mediator in the causal pathway from SHBG to CHD and account for 93% of the total effect of SHBG on CHD, and that SHBG might be a mediator in the causal pathway from TT to CHD and account for 67% of the total effect of TT on CHD. Genetically predicted SHBG and TT were negatively correlated with CHD in both univariable and network MR, which may provide a causal explanation behind the observed conclusion. In addition, TT and SHBG had a bidirectional causal effect. Further work is required to disentangle the downstream effects of SHBG/TT on CHD and the molecular pathways involved, as the simultaneous regulation of SHBG and TT may make it a viable strategy for the prevention or treatment of CHD. • Multivariable MR showed that both SHBG and TT had no direct causal effect with CHD (a SD increase in SHBG: OR (95%CI):0.75(0.57,1.00), P = 0.053; a SD increase in TT: OR (95%CI): 1.05(0.90,1.22), P = 0.53). • In the network MR analysis, the results suggested that TT might act as mediator in the causal pathway from SHBG to CHD and account for 93% of the total effect of SHBG on CHD, and that SHBG might be a mediator in the causal pathway from TT to CHD and account for 67% of the total effect of TT on CHD. [ABSTRACT FROM AUTHOR]

• Hillslope topography is essential for local hydrology and peatland formation. • Microtopographic patterning enhances the positive water balance of the peatland. • Feedback between plant growth and pool development reinforces the stability of the peatland. Some sloping peatlands in northern regions often develop surface microtopographic patterns to maintain their water balance and ecosystem functioning. However, we do not know whether and how spatial patterning would influence the water balance and peat formation of permafrost-affected peatlands in relatively dry regions. Here we used data from the field observations and Unmanned Aerial Vehicle (UAV) survey of a slope peatland at an elevation of around 4800 m in the hinterland of the Qinghai-Tibetan Plateau (QTP) to document and understand the topographic controls of water balance and vegetation growth. Our terrain analysis result shows that the peatland—located on the middle section of a hillslope—has a gentle slope of 5.6° ± 2.5°, while the non-peatland upper section has a steep slope of 12° ± 4.5°. The great upstream catchment area and the presence of shallow impermeable permafrost likely create a saturated condition for peat formation. Our UAV results show obvious spatial patterning of abundant pools and ridges across this peatland, and pool sizes and ridge abundance increase with increasing slopes, suggesting that slope-controlled water flow gradient is the main driver of ridge formation and that ridges is to slow down the runoff. UAV-derived greenness values show a positive relationship with the total pool extent locally (R2 = 0.60) and decrease with increasing distance from the individual pools, suggesting sensitive responses of vegetation growth to surface moisture. Thus, enhanced vegetation growth and likely resultant great peat accumulation immediately around pools potentially further differentiate surface microtopography, strengthening the pool stability. We conclude that the local slope gradient, surface patterning (pools and ridges) and permafrost interact together to regulate water flow and maintain water balance, which in turn regulate the vegetation growth, peat accumulation and peatland stability. Our study implies that the delicate water balance maintained partly by microtopography is sensitive to climate change—especially potential extreme hydroclimate events—and natural and human-induced disturbances that may modify the surface patterning and weaken the peatland's stability, affecting the carbon sequestration ability of this type of peatlands. [ABSTRACT FROM AUTHOR]

To accurately control the longitudinal relative position of a harvester and transport vehicle, such that grain in the harvester can be accurately unloaded into the transport vehicle's granary, this study established a master–slave collaborative harvesting system. Furthermore, this study proposed a calculation method for the longitudinal deviation of two vehicles, analyzed the structure and mathematical model of the hydraulic stepless transmission, identified the proposed stem transfer function of the hydraulic stepless transmission speed, analyzed incremental proportional–integral–derivative (PID), and developed self-adjusting–single-neuron PID control methods. Simulations and field experiments were performed to test the applicability of the proposed system. The experimental results indicated that the maximum overshoot of the longitudinal deviation between the harvester and the transport vehicle did not exceed 0.25 m, the steady-state mean absolute deviation did not exceed 0.08 m, the steady-state maximum deviation did not exceed 0.26 m, and the steady-state standard deviation did not exceed 0.09 m, when the harvester speed was 0.6, 0.8, and 1 m/s. Field-harvesting application experiments showed that the settling time during the alignment process was 13.2 s, and the steady-state maximum deviation was 0.253 m. The grain can be accurately unloaded into the granary of the transport vehicle. These results indicate that the control method and the master–slave collaborative harvesting system proposed in this study can meet the needs of precise collaborative unloading between the harvester and transport vehicle. [ABSTRACT FROM AUTHOR]

Gestational duration has a significant impact on eye diseases. A large number of evidences suggest that cytokines are associated with gestational duration and eye diseases. However, the causal relationships among cytokines, maternal gestational impairment and offspring eye diseases remain unclear. We performed lifecourse-network Mendelian randomization (MR) to explore the causal relationships between maternal gestational duration (from the Early Growth Genetics (EGG) Consortium and the Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH) study, N = 84,689), neonatal/adult cytokines (from the NHGRI-EBI Catalog, N = 764/4,618), and adult eye diseases (from FinnGen consotium, N = 309,154) using summary-level data from large genome-wide association studies. Multiplicative random effects inverse variance weighted (IVW) and multivariable-IVW methods were the main analysis methods, and the other 15 pleiotropy-robust methods, weak IV-robust methods, and outliers-robust methods were used as auxiliary methods. Maternal gestational age (early preterm birth, preterm birth, gestational duration, and post-term birth) had a causal relationship with 42 eye diseases. Four neonatal cytokines, Tumor Necrosis Factor-α(TNF-α), IL10, GROA, and CTACK, as well as four adult cytokines, CTACK, IL10, IL12p70 and IL6 are mediators in the causal relationships between early preterm birth and preterm birth in eight eye diseases. However, after adjusting for these mediators, a null direct causal effect of early preterm birth and preterm birth on eight eye diseases was found. In addition, there was no mediator in the causal relationship between gestational duration and post-term birth to eye diseases. The effects of maternal gestational duration on offspring eye diseases through cytokines are long-term and life-course effects. [ABSTRACT FROM AUTHOR]

• Soil PLFAs increased with altitude in the sedge dominated peatlands but decreased with altitude in the shrub/ Sphagnum dominated peatland. • Soil microbes were co-limited by C and P with the limitations greater in the sedge dominated peatlands than in the shrub/ Sphagnum dominated peatlands. • The P limitation was greater at the high altitudes than that at the low altitudes. • Soil PLFAs and community was regulated by soil physical properties and nutrients, respectively. • The C and P limitation was regulated by soil physical properties and nutrient ratios, respectively. Soil microbes regulate the storage of carbon (C) in peatlands, which is facilitated by nutrients. To date, few researchers have examined the spatial distribution of soil microbial biomass, microbial community structure, and their metabolic nutrient limitations in mountain peatlands at different altitudes. This study aimed to improve the knowledge of how and why soil microbial biomass and their metabolic nutrient limitations varied with altitude. We investigated the phospholipid fatty acids (PLFAs) and enzymatic stoichiometry in surface (0–20 cm) and subsurface (20–50 cm) soil from peatlands with different types of vegetation in the Changbai Mountains. Overall, the soil microbial PLFAs were higher in the sedge-dominated peatlands than in the shrub/ Sphagnum- dominated peatlands. The soil microbial PLFAs in the sedge-dominated peatlands were elevated at high altitudes but decreased with altitude in the shrub/ Sphagnum- dominated peatlands. The soil fungal/bacterial ratios (F/B) in the surface soil increased with altitude in the sedge-dominated peatlands but not in the shrub/ Sphagnum- dominated peatlands. The Gram-positive/Gram-negative bacteria ratios (G+/G−) in the surface soil decreased with altitude in the sedge-dominated and shrub/ Sphagnum- dominated peatlands. The soil F/B ratios were higher, but the G+/G− ratios were lower in the shrub/ Sphagnum- dominated peatlands than in the sedge-dominated peatlands. The soil pH and nutrient ratios explained most of the differences in soil bacterial and fungal PLFAs, respectively. However, the total nutrients of soil were the primary regulators of soil F/B and G+/G−. The soil microbial activities suffered from C- and phosphorus (P)- limitations in the mountain peatlands. The limitations were worse in the shrub/ Sphagnum- dominated peatlands than in the sedge-dominated peatlands. The P limitations were greater at high altitude than at low altitude in both types of peatlands. The C and P limitations on soil microbial metabolism were primarily controlled by soil physical properties and nutrient ratios, respectively. [ABSTRACT FROM AUTHOR]

• Peatland degradation caused a significant loss of testate amoeba (TA) biodiversity. • Unexpectedly, this loss was accompanied by an increase in TA biosilicification. • TA biodiversity was not coupled to protozoic biogeochemical silicon (Si) cycling. • New insights into microbial biogeochemical Si cycling on a continental scale. Anthropogenic peatland degradation is a global threat. As peatlands store large amounts of carbon (C) their potential for mitigation of climate change has been emphasized recently. Global C cycling is linked to silicon (Si) fluxes from the continents into the oceans. These fluxes in turn are driven by biosilicification, the incorporation of inorganic Si into living organisms, in terrestrial ecosystems. Biosilicification by testate amoeba (TA) communities and its potential for Si cycling has been highlighted since the beginning of the 21st century. However, the effects of peatland degradation on TA biodiversity and corresponding protozoic biosilicification on a continental scale remained unresolved so far. We show that TA biodiversity in Asian peatlands is strongly affected by the grade of human impact. This biodiversity decline was accompanied by an unexpected increase in protozoic biosilicification. Our findings provide new insights into the interactions between the biodiversity of soil microorganisms and biogeochemical Si cycling. [ABSTRACT FROM AUTHOR]