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Abstract Background Polygenic risk score (PRS) is a major research topic in human genetics. However, a significant gap exists between PRS methodology and applications in practice due to often unavailable individual-level data for various PRS tasks including model fine-tuning, benchmarking, and ensemble learning. Results We introduce an innovative statistical framework to optimize and benchmark PRS models using summary statistics of genome-wide association studies. This framework builds upon our previous work and can fine-tune virtually all existing PRS models while accounting for linkage disequilibrium. In addition, we provide an ensemble learning strategy named PUMAS-ensemble to combine multiple PRS models into an ensemble score without requiring external data for model fitting. Through extensive simulations and analysis of many complex traits in the UK Biobank, we demonstrate that this approach closely approximates gold-standard analytical strategies based on external validation, and substantially outperforms state-of-the-art PRS methods. Conclusions Our method is a powerful and general modeling technique that can continue to combine the best-performing PRS methods out there through ensemble learning and could become an integral component for all future PRS applications.

Abstract An increasing body of evidence suggests that acylphosphatase-2 (ACYP2) polymorphisms are correlated with an increased susceptibility to a range of malignancies. Nevertheless, its potential functions, molecular mechanisms in hepatocellular carcinoma (HCC) and whether it can be act as a therapeutic target remain uninvestigated. Herein, ACYP2 was found to be lowly expressed in HCC and was negatively correlated with tumor size, tumor differentiation, microvascular invasion and the prognosis of HCC patients. Functional investigations revealed that overexpression of ACYP2 inhibited the proliferation and metastasis of HCC cells while promoting apoptosis; knockdown of ACYP2 had the exact opposite effect. Additionally, it was observed that ACYP2 was distributed in both the cytoplasm and nucleus of HCC cells. According to the mechanistic studies, the expression of potassium calcium-activated channel subfamily N member 4 (KCNN4) was negatively regulated by cytoplasmic ACYP2, resulting in the inhibition of K+ outflow and subsequent inactivation of the ERK pathway, which impeded the growth and metastasis of HCC. Furthermore, the activity of telomerase reverse transcriptase (TERT) was inhibited by nuclear ACYP2, leading to the reduction in length of telomeres and consequent reversal of HCC cell immortalization. Additionally, a novel targeted nanotherapy strategy was developed wherein the pcDNA-ACYP2 vector was encapsulated within polyetherimide nanoparticles (PEI/NPs), which were subsequently coated with HCC cell membranes (namely pcDNA/PEI/NPs@M). Safety and targeting characteristics abound for these nanocomposites, in both subcutaneous graft tumor models and orthotopic mouse models, they inhibited the progression of HCC by impeding TERT activity and the KCNN4/ERK pathway. In conclusion, our research identifies novel molecular mechanisms involving cytoplasmic and nuclear ACYP2 that inhibit the progression of HCC. Moreover, pcDNA/PEI/NPs@M represents a targeted therapeutic strategy for HCC that holds great promising. Graphical Abstract

Abstract Hypertension remains a leading cause of cardiovascular and kidney diseases. Failure to control blood pressure with ≥ 3 medications or control requiring ≥ 4 medications is classified as resistant hypertension (rHTN) and new therapies are needed to reduce the resulting increased risk of morbidity and mortality. Here, we report genetic evidence that relaxin family peptide receptor 2 (RXFP2) is associated with rHTN in men, but not in women. This study shows that adrenal gland gene expression of RXFP2 is increased in men with hypertension and the RXFP2 natural ligand, INSL3, increases adrenal steroidogenesis and corticosteroid secretion in human adrenal cells. To address the hypothesis that RXFP2 activation is an important mechanism in rHTN, we discovered and characterized small molecule and monoclonal antibody (mAb) blockers of RXFP2. The novel chemical entities and mAbs show potent, selective inhibition of RXFP2 and reduce aldosterone and cortisol synthesis and release. The RXFP2 mAbs have suitable rat pharmacokinetic profiles to evaluate the role of RXFP2 in the development and maintenance of rHTN. Overall, we identified RXFP2 activity as a potential new mechanism in rHTN and discovered RXFP2 antagonists for the future interrogation of RXFP2 in cardiovascular and renal diseases.

Abstract Over the past few decades, the number of patients with neurological diseases has increased significantly, posing huge challenges and opportunities for the development of brain imaging technology. As a hybrid imaging method combining optical excitation and acoustic detection techniques, photoacoustic tomography (PAT), has experienced rapid development, due to high optical contrast and spatial resolution at depth inside tissues. With the development of lasers, ultrasonic detectors, and data computations, PAT has been widely applied for the diagnosis of oncology, dermatosis, etc. However, the energy of light and ultrasound would be greatly attenuated while penetrating the skull, due to the reflection, absorption, and scattering effects, resulting in limited application of PAT in brain imaging. In this review, we summarized the achievements of PAT and its application in the detection of brain diseases including glioma, stroke, traumatic brain injury, Alzheimer's disease, epilepsy, and Parkinson's disease. Moreover, various PAT systems and multi‐modality photoacoustic imaging are introduced for potential clinical applications. Finally, the challenges and current limitations of PAT for further brain imaging are also discussed.

Summary: Our understanding of human fetal cerebellum development during the late second trimester, a critical period for the generation of astrocytes, oligodendrocytes, and unipolar brush cells (UBCs), remains limited. Here, we performed single-cell RNA sequencing (scRNA-seq) in human fetal cerebellum samples from gestational weeks (GWs) 18–25. We find that proliferating UBC progenitors distribute in the subventricular zone of the rhombic lip (RLSVZ) near white matter (WM), forming a layer structure. We also delineate two trajectories from astrogenic radial glia (ARGs) to Bergmann glial progenitors (BGPs) and recognize oligodendrogenic radial glia (ORGs) as one source of primitive oligodendrocyte progenitor cells (PriOPCs). Additionally, our scRNA-seq analysis of the trisomy 21 fetal cerebellum at this stage reveals abnormal upregulated genes in pathways such as the cell adhesion pathway and focal adhesion pathway, which potentially promote neuronal differentiation. Overall, our research provides valuable insights into normal and abnormal development of the human fetal cerebellum.

BackgroundThe implementation of family doctor contract service is a pivotal measure to enhance primary medical services and execute the hierarchical diagnosis and treatment system. Achieving service coordination among various institutions is both a fundamental objective and a central element of contract services.ObjectiveThe study aims to assess residents’ evaluations and determining factors related to the coordination of health services within primary medical institutions across different regions of Shandong Province. The findings intend to serve as a reference for enhancing the coordination services offered by these institutions.MethodsThe study employed a multi-stage stratified random sampling method to select three prefecture-level cities in Shandong Province with different economic levels. Within each city, three counties (districts) were randomly sampled using the same method. Within each county (district), three community health service centers and township health centers implementing family doctor contract services were selected randomly. Face-to-face questionnaire surveys were conducted with contracted residents using the coordination dimension of the revised Primary Care Assessment Tools Scale (PCAT) developed by the research team. Data analysis was conducted using such methods as one-way analysis of variance and multiple linear regression.ResultsThe sample included 3,859 contracted residents. The coordination dimension score of primary medical institutions averaged 3.41 ± 0.18, with the referral service sub-dimension scoring 3.60 ± 0.58 and the information system sub-dimension scoring 3.34 ± 0.65. The overall score of the referral service sub-dimension surpassed that of the information system sub-dimension. Regression results indicated that the city’s economic status, the type of contracted institutions, gender, education, marital status, income, occupation, health status, and endowment insurance payment status significantly influenced the coordinated service score of primary medical institutions (p

This study investigated the effect of nitrogen application on the rhizosphere soil microenvironment of sunflower and clarified the relationship between ammonium assimilation and the microenvironment. In a field experiment high (HN, 190 kg/hm2), medium (MN, 120 kg/hm2) and low nitrogen (CK, 50 kg/hm2) treatments were made to replicate plots of sunflowers using drip irrigation. Metagenomic sequencing was used to analyze the community structure and functional genes involved in the ammonium assimilation pathway in rhizosphere soil. The findings indicated that glnA and gltB played a crucial role in the ammonium assimilation pathway in sunflower rhizosphere soil, with Actinobacteria and Proteobacteria being the primary contributors. Compared with CK treatment, the relative abundance of Actinobacteria increased by 15.57% under MN treatment, while the relative abundance decreased at flowering and maturation stages. Conversely, the relative abundance of Proteobacteria was 28.57 and 61.26% higher in the MN treatment during anthesis and maturation period, respectively, compared with the CK. Furthermore, during the bud stage and anthesis, the abundance of Actinobacteria, Proteobacteria, and their dominant species were influenced mainly by rhizosphere soil EC, ammonium nitrogen (NH4+-N), and nitrate nitrogen (NO3--N), whereas, at maturity, soil pH and NO3--N played a more significant role in shaping the community of ammonium-assimilating microorganisms. The MN treatment increased the root length density, surface area density, and root volume density of sunflower at the bud, flowering, and maturity stages compared to the CK. Moreover, root exudates such as oxalate and malate were positively correlated with the dominant species of Actinobacteria and Proteobacteria during anthesis and the maturation period. Under drip irrigation, applying 120 kg/hm2 of nitrogen to sunflowers effectively promoted the community structure of ammonium-assimilating microorganisms in rhizosphere soil and had a positive influence on the rhizosphere soil microenvironment and sunflower root growth.

Automated segmentation of breast tumors in breast ultrasound images has been a challenging frontier issue. The morphological diversity, boundary ambiguity, and heterogeneity of malignant tumors in breast lesions constrain the improvement of segmentation accuracy. To address these challenges, we propose an innovative deep learning-based method, namely Dual-Channel Deep Residual Attention UPerNet (DDRA-net), for efficient and accurate segmentation of breast tumor regions. The core of DDRA-net lies in the Dual-Channel Deep Residual Attention module (DDRA), which integrates depth-wise separable convolution and Convolutional Block Attention Module (CBAM). This design aims to enhance the extraction of crucial features within the receptive field to better capture subtle details of breast lesions. Through extensive experimental evaluation, DDRA-net demonstrates remarkable performance on a publicly available breast ultrasound datasets, exhibiting higher segmentation accuracy and stability compared to contemporary mainstream deep learning methods. Importantly, it is worth emphasizing that the flexibility of this method allows easy integration with other network structures to further improve the performance and applicability of breast tumor segmentation. In the segmentation of the Breast Ultrasound Image dataset, our precision, recall, IoU, F1 score, Dice, and Hausdorff Distance achieved the following values: 95.31%, 90.79%, 88.00%, 92.39%, 95.46%, and 3.02, respectively. Compared to the original UPerNet, DDRA-net demonstrated improvements of 2.71%, 4.03%, 4.61%, 4.38%, 3.14%, and 24.5% in these six metrics on the Breast Ultrasound Image dataset.

Magnet-free acrlongpl vppm are competitive alternatives in electric vehicles where torque-speed operating region, reliability, cost, and energy efficiency are key metrics. However, their modeling and control have so far relied on existing fixed-phase and pole-symmetrical models, limiting their drive capabilities, especially when switching the number of poles on the fly. This paper establishes the acrlong hpd theory as a space- acrlong dft interpretation of the Clarke transformation, decomposing all pole-pair fields into a fixed number of orthogonal subspaces with invariant parameters. The model remains unaltered for all phase-pole configurations, guaranteeing continuity even under phase-pole transitions. Relations of the state and input space vectors, and model parameters to those of the acrlong vsd theory used for multiphase machines are established via the use of the complex winding factor. Experiments confirm the modeling theory and demonstrate its practical usefulness by performing a field-oriented-controlled phase-pole transition. Non-trivial configurations with more than one slot/pole/phase and a fractional phase number are also demonstrated.

ABSTRACTIn this study, an immunocompromised rat model was established by long-term diet control and excessive swimming and treated with extracts of raw licorice (RL) and honey-roasted licorice (HL) to explore the immunomodulatory efficacy and gut microbiota composition with their metabolites. Pharmacological experiment confirmed that honey-roasting enhanced the ability of RL to regulate inflammatory cytokines and gut mucosal-layer homeostasis. The analysis of 16S rRNA sequences showed that both RL and HL regulated the balance of gut microbiota, but HL exhibited better effects than RL in regulating microbiota closely related to inflammatory cytokines (Coriobacteriaceae_UCG-002) as well as short-chain fatty acids-producing bacteria (Dubosiella and Ruminococcus). Moreover, HL improved the contents of butyrate and isobutyrate in feces more significantly than RL. In conclusion, the balance of gut microbiota and short-chain fatty acids might be one of the pathways that honey-roasting improve the immunomodulatory efficacy of licorice.Abbreviations: ANOVA: analysis of variance; BCA: bicinchoninic acid; ELISA: enzyme-linked immunosorbent assay; HRP: horseradish peroxidase; LDA: the linear discriminant analysis; LEfSe: the linear discriminant analysis effect size; MS: mass spectrometry; OTU: operational taxonomic units; PBS: phosphate buffered saline; PCoA: principal coordinate analysis; PVDF: polyvinylidene fluoride; RIPA: radio immunoprecipitation assay; SCFAs: short-chain fatty acids;

Abstract As an economically important insect pest, the flower thrips Frankliniella intonsa (Trybom) causes great damage to host plants by directly feeding and indirectly transmitting various pathogenic viruses. The lack of a well-assembled genomic resource has hindered our understanding of the genetic basis and evolution of F. intonsa. In this study, we used Oxford Nanopore Technology (ONT) long reads and High-through chromosome conformation capture (Hi-C) linked reads to construct a high-quality reference genome assembly of F. intonsa, with a total size of 225.5 Mb and a contig N50 of 3.37 Mb. By performing the Hi-C analysis, we anchored 91.68% of the contigs into 15 pseudochromosomes. Genomic annotation uncovered 17,581 protein-coding genes and identified 20.09% of the sequences as repeat elements. BUSCO analysis estimated over 98% of genome completeness. Our study is at the first time to report the chromosome-scale genome for the species of the genus Frankliniella. It provides a valuable genomic resource for further biological research and pest management of the thrips.

Abstract There have been contradictory reports on the biological role of transforming growth factor‐βs (TGFβs) in breast cancer (BC), especially with regard to their ability to promote epithelial‐mesenchymal transition (EMT). Here, we show that TGFβ2 is preferentially expressed in mesenchymal‐like BCs and maintains the EMT phenotype, correlating with cancer stem cell‐like characteristics, growth, metastasis and chemo‐resistance and predicting worse clinical outcomes. However, this is only true in ERα− BC. In ERα+ luminal‐type BC, estrogen receptor interacts with p‐Smads to block TGFβ signalling. Furthermore, we also identify a microRNAs (miRNAs) signature (miRNAsTGFβ2) that is weakened in TGFβ2‐overexpressing BC cells. We discover that TGFβ2‐Snail1 recruits enhancer of zeste homolog‐2 to convert miRNAsTGFβ2 promoters from an active to repressive chromatin configuration and then repress miRNAsTGFβ2 transcription, forming a negative feedback loop. On the other hand, miRNAsTGFβ2 overexpression reverses the mesenchymal‐like traits in agreement with the inhibition of TGFβ2‐Snail1 signalling in BC cells. These findings clarify the roles of TGFβ2 in BC and suggest novel therapeutic strategies based on the TGFβ2‐Snail1‐miRNAsTGFβ2 loop for a subset type of human BCs.

Simultaneous wireless information and power transfer (SWIPT) has emerged as a pivotal technology in 6G, offering an efficient means of delivering energy to a large quantity of low-power devices while transmitting data concurrently. To address the challenges of obstructions, high path loss, and significant energy consumption associated with long-distance communication, this work introduces a novel alternating iterative optimization strategy. The proposed approach combines active simultaneous transmission and reflection of reconfigurable intelligent surfaces (STAR-RIS) with SWIPT to maximize spectrum efficiency and reduce overall system energy consumption. This method addresses the considerable energy demands inherent in SWIPT systems by focusing on reducing the power output from the base station (BS) while meeting key constraints: the communication rate for information receivers (IRs) and minimum energy levels for energy receivers (ERs). Given complex interactions between variables, the solution involves an alternating iterative optimization process. In the first stage of this approach, the passive beamforming variables are kept constant, enabling the use of semi-definite relaxation (SDR) and successive convex approximation (SCA) algorithms to optimize active beamforming variables. In the next stage, with active beamforming variables fixed, penalty-based algorithms are applied to fine-tune the passive beamforming variables. This iterative process continues, alternating between active and passive beamforming optimization, until the system converges on a stable solution. The simulation results indicated that the proposed system configuration, which leverages active STAR-RIS, achieves lower energy consumption and demonstrates improved performance compared to configurations utilizing passive RIS, active RIS, and passive STAR-RIS. This evidence suggests that the proposed approach can significantly contribute to advancing energy efficiency in 6G systems.

In recent years, the semantic segmentation model has been widely applied in fields such as the extraction of crops due to its advantages such as strong discrimination ability, high accuracy, etc. Currently, there is no standard set of ground true label data for major crops in China, and the visual interpretation process is usually time-consuming and laborious. The sample size also makes it difficult to support the model to learn enough ground features, resulting in poor generalisation ability of the model, which in turn makes the model difficult to apply in fine extraction tasks of large-area crops. In this study, a method to establish a pseudo-label sample set based on the random forest algorithm to train a semantic segmentation model (U-Net) was proposed to perform winter wheat extraction. With the help of the GEE platform, Winter Wheat Canopy Index (WCI) indicators were employed in this method to initially extract winter wheat, and training samples (i.e., pseudo labels) were built for the semantic segmentation model through the iterative process of “generating random sample points—random forest model training—winter wheat extraction”; on this basis, the U-net model was trained with multi-time series remote sensing images; finally, the U-Net model was employed to obtain the spatial distribution map of winter wheat in Henan Province in 2022. The results illustrated that: (1) Pseudo-label data were constructed using the random forest model in typical regions, achieving an overall accuracy of 97.53% under validation with manual samples, proving that its accuracy meets the requirements for U-Net model training. (2) Utilizing the U-Net model, U-Net++ model, and random forest model constructed based on pseudo-label data for 2022, winter wheat mapping was conducted in Henan Province. The extraction accuracy of the three models is in the order of U-Net model > U-Net++ model > random forest model. (3) Using the U-Net model to predict the winter wheat planting areas in Henan Province in 2019, although the extraction accuracy decreased compared to 2022, it still exceeded that of the random forest model. Additionally, the U-Net++ model did not achieve higher classification accuracy. (4) Experimental results demonstrate that deep learning models constructed based on pseudo-labels exhibit higher classification accuracy. Compared to traditional machine learning models like random forest, they have higher spatiotemporal adaptability and robustness, further validating the scientific and practical feasibility of pseudo-labels and their generation strategies, which are expected to provide a feasible technical pathway for intelligent extraction of winter wheat spatial distribution information in the future.

The separation of a toluene/methanol/water ternary mixture is a difficult task due to the toluene/water and toluene/methanol azeotropes. In this article, low-energy pervaporation is proposed for the separation of the ternary azeotrope toluene–methanol–water. This work investigates the effects of feed temperature, feed flow rate, and vacuum on pervaporation and compares the energy consumption of pervaporation with that of distillation. The results showed that at the optimized flow rate of 50 L/h and a permeate side vacuum of 60 kPa at 50 °C, the water and methanol content in the permeate was about 63.2 wt.% and 36.8 wt.%, respectively, the water/ methanol separation factor was 24.04, the permeate flux was 510.7 g/m2·h, the water content in the feed out was reduced from 2.5 wt.% to less than 0.66 wt.%, and the dehydration of toluene methanol could be realized. Without taking into account the energy consumption of pumps and other power equipment, pervaporation requires an energy consumption of 43.53 kW·h to treat 1 ton of raw material, while the energy consumption of distillation to treat 1 ton of raw material is about 261.5 kW·h. Compared to the existing distillation process, the pervaporation process consumes much less energy (about one-sixth of the energy consumption of distillation). There is almost no effect on the surface morphology and chemical composition of the membrane before and after use. The method provides an effective reference for the dehydration of organic solvents from ternary mixtures containing toluene/methanol/water.

The layer-by-layer (LBL) fabrication method allows for controlled microstructure morphology and vertical component distribution, and also offers a reproducible and efficient technique for fabricating large-scale organic solar cells (OSCs). In this study, the polymers D18 and PYIT-OD are employed to fabricate all-polymer solar cells (all-PSCs) using the LBL method. Morphological studies reveal that the use of additives optimizes the microstructure of the active layer, enhancing the cells’ crystallinity and charge transport capability. The optimized device with 2% CN additive significantly reduces bimolecular recombination and trap-assisted recombination. All-PSCs fabricated by the LBL method based on D18/PYIT-OD deliver a power conversion efficiency (PCE) of 15.07%. Our study demonstrates the great potential of additive engineering via the LBL fabrication method in regulating the microstructure of active layers, suppressing charge recombination, and enhancing the photovoltaic performance of devices.

ObjectiveThe purpose of this study was to investigate whether the combination of abnormal systemic immune-inflammation index (SII) levels and hyperglycemia increased the risk of cognitive function decline and reduced survival rate in the United States.MethodsThis cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) database from 2011-2014 and enrolled 1,447 participants aged 60 years or older. Restricted cubic splines (RCS), linear regression and kaplan-meier(KM) curve were employed to explore the combined effects of abnormal SII and hyperglycemia on cognitive function and survival rate, and subgroup analysis was also conducted.ResultsThe RCS analysis revealed an inverted U-shaped relationship between lgSII levels and cognitive function. Linear regression analysis indicated that neither abnormal SII nor diabetes alone significantly contributed to the decline in cognitive function compared to participants with normal SII levels and blood glucose. However, when abnormal SII coexisted with diabetes (but not prediabetes), it resulted to a significant decline in cognitive function. After adjusting for various confounding factors, these results remained significant in Delayed Word Recall (β:-0.76, PConclusionThe findings suggest that the impact of diabetes on cognitive function/survival rate is correlated with SII levels, indicating that their combination enhances predictive power.

Pest and disease damage to forests cannot be underestimated, so it is essential to detect diseased trees in time and take measures to stop their spread. The detection of discoloration standing trees is one of the important means to effectively control the spread of pests and diseases. In the visible wavelength range, early infected trees do not show significant color changes, which poses a challenge for early detection and is only suitable for monitoring middle and late discolor trees. The spectral resolution of hyperspectral restricts the improvement of its spatial resolution, and there are phenomena of different spectral of the same and foreign objects in the same spectrum, which affect the detection results. In this paper, the method of hyperspectral and CCD image fusion is used to achieve high-precision detection of discoloration standing trees. This paper proposes an improved algorithm MSGF-GLP, which uses multi-scale detail boosting and MTF filter to refine high-resolution data. By combining guided filtering with hyperspectral images, the spatial detail difference is enhanced, and the injection gain is interpolated into the difference of each band, so as to obtain high-resolution and high-quality hyperspectral images. This research is based on hyperspectral and CCD data obtained from LiCHy, Chinese Academy of Forestry, Maoershan Experimental Forest Farm, Shangzhi City, Heilongjiang Province. The evaluation framework is used to compare with the other five fusion algorithms to verify the good effect of the proposed method, which can effectively preserve the canopy spectrum and improve the spatial details. The fusion results of forestry remote sensing data were analyzed using the vegetation Normalized Difference Water Index and Plant Senescence Reflectance Index. The fused results can be used to distinguish the difference between discoloration trees and healthy trees by the multispectral vegetation index. The research results can provide good technical support for the practical application of forest remote sensing data fusion, and lay the foundation for promoting the scientific, automatic and intelligent forestry control.

Virtual synchronous generator (VSG) control addresses the issue of decreasing microgrid standby inertia caused by the rise in wind turbines and photovoltaic (PV) penetration. However, various types of perturbations occur frequently making the traditional constant parameter VSG control unable to meet the system performance requirements, and thus a two-parameters fuzzy VSG control is proposed to ensure that microgrid inertia and damping. Firstly, the device-level control of each generation unit in the microgrid is designed based on the wind-PV-battery alternating current (AC) microgrid architecture. Secondly, fuzzy VSG control uses fuzzy rules written in plain language to represent the relationship between the main VSG factors and the power and frequency. Then, the influence of virtual inertia and damping coefficient on the dynamic performance of the system is analyzed through the theory of small-signal model, and a reasonable variation range of VSG parameters are given. Finally, the simulation model of wind-PV-battery AC microgrid is built in MATLAB/Simulink, and compared with other improved VSG control strategies, the fuzzy VSG control proposed in this paper has better dynamic performance and safety stability. This research emphasizes the practicality and importance of utilizing fuzzy control to adjust VSG techniques for developing microgrid configurations incorporating more renewable energy sources to guarantee the reliability and efficiency of microgrid.

Abstract Impaired protein N-glycosylation leads to the endoplasmic reticulum (ER) stress, which triggers adaptive survival or maladaptive apoptosis in renal tubules in diabetic kidney disease (DKD). Therapeutic strategies targeting ER stress are promising for the treatment of DKD. Here, we report a previously unappreciated role played by ENTPD5 in alleviating renal injury by mediating ER stress. We found that ENTPD5 was highly expressed in normal renal tubules; however, ENTPD5 was dynamically expressed in the kidney and closely related to pathological DKD progression in both human patients and mouse models. Overexpression of ENTPD5 relieved ER stress in renal tubular cells, leading to compensatory cell proliferation that resulted in hypertrophy, while ENTPD5 knockdown aggravated ER stress to induce cell apoptosis, leading to renal tubular atrophy and interstitial fibrosis. Mechanistically, ENTPD5-regulated N-glycosylation of proteins in the ER to promote cell proliferation in the early stage of DKD, and continuous hyperglycemia activated the hexosamine biosynthesis pathway (HBP) to increase the level of UDP-GlcNAc, which driving a feedback mechanism that inhibited transcription factor SP1 activity to downregulate ENTPD5 expression in the late stage of DKD. This study was the first to demonstrate that ENTPD5 regulated renal tubule cell numbers through adaptive proliferation or apoptosis in the kidney by modulating the protein N-glycosylation rate in the ER, suggesting that ENTPD5 drives cell fate in response to metabolic stress and is a potential therapeutic target for renal diseases.

The transport and dispersion (T&D) of catalyst particles seeded by weather modification aircraft is crucial for assessing their weather modification effects. This study investigates the capabilities of the Chinese geostationary weather satellite FY-4A for identifying the physical response of cloud seeding with AgI-based catalysts and continuously monitoring its evolution for a weather event that occurred on 15 December 2019 in Henan Province, China. Satellite measurements are also used to verify an operational catalyst T&D algorithm. The results show that FY-4A exhibits a remarkable capability of identifying the cloud-seeding tracks and continuously tracing their evolution for a period of over 3 h. About 60 min after the cloud seeding, the cloud crystallization track became clear in the FY-4A tri-channel composite cloud image and lasted for about 218 min. During this time period, the cloud track moved with the cloud system about 153 km downstream (northeast of the operation area). An operational catalyst T&D model was run to simulate the cloud track, and the outputs were extensively compared with the satellite observations. It was found that the forecast cloud track closely agreed with the satellite observations in terms of the track widths, morphology, and movement. Finally, the FY-4A measurements show that there were significant differences in the microphysical properties across the cloud track. The effective cloud radius inside the cloud track was up to 15 μm larger than that of the surrounding clouds; the cloud optical thickness was about 30 μm smaller; and the cloud-top heights inside the cloud track were up to 1 km lower. These features indicate that the cloud-seeding catalysts led to the development of ice-phase processes within the supercooled cloud, with the formation of large ice particles and some precipitation sedimentation.

The impact of changing meteorological conditions on crop quality has become a trending topic in current agriculture research. In this study, we analyzed the combined effects of both meteorological conditions and key stages on the nutritional quality of maize based on the data of field-staged sowing trials from 2018 to 2022. The results are as follows: (1) The key stage of meteorological conditions affecting the content of major nutritional qualities of maize is from 6 d before to 35 d after flowering. (2) The maximum temperature from 6 d before to 8 d after flowering, average temperature from 5 d before to 20 d after flowering, and minimum temperature from 9–20 d after flowering have significant positive effects on protein, fat, and essential amino acids, respectively; the daily difference in temperature from 9 to 35 d and 24 to 35 d after flowering have a significant negative effect on crude fiber and essential amino acids, respectively, and the daily difference in temperature from 24 to 35 d and the minimum temperature from 5 d before to 35 d after flowering have a significant effect on non-essential amino acids. (3) When the maximum temperature during the key stage of nutritional quality is 31.2 °C, the average temperatures are 24.9 °C and 22.4 °C, the minimum temperature is 18.9 °C, and the daily difference in temperature is 15.0 °C, the contents could reach the optimal values of 9.66% (protein), 4.80% (fat), 4.97% (crude fiber), 40.39 g·kg−1 (essential amino acids), and 58.96 g·kg−1 (non-essential amino acids), respectively. The findings provide a basis for adjusting the sowing period to improve the nutritional quality of maize in the context of climate change.

The integrator complex is required for the synthesis of protein coding and non-coding RNA and contains the protein INTS13. Here, the authors find germline mutations in INTS13 in two families with oral facial digital syndrome and show that the mutation affects the c-terminal domain of the protein and disrupts cilliogenesis.

Abstract Background Circular RNA (circRNA) is crucial to the progression of hepatocellular cancer (HCC). In addition, Mitochondrial calcium uniporter regulatory factor 1 (MCUR1) is commonly overexpressed in HCC to increase cellular ATP levels. Due to the highly aggressive characteristics of HCC, it is essential to identify new diagnostic biomarkers and therapeutic targets that may facilitate the diagnosis of HCC and the development of effective anti-HCC treatments. Methods A series of in vitro and in vivo experiments were undertaken to investigate the biological importance and underlying mechanisms of circ_0000098 in HCC. Results The expression of circ_0000098 was higher in HCC tissues compared to paired adjacent tissues. According to the receiver-operating characteristic curves, circ_0000098 functioned as a potential diagnostic tumor marker in HCC. Our experiments indicated that circ_0000098 served as a key oncogenic circRNA to increase HCC cell proliferation and invasion in vitro and HCC progression in vivo. Furthermore, mechanistic investigation demonstrated that by sequestering miR-383 from the 3′-UTR of MCUR1, circ_0000098 positively regulated MCUR1 expression in HCC cells and finally promoted HCC progression. On the other hand, inhibiting circ_0000098 in HCC cells could diminish doxorubicin (DOX) resistance by decreasing P-glycoprotein (P-gp, MDR1) expression and intracellular ATP levels. Either downregulation of MCUR1 or overexpression of miR-383 improved DOX sensitivity in HCC cells. Subsequently, a short hairpin RNA targeting circ_0000098 (referred to as sh-1) and doxorubicin (DOX) were encapsulated into platelets (PLTs), referred to as DOX/sh-1@PLT. Activated DOX/sh-1@PLT through HCC cells resulted in the creation of platelet-derived particles that were capable of delivering the DOX/sh-1 combination into HCC cells and promoting intracellular DOX accumulation. Furthermore, our in vivo experiments showed that DOX/sh-1@PLT can effectively reduce P-gp expression, promote DOX accumulation, and reverse DOX resistance. Conclusions Our results demonstrated that circ_0000098 is an oncogenic circRNA that promotes HCC development through the miR-383/MCUR1 axis and targeting circ_0000098 with DOX/sh-1@PLT may be a promising and practical therapeutic strategy for preventing DOX resistance in HCC.

Suitable sowing dates are crucial in plant production to cope with climate change and ensure high-quality crop production. We hypothesize that the analysis of the effect of sowing date and climatic resources on maize kernel nutritional quality (KNQ) (crude fiber, starch, crude fat, and crude protein) might contribute to selecting appropriate sowing dates according to different production requirements and meteorological conditions. The study was based on five main local varieties in three experimental stations (early-maturing variety: Zengyu1317, Hongshuo298, Keyu15; medium-maturing variety: Xianyu335; late-maturing variety: Danyu405) in Northeast China from 2018 to 2021. The results showed that: (1) the average starch content (67.7%) and crude protein content (9.1%) of early-maturing variety maize and the crude fiber content (3.3%) and crude fat content (3.6%) of late-maturing variety maize were the highest in Northeast China; (2) the sowing date had no significant effect on the starch content, but significantly affected the crude protein and crude fiber contents, the kernel protein content of early-maturing variety maize was the highest when the sowing date was delayed for 5 days (9.8%), and the crude fiber content of medium-maturing and late-maturing variety maize (4.3% and 5.39%, respectively) was the highest when the sowing date was advanced by 10 days; (3) during the reproductive growth stage, the more light and heat resources, the less starch content and crude protein content and the more crude fat content; when the diurnal temperature range increased by 1 °C, the crude fat content decreased by 0.28%, and the crude protein content increased by 0.77%; for every 100 mm more precipitation, crude fiber and crude protein content decreased by 0.68% and 0.73%, respectively, and fat content increased by 0.15%. Our results provide a meaningful reference for maize production to cope with climate change and improve kernel quality.

A VCF-based mode-matching micromachine-optimized tuning fork gyroscope is proposed to not only maximize the scale factor of the device, but also avoid use of an additional quadrature-nulling loop to prevent structure complexity, pick-up electrode occupation, and coupling with a mode-matching loop. In detail, a mode-matching, closed-loop system without a quadrature-nulling loop is established, and the corresponding convergence and matching error are quantitatively analyzed. The optimal straight beam of the gyro structure is then modeled to significantly reduce the quadrature coupling. The test results show that the frequency split is narrowed from 20 Hz to 0.014 Hz. The scale factor is improved 20.6 times and the bias instability (BI) is suppressed 3.28 times. The observed matching accuracy demonstrates that a mode matching system without a quadrature suppression loop is feasible and that the proposed device represents a competitive design for a mode-matching gyroscope.

The retaining wall is a passive engineering measure to prevent and control unsafe factors caused by rock collapse in the valleys. Existing studies have mainly focused on its functional robustness and safety features, with few exploring its visual quality in the landscape. A multiple regression analysis was applied to evaluate the Scenic Beauty Estimation (SBE) of the giant retaining wall in Jiuzhaigou's (a world natural heritage site) Heye Village, then the factors affecting SBE were analyzed. It is found that enhancing the sense of perspective and spatial hierarchy of retaining-wall murals in narrow roads contributes to the extension of observers' sight, which is the key to improving SBE. Furthermore, the showcase of folk culture in murals can realize the beautification function of the giant retaining walls. In addition, the SBE of giant retaining walls is also linked to coordination, where the walls embellished with the natural landscape and folk culture murals have better SBE performance than those with local stones. This study provides a reference for constructing scenic beauty after fulfilling the safety function of retaining wall engineering.

Plain Language summary Despite the continuous efforts invested in exploring and optimizing therapeutic regimens to improve the success rate of frozen-thawed embryo transfer (FET), we found that there are little evidence to demonstrate whether the initiation time of estrogen stimulation is flexible in the proliferative endometrial phase during the artificial cycle for FET (AC-FET). Thus, we retrospectively reviewed the FET records from a large university-affiliated reproductive medicine center to explore whether the relatively late start of endometrial stimulation for FET influences the pregnancy outcome. Results provided evidences that initiating the estrogen stimulation on after days 2–5 of menses do not exert adverse effects on the ongoing pregnancy rates in AC-FETs. Therefore, FET can be scheduled in a flexible manner, according to the ovulatory and endometrial statuses and patient and/or clinic preference, without compromised clinical outcomes.

In this study, the impact of artificial precipitation enhancement operation on the wet scavenging of air pollutants is investigated based on an aircraft precipitation enhancement operation in the Yangtze River Delta region of China on 1 November 2020. Multiple measurement data are used, including the regional meteorological and environmental data and the comprehensive field observation data at the Nanjing University of Information Science and Technology (NUIST) campus site. The results show that the affected areas of this operation cover part of Anhui and Jiangsu provinces. The precipitation ratio between the target and contrast areas is always greater than 1, indicating the effectiveness of the seeding operation of silver iodide for precipitation enhancement. The regional analysis of air pollutants suggests that the enhanced precipitation can prevent the increase of air pollutants, especially for the particulate matter. The impact of enhanced precipitation on regional trace gases is complex because they are easily affected by the primary emissions. More data analysis at NUIST indicates that two cloud layers appear before the precipitation and merge into one thick cloud layer during the precipitation likely due to the impact of catalysis operation on the upper cloud. After the precipitation, the number concentration of aerosols with a diameter lower than 300 nm reduces significantly, the mass concentration of particulate matter with an aerodynamic diameter less than 2.5 μm decreases by about 39%, and the mass concentrations of nitrogen dioxide, sulfur dioxide, and carbon monoxide also decrease in different degrees. These results indicate that it is effective to reduce air pollutants by artificial precipitation enhancement. More studies are needed in the future.

Plants utilize delicate mechanisms to effectively respond to changes in the availability of nutrients such as iron. The responses to iron status involve controlling gene expression at multiple levels. The regulation of iron deficiency response by a network of transcriptional regulators has been extensively studied and recent research has shed light on post-translational control of iron homeostasis. Although not as considerably investigated, an increasing number of studies suggest that histone modification and DNA methylation play critical roles during iron deficiency and contribute to fine-tuning iron homeostasis in plants. This review will focus on the current understanding of chromatin-based regulation on iron homeostasis in plants highlighting recent studies in Arabidopsis and rice. Understanding iron homeostasis in plants is vital, as it is not only relevant to fundamental biological questions, but also to agriculture, biofortification, and human health. A comprehensive overview of the effect and mechanism of chromatin-based regulation in response to iron status will ultimately provide critical insights in elucidating the complexities of iron homeostasis and contribute to improving iron nutrition in plants.

This study presents a system-level optimization of spectroscopic photoacoustic (PA) imaging for prostate cancer (PCa) detection in three folds. First, we present a spectral unmixing model to segregate spectral system error (SSE). We constructed two noise models (NMs) for the laser spectrotemporal fluctuation and the ultrasound system noise. We used these NMs in linear spectral unmixing to denoise and to achieve high temporal resolution. Second, we employed a simulation-aided wavelength optimization to select the most effective subset of wavelengths. NMs again were considered so that selected wavelengths were not only robust to the collinearity of optical absorbance, but also to noise. Third, we quantified the effect of frame averaging on improving spectral unmixing accuracy through theoretical analysis and numerical validation. To validate the whole framework, we performed comprehensive studies in simulation and an in vivo experiment which evaluated prostate-specific membrane antigen (PSMA) expression in PCa on a mice model. Both simulation analysis and in vivo studies confirmed that the proposed framework significantly enhances image signal-to-noise ratio (SNR) and spectral unmixing accuracy. It enabled more sensitive and faster PCa detection. Moreover, the proposed framework can be generalized to other spectroscopic PA imaging studies for noise reduction, wavelength optimization, and higher temporal resolution.

BackgroundVaccine hesitancy was found in couples seeking artificial reproductive technology (ART) services. As the main vaccine used in China, investigations into the influence of inactivated coronavirus disease 2019 (COVID-19) vaccines on human fertility is needed.MethodsThis retrospective cohort study included data on COVID-19 vaccination, clinical characteristics, and reproductive outcome of 1,000 intrauterine insemination (IUI) cycles in 653 couples from March 2021 to March 2022 in a single university hospital-based center for reproductive medicine. The IUI cycles were divided into two categories based on sperm source, including 725 cycles in 492 women undergoing artificial insemination with their husband's sperm (AIH) and 275 cycles in 161 women undergoing artificial insemination with donor sperm (AID). Women were then divided into two groups. The vaccine exposed group included women vaccinated prior to insemination and the unexposed group included women who were not vaccinated or vaccinated after insemination. Reproductive outcomes including ongoing pregnancy rate, clinical pregnancy rate, and miscarriage rate were assessed.ResultsInactivated COVID-19 vaccinated women prior to intrauterine insemination in AIH cycles have comparable ongoing pregnancy rate (11.1 vs. 10.3%, P = 0.73), clinical pregnancy rate (12.5 vs. 11.3%, P = 0.60) as compared with unvaccinated counterparts. Similarly, there were no significant differences in ongoing pregnancy rate (20.9 vs. 28.1%, P = 0.17), clinical pregnancy rate (21.7 vs. 28.8%, P = 0.19) between vaccine exposed and unexposed groups in AID cycles. Multivariable logistic regression analyses showed that inactivated COVID-19 vaccination status cannot independently influence the reproductive outcomes of AIH and AID cycles. Subgroup analysis of vaccine exposed cycles showed that doses of vaccination and Interval between the last dose of vaccination and insemination have no influence on the reproductive outcomes of AIH cycles.ConclusionsNo negative effects were found on female fertility in IUI cycles following exposure to the inactivated COVID-19 vaccine. These findings indirectly reflect the safety of inactivated COVID-19 vaccine toward reproductive health and help to mitigate vaccine hesitancy among people planning to conceive.

Megalurothrips usitatus (Bagnall) is a destructive pest of legumes, such as cowpea. The biology, population dynamics and control strategies of this pest have been well studied. However, the lack of a high-quality reference genome for M. usitatus has hindered the understanding of key biological questions, such as the mechanism of adaptation to feed preferentially on high-protein host plants and the resistance to proteinase inhibitors (PIs). In this study, we generated a high-resolution chromosome-level reference genome assembly (247.82 Mb, 16 chromosomes) of M. usitatus by combining Oxford Nanopore Technologies (ONT) and Hi-C sequencing. The genome assembly showed higher proportions of GC and repeat content compared to other Thripinae species. Genome annotation revealed 18,624 protein-coding genes, including 4613 paralogs that were preferentially located in TE-rich regions. GO and KEGG enrichment analyses of the paralogs revealed significant enrichment in digestion-related genes. Genome-wide identification uncovered 506 putative digestion-related enzymes; of those, proteases, especially their subgroup serine proteases (SPs), are significantly enriched in paralogs. We hypothesized that the diversity and expansion of the digestion-related genes, especially SPs, could be driven by mobile elements (TEs), which promote the adaptive evolution of M. usitatus to high-protein host plants with high serine protease inhibitors (SPIs). The current study provides a valuable genomic resource for understanding the genetic variation among different pest species adapting to different plant hosts.

Abstract Background During the coronavirus disease 2019 (COVID-19) epidemic, due to the traffic blockade and the shortage of medical resources, more and more premature infants could not receive timely and effective ROP screening, which delayed treatment and even caused children blindness. Therefore, how to carry out ROP screening safely and effectively during the epidemic was very important and urgent. This study aimed to evaluate the safety and feasibility of ROP screening assisted by telemedicine network during COVID-19 outbreak. Methods This retrospective study was conducted at Wuhan Children’s hospital in Wuhan, China, from January to October, 2020. The measures which were performed to make the ROP screening more safe and effective were summarized and the comparison between ROP screening assisted by telemedicine network in 2020 and usual screening in 2019 were analyzed. Results A total of 267 outpatient infants completed ROP screening. The median gestational age was 32 weeks (30w to 34w) and the median birth weight was 1780 g (1460 g to 2100 g). Meanwhile, 149 (55.8%) out of 267 infants were males. During January to May in 2020, 86 screening appointments were received, among which 67 (77.9%) were from telemedicine platform online. The completing percentage of total online ROP appointments was higher than that of total face-to-face appointments (58.1% VS 22. 1%, P = 0.018). As for the number of infants screened between 2020 and 2019 from Februaryto October, 54 infants completed ROP screening in 2020, which was higher than that (51participants) in 2019 on September. Furthermore, compared with the usual screening in 2019, ROP screening assisted by telemedicine network in 2020 had smaller gestational age (32w VS 33w, p

Abstract Background Although preimplantation genetic test (PGT) has been used worldwide, few studies investigated the effect of trophectoderm biopsy of blastocysts on early embryo development. This study aimed to investigate whether trophectoderm (TE) biopsy of blastocysts for a PGT affected serum β-human chorionic gonadotropin (hCG) levels 14 days after transfer. Methods This was a retrospective cohort study conducted at the Third Affiliated Hospital of Guangzhou Medical University. The study population comprised pregnant women undergoing the transfer of single vitrified-warmed blastocysts after PGT between January 1, 2018, and July 30, 2020. The control group had non-PGT cycles with other inclusion criteria identical to those for the study group. Propensity score matching was used to screen a group of patients so that the baseline characteristics were similar between the two groups. Serum β-hCG levels were compared between the PGT and non-PGT cycles. Multiple linear regression was used to analyze the influence of PGT on serum β-hCG levels, while receiver operating characteristic curves (ROC curves) were plotted to predict pregnancy outcomes using serum β-hCG levels. Results Serum β-hCG levels were comparable between the PGT and non-PGT patients: live birth: 2503 ± 1702 mIU/mL vs 2266 ± 1289 mIU/mL (P = 0.219); clinical pregnancy: 2261 ± 1564 mIU/mL vs 2148 ± 1348 mIU/mL (P = 0.461); and ongoing pregnancy: 2412 ± 1589 mIU/mL vs 2278 ± 1308 mIU/mL (P = 0.422). Multiple linear regression analysis indicated no impact of PGT on the serum β-hCG level (standardized coefficient = − 0.001, P = 0.989). For clinical pregnancy, the cutoff value was 482 mIU/mL and 302 mIU/mL for PGT and non-PGT patients, respectively. The threshold to predict live birth was 1345 mIU/mL and 1621 mIU/mL in the PGT and non-PGT cycles, respectively. Conclusion Trophectoderm biopsy of blastocysts for PGT did not affect the serum β-hCG level 14 days after transfer.

Abstract Background Anticentromere antibody (ACA) is a member of the antinuclear antibody (ANA) family, and recent studies have found that ACA may be associated with oocyte maturation disorders; however, the possible mechanism behind this phenomenon remains unknown. We conducted this study to investigate whether ACA could penetrate into the living oocytes and interfere with oocyte meiosis in a mouse model. Methods We divided mice into three groups: human recombinant centromere protein-A (human CENP-A, HA) and complete Freund’s adjuvant (CFA) were used to immunize mice for the study group (HA + CFA), and mice injected with CFA (CFA group) or saline (Saline group), respectively, served as controls. After immunization, serum anti-CENP-A antibody was detected by indirect immunofluorescence assay (IIFT) and enzyme-linked immunosorbent assay (ELISA). Chromosome alignment and intracellular IgG localization in MI- and MII-stage oocytes were investigated by immunofluorescence analysis. Results Positive ACAs were successfully induced by immunization with CENP-A and CFA, and results showed that the serum level of anti-CENP-A antibody was significantly higher in the HA + CFA group compared with the control groups. There was marked increase of chromosome misalignments in MI and MII oocytes in the HA + CFA group compared to the control groups. However, no oocytes from any of the three groups showed intracellular antibody immunofluorescence. Conclusions The development and maturation of oocytes were impaired in peripheral ACA positive mice, which exhibited severe chromosomal misalignments in metaphase meiosis; however, no evidence of ACAs entering the oocytes was observed, thus the underlying mechanism needs further exploration.

Multivariate count data are often modeled via a multivariate Poisson distribution, but it contains an underlying, constraining assumption of data equi-dispersion (where its variance equals its mean). Real data are oftentimes over-dispersed and, as such, consider various advancements of a negative binomial structure. While data over-dispersion is more prevalent than under-dispersion in real data, however, examples containing under-dispersed data are surfacing with greater frequency. Thus, there is a demonstrated need for a flexible model that can accommodate both data types. We develop a multivariate Conway–Maxwell–Poisson (MCMP) distribution to serve as a flexible alternative for correlated count data that contain data dispersion. This structure contains the multivariate Poisson, multivariate geometric, and the multivariate Bernoulli distributions as special cases, and serves as a bridge distribution across these three classical models to address other levels of over- or under-dispersion. In this work, we not only derive the distributional form and statistical properties of this model, but we further address parameter estimation, establish informative hypothesis tests to detect statistically significant data dispersion and aid in model parsimony, and illustrate the distribution’s flexibility through several simulated and real-world data examples. These examples demonstrate that the MCMP distribution performs on par with the multivariate negative binomial distribution for over-dispersed data, and proves particularly beneficial in effectively representing under-dispersed data. Thus, the MCMP distribution offers an effective, unifying framework for modeling over- or under-dispersed multivariate correlated count data that do not necessarily adhere to Poisson assumptions.

Recently, recommender systems based on Graph Convolution Network (GCN) have become a research hotspot, especially in collaborative filtering. However, most GCN-based models have inferior embedding propagation mechanism, leading to low information extraction efficiency. Besides, the existing methods suffer from high computational complexity for large user-item interaction graphs. In order to solve the above problems, we propose LII-GCCF that integrates Linear transformation, Initial residual and Identity mapping into the Graph Convolutional Collaborative Filtering model. First, initial residual and identity mapping are applied to optimize the information propagation of graph convolution, which privide abundant interaction and alleviate information loss problem. Second, LII-GCCF removes the unnecessary nonlinear transformation based on the characteristics of collaborative filtering to simplify the graph convolution process. Comprehensive experiments are conducted on two public datasets, and the results demonstrate that LII-GCCF has a significant improvement over other state-of-the-art methods.

Abstract Background Although prior work has attempted to predict pregnancy outcomes by assaying serum β-hCG levels after blastocyst transfer, no study has focused on pregnancy outcomes in those with initially low serum β-hCG levels. This study sought to investigate pregnancy outcomes of patients with low serum β-hCG levels 14 days after blastocyst transfer. Methods A retrospective study was conducted at the Third Affiliated Hospital of Guangzhou Medical University to study patients whose serum β-hCG levels were at 5–299 mIU/ml 14 days after frozen blastocyst transfer. Rates of live birth, early miscarriage, biochemical pregnancy loss and ectopic pregnancy were analyzed according to the female patients’ age by Chi-squared analysis. Receiver operating characteristic (ROC) curves were plotted to explore the threshold of predicting clinical pregnancy and live births. Results 312 patients had serum β-hCG levels 58.8 mIU/ml, luteal phase support should continue. Another serum β-hCG test and ultrasound should be performed one week later. When an initial serum β-hCG is

PIWI-interacting RNAs (piRNAs) are a novel type of small non-coding RNAs (sncRNAs), which are 26–31 nucleotides in length and bind to PIWI proteins. Although piRNAs were originally discovered in germline cells and are thought to be essential regulators for germline preservation, they can also influence gene expression in somatic cells. An increasing amount of data has shown that the dysregulation of piRNAs can both promote and repress the emergence and progression of human cancers through DNA methylation, transcriptional silencing, mRNA turnover, and translational control. Digestive cancers are currently a major cause of cancer deaths worldwide. piRNAs control the expression of essential genes and pathways associated with digestive cancer progression and have been reported as possible biomarkers for the diagnosis and treatment of digestive cancer. Here, we highlight recent advances in understanding the involvement of piRNAs, as well as potential diagnostic and therapeutic applications of piRNAs in various digestive cancers.

Adjusting the sowing dates of crops is an effective measure for adapting them to climate change, but very few studies have explained how the optimum sowing dates can be determined. In this study, we used the sowing date field data from 2018 to 2021 from Hebei Gucheng Agricultural Meteorology National Observation and Research Station to analyze the effects of the sowing date on growth, development, and yield of maize, and to quantify the impact of light-temperature potential productivity on different stages of the yield formation. The results showed that delayed sowing decreased the vegetative growth period (VGP) and increased the reproductive growth period (RGP) of maize. The light-temperature potential productivity of the whole growth (WG) period had an exponential relationship with the theoretical yield. At least 14,614.95 kg ha−1 of light-temperature potential productivity was needed to produce grain yield. The maximum theoretical yield was approximately 18,052.56 kg ha−1, as indicated by the curve simulation results. The influence of light-temperature potential productivity on theoretical yield was as follows: VGP > RGP > vegetative and reproductive period (VRP). Accordingly, a method for determining the sowing time window based on VGP was established, and the optimal sowing dates were estimated for 1995–2021 and the SSP2-4.5 scenario in CMIP6 in the middle of this century (2030–2060). The simulation results showed that the optimum sowing date of maize “Lianyu 1” at the study site was 20–25 May in 1995–2021. In the middle of this century, the optimal sowing time of maize was ahead of schedule and the suitable sowing window was increased slightly. We conclude that advancing the sowing date of maize is a practical strategy for enhancing yield in the context of climate warming, and this strategy will provide a meaningful reference for scientific optimization of sowing dates to adapt maize to climate change.

The citrus red mite, Panonychus citri (McGregor), is an important pest of citrus in China, where pesticides are commonly used in citrus orchards. In order to reduce the use of chemical pesticides against P. citri and the development of resistance, the screening of biological control agents has attracted the attention of students. In this study, seven plant essential oils with high toxicity were selected from 40 plant essential oils by the leaf-dip bioassay, including plant essential oils of lemongrass, patchouli, juniper berry, sage, clove, frankincense, and citrus. The LC50 after 72 h treatment were 3.198 μL/mL, 8.312 μL/mL, 3.244 μL/mL, 6.701 μL/mL, 8.350 μL/mL, 21.953 μL/mL, and 8.788 μL/mL, respectively. According to the LT50, the essential oils’ acute toxicity to P. citri from high to low were lemongrass, juniper berry, patchouli, citrus, sage, vetiver, and frankincense essential oils. In general, lemongrass and juniper berry essential oils have the best acaricidal effect and have high application value for the biological control of P. citri, which provides a basis for the development of botanical acaricides.

BackgroundNo studies have been done to examine the efficacy of IVF and intrauterine insemination (IUI) for the treatment of young patients with unexplained infertility and low ovarian reserve, although it is becoming an increasingly significant indication for in-vitro fertilization (IVF). The goal of this research was to compare the efficacy of IVF with IUI on Poseidon group 3 patients with unexplained infertility (PG3&UI).MethodsThis was a retrospective analysis of PG3&UI patients who had IVF/intracytoplasmic sperm injection (ICSI) or IUI at the Third Affiliated Hospital of Guangzhou Medical University between January 1, 2015, and March 31, 2021. To equalize the baseline characteristics of the IVF/ICSI and IUI groups, propensity score matching (PSM) was utilized. Intention-to-treat (ITT) and per-protocol (PP) analyses were used to compare the differences in live births. To discover variations in time to biochemical pregnancy leading to live birth, Kaplan-Meier curves were produced. To evaluate the expenses per live birth between two procedures, a cost-effective analysis was done.ResultsAccording to ITT analysis, the live birth rate for the IVF/ICSI group was substantially higher than the cumulative live birth rate (CLBR) for the IUI group (22.6% (38/168) vs. 11.3% (19/168), RR 2.00, 95% CI 1.20-3.32, P = 0.006). In the PP analysis, the live birth rate was 23.0% (38/165) in the IVF/ICSI group and 11.7% (19/162) in the IUI group (RR = 1.96, 95% CI 1.18-3.26, P = 0.007). When censored at 365 days, the Kaplan-Meier analysis revealed that the IVF/ICSI group had a higher live birth rate than the IUI group (log-rank test χ²= 6.025; P = 0.014). However, when the two groups were censored at 180 days, the live birth rates were not substantially different (log-rank test χ²= 3.847; P = 0.05). The number of hospital visits per live birth in the IUI group was higher than in the IVF/ICSI group (85 vs. 48). The overall cost of a live birth was comparable across the two groups (¥132242 vs. ¥131611), while the medical expenses for a live delivery from IVF/ICSI were higher than those from IUI (¥118955 vs. ¥108279).ConclusionsThe livebirth rate per IVF/ICSI cycle with at most one embryo transfer is higher than the CLBR of IUI, with fewer hospital visits and similar expenses.

Cacopsylla citrisuga (Yang & Li) is an important pest-threatening Citrus and Poncirus plants (Rutaceae) and a newly identified insect vector of citrus Huanglongbing. The complete mitochondrial genome of C. citrisuga was 14,906 bp in length, with 37 genes, including 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), two ribosomal RNA genes (rRNAs). The phylogenetic trees inferred from Bayesian inference and maximum likelihood analyses confirmed C. citrisuga as a member of the genus Cacopsylla. Our phylogenetic analyses suggested that the Cacopsylla is paraphyletic, and confirmed C. citrisuga as a member of clade-I under Cacopsylla. The complete mitochondrial genome of C. citrisuga will provide important information for the phylogeny and evolution analysis of Cacopsylla.

Our previous study found that CpG oligodeoxynucleotides 1826 (CpG 1826), combined with mucin 1 (MUC1)-maltose-binding protein (MBP) (M-M), had certain antitumor activity. However, this combination is less than ideal for tumor suppression (tumors vary in size and vary widely among individuals), with a drawback being that CpG 1826 is unstable. To solve these problems, here, we evaluate MF59/CpG 1826 as a compound adjuvant with M-M vaccine on immune response, tumor suppression and survival. The results showed that MF59 could promote the CpG 1826/M-M vaccine-induced tumor growth inhibition and a Th1-prone cellular immune response, as well as reduce the individual differences of tumor growth and prolonged prophylactic and therapeutic mouse survival. Further research showed that MF59 promotes the maturation of DCs stimulated by CpG1826/M-M, resulting in Th1 polarization. The possible mechanism is speculated to be that MF59 could significantly prolong the retention time of CpG 1826, or the combination of CpG 1826 and M-M, as well as downregulate IL-6/STAT3 involved in MF59 combined CpG 1826-induced dendritic cell maturation. This study clarifies the utility of MF59/CpG 1826 as a vaccine compound adjuvant, laying the theoretical basis for the development of a novel M-M vaccine.

Vehicular Ad-Hoc Networks (VANETs) have received a great attention recently due to their potential and various applications. However, the initial phase of the VANET has many research challenges that need to be addressed, such as the issues of security and privacy protection caused by the openness of wireless communication networks among the city-wide applied regions. Specially, anomaly detection for a VANET has become a challenging problem, due to the changes in the scenario of VANETs comparing with traditional wireless networks. Motivated by this issue, we focus on the problem of anomaly detection in VANETs, and propose an effective anomaly detection approach based on the convolutional neural network in this paper. The proposed approach takes into account the spatio-temporal and sparse features of VANET traffic, and it uses a convolutional neural network architecture and a loss function based on Mahalanobis distance to extract and estimate the traffic matrix. Then, reinforcement learning is used to implement anomaly detection. Furthermore, a comprehensive assessment is provided to validate the proposed approach, which illustrates the effectiveness of this approach.

Stress equilibrium time is an important index to judge the homogeneity of rocks. In order to study the relationship between stress equilibrium time and crushing energy consumption before rock destruction, Hopkinson tests were conducted on granite specimens with different length-to-diameter ratios. In this paper, by studying the size and strain rate effects of rocks, five different sizes of granite specimens with different aspect ratios were prepared and Hopkinson impact tests were conducted under four strain rate conditions. Data analysis and processing using the three-wave method to investigate the stress uniformity of granite specimens under impact loading. The energy balance factor was introduced to compare and analyze the stress equilibrium time of five kinds of long-diameter granite specimens, and it was found that the stress equilibrium time of rocks with the same length–diameter ratio decreased with the increase of loading strain rate, while the granite specimens with length–diameter ratio of 0.8 showed a better stress equilibrium time. In order to better find the aspect ratio and loading strain rate that can crush better and maintain a long equilibrium time, the energy consumption of rock crushing is further analyzed. The energy dissipation of granite specimens with loading strain rate of 156.8 s−1 and 253.2 s−1 was found to be more concentrated, and the energy dissipation rate was stable at about 48%. Subsequently, the relationship between stress equilibrium time and energy dissipation was established, and it was proved that the fastest growing time period of the energy dissipation curve was approximately equal to the rock stress equilibrium time, while the length-to-diameter ratio of the granite specimen that could better maintain the stress uniformity before rock crushing was 0.8 and the loading strain rate was 156.8 s−1.

Endometrial cancer (EC) is a common leading cause of cancer-related death in women, which is associated with the increased level of estrogen in the body. Artesunate (ART), an active compound derived from Artemisia annua L., exerted antitumor properties in several cancer types. However, the role of artesunate and the molecular basis on EC remains unclear. Here, we aimed to explore the effects and mechanisms of artesunate. Our results identified that estrogen receptor-α (ER-α) was a key factor for the type I EC (ER-α-positive), which might suppress the downstream LKB1/AMPK/mTOR pathway. Besides, we found ART significantly inhibited tumor proliferation in a dose-dependent manner. Mechanistic studies identified that ART led to tumor cell apoptosis and cell cycle arrest by downregulating the ER-α expression and activating the LKB1/AMPK/mTOR pathway. In addition, we found ART could increase the expression of heart and neural crest derivatives expressed 2 (HAND2) in the ER-α-positive EC cells, which could interact with ER-α. Through the gain-and loss-function experiments, we showed that over expression of HAND2 repressed the proliferation and migration of ER-α-positive EC cells via inhibition of ER-α expression. HAND2 knockdown increased ER-α expression and alleviated the antitumor effect of ART in vitro and in vivo. Overall, our study first showed that ART could be an effective antitumor agent through modulating ER-α-mediated LKB1/AMPK/mTOR pathway in the HAND2 dependent manner. Our findings provide an effective therapeutic agent for ER-α-positive EC treatment.

Extracellular microRNAs (miRNAs) have been proposed to function in cross-kingdom gene regulation. Among these, plant-derived miRNAs of dietary origin have been reported to survive the harsh conditions of the human digestive system, enter the circulatory system, and regulate gene expression and metabolic function. However, definitive evidence supporting the presence of plant-derived miRNAs of dietary origin in mammals has been difficult to obtain due to limited sample sizes. We have developed a bioinformatics pipeline (ePmiRNA_finder) that provides strident miRNA classification and applied it to analyze 421 small RNA sequencing data sets from 10 types of human body fluids and tissues and comparative samples from carnivores and herbivores. A total of 35 miRNAs were identified that map to plants typically found in the human diet and these miRNAs were found in at least one human blood sample and their abundance was significantly different when compared to samples from human microbiome or cow. The plant-derived miRNA profiles were body fluid/tissue-specific and highly abundant in the brain and the breast milk samples, indicating selective absorption and/or the ability to be transported across tissue/organ barriers. Our data provide conclusive evidence for the presence of plant-derived miRNAs as a consequence of dietary intake and their cross-kingdom regulatory function within human circulating system.

This paper aims to fully tap the value of the tourism brand of Changbai Mountains scenic area, give play to the radiation effect of the brand, and create the Greater Changbai Mountains (GCM) tourist area, thereby enhancing the coordinated development of regional tourism. Specifically, symbiosis correlation and symbiosis density were adopted to recognize the tourism symbiosis units in the core region of GCM tourist area, and an evaluation model was established for the tourism symbiosis quality in the core region of GCM tourist area. Based on the evaluation results, the places within the core region were divided into multiple levels. The results show that the core region of GCM tourist area covers Yanji City, Dunhua City, Hunchun City, Antu County, Baishan City, Fusong County, Changbai County, and Tonghua City, and these places fall on three different development levels.