Puerarin-Loaded Liposomes Co-Modified by Ischemic Myocardium-Targeting Peptide and Triphenylphosphonium Cations Ameliorate Myocardial Ischemia-Reperfusion Injury.

Purpose: Mitochondrial damage may lead to uncontrolled oxidative stress and massive apoptosis, and thus plays a pivotal role in the pathological processes of myocardial ischemia-reperfusion (I/R) injury. However, it is difficult for the drugs such as puerarin (PUE) to reach the mitochondrial lesion due to lack of targeting ability, which seriously affects the expected efficacy of drug therapy for myocardial I/R injury. Methods: We prepared triphenylphosphonium (TPP) cations and ischemic myocardium-targeting peptide (IMTP) co-modified puerarin-loaded liposomes (PUE@T/I-L), which effectively deliver the drug to mitochondria and improve the effectiveness of PUE in reducing myocardial I/R injury. Results: In vitro test results showed that PUE@T/I-L had sustained release and excellent hemocompatibility. Fluorescence test results showed that TPP cations and IMTP double-modified liposomes (T/I-L) enhanced the intracellular uptake, escaped lysosomal capture and promoted drug targeting into the mitochondria. Notably, PUE@T/I-L inhibited the opening of the mitochondrial permeability transition pore, reduced intracellular reactive oxygen species (ROS) levels and increased superoxide dismutase (SOD) levels, thereby decreasing the percentage of Hoechst-positive cells and improving the survival of hypoxia-reoxygenated (H/R)-injured H9c2 cells. In a mouse myocardial I/R injury model, PUE@T/I-L showed a significant myocardial protective effect against myocardial I/R injury by protecting mitochondrial integrity, reducing myocardial apoptosis and decreasing infarct size. Conclusion: This drug delivery system exhibited excellent mitochondrial targeting and reduction of myocardial apoptosis, which endowed it with good potential extension value in the precise treatment of myocardial I/R injury.

Identification and Full-Length Sequence Analysis of a Novel Recombinant Goat Astrovirus Genotype in Guangxi, China.

Astroviruses are single-stranded, positive-sense RNA viruses capable of infecting humans as well as a wide range of mammalian and avian species, with a length of approximately 6.6-7.7 kb. In this study, 139 goat fecal samples collected from the Guangxi province were used for the RT-PCR detection, and two of these were positive for goat astrovirus, with a positivity rate of 1.44% (2/139). The complete genome sequence of an astrovirus strain and the partial genome sequence of a strain astrovirus, named GX WZ 2023 and GX HC 2023, were amplified and sequenced, and their sequence lengths were 6284 nt and 6213 nt, respectively. Among them, the capsid protein of goat astrovirus GX HC 2023 showed the highest amino acid identity of 95.9% with ovine astrovirus GX, which belonged to the MAstV-2 genotype. However, the closest relative of the GX WZ 2023 strain was found to be the caprine astrovirus Sichuan, with a nucleotide sequence identity of 76.8%. The ORF1ab nonstructural protein of this strain showed the highest amino acid identities of 89.2 and 95.8% with the ovine astrovirus S5.1 and caprine astrovirus G5.1 strains, respectively. However, its ORF2 capsid protein has 68.4% amino acid identity with the bovine astrovirus (BAstV) 16 2021 CHN strain and only 21.9-64% amino acid identity with all available strains of goat astrovirus. The GX WZ 2023 strain was recombined with the Chinese (BAstV 16 2021 CHN) and Japanese bovine strains (BAstV JPN 2015) in the ORF2 region. Therefore, the goat astrovirus GX WZ 2023 is proposed as a new member of the family goat astroviridae based on the species classification criteria of the International Committee on Taxonomy of Viruses. These findings enhance our understanding of the prevalence and genetic evolution of goat astrovirus and provide a scientific basis for future studies of these viruses in other animals.

Lymphocyte-C-reactive protein ratio combined with albumin upon admission predicts coronary artery dilation and aneurysm formation in pediatric patients with Kawasaki disease: a retrospective cohort study.

BACKGROUND: We aimed to explore simple and effective clinical parameters or combinations to predict coronary artery dilation and aneurysm formation in pediatric patients with Kawasaki disease (KD). DESIGN AND METHODS: This retrospective cohort study included pediatric patients with KD from January, 2013 to December, 2022. Multiple demographic and clinical data were collected, collated, and calculated from the medical records. Then they were divided into the coronary artery dilation and aneurysm formation group or the non-coronary artery dilation and aneurysm formation group. Lymphocyte-C-reactive protein ratio (LCR) was transformed into its natural logarithm and expressed as lnLCR. RESULTS: A total of 64 pediatric patients with KD were enrolled in this cohort study after 1:3 propensity score matching (PSM). For each unit increase in lnLCR, the possibility of coronary artery dilation and aneurysm formation decreased to 0.419 times the original value. The areas under the receiver operating characteristic (ROC) curves of lnLCR combined with albumin (ALB), ALB, and lnLCR to classify pediatric patients with KD into the coronary artery dilation and aneurysm formation group were 0.781, 0.692, and 0.743, respectively. CONCLUSION: LCR combined with ALB upon admission is a promising predictor of coronary artery dilation and aneurysm formation in pediatric patients with KD.

The improved stratified transformer for organ segmentation of Arabidopsis.

Segmenting plant organs is a crucial step in extracting plant phenotypes. Despite the advancements in point-based neural networks, the field of plant point cloud segmentation suffers from a lack of adequate datasets. In this study, we addressed this issue by generating Arabidopsis models using L-system and proposing the surface-weighted sampling method. This approach enables automated point sampling and annotation, resulting in fully annotated point clouds. To create the Arabidopsis dataset, we employed Voxel Centroid Sampling and Random Sampling as point cloud downsampling methods, effectively reducing the number of points. To enhance the efficiency of semantic segmentation in plant point clouds, we introduced the Plant Stratified Transformer. This network is an improved version of the Stratified Transformer, incorporating the Fast Downsample Layer. Our improved network underwent training and testing on our dataset, and we compared its performance with PointNet++, PAConv, and the original Stratified Transformer network. For semantic segmentation, our improved network achieved mean Precision, Recall, F1-score and IoU of 84.20, 83.03, 83.61 and 73.11%, respectively. It outperformed PointNet++ and PAConv and performed similarly to the original network. Regarding efficiency, the training time and inference time were 714.3 and 597.9 ms, respectively, which were reduced by 320.9 and 271.8 ms, respectively, compared to the original network. The improved network significantly accelerated the speed of feeding point clouds into the network while maintaining segmentation performance. We demonstrated the potential of virtual plants and deep learning methods in rapidly extracting plant phenotypes, contributing to the advancement of plant phenotype research.

Construction of an effective method combining in situ capping with electric field-enhanced biodegradation for treating PAH-contaminated soil at abandoned coking sites.

The simultaneous application of in situ capping and electro-enhanced biodegradation may be a suitable method for ensuring the feasibility and safety of reusing abandoned coking sites. However, the capping layer type and applied electric field pattern may affect the efficiency of sequestering and removing pollutants. This study investigated changes in electric current, soil moisture content and pH, polycyclic aromatic hydrocarbon (PAH) concentration, bacterial number, and microbial community structure and metabolic function during soil remediation at abandoned coking plant sites under different applied electric field patterns and barrier types. The results indicated that polarity-reversal electric field was more conducive to maintaining electric current, soil properties, resulting in higher microbial number, community diversity, and functional gene abundance. At 21d, the mean PAH concentrations in contaminated soil, the capping layer's clean soil and barrier were 78.79, 7.56, and 1.57 mg kg-1 lower than those with a unidirectional electric field, respectively. The mean degradation rate of PAHs in the bio-barrier was 10.12 % higher than that in the C-Fe barrier. In the experiment combining a polarity-reversal electric field and a bio-barrier, the mean PAH concentrations in contaminated soil and the capping layer were 706.68 and 27.15 mg kg-1 lower than those in other experiments, respectively, and no PAHs were detected in the clean soil, demonstrating that the combination of the polarity-reversal electric field and the bio-barrier was effective in treating soil at abandoned coking plant sites. The established method of combining in situ capping with electro-enhanced biodegradation will provide technical support for the treatment and reuse of heavily PAH-contaminated soil at abandoned coking plant sites.

Multiple delivery strategies of nanocarriers for myocardial ischemia-reperfusion injury: current strategies and future prospective.

Acute myocardial infarction, characterized by high morbidity and mortality, has now become a serious health hazard for human beings. Conventional surgical interventions to restore blood flow can rapidly relieve acute myocardial ischemia, but the ensuing myocardial ischemia-reperfusion injury (MI/RI) and subsequent heart failure have become medical challenges that researchers have been trying to overcome. The pathogenesis of MI/RI involves several mechanisms, including overproduction of reactive oxygen species, abnormal mitochondrial function, calcium overload, and other factors that induce cell death and inflammatory responses. These mechanisms have led to the exploration of antioxidant and inflammation-modulating therapies, as well as the development of myocardial protective factors and stem cell therapies. However, the short half-life, low bioavailability, and lack of targeting of these drugs that modulate these pathological mechanisms, combined with liver and spleen sequestration and continuous washout of blood flow from myocardial sites, severely compromise the expected efficacy of clinical drugs. To address these issues, employing conventional nanocarriers and integrating them with contemporary biomimetic nanocarriers, which rely on passive targeting and active targeting through precise modifications, can effectively prolong the duration of therapeutic agents within the body, enhance their bioavailability, and augment their retention at the injured myocardium. Consequently, these approaches significantly enhance therapeutic effectiveness while minimizing toxic side effects. This article reviews current drug delivery systems used for MI/RI, aiming to offer a fresh perspective on treating this disease.

Meta-analysis of the effectiveness and safety of Xingnaojing and naloxone in the treatment of carbon monoxide poisoning.

BACKGROUND: To evaluate the effectiveness and safety of Xingnaojing combined with naloxone in the treatment of carbon monoxide poisoning. METHODS: By retrieving the literatures published in the databases of PubMed, Cochrane Library, Web of Science, Embase, Wanfang Database, Weipu Database, and China National Knowledge Infrastructure from January 2010 to September 2021, the data of randomized controlled trials (RCTs) of Xingnaojing combined with naloxone in the treatment of carbon monoxide poisoning were extracted. The methodological quality of the included RCTs was evaluated by using the tools of bias risk evaluation of Cochrane Collaboration, and the data were statistically analyzed by using RevMan 5.3 software. RESULTS: A total of 20 literatures were included, involving in 771 cases treated by Xingnaojing combined with naloxone and 761 cases in the control group. The effective rate of the experimental group is higher than that of the control group [risk ratio (RR) = 1.20, 95% confidence interval (CI) (1.14, 1.26)]. The average awake time (STD mean difference = -2.08, 95% CI [-2.60, -1.56]), physical recovery time (STD mean difference = -2.94, 95% CI [-3.59, -2.28]), delayed encephalopathy (RR = 0.44, 95% CI [0.31, 0.62]), and adverse reactions (RR = 0.23, 95% CI [0.10, 0.54]) was lower than that of the control group. CONCLUSION: Xingnaojing combined with naloxone in the treatment of carbon monoxide poisoning is significantly superior to naloxone, but it still needs to be further verified by high-quality large samples of RCTs.

Effect of electric fields strength on soil factors and microorganisms during electro-bioremediation of benzo[a]pyrene-contaminated soil.

Electro-bioremediation is a promising technology for remediating soils contaminated with polycyclic aromatic hydrocarbons (PAHs). However, the resulting electrokinetic effects and electrochemical reactions may inevitably cause changes in soil factors and microorganism, thereby reducing the remediation efficiency. To avoid negative effect of electric field on soil and microbes and maximize microbial degradability, it is necessary to select a suitable electric field. In this study, artificial benzo [a]pyrene (BaP)-contaminated soil was selected as the object of remediation. Changes in soil factors and microorganisms were investigated under the voltage of 1.0, 2.0, and 2.5 V cm-1 using chemical analysis, real-time PCR, and high-throughput sequencing. The results revealed noticeable changes in soil factors (pH, moisture, electrical conductivity [EC], and BaP concentration) and microbes (PAHs ring-hydroxylating dioxygenase [PAHs-RHDα] gene and bacterial community) after the application of electric field. The degree of change was related to the electric field strength, with a suitable strength being more conducive to BaP removal. At 70 d, the highest mean extent of BaP removal and PAHs-RHDα gene copies were observed in EK2.0 + BIO, reaching 3.37 and 109.62 times those in BIO, respectively, indicating that the voltage of 2.0 V cm-1 was the most suitable for soil microbial growth and metabolism. Changes in soil factors caused by electric fields can affect microbial activity and community composition. Redundancy analysis revealed that soil pH and moisture had the most significant effects on microbial community composition (P < 0.05). The purpose of this study was to determine the appropriate electric field that could be used for electro-bioremediation of PAH-contaminated soil by evaluating the effects of electric fields on soil factors and microbial communities. This study also provides a reference for efficiency enhancement and successful application of electro-bioremediation of soil contaminated with PAHs.

Treatment of PAHs contaminated soil in abandoned industrial site using combined method of improved in situ capping and electrokinetic enhanced-bioremediation.

In situ capping and bioremediation are common technologies for treating contaminated soil at industrial sites. However, these two technologies have some shortcomings for treating soil heavily contaminated with organic matter, such as the limited adsorption in capping layer and the low biodegradation efficiency. This study proposed the method of an improved in situ capping combined with electrokinetic enhanced-bioremediation, and investigated its feasibility for treating heavily polycyclic aromatic hydrocarbons (PAHs) contaminated soil at an abandoned industrial site. By analyzing the changes in soil properties, PAHs concentration, and microbial community in experiments with voltages of 0, 0.8, 1.2, and 1.6 V cm-1, it was found that improved in situ capping could effectively sequester PAHs migration by adsorption and biodegradation, and electric field could enhance PAHs removal from contaminated soil and bio-barrier. In the experiments with electric field, soil environment under the voltage of 1.2 V cm-1 was more favorable for the growth and metabolism of microorganisms, and the residual PAHs concentrations (19.47 ± 0.76 mg kg-1 and 619.38 ± 20.05 mg kg-1) in the bio-barrier and contaminated soil of experiment with 1.2 V cm-1 were the lowest, which indicated that optimization of the electric field conditions could lead to better effects.

Enhanced protection against hypoxia/reoxygenation-induced apoptosis in H9c2 cells by puerarin-loaded liposomes modified with matrix metalloproteinases-targeting peptide and triphenylphosphonium.

Based on the inhibition of mitochondrial permeability transition pore (mPTP) opening, puerarin (PUE) has a good potential to reduce myocardial ischemia/reperfusion injury (MI/RI). However, the lack of targeting of free PUE makes it difficult to reach the mitochondria. In this paper, we constructed matrix metalloproteinase-targeting peptide (MMP-TP) and triphenylphosphonium (TPP) cation co-modified liposomes loaded with PUE (PUE@T/M-L) for mitochondria-targeted drug delivery. PUE@T/M-L had a favorable particle size of 144.9 ± 0.8 nm, an encapsulation efficiency of 78.9 ± 0.6%, and a sustained-release behavior. The results of cytofluorimetric experiments showed that MMP-TP and TPP double-modified liposomes (T/M-L) enhanced intracellular uptake, escaped lysosomal capture, and promoted drug targeting into mitochondria. In addition, PUE@T/M-L enhanced the viability of hypoxia-reoxygenation (H/R) injured H9c2 cells by inhibiting mPTP opening and reactive oxygen species (ROS) production, reducing Bax expression and increasing Bcl-2 expression. It was inferred that PUE@T/M-L delivered PUE into the mitochondria of H/R injured H9c2 cells, resulting in a significant increase in cellular potency. Based on the ability of MMP-TP to bind the elevated expression of matrix metalloproteinases (MMPs), T/M-L had excellent tropism for Lipopolysaccharide (LPS) -stimulated macrophages and can significantly reduce TNF-α and ROS levels, thus allowing both drug accumulation in ischemic cardiomyocytes and reducing inflammatory stimulation during MI/RI. Fluorescence imaging results of the targeting effect using a DiR probe also indicated that DiR@T/M-L could accumulate and retain in the ischemic myocardium. Taken together, these results demonstrated the promising application of PUE@T/M-L for mitochondria-targeted drug delivery to achieve maximum therapeutic efficacy of PUE.

Construction of SNP fingerprint and population genetic analysis of honeysuckle germplasm resources in China.

Introduction: The flower buds of Lonicera japonica Thunb. are widely used in Chinese medicine for their anti-inflammatory properties, and they have played an important role in the fight against SARS COVID-19 and other major epidemics. However, due to the lack of scientific and accurate variety identification methods and national unified standards, scattered and non-standardized management in flower bud production has led to mixed varieties that have caused significant difficulties in the cataloging and preservation of germplasm resources and the identification, promotion, and application of new L. japonica varieties. Methods: In this study, we evaluated the population structure, genetic relationships, and genetic fingerprints of 39 germplasm resources of Lonicera in China using simplified genome sequencing technology. Results: A total of 13,143,268 single nucleotide polymorphisms (SNPs) were identified. Thirty-nine samples of Lonicera were divided into four subgroups, and the population structure and genetic relationships among existing Lonicera germplasm resources were determined using principal component analysis, population structure analysis, and phylogenetic tree analysis. Through several stringent selection criteria, 15 additional streamlined, high-quality DNA fingerprints were filtered out of the validated 50 SNP loci and verified as being able to effectively identify the 39 Lonicera varieties. Discussion: To our knowledge, this is the first comprehensive study measuring the diversity and population structure of a large collection of Lonicera varieties in China. These results have greatly broadened our understanding of the diversity, phylogeny, and population structure of Lonicera. The results may enhance the future analysis of genetic diversity, species identification, property rights disputes, and molecular breeding by providing a scientific basis and reference data for these efforts.

Rapid, specific and sensitive detection of Vibrio parahaemolyticus in seafood by accelerated strand exchange amplification.

Vibrio parahaemolyticus infectious diseases caused by seafood contamination may be life-threatening to people with weak immunity. The detection of the Vibrio parahaemolyticus pathogen in aquatic foods is critical for reducing the outbreak of human Vibrio parahaemolyticus-associated diseases. In this study, a highly sensitive, specific, and time-saving real-time narrow thermal-cycling amplification detection method was developed based on accelerated strand exchange amplification (ASEA). It can detect cultured Vibrio parahaemolyticus at concentrations as low as 25 CFU mL-1. In addition, for artificially spiked scallop meat, the detection limit was 1.8 × 103 CFU g-1 without pre-culture and 18 CFU g-1 of initial inoculum after 3 h enrichment. The whole assay, starting from DNA extraction, can be completed within 20 min. The ASEA detection method established in this study is an effective tool for the rapid detection of Vibrio parahaemolyticus strains in a large number of seafood samples.

Large-scale genomic and transcriptomic profiles of rice hybrids reveal a core mechanism underlying heterosis.

BACKGROUND: Heterosis is widely used in agriculture. However, its molecular mechanisms are still unclear in plants. Here, we develop, sequence, and record the phenotypes of 418 hybrids from crosses between two testers and 265 rice varieties from a mini-core collection. RESULTS: Phenotypic analysis shows that heterosis is dependent on genetic backgrounds and environments. By genome-wide association study of 418 hybrids and their parents, we find that nonadditive QTLs are the main genetic contributors to heterosis. We show that nonadditive QTLs are more sensitive to the genetic background and environment than additive ones. Further simulations and experimental analysis support a novel mechanism, homo-insufficiency under insufficient background (HoIIB), underlying heterosis. We propose heterosis in most cases is not due to heterozygote advantage but homozygote disadvantage under the insufficient genetic background. CONCLUSION: The HoIIB model elucidates that genetic background insufficiency is the intrinsic mechanism of background dependence, and also the core mechanism of nonadditive effects and heterosis. This model can explain most known hypotheses and phenomena about heterosis, and thus provides a novel theory for hybrid rice breeding in future.

Evolution of different rice ecotypes and genetic basis of flooding adaptability in Deepwater rice by GWAS.

BACKGROUND: Rice is the world's second largest food crop and accelerated global climate change due to the intensification of human activities has a huge impact on rice. Research on the evolution of different rice ecotypes is essential for enhancing the adaptation of rice to the unpredictable environments. RESULTS: The sequencing data of 868 cultivated and 140 wild rice accessions were used to study the domestication history and signatures of adaptation in the distinct rice ecotypes genome. The different populations had formed distinct rice ecotypes by phylogenetic analyses and were domesticated independently in the two subspecies of rice, especially deepwater and upland rice. The domestication history of distinct rice ecotypes was confirmed and the four predicted admixture events mainly involved gene flow between wild rice and cultivated rice. Importantly, we identified numerous selective sweeps that have occurred during the domestication of different rice ecotypes and one candidate gene (LOC_Os11g21804) for deepwater based on transcriptomic evidence. In addition, many regions of genomic differentiation between the different rice ecotypes were identified. Furthermore, the main reason for the increase in genetic diversity in the ecotypes of xian (indica) rice was the high proportion of alternative allele frequency in new mutations. Genome-wide association analysis revealed 28 QTLs associated with flood tolerance which contained 12 related cloned genes, and 20 candidate genes within 13 deepwater QTLs were identified by transcriptomic and haplotype analyses. CONCLUSIONS: These results enhanced our understanding of domestication history in different rice ecotypes and provided valuable insights for genetic improvement and breeding of rice in the current changing environments.

A coarse-to-fine cascade deep learning neural network for segmenting cerebral aneurysms in time-of-flight magnetic resonance angiography.

BACKGROUND: Accurate segmentation of unruptured cerebral aneurysms (UCAs) is essential to treatment planning and rupture risk assessment. Currently, three-dimensional time-of-flight magnetic resonance angiography (3D TOF-MRA) has been the most commonly used method for screening aneurysms due to its noninvasiveness. The methods based on deep learning technologies can assist radiologists in achieving accurate and reliable analysis of the size and shape of aneurysms, which may be helpful in rupture risk prediction models. However, the existing methods did not accomplish accurate segmentation of cerebral aneurysms in 3D TOF-MRA. METHODS: This paper proposed a CCDU-Net for segmenting UCAs of 3D TOF-MRA images. The CCDU-Net was a cascade of a convolutional neural network for coarse segmentation and the proposed DU-Net for fine segmentation. Especially, the dual-channel inputs of DU-Net were composed of the vessel image and its contour image which can augment the vascular morphological information. Furthermore, a newly designed weighted loss function was used in the training process of DU-Net to promote the segmentation performance. RESULTS: A total of 270 patients with UCAs were enrolled in this study. The images were divided into the training (N = 174), validation (N = 43), and testing (N = 53) cohorts. The CCDU-Net achieved a dice similarity coefficient (DSC) of 0.616 ± 0.167, Hausdorff distance (HD) of 5.686 ± 7.020 mm, and volumetric similarity (VS) of 0.752 ± 0.226 in the testing cohort. Compared with the existing best method, the DSC and VS increased by 18% and 5%, respectively, while the HD decreased by one-tenth. CONCLUSIONS: We proposed a CCDU-Net for segmenting UCAs in 3D TOF-MRA, and the obtained results show that the proposed method outperformed other existing methods.

Selective and comparative genome architecture of Asian cultivated rice (Oryza sativa L.) attributed to domestication and modern breeding.

INTRODUCTION: Rice, Oryza sativa L. (Os), is one of the oldest domesticated cereals that has also gone through extensive improvement in modern breeding. OBJECTIVES: How rice was domesticated and impacted by modern breeding. METHODS: We performed comprehensive analyses of genomic sequences of 504 accessions of Os and 456 accessions of O. rufipogon/O. nivara (Or). RESULTS: The natural selection on Or before domestication and the natural and artificial selection during domestication together shaped the well-differentiated genomes of two subspecies, geng(j) (japonica) and xian(i) (indica), while breeding has made apparent genomic imprints between landrace and modern varieties of each subspecies, and also between primary modern and advanced modern varieties of xian(i). Selection during domestication and breeding left genome-wide selective signals covering âˆ¼ 22.8 % and âˆ¼ 8.6 % of the Os genome, significantly reduced within-population genomic diversity by âˆ¼ 22 % in xian(i) and âˆ¼ 53 % in geng(j) plus more pronounced subspecific differentiation. Only âˆ¼ 10 % reduction in the total genomic diversity was observed between the Os and Or populations, indicating domestication did not suffer severe genetic bottleneck. CONCLUSION: Our results revealed clear differentiation of the Or accessions into three large populations, two of which correspond to the well-differentiated Os subspecies, geng(j) and xian(i). Improved productivity and common changes in the same suit of adaptive traits in xian(i) and geng(j) during domestication and breeding resulted apparently from compensatory and convergent selections for different genes/alleles acting in the common KEGG terms and/or same gene families, and thus maintaining or even increasing the within population diversity and subspecific differentiation of Os, while more genes/alleles of novel function were selected during domestication than modern breeding. Our results supported the multiple independent domestication of Os in Asia and suggest the more efficient utilization of the rich diversity within Os by exploiting inter-subspecific and among population diversity in future rice improvement.

[Ecological Effects of Species Diversity on Plant Growth and Physico-Chemical Properties in a Pb-Zn Mine Tailings].

The remediation of metalliferous mine tailings remains a challenge in many regions of the world. A field experiment was conducted on representative Pb-Zn mine tailings with different species richness (1-, 4-, 8-, and 16-species) to evaluate the potential roles of species diversity in the phytoremediation of metalliferous mine tailings. The main results were ① high species diversity greatly enhanced vegetation cover and biomass. For example, the average vegetation cover and biomass were 33.4% and 66.7 g ·m-2 in 1-species plots and reached 78.4% and 183.8 g ·m-2 in 16-species plots, respectively. ② Plant species diversity had significant effects on nutrient accumulation. Total organic carbon (TOC), water organic carbon (SOC), total nitrogen (TN) and total phosphorus (TP) significantly increased with the species diversity (TOC:r=0.30,P<0.001; SOC:r=0.20,P<0.05; TN:r=0.24,P<0.05; TP:r=0.20,P<0.05). ③ Species diversity not only reduced the concentration of diethylenetriamine pentaacetate (DTPA)-extracted metals in the mine tailings, but also decreased heavy metal transfer and accumulation in the soil-plant system. With enhanced species diversity, DTPA-extracted Cd, Cu, Pb, and Zn decreased significantly (DTPA-Cd:r=0.20,P<0.05; DTPA-Cu:r=0.19, P<0.05; DTPA-Pb:r=0.23, P<0.05; DTPA-Zn:r=0.23, P<0.05). With increasing species diversity, a slightly decreasing trend was observed for Cd, Cu, Pb, and Zn concentrations in the aboveground parts of plants (Cd:r=-0.16, P<0.01; Cu:r=-0.23, P<0.001; Pb:r=-0.15, P<0.05; Zn:r=-0.18, P<0.001). In conclusion, plant diversity can play an important role in mine reclamation.

Machine learning-based genetic diagnosis models for hereditary hearing loss by the GJB2, SLC26A4 and MT-RNR1 variants.

BACKGROUND: Hereditary hearing loss (HHL) is the most common sensory deficit, which highly afflicts humans. With gene sequencing technology development, more variants will be identified and support genetic diagnoses, which is difficult for human experts to diagnose. This study aims to develop a machine learning-based genetic diagnosis model of HHL-related variants of GJB2, SLC26A4 and MT-RNR1. METHODS: This case-control study included 1898 subjects, among which 1354 were HHL patients and 544 were carriers. Risk assessment models were established based on variants at 144 sites in three genes related to HHL by building six machine learning (ML) models. We compared the ML models with the genetic risk score (GRS) and expert interpretation (EI) to verify the clinical performance. FINDINGS: Among the six ML models, the support vector machine (SVM) showed the best performance. For the prediction of HHL-related gene sites in subjects with variants, the area under the receiver operating characteristic (AUC) of the SVM model was 0.803 (0.680-0.814) in the 10-fold stratified cross-validation and 0.751 (0.635-0.779) in external validation. The predicted results were better than both EI and GRS. Furthermore, 11 sites were identified as the smallest feature set that can be accurately predicted. INTERPRETATION: The developed SVM model has great potential to be an efficient and effective tool for HHL prediction when high throughput sequencing data are available. FUNDING: This study was supported by the National Key Research and Development Program (2017YFC1001800).

Integrating transcriptome and metabolome analyses of the response to cold stress in pumpkin (Cucurbita maxima).

Cucurbita maxima belong to the genus Cucurbita and are of nutritional and economic importance. Physiological activity, transcriptome, and metabolome analyses of leaf samples from the C. maxima inbreding line IL7 treated at 5 °C and 25 °C were performed. Cold stress resulted in a significant increase in the malondialdehyde content, relative electrical conductivity, soluble protein, sugar content, and catalase activity. A total of 5,553 differentially expressed genes were identified, of which 2,871 were up-regulated and 2,682 down-regulated. In addition, the transcription of differentially expressed genes in the plant hormone signal transduction pathway and transcription factor families of AP2/ERF, bHLH, WRKY, MYB, and HSF was activated. Moreover, 114 differentially expressed metabolites were identified by gas chromatography time-of-flight mass spectrometry, particularly through the analysis of carboxylic acids and derivatives, and organooxygen compounds. The demonstration of a series of potential metabolites and corresponding genes highlighted a comprehensive regulatory mechanism. These findings will provide novel insights into the molecular mechanisms associated with the response to cold stress in C. maxima.

Cadmium concentration and its typical input and output fluxes in agricultural soil downstream of a heavy metal sewage irrigation area.

Heavy metal pollution of agricultural soils in sewage irrigation areas is a serious environmental issue. Many prior studies have demonstrated that soil around the irrigation area is polluted with heavy metals, even though they had not been irrigated by wastewater. In this study, a paddy field downstream of the Zhangshi Irrigation Area was selected as the study area. The Cd concentrations and their representative input and output fluxes to and from the topsoil were systematically studied. The results showed that 95.5% of soil samples exceeded the screening value of Cd concentration. The Cd input fluxes via irrigation water and atmospheric deposition, accounting for 56.95% and 42.53% of the total input flux, respectively, were the main sources of Cd in soil. Crop harvesting was the main output pathway, accounting for 89.63% of the total output flux. An estimation of the annual mass balance showed that Cd in the studied area was in a state of accumulation, and the annual increase in Cd concentration in topsoil would be 2.46 µg kg-1 if the observed fluxes remain. These results will provide a reference for the development of strategies to control and reduce heavy metal contamination and diffusion in agricultural soils around irrigation areas.