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Abstract Objectives This study aimed to investigate the associations between changes in blood pressure (BP) and cerebral small vessel disease (CSVD). Methods This study included 401 participants in the magnetic resonance imaging (MRI) sub-study conducted between 2018 and 2020 as a part of the Multidomain Interventions to Delay Dementia and Disability in Rural China project. MRI markers of CSVD were assessed based on international criteria. Individualized linear regression models evaluated changes in BP by estimating the trend of blood pressure changes over time and fitting a straight line from 2014 to 2018. The data were analyzed using logistic and general linear regression models. Result The mean age of the participants was 64.48 ± 2.69 years, with 237 (59.1%) being females. Increases in systolic BP in later life were significantly associated with larger volumes of periventricular white matter hyperintensity (WMH), greater perivascular spaces in the basal ganglia (BG-PVS) burden, and the presence of deep lacunes and cerebral microbleeds. Additionally, increases in diastolic BP in later life were significantly associated with the presence of infratentorial and deep lacunes. Conclusions CSVDs are associated with increased exposure to elevated BP later in life.

ObjectivesCerebral small vessel disease (CSVD) visible on MRI can be asymptomatic. We sought to develop and validate a model for detecting CSVD in rural older adults.MethodsThis study included 1,192 participants in the MRI sub-study within the Multidomain Interventions to Delay Dementia and Disability in Rural China. Total sample was randomly divided into training set and validation set. MRI markers of CSVD were assessed following the international criteria, and total CSVD burden was assessed on a scale from 0 to 4. Logistic regression analyses were used to screen risk factors and develop the diagnostic model. A nomogram was used to visualize the model. Model performance was assessed using the area under the receiver-operating characteristic curve (AUC), calibration plot, and decision curve analysis.ResultsThe model included age, high blood pressure, white blood cell count, neutrophil-to-lymphocyte ratio (NLR), and history of cerebral infarction. The AUC was 0.71 (95% CI, 0.67–0.76) in the training set and 0.69 (95% CI, 0.63–0.76) in the validation set. The model showed high coherence between predicted and observed probabilities in both the training and validation sets. The model had higher net benefits than the strategy assuming all participants either at high risk or low risk of CSVD for probability thresholds ranging 50–90% in the training set, and 65–98% in the validation set.ConclusionA model that integrates routine clinical factors could detect CSVD in older adults, with good discrimination and calibration. The model has implication for clinical decision-making.

Microbes, including bacteria, viruses, fungi, and other eukaryotic organisms, are commonly present in multiple organs of the human body and contribute significantly to both physiological and pathological processes. Nowadays, the development of sequencing technology has revealed the presence and composition of the intratumoral microbiota, which includes Fusobacterium, Bifidobacteria, and Bacteroides, and has shed light on the significant involvement in the progression of colorectal cancer (CRC). Here, we summarized the current understanding of the intratumoral microbiota in CRC and outline the potential translational and clinical applications in the diagnosis, prevention, and treatment of CRC. We focused on reviewing the development of microbial therapies targeting the intratumoral microbiota to improve the efficacy and safety of chemotherapy and immunotherapy for CRC and to identify biomarkers for the diagnosis and prognosis of CRC. Finally, we emphasized the obstacles and potential solutions to translating the knowledge of the intratumoral microbiota into clinical practice.

Abstract Machine learning techniques have been widely used in predicting disease prognosis, including cancer prognosis. One of the major challenges in cancer prognosis is to accurately classify cancer types and stages to optimize early screening and detection, and machine learning techniques have proven to be very useful in this regard. In this study, we aimed at identifying critical genes for diagnosis and outcomes of hepatocellular carcinoma (HCC) patients using machine learning. The HCC expression dataset was downloaded from GSE65372 datasets and TCGA datasets. Differentially expressed genes (DEGs) were identified between 39 HCC and 15 normal samples. For the purpose of locating potential biomarkers, the LASSO and the SVM-RFE assays were performed. The ssGSEA method was used to analyze the TCGA to determine whether there was an association between SPINK1 and tumor immune infiltrates. RT-PCR was applied to examine the expression of SPINK1 in HCC specimens and cells. A series of functional assays were applied to examine the function of SPINK1 knockdown on the proliferation of HCC cells. In this study, 103 DEGs were obtained. Based on LASSO and SVM-RFE analysis, we identified nine critical diagnostic genes, including C10orf113, SPINK1, CNTLN, NRG3, HIST1H2AI, GPRIN3, SCTR, C2orf40 and PITX1. Importantly, we confirmed SPINK1 as a prognostic gene in HCC. Multivariate analysis confirmed that SPINK1 was an independent prognostic factor for overall survivals of HCC patients. We also found that SPINK1 level was positively associated with Macrophages, B cells, TFH, T cells, Th2 cells, iDC, NK CD56bright cells, Th1 cells, aDC, while negatively associated with Tcm and Eosinophils. Finally, we demonstrated that SPINK1 expression was distinctly increased in HCC specimens and cells. Functionally, silence of SPINK1 distinctly suppressed the proliferation of HCC cells via regulating Wnt/β-catenin pathway. The evidence provided suggested that SPINK1 may possess oncogenic properties by inducing dysregulated immune infiltration in HCC. Additionally, SPINK1 was identified as a novel biomarker and therapeutic target for HCC.

Abstract Conventional electrospinning produces nanofibers with smooth surfaces that limit biomineralization ability. To overcome this disadvantage, we fabricated a tetramethylpyrazine (TMP)-loaded matrix-mimicking biomineralization in PCL/Gelatin composite electrospun membranes with bubble-shaped nanofibrous structures. PCL/Gelatin membranes (PG), PCL/Gelatin membranes containing biomineralized hydroxyapatite (HA) (PGH), and PCL/Gelatin membranes containing biomineralized HA and loaded TMP (PGHT) were tested. In vitro results indicated that the bubble-shaped nanofibrous surface increased the surface roughness of the nanofibers and promoted mineralization. Furthermore, sustained-release TMP had an excellent drug release efficiency. Initially released vigorously, it reached stabilization at day 7, and the slow-release rate stabilized at 61.0 ± 1.8% at 28 days. All membranes revealed an intact cytoskeleton, cell viability, and superior adhesion and proliferation when stained with Ghost Pen Cyclic Peptide, CCK-8, cell adhesion, and EdU. In PGHT membranes, the osteogenic and vascularized gene expression of BMSCs and human vascular endothelial cells was significantly upregulated compared with that in other groups, indicating the PGHT membranes exhibited an effective vascularization role. Subsequently, the membranes were implanted in a rat cranium defect model for 4 and 8 weeks. Micro-CT and histological analysis results showed that the PGHT membranes had better bone regenerative patterns. Additionally, the levels of CD31 and VEGF significantly increased in the PGHT membrane compared with those in other membranes. Thus, PGHT membranes could accelerate the repair of cranium defects in vivo via HA and TMP synergistic effects. Graphical Abstract

Abstract Direct seeding of rice is a lightweight and simple cultivation method, which can effectively promote rice production. Anaerobic germination tolerance is one of the main traits of rice adaptability to direct seeding. The mining of related genetic loci, analysis of anaerobic traits and screening of tolerance genes provided valuable genetic resources for improving the anaerobic germination ability of direct seeding rice. This study conducted a dynamic genome-wide association study (GWAS) based on coleoptile-related traits of 591 rice natural populations, and a total of 317 SNP sites were detected. Integrated dynamic widely targeted metabolomics analysis, we found that xanthine, l-alanine and GABA may be key biomarkers that are sensitive and respond strongly to hypoxic stress perception. By WGCNA analysis of targeted metabolomics and transcriptomics, a total of 3 modules were obtained that were significantly correlated with the above three marker metabolites, namely dark green, dark gray and light green modules, respectively, and several key structural genes of OsAlaAT1, OsGAD4, OsAAH and Os09g0424600 that may affect hypoxic germination were screened from the 3 modules. Among them, OsAlaAT1 (Os10g0390500), located in Chr10-12877840, which is within the GWAS location range of CVAN3d, is considered to be a more reliable candidate gene. Overall, in addition to providing new insight into the metabolic regulation of l-alanine, GABA and xanthine during hypoxic germination of rice. This study also provided a reference for the basic theoretical research and breeding application research on the related traits of anaerobic germination in direct-seeding rice.

This study examines the relationship between the variance of others’ contributions, social norms (empirical and normative expectations), and cooperative behavior using a classic linear public goods game. The following results are observed. First, the variance of a participant’s group members’ contributions had a negative impact on their contributions, empirical expectations, and normative expectations. Second, deviations from the mean, whether negative or positive, were deemed less socially appropriate. Third, while there was a strong relationship between variance, social norms, and cooperative behavior, the mediating effect of social norms was found to be insignificant. Finally, there were some notable findings regarding behavior type. Although free riders and cooperators exhibited distinct behavioral patterns, their normative expectations were similar. Free riders expected others to cooperate, but their empirical expectations were significantly lower than cooperators’ expectations, which were aligned with their actual contributions. These findings contribute to research on the relationship between distribution heterogeneity, social norms and cooperative behavior. Furthermore, these findings provide valuable insights into management practices.

Osteogenesis is caused by multiple factors, and the inflammatory response, osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), regeneration of blood vessels, and other factors must be considered in bone tissue engineering. To effectively repair bone defect, it is important to decrease excessive inflammation, enhance the differentiation of mesenchymal stem cells into osteoblasts, and stimulate angiogenesis. Herein, nano-attapulgite (ATP), polyvinyl alcohol (PVA), and gelatin (GEL) scaffolds were produced using 3D printing technology and pioglitazone (PIO)-containing polylactic acid–glycolic acid (PLGA) nanospheres were added. In both in vitro and in vivo studies, material scaffolds with PIO-loaded polylactic acid–glycolic acid nanospheres could reduce the inflammatory response by encouraging macrophage polarization from M1 to M2 and promoting the osteogenic differentiation of BMSCs by activating the BMP2/Smad/RUNX2 signal pathway to repair bone defects. The vascularization of human umbilical vein endothelial cells (HUVECs) through the PI3K/AKT/HIF1-/VEGF pathway was also encouraged. In vivo research using PIO-containing PLGA nanospheres revealed massive collagen deposition in skin models. These findings indicate a potentially effective scaffold for bone healing, when PLGA nanospheres—which contain the drug PIO—are combined with ATP/PVA/GEL scaffolds.

Summary: Detecting visual features in the environment is crucial for animals’ survival. The superior colliculus (SC) is implicated in motion detection and processing, whereas how the SC integrates visual inputs from the two eyes remains unclear. Using in vivo electrophysiology, we show that mouse SC contains many binocular neurons that display robust ocular dominance (OD) plasticity in a critical period during early development, which is similar to, but not dependent on, the primary visual cortex. NR2A- and NR2B-containing N-methyl-D-aspartate (NMDA) receptors play an essential role in the regulation of SC plasticity. Blocking NMDA receptors can largely prevent the impairment of predatory hunting caused by monocular deprivation, indicating that maintaining the binocularity of SC neurons is required for efficient hunting behavior. Together, our studies reveal the existence and function of OD plasticity in SC, which broadens our understanding of the development of subcortical visual circuitry relating to motion detection and predatory hunting.

In plants, nucleotide-binding site and leucine-rich repeat proteins (NLRs) play pivotal roles in effector-triggered immunity (ETI). However, the precise mechanisms underlying NLR-mediated disease resistance remain elusive. Previous studies have demonstrated that the NLR gene pair Pik-H4 confers resistance to rice blast disease by interacting with the transcription factor OsBIHD1, consequently leading to the upregulation of hormone pathways. In the present study, we identified an RNA recognition motif (RRM) protein, OsRRM2, which interacted with Pik1-H4 and Pik2-H4 in vesicles and chloroplasts. OsRRM2 exhibited a modest influence on Pik-H4-mediated rice blast resistance by upregulating resistance genes and genes associated with chloroplast immunity. Moreover, the RNA-binding sequence of OsRRM2 was elucidated using systematic evolution of ligands by exponential enrichment. Transcriptome analysis further indicated that OsRRM2 promoted RNA editing of the chloroplastic gene ndhB. Collectively, our findings uncovered a chloroplastic RRM protein that facilitated the translocation of the NLR gene pair and modulated chloroplast immunity, thereby bridging the gap between ETI and chloroplast immunity.

Abstract Mutation breeding is a significant means of increasing breeding efficiency and accelerating breeding process. In present study, we explored a new method for mutations inducing in rice (Oryza sativa L.) by using direct current electrophoresis bath (DCEB). The results showed that 20 mM NaCl solution is the optimal buffer, and the mortality of rice seeds followed an upward trend with increasing voltage and processing time of DCEB. By exploring the mutagenic effects of γ-irradiation and DCEB on seed vigor and physiological damages, we found that the physiological damages induced by DCEB on seed vigor were significant compared with that by γ-irradiation. We screened two mutants with low filled grain percentage and one mutant with abnormal hull from the M2 generations. These three mutants were confirmed to be authentic mutants based on 48 SSR markers followed by the protocol NY/T 1433–2014. Whole-genome resequencing detected a total of 503 and 537 polymorphisms in the two mutants, respectively, and the DCEB mutagenesis induced mainly InDel variants, while the exon region of mutant genes occupied a large proportion, especially the SNP variants, which occupied about 20% of the mutation sites in the exon region.

Osteoblasts and osteoclasts play a crucial role in the dynamically coupled balance during bone regeneration and remodeling. They complement and restrict each other in the human body. Decreased osteoblasts lead to insufficient bone formation or excessive formation of osteoclasts, leading to increased bone resorption, which will destroy the structure of the bone tissue. This will greatly increase the risk of diseases such as osteoporosis and nonunions caused by bone defects.Herein, gelatin and polycaprolactone were used as substrates, and biomaterial membranes with mesh and sandwich structures were constructed using the electrospinning technology. Naringenin was loaded into the shell, and vitamin K2 was loaded into the core layer of the nanofibrous membrane. The biocompatibility and osteogenic capacity of the membranes were assessed in vitro using mouse bone marrow mesenchymal stem cells (BMSCs). During osteoclast induction, the receptor activator of nuclear factor kappa-Β ligand (RANKL) was used to coculture RAW264.7 cells with various materials. The regulatory effect of various membranes on osteoclast growth was evaluated by detecting the expression levels of osteoclast-related genes and proteins in the cells.Subsequently, we constructed a model of a rat skull defect and implanted different membranes into the defect. Then, we evaluated the new bone formation in the defect using histological staining and micro-computed tomography after 4 and 8 weeks. The results of in vitro experiments confirmed that the incorporation of naringenin and vitamin K2 stimulated the expression of osteogenesis-related genes and the secretion of osteogenesis-related proteins. Simultaneously, the results showed that naringenin and vitamin K2 inhibited the formation and growth of osteoclasts. Therefore, naringenin and vitamin K2 have a synergistic effect in promoting bone growth and regulating osteoclast growth.

【Objective】Rice blast is an important limiting factor in rice production. Exploring and utilizing resistant genes is an important guarantee for achieving high and stable yield of rice. Previous studies have shown that rice blast resistance-related microRNA osa-miR-21 may regulate rice blast resistance by targeting the polyamine oxidase gene OsPAO4. However, the function of Polyamine Oxidases (PAOs) in rice disease resistance has not been reported. In order to further explore the possible biological function of OsPAO4 gene in rice disease resistance, the CRISPR/Cas9 editing technology was used for site-specific editing of ospao4 gene mutants and the edited offspring were also analyzed.【Method】A 20-bp editing target was designed in the second exon of OsPAO4, and the nucleotide fragments of the target was cloned into pRGEB32 vector to obtain OsPAO4 editing vector. Then, the rice Pik-H4 NIL callus was transformed by Agrobacterium-mediated method. Positive transgenic plants were obtained by regeneration culture and hygromycin detection, PCR and sequence analysis were performed on the DNA sequences near the target site in the T0 generation plants.【Result】The results show that the OsPAO4 gene was successfully edited and finally 25 transgenic-positive plants were obtained, and various mutation types were produced in the T0 generation, including 3 homozygous mutants, 18 heterozygous mutants and 4 nonedited plants. In addition, the glume color of the heterozygous mutation ospao4-8 of the T0 generation changed from purple to dark gray, and the activity of catalase (CAT) in the mutants was increased. It was predicted that OsPAO4 might participate in the basis immunization process.【Conclusion】A variety of ospao4 mutants were created in this study, and it was preliminarily determined that OsPAO4 might participate in the regulation of rice immune process, which laid an important foundation for further revealing the specific biological function and molecular regulation mechanism of OsPAO4 gene.

Abstract RAS genes are the most frequently mutated oncogenes and play critical roles in the development and progression of malignancies. The mutation, isoform (KRAS, HRAS, and NRAS), position, and type of substitution vary depending on the tissue types. Despite decades of developing RAS‐targeted therapies, only small subsets of these inhibitors are clinically effective, such as the allele‐specific inhibitors against KRASG12C. Targeting the remaining RAS mutants would require further experimental elucidation of RAS signal transduction, RAS‐altered metabolism, and the associated immune microenvironment. This study reviews the mechanisms and efficacy of novel targeted therapies for different RAS mutants, including KRAS allele‐specific inhibitors, combination therapies, immunotherapies, and metabolism‐associated therapies.

Abstract Psoralea corylifolia L. (PCL), referred to as “Bu-gu-zhi” in Chinese, has great medicinal values since ancient times. PCL is the dried ripe fruit of Psoralea corylifolia L., which has been widely used in traditional Chinese medicine (TCM) for the treatment of kidney-yang deficiency, enuresis and urinary frequency, chills and pain of the waist and knees, dawn diarrhea and vitiligo. In this paper, a systematic of the botany, traditional uses, phytochemistry, pharmacology, toxicology, quality control and pharmacokinetics of PCL was presented, along with future research directions. According to the results, PCL contains approximately 163 chemical components, including coumarins, flavonoids, monoterpene phenols, benzofurans, glycosides, lipids, fatty acids, and volatile oils. PCL and its active ingredients have a variety of pharmacological activities, such as anti-inflammatory, antibacterial, antiviral, antioxidant, antitumor, antiosteoporosis, cardioprotective, neuroprotective, and immunomodulatory. Further study of quality control standards and potential mechanisms of PCL is also needed. In addition, more toxicological studies will also contribute to the progress of clinical trials.

The history of virology, which is marked by transformative breakthroughs, spans microbiology, biochemistry, genetics, and molecular biology. From the development of Jenner’s smallpox vaccine in 1796 to 20th-century innovations such as ultrafiltration and electron microscopy, the field of virology has undergone significant development. In 1898, Beijerinck laid the conceptual foundation for virology, marking a pivotal moment in the evolution of the discipline. Advancements in influenza A virus research in 1933 by Richard Shope furthered our understanding of respiratory pathogens. Additionally, in 1935, Stanley’s determination of viruses as solid particles provided substantial progress in the field of virology. Key milestones include elucidation of reverse transcriptase by Baltimore and Temin in 1970, late 20th-century revelations linking viruses and cancer, and the discovery of HIV by Sinoussi, Montagnier, and Gallo in 1983, which has since shaped AIDS research. In the 21st century, breakthroughs such as gene technology, mRNA vaccines, and phage display tools were achieved in virology, demonstrating its potential for integration with molecular biology. The achievements of COVID-19 vaccines highlight the adaptability of virology to global health.

We utilized a two-branch end-to-end network (MultiSenCNN) for land use and land cover (LULC) classification and flood event mapping using multispectral (MS), panchromatic (Pan) and synthetic aperture radar (SAR) images, where flooding was induced by typhoon Lekima in August 2019. Flood damages were assessed by considering both the LULC and flood maps. We defined three strategies to compare the MS + SAR and MS + Pan images to demonstrate the ability of the MultiSenCNN algorithm for LULC classification. The three strategies yielded an average overall accuracy of ∼98% and an average Kappa of ∼0.98 for LULC classification. The overall accuracy of the fused MS + SAR images is slightly higher than the MS + Pan images when using the same model training samples. The flood mapping shows an overall accuracy of 97.22% and a Kappa of 0.94, with a flood inundation area of 101 km2 that mainly inundated cropland and urban areas. Compared to other LULC types, the flooded cropland has caused more loss of ecosystem service values during typhoon Lekima, accounting for 81.19% of the total. Using SAR mages can well monitor the start/end states of flood events and the inundated areas, providing the flood status information to rescuers and governments for making timely decisions.

Abstract Background The mining of new allelic variation and the induction of new genetic variability are the basis for improving breeding efficiency. Results In this study, in total, 3872 heavy ion-irradiated M2 generation rice seeds and individual leaves were collected. The grain length was between 8 and 10.22 mm. The grain width was between 1.54 and 2.87 mm. The results showed that there was extensive variation in granulotype. The allelic variation in GS3 and GW5 was detected in 484 mixed samples (8:1) using targeted sequencing technology, and 12 mixed samples containing potential mutations and 15 SNPs were obtained; combined with Sanger sequencing and phenotype data, 13 key mutants and their corresponding SNPs were obtained; protein structural and functional analysis of key mutants screened out 6 allelic variants leading to altered grain shape, as well as the corresponding mutants, including long-grain mutants GS3-2 and GS3-7, short-grain mutants GS3-3 and GS3-5, wide-grain mutant GW5-1 and narrow-grain mutant GW5-4; whole genome sequencing identified new grain length gene allelic variants GS3-G1, GS3-G2 and GS3-G3. Conclusion Based on the above studies, we found 6 granulotype mutants and 9 granulotype-related allelic variants, which provided new functional gene loci and a material basis for molecular breeding and genotype mutation and phenotype analysis. We propose a method for targeted identification of allelic variation in rice grain type genes by combining targeted sequencing of mixed samples and whole genome sequencing. The method has the characteristics of low detection cost, short detection period, and flexible detection of traits and genes.

Abstract Anaplastic thyroid carcinoma (ATC) is an extremely malignant type of endocrine cancer frequently accompanied by extrathyroidal extension or metastasis through mechanisms that remain elusive. We screened for the CREB3 transcription-factor family in a large cohort, consisting of four microarray datasets. This revealed that CREB3L1 was specifically up regulated in ATC tissues and negatively associated with overall survival of patients with thyroid cancer. Consistently, high expression of CREB3L1 was negatively correlated with progression-free survival in an independent cohort. CREB3L1 knockdown dramatically attenuated invasion of ATC cells, whereas overexpression of CREB3L1 facilitated the invasion of papillary thyroid carcinoma (PTC) cells. Loss of CREB3L1 inhibited metastasis and tumor growth of ATC xenografts in zebrafish and nude mouse model. Single-cell RNA-sequencing analysis revealed that CREB3L1 expression gradually increased during the neoplastic progression of a thyroid follicular epithelial cell to an ATC cell, accompanied by the activation of the extracellular matrix (ECM) signaling. CREB3L1 knockdown significantly decreased the expression of collagen subtypes in ATC cells and the fibrillar collagen in xenografts. Due to the loss of CREB3L1, ATC cells were unable to activate alpha-smooth muscle actin (α-SMA)-positive cancer-associated fibroblasts (CAFs). After CREB3L1 knockdown, the presence of CAFs inhibited the growth of ATC spheroids and the metastasis of ATC cells. Further cytokine array screening showed that ATC cells activated α-SMA-positive CAFs through CREB3L1-mediated IL-1α production. Moreover, KPNA2 mediated the nuclear translocation of CREB3L1, thus allowing it to activate downstream ECM signaling. These results demonstrate that CREB3L1 maintains the CAF-like property of ATC cells by activating the ECM signaling, which remodels the tumor stromal microenvironment and drives the malignancy of ATC. Graphical Abstract

Abstract Background Little is known about the gender characteristics and the Corona Virus Disease 2019 (COVID-19) impact on psychiatric department outpatients in general hospitals in China. Methods We retrospectively collected 225,947 outpatient clinic records before and during COVID-19 pandemic from January 1, 2019 to December 31, 2020 in the psychiatric clinic of 3 general hospitals, gender composition of patients was analyzed in different five age groups and nine diagnostic categories at three levels: total patient visits, number of patients and number of first-visit patients. Results The total male-to-female ratio of psychiatric outpatient records in 3 general hospitals from 2019 to 2020 was 1:1.69. Women were more common in all age groups. Overall, the proportion of women was further increased in 2020 compared to that in 2019, especially in age group below 34 years and anxiety disorders category. Most mental disorders showed higher demands for females than that for males except mental and behavioral disorders due to psychoactive substance use with the male-to-female ratio was 1:0.05. Conclusions The demand for female psychiatric outpatient services is obviously higher than that for males. It is necessary to pay more attention to explore targeted mechanism or psychosocial service strategy for female patients with mental disorders. Trial registration ChiCTR2100044894, March 31, 2021 retrospectively registered.

【Objective】IQD gene family proteins are plant specific calmodulin-binding target proteins, which play an important role in plant defense and development regulation. The interaction between Pik-H4 and OsIQD1 was found in the yeast double hybrid screening experiment in laboratory. In order to reveal the specific biological functions of OsIQD1 in rice blast resistance, OsIQD1 gene was edited by using CRISPR/Cas9 editing technique.【Method】OsIQD1 was obtained by sequence alignment. Two 20 bp editing targets were designed in exon 1 and exon 5 of OsIQD1 (DUF4005 domain), and the nucleotide fragments of the two targets were cloned into pRGEB32 vector to obtain pRGEB32-OsIQD1 -gRNA vector. The rice Pik-H4 NIL callus was transformed by agrobacterium-mediated method. Transgenic positive plants were obtained by regeneration culture and hygromycin resistance screening. PCR and sequencing were performed on the target region sequences of transgenic plants of T0 generation to analyze the mutation types of osiqd1.【Result】The transgenic regenerated plants were identified by PCR with hygromycin resistance gene HPT Ⅱ, and 30 positive lines were obtained. Sequencing analysis of the sequences near the target site of T0 generation plants showed that OsIQD1 gene was successfully edited, and the editing efficiency of the two sites was 21.67% and 26.67%, respectively. There was one homozygous mutant line in target 2 region.【Conclusion】The study results provide genetic material for further studies on the mechanism of osiqd1 mutation involved in calcium ion/calmodulin signaling pathway, and OsIQD1 is preliminarily presumed to be involved in the basic immune response of plants.

The intricate regulatory process governing rice immunity against the blast fungus Magnaporthe oryzae remains a central focus in plant–pathogen interactions. In this study, we investigated the important role of Osa-miR11117, an intergenic microRNA, in regulating rice defense mechanisms. Stem-loop qRT-PCR analysis showed that Osa-miR11117 is responsive to M. oryzae infection, and overexpression of Osa-miR11117 compromises blast resistance. Green fluorescent protein (GFP)-based reporter assay indicated OsPAO4 is one direct target of Osa-miR11117. Furthermore, qRT-PCR analysis showed that OsPAO4 reacts to M. oryzae infection and polyamine (PA) treatment. In addition, OsPAO4 regulates rice resistance to M. oryzae through the regulation of PA accumulation and the expression of the ethylene (ETH) signaling genes. Taken together, these results suggest that Osa-miR11117 is targeting OsPAO4 to regulate blast resistance by adjusting PA metabolism and ETH signaling pathways.

Large-scale short-term monitoring and prediction of surface deformation are of great significance for the prevention and control of geohazards in rapidly urbanizing developing cities. Most studies focus on individual cities, but it would be more meaningful to address large urban agglomerations and consider the relevance of the regions within them. In addition, the commonly used linear fitting prediction methods cannot accurately capture the dynamic mechanisms of deformation. In this study, we proposed an automatic PS extraction method (named PS-SBAS-InSAR) that improves SBAS-InSAR to extract surface deformation and an Informer-based short-term surface deformation prediction method for case studies in 16 typical cities of the Yangtze River Delta (YRD). The results show that PS-SBAS-InSAR successfully extracted accurate surface deformation sequences of the YRD. During the period from January 2019 to January 2021, the YRD experienced a slight deformation with an average deformation rate within [−4, 4] mm/year. Geographically neighboring cities may have associated deformation distributions and similar deformation trends, as indicated by average deformation rate maps and landscape metrics. Both types of deformation (i.e., subsidence/uplift) tend to occur simultaneously, with specific areas of subsidence/uplift occurring in close proximity to areas of concentrated deformation. The Informer model effectively captured the time-series variation in surface deformation, suggesting a slowdown of deformation over the next two months (February 2021–March 2021). Our work contributes to a better understanding of changes and trends in large-scale surface deformation and provides useful methods for monitoring and predicting surface deformation in coastal areas.

Abstract Background Reconstruction of soft tissue defects following surgical tumor resection is important for quality of life in cancer patients with oral and oropharyngeal squamous cell carcinoma (SCC). This study presents a novel computer-aided reconstruction of soft tissue (CARST) technology employed with these patients. Methods We first described the CARST technology in detail in a report of a 34-year-old male patient with locally invasive right-sided tongue SCC following a nearly total glossectomy and reported the postoperative outcomes. This digital technology was applied to construct a 3D model from CT images, which was used to delineate surgical resection boundaries and design a personalized reconstruction of the soft tissue defect. A nonuniform rational B-spline (NURBS) was generated and applied to transform the 3D model into a 2D flap-cutting guide printed out using a 3D printer. We then reported a case-series study on oral and oropharyngeal SCC patients who were randomly assigned to receive the CARST (n = 15) or a traditional soft tissue reconstruction (n = 15). Clinicopathological features and short- and long-term postoperative outcomes between the two groups were compared. Results The patient with the tongue SCC had a successful CARST following surgical tumor resection without any complications. His speech and swallowing functions recovered well after surgery and he experienced no significant changes to his appearance following recovery. There was no recurrence within a 3-year follow-up period. Results of the case-series study showed that the CARST group had significantly shorter operative and post-operation hospital-stay time, a higher flap utilization rate, and a trend of less and milder postoperative complications, and they experienced no significant difference in intraoperative blood loss and long-term outcomes compared to the traditional group. Conclusion CARST is a safer and more efficient personalized technology of soft tissue reconstruction following surgical tumor resection in patients with oral and oropharyngeal SCC.

ObjectiveTo explore the associations of macular microvascular parameters with cerebral small vessel disease (CSVD) in rural-dwelling older adults in China.MethodsThis population-based cross-sectional study included 195 participants (age ≥ 60 years; 57.4% women) in the optical coherence tomographic angiography (OCTA) sub-study within the Multimodal Interventions to delay Dementia and disability in rural China (MIND-China). Macular microvascular parameters were measured using the OCTA. We automatically estimated volumes of gray matter, white matter, and white matter hyperintensity (WMH), and manually assessed numbers of enlarged perivascular spaces (EPVS) and lacunes on brain magnetic resonance imaging. Data were analyzed with the general linear models.ResultsAdjusting for multiple confounders, lower vessel skeleton density (VSD) and higher vessel diameter index (VDI) were significantly associated with larger WMH volume (P < 0.05). Lower VSD and foveal density-300 (FD-300) of left eye were significantly associated with lower brain parenchymal volume (P < 0.05). In addition, lower areas of foveal avascular zone (FAZ) and FD-300 of left eye were significantly associated with more EPVS (P < 0.05). The associations of abnormal macular microvascular parameters with WMH volume were evident mainly among females. Macular microvascular parameters were not associated with lacunes.ConclusionMacular microvascular signs are associated with WMH, brain parenchymal volume, and EPVS in older adults. The OCTA-assessed macular microvascular parameters can be valuable markers for microvascular lesions in the brain.

Objectives. Endoscopic submucosal dissection (ESD) has become a well-established treatment method for gastric submucosal tumors (SMTs). However, there existed some challenges to perform ESD for prepyloric SMTs on account of the special location. Recently, submucosal tunneling endoscopic resection (STER) provided a novel option for prepyloric SMTs. This study aimed to make a comprehensive comparison between prepyloric STER (P-STER) and ESD for the treatment of prepyloric SMTs. Methods. Patients with prepyloric SMTs undergoing P-STER treatment between January 2016 and October 2021 were retrospectively reviewed and individually matched at 1 : 1 ratio with those with ESD treatment according to lesion size, lesion location, pathologic diagnosis, lesion origin, and surgery date, forming P-STER and ESD group, respectively. A sample size of 12 patients was collected for each group. Treatment outcomes including resection time, en bloc resection rate, complete resection rate, and postoperative hospital stay as well as occurrence of complications were evaluated. Results. Compared with ESD group, P-STER group got shorter resection time (52.50 minutes for ESD group vs. 38.67 minutes for P-STER group, P=0.001), shorter postoperative hospital stay (7.00 day for ESD group vs. 5.50 day for P-STER group, P=0.008), and lower rate of postoperative abdominal pain (50.00% for ESD group vs. 8.33% for P-STER group, P=0.025). No complication was encountered in P-STER group, whereas one patient with postoperative bleeding was found in ESD group. Conclusions. For the treatment of prepyloric SMTs, P-STER appeared to be a more effective endoscopic technique compared with ESD, although further randomized controlled trials were warranted.

The production and selection of driving factors are essential to building a strong Cellular Automata (CA) model of dynamic urban growth simulation. A critical issue that should be addressed is how the spatial representation and the generalization scale of driving factors affect the CA modeling and the simulation results. It is challenging to evaluate the effectiveness of the selected driving factors because they have no true values. To explore the impacts of the generalization scales, we produced nine sets of driving factors at nine scales to calibrate the CA models based on the Particle Swarm Optimization (CAPSO) and applied them to simulate urban growth of Suzhou during 2000–2020. Our results show that the driving factors at a smaller scale have much better performance in explaining urban growth simulations as inferred by the Explained Residual Deviance (ERD) of the Generalized Additive Models (GAMs). Specifically, the ERD declined from 51.9% to 45.9% as the factor scale became larger during 2000–2020, but there was a peak value (52.2%) at Scale-2. For all simulations during 2000–2020, the CAPSO models with larger-scale factors have slightly lower overall accuracy and Figure-of-Merit (FOM), which respectively decreased by 3.1% and 4.4% as compared to the CA models with scale-free factors. We concluded that the driving factors at a smaller scale (200 ~ 400 m for point-like facilities and 7 ~ 14 m for line-like facilities) can build more accurate CA models to simulate urban growth patterns, and the optimal scale for factors can be identified using the ERD. This study contributes to the methods of evaluating the effectiveness of driving factor production and reveals the impacts of spatial representation of factors on the CA modeling and simulation considering the factor generalization scales.

Abstract Background The prognosis of patients with advanced gastric cancer (GC) remains unsatisfactory owing to distant metastasis and resistance to concurrent systemic therapy. Cancer-associated fibroblasts (CAFs), as essential participators in the tumor microenvironment (TME), play a vital role in tumor progression. Thus, CAFs-targeting therapy is appealing for remodeling TME and sensitizing GC to conventional systemic therapy. Methods Amphiphilic SN38 prodrug polymeric micelles (PSN38) and encapsulated the hydrophobic esterase-responsive prodrug of Triptolide (TPL), triptolide-naphthalene sulfonamide (TPL-nsa), were synthesized to form PSN38@TPL-nsa nanoparticles. Then, CAFs were isolated from fresh GC tissues and immortalized. TPL at low dose concentration was used to investigate its effect on CAFs and CAFs-induced GC cells proliferation and migration. The synergistic mechanism and antitumor efficiency of SN38 and TPL co-delivery nanoparticle were investigated both in vitro and in vivo. Results Fibroblast activation protein (FAP), a marker of CAFs, was highly expressed in GC tissues and indicated poorer prognosis. TPL significantly reduced CAFs activity and inhibited CAFs-induced proliferation, migration and chemotherapy resistance of GC cells. In addition, TPL sensitized GC cells to SN38 treatment through attenuated NF-κB activation in both CAFs and GC cells. PSN38@TPL-nsa treatment reduced the expression of collagen, FAP, and α-smooth muscle actin (α-SMA) in tumors. Potent inhibition of primary tumor growth and vigorous anti-metastasis effect were observed after systemic administration of PSN38@TPL-nsa to CAFs-rich peritoneal disseminated tumor and patient-derived xenograft (PDX) model of GC. Conclusion TPL suppressed CAFs activity and CAFs-induced cell proliferation, migration and chemotherapy resistance to SN38 of GC. CAFs-targeted TPL and SN38 co-delivery nanoparticles exhibited potent efficacy of antitumor and reshaping TME, which was a promising strategy to treat advanced GC. Graphical Abstract

Background Persistence of long-term COVID-19 pandemic is putting high pressure on healthcare services worldwide for several years. This article aims to establish models to predict infection levels and mortality of COVID-19 patients in China. Methods Machine learning models and deep learning models have been built based on the clinical features of COVID-19 patients. The best models are selected by area under the receiver operating characteristic curve (AUC) scores to construct two homogeneous ensemble models for predicting infection levels and mortality, respectively. The first-hand clinical data of 760 patients are collected from Zhongnan Hospital of Wuhan University between 3 January and 8 March 2020. We preprocess data with cleaning, imputation, and normalization. Results Our models obtain AUC = 0.7059 and Recall (Weighted avg) = 0.7248 in predicting infection level, while AUC=0.8436 and Recall (Weighted avg) = 0.8486 in predicting mortality ratio. This study also identifies two sets of essential clinical features. One is C-reactive protein (CRP) or high sensitivity C-reactive protein (hs-CRP) and the other is chest tightness, age, and pleural effusion. Conclusions Two homogeneous ensemble models are proposed to predict infection levels and mortality of COVID-19 patients in China. New findings of clinical features for benefiting the machine learning models are reported. The evaluation of an actual dataset collected from January 3 to March 8, 2020 demonstrates the effectiveness of the models by comparing them with state-of-the-art models in prediction.

Abstract Background The safety and efficacy of indocyanine green (ICG) imaging navigational laparoscopic gastrectomy remain controversial. This study is to evaluate the short-term and long-term outcomes of ICG-guided laparoscopic radial gastrectomy in patients with gastric cancer. Methods Consecutive patients with definitive diagnosis of gastric cancer that underwent laparoscopic radical gastrectomy were collected retrospectively. Propensity score matching (PSM) at 1:1 ratio was performed to compare the outcomes of two groups. Results A total of 122 qualified patients were divided into ICG group (n = 34) and non-ICG group (n = 88). PSM yielded 28 patients with comparable baseline characteristics into each group. The number of retrieved lymph node in ICG group was significantly higher than that in non-ICG group (P = 0.0196). There was no statistical difference of perioperative, short-term, and long-term complications between the two groups. Conclusion ICG-guided laparoscopic radical gastrectomy is safe and effective, and ICG-navigated lymphadenectomy improves the number of retrieved lymph nodes for patients with gastric cancer.

Abstract Background Photo-thermo-sensitive genic male sterile (PTGMS) rice (Oryza sativa L.) is usually considered two-line male sterile rice because of its dual-purpose in two-line hybrid rice system: under short days and low temperatures, it is fertile and used for self-propagation, but under long days and high temperatures, it is sterile and used for hybrid seed production. Therefore, photoperiod and temperature conditions are extremely important for the fertility transition of two-line male sterile rice. In recent years, there have been frequent occurrences of abnormally low-temperature (ALT) resulting in failure of two-line hybrid rice seed production. The daily average temperature (DAT) during ALT events is sometimes higher than the critical sterility-inducing temperature (CSIT) of two-line male sterile rice, of which the night temperature is lower than the CSIT. DAT has been traditionally used as the single indicator of pollen fertility transition, but it is unknown why the fertility of two-line male sterile rice in seed production restored fertility under ALT conditions. Results For Hang93S (H93S), a newly released PTGMS line, we hypothesized fertility transition is determined mainly by the cumulative effective low temperature (ELT) and only a certain duration of low temperature is required every day during the fertility-sensitive period. This study simulated ALTs where the DAT was higher than the CSIT while some segments of night temperature were lower than the CSIT. The results showed H93S exhibited a fertility transition to varying degrees. Moreover, fertility was restored under simulated ALT conditions and pollen fertility increased with increasing cumulative ELT, indicating that the fertility transition was affected primarily by the cumulative ELT. Results also indicated that pollen fertility increased as the number of treatment days increased. Conclusions The fertility transition is caused mainly by the cumulative ELT. In two-line male sterile rice breeding, the effects of day length, ALT at night, and continuous response days should be considered together. The present study provides new insight into fertility transition so breeders can more effectively utilize the two-line male sterile rice, H93S, in breeding programs.

Abstract To explore the effects and mechanisms of benzoylaconitine and paeoniflorin on collagen-induced arthritis (CIA) rats. Weight, paw swelling, arthritis index and joint pathologic changes were examined in each group after CIA induction. PGE2, IL-1β, IL-6, IL-10, TNF-α, VEGF, MMP-3, IgG and anti-CII Ab were assessed by ELISA; STAT1 and STAT3 expressions were analyzed immunohistochemically, and the ultrastructure of synovial cells was observed by transmission electron microscopy. Therapeutic effects were determined in CIA rats via injecting benzoylaconitine and paeoniflorin, which could alleviate the degree of swelling and arthritis index (AI) and pathological lesions of the sacroiliac gland; decrease the levels of PGE2, IL-1β, TNF-α, VEGF and IgG in serum; reduce STAT1 and STAT3 expression in the membrane tissue; and inhibit the secretion and proliferation of synovial cells. These results showed that benzoylaconitine and paeoniflorin could significantly palliate the arthritic symptoms of CIA rats, and better therapeutic effects could be achieved if the two components were used in combination.

Although several regulators associated with purple traits in rice have been identified, the genetic basis of the purple sheath remains unclear. In the present study, F2-1 and F2-2 populations were constructed using purple sheath (H93S) and green sheath (R1173 and YHSM), respectively. In order to identify QTL loci in purple sheaths, BSA analyses were performed on the two F2 populations. A crucial QTL for purple sheath was identified, tentatively named qPLSr6, and was located in the 4.61 Mb to 6.03 Mb region of chromosome 6. Combined with expression pattern analysis of candidate genes, LOC_Os06g10350 (OsC1PLSr) was suggested as a candidate gene. The homozygous mutant KO-1 and KO-2 created through CRISPR/Cas9 editing, lost their purple leaf sheath. The RT-PCR revealed that OsC1PLSr, anthocyanin synthase (ANS), diflavonol-4-reductase (DFR), flavanone-3-hydroxylase (F3H), and flavanone-3′-hydroxylase (F3′H) expression levels were dramatically down-regulated in the mutants. The yeast report system indicated that the 145–272 aa region at the C-terminal of OsC1PLSr is a positive transcriptional activation domain. The results indicated that OsC1PLSr synthesized anthocyanins by regulating the expression of ANS, DFR, F3H, and F3′H. This study provides new insights into the genetic basis of the purple sheath.

Early seedling vigor (ESV) is a major breeding target in rice, especially under direct seeding. To identify quantitative trait locus (QTL) affecting ESV, a recombinant inbred line population derived from a cross between 02428 and YZX, two cultivars differing in vigor during early seedling growth, was used for QTL analysis. Nine traits associated with ESV were examined using a high-density map. Of 16 additive loci identified, three were detected in two generations and thus considered stable. Four epistatic interactions were detected, one of which was repeated in two generations. Further analysis of the pyramiding effect of the three stable QTL showed that the phenotypic value could be effectively improved with an increasing number of QTL. These results were combined with results from our previous QTL analysis of the germination index. The lines G58 and G182 combined all the favourable alleles of all three stable QTL for ESV and three QTL for germination speed. These two lines showed rapid germination and strong ESV. A total of 37 candidate differentially expressed genes were obtained from the regions of the three stable QTL by analysis of the dynamic transcriptomic expression profile during the seedling growth period of the two parents. The QTL are targets for ESV breeding and the candidate genes await functional validation. This study provides a theoretical basis and a genetic resource for the breeding of direct-seeded rice.

CASP3 is the gene encoding caspase-3, a specific protease that cleaves substrates such as poly-ADP ribose polymerase and acetyl-DEVD-7-amino-4-methylcoumarin. This enzymatic activity leads to DNA fragmentation, which is a hallmark of apoptosis. Although recent studies have demonstrated that CASP3 plays a vital role in tumour suppression by promoting apoptosis, these reports did not consider systematic pan-cancer analyses. Therefore, we performed a specific pan-cancer analysis using The Cancer Genome Atlas and Genotype-Tissue Expression databases to analyse CASP3 expression in terms of cancer prognosis, DNA methylation status, tumour mutative burden (TMB), and microsatellite instability (MSI), as well as immune cell infiltration in different tumours and the molecular mechanisms underlying these. We found that CASP3 expression was significantly associated with the prognosis of most tumours. Additionally, promoter methylation status was associated with CASP3 expression in bladder urothelial carcinoma, oesophageal carcinoma, kidney renal clear cell carcinoma, kidney renal papillary cell carcinoma, lung squamous cell carcinoma, prostate adenocarcinoma, sarcoma, testicular germ cell tumours, and uterine corpus endometrial carcinoma. TMB and MSI were associated with CASP3 expression in 15 tumours. Moreover, CASP3 expression was correlated with the tumour microenvironment in nearly all tumour types. Further, we observed that in addition to apoptosis, CASP3 action plausibly involves B cell activation, antigen presentation, immune responses, chemokine receptors, and inflammatory function. Our study thus provides a relatively comprehensive understanding of the carcinogenicity of CASP3 in different tumours and suggests that CASP3 is a potential prognostic marker.

Abstract Background In Asian rice production, an increasing number of countries now choose the direct seeding mode because of rising costs, labour shortages and water shortages. The ability of rice seeds to undergo anaerobic germination (AG) plays an important role in the success of direct seeding. Results In this study, we used 2,123,725 single nucleotide polymorphism (SNP) markers based on resequencing to conduct a dynamic genome-wide association study (GWAS) of coleoptile length (CL) and coleoptile diameter (CD) in 209 natural rice populations. A total of 26 SNP loci were detected in these two phenotypes, of which 5 overlapped with previously reported loci (S1_ 39674301, S6_ 20797781, S7_ 18722403, S8_ 9946213, S11_ 19165397), and two sites were detected repeatedly at different time points (S3_ 24689629 and S5_ 27918754). We suggest that these 7 loci (−log10 (P) value > 7.3271) are the key sites that affect AG tolerance. To screen the candidate genes more effectively, we sequenced the transcriptome of the flooding-tolerant variety R151 in six key stages, including anaerobic (AN) and the oxygen conversion point (AN-A), and obtained high-quality differential expression profiles. Four reliable candidate genes were identified: Os01g0911700 (OsVP1), Os05g0560900 (OsGA2ox8), Os05g0562200 (OsDi19–1) and Os06g0548200. Then qRT-PCR and LC-MS/ MS targeting metabolite detection technology were used to further verify that the up-regulated expression of these four candidate genes was closely related to AG. Conclusion The four novel candidate genes were associated with gibberellin (GA) and abscisic acid (ABA) regulation and cell wall metabolism under oxygen-deficiency conditions and promoted coleoptile elongation while avoiding adverse effects, allowing the coleoptile to obtain oxygen, escape the low-oxygen environment and germinate rapidly. The results of this study improve our understanding of the genetic basis of AG in rice seeds, which is conducive to the selection of flooding-tolerant varieties suitable for direct seeding.

Interferometric SAR (InSAR) is a practical technique to derive 3-D structure of the earth's surface. This article conducts a comparative study of digital elevation model (DEM) reconstruction using the single-baseline and multibaseline InSAR techniques. To improve the accuracy of the DEM generated from the single-baseline InSAR, we improve the weight definition approach according to the coherence magnitudes for the fusion of single-baseline InSAR DEMs. For multibaseline InSAR, we adopt a method based on the maximum-likelihood estimation (MLE) algorithm, which uses external DEM as a constraint. A TerraSAR-X dataset comprising four SAR images acquired over Barcelona is used for experimental investigation. The accuracies of four types of DEM are comparatively studied, including DEM by single-baseline InSAR, DEM by the fusion of single-baseline InSAR DEMs, DEM by unconstrained multibaseline InSAR, and DEM by constrained multibaseline InSAR. The results show that the proposed weighted fusion of single-baseline InSAR performed slightly better than the constrained multibaseline InSAR method, and both of them performed better than the single-baseline results, demonstrating that multiple observations can effectively improve the accuracy of the reconstructed DEM.

Abstract Background Rice blast caused by Magnaporthe oryzae (M. oryzae) is one of the most destructive diseases in rice production. Development of resistant varieties through pyramiding of resistant (R) genes is considered as an effective strategy to cope with the disease. However, is it really essential to pyramid more R genes in a specific ecological regions? To answer this question, a set of rice improved lines were developed in this study. Afterwards, the blast disease resistance and agronomic traits of the recurrent parent (RP), donor parents (DPs) and improved lines were investigated. Results We developed seven improved lines, comprising three monogenic lines, three two-gene pyramids and one three-gene pyramid, by introgression of R gene(s) into a common genetic background using marker-assisted backcross breeding (MABB). Based on 302 SSR markers, the recurrent genome of the seven improved lines reached a range of 89.1 to 95.5%, with the average genome recovery of 92.9%. The pathogenicity assays inoculated with 32 different blast isolates under artificial conditions showed that the resistance spectrum of all the improved lines was significantly broadened. The assays further showed that the two-gene pyramids and the three-gene pyramid exhibited wider resistance spectrum than the monogenic lines. At natural nurseries, the three monogenic lines still showed high ratios of infected panicles, whereas the two-gene pyramids and the three-gene pyramid showed high level of panicle blast resistance. However, the two-gene pyramid R504 reached the similar resistance effect of the three-gene pyramid R507 considering resistance spectrum under artificial conditions and panicle blast resistance under field conditions. Generally, the improved lines showed comparable agronomic traits compared with the recurrent parent (RP), but the three-gene pyramid showed reduced grain yield per plant. Conclusions All the improved lines conferred wider resistance spectrum compared with the RP. Yet, the three monogenic lines did not work under field conditions of the two nurseries. Given the similar performances on the main agronomic traits as the RP, the two-gene pyramids have achieved the breeding goals of broad resistance spectrum and effective panicle blast resistance. Whereas, the three-gene pyramid harboring Pi2, Pi46 and Pita seems superfluous considering its reduced yield, although it also showed displayed high level of blast resistance. Thus, rational use of R genes rather than stacking more R genes is recommended to control the disease.

The loss of the shattering ability is one of the key events in rice domestication. The strength of the seed shattering ability is closely related to the harvest yield and the adaptability of modern mechanical harvesting methods. In this study, using a population of 587 natural rice cultivars, quantitative trait loci associated with seed shattering were detected by genome-wide association studies (GWASs). We consider the quantitative trait loci (QTLs) qBTS1 and qBTS3 to be the key loci for seed shattering in rice. Additionally, the abscission zone (AZ) and nonabscission zone (NAZ) of materials with a loss of shattering (DZ129) and easy shattering (W517) were subjected to RNA-Seq, and high-quality differential expression profiles were obtained. The AZ-specific differentially expressed genes (DEGs) of W517 were significantly enriched in plant hormone signal transduction, while the AZ-specific DEGs of DZ129 were enriched in phenylpropanoid biosynthesis. We identified candidate genes for the lignin-associated laccase precursor protein (LOC_Os01g63180) and the glycoside hydrolase family (LOC_Os03g14210) in the QTLs qBTS1 (chromosome 1) and qBTS3 (chromosome 3), respectively. In summary, our findings lay the foundation for the further cloning of qBTS1 and qBTS3, which would provide new insights into seed shattering in rice.

Fatty acid and retinol binding proteins (FAR) are unique proteins found in nematodes and are considered potential targets for controlling these parasites. However, their functions in nematode parasitism and pathogenicity and interaction with hosts are still unclear. In this study, we investigated the specific roles of rice white tip nematodes (RWTNs), Aphelenchoides besseyi, and a protein, Ab-FAR-1, to elucidate the parasitic and pathogenic processes of nematodes. The results showed that the expression level of Ab-far-1 was significantly up-regulated after A. besseyi infection of the plant. The immunofluorescence and subcellular localisation showed that Ab-FAR-1 was secreted into plant tissues mainly through the body wall of nematodes and might act in the nucleus and cytoplasm of plant cells. The pathogenicity of RWTNs was enhanced in Arabidopsis thaliana overexpressing Ab-FAR-1 and inhibited in Ab-far-1 RNAi A. thaliana. Yeast two-hybrid, Co-IP, BiFC, and nematode inoculation experiments showed that Ab-FAR-1 could interact with the A. thaliana actin-depolymerizing factor protein AtADF3, and the A. thaliana adf3 mutant was more susceptible to nematodes. An in vitro actin filament depolymerisation assay demonstrated that Ab-FAR-1 could inhibit AtADF3-mediated depolymerisation of actin filaments, and the turnover process of cellular actin filaments was also affected in A. thaliana overexpressing Ab-FAR-1. In addition, flg22-mediated host defence responses were suppressed in A. thaliana overexpressing Ab-FAR-1 and adf3 mutants. Therefore, this study confirmed that RWTNs can affect the turnover of actin filament remodelling mediated by AtADF3 through Ab-FAR-1 secretion and thus inhibit plant PAMP-triggered immunity (PTI), promoting the parasitism and pathogenicity of nematodes.

The wheat seedlings of 6 days old were daily subjected to ultraviolet irradiation (irradiating for 5, 10, 20, 40, and 60 min/day, respectively), Polyethylene glycol 6000 (5, 10, 15, 20, 25% in 1/2 Hoagland solution, respectively), and salinity solution (10, 25, 50, 100, 200 mM in 1/2 Hoagland solution, respectively), while the control group (CK) was supplied only with the Hoagland solution. The wheatgrass was harvested regularly seven times and the total soluble polysaccharides, ascorbic acid, chlorophyll, total polyphenol, total triterpene, total flavonoid, and proanthocyanins content were tested. The antioxidant capacity was evaluated through 2,2′-azino-bis (3-ethylbenzthia-zoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging ability, and ferric ion reducing power. Technique for order preference by similarity to ideal solution (TOPSIS) mathematical model was adopted to comprehensively assess the functional phytochemicals of the different treatments. The results showed that the accumulation patterns of phytochemicals under abiotic stress were complex and not always upregulated or downregulated. The antioxidant activity and functional phytochemicals content of wheatgrass were significantly affected by both the stress treatments and seedling age, while the latter affected the chemicals more efficiently. The top five highest functional phytochemicals were observed in the 200 mM NaCl treated group on the 21st and 27th day, 25% PEG treated group on the 24th day, 200 mM NaCl treated group on the 24th day, and the group of 40 min/day ultraviolet exposure on 27th day.

Background: The COVID-19 global pandemic has posed unprecedented challenges to health care systems all over the world. The speed of the viral spread results in a tsunami of patients, which begs for a reliable screening tool using readily available data to predict disease progression.Methods: Multicenter retrospective cohort study was performed to develop and validate a triage model. Patient demographic and non-laboratory clinical data were recorded. Using only the data from Zhongnan Hospital, step-wise multivariable logistic regression was performed, and a prognostic nomogram was constructed based on the independent variables identifies. The discrimination and calibration of the model were validated. External independent validation was performed to further address the utility of this model using data from Jinyintan Hospital.Results: A total of 716 confirmed COVID-19 cases from Zhongnan Hospital were included for model construction. Men, increased age, fever, hypertension, cardio-cerebrovascular disease, dyspnea, cough, and myalgia are independent risk factors for disease progression. External independent validation was carried out in a cohort with 201 cases from Jinyintan Hospital. The area under the curve (AUC) was 0.787 (95% confidence interval [CI]: 0.747–0.827) in the training group and 0.704 (95% CI: 0.632–0.777) in the validation group.Conclusions: We developed a novel triage model based on basic and clinical data. Our model could be used as a pragmatic screening aid to allow for cost efficient screening to be carried out such as over the phone, which may reduce disease propagation through limiting unnecessary contact. This may help allocation of limited medical resources.

Abstract Background Appendectomy is considered the first treatment choice for appendicitis. However, controversy exists since conservative therapy is associated with fewer complications than appendectomy for patients with acute appendicitis (AA). This meta-analysis aimed to compare the outcomes between conservative therapy and appendectomy in the management of adult AA. Methods A literature search was performed to screen eligible clinical studies. Subgroup analyses of the uncomplicated population, complicated population and mixed population of randomized clinical trials were subsequently performed. Clinical outcomes included the overall effective rate of treatment, complication rate, relapse rate (reoperation rate) and overall length of stay (LOS). Results Eleven trials totalling 2751 patients (conservative = 1463, appendectomy = 1288) were analysed. Patients receiving conservative treatment had a lower overall effective rate (OR: 0.11 ~ 0.17) and complication rate (OR: 0.21 ~ 0.51). The conservative group had a higher reoperation rate (5.6, 95% CI: 3.1% ~ 10.2%) than the appendectomy group (OR: 9.58 ~ 14.29). Conservative treatment was associated with a shorter overall length of stay (0.47 day, 95% CI: 0.45 ~ 0.5 day) than appendectomy. Conclusions For both uncomplicated and complicated adult AA, non-operative management with antibiotics was associated with significantly fewer complications and a shorter length of stay but a lower effective rate and higher relapse rate.

Abstract Background The development and utilization of genetic markers play a pivotal role in marker-assisted breeding of rice cultivars during pyramiding of valuable genes. Among molecular markers, SNPs have become the most promising due to their wide distribution within genomes and suitability for high -throughput automated genotyping. Although metadata of SNPs have been identified via next generation sequencing in rice, a large gap between the development of SNP markers and the application in breeding still exists. To promote the application of SNP markers based on the KASP (Kompetitive Allele-Specific PCR) method in rice breeding, a set of core SNP arrays was built via the screening of SNP databases and literature resources based on the KASP method. Results Five hundred and ninety six SNPs classified into eight subsets including quality control, indica-indica variation, highly polymorphic, functional genes, key genes targeting sites, gene cloned region, important trait associated and gap filling sites were chosen to design KASP primers and 565 out of them were successfully designed, and the assay design success rate was 94.8%. Finally, 467 out of the 565 successfully-designed SNPs can display diversity at the loci were used to develop a set of core SNP arrays. To evaluate the application value of the core SNP markers in rice breeding, 481 rice germplasms were genotyped with three functional KASP markers designed from the sequences of GBSSI, SSIIa, and Badh2 from the core SNP arrays for estimation of their grain quality performance. Eighteen rice lines, including Xiangwanxian 13, Basmati 370, Ruanhua A, and PR 33319–9–1-1-5-3-5-4-1, harbor all three favorable alleles. The core KASP arrays were also used for rice germplasm assessment, genetic diversity and population evaluation. Four hundred and eighty-one rice germplasms were divided into 3 groups: POP1, POP2 and POP3. POP1 and POP2 were indica rice subgroups consisting of 263 and 186 rice germplasms, respectively. POP3 was a japonica rice subgroup consisting of 32 rice germplasms. The average F ST value for the three subgroups was 0.3501; the F ST value of POP1 and POP3 was the largest (0.5482), while that of POP1 and POP2 was the smallest (0.0721). The results showed that the genetic distance between the japonica and indica rice subspecies was large, indicating that the core SNP markers were effective at discriminating the population structure of the germplasms. Finally, the core KASP arrays were used for association analysis with milled grain traits. A total of 31 KASP markers were significantly associated (P

Single-nucleotide polymorphisms (SNPs) located in the promoter region of the receptor for advanced glycation end products (RAGE) gene have been linked to the activity of RAGE. However, contrary to our expectation, we previously detected no correlation between SNPs within the RAGE promoter and ulcerative colitis (UC) risk in a case-control study. Here, we investigated the methylation of the RAGE promoter and analyzed the collective contribution of methylation and SNPs to UC risk. We found that RAGE promoter hypomethylation was more common in UC patients compared to controls (70% vs. 30%, respectively), as determined via bisulfite sequencing PCR (BSP) and methylation-specific PCR (MSP). Furthermore, we investigated the cooperativity of promoter methylation and SNPs and found that either of two SNPs (rs1800624 or rs1800625) and promoter methylation jointly contributed to UC risk (30 UC patients vs. 30 controls, P

Purpose: Coronavirus disease 2019 (COVID-19) has been associated with acute liver injury in reports worldwide. But no studies to date have described hypoxic hepatitis (HH) in patients with COVID-19. We aim to identify the prevalence of and possible mechanisms of HH in COVID-19 patients in the Intensive Care Unit (ICU).Methods: This retrospective study was conducted on 51 patients with confirmed SARS-CoV-2 infection in the ICU at Zhongnan Hospital of Wuhan University from December 21, 2019, to March 11, 2020. Information on clinical features of enrolled patients was collected for analysis.Results: HH was observed in 5.88% of the ICU patients with SARS-CoV-2 infection. All HH patients were progressing to respiratory failure and peak alanine aminotransferase (ALT) values were 1665, 1414, and 1140 U/L during hospitalization, respectively. All patients with HH died as a result of the deterioration of multiple organ failure (MOF). The dynamic changes of ALT, aspartate transaminase (AST), and total bilirubin (TBIL) levels were more dramatic in HH groups. Levels of TBIL, C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6(IL-6) showed statistically significant elevation in HH cases compared with that in non-HH cases (P < 0.001). Besides, the median survival time of the HH group was significantly shorter than the non-HH group (P < 0.05).Conclusions: In ICU, HH was not a rare condition in patients with severe COVID-19 and has a high mortality. The main causes of HH are respiratory and cardiac failure and may be associated with the immune-mediated inflammatory response. Clinicians should search for any underlying hemodynamic or respiratory instability even in patients with normal ALT levels on admission.

Objective: To investigate the effects of microRNA-137 (MIR137) polymorphisms (rs1198588 and rs2660304) on the risk of schizophrenia in a Han Chinese population.Methods: Schizophrenia was diagnosed according to the DSM-5. Clinical symptoms and cognitive functions were assessed with the Positive and Negative Symptom Scale (PANSS) and Brief Assessment of Cognition in Schizophrenia (BACS), respectively. The polymorphisms were genotyped by improved multiplex ligation detection reaction (iMLDR) technology in 1,116 patients with schizophrenia and 1,039 healthy controls.Results: Significant associations were found between schizophrenia and MIR137 in the distributions of genotypes (p = 0.037 for rs1198588; p = 0.037 for rs2660304, FDR corrected) and alleles (p = 0.043 for rs1198588; p = 0.043 for rs2660304, FDR corrected) of two SNPs. When the population was stratified by sex, we found female-specific associations between MIR137 and schizophrenia in terms of genotype and allele distributions of rs1198588 (χ2 = 4.41, p = 0.036 and χ2 = 4.86, p = 0.029, respectively, FDR corrected) and rs2660304 (χ2 = 4.74, p=0.036 and χ2 = 4.80, p = 0.029, respectively, FDR corrected). Analysis of the MIR137 haplotype rs1198588-rs2660304 showed a significant association with schizophrenia in haplotype T-T [χ2 = 4.60, p = 0.032, OR = 1.32, 95% CI (1.02–1.70)]. Then, significant female-specific associations were found with the haplotypes T-T and G-A [χ2 = 4.92, p = 0.027, OR = 1.62, 95% CI (1.05–2.50); χ2 = 4.42, p = 0.035, OR = 0.62, 95% CI (0.39–0.97), respectively]. When the TT genotype of rs1198588 was compared to the GT+GG genotype, a clinical characteristics analysis also showed a female-specific association in category instances (t = 2.76, p = 0.042, FDR corrected).Conclusion: The polymorphisms within the MIR137 gene are associated with susceptibility to schizophrenia, and a female-specific association of MIR137 with schizophrenia was reported in a Han Chinese population.