Tissue expression of the SARS-CoV-2 cell receptor gene ACE2 in children.

Coronavirus disease 2019 (COVID-19) has become a significant global public health problem. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which causes the disease, utilizes angiotensin-converting enzyme II (ACE2) as a major functional receptor to enter host cells. No study has systematically assessed ACE2 expression in multiple tissues in children. This study investigated ACE2 expression and ACE2 protein's histological distribution in various organs in paediatric patients (the small intestine, thymus, heart and lungs). Our study revealed that ACE2 was highly expressed in enterocytes of the small intestine and widely expressed in the myocardium of heart tissues. The most notable finding was the positive staining of ACE2 in the Hassall's corpuscles epithelial cells. Negligible ACE2 expression in the lung tissues may contribute to a lower risk of infection and fewer symptoms of pneumonia in children than in adults with COVID-19 infection. These findings provide initial evidence for understanding SARS-CoV-2 pathogenesis and prevention strategies in paediatric clinical practice, which should be applicable for all children worldwide.

Natural variation of GmFATA1B regulates seed oil content and composition in soybean.

Soybean (Glycine max) produces seeds that are rich in unsaturated fatty acids and is an important oilseed crop worldwide. Seed oil content and composition largely determine the economic value of soybean. Due to natural genetic variation, seed oil content varies substantially across soybean cultivars. Although much progress has been made in elucidating the genetic trajectory underlying fatty acid metabolism and oil biosynthesis in plants, the causal genes for many quantitative trait loci (QTLs) regulating seed oil content in soybean remain to be revealed. In this study, we identified GmFATA1B as the gene underlying a QTL that regulates seed oil content and composition, as well as seed size in soybean. Nine extra amino acids in the conserved region of GmFATA1B impair its function as a fatty acyl-acyl carrier protein thioesterase, thereby affecting seed oil content and composition. Heterogeneously overexpressing the functional GmFATA1B allele in Arabidopsis thaliana increased both the total oil content and the oleic acid and linoleic acid contents of seeds. Our findings uncover a previously unknown locus underlying variation in seed oil content in soybean and lay the foundation for improving seed oil content and composition in soybean.

Radiotherapy Reduces N-Oxides for Prodrug Activation in Tumors.

Precisely activating chemotherapeutic prodrugs in a tumor-selective manner is an ideal way to cure cancers without causing systemic toxicities. Although many efforts have been made, developing spatiotemporally controllable activation methods is still an unmet challenge. Here, we report a novel prodrug activation strategy using radiotherapy (X-ray). Due to its precision and deep tissue penetration, X-ray matches the need for altering molecules in tumors through water radiolysis. We first demonstrated that N-oxides can be effectively reduced by hydrated electrons (e-aq) generated from radiation both in tubes and living cells. A screening is performed to investigate the structure-reduction relationship and mechanism of the e-aq-mediated reductions. We then apply the strategy to activate N-oxide prodrugs. The anticancer drug camptothecin (CPT)-based N-oxide prodrug shows a remarkable anticancer effect upon activation by radiotherapy. This radiation-induced in vivo chemistry may enable versatile designs of radiotherapy-activated prodrugs, which are of remarkable clinical relevance, as over 50% of cancer patients take radiotherapy.

Radiotherapy-Induced Cleavage of Quaternary Ammonium Groups Activates Prodrugs in Tumors.

Cleavage chemistry offers a new chance to activate chemotherapeutic prodrugs in a tumor-selective manner, yet developing spatiotemporally controllable cleavage chemistry with deep tissue penetration is still a great challenge. Herein, we present a novel radiotherapy-triggered cleavage chemistry that enables controlled drug release in tumors. Quaternary ammonium groups are identified as masking groups that can be efficiently removed by hydrated electrons (e-aq ) from water radiolysis. The subsequently released tertiary amines can be anti-cancer toxins or readily release functional molecules via 1,6-elimination. This radiotherapy-induced cleavage works successfully in living cells and tumor-bearing mice, showing remarkable treatment efficacy when the mice are given carfilzomib prodrug and radiotherapy. This strategy provides a new perspective for combinational radiochemotherapy, which is the first-line treatment for over 50 % of cancer patients.

Challenges of the establishment of rubber-based agroforestry systems: Decreases in the diversity and abundance of ground arthropods.

The global land area devoted to rubber plantations has now reached 13 million hectares, and the further expansion of these rubber plantations at the expense of tropical forests will have significant adverse effects on the ecological environment. Rubber-based agroforestry systems are considered a preferable approach for ameliorating the ecological environment. Many researchers have focused on the positive effects of rubber-based agroforestry systems on the ecological environment, while ignoring the risks involved in the establishment of rubber-based agroforestry systems. The present study investigated the effects of different-aged rubber-based agroforestry systems on the abundance and diversity of ground arthropods. It has been observed that the abundance and taxon richness of ground arthropods generally showed no difference when comparing young and mature rubber plantations. The rubber-based agroforestry systems significantly decreased the understory vegetation species, along with the abundance and taxon richness of ground arthropods compared to the same aged-rubber monoculture plantations. In addition, the change in the abundance and taxon richness of ground arthropods was greatly affected by the understory vegetation species and soil temperature. The abundance and taxon richness of ground arthropods decreased with the decrease in number of species of understory vegetation. The study results indicate that the establishment of rubber-based agroforestry systems have adversely affected the abundance and richness of ground arthropods to an extant greater than expected. Therefore, single, large rubber-based agroforestry systems are not recommended, and the intercropping of rubber and rubber-based agroforestry systems must be designed to promote the migration of ground arthropods between different systems.

[Analysis of TCOF1 mutation in a Chinese patient with Treacher-Collins syndrome].

OBJECTIVE: To detect potential mutation of TCOF1 gene in a Chinese family affected with Treacher-Collins syndrome. METHODS: Clinical data of the patient was collected. The analysis included history taking, clinical examination and genetic testing. All coding regions of the TCOF1 gene were subjected to PCR amplification and Sanger sequencing. RESULTS: A novel mutation c.2261ins G (p.E95X) of the TCOF1 gene was discovered in the patient. The same mutation was not found in his parents and 100 healthy controls. CONCLUSION: The c.2261insG (p.E95X) mutation of the TCOF1 gene probably underlies the disease in the patient. Genetic testing can facilitate diagnosis and genetic counseling for families affected with TCS.

Enhanced yields and soil quality in a wheat-maize rotation using buried straw mulch.

BACKGROUND: Straw return may improve soil quality and crop yields. In a 2-year field study, a straw return method (ditch-buried straw return, DB-SR) was used to investigate the soil quality and crop productivity effects on a wheat-corn rotation system. This study consisted of three treatments, each with three replicates: (1) mineral fertilisation alone (CK0); (2) mineral fertilisation + 7500 kg ha-1 wheat straw incorporated at depth of 0-15 cm (NPKWS); and (3) mineral fertilisation + 7500 kg ha-1 wheat straw ditch buried at 15-30 cm (NPKDW). RESULTS: NPKWS and NPKDW enhanced crop yield and improved soil biotical properties compared to mineral fertilisation alone. NPKDW contributed to greater crop yields and soil nutrient availability at 15-30 cm depths, compared to NPKWS treatment. NPKDW enhanced soil microbial activity and bacteria species richness and diversity in the 0-15 cm layer. NPKWS increased soil microbial biomass, bacteria species richness and diversity at 15-30 cm. CONCLUSIONS: The comparison of the CK0 and NPKWS treatments indicates that a straw ditch buried by digging to the depth of 15-30 cm can improve crop yields and soil quality in a wheat-maize rotation system. © 2016 Society of Chemical Industry.

Fungal community composition in soils subjected to long-term chemical fertilization is most influenced by the type of organic matter.

Organic matter application is a widely used practice to increase soil carbon content and maintain soil fertility. However, little is known about the effect of different types of organic matter, or the input of exogenous species from these materials, on soil fungal communities. In this study, fungal community composition was characterized from soils amended with three types of organic matter over a 30-year fertilization experiment. Chemical fertilization significantly changed soil fungal community composition and structure, which was exacerbated by the addition of organic matter, with the direction of change influenced by the type of organic matter used. The addition of organic matter significantly increased soil fungal richness, with the greatest richness achieved in soils amended with pig manure. Importantly, following addition of cow and pig manure, fungal taxa associated with these materials could be found in the soil, suggesting that these exogenous species can augment soil fungal composition. Moreover, the addition of organic matter decreased the relative abundance of potential pathogenic fungi. Overall, these results indicate that organic matter addition influences the composition and structure of soil fungal communities in predictable ways.

Global epigenomic analysis indicates that epialleles contribute to Allele-specific expression via Allele-specific histone modifications in hybrid rice.

BACKGROUND: For heterozygous genes, alleles on the chromatin from two different parents exhibit histone modification variations known as allele-specific histone modifications (ASHMs). The regulation of allele-specific gene expression (ASE) by ASHMs has been reported in animals. However, to date, the regulation of ASE by ASHM genes remains poorly understood in higher plants. RESULTS: We used chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) to investigate the global ASHM profiles of trimethylation on histone H3 lysine 27 (H3K27me3) and histone H3 lysine 36 (H3K36me3) in two rice F1 hybrids. A total of 522 to 550 allele-specific H3K27me3 genes and 428 to 494 allele-specific H3K36me3 genes were detected in GL × 93-11 and GL × TQ, accounting for 11.09% and 26.13% of the total analyzed genes, respectively. The epialleles between parents were highly related to ASHMs. Further analysis indicated that 52.48% to 70.40% of the epialleles were faithfully inherited by the F1 hybrid and contributed to 33.18% to 46.55% of the ASHM genes. Importantly, 66.67% to 82.69% of monoallelic expression genes contained the H3K36me3 modification. Further studies demonstrated a significant positive correlation of ASE with allele-specific H3K36me3 but not with H3K27me3, indicating that ASHM-H3K36me3 primarily regulates ASE in this study. CONCLUSIONS: Our results demonstrate that epialleles from parents can be inherited by the F1 to produce ASHMs in the F1 hybrid. Our findings indicate that ASHM-H3K36me3, rather than H3K27me3, mainly regulates ASE in hybrid rice.

A SNP in OsMCA1 responding for a plant architecture defect by deactivation of bioactive GA in rice.

Plant architecture directly affects biomass in higher plants, especially grain yields in agricultural crops. In this study, we characterized a recessive mutant, plant architecture determinant (pad), derived from the Oryza sativa ssp. indica cultivar MH86. The mutant exhibited severe dwarf phenotypes, including shorter and stunted leaves, fewer secondary branches during both the vegetative and reproductive growth stages. Cytological studies revealed that pad mutant growth defects are primarily due to the inhibition of cell expansion. The PAD gene was isolated using a map-based cloning strategy. It encodes a plasma membrane protein OsMCA1 and a SNP responsible for a single amino acid change was found in the mutant. PAD was universally expressed in rice tissues from the vegetative to reproductive growth stages, especially in seedlings, nodes and rachillae. Quantitative real-time PCR analysis revealed that the most of the genes responding to gibberellin (GA) metabolism were up-regulated in pad mutant internodes. The endogenous GA content measurement revealed that the levels of GA1 were significantly decreased in the third internode of pad mutants. Moreover, a GA response assay suggested that OsMCA1/PAD might be involved in the regulation of GA metabolism and signal transduction. Our results revealed the pad is a loss-of-function mutant of the OsMCA1/PAD, leading to upregulation of genes related to GA deactivation, which decreased bioactive GA levels.

The OsSec18 complex interacts with P0(P1-P2)2 to regulate vacuolar morphology in rice endosperm cell.

BACKGROUND: Sec18p/N-ethylmaleimide-sensitive factor (NSF) is a conserved eukaryotic ATPase, which primarily functions in vesicle membrane fusion from yeast to human. However, the function of the OsSec18 gene, a homologue of NSF in rice, remains unknown. RESULTS: In the present study, we investigated the function of OsSec18 in rice and found that OsSec18 complements the temperature-sensitive phenotype and interferes with vacuolar morphogenesis in yeast. Overexpression of OsSec18 in rice decreased the plant height and 1000-grain weight and altered the morphology of the protein bodies. Further examination revealed that OsSec18 presented as a 290-kDa complex in rice endosperm cells. Moreover, Os60sP0 was identified a component of this complex, demonstrating that the OsSec18 complex contains another complex of P0(P1-P2)2 in rice endosperm cells. Furthermore, we determined that the N-terminus of OsSec18 can interact with the N- and C-termini of Os60sP0, whereas the C-terminus of OsSec18 can only interact with the C-terminus of Os60sP0. CONCLUSION: Our results revealed that the OsSec18 regulates vacuolar morphology in both yeast and rice endosperm cell and the OsSec18 interacts with P0(P1-P2)2 complex in rice endosperm cell.

The phenotypic predisposition of the parent in F1 hybrid is correlated with transcriptome preference of the positive general combining ability parent.

BACKGROUND: Sprague and Tatum (1942) introduced the concepts of general combining ability (GCA) and specific combining ability (SCA) to evaluate the breeding parents and F1 hybrid performance, respectively. Since then, the GCA was widely used in cross breeding for elite parent selection. However, the molecular basis of GCA remains to unknown. RESULTS: We studied the transcriptomes of three varieties and three F1 hybrids using RNA-Sequencing. Transcriptome sequence analysis revealed that the transcriptome profiles of the F1s were similar to the positive GCA-effect parent. Moreover, the expression levels of most differentially expressed genes (DEGs) were equal to the parent with a positive GCA effect. Analysis of the gene expression patterns of gibberellic acid (GA) and flowering time pathways that determine plant height and flowering time in rice validated the preferential transcriptome expression of the parents with positive GCA effect. Furthermore, H3K36me3 modification bias in the Pseudo-Response Regulators (PRR) gene family was observed in the positive GCA effect parents and demonstrated that the phenotype and transcriptome bias in the positive GCA effect parents have been epigenetically regulated by either global modification or specific signaling pathways in rice. CONCLUSIONS: The results revealed that the transcriptome profiles and DEGs in the F1s were highly related to phenotype bias to the positive GCA-effect parent. The transcriptome bias toward high GCA parents in F1 hybrids attributed to H3K36me3 modification both on global modification level and specific signaling pathways. Our results indicated the transcriptome profile and epigenetic modification level bias to high GCA parents could be the molecular basis of GCA.

Transgenic rice endosperm as a bioreactor for molecular pharming.

Plants provide a promising expression platform for producing recombinant proteins with several advantages in terms of high expression level, lower production cost, scalability, and safety and environment-friendly. Molecular pharming has been recognized as an emerging industry with strategic importance that could play an important role in economic development and healthcare in China. Here, this review represents the significant advances using transgenic rice endosperm as bioreactor to produce various therapeutic recombinant proteins in transgenic rice endosperm and large-scale production of OsrHSA, and discusses the challenges to develop molecular pharming as an emerging industry with strategic importance in China.

Disruption of the thymic microenvironment is associated with thymic involution of transitional cell cancer.

INTRODUCTION: During bladder tumorigenesis, thymopoiesis is usually downregulated. Considering that the thymus is the site of most T-cell development, this phenomenon may be related to thymic involution. However, the mechanisms involved in this phenomenon remain to be elucidated. MATERIALS AND METHODS: An MB 49 murine bladder tumor model was used to identify mechanisms that might underlie this process. RESULTS: The thymuses of tumor-bearing mice showed less cellularity than those of healthy mice. Involution was found to be associated with less proliferation and more apoptosis of thymic epithelial cells (TEC). Foxn1, KGF, and IL-7, three factors known to be involved in thymic development, were also downregulated in the thymuses of tumor bearers. When these mice were intravenously injected with KGF, the thymic microenvironment, thymopoiesis, and T-cell differentiation all returned to near normal status. CONCLUSIONS: The decreases in thymopoiesis and impaired T-cell differentiation may be attributable to changes in the thymic microenvironment. Improving the function of TEC, rather than T-cell progenitors, should be the focus of therapy.

Site-specific controlled-release nanoparticles for immune reprogramming via dual metabolic inhibition against triple-negative breast cancer.

Metabolic heterogeneity and the tumor immunosuppressive microenvironment (TIME) of triple-negative breast cancer (TNBC) hinder therapeutic effectiveness. Although emerging metabolic therapy and immunotherapy show promise, they are limited by off-target effects and immune escape. Here, a redox-activatable, sequentially-releasing nanoparticle (AMANC@M) for tumor-targeted delivery of anticancer agents and CRISPR/Cas9 has been developed. AMANC@M can reverse the TIME through dual metabolic inhibition, thereby enhancing TNBC therapy. AMANC@M demonstrates excellent biosafety and targets tumors precisely through biomimetic hybrid membrane-mediated homologous homing and the enhanced permeability and retention (EPR) effect. Once internalized into tumor cells, the CRISPR/Cas9 system ("energy nanolock") is released through glutathione (GSH) cleavage and effectively knocks down the expression of lactate dehydrogenase A (LDHA) to suppress glycolysis. After peeling off of the gene editing shell, a newly synthesized targeted drug, CPI-Z2 ("nutrihijacker" and "energy nanolock"), is released in a controlled manner to block the mitochondrial tricarboxylic acid (TCA) cycle. Nitric oxide (NO) produced from loaded L-arginine enhances the efficiency of CPI-Z2 and reduces drug resistance. Combined with NO therapy, both blockades of nutrients and energy production transform the hypoxia and acidic TIME into an immunocompetent tumor microenvironment (TME) for tumor elimination. Furthermore, AMANC@M offers capabilities for photothermal (PT) therapy and provides clear imaging through PT, photoacoustic (PA), or computed tomography (CT) signals in tumor tissue. Thus, this study provides a new and promising sequentially stimuli-responsive targeting strategy for nanoparticle development, making it a potential treatment candidate for TNBC and other tumors.

Changing soil available substrate primarily caused by fertilization management contributed more to soil respiration temperature sensitivity than microbial community thermal adaptation.

Substrate depletion and microbial community thermal adaptation are major mechanisms that regulate the temperature sensitivity (Q10) of soil microbial respiration. Traditionally, the Q10 of soil microbial respiration is measured using laboratory incubation, which has limits in the continuous input of available substrates and the time scale for microbial community thermal adaptation. How the available substrate and the soil microbial community regulate the Q10 of soil microbial respiration under natural warming conditions remains unclear. To fill this gap in knowledge, a long-term field experiment was conducted consisting of two years of soil respiration observations combined with a soil available substrate and microbial community thermal adaptation analysis under seasonal warming conditions. The Q10 of soil respiration was calculated using the square root method, and it was more affected by the available substrate than by microbial community thermal adaptation. Fertilization management has a stronger effect on soil available substrate than temperature. As the temperature increased, NH4-N proved itself to be important for the bacterial community in the process of Q10 regulation, while dissolved organic carbon and nitrogen were key factors for the fungal community. Based on the niche breadth of microbial community composition, the changing Q10 of the soil respiration was not only closely associated with the specialist community, but also the generalist and neutralist communities. Furthermore, bacterial community thermal adaptation primarily occurred through shifts in the abundances of specialists and neutralists, while changes in species richness and species replacement occurred for the fungal generalists and neutralists. This work indicates that changing available nitrogen and DOC primarily caused by fertilization management contributed more in regulating the Q10 of soil microbial respiration than microbial community thermal adaptation, and there are different mechanisms for bacterial and fungal community thermal adaptation under warming.

Developing Deep LSTMs With Later Temporal Attention for Predicting COVID-19 Severity, Clinical Outcome, and Antibody Level by Screening Serological Indicators Over Time.

OBJECTIVE: The clinical course of COVID-19, as well as the immunological reaction, is notable for its extreme variability. Identifying the main associated factors might help understand the disease progression and physiological status of COVID-19 patients. The dynamic changes of the antibody against Spike protein are crucial for understanding the immune response. This work explores a temporal attention (TA) mechanism of deep learning to predict COVID-19 disease severity, clinical outcomes, and Spike antibody levels by screening serological indicators over time. METHODS: We use feature selection techniques to filter feature subsets that are highly correlated with the target. The specific deep Long Short-Term Memory (LSTM) models are employed to capture the dynamic changes of disease severity, clinical outcome, and Spike antibody level. We also propose deep LSTMs with a TA mechanism to emphasize the later blood test records because later records often attract more attention from doctors. RESULTS: Risk factors highly correlated with COVID-19 are revealed. LSTM achieves the highest classification accuracy for disease severity prediction. Temporal Attention Long Short-Term Memory (TA-LSTM) achieves the best performance for clinical outcome prediction. For Spike antibody level prediction, LSTM achieves the best permanence. CONCLUSION: The experimental results demonstrate the effectiveness of the proposed models. The proposed models can provide a computer-aided medical diagnostics system by simply using time series of serological indicators.

Global RNA sequencing reveals that genotype-dependent allele-specific expression contributes to differential expression in rice F1 hybrids.

BACKGROUND: Extensive studies on heterosis in plants using transcriptome analysis have identified differentially expressed genes (DEGs) in F1 hybrids. However, it is not clear why yield in heterozygotes is superior to that of the homozygous parents or how DEGs are produced. Global allele-specific expression analysis in hybrid rice has the potential to answer these questions. RESULTS: We report a genome-wide allele-specific expression analysis using RNA-sequencing technology of 3,637-3,824 genes from three rice F1 hybrids. Of the expressed genes, 3.7% exhibited an unexpected type of monoallelic expression and 23.8% showed preferential allelic expression that was genotype-dependent in reciprocal crosses. Those genes exhibiting allele-specific expression comprised 42.4% of the genes differentially expressed between F1 hybrids and their parents. Allele-specific expression accounted for 79.8% of the genes displaying more than a 10-fold expression level difference between an F1 and its parents, and almost all (97.3%) of the genes expressed in F1, but non-expressed in one parent. Significant allelic complementary effects were detected in the F1 hybrids of rice. CONCLUSIONS: Analysis of the allelic expression profiles of genes at the critical stage for highest biomass production from the leaves of three different rice F1 hybrids identified genotype-dependent allele-specific expression genes. A cis-regulatory mechanism was identified that contributes to allele-specific expression, leading to differential gene expression and allelic complementary effects in F1 hybrids.

A proteorhodopsin-based biohybrid light-powering pH sensor.

The biohybrid sensor is an emerging technique for multi-functional detection that utilizes the instinctive responses or interactions of biomolecules. We develop a biohybrid pH sensor by taking advantage of the pH-dependent photoelectric characteristics of proteorhodopsin (pR). The transient absorption kinetics study indicates that the photoelectric behavior of pR is attributed to the varying lifetime of the M intermediate at different environmental pH values. This pR-based biohybrid light-powering sensor with microfluidic design can achieve real-time pH detection with quick response and high sensitivity. The results of this work would shed light on pR and its potential applications.

A water quality assessment method based on an improved grey relational analysis and particle swarm optimization multi-classification support vector machine.

Most of the water quality indicators that affect the results of river water quality assessment are gray and localized, thus the correlation between water quality indicators can be calculated using gray correlation analysis (GRA).However, GRA takes equal weighting for water quality indicators and does not take into account the weighting of the indicators. Therefore, this paper proposes a river water quality assessment method based on improved grey correlation analysis (ACGRA) andparticle swarm optimization multi-classification support vector machine (PSO-MSVM) for assessing river water environment quality. Firstly, the combination weights of water quality indicators were calculated using Analytic Hierarchy Process (AHP)AHP and Criteria Importance Though Intercrieria Correlation (CRITIC)CRITIC, and then the correlation between water quality indicators was calculated for feature selection. Secondly, the PSO-MSVM model was established using the water quality indicators obtained by ACGRA as input parameters for water environment quality assessment. The river water environment assessment methods of ACGRA and PSO-MSVM were applied to the evaluation of water environment quality in different watersheds in the country. Accuracy, precision, recall and root mean square errorRMSE were also introduced as model evaluation criteria. The results show that the river water environment assessment methods based on ACGRA and PSO-MSVM can evaluate the water environment quality more accurately.