Transfection of entomopathogenic Metarhizium species with a mycovirus confers hypervirulence against two lepidopteran pests.

Although most known viruses infecting fungi pathogenic to higher eukaryotes are asymptomatic or reduce the virulence of their host fungi, those that confer hypervirulence to entomopathogenic fungus still need to be explored. Here, we identified and studied a novel mycovirus in Metarhizium flavoviride, isolated from small brown planthopper (Laodelphax striatellus). Based on molecular analysis, we tentatively designated the mycovirus as Metarhizium flavoviride partitivirus 1 (MfPV1), a species in genus Gammapartitivirus, family Partitiviridae. MfPV1 has two double-stranded RNAs as its genome, 1,775 and 1,575 bp in size respectively, encapsidated in isometric particles. When we transfected commercial strains of Metarhizium anisopliae and Metarhizium pingshaense with MfPV1, conidiation was significantly enhanced (t test; P-value < 0. 01), and the significantly higher mortality rates of the larvae of diamondback moth (Plutella xylostella) and fall armyworm (Spodoptera frugiperda), two important lepidopteran pests were found in virus-transfected strains (ANOVA; P-value < 0.05). Transcriptomic analysis showed that transcript levels of pathogenesis-related genes in MfPV1-infected M. anisopliae were obviously altered, suggesting increased production of metarhizium adhesin-like protein, hydrolyzed protein, and destruxin synthetase. Further studies are required to elucidate the mechanism whereby MfPV1 enhances the expression of pathogenesis-related genes and virulence of Metarhizium to lepidopteran pests. This study presents experimental evidence that the transfection of other entomopathogenic fungal species with a mycovirus can confer significant hypervirulence and provides a good example that mycoviruses could be used as a synergistic agent to enhance the biocontrol activity of entomopathogenic fungi.

Adaptive and maladaptive introgression in grapevine domestication.

Domesticated grapevines spread to Europe around 3,000 years ago. Previous studies have revealed genomic signals of introgression from wild to cultivated grapes in Europe, but the time, mode, genomic pattern, and biological effects of these introgression events have not been investigated. Here, we studied resequencing data from 345 samples spanning the distributional range of wild (Vitis vinifera ssp. sylvestris) and cultivated (V. vinifera ssp. vinifera) grapes. Based on machine learning-based population genetic analyses, we detected evidence for a single domestication of grapevine, followed by continuous gene flow between European wild grapes (EU) and cultivated grapes over the past ~2,000 y, especially from EU to wine grapes. We also inferred that soft-selective sweeps were the dominant signals of artificial selection. Gene pathways associated with the synthesis of aromatic compounds were enriched in regions that were both selected and introgressed, suggesting EU wild grapes were an important resource for improving the flavor of cultivated grapes. Despite the potential benefits of introgression in grape improvement, the introgressed fragments introduced a higher deleterious burden, with most deleterious SNPs and structural variants hidden in a heterozygous state. Cultivated wine grapes have benefited from adaptive introgression with wild grapes, but introgression has also increased the genetic load. In general, our study of beneficial and harmful effects of introgression is critical for genomic breeding of grapevine to take advantage of wild resources.

miR156-PvSPL2 controls culm development by transcriptional repression of switchgrass CYTOKININ OXIDASE/DEHYDROGENASE4.

Culm development in grasses can be controlled by both miR156 and cytokinin. However, the crosstalk between the miR156-SPL module and the cytokinin metabolic pathway remains largely unknown. Here, we found CYTOKININ OXIDASE/DEHYDROGENASE4 (PvCKX4) plays a negative regulatory role in culm development of the bioenergy grass Panicum virgatum (switchgrass). Overexpression of PvCKX4 in switchgrass reduced the internode diameter and length without affecting tiller number. Interestingly, we also found that PvCKX4 was always upregulated in miR156 overexpressing (miR156OE) transgenic switchgrass lines. Additionally, upregulation of either miR156 or PvCKX4 in switchgrass reduced the content of isopentenyl adenine (iP) without affecting trans-zeatin (tZ) accumulation. It is consistent with the evidence that the recombinant PvCKX4 protein exhibited much higher catalytic activity against iP than tZ in vitro. Furthermore, our results showed that miR156-targeted SPL2 bound directly to the promoter of PvCKX4 to repress its expression. Thus, alleviating the SPL2-mediated transcriptional repression of PvCKX4 through miR156 overexpression resulted in a significant increase in cytokinin degradation and impaired culm development in switchgrass. On the contrary, suppressing PvCKX4 in miR156OE transgenic plants restored iP content, internode diameter, and length to wild-type levels. Most strikingly, the double transgenic lines retained the same increased tiller numbers as the miR156OE transgenic line, which yielded more biomass than the wild type. These findings indicate that the miR156-SPL module can control culm development through transcriptional repression of PvCKX4 in switchgrass, which provides a promising target for precise design of shoot architecture to yield more biomass from grasses.

Paternal USP26 mutations raise Klinefelter syndrome risk in the offspring of mice and humans.

Current understanding holds that Klinefelter syndrome (KS) is not inherited, but arises randomly during meiosis. Whether there is any genetic basis for the origin of KS is unknown. Here, guided by our identification of some USP26 variations apparently associated with KS, we found that knockout of Usp26 in male mice resulted in the production of 41, XXY offspring. USP26 protein is localized at the XY body, and the disruption of Usp26 causes incomplete sex chromosome pairing by destabilizing TEX11. The unpaired sex chromosomes then result in XY aneuploid spermatozoa. Consistent with our mouse results, a clinical study shows that some USP26 variations increase the proportion of XY aneuploid spermatozoa in fertile men, and we identified two families with KS offspring wherein the father of the KS patient harbored a USP26-mutated haplotype, further supporting that paternal USP26 mutation can cause KS offspring production. Thus, some KS should originate from XY spermatozoa, and paternal USP26 mutations increase the risk of producing KS offspring.

Southern rice black-streaked dwarf virus induces incomplete autophagy for persistence in gut epithelial cells of its vector insect.

Autophagy plays an important role in virus infection of the host, because viral components and particles can be degraded by the host's autophagy and some viruses may be able to hijack and subvert autophagy for its benefit. However, details on the mechanisms that govern autophagy for immunity against viral infections or benefit viral survival remain largely unknown. Plant reoviruses such as southern rice black-streaked dwarf virus (SRBSDV), which seriously threaten crop yield, are only transmitted by vector insects. Here, we report a novel mechanism by which SRBSDV induces incomplete autophagy by blocking autophagosome-lysosome fusion, resulting in viral accumulation in gut epithelial cells of its vector, white-backed planthopper (Sogatella furcifera). SRBSDV infection leads to stimulation of the c-Jun N-terminal kinase (JNK) signaling pathway, which further activates autophagy. Mature and assembling virions were found close to the edge7 of the outer membrane of autophagosomes. Inhibition autophagy leads to the decrease of autophagosomes, which resulting in impaired maturation of virions and the decrease of virus titer, whereas activation of autophagy facilitated virus titer. Further, SRBSDV inhibited fusion of autophagosomes and lysosomes by interacting with lysosomal-associated membrane protein 1 (LAMP1) using viral P10. Thus, SRBSDV not only avoids being degrading by lysosomes, but also further hijacks these non-fusing autophagosomes for its subsistence. Our findings reveal a novel mechanism of reovirus persistence, which can explain why SRBSDV can be acquired and transmitted rapidly by its insect vector.

Population comparative genomics discovers gene gain and loss during grapevine domestication.

Plant domestication are evolutionary experiments conducted by early farmers since thousands years ago, during which the crop wild progenitors are artificially selected for desired agronomic traits along with dramatic genomic variation in the course of moderate to severe bottlenecks. However, previous investigations are mainly focused on small-effect variants, while changes in gene contents are rarely investigated due to the lack of population-level assemblies for both the crop and its wild relatives. Here, we applied comparative genomic analyses to discover gene gain and loss during grapevine domestication using long-read assemblies of representative population samples for both domesticated grapevines (V. vinifera ssp. vinifera) and their wild progenitors (V. vinifera ssp. sylvestris). Only ∼7% of gene families were shared by 16 Vitis genomes while ∼8% of gene families were specific to each accession, suggesting dramatic variations of gene contents in grapevine genomes. Compared to wild progenitors, the domesticated accessions exhibited an increased presence of genes associated with asexual reproduction, while the wild progenitors showcased a higher abundance of genes related to pollination, revealing the transition from sexual reproduction to clonal propagation during domestication processes. Moreover, the domesticated accessions harbored fewer disease-resistance genes than wild progenitors. The SVs occurred frequently in aroma and disease-resistance related genes between domesticated grapevines and wild progenitors, indicating the rapid diversification of these genes during domestication. Our study provides insights and resources for biological studies and breeding programs in grapevine.

Deciphering the genetic basis of resistome and virulome diversity among multidrug-resistant Mycoplasma hominis.

Mycoplasma hominis, a commensal bacterium that commonly inhabits the genital tract, leading to infections in both the genitourinary and extragenital regions. However, the antimicrobial resistance and pathogenic mechanisms of M. hominis isolated from extra-urogenital cystic abscess is largely unknown. This study reports the genomic epidemiological characteristics of a M. hominis isolate recovered from a pelvic abscess sample in China. Genomic DNA was extracted and sequenced using Illumina HiSeq X Ten platform. De novo assembly was performed and in silico analysis was accomplished by multiple bioinformatics tools. For phylogenomic analysis, publicly available M. hominis genomes were retrieved from NCBI GenBank database. Whole genome sequencing data showed that the genome size of M. hominis MH4246 was calculated as 679,746 bp, with 558 protein-coding sequences and a G + C content of 26.9%. M. hominis MH4246 is resistant to fluoroquinolones and macrolides, harboring mutations in the quinolone resistance-determining regions (QRDRs) (GyrA S153L, ParC S91I and ParE V417I) and 23S rRNA gene (G280A, C1500T, T1548C and T2218C). Multiple virulence determinants, such as tuf, hlyA, vaa, oppA, MHO_0730 and alr genes, were identified. Phylogenetic analysis showed that the closest relative of M. hominis MH4246 was the strain MH-1 recovered from China, which differed by 3490 SNPs. Overall, this study contributes to the comprehension of genomic characteristics, antimicrobial resistance patterns, and the mechanisms underlying the pathogenicity of this pathogen.

Activation of Rictor/mTORC2 signaling acts as a pivotal strategy to protect against sensorineural hearing loss.

The Food and Drug Administration­approved drug sirolimus, which inhibits mechanistic target of rapamycin (mTOR), is the leading candidate for targeting aging in rodents and humans. We previously demonstrated that sirolimus could treat ARHL in mice. In this study, we further demonstrate that sirolimus protects mice against cocaine-induced hearing loss. However, using efficacy and safety tests, we discovered that mice developed substantial hearing loss when administered high doses of sirolimus. Using pharmacological and genetic interventions in murine models, we demonstrate that the inactivation of mTORC2 is the major driver underlying hearing loss. Mechanistically, mTORC2 exerts its effects primarily through phosphorylating in the AKT/PKB signaling pathway, and ablation of P53 activity greatly attenuated the severity of the hearing phenotype in mTORC2-deficient mice. We also found that the selective activation of mTORC2 could protect mice from acoustic trauma and cisplatin-induced ototoxicity. Thus, in this study, we discover a function of mTORC2 and suggest that its therapeutic activation could represent a potentially effective and promising strategy to prevent sensorineural hearing loss. More importantly, we elucidate the side effects of sirolimus and provide an evaluation criterion for the rational use of this drug in a clinical setting.

Blocking miR528 function promotes tillering and regrowth in switchgrass.

MiRNAs have been reported to be the key regulators involving a wide range of biological processes in diverse plant species, but their functions in switchgrass, an important biofuel and forage crop, are largely unknown. Here, we reported the novel function of miR528, which has expanded to four copies in switchgrass, in controlling biomass trait of tillering number and regrowth rate after mowing. Blocking miR528 activity by expressing short tandem target mimic (STTM) increased tiller number and regrowth rate after mowing. The quadruple pvmir528 mutant lines derived from genome editing also showed such improved traits. Degradome and RNA-seq analysis, combined with in situ hybridization assay revealed that up-regulation of two miR528 targets coding for Cu/Zn-SOD enzymes, might be responsible for the improved traits of tillering and regrowth in pvmir528 mutant. Additionally, natural variations in the miR528-SOD interaction exist in C3 and C4 monocot species, implying the distinct regulatory strength of the miR528-SOD module during monocot evolution. Overall, our data illuminated a novel role of miR528 in controlling biomass traits and provided a new target for genetic manipulation-mediated crop improvement.

Comprehensive genetic analysis of facioscapulohumeral muscular dystrophy by Nanopore long-read whole-genome sequencing.

BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is a high-prevalence autosomal dominant neuromuscular disease characterized by significant clinical and genetic heterogeneity. Genetic diagnosis of FSHD remains a challenge because it cannot be detected by standard sequencing methods and requires a complex diagnosis workflow. METHODS: We developed a comprehensive genetic FSHD detection method based on Oxford Nanopore Technologies (ONT) whole-genome sequencing. Using a case-control design, we applied this procedure to 29 samples and compared the results with those from optical genome mapping (OGM), bisulfite sequencing (BSS), and whole-exome sequencing (WES). RESULTS: Using our ONT-based method, we identified 59 haplotypes (35 4qA and 24 4qB) among the 29 samples (including a mosaic sample), as well as the number of D4Z4 repeat units (RUs). The pathogenetic D4Z4 RU contraction identified by our ONT-based method showed 100% concordance with OGM results. The methylation levels of the most distal D4Z4 RU and the double homeobox 4 gene (DUX4) detected by ONT sequencing are highly consistent with the BSS results and showed excellent diagnostic efficiency. Additionally, our ONT-based method provided an independent methylation profile analysis of two permissive 4qA alleles, reflecting a more accurate scenario than traditional BSS. The ONT-based method detected 17 variations in three FSHD2-related genes from nine samples, showing 100% concordance with WES. CONCLUSIONS: Our ONT-based FSHD detection method is a comprehensive method for identifying pathogenetic D4Z4 RU contractions, methylation level alterations, allele-specific methylation of two 4qA haplotypes, and variations in FSHD2-related genes, which will all greatly improve genetic testing for FSHD.

Ureaplasma infections: update on epidemiology, antimicrobial resistance, and pathogenesis.

Human Ureaplasma species are being increasingly recognized as opportunistic pathogens in human genitourinary tract infections, infertility, adverse pregnancy, neonatal morbidities, and other adult invasive infections. Although some general reviews have focused on the detection and clinical manifestations of Ureaplasma spp., the molecular epidemiology, antimicrobial resistance, and pathogenesis of Ureaplasma spp. have not been adequately explained. The purpose of this review is to offer valuable insights into the current understanding and future research perspectives of the molecular epidemiology, antimicrobial resistance, and pathogenesis of human Ureaplasma infections. This review summarizes the conventional culture and detection methods and the latest molecular identification technologies for Ureaplasma spp. We also reviewed the global prevalence and mechanisms of antibiotic resistance for Ureaplasma spp. Aside from regular antibiotics, novel antibiotics with outstanding in vitro antimicrobial activity against Ureaplasma spp. are described. Furthermore, we discussed the pathogenic mechanisms of Ureaplasma spp., including adhesion, proinflammatory effects, cytotoxicity, and immune escape effects, from the perspectives of pathology, related molecules, and genetics.

PHOTOLYASE/BLUE LIGHT RECEPTOR2 regulates chrysanthemum flowering by compensating for gibberellin perception.

The gibberellins (GAs) receptor GA INSENSITIVE DWARF1 (GID1) plays a central role in GA signal perception and transduction. The typical photoperiodic plant chrysanthemum (Chrysanthemum morifolium) only flowers when grown in short-day photoperiods. In addition, chrysanthemum flowering is also controlled by the aging pathway, but whether and how GAs participate in photoperiod- and age-dependent regulation of flowering remain unknown. Here, we demonstrate that photoperiod affects CmGID1B expression in response to GAs and developmental age. Moreover, we identified PHOTOLYASE/BLUE LIGHT RECEPTOR2, an atypical photocleavage synthase, as a CRYPTOCHROME-INTERACTING bHLH1 interactor with which it forms a complex in response to short days to activate CmGID1B transcription. Knocking down CmGID1B raised endogenous bioactive GA contents and GA signal perception, in turn modulating the expression of the aging-related genes MicroRNA156 and SQUAMOSA PROMOTER BINDING PROTEIN-LIKE3. We propose that exposure to short days accelerates the juvenile-to-adult transition by increasing endogenous GA contents and response to GAs, leading to entry into floral transformation.

Combination of betulinic acid and EGFR-TKIs exerts synergistic anti-tumor effects against wild-type EGFR NSCLC by inducing autophagy-related cell death via EGFR signaling pathway.

BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of lung cancer patients with mutated EGFR. However, the efficacy of EGFR-TKIs in wild-type EGFR tumors has been shown to be marginal. Methods that can sensitize EGFR-TKIs to EGFR wild-type NSCLC remain rare. Hence, we determined whether combination treatment can maximize the therapeutic efficacy of EGFR-TKIs. METHODS: We established a focused drug screening system to investigate candidates for overcoming the intrinsic resistance of wild-type EGFR NSCLC to EGFR-TKIs. Molecular docking assays and western blotting were used to identify the binding mode and blocking effect of the candidate compounds. Proliferation assays, analyses of drug interactions, colony formation assays, flow cytometry and nude mice xenograft models were used to determine the effects and investigate the molecular mechanism of the combination treatment. RESULTS: Betulinic acid (BA) is effective at targeting EGFR and synergizes with EGFR-TKIs (gefitinib and osimertinib) preferentially against wild-type EGFR. BA showed inhibitory activity due to its interaction with the ATP-binding pocket of EGFR and dramatically enhanced the suppressive effects of EGFR-TKIs by blocking EGFR and modulating the EGFR-ATK-mTOR axis. Mechanistic studies revealed that the combination strategy activated EGFR-induced autophagic cell death and that the EGFR-AKT-mTOR signaling pathway was essential for completing autophagy and cell cycle arrest. Activation of the mTOR pathway or blockade of autophagy by specific chemical agents markedly attenuated the effect of cell cycle arrest. In vivo administration of the combination treatment caused marked tumor regression in the A549 xenografts. CONCLUSIONS: BA is a potential wild-type EGFR inhibitor that plays a critical role in sensitizing EGFR-TKI activity. BA combined with an EGFR-TKI effectively suppressed the proliferation and survival of intrinsically resistant lung cancer cells via the inhibition of EGFR as well as the induction of autophagy-related cell death, indicating that BA combined with an EGFR-TKI may be a potential therapeutic strategy for overcoming the primary resistance of wild-type EGFR-positive lung cancers.

Formate and CO2 Enable Reductive Carboxylation of Imines: Synthesis of Unnatural α-Amino Acids.

Herein, a photocatalytic umpolung strategy for reductive carboxylation of imines for the synthesis of α-amino acids was disclosed. Carbon dioxide radical anion (CO2•-) generated from formate is the key single electron reductant in the reactions. An unprecedentedly broad substrate scope of imines with excellent reaction yields was obtained with carbon dioxide (CO2) and formate salt as carbon sources.

Fermented bile acids improved growth performance and intestinal health by altering metabolic profiles and intestinal microbiome in Micropterus salmoides.

A type of fermented bile acids (FBAs) has been produced through a biological method, and its effects on growth performance, metabolism, and intestinal microbiota in largemouth bass were investigated. The results demonstrated that incorporating 0.03 %-0.05 % FBAs diet could improve the final weight, weight gain and specific growth rate, and decrease the feed conversion ratio. Dietary FBAs did not significantly affect the levels of high-density lipoprotein, low-density lipoprotein, and triglycerides, but decreased the activities of α-amylase in most groups. Adding FBAs to the diet significantly increased the integrity of the microscopic structure of the intestine, thickened the muscular layer of the intestine, and notably enhanced its intestinal barrier function. The addition of FBAs to the diet increased the diversity of the gut microbiota in largemouth bass. At the phylum level, there was an increase in the abundance of Proteobacteria, Firmicutes, Tenericutes and Cyanobacteria and a significant decrease in Actinobacteria and Bacteroidetes. At the genus level, the relative abundance of beneficial bacteria Mycoplasma in the GN6 group and Coprococcus in the GN4 group significantly increased, while the pathogenic Enhydrobacter was inhibited. Meanwhile, the highest levels of AKP and ACP were observed in the groups treated with 0.03 % FBAs, while the highest levels of TNF-α and IL-10 were detected in the group treated with 0.04 % FBAs. Additionally, the highest levels of IL-1ß, IL-8T, GF-ß, IGF-1, and IFN-γ were noted in the group treated with 0.06 % FBAs. These results suggested that dietary FBAs improved growth performance and intestinal wall health by altering lipid metabolic profiles and intestinal microbiota in largemouth bass.

Factors influencing necrotizing enterocolitis in premature infants in China: a systematic review and meta-analysis.

BACKGROUND: Necrotizing enterocolitis (NEC) is a multifactorial gastrointestinal disease with high morbidity and mortality among premature infants. However, studies with large samples on the factors of NEC in China have not been reported. This meta-analysis aims to systematically review the literature to explore the influencing factors of necrotizing enterocolitis in premature infants in China and provide a reference for the prevention of NEC. METHODS: PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database (CBM), Wanfang and VIP databases were systematically searched from inception to February 2023. We used Stata14.0 software to perform the systematic review and meta-analysis. We used fixed or random effects models with combined odds ratios (ORs) and 95% confidence intervals (CIs), and quality was evaluated using the Newcastle‒Ottawa Scale (NOS). RESULTS: The total sample was 8616 cases, including 2456 cases in the intervention group and 6160 cases in the control group. It was found that 16 risk factors and 3 protective factors were related to necrotizing enterocolitis in premature infants. Septicemia (OR = 3.91), blood transfusion (OR = 2.41), neonatal asphyxia (OR = 2.46), pneumonia (OR = 6.17), infection (OR = 5.99), congenital heart disease (OR = 4.80), intrahepatic cholestasis of pregnancy (ICP) (OR = 2.71), mechanical ventilation (OR = 1.44), gestational diabetes mellitus (GDM) (OR = 3.08), respiratory distress syndrome (RDS) (OR = 3.28), hypoalbuminemia (OR = 2.80), patent ductus arteriosus (PDA) (OR = 3.10), respiratory failure (OR = 7.51), severe anemia (OR = 2.86), history of antibiotic use (OR = 2.12), and meconium-stained amniotic fluid (MSAF) (OR = 3.14) were risk factors for NEC in preterm infants in China. Breastfeeding (OR = 0.31), oral probiotics (OR = 0.36), and prenatal use of glucocorticoids (OR = 0.38) were protective factors for NEC in preterm infants. CONCLUSIONS: Septicemia, blood transfusion, neonatal asphyxia, pneumonia, infection, congenital heart disease, ICP, GDM, RDS, hypoproteinemia, PDA, respiratory failure, severe anemia, history of antibiotic use and MSAF will increase the risk of NEC in premature infants, whereas breastfeeding, oral probiotics and prenatal use of glucocorticoids reduce the risk. Due to the quantity and quality of the included literature, the above findings need to be further validated by more high-quality studies.

Biological pathway expression complementation contributes to biomass heterosis in Arabidopsis.

The mechanisms underlying heterosis have long remained a matter of debate, despite its agricultural importance. How changes in transcriptional networks during plant development are relevant to the continuous manifestation of growth vigor in hybrids is intriguing and unexplored. Here, we present an integrated high-resolution analysis of the daily dynamic growth phenotypes and transcriptome atlases of young Arabidopsis seedlings (parental ecotypes [Col-0 and Per-1] and their F1 hybrid). Weighted gene coexpression network analysis uncovered divergent expression patterns between parents of the network hub genes, in which genes related to the cell cycle were more highly expressed in one parent (Col-0), whereas those involved in photosynthesis were more highly expressed in the other parent (Per-1). Notably, the hybrid exhibited spatiotemporal high-parent-dominant expression complementation of network hub genes in the two pathways during seedling growth. This suggests that the integrated capacities of cell division and photosynthesis contribute to hybrid growth vigor, which could be enhanced by temporal advances in the progression of leaf development in the hybrid relative to its parents. Altogether, this study provides evidence of expression complementation between fundamental biological pathways in hybrids and highlights the contribution of expression dominance in heterosis.

Increased long-distance and homo-trans interactions related to H3K27me3 in Arabidopsis hybrids.

In plants, the genome structure of hybrids changes compared with their parents, but the effects of these changes in hybrids remain elusive. Comparing reciprocal crosses between Col × C24 and C24 × Col in Arabidopsis using high-throughput chromosome conformation capture assay (Hi-C) analysis, we found that hybrid three-dimensional (3D) chromatin organization had more long-distance interactions relative to parents, and this was mainly located in promoter regions and enriched in genes with heterosis-related pathways. The interactions between euchromatin and heterochromatin were increased, and the compartment strength decreased in hybrids. In compartment domain (CD) boundaries, the distal interactions were more in hybrids than their parents. In the hybrids of CURLY LEAF (clf) mutants clfCol × clfC24 and clfC24 × clfCol , the heterosis phenotype was damaged, and the long-distance interactions in hybrids were fewer than in their parents with lower H3K27me3. ChIP-seq data revealed higher levels of H3K27me3 in the region adjacent to the CD boundary and the same interactional homo-trans sites in the wild-type (WT) hybrids, which may have led to more long-distance interactions. In addition, the differentially expressed genes (DEGs) located in the boundaries of CDs and loop regions changed obviously in WT, and the functional enrichment for DEGs was different between WT and clf in the long-distance interactions and loop regions. Our findings may therefore propose a new epigenetic explanation of heterosis in the Arabidopsis hybrids and provide new insights into crop breeding and yield increase.

[Bionic design, preparation and clinical translation of oral hard tissue restorative materials].

Oral diseases concern almost every individual and are a serious health risk to the population. The restorative treatment of tooth and jaw defects is an important means to achieve oral function and support the appearance of the contour. Based on the principle of "learning from the nature", Deng Xuliang's group of Peking University School and Hospital of Stomatology has proposed a new concept of "microstructural biomimetic design and tissue adaptation of tooth/jaw materials" to address the worldwide problems of difficulty in treating dentine hypersensitivity, poor prognosis of restoration of tooth defects, and vertical bone augmentation of alveolar bone after tooth loss. The group has broken through the bottleneck of multi-stage biomimetic technology from the design of microscopic features to the enhancement of macroscopic effects, and invented key technologies such as crystalline/amorphous multi-level assembly, ion-transportation blocking, and multi-physical properties of the micro-environment reconstruction, etc. The group also pioneered the cationic-hydrogel desensitizer, digital stump and core integrated restorations, and developed new crown and bridge restorative materials, gradient functionalisation guided tissue regeneration membrane, and electrically responsive alveolar bone augmentation restorative membranes, etc. These products have established new clinical strategies for tooth/jaw defect repair and achieved innovative results. In conclusion, the research results of our group have strongly supported the theoretical improvement of stomatology, developed the technical system of oral hard tissue restoration, innovated the clinical treatment strategy, and led the progress of the stomatology industry.

CNN-HT: A Two-Stage Algorithm Selection Framework.

The No Free Lunch Theorem tells us that no algorithm can beat other algorithms on all types of problems. The algorithm selection structure is proposed to select the most suitable algorithm from a set of algorithms for an unknown optimization problem. This paper introduces an innovative algorithm selection approach called the CNN-HT, which is a two-stage algorithm selection framework. In the first stage, a Convolutional Neural Network (CNN) is employed to classify problems. In the second stage, the Hypothesis Testing (HT) technique is used to suggest the best-performing algorithm based on the statistical analysis of the performance metric of algorithms that address various problem categories. The two-stage approach can adapt to different algorithm combinations without the need to retrain the entire model, and modifications can be made in the second stage only, which is an improvement of one-stage approaches. To provide a more general structure for the classification model, we adopt Exploratory Landscape Analysis (ELA) features of the problem as input and utilize feature selection techniques to reduce the redundant ones. In problem classification, the average accuracy of classifying problems using CNN is 96%, which demonstrates the advantages of CNN compared to Random Forest and Support Vector Machines. After feature selection, the accuracy increases to 98.8%, further improving the classification performance while reducing the computational cost. This demonstrates the effectiveness of the first stage of the CNN-HT method, which provides a basis for algorithm selection. In the experiments, CNN-HT shows the advantages of the second stage algorithm as well as good performance with better average rankings in different algorithm combinations compared to the individual algorithms and another algorithm combination approach.