Chemically induced revitalization of damaged hepatocytes for regenerative liver repair.

In prolonged liver injury, hepatocytes undergo partial identity loss with decreased regenerative capacity, resulting in liver failure. Here, we identified a five compound (5C) combination that could restore hepatocyte identity and reverse the damage-associated phenotype (e.g., dysfunction, senescence, epithelial to mesenchymal transition, growth arrest, and pro-inflammatory gene expression) in damaged hepatocytes (dHeps) from CCl4-induced mice with chronic liver injury, resembling a direct chemical reprogramming approach. Systemic administration of 5C in mice with chronic liver injury promoted hepatocyte regeneration, improved liver function, and ameliorated liver fibrosis. The hepatocyte-associated transcriptional networks were reestablished with chemical treatment as revealed by motif analysis of ATAC-seq, and a hepatocyte-enriched transcription factor, Foxa2, was found to be essential for hepatocyte revitalization. Overall, our findings indicate that the phenotype and transcriptional program of dHeps can be reprogrammed to generate functional and regenerative hepatocytes by using only small molecules, as an alternative approach to liver repair and regeneration.

Risk factors for lower extremity lymphedema after inguinal lymphadenectomy in melanoma patients: A retrospective cohort study.

Background: The aim of lymph node dissection for melanoma patients is to prevent metastasis. However, this procedure is accompanied by a long-term and impaired life-quality complication called extremity lymphedema. This condition involves long-term lower limb swelling, which causes discomfort and impaired function, and affects patients both physically and psychologically. Herein, we conducted a retrospective cohort study at a single center to investigate the risk factors associated with lower extremity lymphedema after inguinal lymphadenectomy. Materials and Methods: We identified 136 inguinal lymphadenectomy melanoma patients treated between January 2010 and January 2021. The patients' demographic, clinical, and pathological data and postoperative outcomes were collected by electronic medical record review and patient follow-up. The patients' postoperative outcomes were defined as lower extremity swelling and lower extremity lymphedema. Univariate and multivariate analyses were used to determine the independent predictors of lower extremity lymphedema. Results: The follow-up results from 85 melanoma patients who underwent inguinal lymphadenectomy were analyzed. Multivariate logistic regression analysis showed that number of lymph nodes removed ≥ 10 was the significant risk factor for postoperative lower extremity lymphedema (odds ratio = 6.468, P = .042, 95% confidence interval: 1.069 to 39.147). Moreover, 8 (100%) patients in the lower extremity lymphedema group and 32 (53.3%) patients in the normal group were female, which indicated that female patients might be more susceptible to postoperative lower extremity lymphedema (P = .012). Conclusion: Our study found that number of inguinal lymph nodes removed ≥ 10 was associated with a significantly higher incidence of lower extremity lymphedema with a 6.5-fold increased risk in melanoma patients. Also, female patients were more likely to develop lower extremity lymphedema after inguinal lymphadenectomy.

Whole-genome analysis of CGS, SAHH, SAMS gene families in five Rosaceae species and their expression analysis in Pyrus bretschneideri.

Cystathionine γ-synthase (CGS), S-adenosyl-L-homocysteine hydrolase (SAHH), and S-adenosy-L-methionine synthetase (SAMS) play an important role in the regulation of plant growth, development, and secondary metabolism. In this study, a total of 6 CGS, 6 SAHH, and 28 SAMS genes were identified from five Rosaceae species (Pyrus bretschneideri, Prunus persica, Prunus mume, Fragaria vesca, and Malus domestica). The evolutionary relationship and microsynteny analysis in five Rosaceae species revealed that duplicated regions were conserved between three gene families (CGS, SAHH, SAMS). Moreover, the chromosomal locations, gene structures, conserved motifs, cis-elements, physicochemical properties, and Ka/Ks analysis were performed by using numerous bioinformatics tools. The expression of different organs showed that the CGS, SAHH and SAMS genes of pear have relatively high expression patterns in flowers and stems, except for PbCGS1. RNA-seq and qRT-PCR combined analysis showed that PbSAMS1 may be involved in the regulation of pear stone cell development. In summary, this study provides the basic information of CGS, SAHH and SAMS genes in five Rosaceae species, further revealing the expression patterns in the pear fruit, which provides the theoretical basis for the regulation of pear stone cells.

Comparative genomic analysis of superoxide dismutase (SOD) genes in three Rosaceae species and expression analysis in Pyrus bretschneideri.

Superoxide dismutases (SODs) are antioxidant enzymes that play a critical role in the polymerization of lignin monomers. Although current research has indicated that SODs are involved in plant growth and development, information on SODs in pear (Pyrus bretschneideri) and their function in lignin formation is scarce. In this study, 25 SODs, containing three kinds of plant SODs (Cu/Zn-SODs, Mn-SODs, and Fe-SODs), were identified from three Rosaceae species, and 11 of these genes were found in pear. According to the evolutionary analysis, the genes were divided into four subgroups, the division of which is consistent with the intron-exon and conserved motif analyses. These PbSODs were randomly scattered across 7 chromosomes. We have analysed the conserved domains and gene family evolution and predicted the cis-elements of the promoter. Ka/Ks analysis pointed that SOD genes mainly underwent purifying selection. Subsequently, the expression patterns of 11 PbSODs were examined in different tissues, at different developmental periods, in different pear varieties and under different hormone treatments. Gene expression analysis showed that PbCSD3 exhibited transcript levels consistent with the typical changes in lignin content. The changes in SOD activity and hydrogen peroxide (H2O2) content combined with the results of a spatio-temporal expression analysis showed that PbCSD3 was a candidate gene in reactive oxygen species (ROS) metabolism during the lignification of pear stone cells. Thus, our research reveals the evolutionary features of the SOD family in Rosaceae species and provide useful information for analysis of functional genome of the SOD family in pear. SUPPLEMENTARY INFORMATION: The online version of this article (10.1007/s12298-021-00926-2) contains supplementary material, which is available to authorized users.

RIGD: A Database for Intronless Genes in the Rosaceae.

Most eukaryotic genes are interrupted by one or more introns, and only prokaryotic genomes are composed of mainly single-exon genes without introns. Due to the absence of introns, intronless genes in eukaryotes have become important materials for comparative genomics and evolutionary biology. There is currently no cohesive database that collects intronless genes in plants into a single database, although many databases on exons and introns exist. In this study, we constructed the Rosaceae Intronless Genes Database (RIGD), a user-friendly web interface to explore and collect information on intronless genes from different plants. Six Rosaceae species, Pyrus bretschneideri, Pyrus communis, Malus domestica, Prunus persica, Prunus mume, and Fragaria vesca, are included in the current release of the RIGD. Sequence data and gene annotation were collected from different databases and integrated. The main purpose of this study is to provide gene sequence data. In addition, attribute analysis, functional annotations, subcellular localization prediction, and GO analysis are reported. The RIGD allows users to browse, search, and download data with ease. Blast and comparative analyses are also provided through this online database, which is available at http://www.rigdb.cn/.

Electric Field-Controlled Multistep Proton Evolution in H x SrCoO2.5 with Formation of H-H Dimer.

Ionic evolution-induced phase transformation can lead to wide ranges of novel material functionalities with promising applications. Here, using the gating voltage during ionic liquid gating as a tuning knob, the brownmillerite SrCoO2.5 is transformed into a series of protonated H x SrCoO2.5 phases with distinct hydrogen contents. The unexpected electron to charge-neutral doping crossover along with the increase of proton concentration from x = 1 to 2 suggests the formation of exotic charge neutral H-H dimers for higher proton concentration, which is directly visualized at the vacant tetrahedron by scanning transmission electron microscopy and then further supported by first principles calculations. Although the H-H dimers cause no change of the valency of Co2+ ions, they result in clear enhancement of electronic bandgap and suppression of magnetization through lattice expansion. These results not only reveal a hydrogen chemical state beyond anion and cation within the complex oxides, but also suggest an effective pathway to design functional materials through tunable ionic evolution.

Comparative analysis of B-BOX genes and their expression pattern analysis under various treatments in Dendrobium officinale.

BACKGROUND: Studies have demonstrated that BBX (B-BOX) genes play crucial roles in regulatory networks controlling plant growth, developmental processes and stress response. Nevertheless, comprehensive study of BBX genes in orchids (Orchidaceae) is not well studied. The newly released genome sequences of Dendrobium officinale and Phalaenopsis equestris have allowed a systematic analysis of these important BBX genes in orchids. RESULTS: Here we identified 19 (DoBBX01-19) and 16 (PeBBX01-16) BBX genes from D. officinale and P. equestris, respectively, and clustered into five clades (I-V) according to phylogenetic analysis. Thirteen orthologous, two DoBBXs paralogous and two PeBBXs paralogous gene pairs were validated. This gene family mainly underwent purifying selection, but five domains experienced positive selection during evolution. Noteworthy, the expression patterns of root, root_tips, stem, leaf, speal, column, lip, and flower_buds revealed that they might contribution to the formation of these tissues. According to the cis-regulatory elements analysis of BBX genes, qRT-PCR experiments were carried out using D. officinale PLBs (protocorm-like bodies) and displayed that these BBX genes were differentially regulated under AgNO3, MeJA (Methyl Jasmonate), ABA (abscisic acid) and SA (salicylic acid) treatments. CONCLUSIONS: Our analysis exposed that DoBBX genes play significant roles in plant growth and development, and response to different environmental stress conditions of D. officinale, which provide aid in the selection of appropriate candidate genes for further functional characterization of BBX genes in plants.

Evolution and functional divergence of MADS-box genes in Pyrus.

MADS-box transcription factors widely regulate all aspects of plant growth including development and reproduction. Although the MADS-box gene family genes have been extensively characterized in many plants, they have not been studied in closely related species. In this study, 73 and 74 MADS-box genes were identified in European pear (Pyrus communis) and Chinese pear (Pyrus bretschneideri), respectively. Based on the phylogenetic relationship, these genes could be clustered into five groups (Mα, Mß, Mr, MIKCC, MIKC*) and the MIKCC group was further categorized into 10 subfamilies. The distribution of MADS-box genes on each chromosome was significantly nonrandom. Thirty-seven orthologs, twenty-five PcpMADS (P. communis MADS-box) paralogs and nineteen PbrMADS (P. bretschneideri MADS-box) paralogs were predicted. Among these paralogous genes, two pairs arose from tandem duplications (TD), nineteen from segmental duplication (SD) events and twenty-three from whole genome duplication (WGD) events, indicating SD/WGD events led to the expansion of MADS-box gene family. The MADS-box genes expression profiles in pear fruits indicated functional divergence and neo-functionalization or sub-functionalization of some orthologous genes originated from a common ancestor. This study provided a useful reference for further analysis the mechanisms of species differentiation and biodiversity formation among closely related species.

Metacaspase gene family in Rosaceae genomes: Comparative genomic analysis and their expression during pear pollen tube and fruit development.

Metacaspase (MC), which is discovered gene family with distant caspase homologs in plants, fungi, and protozoa, may be involved in programmed cell death (PCD) processes during plant development and respond abiotic and biotic stresses. To reveal the evolutionary relationship of MC gene family in Rosaceae genomes, we identified 8, 7, 8, 12, 12, and 23 MC genes in the genomes of Fragaria vesca, Prunus mume, Prunus persica, Pyrus communis, Pyrus bretschneideri and Malus domestica, respectively. Phylogenetic analysis suggested that the MC genes could be grouped into three clades: Type I*, Type I and Type II, which was supported by gene structure and conserved motif analysis. Microsynteny analysis revealed that MC genes present in the corresponding syntenic blocks of P. communis, P. bretschneideri and M. domestica, and further suggested that large-scale duplication events play an important role in the expansion of MC gene family members in these three genomes than other Rosaceae plants (F. vesca, P. mume and P. persica). RNA-seq data showed the specific expression patterns of PbMC genes in response to drought stress. The expression analysis of MC genes demonstrated that PbMC01 and PbMC03 were able to be detected in all four pear pollen tubes and seven fruit development stages. The current study highlighted the evolutionary relationship and duplication of the MC gene family in these six Rosaceae genomes and provided appropriate candidate genes for further studies in P. bretschneideri.

Publisher Correction: Electric-field control of ferromagnetism through oxygen ion gating.

In the original version of this Article, Figs. 4c and 4d contained incorrectly sized error bars. This has now been corrected in both the PDF and HTML versions of the Article.

Electric-field control of ferromagnetism through oxygen ion gating.

Electric-field-driven oxygen ion evolution in the metal/oxide heterostructures emerges as an effective approach to achieve the electric-field control of ferromagnetism. However, the involved redox reaction of the metal layer typically requires extended operation time and elevated temperature condition, which greatly hinders its practical applications. Here, we achieve reversible sub-millisecond and room-temperature electric-field control of ferromagnetism in the Co layer of a Co/SrCoO2.5 system accompanied by bipolar resistance switching. In contrast to the previously reported redox reaction scenario, the oxygen ion evolution occurs only within the SrCoO2.5 layer, which serves as an oxygen ion gating layer, leading to modulation of the interfacial oxygen stoichiometry and magnetic state. This work identifies a simple and effective pathway to realize the electric-field control of ferromagnetism at room temperature, and may lead to applications that take advantage of both the resistance switching and magnetoelectric coupling.

Electric-Field-Controlled Phase Transformation in WO3 Thin Films through Hydrogen Evolution.

Field-effect transistors with ionic-liquid gating (ILG) have been widely employed and have led to numerous intriguing phenomena in the last decade, due to the associated excellent carrier-density tunability. However, the role of the electrochemical effect during ILG has become a heavily debated topic recently. Herein, using ILG, a field-induced insulator-to-metal transition is achieved in WO3 thin films with the emergence of structural transformations of the whole films. The subsequent secondary-ion mass spectrometry study provides solid evidence that electrochemically driven hydrogen evolution dominates the discovered electrical and structural transformation through surface absorption and bulk intercalation.