Demonstration of 651†nm InGaN-based red light-emitting diode with an external quantum efficiency over 6% by InGaN/AlN strain release interlayer.

This work reports a high-performance InGaN-based red-emitting LED with a strain-release interlayer (SRI) consisting of an InGaN stress-release layer (SRL) and an AlN dislocation confinement layer (DCL) in unintentionally doped GaN (u-GaN). The SRL introduces a tensile strain which could decrease the in-plane compressive stress of the u-GaN layer, while the DCL could reduce the dislocation density and thus improve the crystal quality of the u-GaN layer. Consequently, a high-efficiency InGaN-based red-emitting LED with a peak wavelength of 651 nm and an external quantum efficiency of 6.04% is realized. In addition, the room-temperature photoluminescence (PL) mapping emission wavelength is uniform across a 4-inch wafer with a standard deviation of 3.3 nm. Therefore, the proposed SRI offers good potential for mass-producing high-performance and long-wavelength InGaN-based red-emitting LEDs.

Karyotype and LTR-RTs analysis provide insights into oak genomic evolution.

BACKGROUND: Whole-genome duplication and long terminal repeat retrotransposons (LTR-RTs) amplification in organisms are essential factors that affect speciation, local adaptation, and diversification of organisms. Understanding the karyotype projection and LTR-RTs amplification could contribute to untangling evolutionary history. This study compared the karyotype and LTR-RTs evolution in the genomes of eight oaks, a dominant lineage in Northern Hemisphere forests. RESULTS: Karyotype projections showed that chromosomal evolution was relatively conservative in oaks, especially on chromosomes 1 and 7. Modern oak chromosomes formed through multiple fusions, fissions, and rearrangements after an ancestral triplication event. Species-specific chromosomal rearrangements revealed fragments preserved through natural selection and adaptive evolution. A total of 441,449 full-length LTR-RTs were identified from eight oak genomes, and the number of LTR-RTs for oaks from section Cyclobalanopsis was larger than in other sections. Recent amplification of the species-specific LTR-RTs lineages resulted in significant variation in the abundance and composition of LTR-RTs among oaks. The LTR-RTs insertion suppresses gene expression, and the suppressed intensity in gene regions was larger than in promoter regions. Some centromere and rearrangement regions indicated high-density peaks of LTR/Copia and LTR/Gypsy. Different centromeric regional repeat units (32, 78, 79 bp) were detected on different Q. glauca chromosomes. CONCLUSION: Chromosome fusions and arm exchanges contribute to the formation of oak karyotypes. The composition and abundance of LTR-RTs are affected by its recent amplification. LTR-RTs random retrotransposition suppresses gene expression and is enriched in centromere and chromosomal rearrangement regions. This study provides novel insights into the evolutionary history of oak karyotypes and the organization, amplification, and function of LTR-RTs.

Predicting Quercus gilva distribution dynamics and its response to climate change induced by GHGs emission through MaxEnt modeling.

Quercus gilva, an evergreen tree species in Quercus section Cyclobalanopsis, is an ecologically and economically valuable species in subtropical regions of East Asia. Predicting the impact of climate change on potential distribution of Q. gilva can provide a scientific basis for the conservation and utilization of its genetic resources, as well as for afforestation. In this study, 74 distribution records of Q. gilva and nine climate variables were obtained after data collection and processing. Current climate data downloaded from WorldClim and future climate data predicted by four future climate scenarios (2040s SSP1-2.6, 2040s SSP5-8.5, 2060s SSP1-2.6, and 2060s SSP5-8.5) mainly based on greenhouse gases emissions of distribution sites were used in MaxEnt model with optimized parameters to predict distribution dynamics of Q. gilva and its response to climate change. The results showed that the predicted current distribution was consistent with natural distribution of Q. gilva, which was mainly located in Hunan, Jiangxi, Zhejiang, Fujian, Guizhou, and Taiwan provinces of China, as well as Japan and Jeju Island of South Korea. Under current climate conditions, precipitation factors played a more significant role than temperature factors on distribution of Q. gilva, and precipitation of driest quarter (BIO17) is the most important restriction factor for its current distribution (contribution rate of 57.35%). Under future climate conditions, mean temperature of driest quarter (BIO9) was the essential climate factor affecting future change in potential distribution of Q. gilva. As the degree of climatic anomaly increased in the future, the total area of predicted distribution of Q. gilva showed a shrinking trend (decreased by 12.24%-45.21%) and Q. gilva would migrate to high altitudes and latitudes. The research results illustrated potential distribution range and suitable climate conditions of Q. gilva, which can provide essential theoretical references for the conservation, development, and utilization of Q. gilva and other related species.

Ensemble species distribution modeling and multilocus phylogeography provide insight into the spatial genetic patterns and distribution dynamics of a keystone forest species, Quercus glauca.

BACKGROUND: Forests are essential for maintaining species diversity, stabilizing local and global climate, and providing ecosystem services. Exploring the impact of paleogeographic events and climate change on the genetic structure and distribution dynamics of forest keystone species could help predict responses to future climate change. In this study, we combined an ensemble species distribution model (eSDM) and multilocus phylogeography to investigate the spatial genetic patterns and distribution change of Quercus glauca Thunb, a keystone of East Asian subtropical evergreen broad-leaved forest. RESULTS: A total of 781 samples were collected from 77 populations, largely covering the natural distribution of Q. glauca. The eSDM showed that the suitable habitat experienced a significant expansion after the last glacial maximum (LGM) but will recede in the future under a general climate warming scenario. The distribution centroid will migrate toward the northeast as the climate warms. Using nuclear SSR data, two distinct lineages split between east and west were detected. Within-group genetic differentiation was higher in the West than in the East. Based on the identified 58 haplotypes, no clear phylogeographic structure was found. Populations in the Nanling Mountains, Wuyi Mountains, and the southwest region were found to have high genetic diversity. CONCLUSIONS: A significant negative correlation between habitat stability and heterozygosity might be explained by the mixing of different lineages in the expansion region after LGM and/or hybridization between Q. glauca and closely related species. The Nanling Mountains may be important for organisms as a dispersal corridor in the west-east direction and as a refugium during the glacial period. This study provided new insights into spatial genetic patterns and distribution dynamics of Q. glauca.

Spiking GABAergic OPC tumor cells prolong survival in IDH1 mutant glioma.

Prior studies have shown that glioma cells form synapses with neurons to receive synaptic inputs. To discern if glioma cells can send outgoing electrochemical signals in the form of action potentials (APs), we employed Patch-sequencing on surgically-resected human glioma slices. Results showed that half of patched cells in IDH1 mutant (IDH1mut) tumors demonstrate select properties of both neurons and glia and fire single, short APs. To define the transcriptional profiles of these hybrid cells (HCs) and discern if they are tumor derived, we developed a computational tool, Single Cell Rule Association Mining (SCRAM), to annotate features in each cell individually. SCRAM revealed that HCs represent a heterogenous group of tumor and non-tumor cells that are uniformly defined by both GABAergic neuron and oligodendrocyte precursor cell (GABA-OPC) transcriptional signatures. We found that GABA-OPC tumor cells express requisite voltage-gated ion channels needed to fire APs. We validated our findings in human single cell and bulk RNA-seq datasets, confirming that GABA-OPCs represent 40% of IDH1mut tumor cells, correlate with survival outcomes in IDH1mut human patients and are also found in select molecular subtypes of IDH1 wild-type tumors. These studies describe a new cell type in IDH1mut glioma with unique electrophysiological and transcriptomic properties.

Linear and Nonlinear Behaviors of the Photoreceptor Coupled Network.

Photoreceptors are electrically coupled to one another, and the spatiotemporal properties of electrical synapses in a two-dimensional retinal network are still not well studied, because of the limitation of the single electrode or pair recording techniques which do not allow simultaneously measuring responses of multiple photoreceptors at various locations in the retina. A multiple electrode recording system is needed. In this study, we investigate the network properties of the two-dimensional rod coupled array of the salamander retina (both sexes were used) by using the newly available multiple patch electrode system that allows simultaneous recordings from up to eight cells and to determine the electrical connectivity among multiple rods. We found direct evidence that voltage signal spread in the rod-rod coupling network in the absence of I h (mediated by HCN channels) is passive and follows the linear cable equation. Under physiological conditions, I h shapes the network signal by progressively shortening the response time-to-peak of distant rods, compensating the time loss of signal traveling from distant rods to bipolar cell somas and facilitating synchronization of rod output signals. Under voltage-clamp conditions, current flow within the coupled rods follows Ohm's law, supporting the idea that nonlinear behaviors of the rod network are dependent on membrane voltage. Rod-rod coupling is largely symmetrical in the 2D array, and voltage-clamp blocking the next neighboring rod largely suppresses rod signal spread into the second neighboring rod, suggesting that indirect coupling pathways play a minor role in rod-rod coupling.

CACNA1B protects naked mole-rat hippocampal neuron from apoptosis via altering the subcellular localization of Nrf2 after 60Co irradiation.

Although radiotherapy is the most effective treatment modality for brain tumors, it always injures the central nervous system, leading to potential sequelae such as cognitive dysfunction. Radiation induces molecular, cellular, and functional changes in neuronal and glial cells. The hippocampus plays a critical role in learning and memory; therefore, concerns about radiation-induced injury are widespread. Multiple studies have focused on this complex problem, but the results have not been fully elucidated. Naked mole rat brains were irradiated with 60Co at a dose of 10 Gy. On 7 days, 14 days, and 28 days after irradiation, hippocampi in the control groups were obtained for next-generation sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were subsequently performed. Venn diagrams revealed 580 differentially expressed genes (DEGs) that were common at different times after irradiation. GO and KEGG analyses revealed that the 580 common DEGs were enriched in molecular transducer activity. In particular, CACNA1B mediated regulatory effects after irradiation. CACNA1B expression increased significantly after irradiation. Downregulation of CACNA1B led to a reduction in apoptosis and reactive oxygen species levels in hippocampal neurons. This was due to the interaction between CACNA1B and Nrf2, which disturbed the normal nuclear localization of Nrf2. In addition, CACNA1B downregulation led to a decrease in the cognitive functions of naked mole rats. These findings reveal the pivotal role of CACNA1B in regulating radiation-induced brain injury and will lead to the development of a novel strategy to prevent brain injury after irradiation.

High-quality haplotype-resolved genome assembly for ring-cup oak (Quercus glauca) provides insight into oaks demographic dynamics.

Quercus section Cyclobalanopsis represents a dominant woody lineage in East Asian evergreen broadleaved forests. Regardless of its ecological and economic importance, little is known about the genomes of species in this unique oak lineage. Quercus glauca is one of the most widespread tree species in the section Cyclobalanopsis. In this study, a high-quality haplotype-resolved reference genome was assembled for Q. glauca from PacBio HiFi and Hi-C reads. The genome size, contig N50, and scaffold N50 measured 902.88, 7.60, and 69.28 Mb, respectively, for haplotype1, and 913.28, 7.20, and 71.53 Mb, respectively, for haplotype2. A total of 37,457 and 38,311 protein-coding genes were predicted in haplotype1 and haplotype2, respectively. Homologous chromosomes in the Q. glauca genome had excellent gene pair collinearity. The number of R-genes in Q. glauca was similar to most East Asian oaks but less than oak species from Europe and America. Abundant structural variation in the Q. glauca genome could contribute to environmental stress tolerance in Q. glauca. Sections Cyclobalanopsis and Cerris diverged in the Oligocene, in agreement with fossil records for section Cyclobalanopsis, which document its presence in East Asia since the early Miocene. The demographic dynamics of closely related oak species were largely similar. The high-quality reference genome provided here for the most widespread species in section Cyclobalanopsis will serve as an essential genomic resource for evolutionary studies of key oak lineages while also supporting studies of interspecific introgression, local adaptation, and speciation in oaks.

Climate change impacts the distribution of Quercus section Cyclobalanopsis (Fagaceae), a keystone lineage in East Asian evergreen broadleaved forests.

East Asian evergreen broadleaved forests (EBFLs) harbor high species richness, but these ecosystems are severely impacted by global climate change and deforestation. Conserving and managing EBLFs requires understanding dominant tree distribution dynamics. In this study, we used 29 species in Quercus section Cyclobalanopsis-a keystone lineage in East Asian EBLFs-as proxies to predict EBLF distribution dynamics using species distribution models (SDMs). We examined climatic niche overlap, similarity, and equivalency among seven biogeographical regions' species using 'ecospat'. We also estimated the effectiveness of protected areas in the predicted range to elucidate priority conservation regions. Our results showed that the climatic niches of most geographical groups differ. The western species under the Indian summer monsoon regime were mainly impacted by temperature factors, whereas precipitation impacted the eastern species under the East Asian summer monsoon regime. Our simulation predicted a northward range expansion of section Cyclobalanopsis between 2081 and 2100, except for the ranges of the three Himalayan species analyzed, which might shrink significantly. The greatest shift of highly suitable areas was predicted for the species in the South Pacific, with a centroid shift of over 300 km. Remarkably, only 7.56% of suitable habitat is currently inside protected areas, and the percentage is predicted to continue declining in the future. To better conserve Asian EBLFs, establishing nature reserves in their northern distribution ranges, and transplanting the populations with predicted decreasing numbers and degraded habitats to their future highly suitable areas, should be high-priority objectives.

Ferroptosis-related genes as diagnostic markers for major depressive disorder and their correlations with immune infiltration.

Background: Major depression disorder (MDD) is a devastating neuropsychiatric disease, and one of the leading causes of suicide. Ferroptosis, an iron-dependent form of regulated cell death, plays a pivotal role in numerous diseases. The study aimed to construct and validate a gene signature for diagnosing MDD based on ferroptosis-related genes (FRGs) and further explore the biological functions of these genes in MDD. Methods: The datasets were downloaded from the Gene Expression Omnibus (GEO) database and FRGs were obtained from the FerrDb database and other literatures. Least absolute shrinkage and selection operator (LASSO) regression and stepwise logistic regression were performed to develop a gene signature. Receiver operating characteristic (ROC) curves were utilized to assess the diagnostic power of the signature. Gene ontology (GO) enrichment analysis was used to explore the biological roles of these diagnostic genes, and single sample gene set enrichment analysis (ssGSEA) algorithm was used to evaluate immune infiltration in MDD. Animal model of depression was constructed to validate the expression of the key genes. Results: Eleven differentially expressed FRGs were identified in MDD patients compared with healthy controls. A signature of three FRGs (ALOX15B, RPLP0, and HP) was constructed for diagnosis of MDD. Afterwards, ROC analysis confirmed the signature's discriminative capacity (AUC = 0.783, 95% CI = 0.719-0.848). GO enrichment analysis revealed that the differentially expressed genes (DEGs) related to these three FRGs were mainly involved in immune response. Furthermore, spearman correlation analysis demonstrated that these three FRGs were associated with infiltrating immune cells. ALOX15B and HP were significantly upregulated and RPLP0 was significantly downregulated in peripheral blood of the lipopolysaccharide (LPS)-induced depressive model. Conclusion: Our results suggest that the novel FRG signature had a good diagnostic performance for MDD, and these three FRGs correlated with immune infiltration in MDD.

Glycoengineering directs de novo biomanufacturing of UPEC O21 O-antigen polysaccharide based glycoprotein.

Glycoproteins, in which polysaccharides are usually attached to proteins, are an important class of biomolecules that are widely used as therapeutic agents in clinical treatments for decades. Uropathogenic Escherichia coli (UPEC) O21 has been identified as a serogroup that induces urinary tract infections, with a global increasing number among women and young children. Therefore, there is an urgent need to establish protective vaccines against UPEC infection. Herein, we engineered non-pathogenic E. coli MG1655 to achieve robust, cost-effective de novo biosynthesis of O21 O-antigen polysaccharide-based glycoprotein against UPEC O21. Specifically, this glycoengineered E. coli MG1655 was manipulated for high-efficient glucose-glycerol co-utilization and for the gene cluster installation and O-glycosylation machinery assembly. The key pathways of UDP-sugar precursors were also strengthened to enforce more carbon flux towards the glycosyl donors, which enhanced the glycoprotein titer by 5.6-fold. Further optimization of culture conditions yielded glycoproteins of up to 35.34 mg/L. Glycopeptide MS confirmed the preciset biosynthesis of glycoprotein. This glycoprotein elicited antigen-specific IgG immune responses and significantly reduced kidney and bladder colonization. This bacterial cell-based glyco-platform and optimized strategies can provide a guideline for the biosynthesis of other value-added glycoproteins.

Comprehensive analysis of cellular specializations that initiate parallel auditory processing pathways in mice.

The cochlear nuclear complex (CN) is the starting point for all central auditory processing and comprises a suite of neuronal cell types that are highly specialized for neural coding of acoustic signals. To examine how their striking functional specializations are determined at the molecular level, we performed single-nucleus RNA sequencing of the mouse CN to molecularly define all constituent cell types and related them to morphologically- and electrophysiologically-defined neurons using Patch-seq. We reveal an expanded set of molecular cell types encompassing all previously described major types and discover new subtypes both in terms of topographic and cell-physiologic properties. Our results define a complete cell-type taxonomy in CN that reconciles anatomical position, morphological, physiological, and molecular criteria. This high-resolution account of cellular heterogeneity and specializations from the molecular to the circuit level illustrates molecular underpinnings of functional specializations and enables genetic dissection of auditory processing and hearing disorders with unprecedented specificity.

Meta-analysis of the association between RNF213 polymorphisms and clinical features of moyamoya disease in Asian population.

BACKGROUND: We performed this study to explore the relationship between ring finger protein 213 (RNF213) gene polymorphisms and clinical features in moyamoya disease (MMD). METHODS: Electronic databases (PubMed, Google Scholar, Embase, Scopus, Cochrane Library) were conducted from inception to May 15th, 2022. Odds ratios (ORs) with 95 % confidence intervals (CIs) were generated as effect size for binary variants. Subgroup analyses were performed by the RNF213 polymorphisms. Sensitivity was used to examine the robustness of associations. RESULTS: A total of 16 articles and 3061 MMD patients were included and the association of five RNF213 polymorphisms on 9 clinical features of MMD were identified. Patients under 18 years of age at onset, familial MMD, cerebral ischemic stroke and posterior cerebral artery involvement (PCi) were significantly more common in mutant type compared with wild type of RNF213. Compared with each wild type, subgroup analysis showed that rs11273543 and rs9916351 remarkably increased risk of MMD on early onset, but rs371441113 evidently delayed the onset of MMD. Rs112735431 in mutant type was significantly higher than wild type in patients with PCi. Subgroup analysis in mutant type showed that rs112735431 conspicuously decreased intracerebral/ intraventricular hemorrhage (ICH/IVH) risk and yet rs148731719 obviously increased the risk in ICH/IVH. CONCLUSION: More attention should be paid to patients on whom the ischemic MMD occurs younger than 18 years old. RNF213 polymorphism screening and cerebrovascular imaging examination should be performed to evaluate intracranial vascular involvement, to achieve early detection and early treatment and avoid more serious cerebrovascular events.

The complete chloroplast genome sequence of Quercus kerrii (Fagaceae), and comparative analysis with related species.

Quercus kerrii Craib 1911 (section Cyclobalanopsis) is a widespread tree species in the tropical seasonal forests of southwest China and Northern Indo-China areas. In this study, we sequenced, assembled and annotated the complete chloroplast genome of Q. kerrii. The circular genome was 160,743 bp in length and had a GC content of 36.89%. The Q. kerrii chloroplast genome has a typical quadripartite structure, including two inverted repeat regions (length, 25,825 bp; GC content, 42.76%), a large single-copy region (length, 90,196 bp; GC content, 34.74%), and a small single-copy region (length, 18,897 bp; GC content, 30.60%). Genome annotation has indicated that the Q. kerrii chloroplast genome contained 131 genes, including 86 protein-coding genes, 37 tRNA, and eight rRNA. The phylogenetic tree showed that Q. kerrii had a close relationship with Q. schottkyana Rehder & E.H.Wilson 1916.

Spatial genetic patterns and distribution dynamics of Begonia grandis (Begoniaceae), a widespread herbaceous species in China.

Introduction: Begonia L., one of the 10 largest plant genera, contains over 2,100 species, most of which have a very limited distribution range. Understanding the spatial genetic structure and distribution dynamics of a widespread species in this genus will contribute to clarifying the mechanism responsible for Begonia speciation. Methods: In this study, we used three chloroplast DNA markers (ndhF-rpl32, atpI-atpH, and ndhA intron), coupled with species distribution modeling (SDM), to investigate the population genetic structure and distribution dynamics of Begonia grandis Dryand., the species of Begonia with the widest distribution in China. Results: Thirty-five haplotypes from 44 populations clustered into two groups, and haplotype divergence began in the Pleistocene (1.75 Mya). High genetic diversity (H d = 0.894, H T = 0.910), strong genetic differentiation (F ST = 0.835), and significant phylogeographical structure (G ST/N ST = 0.848/0.917, P < 0.05) were observed. The distribution range of B. grandis migrated northwards after the last glacial maximum, but its core distribution area remained stable. Discussion: Combined, the observed spatial genetic patterns and SDM results identified the Yunnan-Guizhou Plateau, the Three Gorges region, and the Daba Mountains as potential refugia of B. grandis. BEAST-derived chronogram and haplotype network analysis do not support the Flora Reipublicae Popularis Sinicae and Flora of China for subspecies classification based on morphological characteristics. Our results support the hypothesis that population-level allopatric differentiation may be an important speciation process for the Begonia genus and a key contributor to its rich diversity.

Cellular composition and circuit organization of the locus coeruleus of adult mice.

The locus coeruleus (LC) houses the vast majority of noradrenergic neurons in the brain and regulates many fundamental functions, including fight and flight response, attention control, and sleep/wake cycles. While efferent projections of the LC have been extensively investigated, little is known about its local circuit organization. Here, we performed large-scale multipatch recordings of noradrenergic neurons in adult mouse LC to profile their morpho-electric properties while simultaneously examining their interactions. LC noradrenergic neurons are diverse and could be classified into two major morpho-electric types. While fast excitatory synaptic transmission among LC noradrenergic neurons was not observed in our preparation, these mature LC neurons connected via gap junction at a rate similar to their early developmental stage and comparable to other brain regions. Most electrical connections form between dendrites and are restricted to narrowly spaced pairs or small clusters of neurons of the same type. In addition, more than two electrically coupled cell pairs were often identified across a cohort of neurons from individual multicell recording sets that followed a chain-like organizational pattern. The assembly of LC noradrenergic neurons thus follows a spatial and cell-type-specific wiring principle that may be imposed by a unique chain-like rule.

Distinct organization of two cortico-cortical feedback pathways.

Neocortical feedback is critical for attention, prediction, and learning. To mechanically understand its function requires deciphering its cell-type wiring. Recent studies revealed that feedback between primary motor to primary somatosensory areas in mice is disinhibitory, targeting vasoactive intestinal peptide-expressing interneurons, in addition to pyramidal cells. It is unknown whether this circuit motif represents a general cortico-cortical feedback organizing principle. Here we show that in contrast to this wiring rule, feedback between higher-order lateromedial visual area to primary visual cortex preferentially activates somatostatin-expressing interneurons. Functionally, both feedback circuits temporally sharpen feed-forward excitation eliciting a transient increase-followed by a prolonged decrease-in pyramidal cell activity under sustained feed-forward input. However, under feed-forward transient input, the primary motor to primary somatosensory cortex feedback facilitates bursting while lateromedial area to primary visual cortex feedback increases time precision. Our findings argue for multiple cortico-cortical feedback motifs implementing different dynamic non-linear operations.

A chromosome-scale genome assembly of Quercus gilva: Insights into the evolution of Quercus section Cyclobalanopsis (Fagaceae).

Quercus gilva is an ecologically and economically important species of Quercus section Cyclobalanopsis and is a dominant species in evergreen broad-leaved forests in subtropical regions of East Asia. In the present study, we reported a high-quality chromosome-scale genome assembly of Q. gilva, the first reference genome for section Cyclobalanopsis, using the combination of Illumina and PacBio sequencing with Hi-C technologies. The assembled genome size of Q. gilva was 889.71 Mb, with a contig number of 773 and a contig N50 of 28.32 Mb. Hi-C scaffolding anchored 859.07 Mb contigs (96.54% of the assembled genome) onto 12 pseudochromosomes, with a scaffold N50 of 70.35 Mb. A combination of de novo, homology-based, and transcript-based predictions predicted a final set of 36,442 protein-coding genes distributed on 12 pseudochromosomes, and 97.73% of them were functionally annotated. A total of 535.64 Mb (60.20%) of repetitive sequences were identified. Genome evolution analysis revealed that Q. gilva was most closely related to Q. suber and they diverged at 40.35 Ma, and Q. gilva did not experience species-specific whole-genome duplication in addition to the ancient gamma (γ) whole-genome triplication event shared by core eudicot plants. Q. gilva underwent considerable gene family expansion and contraction, with 598 expanded and 6,509 contracted gene families detected. The first chromosome-scale genome of Q. gilva will promote its germplasm conservation and genetic improvement and provide essential resources for better studying the evolution of Quercus section Cyclobalanopsis.

Removal of KCNQ2 from parvalbumin-expressing interneurons improves anti-seizure efficacy of retigabine.

Anti-seizure drug (ASD) targets are widely expressed in both excitatory and inhibitory neurons. It remains unknown if the action of an ASD upon inhibitory neurons could counteract its beneficial effects on excitatory neurons (or vice versa), thereby reducing the efficacy of the ASD. Here, we examine whether the efficacy of the ASD retigabine (RTG) is altered after removal of the Kv7 potassium channel subunit KCNQ2, one of its drug targets, from parvalbumin-expressing interneurons (PV-INs). Parvalbumin-Cre (PV-Cre) mice were crossed with Kcnq2-floxed (Kcnq2fl/fl) mice to conditionally delete Kcnq2 from PV-INs. In these conditional knockout mice (cKO, PV-Kcnq2fl/fl), RTG (10 mg/kg, i.p.) significantly delayed the onset of either picrotoxin (PTX, 10 mg/kg, i.p)- or kainic acid (KA, 30 mg/kg, i.p.)-induced convulsive seizures compared to vehicle, while RTG was not effective in wild-type littermates (WT). Immunostaining for KCNQ2 and KCNQ3 revealed that both subunits were enriched at axon initial segments (AISs) of hippocampal CA1 PV-INs, and their specific expression was selectively abolished in cKO mice. Accordingly, the M-currents recorded from CA1 PV-INs and their sensitivity to RTG were significantly reduced in cKO mice. While the ability of RTG to suppress CA1 excitatory neurons in hippocampal slices was unchanged in cKO mice, its suppressive effect on the spike activity of CA1 PV-INs was significantly reduced compared with WT mice. In addition, the RTG-induced suppression on intrinsic membrane excitability of PV-INs in WT mice was significantly reduced in cKO mice. These findings suggest that preventing RTG from suppressing PV-INs improves its anticonvulsant effect.

Hepatoprotective Effect of Oplopanax elatus Nakai Adventitious Roots Extract by Regulating CYP450 and PPAR Signaling Pathway.

O. elatus Nakai is a traditional medicine that has been confirmed to exert effective antioxidant and anti-inflammatory functions, and is used for the treatment of different disorders. However, its potential beneficial effects on drug induced hepatotoxicity and relevant molecular mechanisms remain unclear. This study investigated the protective effect and further elucidated the mechanisms of action of O. elatus on liver protection. O. elatus chlorogenic acids-enriched fraction (OEB), which included chlorogenic acid and isochlorogenic acid A, were identified by HPLC-MS/MS. OEB was administrated orally daily for seven consecutive days, followed by a single intraperitoneal injection of an overdose of APAP after the final OEB administration. The effects of OEB on immune cells in mice liver were analyzed using flow cytometry. APAP metabolite content in serum was detected using HPLC-MS/MS in order to investigate whether OEB affects CYP450 activities. The intestinal content samples were processed for 16 s microbiota sequencing. Results demonstrated that OEB decreased alanine aminotransferase, aspartate aminotransferase contents, affected the metabolism of APAP, and decreased the concentrates of APAP, APAP-CYS and APAP-NAC by inhibiting CYP2E1 and CYP3A11 activity. Furthermore, OEB pretreatment regulated lipid metabolism by affecting the peroxisome proliferator-activated receptors (PPAR) signaling pathway in mice and also increased the abundance of Akkermansia and Parabacteroides. This study indicated that OEB is a potential drug candidate for treating hepatotoxicity because of its ability to affect drug metabolism and regulate lipid metabolism.