Visible-Light-Driven Multicomponent Diamination and Oxyamination of Alkene.

Herein, we describe an effective method for the synthesis of 2-alkoxyamides and 1,2-diamines through visible-light-mediated difunctionalization of alkenes. N-Aminopyridinium salts were employed as appropriate precursors to generate key amidyl radical intermediates via a photoinduced single-electron transfer (SET) process. The amidyl radicals would react with alkenes, followed by oxidation and nucleophilic addition. Excellent functional group tolerance and good yields demonstrate the synthetic potential of this transformation.

The interaction of nicotinic acetylcholine receptor subunits Ldα3, Ldα8 and Ldß1 with neonicotinoids in Colorado potato beetle, Leptinotarsa decemlineata.

The Colorado potato beetle (CPB), Leptinotarsa decemlineata (Say), is an extremely destructive notifiable quarantine pest. Over the last two decades, neonicotinoid insecticides, particularly thiamethoxam and imidacloprid, have been used to control it in Xinjiang, and local field populations have developed different levels of resistance in consequence. However, the contributions of nicotinic acetylcholine receptors (nAChRs) to neonicotinoid resistance are currently poorly understood in CPB. Previous studies have shown that nAChRα1, α3, α8 and ß1 are major target subunits for neonicotinoids in some model and important agricultural insects including nAChRα1 subunit of L. decemlineata (Ldα1). In this study, the expression levels of Ldα3, Ldα8 and Ldß1 following 72 h of treatments with median lethal doses of thiamethoxam and imidacloprid were compared using real-time quantitative PCR. These genes were then individually and simultaneously knocked down with Ldα1 by RNA interference (RNAi) using a double-stranded RNA (dsRNA) feeding method for six days to explore their roles in CPB susceptibility to imidacloprid and thiamethoxam. The results showed that the expressions of Ldα3, Ldα8 and Ldß1 were significantly decreased by 36.99-74.89% after thiamethoxam and imidacloprid treatments, compared with the control. The significant downregulation of the target genes resulting from RNAi significantly reduced the mortality of adults exposed to thiamethoxam and imidacloprid by 34.53% -56.44% and 28.78%-43.93%, respectively. Furthermore, the adult survival rates were not affected by every dsRNA-feeding treatment, while the body weight of the test adults significantly deceased after four and six days of individual gene RNAi. This study showed that Ldα3, Ldα8 and Ldß1 are down-regulated by thiamethoxam and imidacloprid and play important roles in the tolerance of CPB to neonicotinoids.

Unraveling the Role of Scutellaria baicalensis for the Treatment of Breast Cancer Using Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation.

Scutellaria baicalensis is often used to treat breast cancer, but the molecular mechanism behind the action is unclear. In this study, network pharmacology, molecular docking, and molecular dynamics simulation are combined to reveal the most active compound in Scutellaria baicalensis and to explore the interaction between the compound molecule and the target protein in the treatment of breast cancer. In total, 25 active compounds and 91 targets were screened out, mainly enriched in lipids in atherosclerosis, the AGE-RAGE signal pathway of diabetes complications, human cytomegalovirus infection, Kaposi-sarcoma-associated herpesvirus infection, the IL-17 signaling pathway, small-cell lung cancer, measles, proteoglycans in cancer, human immunodeficiency virus 1 infection, and hepatitis B. Molecular docking shows that the two most active compounds, i.e., stigmasterol and coptisine, could bind well to the target AKT1. According to the MD simulations, the coptisine-AKT1 complex shows higher conformational stability and lower interaction energy than the stigmasterol-AKT1 complex. On the one hand, our study demonstrates that Scutellaria baicalensis has the characteristics of multicomponent and multitarget synergistic effects in the treatment of breast cancer. On the other hand, we suggest that the best effective compound is coptisine targeting AKT1, which can provide a theoretical basis for the further study of the drug-like active compounds and offer molecular mechanisms behind their roles in the treatment of breast cancer.

The American Paddlefish Genome Provides Novel Insights into Chromosomal Evolution and Bone Mineralization in Early Vertebrates.

Sturgeons and paddlefishes (Acipenseriformes) occupy the basal position of ray-finned fishes, although they have cartilaginous skeletons as in Chondrichthyes. This evolutionary status and their morphological specializations make them a research focus, but their complex genomes (polyploidy and the presence of microchromosomes) bring obstacles and challenges to molecular studies. Here, we generated the first high-quality genome assembly of the American paddlefish (Polyodon spathula) at a chromosome level. Comparative genomic analyses revealed a recent species-specific whole-genome duplication event, and extensive chromosomal changes, including head-to-head fusions of pairs of intact, large ancestral chromosomes within the paddlefish. We also provide an overview of the paddlefish SCPP (secretory calcium-binding phosphoprotein) repertoire that is responsible for tissue mineralization, demonstrating that the earliest flourishing of SCPP members occurred at least before the split between Acipenseriformes and teleosts. In summary, this genome assembly provides a genetic resource for understanding chromosomal evolution in polyploid nonteleost fishes and bone mineralization in early vertebrates.

Development of Quercus acutissima (Fagaceae) pollen tubes inside pistils during the sexual reproduction process.

MAIN CONCLUSION: Extensive histology of pistillate flowers revealed two pollen tube arresting sites (the style-joining and micropyle) within the pistil of Quercus acutissima during the postpollination-prezygotic stage, which reflects a unique female and male gametophyte recognition/selection mechanism. Sexual reproduction is among the most delicate and essential stages in plant life cycles and involves a series of precise interactions between pistils and male gametophytes. Quercus is a woody genus that dominates Northern Hemisphere forests and is notorious for interspecific hybridization, but its sexual reproduction is poorly understood, especially its pollen tube (PT) growth dynamics within pistils. This study used microtome techniques and scanning electron microscopy to observe the postpollination-prezygotic process in the biennially fruiting oak Quercus acutissima. Many pollen grains germinated at anthesis instantly, and PTs penetrated stigmatic surfaces and elongated through the stylar transmitting tissue, then arrested at style-joining for about 12-13 months. Few PTs resumed growth along the compitum in the upper ovarian locule wall in the subsequent April, concurrent with the rapid growth of rudimentary ovules. PTs arrived in the micropyle, and upper septum during megaspore mother cell meiosis, then arrested again for 7-10 days waiting for the embryo sac maturation. Fertilization occurred one week later. Our study shows a clear female dominant crosstalk growth pattern between PT and the ovule. The intermittent PT growth might reflect a unique male gametophyte recognition/selection mechanism to avoid self-pollination and enhance PT competition while increasing interspecific hybridization.

Effects of ABCB1 DNA methylation in donors on tacrolimus blood concentrations in recipients following liver transplantation.

AIMS: To investigate the effects of ABCB1 DNA methylation in donors on individual differences in tacrolimus blood concentrations following liver transplantation. METHODS: Twenty-three donor liver samples carrying the CYP3A5*3/*3 genotype were classified into 2 groups based on their initial tacrolimus blood concentrations (C0  >10 µg/L or <5 µg/L) following liver transplantation. ABCB1 mRNA levels in liver tissues and HepG2 cells were determined by quantitative reverse transcriptase polymerase chain reaction. DNA methylation status in liver tissues and HepG2 cells was determined using Illumina 850 methylation chip sequencing technology and pyrosequencing. 5-Aza-2dC was used to reverse methylation in HepG2 cells. Intracellular tacrolimus concentrations were determined by liquid mass spectrometry. RESULTS: Genome-wide methylation sequencing and pyrosequencing analyses showed that the methylation levels of 3 ABCB1 CpG sites (cg12501229, cg00634941 and cg05496710) were significantly different between groups with different tacrolimus concentration/dose (C0 /D) ratios. ABCB1 mRNA expression in donor livers was found to be positively correlated with tacrolimus C0 /D ratio (R = .458, P < .05). After treatment with 5-Aza-2-Dc, the methylation levels of the ABCB1 CpG sites in HepG2 cells significantly decreased, and this was confirmed by pyrosequencing; there was also a significant increase in ABCB1 transcription, which induced a decrease in intracellular tacrolimus concentrations. CONCLUSION: ABCB1 CpG site methylation affects tacrolimus metabolism in humans by regulating ABCB1 expression. Therefore, ABCB1 DNA methylation in donor livers might be an important epigenetic factor that affects tacrolimus blood concentrations following liver transplantation.

A novel immune classification reveals distinct immune escape mechanism and genomic alterations: implications for immunotherapy in hepatocellular carcinoma.

BACKGROUND: The tumor immunological microenvironment (TIME) has a prominent impact on prognosis and immunotherapy. However, the heterogeneous TIME and the mechanisms by which TIME affects immunotherapy have not been elucidated in hepatocellular carcinoma (HCC). METHODS: A total of 2195 eligible HCC patients from TCGA and GEO database were collected. We comprehensively explored the different heterogeneous TIME phenotypes and its clinical significance. The potential immune escape mechanisms and what genomic alterations may drive the formation of different phenotypes were further investigated. RESULTS: We identified three phenotypes in HCC: TIME-1, the "immune-deficiency" phenotype, with immune cell depletion and proliferation; TIME-2, the "immune-suppressed" phenotype, with enrichment of immunosuppressive cells; TIME-3, the "immune-activated phenotype", with abundant leukocytes infiltration and immune activation. The prognosis and sensitivity to both sorafenib and immunotherapy differed among the three phenotypes. We also underlined the potential immune escape mechanisms: lack of leukocytes and defective tumor antigen presentation capacity in TIME-1, increased immunosuppressive cells in TIME-2, and rich in immunoinhibitory molecules in TIME-3. The different phenotypes also demonstrated specific genomic events: TIME-1 characterized by TP53, CDKN2A, CTNNB1, AXIN1 and FOXD4 alterations; TIME-2 characterized by significant alteration patterns in the PI3K pathway; TIME-3 characterized by ARID1A mutation. Besides, the TIME index (TI) was proposed to quantify TIME infiltration pattern, and it was a superior prognostic and immunotherapy predictor. A pipeline was developed to classify single patient into one of these three subtypes and calculated the TI. CONCLUSIONS: We identified three TIME phenotypes with different clinical outcomes, immune escape mechanisms and genomic alterations in HCC, which could present strategies for improving the efficacy of immunotherapy. TI as a novel prognostic and immunotherapeutic signature that could guide personalized immunotherapy and clinical management of HCC.

Greener Dye Synthesis: Continuous, Solvent-Free Synthesis of Commodity Perylene Diimides by Twin-Screw Extrusion.

A continuous, scalable, and solvent-free method for the synthesis of various naphthalic imides and perylene diimides (PDIs) using twin-screw extrusion (TSE) is reported. Using TSE, naphthalic imides were obtained quantitatively without the need for excess amine reactant or product purification. With good functional-group tolerance, alkyl and benzyl amine derived PDIs (incl. commercial dyes) were obtained in 50-99 % yield. Use of K2 CO3 , enabled synthesis of more difficult aniline-derived PDIs. Furthermore, an automated continuous TSE process for Pigments Black 31 and 32 is demonstrated, with a throughput rate of about 1500 g day-1 , corresponding to a space time yield of about 30×103  kg m-3  day-1 , which is 1-2 orders of magnitude greater than for solvent-based batch methods. These methods provide substantial waste reductions and improved efficiency compared to conventional solvent-based methods.

The high-quality genome of Brassica napus cultivar 'ZS11' reveals the introgression history in semi-winter morphotype.

Allotetraploid oilseed rape (Brassica napus L.) is an agriculturally important crop. Cultivation and breeding of B. napus by humans has resulted in numerous genetically diverse morphotypes with optimized agronomic traits and ecophysiological adaptation. To further understand the genetic basis of diversification and adaptation, we report a draft genome of an Asian semi-winter oilseed rape cultivar 'ZS11' and its comprehensive genomic comparison with the genomes of the winter-type cultivar 'Darmor-bzh' as well as two progenitors. The integrated BAC-to-BAC and whole-genome shotgun sequencing strategies were effective in the assembly of repetitive regions (especially young long terminal repeats) and resulted in a high-quality genome assembly of B. napus 'ZS11'. Within a short evolutionary period (~6700 years ago), semi-winter-type 'ZS11' and the winter-type 'Darmor-bzh' maintained highly genomic collinearity. Even so, certain genetic differences were also detected in two morphotypes. Relative to 'Darmor-bzh', both two subgenomes of 'ZS11' are closely related to its progenitors, and the 'ZS11' genome harbored several specific segmental homoeologous exchanges (HEs). Furthermore, the semi-winter-type 'ZS11' underwent potential genomic introgressions with B. rapa (Ar ). Some of these genetic differences were associated with key agronomic traits. A key gene of A03.FLC3 regulating vernalization-responsive flowering time in 'ZS11' was first experienced HE, and then underwent genomic introgression event with Ar , which potentially has led to genetic differences in controlling vernalization in the semi-winter types. Our observations improved our understanding of the genetic diversity of different B. napus morphotypes and the cultivation history of semi-winter oilseed rape in Asia.

Visible-Light-Mediated Ring-Opening Strategy for the Regiospecific Allylation/Formylation of Cycloalkanols.

Here we describe a straightforward and efficient approach for regiospecific introduction of an allyl group into cycloalkanol molecules employing a visible-light-mediated ring-opening strategy. A wide range of distally allylated or formylated ketones is furnished from 1-aryl cycloalkanol precursors of variable ring sizes, providing a concise and practical access for the modification of complex natural products. Preliminary mechanistic studies demonstrate that the key O-centered radicals mediate the sequential ring cleavage and allylation/formylation.

Inhibition of Mcl-1 enhances Pevonedistat-triggered apoptosis in osteosarcoma cells.

Neddylation inhibitor Pevonedistat (MLN4924) is a novel anticancer drug and has demonstrated broad-spectrum anticancer activity. Nevertheless, we found that Pevonedistat had only a modest apoptotic effect in osteosarcoma (OS) cells. Moreover, we noted that inhibition of neddylation by Pevonedistat led to accumulation of Mcl-1 protein in OS cells. Because Mcl-1 is an important anti-apoptotic protein and also because apoptosis has been shown to be a major cell death pathway, we hypothesized that Mcl-1 accumulation negatively impacted Pevonedistat-mediated anticancer activity in OS cells. In this regard, we employed genetic or pharmacological approaches to inhibit Mcl-1 expression and to examine the effect on Pevonedistat-induced apoptosis in OS cells. We found that inhibition of Mcl-1 expression by siRNA considerably enhanced Pevonedistat-triggered the activation of caspase-3, PARP cleavage and apoptosis, and also dramatically promoted the ability of Pevonedistat to inhibit colony formation of OS cells. Moreover, we observed that flavopiridol, a FDA approved drug, inhibited Mcl-1 expression and substantially enhanced Pevonedistat-mediated activation of apoptosis signaling and significantly augmented cell killing effect in OS cells. Altogether, our study shows that Mcl-1 is a critical resistance factor to Pevonedistat monotherapy, and suggests that Pevonedistat in combinations with flavopiridol may achieve better anticancer therapy.

p38α MAPK is required for arsenic-induced cell transformation.

Arsenic exposure has been reported to cause neoplastic transformation through the activation of PcG proteins. In the present study, we show that activation of p38α mitogen-activated protein kinase (MAPK) is required for arsenic-induced neoplastic transformation. Exposure of cells to 0.5 µM arsenic increased CRE and c-Fos promoter activities that were accompanied by increases in p38α MAPK and CREB phosphorylation and expression levels concurrently with AP-1 activation. Introduction of short hairpin (sh) RNA-p38α into BALB/c 3T3 cells markedly suppressed arsenic-induced colony formation compared with wildtype cells. CREB phosphorylation and AP-1 activation were decreased in p38α knockdown cells after arsenic treatment. Arsenic-induced AP-1 activation, measured as c-Fos and CRE promoter activities, and CREB phosphorylation were attenuated by p38 inhibition in BALB/c 3T3 cells. Thus, p38α MAPK activation is required for arsenic-induced neoplastic transformation mediated through CREB phosphorylation and AP-1 activation.

The Tarenaya hassleriana genome provides insight into reproductive trait and genome evolution of crucifers.

The Brassicaceae, including Arabidopsis thaliana and Brassica crops, is unmatched among plants in its wealth of genomic and functional molecular data and has long served as a model for understanding gene, genome, and trait evolution. However, genome information from a phylogenetic outgroup that is essential for inferring directionality of evolutionary change has been lacking. We therefore sequenced the genome of the spider flower (Tarenaya hassleriana) from the Brassicaceae sister family, the Cleomaceae. By comparative analysis of the two lineages, we show that genome evolution following ancient polyploidy and gene duplication events affect reproductively important traits. We found an ancient genome triplication in Tarenaya (Th-α) that is independent of the Brassicaceae-specific duplication (At-α) and nested Brassica (Br-α) triplication. To showcase the potential of sister lineage genome analysis, we investigated the state of floral developmental genes and show Brassica retains twice as many floral MADS (for minichromosome maintenance1, AGAMOUS, DEFICIENS and serum response factor) genes as Tarenaya that likely contribute to morphological diversity in Brassica. We also performed synteny analysis of gene families that confer self-incompatibility in Brassicaceae and found that the critical serine receptor kinase receptor gene is derived from a lineage-specific tandem duplication. The T. hassleriana genome will facilitate future research toward elucidating the evolutionary history of Brassicaceae genomes.

The sacred lotus genome provides insights into the evolution of flowering plants.

Sacred lotus (Nelumbo nucifera) is an ornamental plant that is also used for food and medicine. This basal eudicot species is especially important from an evolutionary perspective, as it occupies a critical phylogenetic position in flowering plants. Here we report the draft genome of a wild strain of sacred lotus. The assembled genome is 792 Mb, which is approximately 85-90% of genome size estimates. We annotated 392 Mb of repeat sequences and 36,385 protein-coding genes within the genome. Using these sequence data, we constructed a phylogenetic tree and confirmed the basal location of sacred lotus within eudicots. Importantly, we found evidence for a relatively recent whole-genome duplication event; any indication of the ancient paleo-hexaploid event was, however, absent. Genomic analysis revealed evidence of positive selection within 28 embryo-defective genes and one annexin gene that may be related to the long-term viability of sacred lotus seed. We also identified a significant expansion of starch synthase genes, which probably elevated starch levels within the rhizome of sacred lotus. Sequencing this strain of sacred lotus thus provided important insights into the evolution of flowering plant and revealed genetic mechanisms that influence seed dormancy and starch synthesis.

Microstructure Evolution and Mechanical Properties of 7A52 Aluminum Alloy Thin Sheet Repaired with Friction Stir Surfacing.

A solid-state repair technique based on surface friction welding is investigated in depth to achieve excellent mechanical properties of damaged 7A52 aluminum alloy. The results show that the yield strength and tensile strength along the repair direction are 436 MPa and 502 MPa, respectively, at a rotational speed of 1400 rpm and a travel speed of 300 mm/min, which are about 157.9% and 129.7% of those before the defects were repaired, respectively, while the elongation is 17.2% compared to the base material. Perpendicular to the repair direction, the yield strength and tensile strength are 254 MPa and 432 MPa, which are 111.4% and 129.7% of those before the defects were repaired, respectively, while the elongation is 11.8% compared to the base material. The mechanical properties of the repaired areas are still improved compared to those of the defect-free sheets. On the one hand, this is attributed to the dynamic recrystallization of the nugget zone due to the thermo-mechanical coupling, resulting in the formation of a fine, equiaxed grain structure; on the other hand, the precipitated Mg2Si phase, which is incoherent within the base material, transforms into the Al12(Fe, Mn)3Si phase, as well as the precipitation of the Al6Mn phase and η' phase, resulting in the enhancement of the properties. The material fracture at the junction of the nugget zone and the heat-affected zone occurs after repair, which is attributed to the significant difference in the texture of the nugget zone and the heat-affected zone, as well as to the stress concentration at the junction.

Achieving Equiaxed Transition and Excellent Mechanical Properties in a Novel Near-ß Titanium Alloy by Regulating the Volume Energy Density of Selective Laser Melting.

This research investigated the relationship between volume energy density and the microstructure, density, and mechanical properties of the Ti-5Al-5Mo-3V-1Cr-1Fe alloy fabricated via the SLM process. The results indicate that an increase in volume energy density can promote a transition from a columnar to an equiaxed grain structure and suppress the anisotropy of mechanical properties. Specifically, at a volume energy density of 83.33 J/mm3, the average aspect ratio of ß grains reached 0.77, accompanied by the formation of numerous nano-precipitated phases. Furthermore, the relative density of the alloy initially increased and then decreased as the volume energy density increased. At a volume energy density of 83.33 J/mm3, the relative density reached 99.6%. It is noteworthy that an increase in volume energy density increases the ß grain size. Consequently, with a volume energy density of 83.33 J/mm3, the alloy exhibited an average grain size of 63.92 µm, demonstrating optimal performance with a yield strength of 1003.06 MPa and an elongation of 18.16%. This is mainly attributable to the fact that an increase in volume energy density enhances thermal convection within the molten pool, leading to alterations in molten pool morphology and a reduction in temperature gradients within the alloy. The reduction in temperature gradients promotes equiaxed grain transformation and grain refinement by increasing constitutive supercooling at the leading edge of the solid-liquid interface. The evolution of molten pool morphology mainly inhibits columnar grain growth and refines grain by changing the grain growth direction. This study provided a straightforward method for inhibiting anisotropy and enhancing mechanical properties.

Diluted contrast media combined with high-resolution C-arm CT for evaluating apposition of flow diversions in a porcine model.

BACKGROUND: In intracranial stenting, good stent apposition is crucial, and high-resolution C-arm computer tomography (CT) is utilized to assess whether stent apposition is complete. This study was aimed at finding optimal hypertonic or isotonic contrast media injection concentration for high-resolution C-arm CT to assess apposition of flow diversion (FD) after carotid artery stenting in swine. METHODS: Twelve FD stents were implanted into the left carotid artery of Bama swine through the endovascular method. During high-resolution C-arm CT scanning, 6%, 8%, 10%, 12%, and 14% dilution percentages of hypertonic contrast media (iopromide 370 mg/ml) and 10%, 12%, 14%, 16%, and 18% dilution percentages of isotonic contrast media (iodixanol 320 mg/ml) were separately injected. A radiologist and a neuro-interventional specialist evaluated and qualitatively scored the post-processed images, and intravascular ultrasound (IVUS) was used to verify the accuracy of these images. RESULTS: Overall, 12 FD stents were implanted into the left common carotid artery of 12 swine, with a technical success rate of 100%. The best reconstructed images used to observe stent apposition were achieved with iopromide diluted to a concentration of 12% (all P < .05) or iodixanol diluted to a concentration of 16% (all P < .05). Malapposition was noted in one case, and good apposition was noted in 11 cases. These results were consistent with IVUS observations. CONCLUSION: Injecting iopromide or iodixanol diluted to 12% or 16% during high-resolution C-arm CT scanning, respectively, can help evaluate FD stent apposition and obtain optimal image quality.

Deficiency of betaine-homocysteine methyltransferase activates glucose-6-phosphate dehydrogenase (G6PD) by decreasing arginine methylation of G6PD in hepatocellular carcinogenesis.

Betaine-homocysteine methyltransferase (BHMT) regulates protein methylation and is correlated with tumorigenesis; however, the effects and regulation of BHMT in hepatocarcinogenesis remain largely unexplored. Here, we determined the clinical significance of BHMT in the occurrence and progression of hepatocellular carcinoma (HCC) using tissue samples from 198 patients. BHMT was to be frequently found (86.6%) expressed at relatively low levels in HCC tissues and was positively correlated with the overall survival of patients with HCC. Bhmt overexpression effectively suppressed several malignant phenotypes in hepatoma cells in vitro and in vivo, whereas complete knockout of Bhmt (Bhmt-/-) produced the opposite effect. We combined proteomics, metabolomics, and molecular biological strategies and detected that Bhmt-/- promoted hepatocarcinogenesis and tumor progression by enhancing the activity of glucose-6-phosphate dehydrogenase (G6PD) and PPP metabolism in DEN-induced HCC mouse and subcutaneous tumor-bearing models. In contrast, restoration of Bhmt with an AAV8-Bhmt injection or pharmacological inhibition of G6PD attenuated hepatocarcinogenesis. Additionally, coimmunoprecipitation identified monomethylated modifications of the G6PD, and BHMT regulated the methylation of G6PD. Protein sequence analysis, generation and application of specific antibodies, and site-directed mutagenesis indicated G6PD methylation at the arginine residue 246. Furthermore, we established bidirectionally regulated BHMT cellular models combined with methylation-deficient G6PD mutants to demonstrate that BHMT potentiated arginine methylation of G6PD, thereby inhibiting G6PD activity, which in turn suppressed hepatocarcinogenesis. Taken together, this study reveals a new methylation-regulatory mechanism in hepatocarcinogenesis owing to BHMT deficiency, suggesting a potential therapeutic strategy for HCC treatment.

Cicer super-pangenome provides insights into species evolution and agronomic trait loci for crop improvement in chickpea.

Chickpea (Cicer arietinum L.)-an important legume crop cultivated in arid and semiarid regions-has limited genetic diversity. Efforts are being undertaken to broaden its diversity by utilizing its wild relatives, which remain largely unexplored. Here, we present the Cicer super-pangenome based on the de novo genome assemblies of eight annual Cicer wild species. We identified 24,827 gene families, including 14,748 core, 2,958 softcore, 6,212 dispensable and 909 species-specific gene families. The dispensable genome was enriched for genes related to key agronomic traits. Structural variations between cultivated and wild genomes were used to construct a graph-based genome, revealing variations in genes affecting traits such as flowering time, vernalization and disease resistance. These variations will facilitate the transfer of valuable traits from wild Cicer species into elite chickpea varieties through marker-assisted selection or gene-editing. This study offers valuable insights into the genetic diversity and potential avenues for crop improvement in chickpea.

The use of Xuanbai Chengqi decoction on monkeypox disease through the estrone-target AR interaction.

Introduction: After COVID-19, there was an outbreak of a new infectious disease caused by monkeypox virus. So far, no specific drug has been found to treat it. Xuanbai Chengqi decoction (XBCQD) has shown effects against a variety of viruses in China. Methods: We searched for the active compounds and potential targets for XBCQD from multiple open databases and literature. Monkeypox related targets were searched out from the OMIM and GeneCards databases. After determining the assumed targets of XBCQD for monkeypox treatment, we built the PPI network and used R for GO enrichment and KEGG pathway analysis. The interactions between the active compounds and the hub targets were investigated by molecular docking and molecular dynamics (MD) simulations. Results: In total, 5 active compounds and 10 hub targets of XBCQD were screened out. GO enrichment and KEGG analysis demonstrated that XBCQD plays a therapeutic role in monkeypox mainly by regulating signaling pathways related to viral infection and inflammatory response. The main active compound estrone binding to target AR was confirmed to be the best therapy choice for monkeypox. Discussion: This study systematically explored the interactions between the bioactive compounds of XBCQD and the monkeypox-specific XBCQD targets using network pharmacological methods, bioinformatics analyses and molecular simulations, suggesting that XBCQD could have a beneficial therapeutic effect on monkeypox by reducing the inflammatory damage and viral replication via multiple pathways. The use of XBCQD on monkeypox disease was confirmed to be best worked through the estrone-target AR interaction. Our work could provide evidence and guidance for further research on the treatment of monkeypox disease.