Characterization and Dissolution Mechanism of Low-Molecular-Weight Organic Acids or Inorganic Mesoporous Particle-Based Piperine Amorphous Solid Dispersions.

The objective of the current study is to prepare amorphous solid dispersions (ASDs) containing piperine (PIP) by utilizing organic acid glycyrrhizic acid (GA) and inorganic disordered mesoporous silica 244FP (MSN/244FP) as carriers and to investigate their dissolution mechanism. The physicochemical properties of ASDs were characterized with scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). Fourier transform infrared spectroscopy (FTIR) and one-dimensional proton nuclear magnetic resonance (1H NMR) studies collectively proved that strong hydrogen-bonding interactions formed between PIP and the carriers in ASDs. Additionally, molecular dynamic (MD) simulation was conducted to simulate and predict the physical stability and dissolution mechanisms of the ASDs. Interestingly, it revealed a significant increase in the dissolution of amorphous PIP in ASDs in in vitro dissolution studies. Rapid dissolution of GA in pH 6.8 medium resulted in the immediate release of PIP drugs into a supersaturated state, acting as a dissolution-control mechanism. This exhibited a high degree of fitting with the pseudo-second-order dynamic model, with an R2 value of 0.9996. Conversely, the silanol groups on the outer surface of the MSN and its porous nanostructures enabled PIP to display a unique two-step drug release curve, indicating a diffusion-controlled mechanism. This curve conformed to the Ritger-Peppas model, with an R2 > 0.9. The results obtained provide a clear evidence of the proposed transition of dissolution mechanism within the same ASD system, induced by changes in the properties of carriers in a solution medium of varying pH levels.

Expanding the targeting scope of CRISPR/Cas9-mediated genome editing by Cas9 variants in Brassica.

CRISPR/Cas9, presently the most widely used genome editing technology, has provided great potential for functional studies and plant breeding. However, the strict requirement for a protospacer adjacent motif (PAM) has hindered the application of the CRISPR/Cas9 system because the number of targetable genomic sites is limited. Recently, the engineered variants Cas9-NG, SpG, and SpRY, which recognize non-canonical PAMs, have been successfully tested in plants (mainly in rice, a monocot). In this study, we evaluated the targeted mutagenesis capabilities of these Cas9 variants in two important Brassica vegetables, Chinese cabbage (Brassica rapa spp. pekinensis) and cabbage (Brassica oleracea var. capitata). Both Cas9-NG and SpG induced efficient mutagenesis at NGN PAMs, while SpG outperformed Cas9-NG at NGC and NGT PAMs. SpRY achieved efficient editing at almost all PAMs (NRN > NYN), albeit with some self-targeting activity at transfer (T)-DNA sequences. And SpRY-induced mutants were detected in cabbage plants in a PAM-less fashion. Moreover, an adenine base editor was developed using SpRY and TadA8e deaminase that induced A-to-G conversions within target sites using non-canonical PAMs. Together, the toolboxes developed here induced successful genome editing in Chinese cabbage and cabbage. Our work further expands the targeting scope of genome editing and paves the way for future basic research and genetic improvement in Brassica. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-024-00155-7.

The effects of impurities in carbide slag on the morphological evolution of CaCO3 during carbonation.

Carbide slag (CS) is a kind of solid waste generated by the hydrolysis of calcium carbide for acetylene production. Its major component is Ca(OH)2, which shows great potential in CO2 mineralization to produce CaCO3. However, the types of impurities in CS and their mechanisms for inducing the morphological evolution of CaCO3 are still unclear. In this work, the influence of impurities in CS on the morphology evolution of CaCO3 was investigated. The following impurities were identified in the CS: Al2O3, MgO, Fe2O3, SiO2 and CaCO3. Ca(OH)2 was used to study the influence of impurities (Al2O3 and Fe2O3) on the evolution of CaCO3 morphology during CS carbonation. Calcite (CaCO3) was the carbonation product produced during CS carbonation under varying conditions. The morphology of calcite was changed from cubic to rod-shaped, with increasing solid-liquid ratios. Moreover, rod-shaped calcite was converted into irregular particles with increasing CO2 flow rate and stirring speed. Rod-shaped calcite (CaCO3) was formed by CS carbonation at a solid-liquid ratio of 10:100 under a stirring speed of 600 rpm and a CO2 flow rate of 200 ml/min; and spherical calcite was generated during Ca(OH)2 carbonation under the same conditions. Al2O3 impurities had negligible effects on spherical CaCO3 during Ca(OH)2 carbonation. In contrast, rod-shaped CaCO3 was generated by adding 0.13 wt% Fe2O3 particles, similar to the content of Fe2O3 in CS. Rod-shaped calcite was converted into particulate calcite with increasing Fe2O3 content. The surface wettability and surface negative charge of Fe2O3 appeared to be responsible for the formation of rod-shaped CaCO3. This study enhances our understanding and utilization of CS and CO2 reduction and the fabrication of high-value rod-shaped CaCO3.

Explore the mechanism of Astragalus membranaceus and Poria cocos drug pair in improving immunity based on network pharmacology.

The aim of this study was to investigate the key targets and molecular mechanisms of the drug pair Astragalus membranaceus and Poria cocos (HFDP) in the treatment of immunity. We utilized network pharmacology, molecular docking, and immune infiltration techniques in conjunction with data from the GEO database. Previous clinical studies have shown that HFDP has a positive impact on immune function. We first identified the active ingredients and targets of HFDP from the Traditional Chinese Medicine Systems Pharmacology database and the Swiss Target Prediction database, respectively. Next, we retrieved the differentially expressed genes (DEGs) related to immunity from the GEO databases. The intersection targets of the drugs and diseases were then analyzed using the STRING database for protein-protein interaction (PPI) network analysis, and the core targets were determined through topological analysis. Finally, the intersection genes were further analyzed using the DAVID database for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses. Subsequently, by analyzing the expression and prognostic survival of 12 core targets, 5 core target genes were identified, and molecular docking between the hub genes and immunity was performed. Finally, we used the CIBERSORT algorithm to analyze the immune infiltration of immunity genes In this study, 34 effective ingredients of HFDP, 530 target genes, and 568 differential genes were identified. GO and KEGG analysis showed that the intersection genes of HFDP targets and immunity-related genes were mainly related to complement and coagulation cascades, cytokine receptors, and retinol metabolism pathways. The molecular docking results showed that the 5 core genes had obvious affinity for the active ingredients of HFDP, which could be used as potential targets to improve the immunity of HFDP. Our findings suggest that HFDP is characterized by "multiple components, multiple targets, and multiple pathways" in regulating immunity. It may play an essential role in regulating immunity by regulating the expression and polymorphism of the central target genes ESR1, JUN, CYP3A4, CYP2C9, and SERPINE1.

Personalized prediction of postoperative complication and survival among Colorectal Liver Metastases Patients Receiving Simultaneous Resection using machine learning approaches: A multi-center study.

BACKGROUND: To predict clinical important outcomes for colorectal liver metastases (CRLM) patients receiving colorectal resection with simultaneous liver resection by integrating demographic, clinical, laboratory, and genetic data. METHODS: Random forest (RF) models were developed to predict postoperative complications and major complications (binary outcomes), as well as progression-free survival (PFS) and overall survival (OS) (time-to-event outcomes) of the CRLM patients based on data from two hospitals. The models were validated on an external dataset from an independent hospital. The clinical utility of the models was assessed via decision curve analyses (DCA). RESULTS: There were 1067 patients included in survival prediction analyses and 1070 patients included in postoperative complication prediction analyses. The RF models provided an assessment of the model contributions of features for outcomes and suggested KRAS, BRAF, and MMR status were salient for the PFS or OS predictions. RF model of PFS showed that the Brier scores at 1-, 3-, and 5-year PFS were 0.213, 0.202 and 0.188; and the AUCs of 1-, 3- and 5-year PFS were 0.702, 0.720 and 0.743. RF model of OS revealed that Brier scores of 1-,3-, and 5-year OS were 0.040, 0.183 and 0.211; and the AUCs of 1-, 3- and 5-year OS were 0.737, 0.706 and 0.719. RF model for postoperative complication resulted in an AUC of 0.716 and a Brier score of 0.196. DCA curves clearly demonstrated that the RF models for these outcomes exhibited a superior net benefit across a wide range of threshold probabilities, signifying their favorable clinical utility. The RF models consistently exhibited robust performance in both internal cross-validation and external validation. The individualized risk profile predicted by the models closely aligned with the actual survival outcomes observed for the patients. A web-based tool (https://kanli.shinyapps.io/CRLMRF/) was provided to demonstrate the practical use of the prediction models for new patients in the clinical setting. CONCLUSION: The predictive models and a web-based tool for personalized prediction demonstrated a moderate predictive performance and favorable clinical utilities on several key clinical outcomes of CRLM patients receiving simultaneous resection, which could facilitate the clinical decision-making and inform future interventions for CRLM patients.

Epicardial SMARCA4 deletion exacerbates cardiac injury in myocardial infarction and is related to the inhibition of epicardial epithelial-mesenchymal transition.

The reactivated adult epicardium produces epicardium-derived cells (EPDCs) via epithelial-mesenchymal transition (EMT) to benefit the recovery of the heart after myocardial infarction (MI). SMARCA4 is the core catalytic subunit of the chromatin re-modeling complex, which has the potential to target some reactivated epicardial genes in MI. However, the effects of epicardial SMARCA4 on MI remain uncertain. This study found that SMARCA4 was activated over time in epicardial cells following MI, and some of activated cells belonged to downstream differentiation types of EPDCs. This study used tamoxifen to induce lineage tracing and SMARCA4 deletion from epicardial cells in Wt1-CreER;Smarca4fl/fl;Rosa26-RFP adult mice. Epicardial SMARCA4 deletion reduces the number of epicardial cells in adult mice, which was related to changes in the activation, proliferation, and apoptosis of epicardial cells. Epicardial SMARCA4 deletion reduced collagen deposition and angiogenesis in the infarcted area, exacerbated cardiac injury in MI. The exacerbation of cardiac injury was related to the inhibition of generation and differentiation of EPDCs. The alterations in EPDCs were associated with inhibited transition between E-CAD and N-CAD during the epicardial EMT, coupled with the down-regulation of WT1, SNAIL1, and PDGF signaling. In conclusion, this study suggests that Epicardial SMARCA4 plays a critical role in cardiac injury caused by MI, and its regulatory mechanism is related to epicardial EMT. Epicardial SMARCA4 holds potential as a novel molecular target for treating MI.

Ubiquitin-mediated regulation of APE2 protein abundance.

APE2 plays important roles in the maintenance of genomic and epigenomic stability including DNA repair and DNA damage response. Accumulating evidence has suggested that APE2 is upregulated in multiple cancers at the protein and mRNA levels and that APE2 upregulation is correlative with higher and lower overall survival of cancer patients depending on tumor type. However, it remains unknown how APE2 protein abundance is maintained and regulated in cells. Here, we provide the first evidence of APE2 regulation via the posttranslational modification ubiquitin. APE2 is poly-ubiquitinated via K48-linked chains and degraded via the ubiquitin-proteasome system where K371 is the key residue within APE2 responsible for its ubiquitination and degradation. We further characterize MKRN3 as the E3 ubiquitin ligase for APE2 ubiquitination in cells and in vitro. In summary, this study offers the first definition of the APE2 proteostasis network and lays the foundation for future studies pertaining to the posttranslational modification regulation and functions of APE2 in genome integrity and cancer etiology/treatment.

Transcriptomic analyses to summarize gene expression patterns that occur during leaf initiation of Chinese cabbage.

In Chinese cabbage, rosette leaves expose their adaxial side to the light converting light energy into chemical energy, acting as a source for the growth of the leafy head. In the leafy head, the outer heading leaves expose their abaxial side to the light while the inner leaves are shielded from the light and have become a sink organ of the growing Chinese cabbage plant. Interestingly, variation in several ad/abaxial polarity genes is associated with the typical leafy head morphotype. The initiation of leaf primordia and the establishment of leaf ad/abaxial polarity are essential steps in the initiation of marginal meristem activity leading to leaf formation. Understanding the molecular genetic mechanisms of leaf primordia formation, polar differentiation, and leaf expansion is thus relevant to understand leafy head formation. As Brassica's are mesa-hexaploids, many genes have multiple paralogues, complicating analysis of the genetic regulation of leaf development. In this study, we used laser dissection of Chinese cabbage leaf primordia and the shoot apical meristem (SAM) to compare gene expression profiles between both adaxial and abaxial sides and the SAM aiming to capture transcriptome changes underlying leaf primordia development. We highlight genes with roles in hormone pathways and transcription factors. We also assessed gene expression gradients along expanded leaf blades from the same plants to analyze regulatory links between SAM, leaf primordia and the expanding rosette leaf. The catalogue of differentially expressed genes provides insights in gene expression patterns involved in leaf development and form a starting point to unravel leafy head formation.

To explore the mechanism of Yigong San anti-gastric cancer and immune regulation.

BACKGROUND: Yigong San (YGS) is a representative prescription for the treatment of digestive disorders, which has been used in clinic for more than 1000 years. However, the mechanism of its anti-gastric cancer and regulate immunity are still remains unclear. AIM: To explore the mechanism of YGS anti-gastric cancer and immune regulation. METHODS: Firstly, collect the active ingredients and targets of YGS, and the differentially expressed genes of gastric cancer. Secondly, constructed a protein-protein interaction network between the targets of drugs and diseases, and screened hub genes. Then the clinical relevance, mutation and repair, tumor microenvironment and drug sensitivity of the hub gene were analyzed. Finally, molecular docking was used to verify the binding ability of YGS active ingredient and hub genes. RESULTS: Firstly, obtained 55 common targets of gastric cancer and YGS. The Kyoto Encyclopedia of Genes and Genomes screened the microtubule-associated protein kinase signaling axis as the key pathway and IL6, EGFR, MMP2, MMP9 and TGFB1 as the hub genes. The 5 hub genes were involved in gastric carcinogenesis, staging, typing and prognosis, and their mutations promote gastric cancer progression. Finally, molecular docking results confirmed that the components of YGS can effectively bind to therapeutic targets. CONCLUSION: YGS has the effect of anti-gastric cancer and immune regulation.

Antiviral defense in plant stem cells.

Undifferentiated plant and animal stem cells are essential for cell, tissue, and organ differentiation, development, and growth. They possess unusual antiviral immunity which differs from that in specialized cells. By comparison to animal stem cells, we discuss how plant stem cells defend against viral invasion and beyond.

Multiome in the Same Cell Reveals the Impact of Osmotic Stress on Arabidopsis Root Tip Development at Single-Cell Level.

Cell-specific transcriptional regulatory networks (TRNs) play vital roles in plant development and response to environmental stresses. However, traditional single-cell mono-omics techniques are unable to directly capture the relationships and dynamics between different layers of molecular information within the same cells. While advanced algorithm facilitates merging scRNA-seq and scATAC-seq datasets, accurate data integration remains a challenge, particularly when investigating cell-type-specific TRNs. By examining gene expression and chromatin accessibility simultaneously in 16,670 Arabidopsis root tip nuclei, the TRNs are reconstructed that govern root tip development under osmotic stress. In contrast to commonly used computational integration at cell-type level, 12,968 peak-to-gene linkage is captured at the bona fide single-cell level and construct TRNs at an unprecedented resolution. Furthermore, the unprecedented datasets allow to more accurately reconstruct the coordinated changes of gene expression and chromatin states during cellular state transition. During root tip development, chromatin accessibility of initial cells precedes gene expression, suggesting that changes in chromatin accessibility may prime cells for subsequent differentiation steps. Pseudo-time trajectory analysis reveal that osmotic stress can shift the functional differentiation of trichoblast. Candidate stress-related gene-linked cis-regulatory elements (gl-cCREs) as well as potential target genes are also identified, and uncovered large cellular heterogeneity under osmotic stress.

Aptamer-aided plasmonic nano-urchins for reporter-free surface-enhanced Raman spectroscopy analysis of cortisol.

Cortisol is a vital glucocorticoid hormone reflecting stress levels and related disease processes. In this study, we report an aptamer-functionalized plasmonic nano-urchin (α-FeOOH@Au-aptamer)-aided cortisol-capturing and surface-enhanced Raman spectroscopy (SERS) analysis approach. The designed α-FeOOH@Au-aptamer exhibits a well-patterned plasma structure, which combines the good SERS enhancement ability of reduced nanogaps between the Au plasma and the hot spot-favored structure of anisotropic tips from α-FeOOH urchins, with the high affinity of the aptamer towards cortisol molecules. The α-FeOOH@Au-aptamer achieved reporter-free SERS quantification for cortisol with good sensitivity (limit of detection <0.28 µmol L-1), robust salt (1.0 mol per L NaCl) and protein (5.0 mg per mL bovine serum protein) tolerance, favorable reproducibility, as well as good reusability. We further demonstrated the good cortisol-capturing ability and SERS efficacy of the α-FeOOH@Au-aptamer profiling in the serum and urine samples. Our approach provides an alternative tool for cortisol analysis and a reference strategy for report-free SERS detection of small molecules.

Nodal recurrence mapping and clinical target volumes after resection of intrahepatic cholangiocarcinoma or combined hepatocellular-cholangiocarcinoma.

Background: Scarce evidence exists for clinical target volume (CTV) definitions of regional lymph nodes (LNs) in intrahepatic cholangiocarcinoma (iCCA) or combined hepatocellular-cholangiocarcinoma (cHCC-CCA). We investigated the mapping pattern of nodal recurrence after surgery for iCCA and cHCC-CCA and provided evidence for the nodal CTV definition. Methods: We retrospectively reviewed the medical records of patients with iCCA or cHCC-CCA who underwent surgery between 2010 and 2020. Eligibility criteria included patients pathologically diagnosed with iCCA or cHCC-CCA after surgery and a first recurrent event in regional LNs during follow-up. All recurrent LNs were registered onto reference computed tomography images based on the vascular structures to reconstruct the node mapping. Fifty-three patients were eligible. LN regions were classified into four risk groups. Results: Hepatic hilar and portal vein-vena cava were the most common recurrent regions, with recurrence rates of 62.3 % and 39.6 % (high-risk regions), respectively. Recurrence rates in the left gastric, diaphragmatic, common hepatic, superior mesenteric vessels, celiac trunk, and paracardial regions ranged from 15.1 % to 30.2 % (intermediate-risk regions). There were fewer recurrences in the para-aortic (16a1, a2, b1) and splenic artery and hilum regions, with rates <10 % (low-risk regions). No LN recurrence was observed in the para-oesophageal or para-aortic region (16b2) (very low-risk regions). Based on node mapping, the CTV should include high- and intermediate-risk regions for pathologically negative LN patients during postoperative radiotherapy. Low-risk regions should be included for pathologically positive LN patients. Conclusion: We provide evidence for CTV delineation in patients with iCCA and cHCC-CCA based on recurrent LN mapping.

Multispectral detection of dietary fiber content in Chinese cabbage leaves across different growth periods.

Multispectral imaging, combined with stoichiometric values, was used to construct a prediction model to measure changes in dietary fiber (DF) content in Chinese cabbage leaves across different growth periods. Based on all the spectral bands (365-970 nm) and characteristic spectral bands (430, 880, 590, 490, 690 nm), eight quantitative prediction models were established using four machine learning algorithms, namely random forest (RF), backpropagation neural network, radial basis function, and multiple linear regression. Finally, a quantitative prediction model of RF learning algorithm is constructed based on all spectral bands, which has good prediction accuracy and model robustness, prediction performance with R2 of 0.9023, root mean square error (RMSE) of 2.7182 g/100 g, residual predictive deviation (RPD) of 3.1220 > 3.0. In summary, this model efficiently detects changes in DF content across different growth periods of Chinese cabbage, which offers technical support for vegetable sorting and grading in the field.

LncRNA LUCAT1 Promotes Glioblastoma Progression by Enhancing HIF1α Activity.

BACKGROUND: Hypoxia is associated with poor prognosis in many cancers including glioblastoma (GBM). Glioma stem-like cells (GSCs) often reside in hypoxic regions and serve as reservoirs for disease progression. Long non-coding RNAs (lncRNAs) have been implicated in GBM. However, the lncRNAs that modulate GSC adaptations to hypoxia are poorly understood. Identification of these lncRNAs may provide new therapeutic strategies to target GSCs under hypoxia. METHODS: lncRNAs induced by hypoxia in GSCs were identified by RNAseq. LUCAT1 expression was assessed by qPCR, RNAseq, Northern blot, single molecule FISH in GSCs, and interrogated in IvyGAP, TCGA, and CGGA databases. LUCAT1 was depleted by shRNA, CRISPR/Cas9, and CRISPR/Cas13d. RNAseq, Western blot, immunohistochemistry, co-IP, ChIP, ChIPseq, RNA immunoprecipitation, and proximity ligation assay were performed to investigate mechanisms of action of LUCAT1. GSC viability, limiting dilution assay, and tumorigenic potential in orthotopic GBM xenograft models were performed to assess the functional consequences of depleting LUCAT1. RESULTS: A new isoform of Lucat1 is induced by HIF1α and NRF2 in GSCs under hypoxia. LUCAT1 is highly expressed in hypoxic regions in GBM. Mechanistically, LUCAT1 formed a complex with HIF1α and its co-activator CBP to regulate HIF1α target gene expression and GSC adaptation to hypoxia. Depletion of LUCAT1 impaired GSC self-renewal. Silencing LUCAT1 decreased tumor growth and prolonged mouse survival in GBM xenograft models. CONCLUSIONS: A HIF1α-LUCAT1 axis forms a positive feedback loop to amplify HIF1α signaling in GSCs under hypoxia. LUCAT1 promotes GSC self-renewal and GBM tumor growth. LUCAT1 is a potential therapeutic target in GBM.

Al-MOF-derived porous carbon-modified Pt/C catalyst for constructing a high-performance super fuel cell via an ORR + EDLC parallel-discharge mechanism.

In order to reduce the high polarization caused by the hysteresis effect of O2 diffusion and boost the power density of oxygen cathodes under a transient heavy load, an Al-MOF-derived porous carbon-modified Pt/C catalyst is proposed as a new capacitive ORR catalyst to construct super fuel cells (SFCs) via an ORR + EDLC dual-discharge parallel process. Herein, a capacitive porous carbon material (BTCC-2) with a large specific surface area (SSA) and high graphitization was synthesized via one-step carbonization of Al-MOFs (Al-BTC). After compounding BTCC-2 with commercial Pt/C catalysts, electrochemical tests were performed and revealed that the composite with 40% BTCC-2 provided the highest transient discharge performance. Moreover, the composite had a higher onset potential and limiting current density (5.236 mA cm-2) than Pt/C and a half-wave potential (0.833 V) comparable to that of Pt/C. The abundant pore structure and large surface of BTCC-2 greatly increased the interaction between oxygen and the catalyst surface. Besides, the contained BTCC-2 serve as a significant power bank to remarkably buffer and relieve the rapidly decreasing output voltage under an instant heavy load owing to the oxygen deficiencies in a Zn-air battery through the ORR + EDLC dual-parallel-discharge process. The proposed SFC design has potential as a universal method to solve the sluggish ORR process and provide high transient power density for fuel cell-driven vehicles.

HBV integrations reshaping genomic structures promote hepatocellular carcinoma.

OBJECTIVE: Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), mostly characterised by HBV integrations, is prevalent worldwide. Previous HBV studies mainly focused on a few hotspot integrations. However, the oncogenic role of the other HBV integrations remains unclear. This study aimed to elucidate HBV integration-induced tumourigenesis further. DESIGN: Here, we illuminated the genomic structures encompassing HBV integrations in 124 HCCs across ages using whole genome sequencing and Nanopore long reads. We classified a repertoire of integration patterns featured by complex genomic rearrangement. We also conducted a clustered regularly interspaced short palindromic repeat (CRISPR)-based gain-of-function genetic screen in mouse hepatocytes. We individually activated each candidate gene in the mouse model to uncover HBV integration-mediated oncogenic aberration that elicits tumourigenesis in mice. RESULTS: These HBV-mediated rearrangements are significantly enriched in a bridge-fusion-bridge pattern and interchromosomal translocations, and frequently led to a wide range of aberrations including driver copy number variations in chr 4q, 5p (TERT), 6q, 8p, 16q, 9p (CDKN2A/B), 17p (TP53) and 13q (RB1), and particularly, ultra-early amplifications in chr8q. Integrated HBV frequently contains complex structures correlated with the translocation distance. Paired breakpoints within each integration event usually exhibit different microhomology, likely mediated by different DNA repair mechanisms. HBV-mediated rearrangements significantly correlated with young age, higher HBV DNA level and TP53 mutations but were less prevalent in the patients subjected to prior antiviral therapies. Finally, we recapitulated the TONSL and TMEM65 amplification in chr8q led by HBV integration using CRISPR/Cas9 editing and demonstrated their tumourigenic potentials. CONCLUSION: HBV integrations extensively reshape genomic structures and promote hepatocarcinogenesis (graphical abstract), which may occur early in a patient's life.

Diversity of Endophytes of Actinidia arguta in Different Seasons.

The seasonal changes in environmental conditions can alter the growth states of host plants, thereby affecting the living environment of endophytes and forming different endophytic communities. This study employs Illumina MiSeq next-generation sequencing to analyze the 16SrRNA and ITS rDNA of endophytes in 24 samples of Actinidia arguta stem tissues across different seasons. The results revealed a high richness and diversity of endophytes in Actinidia arguta, with significant seasonal variations in microbial community richness. This study identified 897 genera across 36 phyla for bacteria and 251 genera across 8 phyla for fungi. Notably, 69 bacterial genera and 19 fungal genera significantly contributed to the differences in community structure across seasons. A distinctive feature of coexistence in the endophytic community, both specific and conservative across different seasons, was observed. The bacterial community in winter demonstrated significantly higher richness and diversity compared to the other seasons. Environmental factors likely influence the optimal timing for endophyte colonization. Solar radiation, temperature, precipitation, and relative humidity significantly impact the diversity of endophytic bacteria and fungi. In addition, seasonal variations show significant differences in the nutritional modes of fungal endophytes and the degradation, ligninolysis, and ureolysis functions of bacterial endophytes. This study elucidates the potential role of endophytes in assisting Actinidia arguta in adapting to seasonal changes and provides a theoretical basis for further exploration of functional microbial strains.

Text2Face: Text-based Face Generation with Geometry and Appearance Control.

Recent years have witnessed the emergence of various techniques proposed for text-based human face generation and manipulation. Such methods, targeting bridging the semantic gap between text and visual contents, provide users with a deft hand to turn ideas into visuals via text interface and enable more diversified multimedia applications. However, due to the flexibility of linguistic expressiveness, the mapping from sentences to desired facial images is clearly many-to-many, causing ambiguities during text-to-face generation. To alleviate these ambiguities, we introduce a local-to-global framework with two graph neural networks (one for geometry and the other for appearance) embedded to model the inter-dependency among facial parts. This is based upon our key observation that the geometry and appearance attributes among different facial components are not mutually independent, i.e., the combinations of part-level facial features are not arbitrary and thus do not conform to a uniform distribution. By learning from the dataset distribution and enabling recommendations given partial descriptions of human faces, these networks are highly suitable for our text-to-face task. Our method is capable of generating high-quality attribute-conditioned facial images from text. Extensive experiments have confirmed the superiority and usability of our method over the prior art.