Transcriptome analysis with different leaf blades identifies the phloem-specific phosphate transporter OsPHO1;3 required for phosphate homeostasis in rice.

Phosphate (Pi) is essential for plant growth and development. One strategy to improve Pi use efficiency is to enhance Pi remobilization among leaves. Using transcriptome analysis with first (top) and fourth (down) leaf blades from rice (Oryza sativa) in Pi-sufficient and deficient conditions, we identified 1384 genes differentially expressed among these leaf blades. These genes were involved in physiological processes, metabolism, transport, and photosynthesis. Moreover, we identified the Pi efflux transporter gene, OsPHO1;3, responding to Pi-supplied conditions among these leaf blades. OsPHO1;3 is highly expressed in companion cells of phloem, but not xylem, in leaf blades and induced by Pi starvation. Mutation of OsPHO1;3 led to Pi accumulation in second to fourth leaves under Pi-sufficient conditions, but enhanced Pi levels in first leaves under Pi-deficient conditions. These Pi accumulations in leaves of Ospho1;3 mutants resulted from induction of OsPHT1;2 and OsPHT1;8 in root and reduction of Pi remobilization in leaf blades, revealed by the decreased Pi in phloem of leaves. Importantly, lack of OsPHO1;3 caused growth defects under a range of Pi-supplied conditions. These results demonstrate that Pi remobilization is essential for Pi homeostasis and plant growth irrespective of Pi-supplied conditions, and OsPHO1;3 plays an essential role in Pi remobilization for normal plant growth.

PQSDC: a parallel lossless compressor for quality scores data via sequences partition and run-length prediction mapping.

MOTIVATION: The quality scores data (QSD) account for 70% in compressed FastQ files obtained from the short and long reads sequencing technologies. Designing effective compressors for QSD that counterbalance compression ratio, time cost, and memory consumption is essential in scenarios such as large-scale genomics data sharing and long-term data backup. This study presents a novel parallel lossless QSD-dedicated compression algorithm named PQSDC, which fulfills the above requirements well. PQSDC is based on two core components: a parallel sequences-partition model designed to reduce peak memory consumption and time cost during compression and decompression processes, as well as a parallel four-level run-length prediction mapping model to enhance compression ratio. Besides, the PQSDC algorithm is also designed to be highly concurrent using multicore CPU clusters. RESULTS: We evaluate PQSDC and four state-of-the-art compression algorithms on 27 real-world datasets, including 61.857 billion QSD characters and 632.908 million QSD sequences. (1) For short reads, compared to baselines, the maximum improvement of PQSDC reaches 7.06% in average compression ratio, and 8.01% in weighted average compression ratio. During compression and decompression, the maximum total time savings of PQSDC are 79.96% and 84.56%, respectively; the maximum average memory savings are 68.34% and 77.63%, respectively. (2) For long reads, the maximum improvement of PQSDC reaches 12.51% and 13.42% in average and weighted average compression ratio, respectively. The maximum total time savings during compression and decompression are 53.51% and 72.53%, respectively; the maximum average memory savings are 19.44% and 17.42%, respectively. (3) Furthermore, PQSDC ranks second in compression robustness among the tested algorithms, indicating that it is less affected by the probability distribution of the QSD collections. Overall, our work provides a promising solution for QSD parallel compression, which balances storage cost, time consumption, and memory occupation primely. AVAILABILITY AND IMPLEMENTATION: The proposed PQSDC compressor can be downloaded from https://github.com/fahaihi/PQSDC.

Proteomics identifies new therapeutic targets of early-stage hepatocellular carcinoma.

Hepatocellular carcinoma is the third leading cause of deaths from cancer worldwide. Infection with the hepatitis B virus is one of the leading risk factors for developing hepatocellular carcinoma, particularly in East Asia1. Although surgical treatment may be effective in the early stages, the five-year overall rate of survival after developing this cancer is only 50-70%2. Here, using proteomic and phospho-proteomic profiling, we characterize 110 paired tumour and non-tumour tissues of clinical early-stage hepatocellular carcinoma related to hepatitis B virus infection. Our quantitative proteomic data highlight heterogeneity in early-stage hepatocellular carcinoma: we used this to stratify the cohort into the subtypes S-I, S-II and S-III, each of which has a different clinical outcome. S-III, which is characterized by disrupted cholesterol homeostasis, is associated with the lowest overall rate of survival and the greatest risk of a poor prognosis after first-line surgery. The knockdown of sterol O-acyltransferase 1 (SOAT1)-high expression of which is a signature specific to the S-III subtype-alters the distribution of cellular cholesterol, and effectively suppresses the proliferation and migration of hepatocellular carcinoma. Finally, on the basis of a patient-derived tumour xenograft mouse model of hepatocellular carcinoma, we found that treatment with avasimibe, an inhibitor of SOAT1, markedly reduced the size of tumours that had high levels of SOAT1 expression. The proteomic stratification of early-stage hepatocellular carcinoma presented in this study provides insight into the tumour biology of this cancer, and suggests opportunities for personalized therapies that target it.

Self-Assembled PD-L1 Downregulator to Boost Photodynamic Activated Tumor Immunotherapy Through CDK5 Inhibition.

The immunosuppressive characteristics and acquired immune resistance can restrain the therapy-initiated anti-tumor immunity. In this work, an antibody free programmed death receptor ligand 1 (PD-L1) downregulator (designated as CeSe) is fabricated to boost photodynamic activated immunotherapy through cyclin-dependent kinase 5 (CDK5) inhibition. Among which, FDA approved photosensitizer of chlorin e6 (Ce6) and preclinical available CDK5 inhibitor of seliciclib (Se) are utilized to prepare the nanomedicine of CeSe through self-assembly technique without drug excipient. Nanoscale CeSe exhibits an increased stability and drug delivery efficiency, contributing to intracellular production of reactive oxygen species (ROS) for robust photodynamic therapy (PDT). The PDT of CeSe can not only suppress the primary tumor growth, but also induce the immunogenic cell death (ICD) to release tumor associated antigens. More importantly, the CDK5 inhibition by CeSe can downregulate PD-L1 to re-activate the systemic anti-tumor immunity by decreasing the tumor immune escape and therapy-induced acquired immune resistance. This work provides an antibody free strategy to activate systemic immune response for metastatic tumor treatment, which may accelerate the development of translational nanomedicine with sophisticated mechanism.

Tumor Homing Chimeric Peptide Rhomboids to Improve Photodynamic Performance by Inhibiting Therapy-Upregulated Cyclooxygenase-2.

Negative therapeutic feedback of inflammation would extensively attenuate the antitumor effect of photodynamic therapy (PDT). In this work, tumor homing chimeric peptide rhomboids (designated as NP-Mel) are fabricated to improve photodynamic performance by inhibiting PDT-upregulated cyclooxygenase-2 (COX-2). The hydrophobic photosensitizer of protoporphyrin IX (PpIX) and palmitic acid are conjugated onto the neuropilin receptors (NRPs) targeting peptide motif (CGNKRTR) to obtain tumor homing chimeric peptide (Palmitic-K(PpIX)CGNKRTR), which can encapsulate the COX-2 inhibitor of meloxicam. The well dispersed NP-Mel not only improves the drug stability and reactive oxygen species (ROS) production ability, but also increase the breast cancer targeted drug delivery to intensify the PDT effect. In vitro and in vivo studies verify that NP-Mel will decrease the secretion of prostaglandin E2 (PGE2) after PDT treatment, inducing the downregulation of IL-6 and TNF-α expressions to suppress PDT induced inflammation. Ultimately, an improved PDT performance of NP-Mel is achieved without inducing obvious systemic toxicity, which might inspire the development of sophisticated nanomedicine in consideration of the feedback induced therapeutic resistance.

Energy harvesting from water streaming at charged surface.

Water flowing at a charged surface may produce electricity, known as streaming current/potentials, which may be traced back to the 19th century. However, due to the low gained power and efficiencies, the energy conversion from streaming current was far from usable. The emergence of micro/nanofluidic technology and nanomaterials significantly increases the power (density) and energy conversion efficiency. In this review, we conclude the fundamentals and recent progress in electrical double layers at the charged surface. We estimate the generated power by hydrodynamic energy dissipation in multi-scaling flows considering the viscous systems with slipping boundary and inertia systems. Then, we review the coupling of volume flow and current flow by the Onsager relation, as well as the figure of merits and efficiency. We summarize the state-of-the-art of electrokinetic energy conversions, including critical performance metrics such as efficiencies, power densities, and generated voltages in various systems. We discuss the advantages and possible constraints by the figure of merits, including single-phase flow and flying droplets.

Stereoselective Bioconcentration and Neurotoxicity of Perfluoroethylcyclohexane Sulfonate in Marine Medaka.

Perfluoroethylcyclohexane sulfonate (PFECHS) is an emerging per- and polyfluoroalkyl substance used to replace perfluorooctane sulfonate (PFOS), mainly in aircraft hydraulic fluids. However, previous research indicates the potential neurotoxicity of this replacement chemical. In this study, marine medaka (Oryzias melastigma) was exposed to environmentally relevant concentrations of PFECHS (concentrations: 0, 0.08, 0.26, and 0.91 µg/L) from the embryonic stage for 90 days. After exposure, the brain and eyes of the medaka were collected to investigate the bioconcentration potential of PFECHS stereoisomers and their effects on the nervous systems. The determined bioconcentration factors (BCFs) of PFECHS ranged from 324 ± 97 to 435 ± 89 L/kg and from 454 ± 60 to 576 ± 86 L/kg in the brain and eyes of medaka, respectively. The BCFs of trans-PFECHS were higher than those of cis-PFECHS. PFECHS exposure significantly altered γ-aminobutyric acid (GABA) levels in the medaka brain and disrupted the GABAergic system, as revealed by proteomics, implying that PFECHS can disturb neural signal transduction like PFOS. PFECHS exposure resulted in significant alterations in multiple proteins associated with eye function in medaka. Abnormal locomotion was observed in PFECHS-exposed medaka larvae, which was rescued by adding exogenous GABA, suggesting the involvement of disrupted GABA signaling pathways in PFECHS neurotoxicity.

The pathogenesis of common Gjb2 mutations associated with human hereditary deafness in mice.

Mutations in GJB2 (Gap junction protein beta 2) are the most common genetic cause of non-syndromic hereditary deafness in humans, especially the 35delG and 235delC mutations. Owing to the homozygous lethality of Gjb2 mutations in mice, there are currently no perfect mouse models carrying Gjb2 mutations derived from patients for mimicking human hereditary deafness and for unveiling the pathogenesis of the disease. Here, we successfully constructed heterozygous Gjb2+/35delG and Gjb2+/235delC mutant mice through advanced androgenic haploid embryonic stem cell (AG-haESC)-mediated semi-cloning technology, and these mice showed normal hearing at postnatal day (P) 28. A homozygous mutant mouse model, Gjb235delG/35delG, was then generated using enhanced tetraploid embryo complementation, demonstrating that GJB2 plays an indispensable role in mouse placenta development. These mice exhibited profound hearing loss similar to human patients at P14, i.e., soon after the onset of hearing. Mechanistic analyses showed that Gjb2 35delG disrupts the function and formation of intercellular gap junction channels of the cochlea rather than affecting the survival and function of hair cells. Collectively, our study provides ideal mouse models for understanding the pathogenic mechanism of DFNB1A-related hereditary deafness and opens up a new avenue for investigating the treatment of this disease.

Tissue damage, antioxidant capacity, transcriptional and metabolic regulation of red drum Sciaenops ocellatus in response to nanoplastics exposure and subsequent recovery.

Nanoplastics are recognized as emerging contaminants that can cause severe toxicity to marine fishes. However, limited researches were focusing on the toxic effects of nanoplastics on marine fish, especially the post-exposure resilience. In this study, red drum (Sciaenops ocellatus) were exposed to 5 mg/L polystyrene nanoplastics (100 nm, PS-NPs) for a 7-day exposure experiment, and a 14-day recovery experiment that followed. The aim was to evaluate the dynamic alterations in hepatic and branchial tissue damage, hepatic antioxidant capacity, as well as hepatic transcriptional and metabolic regulation in the red drum during exposure and post-exposure to PS-NPs. Histopathological observation found that PS-NPs primarily triggered hepatic lipid droplets and branchial epithelial liftings, a phenomenon persistently discernible up to the 14 days of recovery. Although antioxidant capacity partially recovered during recovery periods, PS-NPs resulted in a sustained reduction in hepatic antioxidant activity, causing oxidative damage throughout the entire exposure and recovery phases, as evidenced by decreased total superoxide dismutase activities and increased malondialdehyde content. At the transcriptional and metabolic level, PS-NPs primarily induced lipid metabolism disorders, DNA damage, biofilm disruption, and mitochondrial dysfunction. In the gene-metabolite correlation interaction network, numerous CcO (cytochrome c oxidase) family genes and lipid metabolites were identified as key regulatory genes and metabolites in detoxification processes. Among them, the red drum possesses one additional CcO6B in comparison to human and zebrafish, which potentially contributes to its enhanced capacity for maintaining a stable and positive regulatory function in detoxification. This study revealed that nanoplastics cause severe biotoxicity to red drum, which may be detrimental to the survival of wild populations and affect the economics of farmed populations.

Phytochemistry of Genus Buxus and Pharmacology of Cyclovirobuxine D.

BACKGROUND: Genus Buxus plants, commonly known as "boxwood", are widely distributed in China. The stems, branches, and leaves of the plant are traditionally used for rheumatism, toothache, chest pain, abdominal gas, and other diseases. However, an overview of the genus Buxus remains to be provided. PURPOSE: To provide a scientific basis for the appropriate use and further research the recent advancements in the traditional usage, phytochemistry, and, pharmacology of Buxus. STUDY DESIGN: Chemical composition and pharmacological correlation studies through a literature review. METHODS: Between 1970 and 2023, the available data concerning Buxus was compiled from online scientific sources, such as Sci-Finder, PubMed, CNKI, Google Scholar, and the Chinese Pharmacopoeia. Plant names were verified from "The Plant List" (http://www.theplantlist.org/). RESULTS: To date, 266 structurally diverse chemicals have been extracted and identified from the genus Buxus. Alkaloids constitute one of its primary bioactive phytochemicals. A summary of the channels of action of Cyclovirobuxine D on the cytotoxicity of a variety of cancers has been provided. CONCLUSION: Numerous findings from contemporary phytochemical and pharmacological studies support the traditional use, facilitating its application. Further research is necessary to address various shortcomings, including the identification of the active ingredients and quality control of the genus Buxus.

[Research Status and Trend of Screening for Women's Common Diseases in China].

Objective To visualize the research status and hotspots of women's common disease screening based on CiteSpace 6.1.R6,and to provide a reference for the in-depth research in this field thereafter. Methods The relevant articles were retrieved from the China National Knowledge Infrastructure with the time interval from January 1,1992 to December 13,2022.The analysis was conducted on the number of annual publications,countries(regions),institutions,author collaboration networks,keyword co-occurrence,clustering,and bursts. Results A total of 900 papers that met the criteria were included,and the number of annual publications showed a trend of first increasing and then decreasing.The cross-institutional collaboration network was mature.The research hotspots mainly covered women's health,the prevalence of women's diseases,reproductive health,and breast diseases.The hotspots have evolved from an initial focus on reproductive health care to gynecological disease management,and eventually to reproductive health and holistic health care in women. Conclusions The attention should be kept on the screening of women's common diseases.It is advisable to synchronize the screening of women's common diseases with the screening of cervical and breast cancers to expand the screening coverage,promote early disease detection and treatment,and comprehensively safeguard women's health.

Efficient and Stable Tin-Lead Mixed Perovskite Solar Cells Using Post-Treatment Additive with Synergistic Effects.

Inhibiting the oxidation of Sn2+ during the crystallization process of Sn-Pb mixed perovskite film is found to be as important as the oxidation resistance of precursor solution to achieve high efficiency, but less investigated. Considering the excellent reduction feature of hydroquinone and the hydrophobicity of tert-butyl group, an antioxidant 2,5-di-tert-butylhydroquinone (DBHQ) was introduced into Sn-Pb mixed perovskite films using an anti-solvent approach to solve this problem. Interestingly, we find that DBHQ can act as function alterable additive during its utilization. On the one hand, DBHQ can restrict the oxidation of Sn2+ during the crystallization process, facilitating the fabrication of high-quality perovskite film; on the other hand, the generated oxidation product 2,5-di-tert-butyl-1,4-benzoquinone (DBBQ) can functionalize as defect passivator to inhibit the charge recombination. As a result, this synergetic effect renders the Sn-Pb mixed PSC a power conversion efficiency (PCE) up to 23.0 %, which is significantly higher than the reference device (19.6 %). Furthermore, the unencapsulated DBQH-modified PSCs exhibited excellent long-term stability and thermal stability, with the devices maintaining 84.2 % and 78.9 % of the initial PCEs after aging at 25 °C and 60 °C for 800 h and 120 h under N2 atmosphere, respectively. Therefore, the functional alterable strategy provides a novel cornerstone for high-performance Sn-Pb mixed PSCs.

Efficient Lithium/Sodium-Ion Storage by Core-Shell Carbon Nanospheres@TiO2 Decorate by Epitaxial WSe2 Nanosheets Derived from Bimetallic Polydopamine Composites.

Metal-polydopamine coordination chemistry attracts great attention owing to the synergistic effect of adjustable components and advantageous structures. However, few efforts have been devoted to exploring bimetal-polydopamine composites, especially for multistructural composites with high-capacity components and high stability. In this regard, the TiO2 @C-WSe2 core-shell nanospheres are designed and fabricated based on Ti-W-polydopamine composites after selenization, in which the TiO2 nanoparticles are encapsulated or embedded in the carbon nanospheres and the external WSe2 nanosheets are grown epitaxially on the carbon surfaces, featuring multiple channels for ion diffusion and abundant active edges for electrochemical reactions. The introduction of WSe2 not only greatly improves the capacity but also results in exponential growth of the active edge. As a result, the as-prepared TiO2 @C-WSe2 displayed long-term cycling performance in lithium-ion batteries. Furthermore, the anode is assembled into sodium-ion batteries, manifesting a stable capacity of 352 mA h g-1 at 1.0 A g-1 even after 2000 cycles, one of the best performances for polydopamine-based composites. Enhanced performance can be attributed to the synergies of high-capacity components and different dimensional materials. This work highlights that the rational design of functional structures provides a novel inspiration for electrodes with effective nanoarchitectures.

Chimeric Peptide-Engineered Self-Delivery Nanomedicine for Photodynamic-Triggered Breast Cancer Immunotherapy by Macrophage Polarization.

A systemic treatment strategy is urgently demanded to suppress the rapid growth and easy metastasis characteristics of breast cancer. In this work, a chimeric peptide-engineered self-delivery nanomedicine (designated as ChiP-CeR) for photodynamic-triggered breast cancer immunotherapy by macrophage polarization. Among these, ChiP-CeR is composed of the photosensitizer of chlorine e6 (Ce6) and the TLR7/8 agonist of lmiquimod (R837), which is further modified with tumor matrix targeting peptide (Fmoc-K(Fmoc)-PEG8 -CREKA. ChiP-CeR is preferred to actively accumulate at the tumor site via specific recognition of fibronectin, which can eradicate primary tumor growth through photodynamic therapy (PDT). Meanwhile, the destruction of primary tumors would trigger immunogenic cell death (ICD) effects to release high-mobility group box-1(HMGB1) and expose calreticulin (CRT). Moreover, ChiP-CeR can also polarize M2-type tumor-associated macrophages (TAMs) into M1-type TAMs, which can activate T cell antitumor immunity in combination with ICD. Overall, ChiP-CeR possesses superior antitumor effects against primary and lung metastatic tumors, which provide an applicable nanomedicine and a feasible strategy for the systemic management of metastatic breast cancer.

Identification of pyroptosis-related genes and potential drugs in diabetic nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is one of the serious microvascular complications of diabetes mellitus (DM). A growing body of research has demonstrated that the inflammatory state plays a critical role in the incidence and development of DN. Pyroptosis is a new way of programmed cell death, which has the particularity of natural immune inflammation. The inhibition of inflammatory cytokine expression and regulation of pathways related to pyroptosis may be a novel strategy for DN treatment. The aim of this study is to identify pyroptosis-related genes and potential drugs for DN. METHODS: DN differentially expressed pyroptosis-related genes were identified via bioinformatic analysis Gene Expression Omnibus (GEO) dataset GSE96804. Dataset GSE30528 and GSE142025 were downloaded to verify pyroptosis-related differentially expressed genes (DEGs). Least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct a pyroptosis-related gene predictive model. A consensus clustering analysis was performed to identify pyroptosis-related DN subtypes. Subsequently, Gene Set Variation Analysis (GSVA), Gene Ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to explore the differences between DN clusters. A protein-protein interaction (PPI) network was used to select hub genes and DGIdb database was utilized to screen potential therapeutic drugs/compounds targeting hub genes. RESULTS: A total of 24 differentially expressed pyroptosis-related genes were identified in DN. A 16 gene predictive model was conducted via LASSO regression analysis. According to the expression level of these 16 genes, DN cases were divided into two subtypes, and the subtypes are mainly associated with inflammation, activation of immune response and cell metabolism. In addition, we identified 10 hub genes among these subtypes, and predicted 65 potential DN therapeutics that target key genes. CONCLUSION: We identified two pyroptosis-related DN clusters and 65 potential therapeutical agents/compounds for DN, which might shed a light on the treatment of DN.

High extraction efficiency phosphor design applied in laser lighting.

Laser lighting has great potential to be the next generation of general lighting due to its high brightness and directionality. However, the light extraction efficiency and luminous efficiency from the light exit surface are greatly limited since phosphor structure. Here, we design and optimize a phosphor structure by Monte Carlo method (MCM) with optimization algorithm. The results indicate that the optimized Ce:YAG single crystal phosphor is able to improve the extraction efficiency to 0.49, which is much higher than the conventional parallel phosphor. The luminous efficiency of the optimized phosphor can also reach 230 lm/W. In addition, the experiments and simulations show that the extraction efficiency and luminous efficiency will reduce to 0.41 and 190 lm/W if there is scattering in the optimized phosphor. The spatial distribution of the light intensity and thermal stability of the optimized phosphor are also measured. The optimized phosphor is helpful to the design of side heat dissipation structure. In general, the optimized phosphor may play a significant role in the high-flux laser lighting and the method also provides a universal tool for the phosphor design.

Extended angular-spectrum modeling (EASM) of light energy transport in scattering media.

The exact modeling of light transport in scattering media is critical in biological imaging, free-space communication, and phosphor-converted lighting. Angular spectrum is proved to be a fast and effective approach to reconstructing the wavefront dynamics during the propagation in scattering media, however, finding it difficult in acquiring the wavefront and energy change simultaneously. Besides, conventional methods for energy tracing, such as the Monte Carlo method, are inefficient in speed and hard to simulate the wavefront change. Here, we propose an extended angular-spectrum modeling (EASM) approach using tenuous scattering approximate solutions to obtain a time-efficient and accurate method for reconstruction of energy and wavefront dynamics in various scattering media. The generality of our method is numerically simulated and experimentally verified with a set of scattering media with different properties. EASM has a time advantage under the guarantee of calculation accuracy, especially when calculating several thickness changes after the calculation model is established. Furthermore, multi-layered media can also be simulated by EASM with a good precision. The results suggest that EASM performs certain computations more efficiently than the conventional method and thus provides an effective and flexible calculation tool for scattering media.

Macrophage MST1/2 Disruption Impairs Post-Infarction Cardiac Repair via LTB4.

[Figure: see text].

Deep learning nomogram based on Gd-EOB-DTPA MRI for predicting early recurrence in hepatocellular carcinoma after hepatectomy.

OBJECTIVES: The accurate prediction of post-hepatectomy early recurrence in patients with hepatocellular carcinoma (HCC) is crucial for decision-making regarding postoperative adjuvant treatment and monitoring. We aimed to explore the feasibility of deep learning (DL) features derived from gadoxetate disodium (Gd-EOB-DTPA) MRI, qualitative features, and clinical variables for predicting early recurrence. METHODS: In this bicentric study, 285 patients with HCC who underwent Gd-EOB-DTPA MRI before resection were divided into training (n = 195) and validation (n = 90) sets. DL features were extracted from contrast-enhanced MRI images using VGGNet-19. Three feature selection methods and five classification methods were combined for DL signature construction. Subsequently, an mp-MR DL signature fused with multiphase DL signatures of contrast-enhanced images was constructed. Univariate and multivariate logistic regression analyses were used to identify early recurrence risk factors including mp-MR DL signature, microvascular invasion (MVI), and tumor number. A DL nomogram was built by incorporating deep features and significant clinical variables to achieve early recurrence prediction. RESULTS: MVI (p = 0.039), tumor number (p = 0.001), and mp-MR DL signature (p < 0.001) were independent risk factors for early recurrence. The DL nomogram outperformed the clinical nomogram in the training set (AUC: 0.949 vs. 0.751; p < 0.001) and validation set (AUC: 0.909 vs. 0.715; p = 0.002). Excellent DL nomogram calibration was achieved in both training and validation sets. Decision curve analysis confirmed the clinical usefulness of DL nomogram. CONCLUSION: The proposed DL nomogram was superior to the clinical nomogram in predicting early recurrence for HCC patients after hepatectomy. KEY POINTS: • Deep learning signature based on Gd-EOB-DTPA MRI was the predominant independent predictor of early recurrence for hepatocellular carcinoma (HCC) after hepatectomy. • Deep learning nomogram based on clinical factors and Gd-EOB-DTPA MRI features is promising for predicting early recurrence of HCC. • Deep learning nomogram outperformed the conventional clinical nomogram in predicting early recurrence.

YY1 inactivated transcription co-regulator PGC-1α to promote mitochondrial dysfunction of early diabetic nephropathy-associated tubulointerstitial fibrosis.

The development of diabetic nephropathy (DN) could be promoted by the occurrence of tubulointerstitial fibrosis (TIF), which had a closely relationship with mitochondrial dysfunction of renal tubular epithelial cells (RTECs). As a key regulator of metabolic homeostasis, Yin Yang 1 (YY1) played an important role not only in regulating fibrosis process, but also in maintaining mitochondrial function of pancreatic ß cells. However, it was not clear whether YY1 participated in maintaining mitochondrial function of RTECs in early DN-associated TIF. In this study, we dynamically detected mitochondrial functions and protein expression of YY1 in db/db mice and high glucose (HG)-cultured HK-2 cells. Our results showed that comparing with the occurrence of TIF, the emergence of mitochondrial dysfunction of RTECs was an earlier even, besides the up-regulated and nuclear translocated YY1. Correlation analysis showed YY1 expressions were negatively associated with PGC-1α in vitro and in vivo. Further mechanism research demonstrated the formation of mTOR-YY1 heterodimer induced by HG upregulated YY1, the nuclear translocation of which inactivated PGC-1α by binding to the PGC-1α promoter. Overexpression of YY1 induced mitochondrial dysfunctions in normal glucose cultured HK-2 cells and 8-week-old db/m mice. While, dysfunctional mitochondria induced by HG could be improved by knockdown of YY1. Finally, downregulation of YY1 could retard the progression of TIF by preventing mitochondrial functions, resulting in the improvement of epithelial-mesenchymal transition (EMT) in early DN. These findings suggested that YY1 was a novel regulator of mitochondrial function of RTECs and contributed to the occurrence of early DN-associated TIF .