Hypoxia preconditioning increases Notch1 activity by regulating DNA methylation in vitro and in vivo.

BACKGROUND: Our previous research has demonstrated that hypoxic preconditioning (HPC) can improve spatial learning and memory abilities in adult mice. Adult hippocampal neurogenesis has been associated with learning and memory. The Neurogenic locus notch homolog protein (Notch) was involved in adult hippocampal neurogenesis, as well as in learning and memory. It is currently unclear whether the Notch pathway regulates hippocampal neuroregeneration by modifying the DNA methylation status of the Notch gene following HPC. METHOD: The HPC animal model and cell model were established through repeated hypoxia exposure using mice and the mouse hippocampal neuronal cell line HT22. Step-down test was conducted on HPC mice. Real-time PCR and Western blot analysis were used to assess the mRNA and protein expression levels of Notch1 and hairy and enhancer of split1 (HES1). The presence of BrdU-positive cells and Notch1 expression in the hippocampal dental gyrus (DG) were examined with confocal microscopy. The methylation status of the Notch1 was analyzed using methylation-specific PCR (MS-PCR). HT22 cells were employed to elucidate the impact of HPC on Notch1 in vitro. RESULTS: HPC significantly improved the step-down test performance of mice with elevated levels of mRNA and protein expression of Notch1 and HES1 (P < 0.05). The intensities of the Notch1 signal in the control group, the H group and the HPC group were 2.62 ± 0.57 × 107, 2.87 ± 0.84 × 107, and 3.32 ± 0.14 × 107, respectively, and the number of BrdU (+) cells in the hippocampal DG were 1.83 ± 0.54, 3.71 ± 0.64, and 7.29 ± 0.68 respectively. Compared with that in C and H group, the intensity of the Notch1 signal and the number of BrdU (+) cells increased significantly in HPC group (P < 0.05). The methylation levels of the Notch1 promoter 0.82 ± 0.03, 0.65 ± 0.03, and 0.60 ± 0.02 in the C, H, and HPC groups, respectively. The methylation levels of Notch1 decreased significantly (P < 0.05). The effect of HPC on HT22 cells exhibited similarities to that observed in the hippocampus. CONCLUSION: HPC may confer neuroprotection by activating the Notch1 signaling pathway and regulating its methylation level, resulting in the regeneration of hippocampal neurons.

Electrospun MoS2-CNTs-PVA/PVA Hybrid Separator for High-Performance Li/FeS2 Batteries.

As a promising candidate for high-energy-density rechargeable lithium metal batteries, Li/FeS2 batteries still suffer from the large volume change and severe shuttle effect of lithium polysulfides during cycling. To improve the electrochemical performance, great efforts have been made to modify FeS2 cathodes by constructing various nanocomposites. However, energy density is sacrificed, and these materials are not applicable at a large scale. Herein, we report that the electrochemical performance of commercial FeS2 can be greatly enhanced with the application of a double-layer MoS2-CNTs-PVA (MCP)/PVA separator fabricated by electrospinning. The assembled Li/FeS2 batteries can still deliver a high discharge capacity of 400 mAh/g after 200 cycles at a current density of 0.5 C. The improved cycling stability can be attributed to the strong affinity towards lithium polysulfides (LiPSs) of the hydroxyl-rich PVA matrix and the unique double-layer structure, in which the bottom layer acts as an electrical insulation layer and the top layer coupled with MoS2/CNTs provides catalytic sites for LiPS conversion.

Directional Polarization of a Ferroelectric Intermediate Layer Inspires a Built-In Field in Si Anodes to Regulate Li+ Transport Behaviors in Particles and Electrolyte.

The silicon (Si) anode is prone to forming a high electric field gradient and concentration gradient on the electrode surface under high-rate conditions, which may destroy the surface structure and decrease cycling stability. In this study, a ferroelectric (BaTiO3) interlayer and field polarization treatment are introduced to set up a built-in field, which optimizes the transport mechanisms of Li+ in solid and liquid phases and thus enhances the rate performance and cycling stability of Si anodes. Also, a fast discharging and slow charging phenomenon is observed in a half-cell with a high reversible capacity of 1500.8 mAh g-1 when controlling the polarization direction of the interlayer, which means a fast charging and slow discharging property in a full battery and thus is valuable for potential applications in commercial batteries. Simulation results demonstrated that the built-in field plays a key role in regulating the Li+ concentration distribution in the electrolyte and the Li+ diffusion behavior inside particles, leading to more uniform Li+ diffusion from local high-concentration sites to surrounding regions. The assembled lithium-ion battery with a BaTiO3 interlayer exhibited superior electrochemical performance and long-term cycling life (915.6 mAh g-1 after 300 cycles at a high current density of 4.2 A g-1). The significance of this research lies in exploring a new approach to improve the performance of lithium-ion batteries and providing new ideas and pathways for addressing the challenges faced by Si-based anodes.

Learning a Contact Potential Field for Modeling the Hand-Object Interaction.

Estimating and synthesizing the hand's manipulation of objects is central to understanding human behaviour. To accurately model the interaction between the hand and object (referred to as the "hand-object"), we must not only focus on the pose of the hand and object, but also consider the contact between them. This contact provides valuable information for generating semantically and physically plausible grasps. In this paper, we propose an explicit contact representation called Contact Potential Field (CPF). In CPF, we model the contact between a pair of hand-object vertices as a spring-mass system. This system encodes the distance of the pair, as well as a likelihood of that contact being stable. Therefore, the system of multiple extended and compressed springs forms an elastic potential field with minimal energy at the optimal grasp position. We apply CPF to two relevant tasks, namely, hand-object pose estimation and grasping pose generation. Extensive experiments on the two challenging tasks and three commonly used datasets have demonstrated that our method can achieve state-of-the-art in several reconstruction metrics, allowing us to produce more physically plausible hand-object poses even when the ground-truth exhibits severe interpenetration or disjointedness. Our model and source codes are made publicly available at https://github.com/lixiny/CPF.

Hepatocyte-derived exosomes deliver the lncRNA CYTOR to hepatic stellate cells and promote liver fibrosis.

Liver fibrosis is characterized by the activation and transformation of hepatic stellate cells (HSCs) induced by various injury factors. The degree of liver fibrosis can be significantly improved, but persistent injury factors present a significant therapeutic challenge. Hepatocytes are the most important parenchymal cell type in the liver. In this study, we explored the molecular mechanisms by which damaged liver cells activate HSCs through extracellular vesicles. We established a coculture model of LO2 and LX2 and validated its exosomal transmission activity. Subsequently, differentially expressed long noncoding RNAs (lncRNAs) were screened through RNA sequencing and their mechanisms of action as competing endogenous RNAs (ceRNAs) further confirmed using biological methods, such as FISH and luciferase assays. Damaged liver cells induced activation of LX2 and upregulation of liver fibrosis-related markers. Exosomes extracted and identified from the supernatant fraction contained differentially expressed lncRNA cytoskeleton regulator RNA (CYTOR) that competed with microRNA-125 (miR-125) for binding to glial cell line-derived neurotrophic factor (GDNF) in HSCs, in turn, promoting LX2 activation. MiR-125 could target and regulate both CYTOR and GDNF and vice versa, as verified using the luciferase assay. In an in vivo model, damaged liver extracellular vesicles induced the formation of liver fibrosis. Notably, downregulation of CYTOR within extracellular vesicles effectively inhibited liver fibrosis. The lncRNA CYTOR in exosomes of damaged liver cells is upregulated and modulates the expression of downstream GDNF through activity as a ceRNA, providing an effective mechanism for activation of HSCs.

DPPA2/4 Promote the Pluripotency and Proliferation of Bovine Extended Pluripotent Stem Cells by Upregulating the PI3K/AKT/GSK3ß/ß-Catenin Signaling Pathway.

Developmental pluripotency-associated 2 (DPPA2) and DPPA4 are crucial transcription factors involved in maintaining pluripotency in humans and mice. However, the role of DPPA2/4 in bovine extended pluripotent stem cells (bEPSCs) has not been investigated. In this study, a subset of bEPSC-related differentially expressed genes (DEGs), including DPPA2 and DPPA4, was identified based on multiomics data (ATAC-seq and RNA-seq). Subsequent investigations revealed that double overexpression of DPPA2/4 facilitates the reprogramming of bovine fetal fibroblasts (BFFs) into bEPSCs, whereas knockout of DPPA2/4 in BFFs leads to inefficient reprogramming. DPPA2/4 overexpression and knockdown experiments revealed that the pluripotency and proliferation capability of bEPSCs were maintained by promoting the transition from the G1 phase to the S phase of the cell cycle. By activating the PI3K/AKT/GSK3ß/ß-catenin pathway in bEPSCs, DPPA2/4 can increase the nuclear accumulation of ß-catenin, which further upregulates lymphoid enhancer binding factor 1 (LEF1) transcription factor activity. Moreover, DPPA2/4 can also regulate the expression of LEF1 by directly binding to its promoter region. Overall, our results demonstrate that DPPA2/4 promote the reprogramming of BFFs into bEPSCs while also maintaining the pluripotency and proliferation capability of bEPSCs by regulating the PI3K/AKT/GSK3ß/ß-catenin pathway and subsequently activating LEF1. These findings expand our understanding of the gene regulatory network involved in bEPSC pluripotency.

Heterogeneous Brain Abnormalities in Schizophrenia Converge on a Common Network Associated With Symptom Remission.

BACKGROUND AND HYPOTHESIS: There is a huge heterogeneity of magnetic resonance imaging findings in schizophrenia studies. Here, we hypothesized that brain regions identified by structural and functional imaging studies of schizophrenia could be reconciled in a common network. STUDY DESIGN: We systematically reviewed the case-control studies that estimated the brain morphology or resting-state local function for schizophrenia patients in the literature. Using the healthy human connectome (n = 652) and a validated technique "coordinate network mapping" to identify a common brain network affected in schizophrenia. Then, the specificity of this schizophrenia network was examined by independent data collected from 13 meta-analyses. The clinical relevance of this schizophrenia network was tested on independent data of medication, neuromodulation, and brain lesions. STUDY RESULTS: We identified 83 morphological and 60 functional studies comprising 7389 patients with schizophrenia and 7408 control subjects. The "coordinate network mapping" showed that the atrophy and dysfunction coordinates were functionally connected to a common network although they were spatially distant from each other. Taking all 143 studies together, we identified the schizophrenia network with hub regions in the bilateral anterior cingulate cortex, insula, temporal lobe, and subcortical structures. Based on independent data from 13 meta-analyses, we showed that these hub regions were specifically connected with regions of cortical thickness changes in schizophrenia. More importantly, this schizophrenia network was remarkably aligned with regions involving psychotic symptom remission. CONCLUSIONS: Neuroimaging abnormalities in cross-sectional schizophrenia studies converged into a common brain network that provided testable targets for developing precise therapies.

Discovery of 1H-pyrazolo[3,4-b]pyrazine derivatives as selective allosteric inhibitor of protein tyrosine phosphatase SHP2 for the treatment of KRASG12C-mutant non-small cell lung cancer.

The high expression or mutation of SHP2 can induce cancer, so targeting SHP2 has become a new strategy for cancer treatment. In this study, we used the previously reported SHP2 allosteric inhibitor IACS-13909 as a lead drug for structural derivation and modification, and synthesized three SHP2 inhibitors. Among them, 1H-pyrazolo[3,4-b]pyrazine derivative 4b was a highly selective SHP2 allosteric inhibitor, with an IC50 value of 3.2 nM, and its inhibitory activity was 17.75 times than that of the positive control IACS-13909. The cell proliferation experiment detected that compound 4b would markedly inhibit the proliferation of various cancer cells. Interestingly, compound 4b was highly sensitive to KRASG12C-mutant non-small cell lung cancer NCI-H358 cells, with an IC50 value of 0.58 µM and its antiproliferative activity was 4.79 times than that of IACS-13909. Furthermore, the combination therapy of compound 4b and KRASG12C inhibitor sotorasib would play a strong synergistic effect against NCI-H358 cells. The western blot experiment detected that compound 4b markedly downregulated the phosphorylation levels of ERK and AKT in NCI-H358 cells. Molecular docking study predicted that compound 4b bound to the allosteric site of SHP2 and formed H-bond interactions with key residues Thr108, Glu110, Arg111, and Phe113. In summary, this study aims to provide new ideas for the development of SHP2 allosteric inhibitors for the treatment of KRASG12C mutant non-small cell lung cancer.Communicated by Ramaswamy H. Sarma.

Bidirectional visual-tactile cross-modal generation using latent feature space flow model.

Inspired by visual-tactile cross-modal bidirectional mapping of the human brain, this paper introduces a novel approach to bidirectional mapping between visual and tactile data, an area not fully explored in the predominantly unidirectional existing studies. First, we adopt separate Variational AutoEncoder (VAE) models for visual and tactile data. Furthermore, we introduce a conditional flow model built on the VAE latent feature space, enabling cross-modal bidirectional mapping between visual and tactile data using one model. The experimental results show that our method achieves excellent performance in terms of the similarity between the generated data and the original data (Structural Similarity Index (SSIM) of visual data: 0.58, SSIM of tactile data: 0.80), the classification accuracy on generated data (visual data: 91.60%, tactile data: 88.05%), and the zero-shot classification accuracy between generated data and language (visual data: 44.49%, tactile data: 45.03%). To the best of our knowledge, the method proposed in this paper is the first one to utilize a single model to achieve bidirectional mapping between visual and tactile data. Our model and code will be made public after the acceptance of the paper.

Hedgehog-Gli1-derived exosomal circ-0011536 mediates peripheral neural remodeling in pancreatic cancer by modulating the miR-451a/VGF axis.

BACKGROUND: Hedgehog-Gli1 signaling induces development of two common neurological features seen in pancreatic ductal adenocarcinoma (PDAC): peripheral neural invasion (PNI) and peripheral neural remodeling (PNR). However, the underlying molecular mechanisms in cancer cells and nerves within Gli1-derived PNR have not previously been comprehensively analyzed. METHODS: In this study, RNA sequencing was used to screen meaningful circRNAs in PNR. An in vitro model of PNR was subsequently constructed through a co-culture system comprising PDAC cells and murine dorsal root ganglia (DRG) (as the neuronal element), and the relevant mechanisms were explored using a series of molecular biology experiments. A subcutaneous nude mouse tumorigenesis model was established to further verify the occurrence of PNR that was detected in human PDAC samples. RESULTS: We first confirmed the molecular mechanisms of PNR development through crosstalk between exosomal circ-0011536 and DRG. In Gli1-overpressed PDAC, circ-0011536 is mainly secreted by exosomes. After being ingested by DRG, it can promote the activity of DRG by degrading miR-451a and upregulating the expression of VGF. Overexpression of Gli1 can accelerate the proliferation of subcutaneous tumors in mice and is closely related to the density of nerve plexuses, while downregulating circ-RNA inhibits tumor proliferation and reduces the density of nerve plexuses. In addition, TMA results confirmed that Gli1 overexpression significantly increased the expression of VGF and was closely associated with increased nerve plexus density. CONCLUSION: Hedgehog-Gli1-induced exosomal circ-0011536 promoted PNR via the miR-451a/VGF axis, thereby establishing that it may contribute to PDAC-associated nerve changes with activated Hedgehog signaling.

Abnormal interhemispheric functional cooperation in schizophrenia follows the neurotransmitter profiles.

BACKGROUND: Interhemispheric cooperation is one of the most prominent functional architectures of the human brain. In patients with schizophrenia, interhemispheric cooperation deficits have been reported using increasingly powerful neurobehavioural and neuroimaging measures. However, these methods rely in part on the assumption of anatomic symmetry between hemispheres. In the present study, we explored interhemispheric cooperation deficits in schizophrenia using a newly developed index, connectivity between functionally homotopic voxels (CFH), which is unbiased by hemispheric asymmetry. METHODS: Patients with schizophrenia and age- and sexmatched healthy controls underwent multimodal MRI, and whole-brain CFH maps were constructed for comparison between groups. We examined the correlations of differing CFH values between the schizophrenia and control groups using various neurotransmitter receptor and transporter densities. RESULTS: We included 86 patients with schizophrenia and 86 matched controls in our analysis. Patients with schizophrenia showed significantly lower CFH values in the frontal lobes, left postcentral gyrus and right inferior temporal gyrus, and significantly greater CFH values in the right caudate nucleus than healthy controls. Moreover, the differing CFH values in patients with schizophrenia were significantly correlated with positive symptom score and illness duration. Functional connectivity within frontal lobes was significantly reduced at the voxel cluster level compared with healthy controls. Finally, the abnormal CFH map of patients with schizophrenia was spatially associated with the densities of the dopamine D1 and D2 receptors, fluorodopa, dopamine transporter, serotonin transporter and acetylcholine transporter. CONCLUSION: Regional abnormalities in interhemispheric cooperation may contribute to the clinical symptoms of schizophrenia. These CFH abnormalities may be associated with dysfunction in neurotransmitter systems strongly implicated in schizophrenia.

Impact of twice-a-day transcranial direct current stimulation intervention on cognitive function and motor cortex plasticity in patients with Alzheimer's disease.

Background: Non-invasive brain stimulation has improved cognitive functions in patients with Alzheimer's disease (AD), and some studies suggest a close relationship between cognition and plasticity. However, the clinical benefits of transcranial direct current stimulation (tDCS) in patients still need to be evaluated. Aims: This study examined the role of tDCS in improving cognition and whether the improved cognition is related to altered cortical plasticity. Methods: 124 patients with AD were randomly assigned to active tDCS (n=63) or sham tDCS (n=61). The tDCS was applied at the dorsolateral prefrontal cortex for 30 treatment sessions across 6 weeks (5 days per week, 2 days off). The Mini-Mental State Examination and the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) were used for cognition evaluation at baseline, week 2 and week 6. The cortical plasticity was represented by motor-evoked potential (MEP) measured with an electromyogram. Results: The results showed that multiple courses of active tDCS can improve the cognitive functions of patients with AD, especially in the memory domain (word recall, recall of test instructions and word recognition). In addition, the damaged MEP level was enhanced following active treatment. In the active tDCS group, the improvements in ADAS-Cog total and subitem (word recall and word recognition) scores were negatively correlated with the enhancement of MEP. Conclusions: Our research indicates for the first time that twice-a-day tDCS may improve the cognitive function of patients with AD. This study also suggests that cognitive dysfunction may be related to impaired cortical plasticity, which warrants mechanistic investigations of the relationship between cognition and plasticity in the future. Trial registration number: ChiCTR1900021067.

Analysis of global research hotspots and trends in immune cells in intervertebral disc degeneration: A bibliometric study.

Intervertebral disc degeneration is an important pathological basis for spinal degenerative diseases. The imbalance of the immune microenvironment and the involvement of immune cells has been shown to lead to nucleus pulposus cells death. This article presents a bibliometric analysis of studies on immune cells in IDD in order to clarify the current status and hotspots. We searched the WOSCC, Scopus and PubMed databases from 01/01/2001 to 08/03/2023. We analyzed and visualized the content using software such as Citespace, Vosviewer and the bibliometrix. This study found that the number of annual publications is increasing year on year. The journal study found that Spine had the highest number of articles and citations. The country/regions analysis showed that China had the highest number of publications, the USA had the highest number of citations and total link strength. The institutional analysis found that Shanghai Jiao Tong University and Huazhong University of Science Technology had the highest number of publications, Tokai University had the highest citations, and the University of Bern had the highest total link strength. Sakai D and Risbud MV had the highest number of publications. Sakai D had the highest total link strength, and Risbud MV had the highest number of citations. The results of the keyword analysis suggested that the current research hotspots and future directions continue to be the study of the mechanisms of immune cells in IDD, the therapeutic role of immune cells in IDD and the role of immune cells in tissue engineering for IDD.

Modified Kirschner wire percutaneous rotation prying reduction combined with elastic stable intramedullary nailing in children with Judet IV radial neck fracture.

PURPOSE: This study was to investigate the feasibility and treatment effect of using modified Kirschner wire (K-wire) percutaneous rotation prying reduction combined with Elastic Stable Intramedullary Nailing (ESIN) in children with Judet IV radial neck fracture. METHODS: A retrospective analysis was conducted on 47 children with Judet IV radial neck fracture who underwent treatment with modified K-wire percutaneous rotation prying reduction combined with ESIN from April 2019 to November 2022, including 25 males and 22 females, with an average age of 8.79 years old (ranging from 5 to 14). The study recorded the surgical time, fluoroscopy time, reduction time, and reduction quality evaluated according to the Metaizeau radiological standard. During the last follow-up, the flexion-extension and forearm rotation function of the affected and healthy sides were recorded, and the Mayo Elbow Performance index was used to evaluate the elbow joint function. RESULTS: The average duration of the operation was 25.51 min (ranging from 14 to 43 min), with a mode of 2 reset times (ranging from 1 to 5) and 8 fluoroscopic times (ranging from 4 to 15). Based on the Metaizeau radiological standard for assessing reduction quality, 45 cases were deemed excellent, while 2 cases were considered good. Following 3-4 weeks of postoperative long-arm cast immobilization, exercises were performed to promote elbow joint and forearm rotation. The ESIN was removed after satisfactory fracture healing around 4 months postoperatively. The average follow-up period was 26.79 months (ranging from 5 to 48). At the final follow-up, the range of motion for the affected limb in flexion, extension, pronation, and supination was (140.23 ± 4.80)°, (4.43 ± 3.98)°, (84.09 ± 4.97)°, and (83.83 ± 4.55)°, respectively. There was no statistically significant difference compared to the healthy side, which had a range of motion of (141.36 ± 3.27)°, (5.28 ± 2.25)°, (85.66 ± 3.20)°, and (84.98 ± 2.57)° (P > 0.05). According to the Mayo Elbow Performance index, 44 cases were rated as excellent and 1 case was considered good. CONCLUSION: The modified K-wire percutaneous rotation prying reduction combined with ESIN is an effective treatment for severe radial neck fractures in children. This technique offers several advantages, including the ability to easily "capture" significantly displaced radial heads, achieve rapid and accurate reduction, and reduce radiation exposure.

A novel transcriptional repressor specifically regulates xylanase gene 1 in Trichoderma reesei.

BACKGROUND: The well-known industrial fungus Trichoderma reesei has an excellent capability of secreting a large amount of cellulases and xylanases. The induced expression of cellulase and xylanase genes is tightly controlled at the transcriptional level. However, compared to the intensive studies on the intricate regulatory mechanism of cellulase genes, efforts to understand how xylanase genes are regulated are relatively limited, which impedes the further improvement of xylanase production by T. reesei via rational strain engineering. RESULTS: To identify transcription factors involved in regulating xylanase gene expression in T. reesei, yeast one-hybrid screen was performed based on the promoters of two major extracellular xylanase genes xyn1 and xyn2. A putative transcription factor named XTR1 showing significant binding capability to the xyn1 promoter but not that of xyn2, was successfully isolated. Deletion of xtr1 significantly increased the transcriptional level of xyn1, but only exerted a minor promoting effect on that of xyn2. The xylanase activity was increased by ~ 50% with XTR1 elimination but the cellulase activity was hardly affected. Subcellular localization analysis of XTR1 fused to a green fluorescence protein demonstrated that XTR1 is a nuclear protein. Further analyses revealed the precise binding site of XTR1 and nucleotides critical for the binding within the xyn1 promoter. Moreover, competitive EMSAs indicated that XTR1 competes with the essential transactivator XYR1 for binding to the xyn1 promoter. CONCLUSIONS: XTR1 represents a new transcriptional repressor specific for controlling xylanase gene expression. Isolation and functional characterization of this new factor not only contribute to further understanding the stringent regulatory network of xylanase genes, but also provide important clues for boosting xylanase biosynthesis in T. reesei.

Systematic analysis of glutamine metabolism family genes and exploration of the biological role of GPT in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a malignancy of the digestive system with high incidence rate and mortality, and reliable diagnostic and prognostic markers for CRC are still lacking. Glutamine metabolism is crucial to the occurrence and development of CRC. However, no research has systematically analyzed the biological role of glutamine metabolism-related genes (GMRGs) in CRC. METHODS: We downloaded gene expression data and clinical data of CRC patients from the TCGA database. The UCSC database downloads pan-cancer gene expression data and prognosis data. Characteristic GMRGs were screened out using differential analysis and two types of machine learning (SVM-REF and RandomForest). Single-cell RNA-sequencing data from CRC patients were downloaded from GEO data. ROC curve was used to evaluate the diagnostic value. Kaplan-Meier method and univariate Cox regression analysis were used to evaluate the prognostic value. The oncopredict package is used to calculate IC50 values for common drugs in CRC patients. RESULTS: A total of 31 differentially expressed GMRGs were identified, 9 of which were identified as characteristic GMRGs. Further evaluation of diagnostic and prognostic value finally identified GPT as the most important GMRGs in CRC. scRNA-seq analysis revealed that GPT is almost exclusively expressed in epithelial cells. GPT expression is closely related to the tumor microenvironment and can effectively distinguish the sensitivity of different CRC patients to clinical drugs. In addition, pan-cancer analysis showed that GPT is an excellent diagnostic and prognostic marker for multiple cancers. CONCLUSIONS: GPT is a reliable diagnostic, prognostic marker and therapeutic target in CRC.

[Computer-simulated osteotomy based on health-side combined with guide plate technique in treatment of cubitus varus deformity in adolescents].

Objective: To explore the feasibility and early effectiveness of computer-simulated osteotomy based on the health-side combined with guide plate technique in the treatment of cubitus varus deformity in adolescents. Methods: The clinical data of 23 patients with cubitus varus deformity who met the selection criteria between June 2019 and February 2023 were retrospectively analyzed. There were 17 males and 6 females, ranging in age from 4 to 16 years with an average of 8.5 years. The time from injury to operation was 1-4 years. The angle of distal humerus rotation was defined by humeral head posterior inclination angle using low radiation dose CT to scan the patient's upper extremity data at one time, and the preoperative rotation of the distal humerus on the affected side was (33.82±4.39)°. The CT plain scan data were imported into 9yuan3D digital orthopaedic system (V3.34 software) to reconstruct three-dimensional images of both upper extremities. The simulated operation was performed with the healthy upper extremity as the reference, the best osteotomy scheme was planned, overlapped and compared, and the osteotomy guide plate was prepared. The patients were followed up regularly after operation, and the formation of callus in the osteotomy area was observed by X-ray examination. Before and after operation, the carrying angle of both upper extremities (the angle of cubitus valgus was positive, and the angle of cubitus varus was negative) and anteversion angle were measured on X-ray and CT images. At the same time, the flexion and extension range of motion of elbow joint and the external rotation range of motion of upper extremity were measured, and Mayo score was used to evaluate the function of elbow joint. Results: The operation time ranged from 34 to 46 minutes, with an average of 39 minutes. All patients were followed up 5-26 months, with a mean of 14.9 months. All the incisions healed by first intention after the operation; 2 patients had nail path irritation symptoms after Kirschner wire fixation, which improved after dressing change; no complication such as breakage and loosening of internal fixators occurred after regular X-ray review. Continuous callus formed at the osteotomy end at 4 weeks after operation, and the osteotomy end healed at 8-12 weeks after operation. At last follow-up, the carrying angle, anteversion angle, external rotation range of motion, and extension and flexion range of motion of the elbow joint of the affected side significantly improved when compared with preoperative ones ( P<0.05). Except for the extension range of motion of the healthy elbow joint ( P<0.05), there was no significant difference in other indicators between the two sides ( P>0.05). At last follow-up, the Mayo elbow score was 85-100, with an average of 99.3; 22 cases were excellent, 1 case was good, and the excellent and good rate was 100%. Conclusion: Computer-simulated osteotomy based on health-side combined with guide plate technique for treating cubitus varus deformity in adolescents can achieve precise osteotomy, which has the advantages of short operation time and easy operation, and the short-term effectiveness is satisfactory.

Fucoidan Ameliorates Ferroptosis in Ischemia-reperfusion-induced Liver Injury through Nrf2/HO-1/GPX4 Activation.

Background and Aims: Liver ischemia-reperfusion (IR) injury is a common pathological process in liver surgery. Ferroptosis, which is closely related to lipid peroxidation, has recently been confirmed to be involved in the pathogenesis of IR injury. However, the development of drugs that regulate ferroptosis has been slow, and a complete understanding of the mechanisms underlying ferroptosis has not yet been achieved. Fucoidan (Fu) is a sulfated polysaccharide that has attracted research interest due to its advantages of easy access and wide biological activity. Methods: In this study, we established models of IR injury using erastin as an activator of ferroptosis, with the ferroptosis inhibitor ferrostatin-1 (Fer-1) as the control. We clarified the molecular mechanism of fucoidan in IR-induced ferroptosis by determining lipid peroxidation levels, mitochondrial morphology, and key pathways in theta were involved. Results: Ferroptosis was closely related to IR-induced hepatocyte injury. The use of fucoidan or Fer-1 inhibited ferroptosis by eliminating reactive oxygen species and inhibiting lipid peroxidation and iron accumulation, while those effects were reversed after treatment with erastin. Iron accumulation, mitochondrial membrane rupture, and active oxygen generation related to ferroptosis also inhibited the entry of nuclear factor erythroid 2-related factor 2 (Nrf2) into the nucleus and reduced downstream heme oxygenase-1 (HO-1) and glutathione peroxidase 4 (GPX4) protein levels. However, fucoidan pretreatment produced adaptive changes that reduced irreversible cell damage induced by IR or erastin. Conclusions: Fucoidan inhibited ferroptosis in liver IR injury via the Nrf2/HO-1/GPX4 axis.

Micro-Doppler Signature Detection and Recognition of UAVs Based on OMP Algorithm.

With the proliferation of unmanned aerial vehicles (UAVs) in both commercial and military use, the public is paying increasing attention to UAV identification and regulation. The micro-Doppler characteristics of a UAV can reflect its structure and motion information, which provides an important reference for UAV recognition. The low flight altitude and small radar cross-section (RCS) of UAVs make the cancellation of strong ground clutter become a key problem in extracting the weak micro-Doppler signals. In this paper, a clutter suppression method based on an orthogonal matching pursuit (OMP) algorithm is proposed, which is used to process echo signals obtained by a linear frequency modulated continuous wave (LFMCW) radar. The focus of this method is on the idea of sparse representation, which establishes a complete set of environmental clutter dictionaries to effectively suppress clutter in the received echo signals of a hovering UAV. The processed signals are analyzed in the time-frequency domain. According to the flicker phenomenon of UAV rotor blades and related micro-Doppler characteristics, the feature parameters of unknown UAVs can be estimated. Compared with traditional signal processing methods, the method based on OMP algorithm shows advantages in having a low signal-to-noise ratio (-10 dB). Field experiments indicate that this approach can effectively reduce clutter power (-15 dB) and successfully extract micro-Doppler signals for identifying different UAVs.

Scalable engineering of hierarchical layered micro-sized silicon/graphene hybrids via direct foaming for lithium storage.

Low-cost micro-sized silicon is an attractive replacement for commercial graphite anodes in advanced lithium-ion batteries (LIBs) but suffers from particle fracture during cycling. Hybridizing micro-sized silicon with conductive carbon materials, especially graphene, is a practical approach to overcome the volume change issue. However, micro-sized silicon/graphene anodes prepared via the conventional technique encounter sluggish Li+ transport due to the lack of efficient electrolyte diffusion channels. Here, we present a facile and scalable method to establish efficient Li+ transport channels through direct foaming from the laminated graphene oxide/micro-sized silicon membrane followed by annealing. The conductive graphene layers and the Li+ transport channels endow the composite material with excellent electronic and ionic conductivity. Moreover, the interconnected graphene layers provide a robust framework for micro-sized silicon particles, allowing them to transform decently in the graphene layer space. Consequently, the prepared hybrid material, namely foamed graphene/micro-sized Si (f-G-Si), can work as a binder-free and free-standing anode without additives and deliver remarkable electrochemical performance. Compared with the control samples, micro-sized silicon wrapped by laminated graphene layers (G-Si) and commercial micro-sized Si, f-G-Si maximizes the utilization of silicon and demonstrates superior performance, disclosing the role of Li+ diffusion channels. This study sheds light on the rational design and manufacture of silicon anodes and beyond.