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As the new orientation, new requirement and new task to develop higher education, it is necessary to deeply implement the digital strategic action, construct a new form of higher education teaching, give full play to the role of the main channel in the classroom education, and comprehensively promote the ideological and political construction of curriculum. On the basis of the digital intelligence era, this paper deeply explores the ideological and political elements in each chapter according to the characteristics of the course, teaching objectives and teaching contents; it also draws the conclusion about the teaching reform and practice of the ideological and political construction of the course on Food Chemistry and Analysis. It puts forward some strategies: the improvement on educator' ideological and political teaching ability, the digital construction and improvement of high-quality ideological and political resources, the optimization of curriculum setting, and the innovation on "gene implantation" and "one, two, three, four" teaching modes. The ideological and political classroom of professional courses is taken as the carrier, the unity of inner knowledge and action is realized, and meanwhile the ideological and political education system is constructed about the course on Food Chemistry and Analysis, with the purpose to promote both the translation of professional knowledge and value guidance of students', and create a new pattern for the moral education.

The body of health journalism research literature remains scattered across various disciplines and requires comprehensive understanding. This study aims to enhance researchers’ comprehension of the field, by presenting a systematic review of SSCI-indexed articles. Findings reveal two peaks in health journalism research from 1994 to 2023: during the 2009 H1N1 influenza and the COVID-19 outbreak. Using bibliographic coupling analysis, it was possible to define 10 major research themes from the review. They were: How health stories are framed in the news; How audiences engage with health information online; How constructive journalism can improve the news reporting of public health crisis; How fact-checking can improve the news reporting of public health crisis; How health stories are framed from science journalism perspective; Why citizen journalism is significant in health news reporting; How health journalists perceive their journalistic role; Who serves as the news source for health news reporting; How health professionals impact health news reporting; and How peace journalism can be used for health news reporting on vulnerable populations. This research provides insights into the current state of health journalism research and outlines potential areas for further exploration in health journalism, spanning topics such as women and other marginalized communities in health reporting.

The pursuit of effective treatments for brain tumors has increasingly focused on the promising area of nanoparticle-enhanced radiotherapy (NERT). This review elucidates the context and significance of NERT, with a particular emphasis on its application in brain tumor therapy—a field where traditional treatments often encounter obstacles due to the blood-brain barrier (BBB) and tumor cells’ inherent resistance. The aims of this review include synthesizing recent advancements, analyzing action mechanisms, and assessing the clinical potential and challenges associated with nanoparticle (NP) use in radiotherapy enhancement. Preliminary preclinical studies have established a foundation for NERT, demonstrating that nanoparticles (NPs) can serve as radiosensitizers, thereby intensifying radiotherapy’s efficacy. Investigations into various NP types, such as metallic, magnetic, and polymeric, have each unveiled distinct interactions with ionizing radiation, leading to an augmented destruction of tumor cells. These interactions, encompassing physical dose enhancement and biological and chemical radio sensitization, are crucial to the NERT strategy. Although clinical studies are in their early phases, initial trials have shown promising results in terms of tumor response rates and survival, albeit with mindful consideration of toxicity profiles. This review examines pivotal studies affirming NERT’s efficacy and safety. NPs have the potential to revolutionize radiotherapy by overcoming challenges in targeted delivery, reducing off-target effects, and harmonizing with other modalities. Future directions include refining NP formulations, personalizing therapies, and navigating regulatory pathways. NERT holds promise to transform brain tumor treatment and provide hope for patients.

Abstract The glutaminase enzymes GAC and GLS2 catalyze the hydrolysis of glutamine to glutamate, satisfying the ‘glutamine addiction’ of cancer cells. They are the targets of anti-cancer drugs; however, their mechanisms of activation and catalytic activity have been unclear. Here we demonstrate that the ability of GAC and GLS2 to form filaments is directly coupled to their catalytic activity and present their cryo-EM structures which provide a view of the conformational states essential for catalysis. Filament formation guides an ‘activation loop’ to assume a specific conformation that works together with a ‘lid’ to close over the active site and position glutamine for nucleophilic attack by an essential serine. Our findings highlight how ankyrin repeats on GLS2 regulate enzymatic activity, while allosteric activators stabilize, and clinically relevant inhibitors block, filament formation that enables glutaminases to catalyze glutaminolysis and support cancer progression.

Abstract Background It has been confirmed that the ApoB/ApoA1 ratio is closely associated with the incidence of cardiometabolic diseases (CMD). However, due to uncontrolled confounding factors in observational studies, the causal relationship of this association remains unclear. Methods In this study, we extracted the ApoB/ApoA1 ratio and data on CMD and its associated risk factors from the largest European Genome-Wide Association Study. The purpose was to conduct Mendelian Randomization (MR) analysis. The causal relationship between the ApoB/ApoA1 ratio and CMD was evaluated using both univariable and multivariable MR analyses. Furthermore, bidirectional MR analysis was performed to estimate the causal relationship between the ApoB/ApoA1 ratio and risk factors for CMD. The final verification confirmed whether the ApoB/ApoA1 ratio exhibits a mediating effect in CMD and related risk factors. Results In terms of CMD, a noteworthy correlation was observed between the increase in the ApoB/ApoA1 ratio and various CMD, including ischemic heart disease, major adverse cardiovascular events, aortic aneurysm, cerebral ischemic disease and so on (all P FDR

Abstract With rapid progress in simulation of strongly interacting quantum Hamiltonians, the challenge in characterizing unknown phases becomes a bottleneck for scientific progress. We demonstrate that a Quantum-Classical hybrid approach (QuCl) of mining sampled projective snapshots with interpretable classical machine learning can unveil signatures of seemingly featureless quantum states. The Kitaev-Heisenberg model on a honeycomb lattice under external magnetic field presents an ideal system to test QuCl, where simulations have found an intermediate gapless phase (IGP) sandwiched between known phases, launching a debate over its elusive nature. We use the correlator convolutional neural network, trained on labeled projective snapshots, in conjunction with regularization path analysis to identify signatures of phases. We show that QuCl reproduces known features of established phases. Significantly, we also identify a signature of the IGP in the spin channel perpendicular to the field direction, which we interpret as a signature of Friedel oscillations of gapless spinons forming a Fermi surface. Our predictions can guide future experimental searches for spin liquids.

Over the past few decades, nanotechnology has developed rapidly and has been applied to various fields. Gold nanoclusters (AuNCs), which are composed of several hundred atoms, are a new type of nanomaterial. AuNCs are often synthesized using ligands or templates. The interaction between the gold atoms and the groups of the ligands or templates results in unexpected physical and chemical properties. In recent studies, natural proteins have often been used as templates to synthesize AuNCs. The unique structure of natural proteins endows AuNCs with biological functions, such as biocompatibility and enzymatic activity. The unique properties of these natural protein-AuNCs have been verified and applied in various fields. In this article, the synthetic strategies used to produce AuNCs have been divided into two categories: animal-derived and plant-derived protein synthesis. The protein types and synthesis strategies used in the current mainstream research are reviewed, and their applications in detection and biological imaging are summarized. Finally, the problems and future development directions of AuNCs synthesized from natural proteins are discussed, laying a foundation for the biological application of protein-AuNCs.

Ferroptosis is a form of non-apoptotic programmed cell death, and its mechanisms mainly involve the accumulation of lipid peroxides, imbalance in the amino acid antioxidant system, and disordered iron metabolism. The primary organelle responsible for coordinating external challenges and internal cell demands is the endoplasmic reticulum, and the progression of inflammatory diseases can trigger endoplasmic reticulum stress. Evidence has suggested that ferroptosis may share pathways or interact with endoplasmic reticulum stress in many diseases and plays a role in cell survival. Ferroptosis and endoplasmic reticulum stress may occur after ischemic stroke. However, there are few reports on the interactions of ferroptosis and endoplasmic reticulum stress with ischemic stroke. This review summarized the recent research on the relationships between ferroptosis and endoplasmic reticulum stress and ischemic stroke, aiming to provide a reference for developing treatments for ischemic stroke.

Glioma, the most prevalent primary brain tumor in adults, is characterized by significant invasiveness and resistance. Current glioma treatments include surgery, radiation, chemotherapy, and targeted therapy, but these methods often fail to eliminate the tumor completely, leading to recurrence and poor prognosis. Immune checkpoint inhibitors, a class of commonly used immunotherapeutic drugs, have demonstrated excellent efficacy in treating various solid malignancies. Recent research has indicated that unconventional levels of expression of the MAP2K3 gene closely correlates with glioma malignancy, hinting it could be a potential immunotherapy target. Our study unveiled substantial involvement of MAP2K3 in gliomas, indicating the potential of the enzyme to serve as a prognostic biomarker related to immunity. Through the regulation of the infiltration of immune cells, MAP2K3 can affect the prognosis of patients with glioma. These discoveries establish a theoretical foundation for exploring the biological mechanisms underlying MAP2K3 and its potential applications in glioma treatment.

Abstract Protein degraders, emerging as a novel class of therapeutic agents, have gained widespread attention due to their advantages. They have several advantages over traditional small molecule inhibitors, including high target selectivity and ability to target “undruggable” targets and overcome inhibitor drug resistance. Tremendous research and development efforts and massive investment have resulted in rapid advancement of protein degrader drug discovery in recent years. Here, we overview the latest clinical and preclinical updates on protein degraders presented at the 2023 ASH Annual Meeting.

Abstract Background Microvascular invasion (MVI) is an independent prognostic factor that is associated with early recurrence and poor survival after resection of hepatocellular carcinoma (HCC). However, the traditional pathology approach is relatively subjective, time‐consuming, and heterogeneous in the diagnosis of MVI. The aim of this study was to develop a deep‐learning model that could significantly improve the efficiency and accuracy of MVI diagnosis. Materials and Methods We collected H&E‐stained slides from 753 patients with HCC at the First Affiliated Hospital of Zhejiang University. An external validation set with 358 patients was selected from The Cancer Genome Atlas database. The deep‐learning model was trained by simulating the method used by pathologists to diagnose MVI. Model performance was evaluated with accuracy, precision, recall, F1 score, and the area under the receiver operating characteristic curve. Results We successfully developed a MVI artificial intelligence diagnostic model (MVI‐AIDM) which achieved an accuracy of 94.25% in the independent external validation set. The MVI positive detection rate of MVI‐AIDM was significantly higher than the results of pathologists. Visualization results demonstrated the recognition of micro MVIs that were difficult to differentiate by the traditional pathology. Additionally, the model provided automatic quantification of the number of cancer cells and spatial information regarding MVI. Conclusions We developed a deep learning diagnostic model, which performed well and improved the efficiency and accuracy of MVI diagnosis. The model provided spatial information of MVI that was essential to accurately predict HCC recurrence after surgery.

The operating subway tunnel is often damaged due to excessive deformation in China. In order to ensure the safe for operation, remediation and protection measures must be taken, especially in soft soil areas. This paper presents a case study on remedial scheme of damaged TBM (Tunnel Boring Machine) tunnel adjacent to excavation combining with MJS (Metro Jet System) and micro-disturbance grouting technology in Hangzhou, China. The track bed settlement, horizontal displacement and convergence of the TBM tunnel caused by MJS and micro-disturbance grouting construction were analyzed and discussed. The results showed the characteristics of soil layer under the tunnel have significant influence on the treatment effect. Even if multiple grouting was adopted, the treatment failure may occur under the combination action of external loads such as traffic load or surcharge load, which should be considered when civil engineers design remediation scheme. The results can provide practical experience and guidance for similar treatment scheme of damaged TBM tunnel.

Insulin-like-growth factor-1 (IGF-1) is the ligand for insulin-like growth factor-1 receptor (IGF-1R), and the roles of IGF-1/IGF-1R in diabetic nephropathy (DN) are well-characterized previously. However, the biological functions of AG1024 (an IGF-1R inhibitor) in DN remain unknown. This study investigates the roles and related mechanisms of AG-1024 in DN. The experimental DN was established via intraperitoneal injection of streptozotocin, and STZ-induced diabetic rats were treated with AG1024 (20 mg/kg/day) for 8 weeks. The 24 h proteinuria, blood glucose level, serum creatinine, and blood urea nitrogen were measured for biochemical analyses. The increase in 24 h proteinuria, blood glucose level, serum creatinine, and blood urea of DN rats were conspicuously abated by AG1024. After biochemical analyses, the renal tissue specimens were collected, and as revealed by hematoxylin and eosin staining and Masson staining, AG-1024 mitigated typical renal damage and interstitial fibrosis in DN rats. Then, the anti-inflammatory effect of AG-1024 was assessed by western blotting and ELISA. Mechanistically, AG-1024 upregulated SOCS1 and SOCS3 expression and decreased phosphorylated JAK2, STAT1, and STAT3, as shown by western blotting. Collectively, AG-1024 (an IGF-1R inhibitor) ameliorates renal injury in experimental DN by attenuating renal inflammation and fibrosis via the SOCS/JAK2/STAT pathway.

Northwest China is characterized by its high altitude and thin air. The small clearing between the bushings， the charged parts， the grounding bodies of the regulator step-up transformer， and the small safety margin may result in rain flashover. To this end， this paper analyzes the causes of flashover， studies the shortcomings of the bushing structure type， installation and other aspects， and proposes rain flashover protection measures such as optimizing bushing installation， installing auxiliary sheds， increasing the clearings between bushings and grounding bodies. Comsol Multiphysics， a finite element simulation software， is used to establish an electric field simulation model of transformer under raining conditions to study the rain flashover protection clearing between the bushing and the grounding body. The paper also proposes the corresponding optimization measures. The engineering verification shows that the proposed measures can significantly reduce the probability of rain flashover in the bushing and ensure the safe and stable operation of the synchronous condenser.

AgNbO3 (AN) lead-free antiferroelectric material has attracted great attention in recent years. However, little focus has been directed toward a single crystal that can provide more basic information. In this study, we successfully grew high-quality AN single crystals, using a flux method, with dimensions of 5 × 5 × 3 mm3. A systematic investigation into the crystal structure, domain structure, and electrical properties of a [001]-oriented AN single crystal was conducted. X-ray diffraction and domain structure analysis revealed an orthorhombic phase structure at room temperature. Stripe-like 90° domains aligning parallel to the [110] direction with a thickness of approximately 10–20 μm were observed using a polarized light microscope. The temperature dependence of dielectric permittivity showed M1-M2, M2-M3, and M3-O phase transitions along with increasing temperature, but the phase transition temperatures were slightly higher than those of ceramic. The AN single crystal also exhibited double polarization-electric field (P-E) hysteresis loops, which enabled good recoverable energy-storage density and efficiency comparable to ceramic. Additionally, double P-E loops were kept stable at various temperatures and frequencies, demonstrating robust stability and confirming typical antiferroelectric characteristics. Our work provides valuable insights into understanding the fundamental antiferroelectric properties of AN-based materials.

Abstract Functional polymer microspheres have broad application prospects in various fields, such as metal ion detection, adsorption, separation, and controlled drug release. However, integrating different functions in a single microsphere system is a significant challenge in this field. In this work, we prepared multicompartmental emulsion droplets utilizing microfluidic technology. Fe3O4 magnetic nanoparticles were added to one of the compartments of the emulsion droplets as functional particles, and Janus microspheres were obtained after curing. Fluorescent probes enter the two compartments of the Janus microspheres by diffusion. The fluorescence changes of the microspheres were observed in situ and captured through a fluorescence microscope. The images are processed by image recognition software and a Python program. The “fingerprint” of the detected metal ions is obtained by dimensionality reduction of the data through Principal Component Analysis. We employ different algorithms to build Machine Learning models for predicting the metal ion species and concentration. The variation of fluorescence intensity of the three fluorescent probes and the corresponding R, G, and B channel values and time are used as descriptors. The results show that the Random Forest, K‐neighborhood (KNN), and Neural Network models demonstrated a better predicted effect with a variance (R2) greater than 0.9 and a smaller root mean square error; among them, the KNN model predicted the most accurate results.

BackgroundMatrix metalloproteinases (MMPs) are important players in the complex pathophysiology of ischemic stroke (IS). Recent studies have shown that tremendous progress has been made in the research of MMPs in IS. However, a comprehensive bibliometric analysis is lacking in this research field. This study aimed to introduce the research status as well as hotspots and explore the field of MMPs in IS from a bibliometric perspective.MethodsThis study collected 1,441 records related to MMPs in IS from 1979 to 2022 in the web of science core collection (WoSCC) database, among them the first paper was published in 1992. CiteSpace, VOSviewer, and R package “bibliometrix” software were used to analyze the publication type, author, institution, country, keywords, and other relevant data in detail, and made descriptive statistics to provide new ideas for future clinical and scientific research.ResultsThe change in the number of publications related to MMPs in IS can be divided into three stages: the first stage was from 1992 to 2012, when the number of publications increased steadily; the second stage was from 2013 to 2017, when the number of publications was relatively stable; the third stage was from 2018 to 2022, when the number of publications began to decline. The United States and China, contributing more than 64% of publications, were the main drivers for research in this field. Universities in the United States were the most active institutions and contributed the most publications. STROKE is the most popular journal in this field with the largest publications as well as the most co-cited journal. Rosenberg GA was the most prolific writer and has the most citations. “Clinical,” “Medical,” “Neurology,” “Immunology” and “Biochemistry molecular biology” were the main research areas of MMPs in IS. “Molecular regulation,” “Metalloproteinase-9 concentration,” “Clinical translation” and “Cerebral ischemia–reperfusion” are the primary keywords clusters in this field.ConclusionThis is the first bibliometric study that comprehensively mapped out the knowledge structure and development trends in the research field of MMPs in IS in recent 30 years, which will provide a reference for scholars studying this field.

Abstract Background Neuroinflammation and neuronal apoptosis are closely associated with a poor prognosis in patients with subarachnoid hemorrhage (SAH). We investigated the role of C–C motif chemokine receptor 2 (CCR2) in SAH. Methods Pre-processed RNA-seq transcriptome datasets GSE167110 and GSE79416 from the Gene Expression Omnibus (GEO) database were screened for genes differentially expressed between mice with SAH and control mice, using bioinformatics analysis. The endovascular perforation model was performed to establish SAH. RS504393 (a CCR2 antagonist) and LY294002 (PI3K inhibitor) were administered to explore the mechanism of neuroinflammation after SAH. SAH grading, neurological scoring, brain water content and blood–brain barrier (BBB) permeability determination, enzyme-linked immunosorbent assay (ELISA), western blotting, and immunofluorescence were performed. An in vitro model of SAH was induced in H22 cells by hemin treatment. The protective mechanism of CCR2 inhibition was studied by adding RS504393 and LY294002. Clinical cerebrospinal fluid (CST) samples were detected by ELISA. Results Expression of CCR2 was upregulated in both datasets and was identified as a hub gene. CCR2 expression was significantly upregulated in the cytoplasm of neurons after SAH, both in vitro and in vivo. RS significantly reduced the brain water content and blood–brain barrier permeability, alleviated neuroinflammation, and reduced neuronal apoptosis after SAH. Additionally, the protective effects of CCR2 inhibition were abolished by LY treatment. Finally, the levels of CCR2, inflammatory factors, and apoptotic factors were elevated in the CSF of patients with SAH. CCR2 levels were associated with patient outcomes at the 6-month follow-up. Conclusion CCR2 expression was upregulated in both in vitro and in vivo SAH models. Additionally, inhibition of CCR2, at least partly through the PI3K/AKT pathway, alleviated neuroinflammation and neuronal apoptosis in vivo and in vitro. CCR2 levels in the CSF have a moderate diagnostic value for 6-month outcome prediction in patients with SAH.

Objective: To explore changes in the percentage and cell absolute count of lymphocyte subsets in peripheral blood of patients with novel coronavirus pneumonia (COVID-19). Methods: The clinical data of 244 patients with COVID-19 admitted to the Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine from April 25 to May 16, 2022 were retrospectively analyzed and classified into difterent groups according to the types of diseases (mild, ordinary and severe), vaccination status and co-existing underlying diseases. Flow cytometry was used to detect the absolute counts and percentages of different lymphocyte subsets(CD3+T lymphocytes, CD3+CD4+T lymphocytes, CD3+CD8+T lymphocytes, CD16+CD56+NK cells and CD19+B lymphocytes) in each group. Further, we analyzed the relationship between the changes in peripheral blood lymphocyte subsets and the above clinical characteristics in patients. Results: Compared with those in the mild group, the absolute count of each lymphocyte subsets (P

Podocyte injury is an important cause of proteinuria. Angiopoietin-like protein 4 (Angptl4) is a secreted glycoprotein and has a role in proteinuria. However, the exact role of Angptl4 in podocyte injury and its upstream regulators has not been clarified. In this study, we used lipopolysaccharide (LPS)-induced mice and cultured podocytes as podocyte injury models. Our results indicated that LPS increased the expression of podocyte Angptl4 in vivo and in vitro. Furthermore, we showed that Angptl4 overexpression deteriorated LPS-induced podocyte injury by inducing podocyte cytoskeleton rearrangement, reducing the expression of synaptopodin while Angptl4 knockdown alleviated LPS-induced podocyte injury. In addition, we found that inhibitors and siRNA targeting TLR4/MyD88/NF-κB signaling inhibited the upregulation of Angptl4 in LPS-induced podocytes. Moreover, inhibitors and siRNA targeting calcineurin/NFAT signaling also relieved LPS-induced Angptl4 expression and podocyte injury in vivo and in vitro. Taken together, our study has elucidated that both of the TLR4/MyD88/NF-κB and calcineurin/NFAT signaling mediate the upregulation of Angptl4 in LPS-induced podocytes, which has important implications for further understanding the molecular mechanism of LPS-induced podocyte injury.

Sclerotinia ginseng is the primary pathogenic fungus responsible for Sclerotinia rot of ginseng, which significantly reduces plant yield and quality. The density of sclerotia in the soil is closely associated with rot incidence and severity. Whole genome sequencing was conducted to obtain fungal frame maps. The specific primers, q2001F/q2001R, were screened out by pan-genomic analysis using the NCBI database. Recombinant plasmids containing amplicons obtained with this primer set were used as standard plasmids to construct a real-time fluorescence quantitative PCR system. The relationships between the cycle threshold (Ct) values and the soil sclerotium densities were determined by real-time PCR. Real-time PCR had a detection limit of 1.5 × 10−2 g·kg−1 soil for Sclerotinia rot causing fungal mycelium, and the relationship between the density of S. ginseng mycelium n (g·g−1 soil) and the Ct value was n = 10(40.048 − Ct)/6.9541. The detection limit of real-time PCR for measuring soil sclerotia was 3.8 × 10−5 g·g−1 soil, suggesting a sensitivity 100 times that of conventional PCR. The relationship between the sclerotium density n (g·g−1 soil) and the Ct value was n = 10(18.351 − Ct)/7.0914. Compared with the conventional PCR method, the fluorescent quantitative PCR method could detect the population of Sclerotinia spp. in soil more efficiently, accurately, and sensitively.

Background: Leukocyte telomere length shortening is a characteristic of premature senescence, a process that can be accelerated by oxidative stress. In general, patients with end-stage renal disease undergoing regular hemodialysis (HD) are repeatedly exposed to oxidative stress. Patients undergoing HD tend to have cardiovascular diseases associated with oxidative stress and inflammation. Therefore, we assumed that telomere length is associated with HD vintage and the degree of vascular calcification. Methods: A total of 144 patients undergoing regular HD before kidney transplantation and 62 patients on hemodialysis, but not undergoing kidney transplantation, were enrolled. We measured common laboratory values, such as calcium, phosphate, and hemoglobin levels, and assessed the degree of vascular calcification in the patients. The leukocyte telomere length was measured using reverse transcription polymerase chain reaction, and Spearman correlation was used for correlation analysis. Results: The leukocyte telomere length was negatively associated with age (rho = −0.306, P＜0.01); it was shorter in middle-aged patients than in young patients (13.48 ± 4.80 vs. 15.86 ± 4.51, P

Panax ginseng is a valuable medicinal plant which is affected by many diseases during its long cultivation period. Ginseng root rot, caused by Fusarium oxysporum, has become severe in China. This soilborne pathogen comprises many formae speciales based on host specificity. Ten representative isolates from diseased ginseng rot root showed pathogenicity on ginseng. To identify the forma specialis of the F. oxysporum strains, host range tests of three representative isolates were carried out on nine plant species. All three isolates caused severe symptoms only on ginseng, but only slight or no visual symptoms on the other eight hosts, indicating that the strains were host-specific to ginseng. Phylogenetic trees were constructed based on sequences of the translation elongation factor 1-α (EF-1α) gene, two endopolygalacturonase genes (Pg1, Pg5) and two exopolygalacturonase genes (Pgx1 and Pgx4). The ten F. oxysporum isolates from ginseng clustered into a unique group clearly separated from other formae speciales already described. Based on the host range tests and phylogenetic analyses, the isolates of F. oxysporum derived from ginseng have been identified as a new forma specialis, designated Fusarium oxysporum f. sp. ginseng. This is the first report of forma specialis of F. oxysporum on ginseng.

Abstract Background Sarcomatoid hepatocellular carcinoma (HCC) is a rare and highly lethal histological subtype of HCC, with completely unknown genetic etiology and therapeutic targets. Methods We included 16 patients with sarcomatoid HCC receiving radical resection among 6731 cases of pathological confirmed HCC in year 2008 to 2018 in our hospital. We compared the clinical features, prognosis and cancer genome between 15 sarcomatoid HCC and propensity score‐matched 75 non‐sarcomatoid HCC patients. The other concurrent case was analyzed using phylogenetic tree to assess the tumor heterogeneity and evolution. Results Sarcomatoid HCC group showed larger tumor size, more advanced differentiation grade, lower tumor free survival (p = 0.038) and overall survival (p = 0.001), and sarcomatoid type was an independent risk factor for patient death. Integrating sarcomatoid subtype into AJCC staging could increase the diagnostic curve in predicting patient survival. The cancer genome spectrum showed sarcomatoid HCC group had significant higher mutation rates in CDKN2A, EPHA5, FANCM and MAP3K1. Mutations in CDKN2A significantly reduced tumor‐free and overall survival in sarcomatoid HCC patients. Moreover, 46.6% sarcomatoid HCC patients had druggable mutations in cell cycle pathway genes, which were targeted by Abemaciclib, et al. We also found sarcomatoid and non‐sarcomatoid lesions might originate from a common progenitor but progress differently. Conclusion Our cancer genome analysis showed a specific genomic profile of sarcomatoid HCC, which were characterized by a high mutation rate in cell cycle genes particularly CDKN2A. The results indicate CDK4/6 inhibitors including abemaciclib, ribociclib and palbociclib as potential therapeutic targets and may help for therapeutic decision making.

Liver hepatocellular carcinoma (LIHC) is a malignancy with a high mortality and morbidity rate worldwide. However, the pathogenesis of LIHC has still not been thoroughly studied. Transmembrane and coiled-coil domains 3 (TMCO3) encodes a monovalent cation, a member of the proton transducer 2 (CPA2) family of transporter proteins. In the present study, TMCO3 expression and its relationship with cancer prognosis, as well as its immunological role in LIHC were studied by bioinformatic analysis. We found the significant overexpression of TMCO3 in LIHC in the TCGA, HCCDB, and GEO databases. In LIHC patients, high TMCO3 expression was related to poorer overall survival (OS) and TMCO3 had good predictive accuracy for prognosis. Moreover, TMCO3 was linked to the infiltrates of certain immune cells in LIHC. The correlation of TMCO3 with immune checkpoints was also revealed. Moreover, patients with LIHC with low TMCO3 expression showed a better response to immune checkpoint blockade (ICB) than those with LIHC with high TMCO3 expression. GO and KEGG enrichment analyses indicated that TMCO3 was probably involved in the microtubule cytoskeleton organization involved in mitosis, small GTPase mediated signal transduction, and TGF-β pathway. In conclusion, TMCO3 may be a potential biomarker for LIHC prognosis and immunotherapy.

After the first attempt to induce operational tolerance, it has taken decades to implement it in clinical practice. Recipients with Human leukocyte antigen (HLA) identical sibling donors were enrolled. Hematopoietic stem cells (HSCs) infusion was done after HLA identical sibling kidney transplantation (KTx). Three cases included were followed up for over 8 years. The perioperative conditioning protocol included anti-CD20, rabbit anti-thymocyte globulin (ATG), total lymphoid irradiation (TLI), and cyclophosphamide. Infusion of CD3+ cells and CD34+ cells was conducted. The withdrawal of immunosuppression was determined by mixed lymphocyte reaction (MLR) and graft biopsy. Case 1 and Case 2 showed persistent chimerism, while chimerism was not detected in Case 3. All three recipients showed a low-level response to donor-specific stimulation. Case 1 and Case 3 met the withdrawal rules at 16 and 32 months after transplantation, respectively. Graft function was stable, and no rejection signs were observed in routine biopsies until 94 and 61 months after transplantation. Case 2 was diagnosed with graft-versus-host disease (GVHD) 9 months after transplantation and recovered after an enhanced immunosuppression therapy. Steroids were withdrawn after 1 year, and 0.5 mg tacrolimus twice a day is currently the only immunosuppression at 8 years and 8 months. In conclusion, our clinical experience indicated the efficacy of non-myeloablative conditioning protocol for tolerance induction in HLA identical patients. Complete chimerism might be a risk factor for GVHD.

Glioma is the most common primary brain tumor in the human brain. The present study was designed to explore the expression of PIMREG in glioma and its relevance to the clinicopathological features and prognosis of glioma patients. The correlations of PIMREG with the infiltrating levels of immune cells and its relevance to the response to immunotherapy were also investigated. PIMREG expression in glioma was analyzed based on the GEO, TCGA, and HPA databases. Kaplan–Meier survival analysis was used to examine the predictive value of PIMREG for the prognosis of patients with glioma. The correlation between the infiltrating levels of immune cells in glioma and PIMREG was analyzed using the CIBERSORT algorithm and TIMRE database. The correlation between PIMREG and immune checkpoints and its correlation with the patients’ responses to immunotherapy were analyzed using R software and the GEPIA dataset. Cell experiments were conducted to verify the action of PIMREG in glioma cell migration and invasion. We found that PIMREG expression was upregulated in gliomas and positively associated with WHO grade. High PIMREG expression was correlated with poor prognosis of LGG, prognosis of all WHO grade gliomas, and prognosis of recurrent gliomas. PIMREG was related to the infiltration of several immune cell types, such as M1 and M2 macrophages, monocytes and CD8+ T cells. Moreover, PIMREG was correlated with immune checkpoints in glioma and correlated with patients’ responses to immunotherapy. KEGG pathway enrichment and GO functional analysis illustrated that PIMREG was related to multiple tumor- and immune-related pathways. In conclusion, PIMREG overexpression in gliomas is associated with poor prognosis of patients with glioma and is related to immune cell infiltrates and the responses to immunotherapy.

Despite the success of deep learning models, it remains challenging for the over-parameterized model to learn good representation under small-sample-size settings. In this paper, motivated by previous work on out-of-distribution (OoD) generalization, we study the representation learning problem from an OoD perspective to identify the fundamental factors affecting representation quality. We formulate a notion of “out-of-feature subspace (OoFS) noise” for the first time, and we link the OoFS noise in the feature extractor to the OoD performance of the model by proving two theorems that demonstrate that reducing OoFS noise in the feature extractor is beneficial in achieving better representation. Moreover, we identify two causes of OoFS noise and prove that the OoFS noise induced by random initialization can be filtered out via L2 regularization. Finally, we propose a novel data-dependent regularizer that acts on the weights of the fully connected layer to reduce noise in the representations, thus implicitly forcing the feature extractor to focus on informative features and to rely less on noise via back-propagation. Experiments on synthetic datasets show that our method can learn hard-to-learn features; can filter out noise effectively; and outperforms GD, AdaGrad, and KFAC. Furthermore, experiments on the benchmark datasets show that our method achieves the best performance for three tasks among four.

Glioblastoma (GBM) is an aggressive primary brain tumor with a poor prognosis following conventional therapeutic interventions. Moreover, the blood–brain barrier (BBB) severely impedes the permeation of chemotherapy drugs, thereby reducing their efficacy. Consequently, it is essential to develop novel GBM treatment methods. A novel kind of pericyte immunotherapy known as chimeric antigen receptor T (CAR-T) cell treatment uses CAR-T cells to target and destroy tumor cells without the aid of the antigen with great specificity and in a manner that is not major histocompatibility complex (MHC)-restricted. It has emerged as one of the most promising therapy techniques with positive clinical outcomes in hematological cancers, particularly leukemia. Due to its efficacy in hematologic cancers, CAR-T cell therapy could potentially treat solid tumors, including GBM. On the other hand, CAR-T cell treatment has not been as therapeutically effective in treating GBM as it has in treating other hematologic malignancies. CAR-T cell treatments for GBM have several challenges. This paper reviewed the use of CAR-T cell therapy in hematologic tumors and the selection of targets, difficulties, and challenges in GBM.

Stroke is a disease with high incidence, mortality and disability rates. It is also the main cause of adult disability in developed countries. Stroke is often caused by small emboli on the inner wall of the blood vessels supplying the brain, which can lead to arterial embolism, and can also be caused by cerebrovascular or thrombotic bleeding. With the exception of recombinant tissue plasminogen activator (rt-PA), which is a thrombolytic drug used to recanalize the occluded artery, most treatments have been demonstrated to be ineffective. Stroke can also induce peripheral organ damage. Most stroke patients have different degrees of injury to one or more organs, including the lung, heart, kidney, spleen, gastrointestinal tract and so on. In the acute phase of stroke, severe inflammation occurs in the brain, but there is strong immunosuppression in the peripheral organs, which greatly increases the risk of peripheral organ infection and aggravates organ damage. Nonneurological complications of stroke can affect treatment and prognosis, may cause serious short-term and long-term consequences and are associated with prolonged hospitalization and increased mortality. Many of these complications are preventable, and their adverse effects can be effectively mitigated by early detection and appropriate treatment with various medical measures. This article reviews the pathophysiological mechanism, clinical manifestations and treatment of peripheral organ injury after stroke.

Psoriasis is a chronic inflammatory disease that affects approximately 1%–5% of the population worldwide. Considering frequent relapse, adverse drug reactions, and large costs of treatment, it is urgent to identify new medications for psoriasis. Keratinocytes play an essential role during psoriasis development, and they express high levels of β2-Adrenergic receptor (β2-AR), which increases intracellular cAMP levels when activated. Increased level of cAMP is associated with the inhibition of epidermal cell proliferation. In the present study, we observed the effect of salmeterol, a long-acting β2-AR agonist, on the proliferation and apoptosis of keratinocytes as well as imiquimod-induced psoriasis-like skin lesions in mice. As phosphodiesterase 4 (PDE4) inhibitors increases intracellular cAMP concentration by inhibiting its inactivation, we further explored the synergetic effect of a PDE4 inhibitor and salmeterol on psoriasis-like skin lesions in mice. Our results indicated that salmeterol effectively inhibited the proliferation of HaCaT cells induced by TNF-α and serum, and this effect was accompanied by significantly increased apoptosis and CREB phosphorylation, which were reversed by the PKA inhibitor, H89. Salmeterol ameliorated imiquimod-induced psoriasis-like skin lesions in mice, but salmeterol combined with a PDE4 inhibitor had no synergetic effect in improving skin lesions in mice. Of note, the synergistic effects of anti-proliferation and induction of apoptosis in HaCaT cells appeared by inhibiting ERK signaling. In summary, salmeterol, a long-acting β2-AR agonist, alleviates the severity of psoriasis via inhibiting the proliferation and promoting apoptosis of keratinocytes, partially by activating the cAMP/PKA signaling pathway.

BackgroundDiabetic kidney disease (DKD) is the primary cause of end-stage renal disease, raising a considerable burden worldwide. Recognizing novel biomarkers by metabolomics can shed light on new biochemical insight to benefit DKD diagnostics and therapeutics. We hypothesized that serum metabolites can serve as biomarkers in the progression of DKD.MethodsA cross-sectional study of 1,043 plasma metabolites by untargeted LC/MS among 89 participants identified associations between proteinuria severity and metabolites difference. Pathway analysis from differently expressed metabolites was used to determine perturbed metabolism pathways. The results were replicated in an independent, cross-sectional cohort of 83 individuals. Correlation and prediction values were used to examine the association between plasma metabolites level and proteinuria amount.ResultsDiabetes, and diabetic kidney disease with different ranges of proteinuria have shown different metabolites patterns. Cysteine and methionine metabolism pathway, and Taurine and hypotaurine metabolism pathway were distinguishable in the existence of DKD in DC (diabetes controls without kidney disease), and DKD with different ranges of proteinuria. Two interesting tetrapeptides (Asn-Met-Cys-Ser and Asn-Cys-Pro-Pro) circulating levels were elevated with the DKD proteinuria progression.ConclusionsThese findings underscore that serum metabolomics provide us biochemical perspectives to identify some clinically relevant physiopathologic biomarkers of DKD progression.

Cyclin-dependent kinase regulatory subunit 2 (CKS2) is a potential prognostic marker and is overexpressed in various cancers. This study analyzed sequencing and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus, with external validation using the Chinese Glioma Genome Atlas (CGGA) data. CKS2 expression in the normal brain and tumor tissue was compared. cBioPortal and MethSurv were utilized to scrutinize the prognostic value of CKS2 methylation. Gene set enrichment examination and single-sample gene set enrichment analysis were employed to explore the potential biological functions of CKS2. Cell viability, colony formation, and transwell assays were conducted to evaluate the influence of CKS2 on glioma cell proliferation and invasion. Compared with normal brain tissue, the expression of CKS2 was upregulated in glioma samples (p < 0.001). Multivariate data analysis from TCGA and CGGA indicated that increased expression of CKS2 was an independent risk factor for the prognosis of overall survival in glioma patients. CKS2 methylation was negatively associated with CKS2 expression. Patients with CKS2 hypomethylation had worse overall survival compared with patients with CKS2 methylation, as suggested by the analysis of both TCGA and CGGA datasets. The expression level of CKS2 is closely related to tumor immunity, including the correlation of tumor immune cell infiltration, immune score, and co-expression of multiple immune-related genes. In addition, CKS2 is associated with several immune checkpoints and responses to the chemotherapy drug cisplatin. CKS2 knockdown impeded the expansion and aggression of glioma cell lines. The changes in CKS2 expression may provide a novel prognostic biomarker that can be used to improve patient overall survival rates.

BackgroundAcute rejection (AR) in kidney transplantation is an established risk factor that reduces the survival rate of allografts. Despite standard immunosuppression, molecules with regulatory control in the immune pathway of AR can be used as important targets for therapeutic operations to prevent rejection.MethodsWe downloaded the microarray data of 15 AR patients and 37 non-acute rejection (NAR) patients from Gene Expression Omnibus (GEO). Gene network was constructed, and genes were classified into different modules using weighted gene co-expression network analysis (WGCNA). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Cytoscape were applied for the hub genes in the most related module to AR. Different cell types were explored by xCell online database and single-cell RNA sequencing. We also validated the SLAMF8 and TLR4 levels in Raw264.7 and human kidney tissues of TCMR.ResultsA total of 1,561 differentially expressed genes were filtered. WGCNA was constructed, and genes were classified into 12 modules. Among them, the green module was most closely associated with AR. These genes were significantly enriched in 20 pathway terms, such as cytokine–cytokine receptor interaction, chemokine signaling pathway, and other important regulatory processes. Intersection with GS > 0.4, MM > 0.9, the top 10 MCC values and DEGs in the green module, and six hub genes (DOCK2, NCKAP1L, IL2RG, SLAMF8, CD180, and PTPRE) were identified. Their expression levels were all confirmed to be significantly elevated in AR patients in GEO, Nephroseq, and quantitative real-time PCR (qRT-PCR). Single-cell RNA sequencing showed that AR patient had a higher percentage of native T, CD1C+_B DC, NKT, NK, and monocytes in peripheral blood mononuclear cells (PBMCs). Xcell enrichment scores of 20 cell types were significantly different (p

Abstract Background Orbital solitary fibrous tumors (SFTs) are rare neoplasms. Recurrent, hypervascular, malignant variations of orbital SFTs have recently been noted and can present a surgical challenge. Case presentation We describe a case of a 53-year-old Chinese woman with a history of a resected orbital SFT. She presented with proptosis, limited eyeball movement, and visual loss in the right eye, suggestive of a recurrent SFT. Ocular examination with multimodal imaging revealed a large, nonpulsatile, noncompressible, hypervascular mass behind the eyeball. The patient underwent preoperative transarterial embolization of the main blood supply to the tumor in order to control intraoperative blood loss, followed by ocular enucleation to optimize exposure and enable complete resection of the tumor. Embolization of the right ophthalmic artery and the distal branch of the right internal maxillary artery caused an immediate, substantial reduction of vascular flow, which allowed us to enucleate the eyeball and resect the tumor with minimal blood loss and no complications. Conclusions Our case is so far the first Chinese case of successful preoperative embolization of the main blood supply to a large, recurrent, hypervascular orbital SFT. This case also described a different surgical approach to achieve total removal of an orbital SFT without osteotomy.

Generalization is challenging in small-sample-size regimes with over-parameterized deep neural networks, and a better representation is generally beneficial for generalization. In this paper, we present a novel method for controlling the internal representation of deep neural networks from a topological perspective. Leveraging the power of topology data analysis (TDA), we study the push-forward probability measure induced by the feature extractor, and we formulate a notion of “separation” to characterize a property of this measure in terms of persistent homology for the first time. Moreover, we perform a theoretical analysis of this property and prove that enforcing this property leads to better generalization. To impose this property, we propose a novel weight function to extract topological information, and we introduce a new regularizer including three items to guide the representation learning in a topology-aware manner. Experimental results in the point cloud optimization task show that our method is effective and powerful. Furthermore, results in the image classification task show that our method outperforms the previous methods by a significant margin.

The thermo-regulated finishing agents were prepared by high speed shear emulsification with phase change wax as energy storage and temperature control materials, polyvinyl alcohol (PVA) as coating materials, and then the cotton fabrics were treated by the prepared finishing agent by a padding-curing process. The basic properties of the phase change wax and the film forming properties of PVA were analyzed, the effects of the phase change wax and PVA ratios and the amounts of emulsifier on the performance of the finishing agent were investigated, and the surface morphology, heat storage and temperature regulation performance and washing fastness of resultant thermo-regulating cotton fabrics were characterized by SEM, DSC, TG, mini temperature recorder and water washing experiments. The results show that the melting temperature of the phase change wax is 30.24 ℃, the thermal enthalpy value is 190.0 J/g, the degree of supercooling is 5.82 ℃. PVA has high film formation speed, good film-forming ability and strong adhesion to the substrate when the temperature is above 70 ℃; when the ratio of the phase change wax to PVA is 5 :1 and the amount of the emulsifier is 4.8%(mass fraction) of the phase change wax, the prepared thermo-regulating finishing agent is relatively stable; after a padding-curing process, the surface of the cotton fibers is wrapped by an apparent film, and the prepared thermo-regulating cotton fabrics have phase change heat enthalpy of 20.51 J/g and phase transition temperature of 27.67 ℃. Under the same cooling conditions, the finished cotton fabrics exhibit good heat storage and temperature regulation performance, and can withstand 30 times of washing.

Mitochondrial DNA is a useful molecular marker for phylogenetic and evolutionary analysis. In the current study, we determined the complete mitochondrial genome of Eophona personata, the Japanese Grosbeak, and the phylogenetic relationships of E. personata and 16 other species of the family Fringillidae based on the sequences of 12 mitochondrial protein-coding genes. The mitochondrial genome of E. personata consists of 16,771 base pairs, and contains 13 protein-coding genes, 22 transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes, and one control region. Analysis of the base composition revealed an A+T bias, a positive AT skew and a negative GC skew. The mitochondrial gene order and arrangement in E. personata was similar to the typical avian mitochondrial gene arrangement. Phylogenetic analysis of 17 species of Fringillidae, based on Bayesian inference and Maximum Likelihood (ML) estimation, showed that the genera Coccothraustes and Hesperiphona are closely related to the genus Eophona, and further showed a sister-group relationship of E. personata and E. migratoria.

High strength intermediate modulus carbon fiber composites are still the main aviation composites in the world at present and for a long time to come. In recent year, based on the experience of high-strength carbon fiber composites, the industrialization technology of high strength intermediate modulus T800 grade carbon fiber have been broken through in China, and the resin matrix, prepreg and manufacturing process were analysized systematically for the high toughness composites reinforced by Chinese T800 grade carbon fiber. The impact resistance of the resin matrix composites reinforced by Chinese T800H grade carbon fiber is at the same level with that of foreign composites, and the hydrothermal resistance of high toughness epoxy resin matrix composites is better than that of foreign composites with the same CAI level. At the same time, the prepreg of Chinese T800H grade carbon fiber reinforced high toughness composites has excellent process ability, and it can meet the requirements of manual-layup, ATL and AFP. Based on the T800 grade composites, the main research goal is to improve the compression mechanical properties, elastic modulus and CAI based on BVID(barely visible impact damage) for high strength intermediate modulus carbon fiber composites in the future.

BackgroundAn accurate pathological diagnosis of hepatocellular carcinoma (HCC), one of the malignant tumors with the highest mortality rate, is time-consuming and heavily reliant on the experience of a pathologist. In this report, we proposed a deep learning model that required minimal noise reduction or manual annotation by an experienced pathologist for HCC diagnosis and classification.MethodsWe collected a whole-slide image of hematoxylin and eosin-stained pathological slides from 592 HCC patients at the First Affiliated Hospital, College of Medicine, Zhejiang University between 2015 and 2020. We propose a noise-specific deep learning model. The model was trained initially with 137 cases cropped into multiple-scaled datasets. Patch screening and dynamic label smoothing strategies are adopted to handle the histopathological liver image with noise annotation from the perspective of input and output. The model was then tested in an independent cohort of 455 cases with comparable tumor types and differentiations.ResultsExhaustive experiments demonstrated that our two-step method achieved 87.81% pixel-level accuracy and 98.77% slide-level accuracy in the test dataset. Furthermore, the generalization performance of our model was also verified using The Cancer Genome Atlas dataset, which contains 157 HCC pathological slides, and achieved an accuracy of 87.90%.ConclusionsThe noise-specific histopathological classification model of HCC based on deep learning is effective for the dataset with noisy annotation, and it significantly improved the pixel-level accuracy of the regular convolutional neural network (CNN) model. Moreover, the model also has an advantage in detecting well-differentiated HCC and microvascular invasion.

Multimodal sentiment analysis, which aims to recognize the emotions expressed in multimodal data, has attracted extensive attention in both academia and industry. However, most of the current studies on user-generated reviews classify the overall sentiments of reviews and hardly consider the aspects of user expression. In addition, user-generated reviews on social media are usually dominated by short texts expressing opinions, sometimes attached with images to complement or enhance the emotion. Based on this observation, we propose a visual enhancement capsule network (VECapsNet) based on multimodal fusion for the task of aspect-based sentiment analysis. Firstly, an adaptive mask memory capsule network is designed to extract the local clustering information from opinion text. Then, an aspect-guided visual attention mechanism is constructed to obtain the image information related to the aspect phrases. Finally, a multimodal fusion module based on interactive learning is presented for multimodal sentiment classification, which takes the aspect phrases as the query vectors to continuously capture the multimodal features correlated to the affective entities in multi-round iterative learning. Otherwise, due to the limited number of multimodal aspect-based sentiment review datasets at present, we build a large-scale multimodal aspect-based sentiment dataset of Chinese restaurant reviews, called MTCom. The extensive experiments both on the single-modal and multimodal datasets demonstrate that our model can better capture the local aspect-based sentiment features and is more applicable for general multimodal user reviews than existing methods. The experimental results verify the effectiveness of our proposed VECapsNet.

Image translation is a classic problem of image processing and computer vision for transforming an image from one domain to another by learning the mapping between an input image and an output image. A novel Multi-scale Residual Generative Adversarial Network (MRGAN) based on unsupervised learning is proposed in this paper for transforming images between different domains using unpaired data. In the model, a dual generater architecture is used to eliminate the dependence on paired training samples and introduce a multi-scale layered residual network in generators for reducing semantic loss of images in the process of encoding. The Wasserstein GAN architecture with gradient penalty (WGAN-GP) is employed in the discriminator to optimize the training process and speed up the network convergence. Comparative experiments on several image translation tasks over style transfers and object migrations show that the proposed MRGAN outperforms strong baseline models by large margins.