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Abstract Drought poses a significant ecological threat that limits the production of crops worldwide. The objective of this study to examine the impact of soil applied biochar (BC) and peatmoss (PM) on the morpho-biochemical and quality traits of tobacco plants under drought conditions. In the present experiment work, a pot trial was conducted with two levels of drought severity (~ well-watered 75 ± 5% field capacity) and severe drought stress (~ 35 ± 5% field capacity), two levels of peatmoss (PM) @ 5% [PM+ (with peatmoss) and PM- (without peatmoss)] and three levels of rice straw biochar (BC0 = no biochar; BC1 = 150 mg kg− 1; and BC2 = 300 mg kg− 1 of soil) in tobacco plants. The results indicate that drought conditions significantly impacted the performance of tobacco plants. However, the combined approach of BC and PM significantly improved the growth, biomass, and total chlorophyll content (27.94%) and carotenoids (32.00%) of tobacco. This study further revealed that the drought conditions decreased the production of lipid peroxidation and proline accumulation. But the synergistic approach of BC and PM application increased soluble sugars (17.63 and 12.20%), soluble protein (31.16 and 15.88%), decreased the proline accumulation (13.92 and 9.03%), and MDA content (16.40 and 8.62%) under control and drought stressed conditions, respectively. Furthermore, the combined approach of BC and PM also improved the leaf potassium content (19.02%) by limiting the chloride ions (33.33%) under drought stressed conditions. Altogether, the balanced application of PM and BC has significant potential as an effective approach and sustainable method to increase the tolerance of tobacco plants subjected to drought conditions. This research uniquely highlights the combined potential of PM and BC as an eco-friendly strategy to enhance plant resilience under drought conditions, offering new insights into sustainable agricultural practices.

Objective To investigate the impact of human leukocyte antigen (HLA) functional epitope mismatch (EM) on the efficacy of platelet transfusion in patients with hematological diseases. Methods HLA genotyping was performed on platelet donors and patients with hematological diseases who applied for platelet serological cross-matching and HLA antigen matching from June 2021 to June 2023 by PCR-SBT method. HLA platelet matching was based on the principle of CREG to select donors for patients. HLA Matchmaker 4.0 software was used to analyze donor-recipient HLA EM information. The expression level and gene distribution of related HLA functional epitope (Eplet) were searched from the international HLA Epitope registry website (www.Epregistry.com.br). Retrospective analysis was conducted on clinical platelet transfusion data to evaluate the impact of HLA EM on platelet transfusion effectiveness. Results Platelet transfusion efficacy showed no correlation with gender and age, but it was associated with platelet matching strategy. When the total number of HLA EMs was less than 20, a lower total number of donor-recipient HLA EMs resulted in higher platelet transfusion efficiency (χ2=19.311, P=0.001) and higher average value of 24 h corrected count increment (CCI)(F=7.737, P

Liver ischemia-reperfusion injury (LIRI) commonly occurs in liver resection, liver transplantation, shock, and other hemorrhagic conditions, resulting in profound local and systemic effects via associated inflammatory responses and hepatic cell death. Hepatocyte death is a significant component of LIRI and its mechanism was previously thought to be limited to apoptosis and necrosis. With the discovery of novel types of programmed cell death (PCD), necroptosis, ferroptosis, pyroptosis, autophagy, NETosis, and parthanatos have been shown to be involved in LIRI. Understanding the mechanisms underlying cell death following LIRI is indispensable to mitigating the widespread effects of LIRI. Here, we review the roles of different PCD and discuss potential therapy in LIRI.

Subarachnoid hemorrhage (SAH) is a life-threatening acute hemorrhagic cerebrovascular disease, with early brain injury (EBI) being the main cause of high mortality and severe neurological dysfunction. Oxidative stress plays a crucial role in the pathogenesis of EBI. In this study, we synthesized antioxidant stress nanoparticles based on self-assembled oleanolic acid (OA) using the solvent volatilization method. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and transmission electron microscopy (TEM) techniques were employed to analyze and understand the self-assembly mechanism of oleic acid nanoparticles (OA NPs). The TUNEL assay, Nissl staining, and brain water content measurements were conducted to investigate the impact of OA NPs on cortical neuronal injury. Additionally, Western blot analysis was performed to investigate the antioxidant stress mechanism of OA NPs. The result showed that OA NPs exhibited a spherical structure with an average diameter of 168 nm. The application of OA NPs in SAH has been found to contribute to the reduction of keap1 protein levels and an increase in the nuclear level of Nrf2. As a result, the transcription of antioxidant stress proteins, including HO1 and NQO1, is triggered. The activation of the antioxidant stress pathway by OA NPs ultimately leads to a decrease in neuron damage and an improvement in neurological dysfunction. In conclusion, we successfully designed and synthesized OA NPs that can efficiently target the site of SAH. These nanoparticles have demonstrated their potential as antioxidants for the treatment of SAH, offering significant clinical applications.

Fibrous plants with higher biomass, particularly industrial hemp, have ability to withstand and accumulate significant quantities of heavy metals from contaminated environments. The present study aimed to evaluate the dynamics of different levels (ratios) of macronutrients nitrogen, phosphorus and potassium (NPK) viz., NPK1NPK (1:1:1); NPK2NPK (2:1:1); NPK3NPK (3:1:2); NPK4NPK (4:1:2) on hemp growth and Cu contents under various levels of Cu stress (100, 400 and 800 mg kg−1 on dry soil basis using CuSO4·5H2O). Results revealed that by increasing the Cu stress, growth and biomass decreased linearly and lipid per oxidation and enzymatic antioxidants increased. Balanced application of NPK improved the biomass and decreased the membrane damage by the modulation of malonaldehyde contents. Maximum concentration of Cu in roots (377.47 ± 4.90 mg kg−1), shoots (137.45 ± 5.60 mg kg−1) and (150.07 ± 3.57 mg kg−1) was recorded at Cu3NPK2 treatment as compared to control. Maximum translocation factor (TF) and bioaccumulation coefficients (BAC) in the shoots and leaves of hemp plant were noticed where Cu stress was applied at the rate of 100 mg kg−1. However, BAC and TF were below 1. The NPK2 treatment enhanced biomass and increase Cu content both in leaves and stems, rather than the roots. Our study suggests that balanced application of NPK is a practicable approach to alleviate Cu stress and improve biomass production of industrial hemp plant. These findings indicate that optimum nutrient supply, under Cu stress, can maximize the growth potential and overall health of industrial hemp, making it a viable option for phytoremediation and sustainable agriculture on contaminated soils.

Caffeic acid (CA) is a phenolic compound, which has a multifaceted role in the response of plants to various abiotic stresses. Plants must adapt to external stimuli, prompting extensive research into phenolic and flavonoid compounds as potential mitigators of environmental stress impacts. Phenylpropanoids are emphasized for their importance in maintaining plant integrity under stress, while the significance of CA, a cinnamic acid, is interpreted as a key component involved in lignin synthesis and regulating physiological processes. CA deals with different kinds of stress, like salinity-induced stress, chilling stress, and especially drought-induced stress in plants. CA helps plants make certain chemicals called phenolics, which protect them from damage caused by oxidative stress. Researchers are investigating the possible ways that CA functions, including its roles in regulating signals, defending against antioxidants, and preserving the integrity of cells. There is a need to understand the response of CA to abiotic stress factors, which can provide information about its adaptive mechanisms and applications in agriculture. This review proposes genetic advances to increase crop tolerance and provides an overview of the complexities surrounding the role of CA in plant responses to various abiotic conditions. This highlights the need for further research to identify specific mechanisms and interactions with other compounds, as well as the importance of comparative analysis of CA responses in different plant species. It emphasized the importance of meeting the challenges of stress response research and encouraged collaborative efforts for sustainable agriculture and human well-being. This demonstrates CA's importance in enhancing stress resistance and provides a blueprint for future research directions, including the study of specific mechanisms, interactions between components, and applications in the development of stress-resistant products.

IntroductionUnderstanding the pattern of species diversity and underlying ecological determinants driving a forest ecosystem is fundamental to conservation biology and forest management. Boreal forests play an irreplaceable role in providing ecosystem services and maintaining the carbon cycle globally, yet research attention remains disproportionately limited and lacking throughout time.MethodsBased on field measurement data from a large (25 ha) fully-mapped coniferous forest plot, the present study quantified patterns of species diversity and their determinants in Kanas of Xinjiang, northwest China. We applied linear regression analysis to test the effects of biotic and soil factors on alpha-diversity and local contribution of beta diversity (LCBD), and then we adopted path analysis to test the determinants that affected the species diversity index.Results and discussionOur results revealed that alpha-diversity indices did not vary greatly across different subplots, and richness value (between 2 and 6) was low in Kanas. Noteworthy is the discerned negative association between the average diameter at breast height (DBH) and species richness, suggesting that areas with smaller DBH values tend to harbor greater species richness. For beta-diversity, a higher value was observed in the substory layer (0.221) compared to both the canopy layer (0.161) and the understory layer (0.158). We also found that the species abundance distance matrix of biological and soil environmental factors were significantly correlated with species geographic distance matrices. More importantly, our results showed that average DBH and soil pH would affect the alpha diversity indices, and average DBH, soil Ph, average height and soil total Phosphorous would affect the beta diversity indices. Soil pH also indirectly affected the LCBDunder, LCBDsub, and LCBDcan (p ≤ 0.001), upon mediation of alpha diversity indices. Overall, our results provide crucial revelations about species diversity patterns in boreal forests, and insights that can support the protection of forest biodiversity in China.

Abstract Objective To investigate the relationship between dietary carotenoid intake and sleep duration. Methods Adults enrolled in the National Health and Nutrition Examination Survey (NHANES) 2007–2018 without missing information on dietary carotenoid intake (α-carotene, β-carotene, β-cryptoxanthin, lycopene, and lutein + zeaxanthin), sleep duration, and covariates were included. Participants’ carotenoid consumption was divided into three groups by quartiles and sleep duration was grouped as short ( 8 h/night). Multinominal logistic regression was constructed to examine the association between dietary carotenoid intake and sleep duration. Restricted cubic spline (RCS) regression was further utilized to explore their dose-response relationship. The weighted quantile sum (WQS) model was adopted to calculate the mixed and individual effect of 5 carotenoid sub-types on sleep duration. Results Multinominal logistic regression presented that people with higher intakes of α-carotene, β-carotene, β-cryptoxanthin, lycopene, and lutein + zeaxanthin were less likely to sleep too short or too long. Consistent with the findings from multinominal logistic regression, the RCS models suggested a reverse U-shaped relationship between sleep duration and carotenoid intakes. The mixed effects were also significant, where β-cryptoxanthin and lutein + zeaxanthin were the top 2 contributors associated with the decreased risks of short sleep duration, while β-carotene, α-carotene, and β-cryptoxanthin were the main factors related to the lower risk of long sleep duration. Conclusion Our study revealed that the American adults with optimal sleep duration were associated with more dietary carotenoid intake, in comparison to short or long sleepers.

In order to better understand the corrosion risk of single pole operation of high-voltage direct current (HVDC) grounding electrodes on pipelines, a comprehensive review of corrosion monitoring technologies for buried pipelines over recent decades was conducted in this paper; the principles of various corrosion monitoring techniques were introduced, and the application status of different corrosion monitoring technologies in the context of HVDC interference with buried pipelines was summarized; the advantages and disadvantages of four rapid corrosion measurement methods, namely the field burial method, intelligent pile monitoring method, electrochemical reduction (ER) corrosion rate probe method and laboratory simulation experiments, in evaluating the corrosion rate of buried pipelines under HVDC interference were mainly analyzed. Based on this analysis, recommendations for the application of various corrosion monitoring techniques in the field of HVDC interference with buried pipelines were proposed. Additionally, new directions in monitoring technology for corrosion rate of buried pipelines under HVDC interference were explored, providing references for relevant researchers and engineers.

Stem cells offer new therapeutic avenues for the repair and replacement of damaged tissues and organs owing to their self-renewal and multipotent differentiation capabilities. In this paper, we conduct a systematic review of the characteristics of various types of stem cells and offer insights into their potential applications in both cellular and cell-free therapies. In addition, we provide a comprehensive summary of the technical routes of stem cell therapy and discuss in detail current challenges, including safety issues and differentiation control. Although some issues remain, stem cell therapy demonstrates excellent potential in the field of regenerative medicine and provides novel tactics and methodologies for managing a wider spectrum of illnesses and traumas.

ObjectiveThis study aimed to explore the bidirectional causal relationship between periodontal disease-related phenotype (PDRP) and knee osteoarthritis (KOA) in a European population using a two-sample Mendelian Randomization (MR) approach.MethodsWe leveraged publicly available GWAS summary statistics for PDRP (n = 975) and KOA (n = 403,124), assessing their roles as both exposures and outcomes. Our comprehensive MR analysis employed various methods, including inverse variance weighting (IVW), weighted median, Egger regression, simple mode, and weighted mode, to enhance the robustness of our findings. To ensure the reliability of our instrumental variables, we implemented a rigorous screening process based on p-values and F-values, utilized Phenoscanner to investigate potential confounders, and conducted sensitivity analyses.ResultsOur analysis identified five SNPs associated with PDRP and three SNPs with KOA, all surpassing the genome-wide significance threshold, as instrumental variables. The IVW method demonstrated a significant causal relationship from PDRP to KOA (beta = 0.013, SE = 0.007, P = 0.035), without evidence of directional pleiotropy (MR-Egger regression intercept = 0.021, P = 0.706). No support was found for reverse causality from KOA to PDRP, as further MR analyses yielded non-significant P-values. Additionally, funnel plots and Cochran's Q test detected no significant heterogeneity or directional pleiotropy, confirming the robustness of our results. In multivariate analysis, when considering smoking, alcohol consumption, BMI collectively no direct causal relationship between KOA and PDRP. Conversely, smoking and higher BMI were independently associated with an increased risk of KOA.ConclusionIn conclusion, our analysis revealed no direct causal relationship from KOA to PDRP. However, a causal relationship from PDRP to KOA was observed. Notably, when adjusting for potential confounders like smoking, alcohol intake, and BMI, both the causal connection from PDRP to KOA and the inverse relationship were not substantiated.

Laser manipulation of nuclear decay has extremely promising applications. In this study, cutting-edge Gaussian lasers were combined with the latest data on α decay to thoroughly investigate the factors that impact the penetration probability in laser-assisted α decay of nuclei, while considering the deformation of the nucleus. Our calculations reveal that using state-of-the-art laser fields can marginally alter the half-life of α decay by affecting the penetration probability within a narrow range. Moreover, our findings demonstrate two key points: (1) By deriving an analytical formula for the rate of change of the α decay penetration probability in an ultra-intense laser field, we unveil the negative correlation between the α decay energy and the rate of change of the α decay penetration probability. (2) We attribute the wavelength as the determinant of the effect of the average rate of change of the penetration probability, which we explain by reconstructing the laser pulse width and wavelength. This research offers a rapid method to estimate the rate of change of the α-decay penetration probability and serves as a valuable reference for future experimental investigations of laser-nuclear interactions.

Background: The matter of postoperative radiotherapy (PORT) in esophageal cancer (ESCA) was far from conclusive. Some evidence indicated that lymph node status could affect treatment. We evaluated lymph node ratio (LNR) as an indicator that could be applied to predict PORT benefit. Methods: Retrospective cohort study collected the data of N1, N2, N3 stage ESCA patients from the Surveillance, Epidemiology, and End Results database (SEER) to analyze the association between LNR and prognosis from 2004 to 2015. Patients were categorized into two subsets based on the LNR cut-off value of 0.23 using receiver operating characteristic curve (ROC). Kaplan–Meier analysis was utilized to estimate the proportion of overall survival (OS) and esophagus cancer-specific survival (CSS) in two LNR groups. Cox regression analysis and competitive risk model was adopted to investigate the impacts of LNR on prognosis. Results: Of 2,165 ESCA patients identified, 1,165 (53.8%) had LNR>0.23. The LNR was an independent prognostic factor and associated with better OS and CSS of LNR≤0.23 (P 0.23 (HR = 1.71; 95% CI 1.53–1.91). Subgroup analyses indicated that PORT was associated with favorable OS and CSS. Furthermore, when stratified by Node stage, PORT was associated with a survival benefit only in N1 stage with higher LNR (LNR>0.23) after adjusting for other covariates. Conclusions: LNR exceeding 0.23 was negatively associated with prognosis in ESCA. The survival benefit from PORT in ESCA seems to be limited to LNR of 23% or more only in N1 stage. This study highlights the biomarker meaning of LNR on identifying PORT beneficiary in N1 stage.

Abstract Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disorder of the central nervous system (CNS) triggered by autoimmune mechanisms. Microglia are activated and play a pivotal role in response to tissue injury. Triggering receptor expressed on myeloid cells 2 (TREM2) is expressed by microglia and promotes microglial activation, survival and phagocytosis. Here, we identify a critical role for TREM2 in microglial activation and function during AQP4-IgG and complement-induced demyelination. TREM2-deficient mice had more severe tissue damage and neurological impairment, as well as fewer oligodendrocytes with suppressed proliferation and maturation. The number of microglia clustering in NMOSD lesions and their proliferation were reduced in TREM2-deficient mice. Moreover, morphology analysis and expression of classic markers showed compromised activation of microglia in TREM2-deficient mice, which was accompanied by suppressed phagocytosis and degradation of myelin debris by microglia. These results overall indicate that TREM2 is a key regulator of microglial activation and exert neuroprotective effects in NMOSD demyelination. Graphical Abstract

AbstractBackground: Cardiovascular disease (CVD) is widely observed in modern society. CVDs are responsible for the majority of fatalities, with heart attacks and strokes accounting for approximately 80% of these cases. Furthermore, a significant proportion of these deaths, precisely one-third, occurs in individuals under 70. Metabolic syndrome encompasses a range of diseases characterized by various physiological dysfunctions. These include increased inflammation in adipose tissue, enhanced cholesterol synthesis in the liver, impaired insulin secretion, insulin resistance, compromised vascular tone and integrity, endothelial dysfunction, and atheroma formation. These factors contribute to the development of metabolic disorders and significantly increase the likelihood of experiencing cardiovascular complications.Method: We selected studies that proposed hypotheses regarding metabolic disease syndrome and cardiovascular disease (CVD) and the role of Nrf2/HO-1 and factor regulation in CVD research investigations based on our searches of Medline and PubMed.Results: A total of 118 articles were included in the review, 16 of which exclusively addressed hypotheses about the role of Nrf2 on Glucose regulation, while 16 involved Cholesterol regulation. Likewise, 14 references were used to prove the importance of mitochondria on Nrf2. Multiple studies have provided evidence suggesting the involvement of Nrf2/HO-1 in various physiological processes, including metabolism and immune response. A total of 48 research articles and reviews have been used to highlight the role of metabolic syndrome and CVD.Conclusion: This review provides an overview of the literature on Nrf2/HO-1 and its role in metabolic disease syndrome and CVD.

Accurate intracellular cholesterol traffic plays crucial roles. Niemann Pick type C (NPC) proteins NPC1 and NPC2, are two lysosomal cholesterol transporters that mediate the cholesterol exit from lysosomes. However, other proteins involved in this process remain poorly defined. Here, we find that the previously unannotated protein TMEM241 is required for cholesterol egressing from lysosomes through amphotericin B-based genome-wide CRISPR-Cas9 KO screening. Ablation of TMEM241 caused impaired sorting of NPC2, a protein utilizes the mannose-6-phosphate (M6P) modification for lysosomal targeting, resulting in cholesterol accumulation in the lysosomes. TMEM241 is a member of solute transporters 35 nucleotide sugar transporters family and localizes on the cis-Golgi network. Our data indicate that TMEM241 transports UDP-N-acetylglucosamine (UDP-GlcNAc) into Golgi lumen and UDP-GlcNAc is used for the M6P modification of proteins including NPC2. Furthermore, Tmem241-deficient mice display cholesterol accumulation in pulmonary cells and behave pulmonary injury and hypokinesia. Taken together, we demonstrate that TMEM241 is a Golgi-localized UDP-GlcNAc transporter and loss of TMEM241 causes cholesterol accumulation in lysosomes because of the impaired M6P-dependent lysosomal targeting of NPC2.

ABSTRACT: In the current era, the most crucial matter is to increase crop yields sustainably. Biological agents’ usage is an effective and environmentally friendly way to boost plant growth by activating the antioxidative defense system and improving soil health. The present investigation aimed at evaluating the bacterial (Bacillus subtilis, Bacillus amyloliquefaciens) and fungal (Trichoderma harzianum) bioagents in the sole and synergistic forms to improve tobacco (cultivar: Yunyan 87) growth by the mediation of antioxidant defense system and soil health. Bioagents were applied as root application at the rate of 100 ml suspension per plant after that same concentrations were applied 25 days of planting with four times taking 15 days intervals. Results revealed that soil application of these bioagents significantly enhanced growth, photosynthetic attributes, enzymatic antioxidants, and soil enzymatic activities. Combined application of bacterial and fungal bioagents improved the leaf area (121.50%), total chlorophyll contents (131.48%), polyphenol oxidase (PPO) (77.57%) and phenylalanine ammonia-lyase (PAL) activities (43.52%) as compared with control. Fungal bioagents marked better performance as compared to bacterial bioagents and control. The co-application of bioagents significantly enhanced the leaf quality attributes by decreasing the accumulation of proline, malondialdehyde content, and accumulation of chloride ions in tobacco leaves. The higher soil enzyme activities and essential nutrients were observed in the treatment of bacterial and fungal bioagents (application of Bacillus and Trichoderma spp.). In crux, the findings confirmed that the combined use of Bacillus and Trichoderma spp could contribute as a new cultivation practice for sustainable growth, productivity and quality of tobacco crop and can be recommended as safe and eco-friendly alternatives to preserve plant, soil, and human health for achieving the sustaibalility.

COVID-19 is a disease caused by a virus named SARS-CoV-2. SARS-CoV-2 is a single-stranded positive-sense RNA virus. Reverse transcription quantitative PCR (RT–qPCR) assays are the gold standard molecular test for detection of RNA viruses. The aim of this study was to construct an RNA-positive control based on MS2 phage-like particles (MS2 VLPs) to detect SARS-CoV-2 RNA. pCDFDuet-1 was used as a one-plasmid double-expression system to construct MS2 VLPs containing ssRNA of SARS-CoV-2. The sequence encoding one copy of maturase, His-tag and coat protein dimer was cloned and inserted into MCS1 of the plasmid; the fragment encoding protein N and ORF1ab from SARS-CoV-2 was cloned and inserted into MCS2. The prepared plasmid was transformed into Escherichia coli strain BL2 (DE3), and expression of the construct was induced by 1 mM isopropyl-L-thio-D-galactopyranoside (IPTG) at 30°C for 12 hours. MS2 VLPs were purified and collected with Ni-NTA affinity chromatography columns. The size and shape of the MS2 VLPs were verified by transmission electron microscopy, and the stability of MS2 VLP packaged RNA was evaluated by treatment with RNase A. Effects of storage temperature and buffer on MS2 VLP stability were also investigated. The results showed that SARS-CoV-2 MS2 VLPs could be successfully produced by this one-plasmid double-expression system. MS2 VLPs showed high stability and may be used as a positive control in molecular diagnosis of COVID-19.

Accurate stroke assessment and consequent favorable clinical outcomes rely on the early identification and quantification of aneurysmal subarachnoid hemorrhage (aSAH) in non-contrast computed tomography (NCCT) images. However, hemorrhagic lesions can be complex and difficult to distinguish manually. To solve these problems, here we propose a novel Hybrid 2D/3D UNet deep-learning framework for automatic aSAH identification and quantification in NCCT images. We evaluated 1824 consecutive patients admitted with aSAH to four hospitals in China between June 2018 and May 2022. Accuracy and precision, Dice scores and intersection over union (IoU), and interclass correlation coefficients (ICC) were calculated to assess model performance, segmentation performance, and correlations between automatic and manual segmentation, respectively. A total of 1355 patients with aSAH were enrolled: 931, 101, 179, and 144 in four datasets, of whom 326 were scanned with Siemens, 640 with Philips, and 389 with GE Medical Systems scanners. Our proposed deep-learning method accurately identified (accuracies 0.993–0.999) and segmented (Dice scores 0.550–0.897) hemorrhage in both the internal and external datasets, even combinations of hemorrhage subtypes. We further developed a convenient AI-assisted platform based on our algorithm to assist clinical workflows, whose performance was comparable to manual measurements by experienced neurosurgeons (ICCs 0.815–0.957) but with greater efficiency and reduced cost. While this tool has not yet been prospectively tested in clinical practice, our innovative hybrid network algorithm and platform can accurately identify and quantify aSAH, paving the way for fast and cheap NCCT interpretation and a reliable AI-based approach to expedite clinical decision-making for aSAH patients.

Objective: To study the inhibitory effects on colorectal cancer (CRC) and the underlying mechanism of the petroleum ether extract of Aegiceras corniculatum leaves (PACL). Materials and Methods: The effect of PACL on the proliferation of CRC cell lines DLD-1, HT-29, and SW480 was measured by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay and colony-forming assay. And then, a wound-healing assay was used to measure the migration ability of three CRC cells. The cell cycle and apoptosis of three CRC cells were measured by PI/RNase staining and annexin V-FITC/double staining, respectively, and the intrinsic apoptosis pathway was studied by the Western blot. The anti-CRC effect of PACL in vivo was evaluated by HT-29 xenograft zebrafish embryos. Results: PACL inhibited cell viability and proliferation in DLD-1, HT-29, and SW480 cells in a dose- and time-dependent manner. PACL can inhibit cell migration in DLD-1 and SW480 cells but not in the less mobile phenotype cell HT-29. PACL treatment resulted in cell cycle arrest of DLD-1 and HT-29 cells in the G2/M phase. Moreover, PACL can induce apoptosis in all three CRC cells, which may be achieved by regulating the intrinsic apoptosis pathway mediated by mitochondria and the endoplasmic reticulum. Interestingly, the tumor sizes were decreased after treatment with PACL and PACL combined with fluorouracil in HT-29 xenograft zebrafish embryos. Conclusions: These findings suggested that PACL may exert its anti-CRC effect by inducing apoptosis through the intrinsic apoptosis pathway and show a significant anti-CRC effect in vitro and in vivo, so it might be potentially developed as an anti-CRC agent.

Background: The prognosis of middle-aged patients with colorectal cancer (CRC) treated by laparoscopic resection (LR) is unclear. This study aimed to evaluate the survival outcomes of LR compared with open resection (OR) for middle-aged patients with CRC. Patients and Methods: This retrospective cohort study used the data from a database of all consecutive colorectal resections performed between January 2009 and December 2017. Propensity score matching (PSM) was performed to handle the selection bias based on age, gender, body mass index, tumour location, AJCC stage and admission year. Univariate and multivariate COX regression model was used to identify risk factors of overall survival (OS) and disease-free survival (DFS). Results: After PSM, 154 patients were included in each group. Compared with the OR group in the total cohort, there were better survival outcomes in the LR group for 5-year OS and 5-year DFS (both P < 0.001). These differences were observed for Stage II and III diseases and for all CRC, irrespective of location. The multivariate analysis showed that tumour ≥5 cm (hazard ratio [HR] = 1.750, 95% confidence interval [CI]: 1.026–2.986, P = 0.040), Stage III (HR = 14.092, 95% CI: 1.894–104.848, P = 0.010) and LR (HR = 0.300, 95% CI: 0.160–0.560, P < 0.001) were independently associated with OS. Pre-operative carcinoembryonic antigen ≥5 ng/ml (HR = 3.954, 95% CI: 1.363–11.473, P = 0.011), Stage III (HR = 6.206, 95% CI: 1.470–26.200, P = 0.013) and LR (HR = 0.341, 95% CI: 0.178–0.653, P = 0.001) were independently associated with DFS. Conclusions: In middle-aged patients with CRC, LR achieves better survival than OR. Complications are similar, except for less blood loss and shorter post-surgical hospital stay with LR.

The genus Metarhizium is one of the most significant entomopathogenic fungi with diverse morphological characteristics and host species. Species of Metarhizium have been widely used for pest control as an environmentally safe alternative to chemical pesticides. This study reports a new species of Metarhizium and a new record of M. bibionidarum from China. The taxonomic positions of the two species within Metarhizium were assessed by morphological and multi-gene phylogenetic data. This assessment confirmed that the new species M. dianzhongense on white grubs (Coleoptera) is a sister to M. ellipsoideum on adult leafhoppers (Hemiptera) and represents a distinctive fungus according to the morphological and phylogenetic evidence. The two species, M. dianzhongense and M. bibionidarum, were described and illustrated. Pathogenicity tests by M. bibionidarum and M. dianzhongense were performed on early instar larvae of the significant agricultural pest Spodoptera frugipera (Lepidoptera). The results demonstrated that both M. bibionidarum and M. dianzhongense exhibit significant insecticidal activity against larvae of S. frugipera, providing new fungal resources for the development of an eco-friendly biocontrol agent against this pest.

A novel mode-locking method based on nonlinear multimode interference (NLMI) using a distributed large-core (105 μm) graded-index multimode fiber (GIMF)-based saturable absorber (SA) capable of generating four pulse modes is proposed. The distributed SA geometry consists of two GIMFs located at different positions in the resonant cavity. The coupling and joint operation not only facilitate resistance to pulse fragmentation but also provide a sophisticated and widely tunable transmission with saturable and reverse saturable absorption phenomena. Based on this, dissipative soliton (DS), dissipative soliton resonance (DSR), wedge-shaped, and staircase pulses are achieved without additional filters. The DS has accessible output power, pulse energy, bandwidth, and duration of up to 15.33 mW, 2.02 nJ, 22.63 nm, and ~1.68 ps. The DSR has an achievable pulse duration and energy of ~32.39 ns, 30.3 nJ. The dispersion range that allows DS operation is studied, and the dynamics of the evolution from DS to DSR are observed. The versatility, flexibility, and simplicity of the SA device, combined with the possibility of scaling the pulse energy, make it highly attractive for ultrafast optics and nonlinear dynamics.

Background: It is unclear whether serum calcium on admission is associated with clinical outcomes in dilated cardiomyopathy (DCM). In this study, we conducted a retrospective study spanning a decade to investigate the prognostic value of baseline calcium in elderly patients with DCM. Methods: A total of 1,089 consecutive elderly patients (age ≥60 years) diagnosed with DCM were retrospectively enrolled from January 2010 to December 2019. Univariate and multivariate analyses were performed to investigate the association of serum calcium with their clinical outcomes. Results: In this study, the average age of the subjects was 68.36 ± 6.31 years. Receiver operating characteristic (ROC) curve analysis showed that serum calcium level had a great sensitivity and specificity for predicting in-hospital death, with an AUC of 0.732. Kaplan–Meier survival analysis showed that patients with a serum calcium >8.62 mg/dL had a better prognosis than those with a serum calcium ≤8.62 mg/dL (log-rank χ2 40.84, p < 0.001). After adjusting for several common risk factors, a serum calcium ≤8.62 mg/dL was related to a higher risk of long-term mortality (HR: 1.449; 95% CI: 1.115~1.882; p = 0.005). Conclusions: Serum calcium level could be served as a simple and affordable tool to evaluate patients’ prognosis in DCM.

Phyllosticta yuccae is an important plant pathogen causing leaf spot disease in Yucca gigantea Lem. It is imperative to note that the amount of information available about the mitogenome of this subject is severely limited. This must be addressed immediately, as it is crucial to our understanding and progress in this field. To better understand the mitogenomic characteristics of P. yuccae, we conducted its sequencing by MGISEQ. Afterwards, the mitogenome was assembled and annotated. The mitogenomic characteristics and phylogenetic placement of the P. yuccae strain KUMCC 6213 were analyzed. The study revealed that the mitogenome of P. yuccae is a circular DNA molecule, consisting of 178,540 base pairs. It contains a total of 64 genes, including 14 protein-coding genes (PCGs), 26 transfer RNA genes (tRNA), 2 ribosomal RNA genes (rRNA), and 22 open reading frame genes (ORF), accounting for 80.98% of the total size. Repetitive sequences accounted for 15.42% of the mitogenome. The analysis of codon usage indicated that the codon UUA was the most commonly utilized, whereas the amino acid Leu was the most frequently employed. A comparative analysis of mitogenomes between P. yuccae and Macrophomina phaseolina (Tassi) Goid. showed notable variations in the position and size of gene clusters, with cox1, nad4, and nad4L genes exhibiting relatively low conservation. Phylogenetic analysis based on the 14 PCGs revealed that P. yuccae has the closest genetic relationship with M. phaseolina (Botryosphaeriaceae, Botryosphaeriales). This study first reports the mitogenome of P. yuccae and validates its phylogenetic placement. The findings enhance the knowledge of mitogenomes in Botryosphaeriales, offering novel perspectives on the genetics and evolution of the plant pathogen P. yuccae. This is crucial for the accurate prevention and management of leaf spot disease in Y. gigantea.

Background Storage of potato tubers is an essential stage of the supply chain, from farm to consumer, to efficiently match supply and demand. However, the quality and yield of potatoes are influenced by physiological changes during storage. Methods This study tested the physiological and biochemical indices in three potato varieties (YunSu 108, YunSu 304 and YunSu 306) during their dormancy periods. Results Three potato varieties with different dormancy periods were used to follow changes in starch, protein and several enzymes during storage. The starch and sugar content of the long-dormant variety (YunSu 108, LDV) were stable, whereas those of the short-dormant variety (YunSu 306, SDV) were variable. Starch synthase activity in the three varieties was initially high, then decreased; the starch content of LDV was relatively stable, that of the medium-dormant variety (YunSu 304, MDV) increased with storage time and peaked at sprouting, and that of SDV was low but variable. The sucrose synthase activity of LDV was significantly higher (p

Neuromyelitis optica spectrum disorders (NMOSD) are demyelinating diseases of the central nervous system, have drawn the attention of many researchers due to the relapsing courses and cumulative disability. A first bibliometric analysis of NMOSD was conducted to identify the research hotspots and emerging trends. Articles relevant to NMOSD published in the core collection of Web of Science were retrieved and analyzed through visualized analysis using CiteSpace and VOSviewer, focusing on annual publication trends, countries, institutions, authors, journals, and keywords. The analysis showed that over the past 30 years, publications related to NMOSD had shown steady growth with slight fluctuations. The United States played an important part in this field, with the highest outputs and the greatest number of citations. Research hotspots of NMOSD had gradually shifted from the definition, biomarkers, and diagnostic criteria to diagnosis and treatment, particularly immunotherapy. This bibliometric analysis provides researchers with a theoretical basis for studying NMOSD and offers guidance for future research directions.

Stroke is the leading cause of death and disability. Currently, there is no effective pharmacological treatment for this disease, which can be partially attributed to the inability to efficiently deliver therapeutics to the brain. Here we report the development of natural compound-derived nanoparticles (NPs), which function both as a potent therapeutic agent for stroke treatment and as an efficient carrier for drug delivery to the ischemic brain. First, we screened a collection of natural nanomaterials and identified betulinic acid (BA) as one of the most potent antioxidants for stroke treatment. Next, we engineered BA NPs for preferential drug release in acidic ischemic tissue through chemically converting BA to betulinic amine (BAM) and for targeted drug delivery through surface conjugation of AMD3100, a CXCR4 antagonist. The resulting AMD3100-conjugated BAM NPs, or A-BAM NPs, were then assessed as a therapeutic agent for stroke treatment and as a carrier for delivery of NA1, a neuroprotective peptide. We show that intravenous administration of A-BAM NPs effectively improved recovery from stroke and its efficacy was further enhanced when NA1 was encapsulated. Due to their multifunctionality and significant efficacy, we anticipate that A-BAM NPs have the potential to be translated both as a therapeutic agent and as a drug carrier to improve the treatment of stroke.

Abstract Background Karst-adapted plant, Lysionotus pauciflours accumulates special secondary metabolites with a wide range of pharmacological effects for surviving in drought and high salty areas, while researchers focused more on their environmental adaptations and evolutions. Nevadensin (5,7-dihydroxy-6,8,4'-trimethoxyflavone), the main active component in L. pauciflours, has unique bioactivity of such as anti-inflammatory, anti-tubercular, and anti-tumor or cancer. Complex decoration of nevadensin, such as hydroxylation and glycosylation of the flavone skeleton determines its diversity and biological activities. The lack of omics data limits the exploration of accumulation mode and biosynthetic pathway. Herein, we integrated transcriptomics, metabolomics, and microbial recombinant protein system to reveal hydroxylation and glycosylation involving nevadensin biosynthesis in L. pauciflours. Results Up to 275 flavonoids were found to exist in L. pauciflorus by UPLC-MS/MS based on widely targeted metabolome analysis. The special flavone nevadensin (5,7-dihydroxy-6,8,4'-trimethoxyflavone) is enriched in different tissues, as are its related glycosides. The flavonoid biosynthesis pathway was drawn based on differential transcripts analysis, including 9 PAL, 5 C4H, 8 4CL, 6 CHS, 3 CHI, 1 FNSII, and over 20 OMTs. Total 310 LpCYP450s were classified into 9 clans, 36 families, and 35 subfamilies, with 56% being A-type CYP450s by phylogenetic evolutionary analysis. According to the phylogenetic tree with AtUGTs, 187 LpUGTs clustered into 14 evolutionary groups (A-N), with 74% being E, A, D, G, and K groups. Two LpCYP82D members and LpUGT95 were functionally identified in Saccharomyces cerevisiae and Escherichia coli, respectively. CYP82D-8 and CYP82D-1 specially hydroxylate the 6- or 8-position of A ring in vivo and in vitro, dislike the function of F6H or F8H discovered in basil which functioned depending on A-ring substituted methoxy. These results refreshed the starting mode that apigenin can be firstly hydroxylated on A ring in nevadensin biosynthesis. Furthermore, LpUGT95 clustered into the 7-OGT family was verified to catalyze 7-O glucosylation of nevadensin accompanied with weak nevadensin 5-O glucosylation function, firstly revealed glycosylation modification of flavones with completely substituted A-ring. Conclusions Metabolomic and full-length transcriptomic association analysis unveiled the accumulation mode and biosynthetic pathway of the secondary metabolites in the karst-adapted plant L. pauciflorus. Moreover, functional identification of two LpCYP82D members and one LpUGT in microbe reconstructed the pathway of nevadensin biosynthesis.

Background2021 World Health Organization (WHO) Central Nervous System (CNS) tumor classification increasingly emphasizes the important role of molecular markers in glioma diagnoses. Preoperatively non-invasive “integrated diagnosis” will bring great benefits to the treatment and prognosis of these patients with special tumor locations that cannot receive craniotomy or needle biopsy. Magnetic resonance imaging (MRI) radiomics and liquid biopsy (LB) have great potential for non-invasive diagnosis of molecular markers and grading since they are both easy to perform. This study aims to build a novel multi-task deep learning (DL) radiomic model to achieve preoperative non-invasive “integrated diagnosis” of glioma based on the 2021 WHO-CNS classification and explore whether the DL model with LB parameters can improve the performance of glioma diagnosis.MethodsThis is a double-center, ambispective, diagnostical observational study. One public database named the 2019 Brain Tumor Segmentation challenge dataset (BraTS) and two original datasets, including the Second Affiliated Hospital of Nanchang University, and Renmin Hospital of Wuhan University, will be used to develop the multi-task DL radiomic model. As one of the LB techniques, circulating tumor cell (CTC) parameters will be additionally applied in the DL radiomic model for assisting the “integrated diagnosis” of glioma. The segmentation model will be evaluated with the Dice index, and the performance of the DL model for WHO grading and all molecular subtype will be evaluated with the indicators of accuracy, precision, and recall.DiscussionSimply relying on radiomics features to find the correlation with the molecular subtypes of gliomas can no longer meet the need for “precisely integrated prediction.” CTC features are a promising biomarker that may provide new directions in the exploration of “precision integrated prediction” based on the radiomics, and this is the first original study that combination of radiomics and LB technology for glioma diagnosis. We firmly believe that this innovative work will surely lay a good foundation for the “precisely integrated prediction” of glioma and point out further directions for future research.Clinical trail registrationThis study was registered on ClinicalTrails.gov on 09/10/2022 with Identifier NCT05536024.

Hepato-pancreato-biliary (HPB) cancer is a serious category of cancer including tumors originating in the liver, pancreas, gallbladder and biliary ducts. It is limited by two-dimensional (2D) cell culture models for studying its complicated tumor microenvironment including diverse contents and dynamic nature. Recently developed three-dimensional (3D) bioprinting is a state-of-the-art technology for fabrication of biological constructs through layer-by-layer deposition of bioinks in a spatially defined manner, which is computer-aided and designed to generate viable 3D constructs. 3D bioprinting has the potential to more closely recapitulate the tumor microenvironment, dynamic and complex cell-cell and cell-matrix interactions compared to the current methods, which benefits from its precise definition of positioning of various cell types and perfusing network in a high-throughput manner. In this review, we introduce and compare multiple types of 3D bioprinting methodologies for HPB cancer and other digestive tumors. We discuss the progress and application of 3D bioprinting in HPB and gastrointestinal cancers, focusing on tumor model manufacturing. We also highlight the current challenges regarding clinical translation of 3D bioprinting and bioinks in the field of digestive tumor research. Finally, we suggest valuable perspectives for this advanced technology, including combination of 3D bioprinting with microfluidics and application of 3D bioprinting in the field of tumor immunology.

With the improvement in people’s living standards, the development and application of smart textiles are receiving increasing attention. In this study, a carbon nanosurface was successfully coated with a SiO2 layer to form C@SiO2 nanomaterials, which improved the dispersion of carbon nanomaterials in an aqueous solution and enhanced the absorption of light by the carbon nanoparticles. C@SiO2 nanoparticles were coupled on the surface of silk fabric with the silane coupling agent KH570 to form C@SiO2 nanosilk fabric. The silk fabric that was subjected to such surface modification was endowed with a special photothermal function. The results obtained with scanning electron microscopy (SEM), energy dispersive spectrometer (EDS), and infrared spectroscopy (FTIR) showed that C@SiO2 nanoparticles were successfully modified on the surface of the silk fabric. In addition, under the irradiation of near-infrared light with a power of 20 W and a wavelength of 808 nm, the C@SiO2 nanosilk fabric experienced rapid warming from 23 °C to 60 °C within 30 s. After subjecting the functional fabric to hundreds of photothermal experiments and multiple washes, the photothermal efficiency remained largely unchanged and proved to be durable and stable. In addition, the thermogravimetric (TG) analysis results showed that the C@SiO2 nanoparticles contributed to the thermal stability of the silk fabric. The UV transmittance results indicated that C@SiO2 nanofabric is UV-resistant. The silk modification method developed in this study is low-cost, efficient, and environmentally friendly. It has some prospects for future applications in the textile industry.

Objective: To investigate the effects of IMR, iDose4 and FBP reconstruction algorithms on the image quality of multi-row spiral CT in the chest before costal cartilage rhinoplasty. Methods: A total of 60 patients who met the inclusion criteria and planned to receive autogenous costal cartilage rhinoplasty were collected. All patients underwent chest CT examination before operation and completed relevant 3D reconstruction based on images generated by IMR, iDose4 and FBP reconstruction algorithms, and the image quality of the three reconstruction algorithms was analyzed. The subjective evaluation score and objective evaluation indexes of image quality in each group were recorded and compared including costal cartilage CT value, noise, signal-to-noise ratio and contrast noise ratio. Results: The CT reconstruction images obtained by the three algorithms could all accurately assess the degree of costal cartilage calcification. Subjective evaluation of image quality showed that the IMR group obtained higher score and held obvious advantages, mainly reflected in the IMR reconstruction algorithm compared with iDose4 and FBP two algorithms in the costal cartilage calcification spot edge display and inhibition of liver, gastrointestinal content and weakened heart beating artifacts. Objective evaluation of costal cartilage CT value, SNR, contrast noise ratio and statistical analysis, the final statistical results showed that IMR, iDose4 and FBP reconstruction algorithm group showed significant statistical differences, IMR group showed obviously the best image quality. Conclusion: All three reconstruction algorithms of IMR, idose4 and FBP can accurately evaluate the presence and degree of calcification of autologous costal cartilage. Under the same scanning conditions, compared with the reconstruction algorithms of FBP and iDose4, IMR reconstruction algorithms can reducecan significantly reduce image noise, improve CNR and SNR, and improve the subjective image quality of costal cartilage. It is more acceptable to clinical surgeons and can be used as the preferred algorithm reconstruction technique for costal cartilage CT examination, which is most worthy of promotion.

As a class of novel biomaterials manufactured by synthetic biology technologies, recombinant collagens are candidates for a variety of medical applications. In this article, a regulatory scientific perspective on recombinant collagens and their medical devices is presented with a focus on the definition, translation, classification and technical review. Recombinant collagens are categorized as recombinant human collagen, recombinant humanized collagen and recombinant collagen-like protein, as differentiated by specific compositions and structures. Based on their intended uses and associated risks, recombinant collagen-based medical devices are generally classified as Class Ⅱ or Ⅲ in China. The regulatory review of recombinant collagen-based medical devices aims to assess their safety and efficacy demonstrated by scientific evidences generated from preclinical and clinical evaluations. Taken together, opportunities as well as challenges for their future clinical translation of recombinant collagen-based medical devices abound, which highlights the essential role of regulatory science to provide new tools, standards, guidelines and methods to evaluate the safety and efficacy of medical products.

Animal studies play a vital role in validating the concept, feasibility, safety, performance and efficacy of biomaterials products during their bench-to-clinic translation. This article aims to share regulatory considerations for animal studies of biomaterial products. After briefly emphasizing the importance of animal studies, issues of animal studies during biomaterial products’ translation are discussed. Animal studies with unclear purposes, flawed design and poor reporting quality could significantly reduce the translation efficiency and create regulatory challenges. Regulatory perspectives on the purpose, principle, quality and regulatory science of animal studies are also presented. Animal studies should have clear purposes, follow principles of 3R+DQ (replacement, reduction, refinement, design and quality) and execute under an efficiently operating quality management system. With the advancement of regulatory science, National Medical Products Administration of China has been developing a series of standards and guidance documents on animal studies of medical devices. Case studies of making decisions on whether to conduct animal studies are provided in the end with drug-eluting stents as examples. In summary, animal studies of biomaterial products should pay close attention to the rationale, design and quality in order to achieve their purposes.

Objective: To investigate the optimal dosage of contrast agent in three-dimensional dynamic enhanced magnetic resonance angiography (3D CE-MRA) in the imaging of arterial lesions of both lower limbs. Methods: 45 patients who underwent 3D CE-MRA angiography of lower extremity arteries in our hospital were randomly divided into three groups A, B and C. The gadolinium dosages of the three groups were respectively 0.1 mmol/kg, 0.2 mmol/kg and 0.3 mmol/kg. They were injected intravenously with saline at the ratio of 1:1. The images of different dose scanning schemes were scored subjectively and objectively. Subjective scoring: the lower limb arteries were divided into femoral artery, popliteal artery and calf artery (posterior tibial artery, anterior tibial artery and common peroneal artery). The quality of MIP reconstruction images was evaluated, and the overall venous overlap scoring of calf and foot vessels was also carried out. Finally, the differences of the three scanning schemes were compared by Wilcoxon test.The objective scoring is to measure and calculate the signal intensity Si, signal-to-noise ratio SNR and contrast-to-noise ratio of the original enhanced images of the three groups, compare the horizontal signal intensity differences of femoral artery, popliteal artery and calf artery, and compare the differences of the three scanning schemes by t-test. Results: When the contrast medium dosage was 0.1 mmol/kg, the image quality scores of femoral artery, popliteal artery and calf artery were (3.35±0.25), (2.97±0.25), (2.35±1.15) respectively; When the dosage of contrast agent was 0.2 mmol/kg, the scores of the above parts were (3.75±0.35), (3.55±0.32), (2.97±0.70) respectively; When the dosage of contrast agent was 0.3 mmol/kg, the scores of the above parts were (3.90±0.41), (3.83±0.52), (3.10±0.75) respectively. 33.33% of the images in group A did not meet the diagnostic needs, while all the images in group B and C met the diagnostic needs. There was significant difference between group A and group B, and there was no significant difference between group B and group C. B The Si, SNR and CNR of femoral artery and popliteal artery in group C were significantly higher than those in group A, and there was no significant difference between group B and C. The images of group B and C were better than those of group A. Conclusion: Appropriate increase of the contrast medium dosage is helpful to improve the 3D CE-MRA imaging quality of both lower limb arteries. The contrast medium dosage of 0.2 mmol/kg is reliable and accurate for the evaluation of blood vessels, and can provide accurate and reliable imaging basis for the formulation of treatment plan for patients with peripheral artery diseases.

Abstract Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor. The unregulated expression of Claudin-4 (CLDN4) plays an important role in tumor progression. However, the biological role of CLDN4 in GBM is still unknown. This study aimed to determine whether CLDN4 mediates glioma malignant progression, if so, it would further explore the molecular mechanisms of carcinogenesis. Our results revealed that CLDN4 was significantly upregulated in glioma specimens and cells. The inhibition of CLND4 expression could inhibit mesenchymal transformation, cell invasion, cell migration and tumor growth in vitro and in vivo. Moreover, combined with in vitro analysis, we found that CLDN4 can modulate tumor necrosis factor-α (TNF-α) signal pathway. Meanwhile, we also validated that the transforming growth factor-β (TGF-β) signal pathway can upregulate the expression of CLDN4, and promote the invasion ability of GBM cells. Conversely, TGF-β signal pathway inhibitor ITD-1 can downregulate the expression of CLDN4, and inhibit the invasion ability of GBM cells. Furthermore, we found that TGF-β can promote the nuclear translocation of CLDN4. In summary, our findings indicated that the TGF-β/CLDN4/TNF-α/NF-κB signal axis plays a key role in the biological progression of glioma. Disrupting the function of this signal axis may represent a new treatment strategy for patients with GBM.

Improved treatment of glioblastoma (GBM) can be achieved by inducing differentiation of glioblastoma stem cells (GSCs). Here, the authors show that zinc finger protein 117 (ZNF117) is a regulator of GSC differentiation via Notch signaling through interaction with JAG2, and can be targeted for therapy.