Curzerene suppresses hepatocellular carcinoma progression through the PI3K/AKT/MTOR pathway.

Background: Hepatocellular carcinoma (HCC) is one of the most aggressive cancers worldwide. Curzerene is a sesquiterpene and component of Curcuma rhizomes and has anti-tumor and anti-inflammatory properties. Objective: The study aimed to investigate the effects of curzerene on the malignant phenotypes and tumor growth in HCC. Methods: Various concentrations of curzerene were used to treat human HCC cells (Huh7 and HCCLM3). Cell viability, apoptosis, cell cycle, invasion, and migration were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry, Transwell, and wound healing assays. Cell cycle-, apoptosis-, and signaling pathway-related proteins were analyzed by Western blot analysis. A mouse xenograft model was established to analyze the anti-tumor effects of curzerene in vivo. Results: Curzerene repressed the proliferation, invasion, and migration of Huh7 and HCCLM3 cells. Curzerene also induced G2/M cycle arrest and cell apoptosis. Curzerene downregulated the CDK1, cyclin B1, PCNA, Bcl-2, matrix metallopeptidases (MMP)2, and MMP9 protein expression and upregulated the Bax, cleaved caspase3, and cleaved poly ADPribose polymerase protein expression in HCC cells. Curzerene restrained the phosphorylation of PI3K, AKT, and the Mammalian target of rapamycin (mTOR) in Huh7 and HCCLM3 cells. The in vivo data revealed that curzerene inhibited HCC tumor growth and decreased the expression of phosphorylated mTOR in xenograft mouse models. Conclusion: Curzerene inhibited cell malignancy in vitro and tumor growth in vivo in HCC, suggesting that curzerene may be a candidate agent for anti-HCC therapy.

Ursolic acid represses influenza A virus-triggered inflammation and oxidative stress in A549 cells by modulating the miR-34c-5p/TLR5 axis.

BACKGROUND: Ursolic acid (UA) is a pentacyclic triterpenoid compound with a wide range of anti-tumor, anti-inflammatory, hypotensive and other pharmacological effects. Here, the biological roles and regulatory mechanisms of UA in influenza A virus (IAV)-treated A549 cells were investigated. METHOD: The cytotoxic impacts of UA on A549 cells with or without IAV treatment were determined using MTT and LDH assays. The inflammatory responses and oxidative stress of IAV-treated A549 cells were measured by RT-qPCR, ELISA, DCFH-DA probe, and colorimetric assays. A dual luciferase assay was carried out to validate the molecular interaction between miR-34c-5p and TLR5. Promoter methylation was detected by MSP experiment. Methylation-related proteins were quantified by western blot. Virus replication was assessed by TCID50 and western blot assays. RESULTS: UA significantly ameliorated IAV-triggered cell injury and inflammatory response, virus replication and oxidative stress by elevating cell viability, ROS level and the activities of SOD and GSH-Px but reducing the LDH, MDA, and TCID50 values and the expression of virus-related proteins (NP) and cytokines (TNF-α, IL-1ß, IL-6, and IL-18). Moreover, UA promoted miR-34c-5p expression by repressing DNMTs-mediated methylation. TLR5 was verified to be a direct target of miR-34c-5p and could be downregulated by UA. Rescue experiments revealed that silencing miR-34c-5p diminished the regulatory roles of UA in IAV-treated A549 cells. CONCLUSION: Our data elucidated that UA attenuated IAV-triggered inflammatory responses and oxidative stress in A549 cells by regulating the miR-34c-5p/TLR5 axis, suggesting that UA plays a protective role in IAV-induced pneumonia.

Hyaluronic Acid Compound Filling Plus Mesotherapy vs Botulinum Toxin A for the Treatment of Horizontal Neck Lines: A Multicenter, Randomized, Evaluator-Blinded, Prospective Study in Chinese Subjects.

BACKGROUND: Although energy devices and botulinum toxin A (BTX-A) can alleviate age-related laxity, ptosis, and platysmal bands, they have limited efficacy on horizontal neck lines. OBJECTIVES: The purpose of this study was to investigate the efficacy, safety, and subject satisfaction of a combined treatment of non-cross-linked hyaluronic acid (HA) compound filling plus mesotherapy for the correction of horizontal neck lines, in comparison with BTX-A. METHODS: This multicenter, randomized, evaluator-blinded, prospective study enrolled female patients with moderate-to-severe horizontal neck lines corrected with either 2 or 3 sessions of of non-cross-linked HA compound filling plus mesotherapy or 1 session of BTX-A injection. Improvement of the neck lines grades, Global Aesthetic Improvement Scale (GAIS), patient satisfaction, and adverse events (AEs) were evaluated and compared at 1, 3, 6, and 10 months after the final treatment. RESULTS: Twenty-five patients received HA filling plus mesotherapy and 23 received BTX-A injection. Compared with BTX-A, the HA compound filling plus mesotherapy significantly improved the horizontal neck lines grades on all follow-up visits (P = 0.000). Cases of different baseline grades (2, 2.5, and 3) demonstrated similar outcomes. The GAIS and patients' satisfaction ratings were significantly higher for the HA filling plus mesotherapy treatment group (P = 0.000). Significantly higher pain ratings, higher incidence, and longer recovery of AEs (erythema, edema, and ecchymosis) were noticed in the combined treatment group (P < 0.001). No serious AEs occurred. CONCLUSIONS: Compared with BTX-A, combined treatment with HA compound filling plus mesotherapy significantly improved moderate-to-severe horizontal neck lines and achieved a high level of patient satisfaction.

Isolation and characterization of antagonistic Paenibacillus polymyxa HX-140 and its biocontrol potential against Fusarium wilt of cucumber seedlings.

OBJECTIVE: The aim of this study is to evaluate the efficacy of the strain Paenibacillus polymyxa HX-140, isolated from the rhizosphere soil of rape, to control Fusarium wilt of cucumber seedlings caused by Fusarium oxysporum f. sp. cucumerinum. RESULTS: Strain HX-140 was able to produce protease, cellulase, ß-1,3-glucanase and antifungal volatile organic compounds. An in vitro dual culture test showed that strain HX-140 exhibited broad spectrum antifungal activity against soil-borne plant pathogenic fungi. Strain HX-140 also reduced the infection of Fusarium wilt of cucumber seedlings by 55.6% in a greenhouse pot experiment. A field plot experiment confirmed the biocontrol effects and further revealed that antifungal activity was positively correlated with inoculum size by the root-irrigation method. Here, inoculums at 106 107 and 108 cfu/mL of HX-140 bacterial suspension reduced the incidence of Fusarium wilt of cucumber seedling by 19.5, 41.1, and 50.9%, respectively. CONCLUSIONS: Taken together, our results suggest that P. polymyxa HX-140 has significant potential in the control of Fusarium wilt and possibly other fungal diseases of cucumber.

Construction of the optimization prognostic model based on differentially expressed immune genes of lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common pathology subtype of lung cancer. In recent years, immunotherapy, targeted therapy and chemotherapeutics conferred a certain curative effects. However, the effect and prognosis of LUAD patients are different, and the efficacy of existing LUAD risk prediction models is unsatisfactory. METHODS: The Cancer Genome Atlas (TCGA) LUAD dataset was downloaded. The differentially expressed immune genes (DEIGs) were analyzed with edgeR and DESeq2. The prognostic DEIGs were identified by COX regression. Protein-protein interaction (PPI) network was inferred by STRING using prognostic DEIGs with p value< 0.05. The prognostic model based on DEIGs was established using Lasso regression. Immunohistochemistry was used to assess the expression of FERMT2, FKBP3, SMAD9, GATA2, and ITIH4 in 30 cases of LUAD tissues. RESULTS: In total,1654 DEIGs were identified, of which 436 genes were prognostic. Gene functional enrichment analysis indicated that the DEIGs were involved in inflammatory pathways. We constructed 4 models using DEIGs. Finally, model 4, which was constructed using the 436 DEIGs performed the best in prognostic predictions, the receiver operating characteristic curve (ROC) was 0.824 for 3 years, 0.838 for 5 years, 0.834 for 10 years. High levels of FERMT2, FKBP3 and low levels of SMAD9, GATA2, ITIH4 expression are related to the poor overall survival in LUAD (p < 0.05). The prognostic model based on DEIGs reflected infiltration by immune cells. CONCLUSIONS: In our study, we built an optimal prognostic signature for LUAD using DEIGs and verified the expression of selected genes in LUAD. Our result suggests immune signature can be harnessed to obtain prognostic insights.

Optimal optical path difference of an asymmetric common-path coherent-dispersion spectrometer.

Optical path difference (OPD) is a very significant parameter in the asymmetric common-path coherent-dispersion spectrometer (CODES), which directly determines the performance of the CODES. In order to improve the performance of the instrument as much as possible, a temperature-compensated optimal optical path difference (TOOPD) method is proposed. The method does not only consider the influence of temperature change on the OPD but also effectively solves the problem that the optimal OPD cannot be obtained simultaneously at different wavelengths. Taking the spectral line with a Gaussian-type power spectral density distribution as a representative, the relational expression between the OPD and the visibility of interference fringes formed by the CODES is derived for the stellar absorption/emission line. Further, the optimal OPD is deduced according to the efficiency function, and the relationship between the optimal OPD and wavelength is analyzed. Then, based on the materials' dispersion characteristics, different optical materials are combined and added to the interferometer's reflected and transmitted optical path to implement the optimal OPD at different wavelengths, thereby improving the detection precision. Meanwhile, the materials whose refractive index negatively changes with temperature are selected to reduce or even offset the temperature impact on OPD, and hence the system's stability is improved and further improves the detection precision. Under certain input conditions, the material combination that approximates the optimal OPD is performed within the range of 0.66-0.9 µm. The simulation results show that the maximal difference between the optimal OPD obtained by the efficiency function and the OPD produced by the material combination is 0.733 mm for the absorption line and 1.122 mm for the emission line, which is reduced by 1 time compared with only one material. The influence of temperature on the OPD can be reduced by 2-3 orders of magnitude by material combination, which greatly ameliorates the stability of the whole spectrometer. Hence, the TOOPD method provides a new idea for further improving the high-precision radial velocity detection of the asymmetric common-path CODES.

[A Research on Filed-of-View (FOV) Widening and Thermal-Phase-Drift (TPD) Compensating Technology Applied in a Polarized Interference Imaging Spectrometer (PIIS)].

The Polarized Interference Imaging Spectrometer (PIIS), which is based on the theory of Fourier Transform Spectroscopy, is consisted of a series of birefringent crystals such as polarizers, a beam splitter as well as various lengths of birefringent crystals required to achieve large delays. The PIIS, compared with a traditional grating-based dispersion spectrometer, has various advantages of multiple-channel measurements, simultaneous information acquisition of both original images and fringes containing spectral details, large light flux, better light signal-to-noise ratio (SNR) as well as anti-vibration etc. Therefore, the PIIS has also been developed in a range of astronomy and astrophysics areas such as remote sensing, extrasolar planet radial velocity measurements, spacecraft design, lunar exploration etc. However, by reviewing of former works and references, two major drawbacks still remain in PIIS and need to be fixed. For one thing, the classic PIIS has a very limited field-of-view (FOV) around ±2°, which means the acquired fringes on the image plane will show quite strong non-linear distortion and hence degrade the accuracy of spectral reconstruction via Fourier transform. For another, the random thermal-phase-drift (TPD), given rise from both thermal expansion and birefringence variation caused by the environmental temperature fluctuation, has barely been studied before and will inevitably result in extra radial velocity error based on Doppler Spectroscopy. In this paper, a noble polarization interference imaging spectrometer with the emphasis on the FOV widening technology is introduced. This technology, using a compensated Savart plate containing a half-wave plate sandwiched between two orthogonally placed displacer plates as a compensated Savart plate, produces an angle-dependent phase shear to create parallel spatial interference fringes with a FOV around ±10°. This improvement not only enhances the accuracy of Fourier Transform algorithm but also increases input luminous flux and therefore even weak input spectrum detection and calibration results with high SNR can be fully accomplished. Also, a secondary set of birefringent plates (α-BBO and LiNbO3) with opposite thermal properties is proposed to passively diminish TPD caused by temperature fluctuation. The experiment shows that thermal-drift-phase error is perfectly restricted within 0.02 rad in the laboratory environment. As a consequence, this advanced PIIS is eligible to realize the fast and accurate measurement and calibration application in the field of large astronomical spectral instruments with ultra-high spectral resolution occasions such as Astronomical Frequency Comb.

RNA interference against cancer/testis genes identifies dual specificity phosphatase 21 as a potential therapeutic target in human hepatocellular carcinoma.

UNLABELLED: Cancer/testis (CT) antigens have been considered therapeutic targets for treating cancers. However, a central question is whether their expression contributes to tumorigenesis or if they are functionally irrelevant by-products derived from the process of cellular transformation. In any case, these CT antigens are essential for cancer cell survival and may serve as potential therapeutic targets. Recently, the cell-based RNA interference (RNAi) screen has proven to be a powerful approach for identifying potential therapeutic targets. In this study we sought to identify new CT antigens as potential therapeutic targets for human hepatocellular carcinoma (HCC), and 179 potential CT genes on the X chromosome were screened through a bioinformatics analysis of gene expression profiles. Then an RNAi screen against these potential CT genes identified nine that were required for sustaining the survival of Focus and PLC/PRF/5 cells. Among the nine genes, the physiologically testis-restricted dual specificity phosphatase 21 (DUSP21) encoding a dual specificity phosphatase was up-regulated in 39 (33%) of 118 human HCC specimens. Ectopic DUSP21 had no obvious impact on proliferation and colony formation in HCC cells. However, DUSP21 silencing significantly suppressed cell proliferation, colony formation, and in vivo tumorigenicity in HCC cells. The administration of adenovirus-mediated RNAi and an atelocollagen/siRNA mixture against endogenous DUSP21 significantly suppressed xenograft HCC tumors in mice. Further investigations showed that DUSP21 knockdown led to arrest of the cell cycle in G1 phase, cell senescence, and expression changes of some factors with functions in the cell cycle and/or senescence. Furthermore, the antiproliferative role of DUSP21 knockdown is through activation of p38 mitogen-activated protein kinase in HCC. CONCLUSION: DUSP21 plays an important role in sustaining HCC cell proliferation and may thus act as a potential therapeutic target in HCC treatment.

Fast temporal phase unwrapping method for the fringe reflection technique based on the orthogonal grid fringes.

In traditional temporal phase unwrapping (TPU) algorithms, wrapped phases with different spatial frequencies are obtained from several groups of phase shift fringes to calculate the unwrapped phase. Therefore, the necessary quantity of captured fringes is very large, especially for the fringe reflection technique (FRT), since a pair of phases should be unwrapped to get the slopes of two perpendicular directions. In this paper, we propose a fast TPU algorithm based on the orthogonal grid fringes by which only one image is needed to extract the two integer phases for each frequency instead of two groups of phase shift fringes, and then they can be added into the wrapped phases separately to complete the unwrapping. There are ridge errors in the direct unwrapped phases, but they are significantly suppressed by our pseudo-phase-shift strategy without any extra captured fringes. The proposed method is robust and effective where the fringe amount used for unwrapping is only 1/4 of the previous similar algorithm and 1/6-1/8 of the traditional TPU methods. The detailed comparison of measurement time is also given, which demonstrate that the FRT measurement can be accelerated in most cases by our method. The algorithm is validated by the experiments, which still works well for the severely defocusing fringes or complex specimen.

The ameliorative effect on chemotherapy-induced injury and tumor immunosuppressive microenvironment of the polysaccharide from the rhizome of Menispermum dauricum DC.

Combined medication has attracted increasing attention as an important treatment option for tumors due to the serious adverse effects of chemotherapy. In this study, as a new therapy strategy, a combination treatment of MDP (a polysaccharide from the rhizome of Menispermum dauricum DC.) with cyclophosphamide (CTX) was investigated. The results showed that combination treatment with MDP and CTX exerted a significantly synergistic anti-tumor effect in Lewis tumor-bearing mice, improved CTX-induced emaciation and hair loss, as well as increased the number of leukocytes, erythrocytes, hemoglobin, and platelets in the peripheral blood. In addition, compared with CTX alone, the thymus index and spleen index of the MDP + CTX group were increased, the number of CD3 + T cells, CD8 + T cells, white blood cells and B cells in spleen also increased significantly. MDP could also ameliorate the increase in liver and kidney index caused by CTX. In the Lewis lung cancer model, MDP showed a certain degree of anti-tumor effects, which may be related to its promotion of tumor-associated macrophages (TAMs) to M1 phenotype polarisation, enhancement of the number of T cells in tumor tissues and promotion of Th cells in tumor tissues to Th1 phenotype polarisation, thus alleviating the immunosuppressive microenvironment in tumor tissues. This study laid the foundation for the development of MDP as a polysaccharide drug for the treatment or adjuvant therapy of tumors and has important significance for the further clinical application of polysaccharides.

Water extractability of the zinc protoporphyrin IX-myoglobin complex from Parma ham is pH-dependent.

The bright red color of Parma ham is mainly derived from zinc protoporphyrin IX (ZnPP), which exists in both water-soluble and insoluble states. Water-soluble ZnPP mainly binds to hemoglobin, however, the presence of water-insoluble ZnPP remains unexplained. Therefore, we aimed to elucidate how ZnPP exists in a water-insoluble state by focusing on its binding substance. Depending on the skeletal muscle, water-insoluble ZnPP comprised 30-50% of total ZnPP. The ZnPP water extractability was positively correlated with muscle pH. Water-insoluble ZnPP was extractable with a high-pH solution and existed as a complex with myoglobin or hemoglobin; nevertheless, myoglobin-binding ZnPP was more abundant. Furthermore, the water solubility of the myoglobin globin moiety at pH 5.5-6.0 was reduced by ZnPP binding. These results suggest that water-insoluble ZnPP mainly exists as a ZnPP-Mb complex, with low solubility attributed to the low pH of the ham.

Multiple omics revealed the growth-promoting mechanism of Bacillus velezensis strains on ramie.

Beneficial bacteria that promote plant growth can shield plants from negative effects. Yet, the specific biological processes that drive the relationships between soil microbes and plant metabolism are still not fully understood. To investigate this further, we utilized a combination of microbiology and non-targeted metabolomics techniques to analyze the impact of plant growth-promoting bacteria on both the soil microbial communities and the metabolic functions within ramie (Boehmeria nivea) tissues. The findings indicated that the yield and traits of ramie plants are enhanced after treatment with Bacillus velezensis (B. velezensis). These B. velezensis strains exhibit a range of plant growth-promoting properties, including phosphate solubilization and ammonia production. Furthermore, strain YS1 also demonstrates characteristics of IAA production. The presence of B. velezensis resulted in a decrease in soil bacteria diversity, resulting in significant changes in the overall structure and composition of soil bacteria communities. Metabolomics showed that B. velezensis significantly altered the ramie metabolite spectrum, and the differential metabolites were notably enriched (P < 0.05) in five main metabolic pathways: lipid metabolism, nucleotide metabolism, amino acid metabolism, plant secondary metabolites biosynthesis, and plant hormones biosynthesis. Seven common differential metabolites were identified. Correlation analysis showed that the microorganisms were closely related to metabolite accumulation and yield index. In the B. velezensis YS1 and B. velezensis Y4-6-1 treatment groups, the relative abundances of BIrii41 and Bauldia were significantly positively correlated with sphingosine, 9,10,13-TriHOME, fresh weight, and root weight, indicating that these microorganisms regulate the formation of various metabolites, promoting the growth and development of ramie. Conclusively, B. velezensis (particularly YS1) played an important role in regulating soil microbial structure and promoting plant metabolism, growth, and development. The application of the four types of bacteria in promoting ramie growth provides a good basis for future application of biological fertilizers and bio-accelerators.

Erratum: Overexpression of ZEB1 and YAP1 is related to poor prognosis in patients with gliomas with different IDH1 status.

[This corrects the article on p. 138 in vol. 16, PMID: 37559682.].

Dissociation of ferriheme from oxidized heme proteins and re-reduction of ferriheme to ferroheme are crucial for the formation of zinc protoporphyrin IX in nitrite/nitrate-free dry-cured meat products.

Zinc protoporphyrin IX (ZnPP) is the dominant red pigment in nitrate/nitrite-free dry-cured meat products such as Parma ham, and it is considered to be a potential alternative to nitrite/nitrate for reddening dry-cured meat products. Ferroheme and ferriheme dissociated from heme proteins in meat were proposed as substrates to form ZnPP. To elucidate their specific formation mechanism, nitric oxide, carbon monoxide, and azide were used to stable heme in heme proteins. The exogenous hemoglobin derivatives bound with these ligands showed lower heme dissociation compared with exogenous oxyhemoglobin and did not contribute to ZnPP formation. Meanwhile, azide inhibited almost all ZnPP formation by binding to ferriheme, indicating ferriheme dissociation from oxidized heme proteins, predominantly for ZnPP formation. Free ferriheme could not be converted to ZnPP unless it was reduced to ferroheme. Overall, ferriheme dissociated from oxidized heme proteins was the dominant substrate for conversion to ZnPP after re-reduction to ferroheme.

Global trends in research on oxidative stress related to heart failure from 2012 to 2021: a bibliometric analysis and suggestion to researchers.

Background: Oxidative stress leads to an increase in reactive oxygen in the body. During heart failure (HF), when the body's antioxidant defense system fails to remove excessive reactive oxygen species, myocardial cells will be damaged or even die. Over the past ten years, the number of research publications on oxidative stress related to HF has increased. Methods: We searched publications published in 2012-2021 and the Web of Science Core Collection (WoSCC) recording information. Based on the VOSviewer and CiteSpace, we conducted a bibliometric analysis of the overall distribution of journals, keywords, authors, major countries, annual output, active institutions, and cocited literature. The Global Citation Score (GCS) was used to evaluate the impact and quality of highly cited papers. Results: We retrieved 5,616 articles and reviews. Over the past ten years, the number of annual publications on oxidative stress related to HF has increased. USA has published the largest number of articles and obtained the highest number of citations (NC) and H-index. The University of California and PLoS One are the most productive affiliations and journals in terms of publications on oxidative stress related to HF. The GCS of articles written by Paulus WJ in 2013 was 1,632, which was the top ranking. The most frequent keywords are "oxidative stress", "heart failure", "inflammation", "dysfunction" and "apoptosis". The top three authors are Kang Yuming, Ren Jun and Okoshi Katashi. "Impact", "induced myocardial infarction", "cardiovascular outcome", "empagliflozin", "sglt2 inhibitor", "protect", and "Na+/H+ exchanger" have become popular research topics. Conclusions: Our research shows the research focus and development trends of oxidative stress related to HF in the past decade. Understanding the most important indicators of oxidative stress related to HF and the hot spots in the field of oxidative stress research related to HF can assist scholars, countries and policy-makers in the field in better understanding oxidative stress related to HF and can also lead to better decisions in oxidative stress treatment.

Overexpression of ZEB1 and YAP1 is related to poor prognosis in patients with gliomas with different IDH1 status.

OBJECTIVE: Whether there is a correlation between zinc-finger E-box-binding homolog 1 (ZEB1) and Yes-associated protein 1 (YAP1) with clinical outcome in gliomas remains unclear. Hence, this study aimed to investigate the effects of ZEB1 and YAP1 on the prognosis of human gliomas and its relationship with the isocitrate dehydrogenase 1 (IDH1) gene state. METHODS: Immunohistochemical staining was used to record the expression levels of ZEB1, YAP1, and p-YAP1 in 122 cases of low-grade glioma (LGGs) and 69 cases of glioblastoma (GBMs). The correlations of ZEB1 and YAP1 with pathological data were determined by Pearson's Chi-square test. Spearman correlation analysis was then used for analyzing the relationship among YAP1, ZEB1, and IDH1 gene status. The effects of ZEB1 and YAP1 on prognosis were investigated through survival analysis. RESULTS: We detected high ZEB1 expression levels in 29 LGGs (23.8%) and 39 GBMs (56.5%), and high YAP1 expression levels in 22 LGGs (18.0%) and 44 of GBM (63.8%). These results revealed that the protein expression levels of ZEB1 and YAP1 were higher in GBM (P < 0.001). There was a significantly positive correlation between ZEB1 and YAP1 (P < 0.001; r = 0.533). High ZEB1 expression was related to tumor grade (P < 0.001) and Ki-67 (P = 0.0037). YAP1 overexpression was correlated with Ki-67 (P < 0.001), P53 (P = 0.009), tumor grade (P < 0.001), and tumor location (P = 0.018). Patients with ZEB1 and YAP1 high expression had worse overall survival (OS) (P < 0.001). The multivariate analysis showed that YAP1 was an independent prognostic factor for OS. In the LGG group, worse OS were observed in glioma patients with elevated YAP1 expression level. Spearman correlation analysis revealed no association between ZEB1 expression and IDH1 state (P = 0.360; r = -0.084), and YAP1 expression had a negative correlation with IDH1 mutation (P < 0.001, r = -0.364). CONCLUSIONS: Our study showed that ZEB1 and YAP1 were significantly activated in GBM, and patients with high ZEB1 and YAP1 expression had worse OS. ZEB1 expression was significantly correlated with YAP1 in glioma. ZEB1 and YAP1 coexpression may serve as a useful prognostic biomarker for glioma, and aberrant YAP1 expression may be associated with IDH1 gene state.

Zhuang medicine Shuanglu Tongnao Compound Recipe treats stroke by affecting the intestinal flora regulated by the TLR4/NF-κB signaling pathway.

Background: The standardized treatment of ischemic stroke (IS) with Shuanglu Tongnao Compound Recipe (SLTNCR) combined with Western medicine has improved the life quality and neurological function of patients and achieved a satisfactory clinical effect. However, the underlying mechanisms of SLTNCR in the treatment of IS remain unclear. Methods: A rat model of IS was prepared using Longa's wire bolus method. SLTNCR was administered by gavage with following doses: low dose, 7.16 g·kg-1; middle dose, 14.33 g·kg-1; high dose, 28.66 g·kg-1. The expressions of toll-like receptor 4 (TLR4), tumor necrosis factor (TNF-α), interleukin-1ß (IL-1ß), IL-6, nuclear factor-κB (NF-κB), etc., brain neuron damage, small intestine structure, and the structure of intestinal flora of rats in the high, medium, and low dose SLTNCR groups as well as the Injury + Clostridium butyricum and Injury + Edaravone groups were detected by 16SrRNA gene sequencing, western blot, hematoxylin-eosin (HE) staining, enzyme-linked immunosorbent assay (ELISA), and polymerase chain reaction (PCR). Results: SLTNCR significantly reduced the brain water content, decreased the cerebral infarct size, and improved the neurological deficits, neuronal damage, small bowel tissue damage, and expression of inflammatory factors [B-cell CLL/lymphoma 2 (Bcl-2), BCL2 associated agonist of cell death (Bad), cleaved-caspase-3] in brain tissue. SLTNCR administration significantly inhibited expressions of TLR4, NF-κB, and inhibitor of nuclear factor kappa B (IκB), and decreased phosphorylation levels of NF-κB and IκB in the small intestinal tissues of IS rats. Moreover, SLTNCR also significantly upregulated the expression of intestinal barrier function-related molecules [zona occludens 1 (ZO-1), occludin, claudin-5] and regulated the expression of colonic TLR4, TNF-α, IL-6, and IL-1ß. SLTNCR can improve the symptoms of IS rats by improving brain and small intestinal function, particularly by regulating the TLR4/NF-κB signaling pathway, apoptotic proteins, and inflammatory factors in brain tissue. Gut microbiota analysis helped to identify the pharmacological mechanisms underlying the effects of SLTNCR on intestinal bacterial diversity and flora structure in IS rats. Conclusions: SLTNCR can alleviate symptoms of IS and the potential mechanism of its effect is to protect brain tissue by suppressing inflammation. SLTNCR can also alter the structure and diversity of the bacterial community in IS.

Lactate dehydrogenase and the severity of adenoviral pneumonia in children: A meta-analysis.

Background: Children with severe adenoviral pneumonia (ADVP) have poor prognosis and high risk of mortality. We performed a meta-analysis to evaluate the association between pretreatment lactate dehydrogenase (LDH) and severity, postinfectious bronchiolitis obliterans (PIBO), and mortality in children with ADVP. Methods: Relevant observational studies were identified by search of PubMed, Embase, Web of Science, Wanfang, and CNKI databases from inception to August 3, 2022. A random effect model was used to pool the results by incorporating the potential between-study heterogeneity. Results: Overall, 23 studies with 4,481 children with ADVP were included in this meta-analysis. Results of meta-analysis showed that children with severe ADVP had a significantly higher level of pretreatment LDH as compared to those with non-severe ADVP (standard mean difference [SMD]: 0.51, 95% confidence interval [CI]: 0.36 to 0.66, p < 0.001; I 2 = 69%). Besides, pooled results also suggested that the pretreatment LDH was significantly higher in children who developed PIBO as compared to those who did not (SMD: 0.47, 95% CI: 0.09 to 0.84, p = 0.02, I 2 = 80%). Finally, results of the meta-analysis also confirmed that a higher pretreatment LDH (>500 IU/L) was a risk factor of increased mortality during hospitalization (odds ratio: 3.10, 95% CI: 1.62 to 5.92, p < 0.001, I 2 = 0%). Sensitivity analyses by excluding one dataset at a time showed consistent results. Conclusion: High pretreatment LDH may be associated with disease severity, development of PIBO, and increased risk of mortality in children with ADVP.

Resilient Delayed Impulsive Control for Consensus of Multiagent Networks Subject to Malicious Agents.

Impulsive control is widely applied to achieve the consensus of multiagent networks (MANs). It is noticed that malicious agents may have adverse effects on the global behaviors, which, however, are not taken into account in the literature. In this study, a novel delayed impulsive control strategy based on sampled data is proposed to achieve the resilient consensus of MANs subject to malicious agents. It is worth pointing out that the proposed control strategy does not require any information on the number of malicious agents, which is usually required in the existing works on resilient consensus. Under appropriate control gains and sampling period, a necessary and sufficient graphic condition is derived to achieve the resilient consensus of the considered MAN. Finally, the effectiveness of the resilient delayed impulsive control is well demonstrated via simulation studies.