Small-molecule Molephantin induces apoptosis and mitophagy flux blockage through ROS production in glioblastoma.

Glioblastoma (GBM), one of the most malignant brain tumors in the world, has limited treatment options and a dismal survival rate. Effective and safe disease-modifying drugs for glioblastoma are urgently needed. Here, we identified a small molecule, Molephantin (EM-5), effectively penetrated the blood-brain barrier (BBB) and demonstrated notable antitumor effects against GBM with good safety profiles both in vitro and in vivo. Mechanistically, EM-5 not only inhibits the proliferation and invasion of GBM cells but also induces cell apoptosis through the reactive oxygen species (ROS)-mediated PI3K/Akt/mTOR pathway. Furthermore, EM-5 causes mitochondrial dysfunction and blocks mitophagy flux by impeding the fusion of mitophagosomes with lysosomes. It is noteworthy that EM-5 does not interfere with the initiation of autophagosome formation or lysosomal function. Additionally, the mitophagy flux blockage caused by EM-5 was driven by the accumulation of intracellular ROS. In vivo, EM-5 exhibited significant efficacy in suppressing tumor growth in a xenograft model. Collectively, our findings not only identified EM-5 as a promising, effective, and safe lead compound for treating GBM but also uncovered its underlying mechanisms from the perspective of apoptosis and mitophagy.

Characterization and Analysis of Corrosion Resistance of Rubber Materials for Downhole Tools in a High-Stress Environment with Coupled H2S-CO2.

In the process of constructing deep natural gas wells in Sichuan and Chongqing, gas wells encounter various technical challenges such as high temperature, high pressure, and a corrosive environment containing H2S and CO2. The corrosion of rubber materials in these acidic environments can easily lead to seal failure in downhole tools. To better investigate the corrosion resistance of rubber materials in acidic environments, we utilized a dynamic cyclic corrosion experimental device capable of simulating the service conditions experienced by downhole tools under high-temperature, high-pressure multiphase flow. Corrosion-resistance tests were conducted on fluororubbers (FKM) 1, 2, 3, and HNBR (hydrogenated nitrile-butadiene rubber) under acidic conditions (80 °C and 160 °C), along with sealing corrosion tests on O-rings. These tests aimed to analyze the mechanical properties, hardness, and corrosion resistance before and after exposure to acid media as well as the sealing performance of O-rings. Ultimately, our goal was to identify suitable rubber materials for acidic pressure environments. Experimental results revealed that all four types of rubber exhibited decreased elongation at break after undergoing corrosion testing; however, fluororubber 3 demonstrated significant susceptibility to temperature effects while the other three types showed minimal impact from temperature variations. Fluororubber 1 and fluororubber 3 displayed substantial deformation levels whereas mechanical properties greatly deteriorated for fluororubber 2. Overall, HNBR showcased superior comprehensive performance.

Imaging Evaluation of Peritoneal Metastasis: Current and Promising Techniques.

Early diagnosis, accurate assessment, and localization of peritoneal metastasis (PM) are essential for the selection of appropriate treatments and surgical guidance. However, available imaging modalities (computed tomography [CT], conventional magnetic resonance imaging [MRI], and 18fluorodeoxyglucose positron emission tomography [PET]/CT) have limitations. The advent of new imaging techniques and novel molecular imaging agents have revealed molecular processes in the tumor microenvironment as an application for the early diagnosis and assessment of PM as well as real-time guided surgical resection, which has changed clinical management. In contrast to clinical imaging, which is purely qualitative and subjective for interpreting macroscopic structures, radiomics and artificial intelligence (AI) capitalize on high-dimensional numerical data from images that may reflect tumor pathophysiology. A predictive model can be used to predict the occurrence, recurrence, and prognosis of PM, thereby avoiding unnecessary exploratory surgeries. This review summarizes the role and status of different imaging techniques, especially new imaging strategies such as spectral photon-counting CT, fibroblast activation protein inhibitor (FAPI) PET/CT, near-infrared fluorescence imaging, and PET/MRI, for early diagnosis, assessment of surgical indications, and recurrence monitoring in patients with PM. The clinical applications, limitations, and solutions for fluorescence imaging, radiomics, and AI are also discussed.

Engineering the Tat-secretion pathway of Bacillus licheniformis for the secretion of cytoplasmic enzyme arginase.

The industrial bacterium Bacillus licheniformis has long been used as a microbial factory for the production of enzymes due to its ability to secrete copious amounts of native extracellular proteins and its generally regarded as safe (GRAS) status. However, most attempts to use B. licheniformis to produce heterologous and cytoplasmic enzymes primarily via the general secretory (Sec) pathway have had limited success. The twin-arginine transport (Tat) pathway offers a promising alternative for the extracellular export of Sec-incompatible proteins because it transports full, correctly folded proteins. However, compared to the Sec pathway, the yields of the Tat pathway have historically been too low for commercial use. To improve the export efficiency of the Tat pathway, we identified the optimal Tat-dependent signal peptides and increased the abundance of the Tat translocases, the signal peptidase (SPase), and the intracellular chaperones. These strategic modifications significantly improved the Tat-dependent secretion of the cytoplasmic enzyme arginase into the culture medium using B. licheniformis. The extracellular enzymatic activity of arginase showed a 5.2-fold increase after these modifications. Moreover, compared to the start strain B. licheniformis 0F3, the production of extracellular GFP was improved by 3.8 times using the strategic modified strain B. licheniformis 0F13, and the extracellular enzymatic activity of SOX had a 1.3-fold increase using the strain B. licheniformis 0F14. This Tat-based production chassis has the potential for enhanced production of Sec-incompatible enzymes, therefore expanding the capability of B. licheniformis as an efficient cellular factory for the production of high-value proteins. KEY POINTS: • Systematic genetic modification of Tat-pathway in B. licheniformis. • Significant enhancement of the secretion capacity of Tat pathway for delivery the cytoplasmic enzyme arginase. • A new platform for efficient extracellular production of Sec-incompatible enzymes.

The dynamic changes in pigment metabolites provide a new understanding of the colouration of Pyracantha fortuneana at maturity.

The type, content and accumulation characteristics of pigments are the material basis for fruit colour and the evaluation basis of the fruit maturity and nutritional value of P. fortuneana. However, little information is available on the changes in carotenoids, anthocyanins, procyanidins and major flavones during the ripening process of P. fortuneana fruits. Thus, this study investigated the colour conversion characteristics, the main changes in the above four metabolites and the association landscape with those metabolites. The results showed that thirty-nine kinds of carotenoids and derivatives, eighteen anthocyanins, five procyanidins and five flavone compounds were identified in the fruits of P. fortuneana. The total content and contents of most individual carotenoids, anthocyanins, procyanidins and flavones reached the highest values at the TS2, TS4, TS1 and TS1 stages, respectively. Among the variations, the contents of ß-carotene and lutein increased first and then decreased, cyanidin-3-galactoside and cyanidin-3-glucoside accumulated, the concentrations of procyanidin C1 and procyanidin B2 decreased, and the contents of rutin and quercetin-3-O-glucoside also decreased; these changers were responsible for the main changes in carotenoids, anthocyanidin, procyanidins and flavones, respectively. For the correlation analysis results, there might be two modes of action that together affected the colour conversion of P. fortuneana fruits during ripening, i.e., (E/Z)-phytoene communicated with the carotenoid metabolic pathway that might promote the accumulated ABA content, which might cause the increased anthocyanidin (primarily through cyanidin-3-(6-malonyl-beta-d-glucoside) (C3MG)) at the final stage; most of the decreased flavone and procyanidin metabolites produced by the flavonoid metabolic pathway were another important factor affecting the accumulation of C3MG.

Combined gas well hydrate prevention and control technology and its application.

The high pressure in some gas wells, such as those in the Xushen gas field in Daqing, China, makes them susceptible to freezing and hydrate blockages. Downhole throttling technology is widely used to reduce costs during well construction, however, due to the limitations of temperature, pressure and depth structure, this technology is sometime applied independently in some gas wells in which freezing and blockages are a frequent problem that can seriously affect production capacity. Moreover, artificial alcohol injection of 'passive plugging' to prevent hydrate formation not only consumes significant amounts of methanol but its efficiency is also dependent on factors such as weather, personnel and equipment, so it is not a continuous solution. In order to solve the above problems, the mechanism of hydrate formation was analyzed in this study, from which a combined mechanical and chemical hydrate control process was developed. OLGA software was used to design the process parameters of the novel mechanical and chemical inhibition technology for hydrate prevention and control, and also to simulate and analyze the wellhead temperature, pressure and hydrate generation once the process was implemented. Based on the results of the parameters calculation, the downhole throttle and hydrate inhibitor automatic filling device are used to realize the functions of downhole throttle depressurization and hydrate inhibitor continuous filling, reduce the wellhead pressure and hydrate generation temperature, and ensure the continuous production of gas well. This novel combination process was subsequently tested in three wells in the Daqing gas oilfield. Measurements showed that the average daily gas increase from a single well was 0.5×104m3, methanol consumption was reduced from the original maximum daily amount of 1750 kg to just 60 kg, the manual maintenance workload was reduced by 80%, and the rate of the well openings was increased from 45% to 100%. These results proved that this technology is feasible and efficient for applications in gas wells with high downhole pressure and low wellhead temperature, and, thus, provides important technical support for the prevention of gas hydrate and improvement of gas well production.

µ opioid receptor carboxyl terminal-derived peptide alleviates morphine tolerance by inhibiting ß-arrestin2.

The interaction between the µ opioid receptor (MOR) and ß-arrestin2 serves as a model for addressing morphine tolerance. A peptide was designed to alleviate morphine tolerance through interfering with the interaction of MOR and ß-arrestin2. We developed a peptide derived from MOR. The MOR-TAT-pep peptide was expressed in E. coli Bl21(DE3) and purified. The effects of MOR-TAT-pep in alleviating morphine tolerance was examined through behavior tests. The potential mechanism was detected by Western blotting, Mammalian Two-Hybrid and other techniques. The pretreatment with MOR-TAT-pep prior to morphine usage led to an enhanced analgesic effectiveness of morphine and a significant reduction in the development of morphine tolerance. The peptide directly interacted with ß-arrestin2 during morphine treatment and deceased the membrane recruitment of ß-arrestin2. MOR-TAT-pep effectively suppressed the increase of ß-arrestin2 induced by morphine. The MOR-TAT-pep could alleviate morphine tolerance through inhibition of ß-arrestin2.

Elicitation with hydrogen peroxide promotes growth, phenolic-enrichment, antioxidant activity and nutritional values of two hydroponic lettuce genotypes.

Dietary vegetables rich in bioactive compounds are major responsible for promoting human health. Herein, the effect of hydrogen peroxide (H2O2), an important signaling compound, on growth and quality of two hydroponic lettuce genotypes was investigated. The maximum enhancement of growth traits was shown in lettuce elicited with 10 mmol/L H2O2, while 40 mmol/L H2O2 significantly reduced above growth traits. H2O2 elicitation increased pigment contents and photosynthetic process, which consequently caused enhancements of phenolic compounds, ascorbic acid, glutathione, carotenoids, soluble sugars, free amino acids, soluble protein, minerals, and antioxidant capacity, while above alterations appeared in a genotype-dependent manner. The phenolic accumulation was correlated with improved activity of phenylalanine ammonia lyase (PAL) and expression levels of genes related to phenolic biosynthesis, including PAL, chalcone synthase, flavanone 3-hydroxylase, dihydroflavonol-4 reductase, and UDP-glucose: flavonoid 3-O-glucosyltransferase. Therefore, elicitation with H2O2 is a promising strategy to develop lettuce with high bioactive compounds and biomass.

Creation of a Rat Takotsubo Syndrome Model and Utilization of Machine Learning Algorithms for Screening Diagnostic Biomarkers.

Introduction: Ferroptosis, a crucial type of programmed cell death, is directly linked to various cardiac disorders. However, the contribution of ferroptosis-related genes (FRGs) to Takotsubo syndrome (TTS) has not been completely understood. Purpose: The objective of this study was to investigate the relationship between the FRGs and TTS. Methods: TTS rat models were established by isoprenaline injection. Heart tissues were subsequently harvested for total RNA extraction and library construction. Transcriptome data wereobtained transcriptome data for TTS and FRGs from our laboratory, and sources such as the Ferroptosis Database (FerrDb) and the Gene Expression Omnibus Database (GEO). 57 differentially expressed FRGs (DE-FRGs) were discovered. The LASSO and SVM-RFE algorithms were employed to identify Enpp2, Pla2g6, Etv4, and Il1b as marker genes, and logistic regression was applied to construct a diagnostic model. The important genes were validated by real time PCR and the external dataset. Finally, the extent of immune infiltration was explored. Results: Among the 57 genes, there were 36 up-regulated and 21 down-regulated genes that exhibited distinct expression patterns in the TTS and healthy control samples. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that the enriched pathways were primarily associated with pathways of neurodegeneration-multiple disease, while Gene Ontology (GO) analysis revealed that these genes were primarily linked to cellular response to external stimuli, outer membrane functions, and ubiquitin protein ligase binding. After the identification of four marker genes as potentially effective biomarkers for TTS diagnosis, subsequent logistic regression modeling revealed a receiver operating characteristic curve (ROC) with an AUC of 1.0. The examination of immune cell infiltration showed significantly higher prevalence of activated CD4+ T cells, mast cells, etc., in TTS. Conclusion: Our findings support the theoretical importance of ferroptosis in TTS, highlighting Enpp2, Pla2g6, Etv4, and Il1b as potential diagnostic and therapeutic biomarkers for TTS.

Influence Mechanism of Gas Pressure on Multiscale Dynamic Apparent Diffusion-Permeability of Coalbed Methane.

The permeability and diffusion coefficient of coal show multiscale characteristics due to the influence of multiscale pore sizes. The gas pressure will continuously decrease during the coalbed methane (CBM) extraction. However, there are contradictory perceptions in the effect of gas pressure on the diffusion coefficient and permeability. Therefore, it is essential to clarify the influence mechanism of gas pressure on multiscale diffusion-seepage. Diffusion-seepage experiments are carried out using particle coal and cylindrical coal without stress loading. Meanwhile, seepage experiments measured by the steady-state method are conducted under stress loading. The results show that the apparent diffusion coefficient is dynamically attenuated with time in the experiments of particle and cylindrical coal. A new model of multiscale dynamic apparent diffusion is proposed. The mechanism of gas flow in multiscale pores is elucidated. The multiscale pores determine the attenuation of the diffusivity and permeability of coal. The initial apparent permeability decreases and then increases with the increase of gas pressure, which is caused by the effect of gas pressure stretching and multiscale flow regime. Three patterns of permeability with gas pressure, monotonically increasing, monotonically decreasing, and U-shaped changes, will occur.

Hepatocellular carcinoma cell differentiation trajectory predicts immunotherapy, potential therapeutic drugs, and prognosis of patients.

The aim of this study is to explore a novel classification and investigate the clinical significance of hepatocellular carcinoma (HCC) cells. We analyzed integrated single-cell RNA sequencing and bulk RNA-seq data obtained from HCC samples. Cell trajectory analysis divided HCC cells into three subgroups with different differentiation states: state 1 was closely related to phosphoric ester hydrolase activity, state 2 was involved in eukaryotic initiation factor 4E binding, translation regulator activity and ribosome, and state 3 was associated with oxidoreductase activity and metabolism. Three molecular classes based on HCC differentiation-related genes (HDRGs) from HCC samples were identified, which revealed immune checkpoint gene expression and overall survival (OS) of HCC patients. Moreover, a prognostic risk scoring (RS) model was generated based on eight HDRGs, and the results showed that the OS of the high-risk group was worse than that of the low-risk group. Further, potential therapeutic drugs were screened out based on eight prognostic RS-HDRGs. This study highlights the importance of HCC cell differentiation in immunotherapy, clinical prognosis, and potential molecular-targeted drugs for HCC patients, and proposes a direction for the development of individualized treatments for HCC.

The activation of GABAergic neurons in the hypothalamic tuberomammillary nucleus attenuates sevoflurane and propofol-induced anesthesia in mice.

Background: The histaminergic neurons in the hypothalamic tuberomammillary nucleus (TMN) have been suggested to play a vital role in maintaining a rising state. But the neuronal types of the TMN are in debate and the role of GABAergic neurons remains unclear. Methods: In the present study, we examined the role of TMN GABAergic neurons in general anesthesia using chemogenetics and optogenetics strategies to regulate the activity of TMN GABAergic neurons. Results: The results indicated that either chemogenetic or optogenetic activation of TMN GABAergic neurons in mice decreased the effect of sevoflurane and propofol anesthesia. In contrast, inhibition of the TMN GABAergic neurons facilitates the sevoflurane anesthesia effect. Conclusion: Our results suggest that the activity of TMN GABAergic neurons produces an anti-anesthesia effect in loss of consciousness and analgesia.

Analysis of N6-methyladenosine reveals a new important mechanism regulating the salt tolerance of sugar beet (Beta vulgaris).

Salinity is an important environmental factor in crop growth and development. N6-methyladenosine (m6A) is an essential epigenetic modification that regulates plant-environment interaction. Sugar beet is a major sugar-yielding crop that has a certain tolerance to salt, but the dynamic response elicited by the m6A modification of transcripts under salt stress remains unknown. In this study, sugar beet was exposed to 300 mM NaCl to investigate its physiological response to high salinity and transcriptome-wide m6A modification profile. After the salt treatment, 7737 significantly modified m6A sites and 4981 differentially expressed genes (DEGs) were identified. Among the 312 m6A-modified DEGs, 113 hypomethylated DEGs were up-regulated and 99 hypermethylated DEGs were down-regulated, indicating a negative correlation between m6A modification and gene expression. Well-known salt tolerance genes (e.g., sodium/hydrogen exchanger 1, choline monooxygenase, and nucleoredoxin 2) and phospholipid signaling pathway genes (phosphoinositol-specific phospholipase C, phospholipase D, diacylglycerol kinase 1, etc.) were also among the m6A-modified genes. Further analysis showed that m6A modification may regulate salt-tolerant related gene expression by controlling mRNA stability. Therefore, changes in m6A modification may negatively regulate the expression of the salt-resistant genes in sugar beet, at least in part by modulating the stability of the mRNA via demethylase BvAlkbh10B. These findings could provide a better understanding of the epigenetic mechanisms of salt tolerance in sugar beets and uncover new candidate genes for improving the production of sugar beets planted in high-salinity soil.

Unique Features of the m6A Methylome and Its Response to Salt Stress in the Roots of Sugar Beet (Beta vulgaris).

Salt is one of the most important environmental factors in crop growth and development. N6-methyladenosine (m6A) is an epigenetic modification that regulates plant-environment interaction at transcriptional and translational levels. Sugar beet is a salt-tolerant sugar-yielding crop, but how m6A modification affects its response to salt stress remains unknown. In this study, m6A-seq was used to explore the role of m6A modification in response to salt stress in sugar beet (Beta vulgaris). Transcriptome-wide m6A methylation profiles and physiological responses to high salinity were investigated in beet roots. After treatment with 300 mM NaCl, the activities of peroxidase and catalase, the root activity, and the contents of Na+, K+, and Ca2+ in the roots were significantly affected by salt stress. Compared with the control plants, 6904 differentially expressed genes (DEGs) and 566 differentially methylated peaks (DMPs) were identified. Association analysis revealed that 243 DEGs contained DMP, and 80% of these DEGs had expression patterns that were negatively correlated with the extent of m6A modification. Further analysis verified that m6A methylation may regulate the expression of some genes by controlling their mRNA stability. Functional analysis revealed that m6A modifications primarily affect the expression of genes involved in energy metabolism, transport, signal transduction, transcription factors, and cell wall organization. This study provides evidence that a post-transcriptional regulatory mechanism mediates gene expression during salt stress by affecting the stability of mRNA in the root.

Effects of elevated CO2 concentration on cell structure and stress resistance physiology of Setaria italica under drought stress.

The frequency of drought will increase under further warming. The increase in atmospheric CO2 concentration, along with more frequent drought, will affect crop growth. We examined the changes of cell structure, photosynthetic physiology, antioxidant enzymes, osmotic regulatory substances, and yield of foxtail millet (Setaria ita-lica) leaves under different CO2 concentrations (ambient air CO2 concentration and ambient atmospheric CO2 concentration + 200 µmol·mol-1) and water treatment (soil moisture content maintained at 45%-55%, and 70%-80% of field capacity, representing mild drought and normal water condition, respectively). The results showed that elevated CO2 concentration increased the number of starch grains, the area of single starch grains, and the total area of starch grains in the chloroplast of millet mesophyll cells. Under mild drought condition, elevated CO2 concentration increased net photosynthetic rate of millet leaves at the booting stage by 37.9%, but did not affect water use efficiency at this stage. Elevated CO2 concentration increased net photosynthetic rate and water use efficiency of millet leaves under mild drought condition at the filling stage by 15.0% and 44.2%, respectively. Under mild drought condition, elevated CO2 concentration increased the content of peroxidase (POD) and soluble sugar in millet leaves at the booting stage by 39.3% and 8.0%, respectively, but decreased proline content by 31.5%. It increased the content of POD in millet leaves at the filling stage by 26.5% but decreased the content of MDA and proline by 37.2% and 39.3%, respectively. Under mild drought condition, elevated CO2 concentration significantly increased the number of grain spikes by 44.7% and yield by 52.3% in both years compared with normal water condition. The effect of elevated CO2 concentration on grain yield under mild drought conditions was higher than that under normal water condition. Under mild drought conditions, elevated CO2 concentration increased leaf thickness, vascular bundle sheath cross-sectional area, net photosynthetic rate, and water use efficiency of millet, improved the antioxidant oxidase activity, and changed the concentration of osmotic regulatory substances, alleviated the nega-tive effect of drought on foxtail millet, and finally increased the number of grains per ear and yield of foxtail millet. This study would provide a theoretical basis for millet production and sustainable agricultural development in arid areas under future climate change.

Modulating Myofibroblastic Differentiation of Fibroblasts through Actin-MRTF Signaling Axis by Micropatterned Surfaces for Suppressed Implant-Induced Fibrosis.

Myofibroblasts, the primary effector cells for implant-induced fibrosis, contribute to this process by secreting excessive collagen-rich matrix and contracting. Thus, approaches that suppress myofibroblasts may achieve desirable suppression effects in the fibrotic process. As one of the important physical properties of materials, material topographical structures have been proven to affect various aspects of cell behaviors, so is it possible to manipulate the formation of myofibroblasts by tailoring the topographical properties of medical devices? In this study, polycaprolactone (PCL) surfaces with typical micropatterns (micro column and micro pit) were fabricated. The regulatory effects of surface micropatterns on the myofibroblastic differentiation of fibroblasts were investigated. Compared to the flat surfaces and surfaces with micro pit, surfaces with micro columns triggered the F- to G-actin transition, inhibiting the nuclear transfer of myocardin-related transcription factor-A. Subsequently, the downstream gene α-smooth muscle actin, which is a marker of myofibroblasts, was suppressed. Further in vivo investigation showed that PCL implants with micro-column-patterned surfaces inhibited the formation of peri-implant fibrotic capsules. Our results demonstrate that surface topographical properties are a potent regulator of fibroblast differentiation into myofibroblasts and highlight the antifibrotic potential of modifying surfaces with micro-column patterns.

The evaluation of tumor microenvironment infiltration and the identification of angiogenesis-related subgroups in skin cutaneous melanoma.

BACKGROUND: There are limited studies on the association between angiogenesis-related genes (ARGs) and the predictive risk of melanoma, even though angiogenic factors, which are essential for tumor growth and metastasis, might be secreted by angiogenesis-related protein in skin cutaneous melanoma (SKCM). To forecast patient outcomes, this study attempts to develop a predictive risk signature linked to angiogenesis in cutaneous melanoma. METHODS: In 650 patients with SKCM, the expression and mutation of ARGs were examined, and this information was related to the clinical prognosis. SKCM patients were split into two groups based on how well they performed on the ARG. The link between ARGs, risk genes, and immunological microenvironment was examined using a range of algorithmic analysis techniques. Based on these five risk genes, an angiogenesis risk signature was created. We developed a nomogram and examined the sensitivity of antineoplastic medications to help the proposed risk model's clinical applicability. RESULTS: The risk model developed by ARGs revealed that the prognosis for the two groups was significantly different. The predictive risk score was negatively connected with memory B cells, activated memory CD4 + T cells, M1 macrophages, and CD8 + T cells, and favorably correlated with dendritic cells, mast cells, and neutrophils. CONCLUSIONS: Our findings offer fresh perspectives on prognostic evaluation and imply that ARG modulation is implicated in SKCM. Potential medications for the treatment of individuals with various SKCM subtypes were predicted by drug sensitivity analysis.

Integrated analysis of C3AR1 and CD163 associated with immune infiltration in intracranial aneurysms pathogenesis.

Background: To identify potential immune-related biomarkers, molecular mechanism, and therapeutic agents of intracranial aneurysms (IAs). Methods: We identified the differentially expressed genes (DEGs) between IAs and control samples from GSE75436, GSE26969, GSE6551, and GSE13353 datasets. We used weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) analysis to identify immune-related hub genes. We evaluated the expression of hub genes by using qRT-PCR analysis. Using miRNet, NetworkAnalyst, and DGIdb databases, we analyzed the regulatory networks and potential therapeutic agents targeting hub genes. Least absolute shrinkage and selection operator (LASSO) logistic regression was performed to identify optimal biomarkers among hub genes. The diagnostic value was validated by external GSE15629 dataset. Results: We identified 227 DEGs and 22 differentially infiltrating immune cells between IAs and control samples from GSE75436, GSE26969, GSE6551, and GSE13353 datasets. We further identified 41 differentially expressed immune-related genes (DEIRGs), which were primarily enriched in the chemokine-mediated signaling pathway, myeloid leukocyte migration, endocytic vesicle membrane, chemokine receptor binding, chemokine activity, and viral protein interactions with cytokines and their receptors. Among 41 DEIRGs, 10 hub genes including C3AR1, CD163, CCL4, CXCL8, CCL3, TLR2, TYROBP, C1QB, FCGR3A, and FCGR1A were identified with good diagnostic values (AUC >0.7). Hsa-mir-27a-3p and transcription factors, including YY1 and GATA2, were identified the primary regulators of hub genes. 92 potential therapeutic agents targeting hub genes were predicted. C3AR1 and CD163 were finally identified as the best diagnostic biomarkers using LASSO logistic regression (AUC = 0.994). The diagnostic value of C3AR1 and CD163 was validated by the external GSE15629 dataset (AUC = 0.914). Conclusions: This study revealed the importance of C3AR1 and CD163 in immune infiltration in IAs pathogenesis. Our finding provided a valuable reference for subsequent research on the potential targets for molecular mechanisms and intervention of IAs.

Fabrication and characterization of highly sensitive flexible strain sensor based on biodegradable gelatin nanocomposites and double strain layered structures with crack for gesture recognition.

Flexible sensors have attracted extensive attention in the field of human-computer interaction. However, it is still a challenging task to realize accuracy gesture recognition with flexible sensor, which requires sensor not only have high sensitivity, but also have appropriate strain detection range. Here, a high gauge factor flexible sensor (gauge factor âˆ¼ 1296 under 12-20 % strain) based on crack structure is reported. The sensor is made of a biodegradable and stretchable gelatin composite combined with fabric bases, with good repeatability (6000 cycles) and a fast response (60 ms). Because of the double-layer structure, it has a suitable detection range (20 % strain). The sensor is manufactured by a screen-printing process, and it has been used to make data gloves and has realized 9 gestures recognition with machine learning algorithm (99.6 % accuracy). In general, this study offers a wearable gestures recognition scheme through the proposed sensor.

Research progress of Astragalus membranaceus in treating peritoneal metastatic cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Peritoneal metastasis is a manifestation of advanced cancer often associated with a poor prognosis and poor response to treatment. Astragalus membranaceus (Fisch.) Bunge is a commonly used medicinal material in traditional Chinese medicine with various biological activities. In patients with cancer, Astragalus membranaceus has demonstrated anti-tumor effects, immune regulation, postoperative recurrence and metastasis prevention, and survival prolongation. AIM OF THE STUDY: Peritoneal metastasis results from tumor cell and peritoneal microenvironment co-evolution. We aimed to introduce and discuss the specific mechanism of action of Astragalus membranaceus in peritoneal metastasis treatment to provide a new perspective for treatment and further research. MATERIALS AND METHODS: We consulted reports on the anti-peritoneal metastases effects of Astragalus membranaceus from PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang databases, as well as Google Scholar. Meanwhile, we also obtained data from published medical works and doctoral and master's theses. Then, we focused on the research progress of Astragalus membranaceus in peritoneal metastatic cancer treatment. Plant names are provided in accordance with "The Plant List" (www.theplantlist.org). RESULTS: To date, more than 200 compounds have been isolated from Astragalus membranaceus. Among them, Astragalus polysaccharides, saponins, and flavonoids are the main bioactive components, and their effects on cancer have been extensively studied. In this review, we systematically summarize the effects of Astragalus membranaceus on the peritoneal metastasis microenvironment and related mechanisms, including maintaining the integrity of peritoneal mesothelial cells, restoring the peritoneal immune microenvironment, and inhibiting the formation of tumor blood vessels, matrix metalloproteinase, and dense tumor spheroids. CONCLUSIONS: Our analysis demonstrates that Astragalus membranaceus could be a potential therapeutic for preventing the occurrence of peritoneal metastasis. However, it might be too early to recommend its use owing to the paucity of reliable in vivo experiment, clinical data, and evidence of clinical efficacy. In addition, previous studies of Astragalus membranaceus report inconsistent and contradictory findings. Therefore, detailed in vitro, in vivo, and clinical studies on the mechanism of Astragalus membranaceus in peritoneal metastatic cancer treatment are warranted.