Identification of hub genes related to metastasis and prognosis of osteosarcoma and establishment of a prognostic model with bioinformatic methods.

Osteosarcoma (OS) is the most common primary malignant bone tumor occurring in children and adolescents. Improvements in our understanding of the OS pathogenesis and metastatic mechanism on the molecular level might lead to notable advances in the treatment and prognosis of OS. Biomarkers related to OS metastasis and prognosis were analyzed and identified, and a prognostic model was established through the integration of bioinformatics tools and datasets in multiple databases. 2 OS datasets were downloaded from the Gene Expression Omnibus database for data consolidation, standardization, batch effect correction, and identification of differentially expressed genes (DEGs); following that, gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the DEGs; the STRING database was subsequently used for protein-protein interaction (PPI) network construction and identification of hub genes; hub gene expression was validated, and survival analysis was conducted through the employment of the TARGET database; finally, a prognostic model was established and evaluated subsequent to the screening of survival-related genes. A total of 701 DEGs were identified; by gene ontology and KEGG pathway enrichment analyses, the overlapping DEGs were enriched for 249 biological process terms, 13 cellular component terms, 35 molecular function terms, and 4 KEGG pathways; 13 hub genes were selected from the PPI network; 6 survival-related genes were identified by the survival analysis; the prognostic model suggested that 4 genes were strongly associated with the prognosis of OS. DEGs related to OS metastasis and survival were identified through bioinformatics analysis, and hub genes were further selected to establish an ideal prognostic model for OS patients. On this basis, 4 protective genes including TPM1, TPM2, TPM3, and TPM4 were yielded by the prognostic model.

Are carbon emissions trading and green financial instruments synergistic? -Comprehensive quantitative research based on content analysis.

Coordinating policies is an essential guarantee for carbon emission reduction and sustainable development. Based on the theoretical framework of the policy paradigm, we quantitatively analyze 266 policy documents on promoting carbon emission trading and green financial policies from 2011 to 2022 using the content analysis research method. Based on the matching network of "policy objectives-policy tools," we analyze the synergistic characteristics of carbon emission trading policies and green financial policies in promoting carbon emission reduction targets and reveal the matching mode of "objectives-tools" of green financial policies by using social network analysis. It is found that, first, from the perspective of policy objectives, the main policy objectives of carbon emissions trading are to promote green innovation of enterprises, and the main policy objectives of green finance are to promote green development, which reflects the consistency and endogenous motivation of policy objectives. Secondly, command-control and market incentive policy tools are the main policy tools in the structure of policy tools. The proportion of public participation policy tools is small, and there is a structural asymmetry. Third, carbon emissions trading tools focus on supervision, adjustment, and platform construction. The green financial policy tools have the characteristics of guidance, public welfare, and externality. The two constitute a complementary, embedded, and integrated ' double synergy ' carbon emission reduction policy. Based on this, this paper puts forward some suggestions to promote policy coordination and provides a reference for China to achieve the dual carbon goal.

Preparation of reed fibers reinforced graft-modified starch-based adhesives based on quantum mechanical simulation and molecular dynamics simulation.

Starch is a biomass polymer material with a high yield and comprehensive source. It is used as a raw material for preparing adhesives because of its highly active hydroxyl group. However, poor adhesion and water resistance hinder the application of starch-based adhesives (SBAs). Based on this, the starch was modified through graft copolymerization with itaconic acid as a cross-linking agent, methyl methacrylate and methyl acrylate as copolymers. Additionally, reed fibers were synergistically modified with polydopamine deposition to prepare an environmentally friendly SBA used in plywood production. Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (1H NMR), X-ray diffraction (XRD), and thermogravimetric analysis (TG) demonstrate that copolymerization of methyl methacrylate and methyl acrylate with starch improves the shear strength, water resistance, and thermal stability of the SBA. Compared to unmodified starch, the modified SBA exhibits a 129 % increase in dry strength and achieves a wet strength of 1.36 MPa. Fukui function, Frontier orbit theory, and molecular dynamics simulation have shown that itaconic acid promotes the copolymerization of starch and acrylate monomers. The modified starch has fewer hydrogen bonds, less order, and a denser macromolecular network structure, which provides a reference for studying the molecular interaction mechanisms of SBAs.

Limiting Temperature Rise in Cochlear Implantation Bone Drilling: A Novel Approach.

OBJECTIVE: In the process of cochlear implantation surgery, it is crucial to develop a method to control the temperature during the drilling of the implant channel since high temperatures can result in damage to bone and nerve tissue. METHODS: This paper simplified the traditional point heat source temperature rise model and proposed a novel extreme peck drilling model to quantitatively calculate the maximum temperature rise value. It is also innovatively introduced a new method for calculating the best peck drilling duty cycle to strictly control the maximum temperature rise value. Besides, the neural network is trained with virtual data to identify two important thermal parameters in the temperature rise model. RESULTS: In the experiment of epoxy resin and temporal bone, the difference between predicted maximum temperature and actual maximum temperature was less than 1.5 °C, and the error rate was less than 10%. And the error source was analyzed by variational mode decomposition, along with discussion of potential solutions. In the temperature control experiment, the model successfully controlled the maximum temperature rise within 10 °C.For cochlear implantation surgery, we also divide the implantation channel into different stages based on the bone density in CT images to identify thermal parameters and calculate drilling strategies. CONCLUSION: This method provides a new strategy for accurate and effective control of borehole heat generation. SIGNIFICANCE: These achievements provide new ideas and directions for research in cochlear implantation surgery and related fields, and are expected to have extensive application in medical practice.

Remarkable Pyro-Catalysis of g-C3N4 Nanosheets for Dye Decoloration under Room-Temperature Cold-Hot Cycle Excitation.

Pyroelectric materials have the ability to convert the environmental cold-hot thermal energy such as day-night temperature alternation into electrical energy. The novel pyro-catalysis technology can be designed and realized on the basis of the product coupling between pyroelectric and electrochemical redox effects, which is helpful for the actual dye decomposition. The organic two-dimensional (2D) graphic carbon nitride (g-C3N4), as an analogue of graphite, has attracted considerable interest in the field of material science; however, its pyroelectric effect has rarely been reported. In this work, the remarkable pyro-catalytic performance was achieved in the 2D organic g-C3N4 nanosheet catalyst materials under the continuous room-temperature cold-hot thermal cycling excitation from 25 °C to 60 °C. The pyro-catalytic RhB dye decoloration efficiency of the 2D organic g-C3N4 can reach ~92.6%. Active species such as the superoxide radicals and hydroxyl radicals are observed as the intermediate products in the pyro-catalysis process of the 2D organic g-C3N4 nanosheets. The pyro-catalysis of the 2D organic g-C3N4 nanosheets provides efficient technology for wastewater treatment applications, utilizing the ambient cold-hot alternation temperature variations in future.

Thermal Behaviors and Interaction Mechanism of Ammonium Dinitramide with Nitrocellulose.

The initial interaction mechanism is very important for the design and safety of nano-scale composite energetic materials composed of ammonium dinitramide (ADN) and nitrocellulose (NC). The thermal behaviors of ADN, NC and an NC/ADN mixture under different conditions were studied by using differential scanning calorimetry (DSC) with sealed crucibles, an accelerating rate calorimeter (ARC), a self-developed gas pressure measurement instrument and a DSC-thermogravimetry (TG)-quadrupole mass spectroscopy (MS)-Fourier transform infrared spectroscopy (FTIR) combined technique. The results show that the exothermic peak temperature of the NC/ADN mixture shifted forward greatly in both open and closed circumstances compared to those of NC or ADN. After 585.5 min under quasi-adiabatic conditions, the NC/ADN mixture stepped into the self-heating stage at 106.4 °C, which was much less than the initial temperatures of NC or ADN. The significant reduction in net pressure increment of NC, ADN and the NC/ADN mixture under vacuum indicates that ADN initiated the interaction of NC with ADN. Compared to gas products of NC or ADN, two new kinds of oxidative gases O2 and HNO2 appeared for the NC/ADN mixture, while NH3 and aldehyde disappeared. The mixing of NC with ADN did not change the initial decomposition pathway of either, but NC made ADN more inclined to decompose into N2O, which resulted in the formation of oxidative gases O2 and HNO2. The thermal decomposition of ADN dominated the initial thermal decomposition stage of the NC/ADN mixture, followed by the oxidation of NC and the cation of ADN.

The translational landscape of bread wheat during grain development.

The dynamics of gene expression in crop grains has typically been investigated at the transcriptional level. However, this approach neglects translational regulation, a widespread mechanism that rapidly modulates gene expression to increase the plasticity of organisms. Here, we performed ribosome profiling and polysome profiling to obtain a comprehensive translatome data set of developing bread wheat (Triticum aestivum) grains. We further investigated the genome-wide translational dynamics during grain development, revealing that the translation of many functional genes is modulated in a stage-specific manner. The unbalanced translation between subgenomes is pervasive, which increases the expression flexibility of allohexaploid wheat. In addition, we uncovered widespread previously unannotated translation events, including upstream open reading frames (uORFs), downstream open reading frames (dORFs), and open reading frames (ORFs) in long noncoding RNAs, and characterized the temporal expression dynamics of small ORFs. We demonstrated that uORFs act as cis-regulatory elements that can repress or even enhance the translation of mRNAs. Gene translation may be combinatorially modulated by uORFs, dORFs, and microRNAs. In summary, our study presents a translatomic resource that provides a comprehensive and detailed overview of the translational regulation in developing bread wheat grains. This resource will facilitate future crop improvements for optimal yield and quality.

Mechanisms of theaflavins against gout and strategies for improving the bioavailability.

BACKGROUND: Gout is a crystal related arthropathy caused by monosodium urate deposition. At present, the identification of appropriate treatments and new drugs to reduce serum uric acid levels and gout risk is a major research area. PURPOSE: Theaflavins are naturally occurring compounds characterized by a benzodiazepine skeleton. The significant benefits of theaflavins have been well documented. A large number of studies have been carried out and excellent anti-gout results have been achieved in recent years. STUDY DESIGN: A comprehensive analysis of the mechanism of the anti-gout effect of theaflavins is presented through a literature review and network pharmacology prediction, and strategies for increasing the bioavailability of theaflavins are summarized. METHODS: In this review, the active components and pharmacological mechanisms of theaflavins in the treatment of gout were summarized, and the relationship between theaflavins and gout, the relevant components, and the potential mechanisms of anti-gout action were clarified by reviewing the literature on the anti-gout effects of theaflavins and network pharmacology. RESULTS: Theaflavins exert anti-gout effects by down regulating the gene and protein expression of glucose transporter 9 (GLUT9) and uric acid transporter 1 (URAT1), while upregulating the mRNA expression levels of organic anion transporter 1 (OAT1), organic cation transporter N1 (OCTN1), organic cation transporters 1/2 (Oct1/2), and organic anion transporter 2 (OAT2). Network pharmacology prediction indicate that theaflavins can regulate the AGE-RAGE and cancer signaling pathways through ATP-binding cassette subfamily B member 1 (ABCB1), recombinant mitogen activated protein kinase 14 (MAPK14), telomerase reverse tranase (TERT), signal transducer and activator of transcription 1 (STAT1), matrix metalloproteinase 2 (MMP2), B-cell lymphoma-2 (BCL2), and matrix metalloproteinase 14 (MMP14) targets for anti-gout effects. CONCLUSION: This review presents the mechanisms of anti-gout action of theaflavins and strategies for improving the bioavailability of theaflavins, as well as providing research strategies for anti-gout treatment measures and the development of novel anti-gout drugs.

Designing Heteroatom-Codoped Iron Metal-Organic Framework for Promotional Photoreduction of Carbon Dioxide to Ethylene.

Rational engineering active sites and vantage defects of catalysts are promising but grand challenging task to enhance photoreduction CO2 to high value-added C2 products. In this study, we designed an N,S-codoped Fe-based MIL-88B catalyst with well-defined bipyramidal hexagonal prism morphology via a facile and effective process, which was synthesized by addition of appropriate 1,2-benzisothiazolin-3-one (BIT) and acetic acid to the reaction solution. Under simulated solar irradiation, the designed catalyst exhibits high C2 H4 evolution yield of 17.7 µmol g-1 ⋅h, which has been rarely achieved in photocatalytic CO2 reduction process. The synergistic effect of Fe-N coordinated sites and reasonable defects in the N,S-codoped photocatalyst can accelerate the migration of photogenerated carriers, resulting in high electron density, and this in turn helps to facilitate the formation and dimerization of C-C coupling intermediates for C2 H4 effectively.

The medicinal value of tea drinking in the management of COVID-19.

Corona Virus Disease 2019 (COVID-19) is presently the largest international public health event, individuals infected by the virus not only have symptoms such as fever, dry cough, and lung infection at the time of onset, but also possibly have sequelae in the cardiovascular system, respiratory system, nervous system, mental health and other aspects. However, numerous studies have depicted that the active ingredients in tea show good antiviral effects and can treat various diseases by regulating multiple pathways, and the therapeutic effects are associated with the categories of chemical components in tea. In this review, the differences in the content of key active ingredients in different types of tea are summarized. In addition, we also highlighted their effects on COVID-19 and connected sequelae, further demonstrating the possibility of developing a formulation for the prevention and treatment of COVID-19 and its sequelae through tea extracts. We have a tendency to suggest forestalling and treating COVID-19 and its sequelae through scientific tea drinking.

NUF2 Drives Clear Cell Renal Cell Carcinoma by Activating HMGA2 Transcription through KDM2A-mediated H3K36me2 Demethylation.

The poor sensitivity of clear cell renal cell carcinoma (ccRCC) to conventional chemotherapy and radiotherapy makes its treatment challenging. The Ndc80 kinetochore complex component (NUF2) is involved in the development and progression of several cancers. However, its role in ccRCC remains unclear. In this study, we investigated the biological functions and underlying mechanism of NUF2 in ccRCC. We found that NUF2 expression was increased in ccRCC and associated with poor prognosis. Altering NUF2 level affected cell proliferation, migration, and invasion. Moreover, NUF2 acted as a potential oncogene to promote the progression of ccRCC through epigenetic activation of high-mobility group AT-hook 2 (HMGA2) transcription by suppressing lysine demethylase 2A expression and affecting its occupancy on the HMGA2 promoter region to regulate histone H3 lysine 36 di-methylation modification. In addition, Kaplan-Meier and multivariate analysis revealed that patients whose NUF2 and HMGA2 were both elevated showed the shortest survival; and the number of upregulated markers acted as an independent predictor to evaluate survival probability. Thus, our results demonstrate that NUF2 promotes ccRCC progression, at least partly by epigenetically regulating HMGA2 transcription, and that the NUF2-HMGA2 axis could be an ideal therapeutic target and a promising prognostic indicator for ccRCC.

PAC-UF Process Improving Surface Water Treatment: PAC Effects and Membrane Fouling Mechanism.

In this study, the water purification effect and membrane fouling mechanism of two powdered activated carbons (L carbon and S carbon) enhancing Polyvinylidene Fluoride (PVDF) ultrafiltration (UF) membranes for surface water treatment were investigated. The results indicated that PAC could effectively enhance membrane filtration performance. With PAC addition, organic removal was greatly enhanced compared with direct UF filtration, especially for small molecules, i.e., the S-UF had an additional 25% removal ratio of micro-molecule organics than the direct UF. The S carbon with the larger particle size and lower specific surface area exhibited superior performance to control membrane fouling, with an operation duration of S-UF double than the direct UF. Therefore, the particle size and pore structure of carbon are the two key parameters that are essential during the PAC-UF process. After filtration, acid and alkaline cleaning of UF was conducted, and it was found that irreversible fouling contributed the most to total filtration resistance, while the unrecoverable irreversible resistance ratio with acid cleaning was greater than that with alkaline cleaning. With PAC, irreversible UF fouling could be relieved, and thus, the running time could be extended. In addition, the membrane foulant elution was analyzed, and it was found to be mainly composed of small and medium molecular organic substances, with 12% to 21% more polysaccharides than proteins. Finally, the hydrophilicity of the elution was examined, and it was observed that alkaline cleaning mainly eluted large, medium, and small molecules of hydrophilic and hydrophobic organic matter, while acid cleaning mainly eluted small molecules of hydrophilic organic matter.

Microwave hydrothermal renovating and reassembling spent lithium cobalt oxide for lithium-ion battery.

With the growing number of lithium-ion batteries (LIBs) that are consumed by worldwide people, recycling is necessary for addressing environmental problems and alleviating energy crisis. Especially, it is meaningful to regenerate LIBs from spent batteries. In this paper, the microwave hydrothermal method is used to replenish lithium, assemble particles and optimize the crystal structure of the spent lithium cobalt oxide. The microwave hydrothermal process can shorten the reaction time, improve the internal structure, and uniformize the particle size distribution of lithium cobalt oxide. It helps to construct a regenerated lithium cobalt oxide (LiCoO2) battery with high-capacity and high-rate properties (141.7 mAh g-1 at 5C). The cycle retention rate is 94.5% after 100 cycles, which is far exceeding the original lithium cobalt oxide (89.7%) and LiCoO2 regenerated by normal hydrothermal method (88.3%). This work demonstrates the feasibility to get lithium cobalt oxide batteries with good structural stability from spent lithium cobalt oxide batteries.

Protective effect and mechanism of Lycium barbarum L. polyphenol on cognitive impairment induced by ethanol in mice.

BACKGROUND: Chronic excessive ethanol consumption damages the central nervous system and causes neurobehavioral changes, such as cognitive impairment, which is related to oxidative stress and inhibition of neurogenesis in the hippocampus. It is known that promoting neurogenesis improves learning memory, anxiety and depression. Lycium barbarum L. polyphenol (LBP) is the main active ingredient of Lycium barbarum L., which has excellent neuroprotective effects. However, the effects and mechanisms of LBP on ethanol-induced cognitive impairment are unclear. PURPOSE: To assess the effects and mechanisms of LBP on ethanol-induced cognitive impairment in mice. METHODS: Eight-weeks-old adult C57BL/6J mice were allowed to drink ethanol (10%) to establish a model of ethanol-induced cognitive impairment. From the 29th day of LBP (25, 50, 100, 200, 400 mg/kg, intragastric administration), the locomotor activity, novel object recognition (NOR), Y maze and Morris water maze (MWM) were sequentially performed to investigate the effect of LBP on ethanol-induced cognitive impairment in mice. Next, enzyme-linked immunosorbent assay, immunofluorescence, and western blotting were used to study the underlying mechanism of LBP on ethanol-induced cognitive impairment. RESULTS: LBP significantly decreased the escape latency and increased the number of crossings of the original platform in MWM, increased the spontaneous alteration behavior in the Y maze, and increased the preference index in the NOR in ethanol-induced mice. Notably, LBP significantly promoted the proliferation of neural stem cells, neural progenitor cells and neuroblasts, and increased the proportion of activated NSCs in mice with ethanol-induced cognitive impairment. Similarly, LBP significantly increased the number of newborn immature neurons and mature neurons. Moreover, LBP increased the levels of nuclear factor erythroid2-related factor 2 (Nrf2) and the downstream heme oxygenase-1(HO-1) protein expression, which led to a decrease of oxidative stress levels. CONCLUSION: LBP significantly improves cognitive impairment in ethanol-induced mice, which is attributed to the promotion of hippocampal neurogenesis and reduction of oxidative stress.

Application of Coagulation-Membrane Rotation to Improve Ultrafiltration Performance in Drinking Water Treatment.

The combination of conventional and advanced water treatment is now widely used in drinking water treatment. However, membrane fouling is still the main obstacle to extend its application. In this study, the impact of the combination of coagulation and ultrafiltration (UF) membrane rotation on both fouling control and organic removal of macro (sodium alginate, SA) and micro organic matters (tannic acid, TA) was studied comprehensively to evaluate its applicability in drinking water treatment. The results indicated that membrane rotation could generate shear stress and vortex, thus effectively reducing membrane fouling of both SA and TA solutions, especially for macro SA organics. With additional coagulation, the membrane fouling could be further reduced through the aggregation of mediate and macro organic substances into flocs and elimination by membrane retention. For example, with the membrane rotation speed of 60 r/min, the permeate flux increased by 90% and the organic removal by 35% in SA solution, with 40 mg/L coagulant dosage, with an additional 70% increase of flux and 5% increment of organic removal to 80% obtained. However, too much shear stress could intensify the potential of fiber breakage at the potting, destroying the flocs and resulting in the reduction of permeate flux and deterioration of effluent quality. Finally, the combination of coagulation and membrane rotation would lead to the shaking of the cake layer, which is beneficial for fouling mitigation and prolongation of membrane filtration lifetime. This study provides useful information on applying the combined process of conventional coagulation and the hydrodynamic shear force for drinking water treatment, which can be further explored in the future.

Precise laminae segmentation based on neural network for robot-assisted decompressive laminectomy.

BACKGROUND AND OBJECTIVE: The decompressive laminectomy is one of the most common operations to treat lumbar spinal stenosis by removing the laminae above the spinal nerve. Recently, an increasing number of robots are deployed during the surgical process to reduce the burden on surgeons and to reduce complications. However, for the robot-assisted decompressive laminectomy, an accurate 3D model of laminae from a CT image is highly desired. The purpose of this paper is to precisely segment the laminae with fewer calculations. METHODS: We propose a two-stage neural network SegRe-Net. In the first stage, the entire intraoperative CT image is inputted to acquire the coarse segmentation of vertebrae with low resolution and the probability map of the laminar centers. The second stage is trained to refine the segmentation of laminae. RESULTS: Three public available datasets were used to train and validate the models. The experimental results demonstrated the effectiveness of the proposed network on laminar segmentation with an average Dice coefficient of 96.38% and an average symmetric surface distance of 0.097 mm. CONCLUSION: The proposed two-stage network can achieve better results than those baseline models in the laminae segmentation task with less calculation amount and learnable parameters. Our methods improve the accuracy of laminar models and reduce the image processing time. It can be used to provide a more precise planning trajectory and may promote the clinical application for the robot-assisted decompression laminectomy surgery.

Synergy of ferroelectric polarization and oxygen vacancy to promote CO2 photoreduction.

Solar-light driven CO2 reduction into value-added chemicals and fuels emerges as a significant approach for CO2 conversion. However, inefficient electron-hole separation and the complex multi-electrons transfer processes hamper the efficiency of CO2 photoreduction. Herein, we prepare ferroelectric Bi3TiNbO9 nanosheets and employ corona poling to strengthen their ferroelectric polarization to facilitate the bulk charge separation within Bi3TiNbO9 nanosheets. Furthermore, surface oxygen vacancies are introduced to extend the photo-absorption of the synthesized materials and also to promote the adsorption and activation of CO2 molecules on the catalysts' surface. More importantly, the oxygen vacancies exert a pinning effect on ferroelectric domains that enables Bi3TiNbO9 nanosheets to maintain superb ferroelectric polarization, tackling above-mentioned key challenges in photocatalytic CO2 reduction. This work highlights the importance of ferroelectric properties and controlled surface defect engineering, and emphasizes the key roles of tuning bulk and surface properties in enhancing the CO2 photoreduction performance.

Synergistic Polarization Engineering on Bulk and Surface for Boosting CO2 Photoreduction.

Sluggish charge kinetics and low CO2 affinity seriously inhibit CO2 photoreduction. Herein, the synchronous promotion of charge separation and CO2 affinity of Bi4 Ti3 O12 is realized by coupling corona poling and surface I-grafting. Corona poling enhances ferroelectric polarization of Bi4 Ti3 O12 by aligning the domains direction, which profoundly promotes charge transfer along opposite directions across bulk. Surface I-grafting forms a surface local electric field for further separating charge carriers and provides abundant active sites to enhance CO2 adsorption. The two modifications cooperatively further increase the ferroelectric polarization of Bi4 Ti3 O12 , which maximize the separation efficiency of photogenerated charges, resulting in an enhanced CO production rate of 15.1 µmol g-1 h-1 (nearly 9 times) with no sacrificial agents or cocatalysts. This work discloses that ferroelectric polarization and surface ion grafting can promote CO2 photoreduction in a synergistic way.

Tenacissoside H Induces Autophagy and Radiosensitivity of Hepatocellular Carcinoma Cells by PI3K/Akt/mTOR Signaling Pathway.

Tenacissoside H (TEH), which has anti-inflammatory and anti-tumor effects, is a major active ingredient extracted from the stem of Marsdenia tenacissima. However, the effect of TEH on hepatocellular carcinoma (HCC) as well as the underlying mechanisms are still indistinct. Presently, HCC cells (including Huh-7 and HepG2) were dealt with different concentrations of TEH. The proliferation and apoptosis of HCC cells were determined via Cell Counting Kit-8 (CCK8) assay and flow cytometry. In addition, Western blot was conducted to evaluate the expressions of autophagy-and apoptosis-related proteins. Tissue immunofluorescence was carried out to evaluate LC3B expression in the tumor tissues. The data showed that TEH suppressed the growth of HCC cells in a concentration-dependent manner. Besides, TEH enhanced radiosensitivity and promoted the apoptosis of HCC cells. Moreover, the mRNA and protein levels of autophagy-related genes (LC3-II/LC2-I, ATG5, Beclin-1) were significantly promoted by TEH. Mechanistically, TEH attenuated the activation of PI3K/Akt/mTOR signaling pathway. However, inhibition of PI3 K pathway abolished the anti-tumor effects of TEH in HCC cells. Collectively, this study suggested that TEH increases the radiosensitivity of HCC cells via inducing autophagy and apoptosis through downregulating PI3K/Akt/mTOR signaling pathway.

Evaluation of Biological Mechanisms of Eucommiae Folium in Hypertensive Kidney Injury by Integration of Untargeted Metabolomics and Network Pharmacology.

Hypertensive kidney injury (Hki) is one of the most common complications of hypertension. Early prevention and treatment of renal injury in patients with hypertension is great significance. The study, which used an integrated ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS) analysis, network pharmacology approach, and plasma metabolomics, aimed to discover the active ingredients and therapeutic mechanisms of Eucommiae folium (Ef) in treating Hki. The chemical components of Ef were analyzed by UPLC-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS), and the "compound-target-disease" network was constructed by screening the closely related drug targets from the drug-target database, then the signaling pathways related to Hki were analyzed. Finally, the enzyme-linked immunosorbent assay (ELISA) and real-time quantitative reverse-transcription polymerase chain reaction were used to test and verify the key targets in the common pathways of metabolomics and network pharmacology. The results indicated that Eucommiae folium might play an excellent role in treating Hki, likely through regulating the vascular endothelial growth factor signaling pathway, hypoxia inducible factor 1 (HIF-1) signaling pathway, and glycerophospholipid metabolism pathway, which were validated by increasing levels of nitric oxide, endothelial nitric oxide synthase and reducing levels of endothelin 1, angiotensin II, renin, cyclic guanosine monophosphate, blood urea nitrogen, and serum creatinine, as well as the reduced gene expression of Ache, Ddah2, Egfr, Lcat, Pla2g2a, Stat3 and Vegfa. The study systematically explored the protective mechanisms of Ef against Hki and also provided the practical treatment strategies of Hki from the Chinese herb.