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Polyphyllin II (PPII) has been proven to have significant anti-liver cancer activity, but its application is limited by poor solubility, low bioavailability, and systemic toxicity caused by non-selectivity. To address the above problem, PPII was encapsulated into the Poly (lactic-co-glycolic acid) (PLGA) by precipitation method (PPII-NPs) for hepatocellular carcinoma treatment. Subsequently, Box–Behnken design (BBD) with three variables-three levels (33) was utilized to optimize the PPII-NPs formulation. Under optimal conditions, the drug loading of nanoparticles reached 7.29 ± 0.08% and encapsulation efficiency was 80.98 ± 1.63%. Furthermore, aptamer AS1411 was adopted to enhance the tumor-targeting ability of nanoparticles (Apt/PPII-NPs). The drug loading of Apt/PPII-NPs was 6.25 ± 0.26%, had a spherical shape with a rough surface, a particle size of 252.3 ± 3.6 nm, and showed good slow-release performance and stability. In vitro, assays showed that the targeted modified nanoparticles had significant tumor selectivity and exerted efficient anti-tumor effects by inducing tumor cell apoptosis via the mitochondrial apoptotic pathway and death‐receptor pathway. In vivo, anti-tumor evaluation further demonstrated Apt/PPII-NPs not only effectively inhibited the growth of tumors, but also reduced PPII damage to normal tissues. In summary, this report strongly illustrated the advantages of a targeted nanoparticle platform for providing a solution for the rational application of PPII and improving the therapeutic effect of hepatocellular carcinoma.

Abstract Vitrification is widely recognized as a promising method for the geological disposal of high-level radioactive waste (HLW) worldwide. To ensure the safe disposal of radioactive waste, the borosilicate glass that vitrifies HLW must exhibit exceptional water resistance to prevent the possibility of groundwater corrosion and subsequent radioactive leaks. Radiation might change the water resistance of borosilicate glass. A series of zirconium-containing borosilicate glass with an irradiation dose of 0.3 dpa were utilized to examine the radiation effect on glass-water interaction. Scanning electron microscopy (SEM), Time-of-Flight Secondary ion mass spectrometry (ToF-SIMS), X-ray photoelectron spectroscopy (XPS), Inductively Coupled Plasma Optical Emission spectroscopy (ICP-OES) and Fourier transform infrared spectroscopy (FTIR) were used to investigate the leaching behavior of the non- and irradiated samples. The depth profile of the leached samples implied the interdiffusion dominated glass-water interaction. The results from FTIR and ICP-OES indicated that, after irradiation, the initial leaching rate increased by threefold. Additionally, the impact of different zirconium contents on the water resistance of borosilicate glass was also presented.

FeCrAl ODS steel is the promising candidate cladding material for the accident tolerant fuel (ATF) of the light water reactors (LWR), due to the formation of Al2O3 in alloys which could suppress the oxidation reaction with hot steam. In the present work, change in microstructures and the corresponding irradiation hardening of two kinds of FeCrAl ODS alloys (15.5Cr-4Al), with 0.6 wt% Zr (denoted as P1) or 0.8 wt% Hf addition (denoted as P2), were investigated. Electron backscattered diffraction (EBSD) and transmitted electron microscopy (TEM) were used to characterize grains and dispersion morphology of oxides, respectively. Compared to P1, P2 has finer and denser oxides. 56Fe17+ ions with kinetic energy of 352.8 MeV were used to produce a quasi-uniformly distributed damage region from the near-surface to a depth of 24 μm in the specimens by using an energy degrader. A damage level of 0.8 dpa (displacement per atom) was attained in the specimens of both alloys simultaneously at 200℃. The Vickers hardness test shows that both specimens exhibited an apparent irradiation hardening. The extent of hardening of P2 (6 %) is significantly lower than P1 (12 %). TEM results show that irradiation-induced dislocation loops occur in both specimens but with a relatively smaller average size in P2. The results demonstrate that compared to the 0.6 wt% Zr addition, the 0.8 wt% Hf addition improves more significantly the hardening resistance, which was discussed in terms of the calculated sink strength originating from the oxides/matrix interface.

This work studies the defect features in a dilute FeMnNi alloy by an Object Kinetic Monte Carlo (OKMC) model based on the ''grey-alloy'' method. The dose rate effect is studied at 573 K in a wide range of dose rates from 10−8 to 10−4 displacement per atom (dpa)/s and demonstrates that the density of defect clusters rises while the average size of defect clusters decreases with increasing dose rate. However, the dose-rate effect decreases with increasing irradiation dose. The model considered two realistic mechanisms for producing -type self-interstitial atom (SIA) loops and gave reasonable production ratios compared with experimental results. Our simulation shows that the proportion of -type SIA loops could change obviously with the dose rate, influencing hardening prediction for various dose rates irradiation. We also investigated ways to compensate for the dose rate effect. The simulation results verified that about a 100 K temperature shift at a high dose rate of 1 × 10−4 dpa/s could produce similar irradiation microstructures to a lower dose rate of 1 × 10−7 dpa/s irradiation, including matrix defects and deduced solute migration events. The work brings new insight into the OKMC modeling and the dose rate effect of the Fe-based alloys.

Abstract Background Chronic obstructive pulmonary disease (COPD) is one of the major health issues worldwide. Pathophysiological changes in COPD are mainly reflected in the deterioration of lung function with aging. Methods Considering that telomere length is a hallmark of biological aging, we first performed a meta-analysis to summarize the current knowledge about the relationship between telomere length and COPD and then employed individual-level data from the continuous National Health and Nutrition Examination Survey (NHANES) to investigate whether telomere length could reflect accelerated aging in COPD and serve as an independent predictor. A mediation study was further performed to examine whether the association between telomeres and COPD could be mediated by inflammation, as one of the most important etiologies and characteristics of COPD. Results The four studies included in our meta-analysis were with high heterogeneity (I2 = 95.7%, P het

Aims: The study aimed to evaluate the correlation of different microparticle (MP) phenotypes with plaque burden and their diagnostic value and preliminarily explore the role of MPs in atherosclerosis (AS).Methods: Carotid intima-media thickness (CIMT) and maximal plaque area in 23 patients with carotid atherosclerosis (CAS) and 22 healthy subjects were measured by ultrasound. Transmission electron microscopy, nanoparticle tracking analysis and western blot were used to identify MPs. Flow cytometry assay measured absolute number of MPs, and receiver operating characteristic (ROC) analysis was used to assess the relationship between plaque burden and MPs. To study the preliminary mechanism of MPs in AS, MPs were administered to 32 male Kunming mice, which were randomly divided into control, CAS, healthy, and tetrahydrobiopterin (BH4) groups. Hematoxylin-eosin staining, immunohistochemistry staining, and Western blot were adopted to detect relevant indexes 24 h after the injection.Results: The plasma levels of CD45+ leukocyte-derived microparticle (LMP), CD11a+ LMP, CD11a+/CD45+ LMP, and CD31+/CD42b+ platelet-derived microparticle (PMP) in CAS patients were significantly higher than those in healthy subjects, and were positively correlated with the maximal plaque area. Moreover, the levels of CD11a+ LMP, CD11a+/CD45+ LMP were also positively correlated with CIMT. The area under the ROC curve of the four MPs was 0.689, 0.747, 0.741, and 0.701, respectively. Compared with healthy subjects, MPs from CAS patients resulted in a significantly lower expression of endothelial nitric oxide synthase (eNOS) dimer/monomer, and BH4 could improve eNOS uncoupling. Moreover, the level of VCAM-1 in intima in the CAS group was significantly higher than in the other three groups.Conclusion: CD11a+ LMP and CD11a+/CD45+ LMP might be potential biomarkers for CAS prediction. BH4-related eNOS uncoupling occurs in CAS patients, and circulating MPs from them lead to endothelial dysfunction through eNOS uncoupling.

BackgroundAlthough studies have shown that cell pyroptosis is involved in the progression of asthma, a systematic analysis of the clinical significance of pyroptosis-related genes (PRGs) cooperating with immune cells in asthma patients is still lacking.MethodsTranscriptome sequencing datasets from patients with different disease courses were used to screen pyroptosis-related differentially expressed genes and perform biological function analysis. Clustering based on K-means unsupervised clustering method is performed to identify pyroptosis-related subtypes in asthma and explore biological functional characteristics of poorly controlled subtypes. Diagnostic markers between subtypes were screened and validated using an asthma mouse model. The infiltration of immune cells in airway epithelium was evaluated based on CIBERSORT, and the correlation between diagnostic markers and immune cells was analyzed. Finally, a risk prediction model was established and experimentally verified using differentially expressed genes between pyroptosis subtypes in combination with asthma control. The cMAP database and molecular docking were utilized to predict potential therapeutic drugs.ResultsNineteen differentially expressed PRGs and two subtypes were identified between patients with mild-to-moderate and severe asthma conditions. Significant differences were observed in asthma control and FEV1 reversibility between the two subtypes. Poor control subtypes were closely related to glucocorticoid resistance and airway remodeling. BNIP3 was identified as a diagnostic marker and associated with immune cell infiltration such as, M2 macrophages. The risk prediction model containing four genes has accurate classification efficiency and prediction value. Small molecules obtained from the cMAP database that may have therapeutic effects on asthma are mainly DPP4 inhibitors.ConclusionPyroptosis and its mediated immune phenotype are crucial in the occurrence, development, and prognosis of asthma. The predictive models and drugs developed on the basis of PRGs may provide new solutions for the management of asthma.

High levels of M2 macrophage infiltration invariably contribute to poor cancer prognosis and can be manipulated by metabolic reprogramming in the tumor microenvironment. However, the metabolism-related genes (MRGs) affecting M2 macrophage infiltration and their clinical implications are not fully understood. In this study, we identified 173 MRGs associated with M2 macrophage infiltration in cases of gastric cancer (GC) using the TCGA and GEO databases. Twelve MRGs were eventually adopted as the prognostic signature to develop a risk model. In the high-risk group, the patients showed poorer survival outcomes than patients in the low-risk group. Additionally, the patients in the high-risk group were less sensitive to certain drugs, such as 5-Fluorouracil, Oxaliplatin, and Cisplatin. Risk scores were positively correlated with the infiltration of multiple immune cells, including CD8+ T cells and M2 macrophages. Furthermore, a difference was observed in the expression and distribution between the 12 signature genes in the tumor microenvironment through single-cell sequencing analysis. In vitro experiments proved that the M2 polarization of macrophages was suppressed by Sorcin-knockdown GC cells, thereby hindering the proliferation and migration of GC cells. These findings provide a valuable prognostic signature for evaluating clinical outcomes and corresponding treatment options and identifying potential targets for GC treatment.

The pathogenesis of allergic asthma is complex, it is usually caused by immune system imbalance. Th1, Th2, regulatory T cells (Treg) and T helper 17 (Th17) cells have an important role in the pathogenesis of eosinophilic asthma. Yet, the exact role of Th1, Th2, Treg and Th17 cells in eosinophilic asthmatic disease is not fully understood. This study used an untargeted plasma metabolomics combine 16S rDNA technology to identify new biomarkers of plasma metabolites and gut microbiota in ovalbumin-induced eosinophilic allergic asthma in BALB/c mice to further explore the biomarkers in regulating the immune balance or the immune response. We discovered that malate, l-dihydroorotate were associated with Th1/Th2 and Treg/Th17 cells balance, imidazoleacetic acid was associated with Th1/Th2 cell balance, 1,5-anhydro-d-sorbitol was associated with Treg/Th17 cell balance. The results also found that genus Candidatus Arthromitus of gut microbiota were associated with Th1/2, Treg/Th17 balance, genus Ruminiclostridium 6, they were all associated with Th1/2 and Treg/Th17 cell balance, while the gut microbiota were not associated with penh value which reflect airway hyperresponsiveness (AHR) in the eosinophilic asthma mice model. Interestingly, the plasma metabolite biomarkers of malate, l-dihydroorotate are associated with genus Ruminiclostridium 6, they were all associated with Th1/2 and Treg/Th17 cell balance, while imidazoleacetic acid is associated with genus Ruminiclostridium 6 which is associated with Th1/2 balance. Among the differential plasma metabolites, 1,5-anhydro-d-sorbitol is associated with genus Ruminiclostridium 6 and genus Candidatus Arthromitus. Among them, malate participate in the T cell activation, T cell differentiation and activation may be a new research direction in eosinophilic allergic asthma. We firstly study the gut microbiota and plasma metabolites markers of immune balance in eosinophilic asthma in mice model, laying a foundation for drug treatment in eosinophilic allergic asthma.

Tuo-Min-Ding-Chuan decoction (TMDCT) is a Traditional Chinese Medicine (TCM) formula consisting of twelve herbs that can relieve the symptoms and treat allergic asthma. Yet, the underlying mechanism of action is still unclear. In this study, we investigated the effect of TMDCT in regulating Treg/Th17 cells immune balance and explored potential metabolic and gut biomarkers associated with Treg and Th17 cells in eosinophilic asthma mice treated by TMDCT. We found that TMDCT increases Treg cells percentage and decreases Th17 cells percentage in the ovalbumin (OVA) -induced eosinophilic asthma mice model. Furthermore, Imidazoleacetic acid, dL-glutamine, L-pyroglutamic acid, 2-deoxy-d-glucose were preliminary identified as biomarkers in plasma metabolites treated by TMDCT, meanwhile genus Desulfovibrio, genus Butyricimonas and genus Prevotella 9 were preliminary identified as gut microbiota biomarkers after TMDCT treatment. These results provide an experimental foundation for the treatment of allergic asthma with Chinese herbal compounds.

Objective: In this study, we used HepG2 human hepatocellular carcinoma cells to study the effects of Compound Xishu Granule (CXG) on cell proliferation, apoptosis, and the cell cycle in vitro. We also used a xenograft tumor model to study the anti-tumor effects of CXG and related mechanisms in vivo. Methods: The effect of CXG on cell viability was measured using Cell Counting Kit-8 and a colony formation assay. The effect of CXG on apoptosis and the cell cycle was analyzed using flow cytometry. The in vivo anti-tumor effect of CXG was assessed by measuring the volume change in xenograft tumors after drug administration. The CXG anti-tumor mechanism was studied using western blotting assay to detect cell cycle and apoptotic associated proteins. Results: CXG suppressed HepG2 cell proliferation in a time- and dose-dependent manner in vitro. Colony formation experiments showed that CXG administration for 24 h significantly reduced HepG2 cell formations (P

Background: “Treating the same disease with different methods” is a Traditional Chinese medicine (TCM) therapeutic concept suggesting that, while patients may be diagnosed with the same disease, they may also have different syndromes that require distinct drug administrations.Objective: This study aimed to identify the differentially expressed genes and related biological processes in dyslipidemia in relation to phlegm–dampness retention (PDR) syndrome and spleen and kidney Yang deficiency (SKYD) syndrome using transcriptomic analysis.Methods: Ten ApoE−/− mice were used for the establishment of dyslipidemic disease–syndrome models via multifactor-hybrid modeling, with five in the PDR group and five in the SKYD group. Additionally, five C57BL/6J mice were employed as a normal control group. Test model-quality aortic endothelial macrophages in mice were screened using flow cytometry. Transcriptomic analysis was performed for macrophages using RNA-Seq.Results: A quality assessment of the disease–syndrome model showed that levels of lipids significantly increased in the PDR and SKYD groups, compared to the normal control group, p < 0.05. Applying, in addition, hematoxylin and eosin staining of aorta, the disease model was also successfully established. A quality assessment of the syndrome models showed that mice in the PDR group presented with typical manifestations of PDR syndrome, and mice in the SKYD group had related manifestations of SKYD syndrome, indicating that the syndrome models were successfully constructed as well. After comparing the differentially expressed gene expressions in macrophages of the dyslipidemic mice with different syndromes, 4,142 genes were identified with statistical significance, p < 0.05. Gene ontology analysis for the differentially expressed genes showed that the biological process of difference between the PDR group and the SKYD group included both adverse and protective processes.Conclusion: The differentially expressed genes between PDR syndrome and SKYD syndrome indicate different biological mechanisms between the onsets of the two syndromes. They have distinctive biological processes, including adverse and protective processes that correspond to the invasion of pathogenic factors into the body and the fight of healthy Qi against pathogenic factors, respectively, according to TCM theory. Our results provide biological evidence for the TCM principle of “treating the same disease with different treatments.”

Multiple myeloma (MM) is a tumor type characterized by the unregulated proliferation of clonal plasma cells in the bone marrow. Immunotherapy based on chimeric antigen receptor T cell (CAR-T) therapy has achieved exciting success in the treatment of hematological malignant tumors. CD38 is highly and evenly expressed in MM and is an attractive target for MM treatment. Here, we successfully constructed two novel second-generation CAR-T cells targeting CD38 by retroviral vector transduction. CD38 CAR-T cells could be activated effectively after stimulation with CD38-positive tumor cells and secrete cytokines such as IFN-γ and TNF-α to promote tumor cell apoptosis in in vitro experiments. Real-time fluorescence monitoring experiments, luciferase detection experiments and flow cytometry experiments revealed the efficient and specific killing abilities of CD38 CAR-T cells against CD38-positive tumor cells. The proliferation ability of CD38 CAR-T cells in vitro was higher than that of untransduced T cells. Further antitumor experiments in vivo showed that CD38 CAR-T cells could be quickly activated to secrete IFN-γ and eliminate tumors. Thus, novel CD38-targeted second-generation CAR-T cells have efficient and specific antitumor activity and may become a novel therapy for the clinical treatment of MM.

Allergic diseases are significant diseases that affect many patients worldwide. In the past few decades, the incidence of allergic diseases has increased significantly due to environmental changes and social development, which has posed a substantial public health burden and even led to premature death. The understanding of the mechanism underlying allergic diseases has been substantially advanced, and the occurrence of allergic diseases and changes in the immune system state are known to be correlated. With the identification and in-depth understanding of innate lymphoid cells, researchers have gradually revealed that type 2 innate lymphoid cells (ILC2s) play important roles in many allergic diseases. However, our current studies of ILC2s are limited, and their status in allergic diseases remains unclear. This article provides an overview of the common phenotypes and activation pathways of ILC2s in different allergic diseases as well as potential research directions to improve the understanding of their roles in different allergic diseases and ultimately find new treatments for these diseases.

Middle cerebral artery occlusion (MCAO), with the characteristics of high morbidity, high recurrence rate, high mortality, and disability rate, is a typical manifestation of ischemic stroke and has become a hot research topic in the clinical field. The protective effects of nuciferine on brain injury MCAO rats were investigated and its mechanisms of actions were revealed. The MCAO rats were established by the suture method. The pathological staining of the rat brain was processed and observed, the pharmacodynamics assay of nuciferine were studied, and the gene expression regulation by nuciferine was detected by transcriptome technology. The results showed that nuciferine significantly alleviated brain damage in MCAO rats, and the transcriptomic results suggested that nuciferine could exert therapeutic effects through the regulation of lipid metabolism, including arachidonic acid metabolism, sphingolipid metabolism, the PPAR signaling pathway and other related pathways. This finding provided new perspectives on the treatment of MCAO with nuciferine and facilitates the development of novel drugs for this disease.

As Beryllium is an important element in primary nucleosynthesis, its nuclear reaction cross-sections induced by charged projectiles need to be measured precisely. The astrophysical S(Ei) factors were measured in the ultra-low energy range from Elab=18 to 100 keV in 2-keV increments (42 points). Both the astrophysical S(E) curve (Sbare(0)=16.2±1.8MeVb) and the screening energy (Us=545±98eV) were deduced. In regard to astrophysical applications of the Sbare(E) curve, the present results are consistent with Zahnow's direct measurement. For the long-standing problem of ‘abnormal’ screening effect, our screening energy result also agrees with that obtained using the Trojan-horse method (Us=676±86eV) but smaller than Zahnow's value (900±50eV), although all results are much larger than that obtained in the adiabatic limit (∼264 eV). Keywords: p–9Be reaction, Screening potential, Astrophysical factor

The incidence of type 1 diabetes mellitus (T1DM) is increasing year by year, gut microbiota is considered to be closely related to the occurrence and development of T1DM in recent years. In this study, Sprague Dawley (SD) rats were intraperitoneally injected with 75mg/kg streptozotocin to establish T1DM model, fecal samples were collected and DNA were extracted, 16S rRNA microbial gene clone library were constructed, and lastly high-throughput sequencing and bioinformatics analysis were performed. The results showed that the abundances of pathogenic bacteria such as Ruminococcaceae, Shigella, Enterococcus, Streptococcus, Rothia and Alistipes associated with infection and inflammation in T1DM rats were up-regulated, while the abundances of beneficial bacteria such as Lactobacillus, Faecalitalea, Butyricicoccus and Allobaculum were reduced. Among them, Butyricicoccus and Allobaculum protect intestinal barrier function by producing short-chain fatty acids. This study suggests that intestinal inflammation and reduction of short chain fatty acids (SCFAs) caused by the imbalance of gut microbiota are crucial to the pathogenesis of T1DM.

Objective: Yiqi Jiedu (YQJD) decoction is a Chinese herbal prescription, based on an experienced expert of traditional Chinese medicine. It is used for the injuries caused by radiotherapy. The current study was designed to investigate the protective effects of YQJD decoction on radiation damage of testis in mice, and to explore its potential mechanisms. Methods: Mice were randomly divided into blank control group (Ctrl), model group (IR), positive drug group (IRA), and YQJD decoction group (IRY). After 10-day period intervention, they were whole-body irradiated with 2 Gy 60Co γ-rays and sacrificed on 7th day after irradiation. The indicators including the index and histopathology examination of testis, spermatogenic cell types and apoptosis, and the expression of TLR5, MyD88, NF-κB, TNF-α, IL-6 and Bcl-2 in testis. Results: The testis atrophied significantly on 7th day of exposure to radiation, while YQJD decoction promoted the recovery of testis index and structure. Moreover, spermatogenic cell types and apoptosis had significant changes after irradiation. YQJD decoction protected the testicular function of spermatogenesis, as while as reduced the apoptosis rate of spermatogenic cells. In addition, RT-PCR and immunohistochemical analysis showed that YQJD decoction up-regulated the expression of TLR5 in testis. The levels of TLR5's downstream factors were also up-regulated in YQJD decoction group, which indicated that TLR5 signaling pathway might play an important role in the protective effects of YQJD decoction. Conclusions: The results showed that YQJD decoction attenuated irradiation induced testis injury in mice. Its potential mechanism was related to TLR5 signaling pathway.

With the improvement of people's living standard and the changes of environment, the incidence of diabetes mellitus (DM) is on the rise day by day, while clinical treatment mainly aims at lowering blood glucose, instead of fundamental prevention and treatment. What's worse, the measures of prevention and treatment of DM complications remain inadequate. Both Chinese and modern medicine have advantages and disadvantages in treating DM, therefore, it would be a worthy attempt to break through the bottleneck of DM treatment by combining the advantages of both, and explore the new measures to prevent and deal with DM from the perspective of the combination of Traditional Chinese Medicine (TCM) syndrome and modern medicine. In this paper, modern research methods and possible indicators of TCM syndromes of DM were expounded from clinical and basic research aspects, aiming to find specific biomarkers of TCM syndromes, and providing experimental supports for the diagnosis and treatment of DM and the verification of TCM theory.

Investigating the irradiation effects on borosilicate glass is of great significance for understanding the long-term evolutions of this substance in radioactive environments. In the present study, the hardness and modulus of conventional and ion-irradiated borosilicate glass were investigated through nanoindentation measurements. The obtained results show that the maximum decrease of the mean hardness after He and Ar ion irradiation was 8.4% and 17.0%, respectively, when the fluence reached 1.1 × 1015. It was found that the hardness reduction had a significant ionic correlation. Meanwhile, it was observed that the mean modulus increased by less than 5.0%, while there was no meaningful ionic correlation. The variation in hardness and modulus were primarily the consequence of nuclear energy deposition. The hardness recovery was observed under Ar-irradiated and He-irradiated Ar pre-damaged samples. It was concluded that the hardness recovery mainly originates from electronic energy deposition induced by ion irradiation.

Hypertension is one of the most common cardiovascular diseases, resulting in serious complications such as cardiovascular damage and chronic kidney disease. Tianshu capsule (TSC), composed of Chuanxiong (Ligusticum chuanxiong Hort) and Tianma (Gastrodiaelata Blume), has been widely used to treat the blood stasis type of headache and migraine in clinic. Results of previous research showed its antihypertensive effects, but the underlying mechanisms were still unclear. The purpose of this study was to evaluate the antihypertensive effect of TSC on spontaneously hypertensive rats by 1H NMR-based metabonomics and enzyme-linked immunosorbent assay (ELIAS), explore potential biomarkers and targets, and probe the potential mechanism of TSC on antihypertensive treatment. The results showed that TSC could decrease the product of oxidative stress (MDA) and enhance the activities of SOD and GSH-Px, down-regulate the expression of enzymes (LDHA, PKM2 and HK2) related to glycolysis, and perturb the levels of a series of amino acids (isoleucine, alanine, asparagine, citrate, etc.) and pathways. Multivariate statistical analyses showed remarkable changes in some endogenous metabolites after administrating TSC related to oxidative stress, amino acid metabolism and energy metabolism disturbances. Some enzymes (alanine-glyoxylate aminotransferase-2, tyrosine hydroxylase, dopa decarboxylase, etc.) related to metabolic biomarkers were predicted as the potential targets of TSC treatment on SHRs. The discoveries are helpful to understand the antihypertensive mechanism of TSC and provide theoretical evidence for its future research, development and clinical use.

TFDP3, also be known as HCA661, was one of the cancer-testis antigens, which only expressed in human tissues. The recent researches about TFDP3 mostly focused on its ability to control the drug resistance and apoptosis of tumor cells. However, the role of TFDP3 in the progress of the cell cycle is rarely involved. In this study, we examined the expression of TFDP3 in human liver tissues firstly. After that, we detect the expression of TFDP3 at the RNA level and protein level in L-02 cell line and HepG2 cell line, and the location of TFDP3 was defined by immunofluorescence technique. Furthermore, we synchronized the cells to G1 phase, S phase and G2 phase, and arrested cell mitosis. The localization of TFDP3 and co-localization with E2F1 molecules in different phases of hepatocyte lines. Finally, TFDP3 gene knockout was performed on L-02 and HepG2 cell lines, and detected the new cell cycles by flow cytometry. The result showed that the expression of TFDP3 molecule is negative in normal liver tissue, but positive in immortalized human hepatocyte cell line, and the expression level is lower than in hepatocellular carcinoma cell line. The expression level of TFDP3 was in the dynamic change of L-02 and HepG2 cell lines, and was related to the phase transition. TFDP3 can bind to E2F1 molecule to form E2F/TFDP3 complex; and the localizations of TFDP3 and E2F1 molecules and the co-localization were different in different phases of cell cycle in the nucleus and cytoplasm, which indicated that the E2F/TFDP3 complex involved in the process of regulating the cell cycle. By knocking down the TFDP3 expression level in L-02 and HepG2 cell lines, the cell cycle would be arrested in S phase, which confirmed that TFDP3 can be a potential target for tumor therapy.