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Yu Chen,1 Ruohuang Lu,2 Yang Wang,3 Pingping Gan1 1Department of Oncology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Department of Stomatology, Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 3Department of Integrated Traditional Chinese and Western Medicine, Institute of Integrative Medicine, Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Pingping Gan, Department of Oncology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China, Tel +86 13874975101, Email gppxy@csu.edu.cnPurpose: Paclitaxel-induced peripheral neuropathy (PIPN) is increasingly becoming one of the most widespread adverse effects in the treatment of cancer patients, and further precipitate neuroinflammation in the nervous system. Interestingly, Shaoyao Gancao Decoction (SGD), a traditional Chinese analgesic prescription, has emerged as a primary adjuvant to chemotherapy in relieving side effects, especially in the case of PIPN. However, the underlying mechanism of SGD functioning in PIPN remains elusive. Accordingly, the current study set out to explore the potential axis implicated in the functioning of SGD in PIPN.Methods: First, network pharmacology was adopted to predict the role of the transient receptor potential vanilloid type 1 (TRPV1) protein in treating PIPN with SGD. Subsequently, the effects of SGD treatment on mechanical allodynia and thermal hyperalgesia were evaluated in rat PIPN models. Based on the bioinformatics information and current literature, paclitaxel activates toll-like receptor 4 (TLR4) induces the sensitization of TRPV1 mechanistically. Thereafter, TLR4-myeloid-differentiation response gene 88 (MyD88) signaling and TRPV1 expression patterns in dorsal root ganglias (DRGs) were measured by means of Western blotting, qPCR and immunofluorescence.Results: Initial bioinformatics reared a total of 105 bioactive compounds and 1075 target genes from SGD. In addition, 40 target genes intersected with PIPN were considered as potential therapeutic genes. Based on the network analysis, SGD was found to exert its analgesic effect by reducing the expression of TRPV1. Further experimentation validated that SGD exerted an analgesic effect on thermal hyperalgesia in PIPN models, such that this protective effect was associated with the suppression of TRPV1 and TLR4-MyD88 Signaling over-expression.Conclusion: Collectively, our findings indicated that SGD ameliorates PIPN by inhibiting the over-expression of TLR4-MyD88 Signaling and TRPV1, and further highlights the use of SGD as a potential alternative treatment for PIPN.Keywords: paclitaxel-induced peripheral neuropathy, Shaoyao Gancao Decoction, transient receptor potential vanilloid type 1, network pharmacology, paclitaxel, toll-like receptor 4

The microparticle-initiated breakdown plays a key role in the failure of gas switches and has become an active area of investigation in gas discharge recently. The mechanism of the microparticle-initiated breakdown in a 2-mm air gap is studied by experiments and simulations in this article. The dynamics of the microparticle in the electric field is obtained, and four breakdown modes are acquired from the picture of the high-speed camera. The probabilities of breakdown for the 200-, 300-, and 500- $\mu \text{m}$ Cu microparticles under different voltages are presented, and the corresponding lowest breakdown voltages reduce to 65%, 56%, and 47% of the static-breakdown voltage. The relation between the breakdown voltage and position of the microparticle is calculated based on the Townsend theory. The simulated results agree well with the experimental results. The breakdown process and evolution of the plasma are also revealed with PIC simulations.

Sharenting (using social media to share content about one’s child) is a progressively common phenomenon enabled by society’s increased connection to digital technology. Although it can encourage positive connections to others, it also creates concerns related to children’s privacy and well-being. In this paper, we establish boundaries and terminology related to sharenting in an evolving digital world. We conceptualize a modern sharenting ecosystem involving key stakeholders (parents, children, community, commercial institutions, and policymakers), by applying consumer vulnerability theory to explore the increased online connection that occurs as work, school, and socialization become increasingly more virtual. Next, we expand the characterization of sharenting by introducing a spectrum of sharenting awareness that categorizes three types of sharenting (active, passive, and invisible). Finally, we provide a research agenda for policymakers and consumer welfare researchers.

The Nuclear Science and Instrumentation Laboratory (NSIL) is currently establishing a Neutron Science Facility (NSF) based on two compact neutron generators: Deuterium-Deuterium (DD), resulting in 2.45 MeV neutrons, and Deuterium-Tritium (DT), resulting in 14.1 MeV neutrons, with maximum source intensities up to 5 × 106 n/s and 4 × 108 n/s over 4π, respectively. Neutron/X-ray radiography and tomography are two of the applications the NSF will be equipped with. In this paper, we report the state of the radiography and tomography system, and the neutron/X-ray radiography and tomography experiments we performed. Good radiographs and tomographs are obtained with X-ray. The spatial resolution of the X-ray radiography system is measured to be about 0.1 mm. The thermal neutron radiographs and fast neutron radiographs have proved that the DD neutron generator will be beneficial to demonstrate neutron radiography capabilities for educational purposes. Additionally, the detail of the collimator optimization of the DD neutron radiography was presented.

Background. Traumatic brain injury (TBI) is one of the most common neurosurgical diseases and refers to brain function impairment or brain pathological changes induced by external causes. A traditional Chinese medicine, Xuefu-Zhuyu Decoction (XFZYD), has been indicated to harbor therapeutic properties against TBI. Transfer RNA (tRNA)-derived small RNAs, that is, tsRNAs (a group of small RNAs derived from tRNAs), are multifunctional regulatory noncoding RNAs generated under pressure and implicated in the progression of TBI. Methods. A TBI model was successfully constructed using rats. We further performed sequencing and omics analyses to identify novel tsRNAs as drug targets for XFZYD therapy against TBI in the rat hippocampus. qPCR assays were used to further verify the experimental results. Gene Ontology (GO) was used to analyze the signaling pathways of downstream target genes of tsRNAs in the XFZYD-regulated TBI model. qPCR was used to detect the influence of overexpressed tsRNA mimics/inhibitors on their target genes in PC12 cells. Results. Our RNA-Seq data illustrate that 11 tsRNAs were mediated by XFZYD. The experimental data revealed AS-tDR-002004 and AS-tDR-002583 as potential targets for XFZYD therapy and showed that they influenced TBI via the cadherin signaling pathway, cocaine addiction, circadian entrainment, and the nicotine pharmacodynamics pathway. We also confirmed that Pi4kb, Mlh3, Pcdh9, and Ppp1cb were target genes of 2 XFZYD-regulated tsRNAs in the hippocampus of a rat model and PC12 cells. Furthermore, biological function analysis revealed the potential therapeutic effects of tsRNAs, and the results showed that Mapk1 and Gnai1 were related genes for XFZYD therapy against TBI. Conclusion. Our work successfully illuminates the efficiency of XFZYD in the treatment of TBI. The experimental data revealed AS-tDR-002004 and AS-tDR-002583 as potential targets for XFZYD therapy and showed that they influenced TBI via the cadherin signaling pathway, cocaine addiction, circadian entrainment, and the nicotine pharmacodynamics pathway in a TBI rat model.

Background: Traumatic brain injury (TBI) is one of the most common neurosurgical diseases which refers to brain function impairment or brain pathological changes induced by external causes. A traditional Chinese medicine, Xuefu Zhuyu Decoction (XFZYD), has been indicated to harbor therapeutic property against TBI. Transfer RNA (tRNA)-derived small RNAs i.e., tsRNAs (a group of small RNAs derived from tRNAs) are multifunctional regulatory non-coding RNAs generated under pressure and implicated in the progression of TBI.Methods: TBI model was successfully constructed by using of rats. Further using sequencing and omics to identify novel tsRNAs as drug targets for XFZYD therapy against TBI in rat hippocampus. qPCR assay was used to further verify the experimental results. GO analyzed the signaling pathways of downstream target genes of tsRNA in XFZYD regulated TBI model. qPCR was used to detect the influence of over-expressed tsRNA mimic/inhibitor on their target genes in PC12 cell.Results: Our RNA-Seq data illustrates that 11 tsRNAs were mediated by the XFZYD. The experimental data revealed AS-tDR-002004 and AS-tDR-002583 as potential targets for XFZYD therapy and influenced TBI via the cadherin signaling pathway, cocaine addiction, circadian entrainment and nicotine pharmacodynamics pathway. We also confirm that Pi4kb, Mlh3, Pcdh9, and Ppp1cb were targets genes of 2 XFZYD regulated tsRNAs in hippocampus of rat model and PC12 cells. Furthermore, biological function analysis revealing potential therapeutic effects of tsRNAs, and results found Mapk1, Gnai1 was the related genes of for XFZYD therapy against TBI.Conclusion: Our work successfully illuminates the efficiency of XFZYD for the treatment of TBI. The experimental data revealed AS-tDR-002004 and AS-tDR-002583 as potential targets for XFZYD therapy and influenced TBI via the cadherin signaling pathway, cocaine addiction, circadian entrainment and nicotine pharmacodynamics pathway in TBI rat model.

The present study aims to evaluate the feasibility, safety, and effects of the combined use of submandibular transcatheter perfusion with lingual nerve block and subcutaneous infiltration for anesthetic purposes during submandibular gland surgery. A total of 38 patients with benign tumors, who had undergone resection by submandibular gland surgery were randomly divided into 2 groups. Patients in group A were administered with submandibular anesthesia through catheter perfusion, lingual nerve block, and subcutaneous infiltration anesthesia. Patients in the group B were only treated with lingual nerve block and subcutaneous infiltration anesthesia. The submandibular gland surgery was performed within 5 minutes following anesthesia administration, after which the numerical rating scale (NRS) was evaluated before surgery, during skin incision (T1), during the pulling process of the submandibular gland (T2), during the removal of the submandibular gland (T3), and at 2, 6, 12, and 24 hours post-surgery. The dosage of analgesic drugs was also measured after surgery. The findings revealed no significant difference in NRS before surgery, at T1, 6, 12, and 24 hours after surgery (P > 0.01) while NRS was much lower in group A patients as observed at T2, T3, and 2 hours after surgery when compared with group B (P < 0.01). The combined application of submandibular transcatheter perfusion with lingual nerve block and subcutaneous infiltration can be used as an effective anesthetic method during submandibular gland surgery.

Licorice is the dried roots and rhizomes of Glycyrrhiza uralensis Fisch (Leguminosae), which is often used with paclitaxel to alleviate paclitaxel-induced pain in clinics. However, the herb–drug interaction between licorice and paclitaxel is still unknown. Our study evaluates the effects of oral licorice on the paclitaxel in rats via pharmacokinetic studies. A simple and rapid ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to determine paclitaxel in rat. SD rats were randomly divided into 3 groups of 6 animals each as follows: two groups of rats that were pretreated with a daily gavage of licorice (3 g/kg) for 1 or 14 successive days; Control group that was administered distilled water. All rats were then intravenously administered with paclitaxel (3 mg/kg). The results showed that 14 days pretreatment of licorice could decrease the area under the curve (AUC0–t) (from 7483.08 ± 528.78 to 6679.12 ± 266.56 mg/L × h) (P 0.05) and CL (from 0.36 ± 0.02 to 0.36 ± 0.01 L/h/kg) (P > 0.05). The results will contribute to better use of licorice in the adjunctive therapy and provide information to study the interaction between herbs and chemotherapy.

Backgrounds. Chaihu-Shugan-San (CSS) is a classic traditional Chinese herbal prescription for treating depression. However, the underlying mechanism of the Chinese syndrome-specific efficacy of CSS is poorly understood. Aim of the Study. From traditional Chinese medicine and pharmacogenetics perspectives, the present study aimed to investigate the antidepressant effects of CSS on a mouse model of Liver-Qi Stagnation (LQS) syndrome and its underlying mechanisms. Methods and Materials. We used two main mouse models of depressive syndromes in the study, including LQS and liver stagnation and spleen deficiency (LSSD) syndrome. Tail suspension and forced swimming tests were used to evaluate the effects of CSS on animal behaviour. The expression level of the CYP450 enzyme from liver microsomes was analysed by western blot (WB) analysis and quantitative real-time polymerase chain reaction (qRT-PCR). More specifically, we analysed the key compounds of CSS that are responsible for CYP450 regulation via bioinformatics. Ultimately, luciferase assays were employed to confirm the prediction in vitro. Results. CSS remarkably reduced the immobile time in LQS rather than in LSSD mice. Although CSS significantly upregulated CYP2C9 in mice with both syndromes, activated translation of CYP3A4 induced by CSS was only observed in the LQS group. Bioinformatics analysis revealed that the unique regulation of CYP3A4 was responsible for the effects of glycyrrhetinic acid (GA) from CSS. Further luciferase assays confirmed the enhancement of CYP3A4 expression via the pregnane X receptor (PXR) pathway in vitro. Conclusions. CSS specifically upregulates the translation of CYP3A4 via the PXR pathway in depressed LQS mice. GA, a bioactive compound that originates from CSS, contributes to this activation. This work provides novel insight into Chinese syndrome-based therapy for depression.

The proposed Compact Intense Fast NEutron Facility (CIFNEF) will have a wide range of applications, including the investigation of the exotic structure of neutron-rich nuclei, data for the nuclear fission , and the simulation of the neutron field in a star. To satisfy aims of producing high-intensity fast neutrons and forward neutrons with very low environmental background, the CIFNEF linac should have the capacity of accelerating continuous wave (CW) deuteron (D + ), hydrogen ( H 2 + ) and lithium (7Li 3 + ) beams to 2.5 MeV/u with maximum beam currents of 10 mA, 5 mA and 10 uA, respectively. Based on the above requirements, we proposed a novel compact linac using a combination of RFQ and DTL structures. The dynamics of RFQ and DTL are completed to meet all requirements and start-to-end simulation results show that the three ion species can be accelerated to the final energy with transmission efficiency above 99% as well as good beam quality with lower emittance growth. In addition, we performed error sensitivity analysis and combined error study to evaluate the error tolerance limits of the obtained design.

Alumina ceramics are widely used as high-voltage insulation material due to its good electric insulation. As we all know that the defects inside the ceramic have great impact on the insulation property of the ceramics, especially the pores. For a better understanding of the effect of the pores, we carried out the fundamental study of how the pores affect the electric field distribution inside alumina ceramics by simulation and theoretical analysis. The results showed that the electric field strength inside the pore is higher than that without any pores inside the ceramic and the increased proportion is almost constant which is not relative to the size and location of the pore.

The present study proposes a new approach for direct CO

Melanoma is an aggressive form of skin cancer characterized by rapid invasion and metastasis. CD147 is known to be functioning in cell invasion. In this study, we showed that CD147 was translocated from the cell membrane to the mitochondria in advanced melanoma. Melanoma patients with CD147 localized to the mitochondria confer a worse prognosis. The mitochondrial CD147 levels are correlated with the invasion potential of various melanoma cell lines as well as mitochondrial energy metabolism. Depletion of CD147 decreased the activity of mitochondrial complex V. STRING analysis for protein-protein interaction networks (PPIN) in CD147-depleted melanoma cells showed that mitochondrial proteins HSP60 and ATP5B, a subunit of mitochondrial complex V, were node proteins. HSP60 upregulation was correlated with a worse prognosis of melanoma patients. Co-immunoprecipitation (Co-IP) assay indicates that CD147 interacts with HSP60. These data suggested that mitochondrial CD147 may prompt HSP60 to activate ATP5B, thereby promoting the mitochondrial aerobic oxidation and the invasive abilities of melanoma cells. Correlation analysis of the data acquired from patients was helpful to draw a 5-year survival curve for patients who screened positive and negative for mitochondrial CD147. This study unravels the function of CD147 in tumor invasion and highlights it as a potential tumor therapeutic target.

Background: We aimed to preserve parotid function in patients with buccal carcinoma by applying a new surgical protocol based on reconstruction of parotid ductal defect with submandibular gland duc...

For a high-current Radio Frequency Quadrupole (RFQ) accelerator, space charge will strongly affect the stability of beams, which brings challenges and difficulties to the beam dynamics design. For an in-depth study of this space charge effect, a project has been proposed by Peking University and the Institute of Modern Physics of the Chinese Academy of Sciences. This project requires a 162.5 MHz RFQ to accelerate a 100-mA continuous-wave (CW) proton beam to 3 MeV. The beam dynamics design of this RFQ is based on the four-section procedure with improved radial focusing strength along the RFQ. We have investigated the relationship between limiting current and beam transmission to analyze the reasons for emittance growth and beam loss. We have also carried out an irradiation experiment based on this beam dynamics design to study the irradiation damage of the electrode surface, as this can be one main reason for reduced transmission or unstable operation that most existing high-current RFQs encounter after long-time operation. The results show that low-energy beam losses need to be kept as low as possible to prolong the life of the RFQ electrodes. The final simulated transmission efficiency reached 99.8%, as confirmed by the code toutatis .

// Dandan Feng 1 , Zian Xia 1 , Jing Zhou 1 , Hongmei Lu 2 , Chunhu Zhang 1 , Rong Fan 1 , Xingui Xiong 1 , Hanjin Cui 1 , Pingping Gan 3 , Wei Huang 1 , Weijun Peng 4 , Feng He 5 , Zhiming Wang 5 , Yang Wang 1 and Tao Tang 1 1 Institute of Integrative Chinese Medicine, Xiangya Hospital, Central South University, Changsha 410008, P.R. China 2 Research Center of Modernization of Traditional Chinese Medicines, College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, P.R. China 3 Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, P.R. China 4 Department of Integrated Chinese and Western Medicine, The Second Xiangya Hospital, Central South University, Changsha 410011, P.R. China 5 Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha 410008, P.R. China Correspondence to: Yang Wang, email: wangyang_xy87@csu.edu.cn Tao Tang, email: falcontang@126.com Keywords: metabolomics, acute traumatic brain injury, traditional Chinese medicine, Xuefu Zhuyu Decoction, gas chromatography/mass spectrometry Received: February 21, 2017 Accepted: September 03, 2017 Published: October 16, 2017 ABSTRACT Xuefu Zhuyu Decoction (XFZY), an important traditional Chinese herbal formula, has been reported effective on traumatic brain injury (TBI) in rats. However, its cerebral protection mechanism has not been clarified at the metabolic level. This work aims to explore the global metabolic characteristics of XFZY in rats during the acute phase of TBI on days 1 and 3. A plasma metabolomics method based on gas chromatography-mass spectrometry coupled with univariate analysis and multivariate statistical analysis was performed in three groups (Sham, Vehicle, XFZY). Then, a pathway analysis using MetaboAnalyst 3.0 was performed to illustrate the pathways of therapeutic action of XFZY in TBI. XFZY treatment attenuates neurological dysfunction and cortical lesion volume post-injury on day 3, and reverses the plasma metabolite abnormalities (glutamic acid, lactic acid, 3-hydroxybutyric acid, and ribitol, etc.). These differential metabolites are mainly involved in D-glutamine and D-glutamate metabolism, alanine, aspartate and glutamate metabolism, and inositol phosphate metabolism. Our study reveals potential biomarkers and metabolic networks of acute TBI and neuroprotection effects of XFZY, and shows this metabolomics approach with MetaboAnalyst would be a feasible way to systematically study therapeutic effects of XFZY on TBI.

// Yun Peng 1 , Jun Cao 2 , Xiao-Yi Yao 3 , Jian-Xin Wang 4 , Mei-Zuo Zhong 3 , Ping-Ping Gan 3 and Jian-Huang Li 3 1 International Medical Center, Xiangya Hospital, Central South University, Changsha 410008, P.R. China 2 Department of Medical Oncology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410008, P.R. China 3 Department of Oncology, Xiangya Hospital, Central South University, Changsha 410008, P.R. China 4 School of Information Science and Engineering, Central South University, Changsha 410008, P.R. China Correspondence to: Jian-Huang Li, email: jianhuang_l@126.com Keywords: non-small cell lung cancer, A549 cells, tumor suppressor candidate 3, Wnt/β-catenin signaling pathway, autophagy Received: October 31, 2016 Accepted: March 19, 2017 Published: May 08, 2017 ABSTRACT We investigated the effects of tumor suppressor candidate 3 ( TUSC3 ) on autophagy in human non-small cell lung cancer (NSCLC) cells. A total of 118 NSCLC patients (88 males and 30 females) who underwent surgery at our institute were enrolled in the study. Immunohistochemical analysis revealed that TUSC3 protein expression was lower in NSCLC specimens than adjacent normal tissue. Correspondingly, there was greater methylation of TUSC3 in NSCLC than adjacent normal tissue. After transient transfection of A549 NSCLC cells with constructs designed to up-regulate or down-regulate TUSC3 expression, we analyzed the effects of inhibiting the Wnt pathway (XAV939) and autophagy (chloroquine, CQ) on the behavior of NSCLC cells. We also performed TOP/FOP-Flash reporter assays, MTT assays, Annexin V-FITC/propidium iodide staining, and acridine orange staining to evaluate Wnt/β-catenin signaling, cell proliferation, apoptosis, and autophagy, respectively. Expression of Wnt/β-catenin pathway components and autophagy-related proteins was analyzed using qRT-PCR and Western blotting. We found that TUSC3 inhibited cell proliferation and promoted both apoptosis and autophagy in A549 cells. In addition, TUSC3 increased expression of autophagy-related proteins. It also increased expression of Wnt/β-catenin signaling pathway components and promoted nuclear transfer of β-catenin, resulting in activation of Wnt/β-catenin signaling. TUSC3 thus induces autophagy in human NSCLC cells through activation of the Wnt/β-catenin signaling pathway.

To investigate the effect of Shaoyao Gancao Decoction (芍药甘草汤, SGD) on the pharmacokinetics of intravenously administered paclitaxel in rats. Paclitaxel was intravenously administered to rats (3 mg/kg) with or without the concomitant administration of SGD (752 mg/kg, a single day or 14 consecutive days pretreatment). The paclitaxel in the serum was quantified using a simple and rapid ultra performance liquid chromatography (UPLC) method for the pharmacokinetic study. The pharmacokinetic parameters were calculated via a non-compartment model using the computer program DAS 2.0. The pharmacokinetic parameters of paclitaxel were significantly altered in response to 14 consecutive days of pretreatment with SGD. The area under the curve (AUC0-t, from 4 820±197 to 4 205±186 ng·mL-1·-1) and AUC0-∞ (from 5 237±280 to 4 514±210 ng·mL-1·-1) significantly decreased in response to the 14-day pretreatment with SGD. The values of Vdss (L/kg) were 10.74±1.08 and 9.35±0.49, those of CL (L/kg) were 0.67±0.03 and 0.57±0.03 and the t1/2 (h) values were 11.17±0.84 and 11.32±0.93, respectively, for the 14-day SGD pretreatment and intravenous paclitaxel alone. The AUC0-t and AUC0-∞ values decreased by 13% and 14% (P

Free radical-induced oxidative damage occurs rapidly and is of primary importance during the secondary pathophysiological cascades of traumatic brain injury (TBI). Hydroxysafflor yellow A (HSYA) is a constituent of the flower petals of Carthamus tinctorius (safflower) and may represent a potential therapeutic strategy to improve outcomes following TBI. The present study aimed to identify HSYA in the brain tissues of rats exposed to TBI to determine its absorption and to investigate the underlying effects of HSYA on antioxidant enzymes in the brain tissues of TBI rats. To determine the absorption of HSYA for the investigation of the underlying antioxidant effects of HSYA in TBI, the presence of HSYA in the brain tissues of the TBI rats was identified using an ultra performance liquid chromatography‑tandem mass spectrometry method. Subsequently, the state of oxidative stress in the TBI rat model following the administration of HSYA was investigated by determining the levels of antioxidant enzymes, including superoxide dismutase (SOD), malondialdehyde (MDA) and catalase (CAT), and the ratio of glutathione (GSH)/glutathione disulfide (GSSG). The data obtained demonstrated that HSYA was absorbed in the brain tissues of the TBI rats. HSYA increased the activities of SOD and CAT, the level of GSH and the GSH/GSSG ratio. However, HSYA concomitantly decreased the levels of MDA and GSSG. These preliminary data suggest that HSYA has the potential to be utilized as a neuroprotective drug in cases of TBI.

Self-assembling natural drug hydrogels formed without structural modification and able to act as carriers are of interest for biomedical applications. A lack of knowledge about natural drug gels limits there current application. Here, we report on rhein, a herbal natural product, which is directly self-assembled into hydrogels through noncovalent interactions. This hydrogel shows excellent stability, sustained release and reversible stimuli-responses. The hydrogel consists of a three-dimensional nanofiber network that prevents premature degradation. Moreover, it easily enters cells and binds to toll-like receptor 4. This enables rhein hydrogels to significantly dephosphorylate IκBα, inhibiting the nuclear translocation of p65 at the NFκB signalling pathway in lipopolysaccharide-induced BV2 microglia. Subsequently, rhein hydrogels alleviate neuroinflammation with a long-lasting effect and little cytotoxicity compared to the equivalent free-drug in vitro. This study highlights a direct self-assembly hydrogel from natural small molecule as a promising neuroinflammatory therapy., There is interest in the development of drug-based hydrogels for responsive sustained drug release. Here, the authors report on the self-assembly of natural small molecule, rhein, into hydrogels and the application of the hydrogels as stable controlled release agents for neuro-inflammatory therapy

As high-intensity beams are required for various applications, high-power, high-current, continuous-wave (CW) radio-frequency quadrupole (RFQ) accelerators have become a research focus in recent years and also a direction for development in the future. To master and accumulate the advanced technology in design, fabrication and operation of high-current CW RFQs, the RFQ group at Peking University has built a window-type CW RFQ, operating at 162.5[Formula: see text]MHz, to accelerate a 50-mA deuteron beam from 50[Formula: see text]keV to 1[Formula: see text]MeV. It is the first relatively high-frequency window-type CW RFQ in the world. A [Formula: see text] ion beam extracted from an electron cyclotron resonance (ECR) ion source was used for the beam commissioning because deuteron beam acceleration will produce a serious radiation risk. We compared and analyzed the measurement results obtained during the beam commissioning with simulations. The data show good consistency in many respects. For the discrepancies, we explain the issues in detail. We achieved stable and robust acceleration of about 1.5[Formula: see text]mA CW [Formula: see text] for 1[Formula: see text]h. Finally, we discuss the differences between [Formula: see text] ion beam acceleration and deuteron beam acceleration.

Background Chinese herbal formula Shaoyao Gancao decoction (SGD) is often used as an adjuvant with chemotherapeutic agents to treat cancer. Due to the herb-drug interactions, the alternations of drug metabolic enzyme and drug transporters induced by SGD deserve to be explored. We aimed to investigate the effect of SGD on the pregnane X receptor (PXR)-mediated transcriptional regulation of cytochrome P450 3A4 (CYP3A4) and drug transporter multidrug resistance protein 1 (MDR1) in vitro. Besides, we assessed the contribution of constituent herbs to SGD on the regulation of CYP3A4 and MDR1. Methods The dual luciferase reporter gene system containing the hPXR expression plasmid and the reporter gene plasmid of CYP3A4 or MDR1 was co-transfected to HepG2 and Caco2 cells. Luciferase activities were determined using a Dual-luciferase reporter assay kit. The gene expression of CYP3A4 and MDR1 in the hPXR-transfected LS174T cells were assessed by real-time qPCR. Finally, the contribution of constituent herbs from SGD was evaluated. Results SGD, Shaoyao and Gancao concentration-dependently increased promoter activities of CYP3A4 and MDR1 in vitro. Moreover, SGD, Shaoyao and Gancao up-regulated CYP3A4 and MDR1 mRNA in hPXR-transfected LS174T cells. As the herbal constituent of SGD, Gancao possesses significantly higher levels of metabolic enzyme and drug transporters compared with Shaoyao. Conclusion SGD tends to enhance CYP3A4 and MDR1 expression via PXR pathway, especially Gancao provides the main contribution. This study highlights a potential in vitro mechanism for SGD on the regulation of drug metabolic enzymes and drug transporters.

Self-assembling natural drug hydrogels formed without structural modification and able to act as carriers are of interest for biomedical applications. A lack of knowledge about natural drug gels limits there current application. Here, we report on rhein, a herbal natural product, which is directly self-assembled into hydrogels through noncovalent interactions. This hydrogel shows excellent stability, sustained release and reversible stimuli-responses. The hydrogel consists of a three-dimensional nanofiber network that prevents premature degradation. Moreover, it easily enters cells and binds to toll-like receptor 4. This enables rhein hydrogels to significantly dephosphorylate IκBα, inhibiting the nuclear translocation of p65 at the NFκB signalling pathway in lipopolysaccharide-induced BV2 microglia. Subsequently, rhein hydrogels alleviate neuroinflammation with a long-lasting effect and little cytotoxicity compared to the equivalent free-drug in vitro. This study highlights a direct self-assembly hydrogel from natural small molecule as a promising neuroinflammatory therapy.

Ethnopharmacological relevance Zhiqiao–Houpu herb-pair (ZQHPHP), composed of Fructus Aurantii (Zhiqiao [ZQ] in Chinese) and Magnolia officinalis (Houpu [HP] in Chinese), is a traditional herbal formula that has been extensively used for treating gastrointestinal motor dysfunction. The aim of the study was to evaluate the effect and possible mechanism of ZQHPHP on gastric emptying (GE) and gastric antral smooth muscle contractility (GASMC). Materials and methods This study includes four parts: (a) study of ZQHPHP's effect on GE; (b) study of ZQHPHP's effect on gastric antral smooth muscle contractility (GASMC); (c) comparing the effects of ZQHPHP, ZQ and HP on GASMC; (d) study of antagonists or agonists on ZQHPHP-induced GASMC. A test meal of Evans blue was adopted to estimate GE in rats. A polygraph was used to measure GASMC in rats. Results The in vivo experiments demonstrated that, at the doses of 10 mg/kg bw and 20 mg/kg bw, ZQHPHP could promote GE. While, at the higher dose of 30 mg/kg bw, ZQHPHP delayed the GE. From the in vitro experiments we found that ZQHPHP (3–10 μg/ml) concentration-dependently increased the mean amplitude of contractions in the antral circular strip compared to untreated controls. While, in the concentration of 30 μg/ml, ZQHPHP prohibited GASMC. Besides, atropine blocked the stimulatory effect of ZQHPHP on GASMC and norepinephrine partly prohibited the stimulatory effect of ZQHPHP on GASMC, whereas isoproterenol showed no effect. From the in vitro experiment, we also found that ZQ and HP used together can synergistically increase gut motor. Conclusions The experiment indicated that ZQHPHP could induce bidirectional regulation on gastric motility. ZQ and HP used together can synergistically increase gut motor at a certain dosage. Lower dosage of ZQHPHP increases gastric motility, while higher dosage produces inhibition. In addition, the improvement of gastric motility by ZQHPHP is predominantly involved with muscarinic receptors and secondarily with alpha-receptors.

A simple, novel, specific, rapid and reproducible ultra-performance liquid chromatography electrospray ionization tandem mass spectrometry method has been developed and validated for the determination of hydroxysafflor yellow A (HSYA) in biological fluids (plasma, urine and cerebrospinal fluid) of patients with traumatic brain injury after intravenous injection of Xuebijing (XBJ). Liquid-liquid extraction was performed, and separation was carried out on an Acquity UPLC™ BEH C18 column, with gradient elution using a mobile phase composed of methanol and 0.1% formic acid at a flow rate of 0.3 mL/min. A triple quadrupole tandem mass spectrometer with electrospray ionization was used for the detection of HSYA. The mass transition followed was m/z 611.0 → 491. The retention time was less than 3.0 min. The calibration curve was linear in the concentration range from 2 to 6125 ng/mL for cerebrospinal fluid, plasma and urine. The intra- and inter-day precisions were

Oxidative stress chiefly contributes to the disruption of the BBB following traumatic brain injury (TBI). The Chinese herbal medicine rhubarb is a promising antioxidant in treating TBI. Here we performed in vivo and in vitro experiments to determine whether rhubarb and its absorbed bioactive compound protected the BBB after TBI by increasing ZO-1 expression through inhibition of gp91phox subunit of NADPH oxidase/ROS/ERK/MMP-9 pathway. Rats were subjected to the controlled cortical impact (CCI) model, and primary rat cortical astrocytes were exposed to scratch-wound model. The liquid chromatography with tandem mass spectrometry method showed that rhein was the compound absorbed in the brains of CCI rats after rhubarb administration. The wet-dry weights and Evans blue measurements revealed that rhubarb and rhein ameliorated BBB damage and brain edema in CCI rats. Western blots showed that rhubarb and rhein downregulated GFAP in vitro. RT-PCR, immunohistochemistry, Western blot and dichlorodihydrofluorescein diacetate analysis indicated that rhubarb prevented activation of gp91phox subunit of NADPH oxidase induced ROS production, subsequently inhibited ERK/MMP-9 pathway in vivo and in vitro. Interestingly, rhein and rhubarb similarly protected the BBB by inhibiting this signaling cascade. The results provide a novel herbal medicine to protect BBB following TBI via an antioxidative molecular mechanism.

A compact accelerator-driven neutron source (CANS) has been proposed and designed by the Peking University (PKU) RFQ group. The source is based on a compact deuteron RF accelerator that delivers an average current of a few mA of deuterons at 11[Formula: see text]MeV to the target. The accelerator consists of a short radio frequency quadrupole (RFQ) followed by efficient interdigital H-mode drift tube linac (IH-DTL) structure. The total length of the whole accelerator structure is 4.96[Formula: see text]m, including 1.76[Formula: see text]m for the 4-vane RFQ and 2.70[Formula: see text]m for the IH-DTL. The dynamic simulation results show that the beam has excellent quality, with transmission efficiency higher than 99%. The transverse and longitudinal normalized rms emittance at the DTL exit is 0.29[Formula: see text]mm⋅mrad and 0.12 MeV⋅deg, respectively. Details of the beam dynamics of the RFQ and IH-DTL are presented in this paper.

In order to reduce the beam impedance and refrigeration power dramatically, we have designed a high temperature superconductor (HTS) coated beam screen to screen the cold chamber walls of the super proton-proton collider bending magnets from beam-induced heat loads. It employs an absorber, inspired by the future circular collider studies, to absorb the immense synchrotron radiation power of 12.8 W/m emitted from the 37.5 TeV proton beams. Such a structure has the advantage of decreasing the electron cloud effect and improving the beam vacuum. We have compared the critical magnetic field and current density and accessibility of two potential HTS materials for the beam screen, TlBa2Ca2Cu3O9−δ (Tl-1223) and Yttrium Barium Copper Oxide (YBCO) and finally chose YBCO for coating. The beam screen is tentatively designed to work at 55-70 K because of the limited development of the YBCO material. The thermal analysis with oxygen cooling fluid indicates that the YBCO conductor can maintain its superconductivity even if the synchrotron radiation hits the YBCO-coated surface and the mechanical analysis shows that the structure has the ability to resist the Lorenz force during magnet quenches.In order to reduce the beam impedance and refrigeration power dramatically, we have designed a high temperature superconductor (HTS) coated beam screen to screen the cold chamber walls of the super proton-proton collider bending magnets from beam-induced heat loads. It employs an absorber, inspired by the future circular collider studies, to absorb the immense synchrotron radiation power of 12.8 W/m emitted from the 37.5 TeV proton beams. Such a structure has the advantage of decreasing the electron cloud effect and improving the beam vacuum. We have compared the critical magnetic field and current density and accessibility of two potential HTS materials for the beam screen, TlBa2Ca2Cu3O9−δ (Tl-1223) and Yttrium Barium Copper Oxide (YBCO) and finally chose YBCO for coating. The beam screen is tentatively designed to work at 55-70 K because of the limited development of the YBCO material. The thermal analysis with oxygen cooling fluid indicates that the YBCO conductor can maintain its superconductivity eve...

Neuroinflammation is central to the pathology of traumatic brain injury (TBI). Xuefu Zhuyu decoction (XFZY) is an effective traditional Chinese medicine to treat TBI. To elucidate its potential molecular mechanism, this study aimed to demonstrate that XFZY functions as an anti-inflammatory agent by inhibiting the PI3K-AKT-mTOR pathway. Sprague-Dawley rats were exposed to controlled cortical impact to produce a neuroinflammatory response. The treatment groups received XFZY (9 g/kg and 18 g/kg), Vehicle group and Sham group were gavaged with equal volumes of saline. The modified neurologic severity score (mNSS) and the Morris water maze test were used to assess neurological deficits. Arachidonic acid (AA) levels in brain tissue were measured using tandem gas chromatography-mass spectrometry. TNF-α and IL-1β levels in injured ipsilateral brain tissue were detected by ELISA. AKT and mTOR expression were measured by western blot analysis. The results indicated that XFZY significantly enhanced spatial memory acquisition. XFZY (especially at a dose of 9 g/kg) markedly reduced the mNSS and levels of AA, TNF-α and IL-1β. Significant downregulation of AKT/mTOR/p70S6K proteins in brain tissues was observed after the administration of XFZY (especially at a dose of 9 g/kg). XFZY may be a promising therapeutic strategy for reducing inflammation in TBI.

A simple, novel, specific, rapid and reproducible ultra-performance liquid chromatography electrospray ionization tandem mass spectrometry method has been developed and validated for the determination of hydroxysafflor yellow A (HSYA) in biological fluids (plasma, urine and cerebrospinal fluid) of patients with traumatic brain injury after intravenous injection of Xuebijing (XBJ). Liquid-liquid extraction was performed, and separation was carried out on an Acquity UPLC™ BEH C18 column, with gradient elution using a mobile phase composed of methanol and 0.1% formic acid at a flow rate of 0.3 mL/min. A triple quadrupole tandem mass spectrometer with electrospray ionization was used for the detection of HSYA. The mass transition followed was m/z 611.0 → 491. The retention time was less than 3.0 min. The calibration curve was linear in the concentration range from 2 to 6125 ng/mL for cerebrospinal fluid, plasma and urine. The intra- and inter-day precisions were10%, and the relative standard deviation of recovery was15% for HSYA in biological matrices. The method was successfully applied for the first time to quantify HSYA in the biological fluids (especially in cerebrospinal fluid) of patients with traumatic brain injury following intravenous administration of XBJ.

Shaoyao-Gancao-Tang (SGT) is a traditional Chinese prescription containing Radix Paeoniae alba and Radix Glycyrrhizae and is commonly used to relieve pains. Albiflorin and paeoniflorin are the main effective compounds of Radix Paeoniae alba, and the pharmacokinetic differences of the two compounds in rats after oral administration of SGT and single herb Paeony decoction were studied. At different time points (5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, and 540 min) after administration, plasma concentrations of albiflorin and paeoniflorin were determined using a simple and reliable UPLC method, and main pharmacokinetic parameters were evaluated. It was found that there were significant differences (p

Multidrug resistance (MDR) to anticancer drugs is a major obstacle to successful chemotherapy of tumors. Understanding the molecular basis to chemoresistance is likely to provide better treatment. Cell lines resistant to cis-diamminedichloroplatinum (CNE2/cDDP) were established from human nasopharyngeal carcinoma (NPC) cell lines CNE2. Comparative proteomics involving 2-dimensional gel electrophoresis (2-DE) and ESI-Q-TOF-MS were performed on protein extracted from CNE2 and CNE2/cDDP cell lines to screen drug resistance-related proteins. Keratin 1 (KRT1), cathepsin D (CTSD) and annexin a5 (ANXA5) were identified as three proteins showing higher expression in CNE2/cDDP compared to CNE2. Furthermore, suppression of KRT1 expression by siRNA resulted in decreased MDR in siRNA-CNE2/cDDP cells. And upregulation of KRT1 could result in increased of drug resistance in NPC cell lines. Taken together, KRT1 protein and its activity levels were higher in cDDP-resistant NPC cell lines compared to their parental cell lines. These data clearly linked KRT1 and cDDP resistance mechanisms. KRT1 could serve as a biomarker for chemotherapy sensitivity of NPC.