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Yuxun Wei,1– 4,* Yumeng Wei,1– 4,* Lin Sheng,1– 4 Jingwen Ma,1– 4 Zhilian Su,1– 4 Jie Wen,1– 4 Lanmei Li,5 Qiang Jia,2,6 Huiyang Liu,1– 4 Hui Si,2,4 Linjin Xiong,1– 4 Jinglin Chen,1– 4 Ju Cheng,3,4 Ying Zuo,2,7 Hongru Yang,8 Ling Zhao2– 4 1Key Laboratory of Medical Electrophysiology, Ministry of Education, School of Pharmacy of Southwest Medical University, Luzhou, People’s Republic of China; 2Key Laboratory of Medical Electrophysiology, Ministry of Education, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University; Luzhou, Sichuan, People’s Republic of China; 3Central Nervous System Drug Key Laboratory of Sichuan Province, School of Pharmacy of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 4Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 5Nanchong Key Laboratory of Individualized Drug Therapy, Department of Pharmacy, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, Sichuan, People’s Republic of China; 6Ethics Committee Office, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 7Department of Comprehensive Medicine, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 8Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ling Zhao, Key Laboratory of Medical Electrophysiology, Ministry of Education, Luzhou Key Laboratory of Traditional Chinese Medicine for Chronic Diseases Jointly Built by Sichuan and Chongqing, The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China, Tel/Fax +86 830 3160093, Email zhaoling-998@163.com Hongru Yang, Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China, Tel/Fax +86 830 8585668, Email yanghongru801@126.comPurpose: The present study aimed to construct a co-loading platform encapsulating curcumin and paclitaxel at ratios of 2:1– 80:1 (w/w) designated “CU-PTX-LNP” and explored the synergistic effects of CU-PTX at different composite proportions on liver cancer cells using the combination index (CI) method.Methods: The CU lipid nanoplatform (CU-LNP) formulation was optimized via single-factor and orthogonal experiments. Various concentrations of PTX were added to the optimal formulation of CU-LNP to generate CU-PTX-LNP and the nanoplatform characterized via differential scanning calorimetry (DSC), transmission electron microscope (TEM), X-ray diffraction (XRD), zeta potential, polydispersity index (PDI), and size analyses. The cumulative release, stability, and cytotoxicity of CU-PTX-LNP in LO2, HepG2, and SMMC-7221 cells were assessed in vitro, followed by safety investigation and pharmacokinetic studies in vivo. The anti-tumor activity of CU-PTX-LNP was also evaluated using nude mice.Results: CU-PTX-LNP formulations containing CU:PTX at a range of proportions (2:1– 80:1; w/w) appeared as uniformly dispersed nanosized spherical particles with high entrapment efficiency (EE> 90%), sustained release and long-lasting stability. Data from in vitro cytotoxicity assays showed a decrease in the IC50 value of PTX of CU-PTX-LNP (by 5.47– 332.7 times in HepG2 and 4.29– 143.21 times in SMMC-7221 cells) compared to free PTX. In vivo, CU-PTX-LNP displayed excellent biosafety, significant anti-tumor benefits and enhanced pharmacokinetic behavior with longer mean residence time (MRT(0-t); CU: 4.31-fold, PTX: 4.61-fold) and half-life (t1/2z; CU: 1.83-fold, PTX: 2.28-fold) relative to free drugs.Conclusion: The newly designed CU-PTX-LNP platform may serve as a viable technological support system for the successful production of CU-PTX composite preparations.Keywords: curcumin, paclitaxel, lipid nano platform, synergistic effect

Radish seed (RS), the dried ripe seed of Raphanus sativus L., is widely used in traditional Chinese medicine (TCM) to reduce blood pressure. However, the molecular and pharmacological mechanisms underlying its therapeutic effects are still unclear. In this study, we analyzed the effects of RS in a rat model of prehypertension and assessed the mechanistic basis by integrating transcriptomics and metabolomics. RS administration significantly reduced blood pressure in prehypertensive male Wistar rats, negatively regulated endothelin-1, increased nitric oxide levels, and reduced the exfoliation of endothelium cells. In vitro vascular ring experiments further confirmed the effects of RS on vascular endothelial cells. Furthermore, we identified 65 differentially expressed genes (DEGs; P a d j < 0.05 and fold change (FC) > 2) and 52 metabolites (VIP > 1, P < 0.05 and FC ≥ 2 or ≤0.5) in the RS intervention group using RNA-seq and UPLC-MS/MS, respectively. A network of the DEGs and the metabolites was constructed,q which indicated that RS regulates purine metabolism, linoleic acid metabolism, arachidonic acid metabolism, circadian rhythm, and phosphatidylinositol signaling pathway, and its target genes are Pik3c2a, Hspa8, Dnaja1, Arntl, Ugt1a1, Dbp, Rasd1, and Aldh1a3. Thus, the antihypertensive effects of RS can be attributed to its ability to improve vascular endothelial dysfunction by targeting multiple genes and pathways. Our findings provide new insights into the pathological mechanisms underlying prehypertension, along with novel targets for the prevention and treatment of hypertension.

Compared with the T-cell potential of particulate matter (PM) in animal studies, comprehensive evaluation on the impairments of T-cell response and exposure-response from PM and its components in human population is limited. There were 768 participants in this study. We measured environmental PM and its polycyclic aromatic hydrocarbons (PAHs) and metals and urinary metabolite levels of PAHs and metals among population. T lymphocyte and its subpopulation (CD4

Epigallocatechin-3-gallate (EGCG) possesses anti-fibrotic potential in diverse tissues; however, the molecular mechanisms underlying the impacts of EGCG on diabetes-induced myocardial fibrosis remain unclear. This present study aimed to unravel the anti-fibrotic effects of EGCG on the heart in type 2 diabetic rats and investigate its molecular mechanisms. Rats were randomly assigned to the following four groups: Normal (NOR), diabetic cardiomyopathy (DCM), DCM + 40 mg/kg EGCG, and DCM + 80 mg/kg EGCG groups. After 8 weeks of EGCG treatment, fasting blood glucose, left ventricular hemodynamic indices, heart index, and myocardial injury-related parameters were measured. Hematoxylin and eosin staining and Sirius Red staining were used to evaluate myocardial pathological alterations and collagen accumulation. The contents of myocardial hydroxyproline, collagen-I, collagen-III, transforming growth factor (TGF)-β1, matrix metalloprotease (MMP)-2, and MMP-9 were measured. The gene expression levels of myocardial TGF-β1, MMP-2, and MMP-9 were detected. Autophagic regulators, including adenosine 5’-monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR), and autophagic markers, including microtubule-associated protein-1 light chain 3 and Beclin1 were estimated. The results indicated that diabetes significantly decreased cardiac contractile function and aggravated myocardial hypertrophy and injury. Furthermore, diabetes repressed the activation of autophagy in myocardial tissue and promoted cardiac fibrosis. Following ingestion with different doses of EGCG, myocardial contractile dysfunction, hypertrophy and injury were ameliorated; myocardial autophagy was activated, and myocardial fibrosis was alleviated in the EGCG treatment groups. In conclusion, these findings suggested that EGCG could attenuate cardiac fibrosis in type 2 diabetic rats, and its underlying mechanisms associated with activation of autophagy via modulation of the AMPK/mTOR pathway and then repression of the TGF-β/MMPs pathway.

In view of the abnormal areas of soil elements and organic pollutants found in the regional distribution, according to the previous sampling and testing results of surface soil, the abnormal areas in the investigation area of the Yellow River Delta were verified by the profile. Through sampling and testing, the vertical distribution of 12 elements, such As, Cr, etc., and the influence of soil forming process on 12 elements were analyzed, and the influencing factors of migration and transformation of heavy metal elements in topsoil were analyzed, which provided scientific basis for soil pollution and prevention.

Epigallocatechin-3-gallate (EGCG), an essential polyphenolic constituent found in tea leaves, possesses various potent biological activities. This research was undertaken to investigate the impact of EGCG against endoplasmic reticulum (ER) stress-mediated inflammation and to clarify the underlying molecular mechanism in type 2 diabetic kidneys. The male rats were randomized into four groups: normal, diabetic, low-dose EGCG, and high-dose EGCG. In type 2 diabetic rats, hyperglycemia and hyperlipidemia noticeably caused renal structural damage and dysfunction and aggravated ER stress. Meanwhile, sustained ER stress activated the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and then upregulated the contents of inflammatory cytokines in the diabetic kidney. Following supplementation with 40 mg/kg and 80 mg/kg EGCG, hyperglycemia, hyperlipidemia, and renal histopathological alterations and dysfunction were noticeably ameliorated; renal ER stress, NLRP3 inflammasome, and inflammatory response were markedly repressed in the EGCG treatment groups. In summary, the current study highlighted the renoprotective effects of EGCG in type 2 diabetes and its mechanisms are mainly associated with the repression of ER stress-mediated NLRP3 inflammasome overactivation.

This work investigates the tracking consensus problem of multiagent systems over directed networks, where the control gains follow certain volatile patterns. Some event-based consensus protocols are formulated so as to reduce the redundant execution of control. By using an extended differential inequality with a time-dependent coefficient, criteria for tracking consensus under time- and state-dependent triggering conditions are constructed, respectively. It is proved that the time average of the control gain, together with the agent dynamics, network topology, and triggering conditions, governs the consensus despite the fluctuation of control gain. The derived theorem can be utilized to ensure consensus with intermittent strategies aiming to lessen the burden in communications, including aperiodic on-off control with periodic perturbation and pulse-modulated on-off control. Unlike existing works, the requirement of a positive lower bound of control ratios is removed and, thus, a wide range of control gain patterns is possible, signifying higher flexibility in intermittent policy design. Finally, numerical examples are provided to further illustrate the theoretical results.

Kidney injury caused by transplant-associated thrombotic microangiopathy (TA-TMA) in patients who underwent allogeneic hematopoietic stem cell transplantation (allo HSCT) is relatively frequent. However, it is rarely reported in patients undergoing autologous HSCT (aHSCT). There are a few studies reported that TA-TMA could occur in pediatric patients undergoing aHSCT, but the condition in adult patients is rarely described. Furthermore, almost all the patients who suffered from TA-TMA developed typical and severe manifestations which should be treated with aggressive target therapy. Nevertheless, we presented two cases of kidney injury caused by TA-TMA after aHSCT with specific clinical features. Case 1, a 33-year-old Chinese male diagnosed with Hodgkin's lymphoma developed TA-TMA -associated kidney injury 4 months after transplantation. Case 2, a 49-year-old Chinese female with central nervous lymphoma developed TA-TMA-related kidney injury 3 months after transplantation. Both patients presented "mild" and atypical features of TA-TMA and their kidney function was managed effectively with low-dose prednisone therapy. TA-TMA related kidney injury can occur in patients who underwent aHSCT. Patients with TA-TMA could develop atypically "mild" features. Low-dose prednisone may be effective in place of routine eculizumab treatment regimen. We recommend that clinicians prompt an investigation for TA-TMA in patients presenting kidney injury in the background of aHSCT to facilitate early diagnosis.

Table S1: Primers for real-time PCR. Table S2: Patient characteristics at initial diagnosis.

The weights of lungs from mice described in Figure 5E and F.

Purpose: Agents extracted from natural sources with antitumor property have attracted considerable attention from researchers and clinicians because of their safety, efficacy, and immediate availability. Degalactotigonin (DGT), extracted from Solanum nigrum L., has anticancer properties without serious side effects. Here, we explored whether DGT can inhibit the growth and metastasis of osteosarcoma.Experimental Design: MTT, colony formation, and apoptosis assays were performed to analyze the effects of DGT on osteosarcoma cell viability in vitro. The migration and invasion abilities were measured using a Transwell assay. Animal models were used to assess the roles of DGT in both tumor growth and metastasis of osteosarcoma. Gli1 expression and function were measured in osteosarcoma cells and clinical samples. After DGT treatment, Gli1 activation and the phosphorylation status of multiple cellular kinases were measured with a luciferase reporter and phospho-kinase antibody array.Results: DGT inhibited proliferation, induced apoptosis, and suppressed migration and invasion in osteosarcoma cells. DGT, injected intraperitoneally after tumor inoculation, significantly decreased the volume of osteosarcoma xenografts and dramatically diminished the occurrence of osteosarcoma xenograft metastasis to the lungs. Mechanistically, DGT inhibited osteosarcoma growth and metastasis through repression of the Hedgehog/Gli1 pathway, which maintains malignant phenotypes and is involved in the prognosis of osteosarcoma patients. DGT decreased the activity of multiple intracellular kinases that affect the survival of osteosarcoma patients, including GSK3β. In addition, DGT represses the Hedgehog/Gli1 pathway mainly through GSK3β inactivation.Conclusions: Our studies provide evidence that DGT can suppress the growth and metastasis of human osteosarcoma through modulation of GSK3β inactivation–mediated repression of the Hedgehog/Gli1 pathway. Clin Cancer Res; 24(1); 130–44. ©2017 AACR.

Background：Silicosis is a lung disease with diffuse nodular pulmonary fibrosis because of long-term inhalation of a large number of free silica dust. Research has been reported that dysbiosis of fecal microbiota was existed in silicosis patients. However, few studies have examined the effects of silica on the intestinal tract. Objective: In this study, we aimed to investigate the change of fecal microbiota, lung and ileum tissues of rats exposed to silica dust and explore the regulatory role of fecal microbiota in rats after silica exposure. Methods: The Wistar male rats were intratracheally instilled with 50 mg/mL silicon dioxide (1 mL per rat). Hematoxylin and eosin (HE), Masson staining, enzyme-linked immunosorbent assay (ELISA) and Western blot were used to exam the pulmonary inflammation and fibrosis in rats. HE, Western blot and Transmission Electron Microscopy (TEM) were used to exam the ileac injury. The 16s rRNA gene sequences, non-targeted metabolomics, transcriptome analysis were used to exam the fecal microbiota, metabolites and ileac mRNAs respectively. Then, we employed fecal microbiota transplantation (FMT) experiment to examine whether fecal microbiota play the important roles in the change of silica-induced pulmonary inflammation, fibrosis and ileum injury. Meanwhile, Pearson correlation tests were used to detect the differential microbiota and metabolites of feces, and mRNAs of ileum on day 56. Results: The results showed that silica exposure resulted in dynamic change of pulmonary inflammation, fibrosis, fecal microbiota dysbiosis and ileum epithelial injury. FMT up-regulated the level of Bifidobacterium, restored the level of tight junction proteins of ileum. Then we found the level of Bifidobacterium was significantly down-regulated on day 56 in silica-exposed rats. Further we mainly predicted 3 potential mechanisms through conjoint analysis and KEGG analysis: (ⅰ) the change of Bifidobacterium may be related to the production of oleoyl 3-carba cyclic phosphatidic acid (3-CCPA) and the expression of Cldn8, which involved in silica-induced pulmonary inflammatory response and ileac barrier function injury; (ⅱ) Silica-induced fecal microecological dysbiosis and inflammatory respond may affect the arginine biosynthesis and utilization of arginine by regulating the level of N-Acetyl-L-Glutamic Acid and Nos2, which effect ileac architectural integrity; and (ⅲ) Silica-induced fecal microecology disorder may induce ileac injury by regulating Ido1, Kynu and Indole-3-ethanol mediated “Tryptophan metabolism” pathway. Discussion: This study provided evidence that silica could alter fecal microbiota which may in turn play an important role in silica-induced pulmonary fibrosis and ileac barrier injury in rats. Three predicted mechanistic pathways deserved further study. The findings may provide a starting roadmap to intervene in the development of silica-induced pulmonary fibrosis.

Purpose This study aimed to assess the short-term therapeutic response after radioiodine (131I) adjuvant therapy (RAT) and long-term clinical outcome for postoperative papillary thyroid carcinoma (PTC) patients with elevated thyroglobulin (Tg) but no structural disease, and to investigate the related factors affecting the response. Methods From April 2016 to June 2019, 165 postoperative PTC patients with preablative stimulated thyroglobulin (ps-Tg) > 10 ng/ml but no structurally evident disease who undertook RAT in our institutions were retrospectively enrolled. The responses were assessed 6 months post RAT and at the end of follow-up. Univariate and multivariate analyses were used to investigate the effects of 10 observed factors on the long-term therapeutic response. A receiver operating characteristic (ROC) curve was used to determine the cut-off values of Tg to predict incomplete response (IR). Results Six months after RAT, ER, IDR, BIR, SIR were achieved in 13.94%, 29.70%, 30.30%, 26.06% of 165 patients, respectively. With a median follow-up of 58 months, the responses were identified in 33.30%, 21.82%, 15.15%, 29.70%, respectively. The N stage (OR: 3.874, P=0.002) was independent factor associated with SIR and suppressed Tg (sup-Tg) 6 months post RAT (OR: 2.256, PConclusion The proportion of patients developing structural disease within 5 years was close to 30% in postoperative PTC patients with unexplained elevated Tg. The N stage and sup-Tg 6 months post RAT were conducive to predict the long-term treatment response of these patients.

Microbially induced calcium carbonate deposition (MICP) restoration technology has good restoration effects and low environmental pollution compared with traditional restoration methods, and this technology has been applied in actual projects. However, grouting components such as bacterial solutions are easily lost in vertical cracks due to their low viscosity as well as their self-weight. In this paper, cracks were repaired using microbial mineralization by sealing the bottom of vertical cracks and pressure grouting. Controlled tests were designed based on three variables: crack width, presence or absence of media in the crack, and grouting method. The results show that the smaller the crack width, the easier it is to achieve a seal. The addition of media in the cracks can improve the repair efficiency. As the amount of grouting increases, the amount of calcium carbonate production in the cracks gradually increases, and the height and thickness of calcium carbonate deposition also gradually increases. The bottom closure pressure grouting method can not only reduce the amount of grouting fluid, but also shorten the test period. This method overcomes the difficulty that grouting poses as it should not be left in vertical cracks and plays an important role in reducing costs and shortening repair time.

Thyroid papillary carcinoma (PTC) is the most common endocrine tumor, Hashimoto's thyroiditis (HT) is considered to be closely related to PTC pathogenesis, but their relationship still needs verification and exploration. Aim of the study. To analyze the differences and similarities of the metabolic mechanism of thyroid papillary carcinoma in normal and HT background, and to explore the relationship between HT and PTC. The Ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF/MS) technology was used to analyze 61 PTC patient tissues (31 HT background and 30 normal tissue (NC) background). Potential biomarkers were screened from principal component analysis (PCA) to orthogonal partial least square (OPLS) discriminant analysis and further evaluated by ROC analysis. The HMDB was searched to identify potential differential metabolites and the final metabolic pathway analysis was performed by MetaboAnalyst 5.0. The HT and NC group had common metabolic pathways, such as taurine and hypo-taurine metabolism, arginine biosynthesis, alanine, aspartate and glutamate metabolism, arginine and proline metabolism and D-glutamine and D-glutamate metabolism. Furthermore, arginine, glutamic acid, cysteine, citric acid, malic acid, uracil and taurine showed statistical significance in PTC diagnosis (the area under the curve values of HT group and NC group were 0.867 and 0.973 respectively). The HT group had specific metabolic pathways, including aminoacyl-tRNA biosynthesis, glycine, serine and threonine metabolism. The metabolic profiles of the NC and HT groups had important similarities and differences in thyroid cancer. The correlation of PTC with HT may be related to aminoacyl-tRNA biosynthesis, serine and threonine metabolism.

In order to meet the needs of social development, increasing research attention has been paid to multifunctional molecular-based phase-transition materials. The traditional phase-transition materials with a single functional property can be transformed into magnificent ones by adding additional functional properties-for instance photoluminescence and magnetic order- because having two or more functional properties simultaneously greatly broadens the fields of their applications. At present, there are very few multifunctional phase-transition materials showing excellent performance, and the crystal structure design and performance optimization of materials still need to be studied in depth. Herein, we report the development of two organic-inorganic hybrid materials: (MBA)

With vigorous development of the photovoltaic hot topic, the organic-inorganic hybrid perovskite (OIHP) have become the focus in the search for functional materials. Among them, layered 2D OIHPs provide the...

To investigate the factors influencing the outcome of initial 131I remnant ablative therapy in intermediate- to high-risk patients with papillary thyroid microcarcinoma (PTMC).We divided 99 patients with PTMC who underwent total thyroidectomy into two groups according to their response to initial 131I remnant ablative therapy: excellent response (ER) and non-ER groups. Clinical and laboratory characteristics were collected and retrospectively analyzed using univariate and multivariate binary logistic regression. Receiver operator characteristic (ROC) curves and diagnostic cutoff values were analyzed to evaluate the predictive value of significant quantitative influencing factors for 131I treatment outcomes. A prognostic nomogram model based on the above independent risk factors was established.Of the 99 eligible patients who accepted the initial 131I treatment following total thyroidectomy, 76 (76.7%) were classified into the ER group and 23 (23.3%) into the non-ER group. The univariate and multivariate analyses showed that extrathyroidal extension [ETE; odds ratio (OR) = 4.769; P = 0.041], preablative thyrotropin (TSH; OR = 0.972; P = 0.017), and stimulated thyroglobulin (sTg; OR = 1.614; P = 0.040) were independent predictors for the therapeutic effect of 131I treatment. Patients with higher sTg (1.37 ng/ml) and lower TSH (67.97 mU/l) and ETE tended to have a poor response to initial 131I treatment. The quantification of the therapeutic effect of initial 131I therapy in patients with PTMC using our newly constructed nomogram showed that ETE, preablative sTg, and TSH were contributors to non-ER.Intermediate- to high-risk patients with PTMC after total thyroidectomy who had low pretreatment sTg and high preablative TSH levels and negative ETE were more likely to achieve satisfactory response to initial 131I remnant ablative therapy. Our prognostic nomogram is a valuable tool to enable patients and clinical professionals to be better informed about patients' therapeutic response to initial 131I remnant ablative therapy.

Bovine serum albumin (BSA) has been employed as a mild biological template in nanoscale particles. Copper sulfide (CuS) has been used for photothermal therapy (PTT) in several studies. In this study, we aimed to synthesize the

A two-dimensional organic–inorganic hybrid perovskite with blue-white emission and high phase transition temperature is presented.

Improving the phase transition temperature and enriching optoelectronics properties have become the top priorities. Herein, we have successfully synthesized two bilayer (2D/3D) perovskite materials based on a single layer perovskite.