Zuogui pill disrupt the malignant cycle in breast cancer bone metastasis through the Piezo1-Notch-1-GPX4 pathway and active molecules fishing.

BACKGROUND: Breast cancer bone metastasis is closely associated with the bone microenvironment. Zuogui Pill (ZGP), a clinically approved formulation in China, effectively regulates the bone microenvironment for the prevention and treatment of osteoporosis. PURPOSE: Few reports have utilized the ZGP for bone metastasis models. This study investigated the intervention and bone-protective properties of ZGP against breast cancer bone metastasis, explored the potential mechanism, and screened for its active compositions by molecules fishing. METHODS: To investigate the intervention efficacy of ZGP and its protein-level mechanism of action, the mouse bone metastasis model and in vitro cell co-culture model were constructed. Affinity ultrafiltration, molecular docking, cellular thermal shift assay and physical scale detection were used to investigate the affinity components of the RANKL protein in ZGP. RESULTS: The administration of ZGP combined with zoledronic acid inhibited the development of tumors and secondary lung metastasis in mice. This translated to a prolonged survival period and enhanced quality of life. ZGP could disrupt the malignant cycle by modulating the Piezo1-Notch-1-GPX4 signaling pathway in the "bone-cancer" communication in the cell co-culture model. Furthermore, 25 chemical components of ZGP were identified, with 10 active compounds exhibiting significant affinity for the RANKL protein. CONCLUSION: The findings of this work highlighted ZGP's potential for intervening in the progression of breast cancer bone metastasis. Thus, this investigation served as an experimental foundation for expanding the application scope of ZGP and for advancing drug development efforts in bone metastasis treatment.

Designing a Coupling Agent with Aliphatic Polyether Chain and Exploring Its Effect on Silica/Natural Rubber Nanocomposites under the Action of Non-Rubber Contents.

In order to prepare engineering tires with lower rolling resistance and better wet slip resistance in a more environmentally friendly way. In this study, a series of low volatile organic compound (VOC) Mx-Si69 coupling agents (x = 1, 2, 3, 4, 5, 6, which means the number of ethoxy group in bis-(γ-triethoxysilylpropyl)-tetrasulfide (Si69) substituted by the aliphatic polyether chain) were applied to silica/NR nanocomposites to prepare tire tread with excellent performance. Firstly, M1-Si69 was substantiated as the best choice of Mx-Si69 and Si69 to achieve comprehensive optima in the mechanical properties of silica/NR nanocomposites characterized by dynamic and static mechanical properties. Afterwards, the modification of silica with M1-Si69 induced by Non-Rubber Contents (NRCs) in silica/NR nanocomposites was revealed by comparing the filler network, micromorphology, and mechanical properties of isoprene rubber (IR) and NR nanocomposites. Furthermore, compared with Si69, the M1-Si69 coupling agent was found to conspicuously reduce the energy loss and improve the safety performance of engineering tires according to evaluations of the rolling resistance and dynamic thermomechanical properties of the silica/NR nanocomposites. Finally, the critical function of M1-Si69 in reducing ethanol (a kind of volatile organic compound (VOC)) emissions from the reaction of coupling agent and silica was disclosed by gas chromatography-mass spectrometry.

Study on in vitro NR biosynthesis by rapid quantitative determination of substrate depletion.

A convenient and nonradioactive method for quantifying in vitro NR biosynthesis is presented that is based upon the quantitation of substrate depletion by ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). NR oligomers could be in vitro biosynthesized with the enzyme source from Hevea brasiliensis (Hevea) or Taraxacum kok-saghyz (TKS) by exogenous monomers (IPP) and initiators (FPP). The IPP incorporation rate and FPP consumption rate were 62.24% and 51.14% respectively when the washed rubber particles (WRP) of Hevea was the enzyme source. The IPP incorporation rate and the FPP consumption rate were 74.49% and 95.90% respectively when the sediment bottom fraction (BF) of Hevea was the enzyme source. The in vitro NR biosynthesis can be divided into two stages:(1) the initiation reaction of FPP, which occurs more in BF, and (2) the growth reaction of IPP, which occurs more in WRP. In addition, the IPP incorporation and FPP consumption rates were 59.39% and 34.15% respectively when the BF of TKS was selected as an enzyme source.

Association between the LRP5 rs556442 gene polymorphism and the risks of NAFLD and CHD in a Chinese Han population.

BACKGROUND: Multiple studies have demonstrated the involvement of low-density lipoprotein receptor-related protein 5 (LRP5) in metabolism-related diseases. This study explored the relationship between the LRP5 rs556442 gene polymorphism and the risks of non-alcoholic fatty liver disease (NAFLD) and coronary heart disease (CHD) in a Chinese Han population. METHODS: This retrospective case-control study included 247 patients with NAFLD, 200 patients with CHD, 118 patients with both NAFLD and CHD, and 339 healthy controls from June 2018 to June 2019 at Qingdao Municipal Hospital. Basic information and clinical characteristics were collected for all subjects. The genotype and allele frequency of LRP5 rs556442 were determined. RESULTS: The genotype distributions of LRP5 rs556442 differed significantly between the CHD and NAFLD + CHD groups (P < 0.05). The LRP5 rs556442 GG genotype markedly promoted the risk of NAFLD in CHD patients [odds ratio (OR) = 2.857, 95% confidence interval (CI): 1.196-6.824, P = 0.018). After adjustment for sex, age, and body mass index (BMI), this association remained significant (OR = 3.252, 95% CI: 1.306-8.102, P = 0.011). In addition, the LRP5 rs556442 AA + AG genotype was associated with an increased BMI in obese NAFLD patients (OR = 1.526, 95% CI: 1.004-2.319, P = 0.048). However, after adjustment for sex and age, this association was no longer significant (OR = 1.504, 95% CI: 0.991-2.282, P = 0.055). CONCLUSIONS: This study found that the LRP5 rs556442 GG genotype increased the risk of NAFLD in CHD patients and AA + AG genotype may be associated with an increased BMI in obese NAFLD patients among a Chinese Han population. Trial registration ChiCTR, ChiCTR1800015426. Registered 28 March 2018-Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=26239 .

Serum Resistin Levels in Adult Patients with Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Previous studies reported that serum resistin levels were remarkably changed in patients with nonalcoholic fatty liver disease (NAFLD) but the conclusions were inconsistent. The aim of this study was to investigate accurate serum resistin levels in adult patients with NAFLD. METHODS: A complete literature research was conducted in the PubMed, Embase, and Cochrane Library databases, and all the available studies up to 7 May 2020 were reviewed. The pooled standardized mean difference (SMD) values were calculated to investigate the serum resistin levels in patients with NAFLD and healthy controls. RESULTS: A total of 28 studies were included to investigate the serum resistin levels in patients with NAFLD. Patients with NAFLD had higher serum resistin levels than controls (SMD=0.522, 95% confidence interval [CI]: 0.004-1.040, I 2=95.9%). Patients with nonalcoholic steatohepatitis (NASH) had lower serum resistin levels than the healthy controls (SMD=-0.44, 95% CI: -0.83-0.55, I 2=74.5%). In addition, no significant difference of serum resistin levels was observed between patients with NAFL and healthy controls (SMD=-0.34, 95% CI: -0.91-0.23, I 2=79.6%) and between patients with NAFL and NASH (SMD=0.15, 95% CI: -0.06-0.36, I 2=0.00%). Furthermore, subgroup and sensitivity analyses suggested that heterogeneity did not affect the results of meta-analysis. CONCLUSIONS: This meta-analysis investigated the serum resistin levels in adult patients with NAFLD comprehensively. Patients with NAFLD had higher serum resistin levels and patients with NASH had lower serum resistin levels than healthy controls. Serum resistin could serve as a potential biomarker to predict the development risk of NAFLD.

A Chiral Metal-Organic 1D-Coordination Polymer Upon Complexation of Phenylene-Bridged Bipyrrole and Palladium (II) Ion.

Metal-organic 1D-coordination polymers, having unique electronic and optical properties, are expected to be a novel advanced functional material capable of fabricating smart plastics, films, and fibers. In this study, we have synthesized a novel metal-organic 1D-coordination polymer composed of a phenylene-bridged bipyrrole bearing N-alkylimino groups (BPI) and palladium(II) ion. The BPI and Pd(II) form square planar bis(bidentate) complex to form a metal coordinated π-conjugation polymer (Poly-BPI/Pd). It is stable in solutions at room temperature, and allowed measurement of its average molecular weight in SEC (M w = 106,000 and M n = 18,000, M w/M n = 5.88). It also provided a reversible multi redox profile in cyclic voltammetry, most likely originating from strong π-electronic interactions between the BPI components via Pd ion. A variety of substituent groups can be attached to the imino-nitrogens of BPI. A coordination polymer composed of a BPI derivative bearing chiral alkyl chains and Pd(II) showed strong circular dichroism (CD) in the solution due to the unidirectional chiral conformation of the BPI components in the polymer backbone.

Constructing a Multiple Covalent Interface and Isolating a Dispersed Structure in Silica/Rubber Nanocomposites with Excellent Dynamic Performance.

Realizing and manipulating a fine dispersion of silica nanoparticles (NPs) in the polymer matrix is always a great challenge. In this work, we first successfully synthesized N, N'-bis[3-(triethoxysilyl)propyl-isopropanol]-propane-1,3-diamine (TSPD), which was a new interface modifier, aiming to promote the dispersion of silica NPs. Through Fourier transform infrared spectroscopy, nuclear magnetic resonance analysis, and mass spectroscopy, we verified that TSPD contains together six ethoxy groups at its two ends. Then, we used this TSPD to modify the pure silica NPs, and this modified silica was abbreviated as D-MS, which is realized by the thermal gravimetric analysis examination, scanning electron microscopy analysis, and dynamic light scattering results. It was clearly observed that D-MS NPs are connected to one another but are not conglutinated tightly, exhibiting a novel predispersed structure with around 1-2 nm certain extent of interparticle distance. Next, we fabricated the following four elastomer nanocomposites such as pure silica/natural rubber (NR) composite (PS-NR), D-MS/NR composite (DMS-NR), bis-(γ-triethoxysilylpropyl)-tetrasulfide (TESPT)-modified silica/NR composite (TS-NR), and TESPT-modified D-MS/NR composite (T&DMS-NR) and found that the Payne effect is the smallest for T&DMS-NR via the combination use of the D-MS and the traditional coupling agent TESPT, which is attributed to its best dispersion state evidenced by the transmission electron microscopy results. Moreover, by measuring a series of other important mechanical performances such as the stress-strain curve, the dynamic strain dependence of the loss factor, and the heat build-up, we concluded that the T&DMS-NR system greatly exceeds those of the three other rubber composites. In general, this new approach provides a good opportunity to prepare a silica/rubber composite with excellent properties in mechanical strength and dynamic behavior by tailoring the fine dispersion of NPs.

Silica Modified by Alcohol Polyoxyethylene Ether and Silane Coupling Agent Together to Achieve High Performance Rubber Composites Using the Latex Compounding Method.

The study of preparing silica/rubber composites used in tires with low rolling resistance in an energy-saving method is fast-growing. In this study, a novel strategy is proposed, in which silica was modified by combing alcohol polyoxyethylene ether (AEO) and 3-mercaptopropyltriethoxysilane (K-MEPTS) for preparing silica/natural rubber (NR) master batches. A thermal gravimetric analyzer and Raman spectroscopy results indicated that both AEO and K-MEPTS could be grafted on to the silica surface, and AEO has a chance to shield the mercaptopropyl group on K-MEPTS. Silica modified by AEO and K-MEPTS together was completely co-coagulated with the rubber in preparing silica/NR composites using the latex compounding method with the help of the interaction between AEO and K-MEPTS. The performance of composites prepared by silica/NR master batches was investigated by a rubber process analyzer (RPA), transmission electron microscopy (TEM) and a tensile tester. These results demonstrate that AEO forms a physical interface between silica and rubber, resulting in good silica dispersion in the matrix. K-MEPTS forms a chemical interface between silica and rubber, enhancing the reinforcing effect of silica and reducing the mutual friction between silica particles. In summary, using a proper combination of AEO and K-MEPTS is a user-friendly approach for preparing silica/NR composites with excellent performance.