Performance evaluation of nano-graphene lubricating oil with high dispersion and low viscosity used in diesel engines.

The basic tribological experiments have reported that nano-graphene lubricating oil has excellent anti-friction and anti-wear properties, which has been widely concerned. However, the real anti-friction effect of nano-graphene lubricating oil and its impact on engine power performance, economic performance and emission performance remain to be proved. This has seriously hindered the popularization and application of nano-graphene lubricating oil in the engine field. In this paper, nano-graphene powder was chemically grafted to prepare nano-graphene lubricating oil with high dispersion stability. The influence of nano-graphene on physicochemical properties of lubricating oil was studied, and the influence of nano-graphene on engine power performance, economic performance and emission performance was explored. The results show that after modification, the dispersion of nano-graphene in lubricating oil is improved. Compared with pure lubricating oil, the addition of nano-graphene makes the kinematic viscosity of lubricating oil slightly lower, and has little effect on the density, flash point, pour point and total acid value of lubricating oil. The reversed towing torque of nano-graphene lubricating oil is reduced by 1.82-5.53%, indicating that the friction loss decreases. The specific fuel consumption of the engine is reduced, which indicates that the fuel economic performance is improved. Engine HC+NOX, CH4, CO2 emissions do not change much, but particulate matter (PM) emissions increase by 8.85%. The quantity concentration of nuclear particles, accumulated particles and total particles of nano-graphene lubricating oil are significantly higher than that of pure lubricating oil. And the increase of the quantity concentration of accumulated particles is more obvious than that of nuclear particles, and the larger the load, the more obvious this phenomenon. In order to apply nano-graphene lubricating oil to the engine, it is also necessary to further study its impact on the post-processing system, adjust the control strategy of the post-processing system and then test and calibrate.

Evaluation of the value of Synechococcus 7942 as a sensitizer for photo-sonodynamic therapy against breast cancer.

This study was conducted to investigate the value of Synechococcus 7942 (Syne) as a sensitizer for photo-sonodynamic therapy (PSDT). Syne was characterized. The efficacy of Syne-mediated PSDT were verified in vitro (in 4T1 breast cancer cells) and in vivo (in a breast tumor-bearing mouse model). The safety of Syne-mediated PSDT was verified in vivo. Results indicated that Syne triggered the generation of oxygen and ROS during PSDT, thereby inducing cell death in 4T1 cells. Syne-mediated PSDT induced the death of tumor cells both in vitro and in vivo. The speed of tumor growth was delayed in animals receiving PSDT. Syne-mediated PSDT was more effective than photodynamic therapy or sonodynamic therapy alone. In addition, administration of a Syne monomer resulted in satisfactory tumor targeting. Syne-mediated PSDT affected neither the animal body weight nor the major organs, indicating satisfactory safety. Accordingly, Syne is an efficient, safe, and readily available sensitizer that is ideal for potential clinical use of PSDT to treat breast cancer. The findings of this study are useful for exploration of a novel sensitizer for PSDT, which might be a promising alternative therapy against breast cancer.

Effect of senior executives' overseas experience on corporate green innovation.

Against the background of increasingly severe environmental problems, green development has gained widespread attention, and green innovation has thus become crucial for enterprises. This study used 2007-2019 data from listed A-share companies in China to evaluate the effect of senior executives' overseas experience on corporate green innovation. The results showed that senior executives' overseas experience could promote green innovation in companies. This positive effect was more significant for private enterprises and high-tech enterprises, especially in eastern China. The CEO pay regulation have a significant negative moderating effect on this positive effect. This study enriches upper echelons theory and provides theoretical support for government agencies to accelerate innovative green development strategies. The results can also provide a decision-making basis for governments to formulate policies to promote enterprises' green development.

Effect of nano-graphene lubricating oil on particulate matter of a diesel engine.

Nano-graphene lubricating oil with appropriate concentration shows excellent performance in reducing friction and wear under different working conditions of diesel engines, and has been widely concerned. Lubricating oil has a significant impact on particulate matter (PM) emissions. At present, there are few studies on the impact of nano-graphene lubricating oil on the physicochemical properties of PM. In order to comprehensively evaluate the impact of nano-graphene lubricating oil on diesel engines, this paper mainly focused on the effects of lubricating oil nano-graphene additives on the particle size distribution and physicochemical properties of PM. The results show that, compared with pure lubricating oil, the total number of nuclear PM and accumulated PM of nano-graphene lubricating oil is significantly increased. The fractal dimension of PM of nano-graphene lubricating oil increases and its structure becomes more compact. The average fringe separation distance of basic carbon particles decreases, the average fringe length increases. The degree of ordering and graphitization of basic carbon particles are higher. The fringe tortuosity of basic carbon particles decreases, and the fluctuation of carbon layer structure of basic carbon particles decreases. Aliphatic substances in PM are basically unchanged, aromatic components and oxygen functional groups increase. The initial PM oxidation temperature and burnout temperature increase, the maximum oxidation rate temperature and combustion characteristic index decrease, and the activation energy increases, making it more difficult to oxidize. This was mainly caused by the higher graphitization degree of PM of nano-graphene lubricating oil and the increased content of aromatic substances.

Cas13b-mediated RNA targeted therapy alleviates genetic dilated cardiomyopathy in mice.

BACKGROUND: Recent advances in gene editing technology have opened up new avenues for in vivo gene therapy, which holds great promise as a potential treatment method for dilated cardiomyopathy (DCM). The CRISPR-Cas13 system has been shown to be an effective tool for knocking down RNA expression in mammalian cells. PspCas13b, a type VI-B effector that can be packed into adeno-associated viruses and improve RNA knockdown efficiency, is a potential treatment for diseases characterized by abnormal gene expression. RESULTS: Using PspCas13b, we were able to efficiently and specifically knockdown the mutant transcripts in the AC16 cell line carrying the heterozygous human TNNT2R141W (hTNNT2R141W) mutation. We used adeno-associated virus vector serotype 9 to deliver PspCas13b with specific single guide RNA into the hTNNT2R141W transgenic DCM mouse model, effectively knocking down hTNNT2R141W transcript expression. PspCas13b-mediated knockdown significantly increased myofilament sensitivity to Ca2+, improved cardiac function, and reduced myocardial fibrosis in hTNNT2R141W DCM mice. CONCLUSIONS: These findings suggest that targeting genes through Cas13b is a promising approach for in vivo gene therapy for genetic diseases caused by aberrant gene expression. Our study provides further evidence of Cas13b's application in genetic disease therapy and paves the way for future applicability of genetic therapies for cardiomyopathy.

Tumor Microenvironment-Responsive One-for-All Molecular-Engineered Nanoplatform Enables NIR-II Fluorescence Imaging-Guided Combinational Cancer Therapy.

The activable NIR-based phototheranostic nanoplatform (NP) is considered an efficient and reliable tumor treatment due to its strong targeting ability, flexible controllability, minimal side effects, and ideal therapeutic effect. This work describes the rational design of a second near-infrared (NIR-II) fluorescence imaging-guided organic phototheranostic NP (FTEP-TBFc NP). The molecular-engineered phototheranostic NP has a sensitive response to glutathione (GSH), generating hydrogen sulfide (H2S) gas, and delivering ferrocene molecules in the tumor microenvironment (TME). Under 808 nm irradiation, FTEP-TBFc could not only simultaneously generate fluorescence, heat, and singlet oxygen but also greatly enhance the generation of reactive oxygen species to improve chemodynamic therapy (CDT) and photodynamic therapy (PDT) at a biosafe laser power of 0.33 W/cm2. H2S inhibits the activity of catalase and cytochrome c oxidase (COX IV) to cause the enhancement of CDT and hypothermal photothermal therapy (HPTT). Moreover, the decreased intracellular GSH concentration further increases CDT's efficacy and downregulates glutathione peroxidase 4 (GPX4) for the accumulation of lipid hydroperoxides, thus causing the ferroptosis process. Collectively, FTEP-TBFc NPs show great potential as a versatile and efficient NP for specific tumor imaging-guided multimodal cancer therapy. This unique strategy provides new perspectives and methods for designing and applying activable biomedical phototheranostics.

The impact of two dietary patterns on hyperuricemia in adults: A meta analysis of observational studies.

BACKGROUND: Hyperuricemia (HUA) is a crucial factor contributing to some chronic diseases among adults. In past observational literatures, scholars have debated the effectiveness of dietary pattern on HUA and inconsistencies exist. Given this condition, the study aimed to provide a comparative assessment of the relation between dietary pattern and HUA risk and offer implications to policy makers. METHODS: A systematic research was undertaken in PubMed, Web of Science, Cochrane, Embase, Medicine, ScienceDirect and Medline to identify observational studies examining the effect of dietary pattern on HUA, and search period was from past to January 2022. Meta analysis was applied by using the Stata version 11.0 software. RESULTS: A total of 34,583 adults from 8 observational studies, 45,525 adults from 6 observational studies were included to examine the effectiveness of "healthy" and "meat/western" dietary patterns on HUA risk respectively. The findings suggested that "healthy" dietary pattern significantly decreased the HUA risk (OR = 0.73; 95% CI: 0.61-0.88) both in Eastern countries (OR = 0.79; 95% CI: 0.64-0.98) and Western countries (OR = 0.53; 95% CI: 0.30-0.92) while the "Meat/Western" pattern increased the HUA possibilities (OR = 1.26; 95% CI: 1.17-1.37). Stratified analysis exhibited that "healthy" pattern reduced HUA risk in adults was more effective in cohort study (OR = 0.79; 95% CI: 0.72-0.86). CONCLUSIONS: This study's findings highlighted the potential benefit of healthy dietary pattern in decreasing HUA risk. Accordingly, implementing policy makers of countries should enhance to appeal adults to keep a healthy diet, offer financial support to low-income staff, or provide guidelines for adult's dietary behavior changes. TRIAL REGISTRATION NUMBER: INPLASY: INPLASY202290034.

Cu-mediated enantioselective C-H alkynylation of ferrocenes with chiral BINOL ligands.

A wide range of Cu(II)-catalyzed C-H activation reactions have been realized since 2006, however, whether a C-H metalation mechanism similar to Pd(II)-catalyzed C-H activation reaction is operating remains an open question. To address this question and ultimately develop ligand accelerated Cu(II)-catalyzed C-H activation reactions, realizing the enantioselective version and investigating the mechanism is critically important. With a modified chiral BINOL ligand, we report the first example of Cu-mediated enantioselective C-H activation reaction for the construction of planar chiral ferrocenes with high yields and stereoinduction. The key to the success of this reaction is the discovery of a ligand acceleration effect with the BINOL-based diol ligand in the directed Cu-catalyzed C-H alkynylation of ferrocene derivatives bearing an oxazoline-aniline directing group. This transformation is compatible with terminal aryl and alkyl alkynes, which are incompatible with Pd-catalyzed C-H activation reactions. This finding provides an invaluable mechanistic information in determining whether Cu(II) cleaves C-H bonds via CMD pathway in analogous manner to Pd(II) catalysts.

G protein-coupled receptor 158 modulates sensitivity to the sedative-hypnotic effect of ethanol in male mice.

BACKGROUND: Sensitivity to ethanol provides an index of the predisposition to recover from unconsciousness induced by a dose of ethanol. The role of the G protein-coupled receptor 158 (GPR158) in modulating sensitivity to the sedative-hypnotic effect of ethanol has not been investigated. METHODS: Loss of righting reflex (LORR) is a behavioral indicator of hypnosis in rodents. In this study, Gpr158-/- mice and wild-type (WT) littermates (n = 8/genotype) were tested using LORR induced by a dose of 3.5 g/kg ethanol, an open-field test (OFT), and a measure of blood ethanol concentration. The OFT was used to examine the role of GPR158 in the ethanol effect on motor activity in Gpr158-/- mice (n = 6/genotype). We also tested CamK2A-Cre;Gpr158fl/fl (n = 9) and Vgat-Cre;Gpr158fl/fl mice (n = 10) using the LORR test and OFT to compare with controls (n = 9 and 8, respectively). RESULTS: Gpr158 deficiency prolonged the LORR duration by 110.6%, t(14) = -5.241, p = 0.0001, without altering spontaneous activity, t(14) = -0.718, p = 0.485, or ethanol metabolism, F(1, 8) = 0.259, p = 0.625. Gpr158 knockout did not change the ethanol effect on locomotion, F(1, 10) = 0.262, p = 0.62. The LORR duration increased by 69% in the conditional knockouts of Gpr158 within calcium/calmodulin-dependent protein kinase II alpha-positive (CamK2A+ ) neurons, t(16) = -2.914, p = 0.01, and by 92% in the vesicular GABA transporter-positive (Vgat+ ) neurons, t(9.802) = -2.519, p = 0.023. Locomotion was not altered in Camk2A-Cre;Gpr158fl/fl , t(16) = 0.49, p = 0.631 or Vgat-Cre;Gpr158fl/fl mice, t(16) = 0.035, p = 0.972. CONCLUSIONS: This study reveals the key role of neuronal GPR158 in shaping sensitivity to the sedative-hypnotic effect of ethanol. These findings contribute to our understanding of the neurobiology of ethanol intoxication.

Hydroxychloroquine Ameliorates Hematuria in Children with X-Linked Alport Syndrome: Retrospective Case Series Study.

Purpose: As a rare collagen type IV hereditary kidney disease, X-linked Alport syndrome (XLAS) is the most common form of Alport syndrome, the prevalence of which is estimated at 1:10,000 of the population, four times higher than the prevalence rate of autosomal recessive Alport syndrome. To describe a series of eight XLAS children with persistent hematuria and proteinuria and the clinical outcomes after hydroxychloroquine (HCQ) treatment to assess its efficacy as early intervention. Patients and Methods: The study retrospectively analysed 8 patients with persistent hematuria and proteinuria at different onset ages who were diagnosed with XLAS and been treated with HCQ. The urinary erythrocyte count, urinary albuminn were measured. Descriptive statistics were used to estimate the patients' responses to HCQ treatment after one month, three months, and six months. Results: After the first month, the three months, and the six months of HCQ treatment, the urinary erythrocyte counts of four, seven, and eight children were significantly reduced; the decreasing proteinuria was found in two, four, and five children. Only one child with increasing proteinuria was found after 1-month HCQ treatment. This proteinuria was maintained after 3-month HCQ treatment but decreased to minor after 6-month HCQ treatment. Conclusion: We present the first potential efficacy of HCQ treatment in XLAS with hematuria and persistent proteinuria. It suggested that HCQ could be an effective treatment to ameliorate hematuria and proteinuria.

Artificial Intelligence Technology in Basketball Training Action Recognition.

The primary research purpose lies in studying the intelligent detection of movements in basketball training through artificial intelligence (AI) technology. Primarily, the theory of somatosensory gesture recognition is analyzed, which lays a theoretical foundation for research. Then, the collected signal is denoised and normalized to ensure that the obtained signal data will not be distorted. Finally, the four algorithms, decision tree (DT), naive Bayes (NB), support vector machine (SVM), and artificial neural network (ANN), are used to detect the data of athletes' different limb movements and recall. The accuracy of the data is compared and analyzed. Experiments show that the back propagation (BP) ANN algorithm has the best action recognition effect among the four algorithms. In basketball training athletes' upper limb movement detection, the average accuracy rate is close to 93.3%, and the average recall is also immediate to 93.3%. In basketball training athletes' lower limb movement detection, the average accuracy rate is close to 99.4%, and the average recall is immediate to 99.4%. In the detection of movements of upper and lower limbs: the recognition method can efficiently recognize the basketball actions of catching, passing, dribbling, and shooting, the recognition rate is over 95%, and the average accuracy of the four training actions of catching, passing, dribbling, and shooting is close to 98.95%. The intelligent basketball training system studied will help basketball coaches grasp the skilled movements of athletes better to make more efficient training programs and help athletes improve their skill level.

Efficacy of Human Adipose Derived Mesenchymal Stem Cells in Promoting Skin Wound Healing.

Background: The aim of this pilot clinical study is to evaluate the efficacy of human adipose derived mesenchymal stem cells (HAMSCs) treatment for the wound healing with patients. Methods: This study was a clinical trial to investigate the efficacy of human adipose derived mesenchymal stem cells treatment for the wound healing with patients. 346 patients with skin wounds attending the central hospital of Yue Yang were enrolled in the study, setting in the period from January 2016 to January 2021. Patients were randomly allocated into two groups: experimental group received treatment with human adipose derived mesenchymal stem cells for each 10 cm2 of wound and control group received conventional dressing with normal saline for each 10 cm2 of wound. Results: No adverse events were recorded during the period of treatment. The granulation tissue coverage rate and thickness of granulation tissue after 10 days of treatment in experimental group were significantly improved compared with control group. Furthermore, the occurrence of bleeding of wound and suppurative wounds between two groups had significant difference (P < 0.05). Conclusion: The data in this pilot study indicated that human adipose derived mesenchymal stem cells may be a safe and effective alternative therapy for wound healing. Moreover, larger, placebo-controlled, perspective studies are necessity to evaluate the efficacy and safety of human adipose derived mesenchymal stem cells treatment for wound healing patients.

Determination of the pathogenicity of a novel COL4A5 missense variant by CRISPR-Cas9 in kidney podocytes.

OBJECTIVE: The main purpose of this research was to investigate the influence of the novel COL4A5 missense mutation on collagen type IV. METHODS: Clinical data and detailed family history were collected. Targeted next-generation sequencing (NGS) was applied to examine potential pathogenic variants in COL4A3, COL4A4, COL4A5 genes in the proband, and then the variants were analyzed using bioinformatics tools and pedigree analysis. The CRISPR/Cas9 gene editing was used to knock in potential pathogenic variants in human podocytes, and then western blot analyses and immunofluorescence assays were used to measure COL4A5 protein expression. RESULTS: Three patients (I: 2, II: 1 and II: 2) presented with microscopic hematuria and proteinuria, and the patient II: 1 progressed to abnormal renal function by age 14. A novel missense variant, c.2641G>A (p. Gly881Arg), located in exon 31 of COL4A5 gene, was chosen as a possible pathogenic variant. The variant significantly decreased collagen IV α5 chain expression in CRISPR/Cas9 gene edited podocytes. CONCLUSION: By conducting NGS and CRISPR/Cas9 gene-editing of podocytes, a novel COL4A5 missense variant, c.2641G>A (p. Gly881Arg), was confirmed to be the genetic defect of X-linked Alport syndrome in the Chinese family. Our findings extend the genetic spectrum of X-linked Alport syndrome with COL4A5 mutations and provide a method for evaluating the functional significance of novel COL4A5 missense variants in vitro.

Breast surgery for young women with early-stage breast cancer: Mastectomy or breast-conserving therapy?

ABSTRACT: Whether breast-conserving therapy (BCT) should be chosen as a local treatment for young women with early-stage breast cancer is controversial. This study compared the survival benefits of BCT or mastectomy in young women under 40 with early-stage breast cancer and further explored age-stratified outcomes. This study investigated whether there is a survival benefit when young women undergo BCT compared with mastectomy.The characteristics and prognosis of white women under 40 with stage I-II breast cancer from 1988 to 2016 were analyzed using the Surveillance, Epidemiology, and End Results (SEER) database. These women were either treated with BCT or mastectomy. The log-rank test of the Kaplan-Meier survival curve and Cox proportional risk regression model were used to analyze the data and survival. The analysis was stratified by age (18-35 and 36-40 years).A total of 23,810 breast cancer patients were included, of whom 44.9% received BCT and 55.1% underwent mastectomy, with a median follow-up of 116 months. Patients undergoing mastectomy had a higher tumor burden and younger age. By the end of the 20th century, the proportion of BCT had grown from nearly 35% to approximately 60%, and then gradually fell to 35% into the 21st century. Compared with the mastectomy group, the BCT group had improved breast cancer-specific survival (BCSS) (hazard ratio [HR] 0.917; 95% CI, 0.846-0.995, P = .037) and overall survival (OS) (HR 0.925; 95% CI, 0.859-0.997, P = .041). In stratified analysis according to the different ages, the survival benefit of BCT was more pronounced in the slightly older (36-40 years) group while there was no significant survival difference in the younger group (18-35 years).In young women with early-stage breast cancer, BCT showed survival benefits that were at least no worse than mastectomy, and these benefits were even better in the 36 to 40 years age group. Young age may not be a contraindication for BCT.

Comparison of the ductal carcinoma in situ between White Americans and Chinese Americans.

ABSTRACT: Currently, the wide-spread use of screening mammography has led to dramatic increases in ductal carcinoma in situ (DCIS). However, DCIS of Chinese Americans, the largest Asian subgroup in American, has rarely been comprehensively studied over the past decade. This work compared the DCIS characteristics and prognosis of Chinese American patients with White Americans in the USA to determine the characteristics and prognosis of DCIS patients of Chinese Americans.The data were obtained using the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) data. The diagnosis and treatment variables between the two groups were compared by means of Chi-square tests. Survival was determined with the use of the Kaplan-Meier method and the multivariable Cox proportional hazard regression model.From 1975 to 2016, 81,745 White Americans and 2069 Chinese Americans were diagnosed with ductal carcinoma in situ. Compared with the white patients, the Chinese Americans were younger (P < .001) with smaller tumors (P < .001) and higher family income (P < .001). DCIS patients of Chinese American group accounted for a higher percentage of all breast cancers than the whites (P < .001). In the multivariable Cox proportional hazard regression analysis, Chinese American was an independent favorable prognostic factor in terms of overall survival (OS) (HR, 0.684; 95% CI, 0.593-0.789; P < .001) compared with the white group.In conclusion, DCIS characteristics of the Chinese group, which exhibited a higher proportion of younger age, a higher DCIS ratio, and a better prognosis, were distinct from those of the White Americans.

Neuroprotective gain of Apelin/APJ system.

Apelin is an endogenous ligand of G protein-coupled receptor APJ. In recent years, many studies have shown that the apelin/APJ system has neuroprotective properties, such as anti-inflammatory, anti-oxidative stress, anti-apoptosis, and regulating autophagy, blocking excitatory toxicity. Apelin/APJ system has been proven to play a role in various neurological diseases and may be a promising therapeutic target for nervous system diseases. In this paper, the neuroprotective properties of the apelin/APJ system and its role in neurologic disorders are reviewed. Further understanding of the pathophysiological effect and mechanism of the apelin/APJ system in the nervous system will help develop new therapeutic interventions for various neurological diseases.

Hydrogen sulfide attenuates postoperative cognitive dysfunction through promoting the pathway of Warburg effect-synaptic plasticity in hippocampus.

Postoperative cognitive dysfunction (POCD) is deemed to a severe surgical complication without effective treatment. Previous work has confirmed the important modulatory role of hydrogen sulfide (H2S) in cognitive function. This study was proposed to explore whether H2S relieves POCD and the possible mechanisms. We demonstrated that NaHS (a donor of H2S) reversed the inhibited endogenous H2S generation in the hippocampus of postoperative rats. NaHS attenuated the cognitive impairment of postoperative rats in the Y-maze, Novel object recognition, and Morris water maze tests. NaHS enhanced the expressions of synaptic plasticity-related proteins, synapsin-1 and PSD-95, increased the synaptic density, and decreased the destruction of synaptic structures in the hippocampus of postoperative rats. Moreover, NaHS promoted Warburg effect in the hippocampus of postoperative rats, as reflected by increases in the expressions of hexokinase 2, pyruvate kinase M2, lactate dehydrogenase A, and pyruvate dehydrogenase kinase 1, an enhancement in the content of lactate, and a reduction in the expression of pyruvate dehydrogenase. The inhibitor of Warburg effect, 2-Deoxy-D-glucose (2-DG), not only reversed NaHS-enhanced Warburg effect in the hippocampus of postoperative rats, but also significantly abolished NaHS-exerted protective effect on cognitive function. Furthermore, 2-DG reversed NaHS-exerted enhancement in the expressions of synapsin-1 and PSD-95, increase in the synaptic density, and decrease in the destruction of synaptic structures in the hippocampus of postoperative rats. Collectively, these results indicate that H2S alleviates POCD through enhancing hippocampal Warburg effect, which subsequently improves synaptic plasticity in the hippocampus.

[Effects of propofol on TGF-ß1 induced activation of hepatic stellate cells and its mechanism].

Objective: To observe the effects of propofol on the activation of hepatic stellate cell line HSC2-T6 induced by transforming growth factor-beta 1 (TGF-ß1) and explore its possible mechanism.Methods: The cells were divided into control group, TGF-ß1 group, propofol group, TGF-ß1 + propofol group, rapamycin group, TGF-ß1 + propofol + rapamycin group. Cells were treated with rapamycin (5 µmol/L) for 1 hour, propofol (100 µmol/L) for 1 hour, then TGF-ß1 (5 ng/ml) was added to co-culture for 24 hours. Cell proliferation was measured by MTT assay. The concentrations of hyaluronic acid (HA), collagen IV (IV-C) and laminin (LN) in the supernatant of cell culture medium were measured by ELISA. The ultrastructure of cells was observed by transmission electron microscopy. The expressions of alpha-smooth muscle actin (α-SMA), mammalian rapamycin target protein (mTOR), phosphorylated mTOR (p-mTOR) and the autophagy related gene Beclin 1, LC3 and p62 were measured by Western blot. Results: Compared with control group, cell proliferation, the expression of α-SMA, the concentrations of HA, IV-C and LN in culture supernatant, the number of autophages, the expressions of Beclin-1 and LC3-II, the ratio of LC3-II/LC3-I in HSC2-T6 cells were increased significantly, while the expression of p-mTOR, the ratio of p-mTOR/mTOR and the expression of p62 protein were decreased significantly in TGF-ß1 group (All P＜0.05). Compared with TGF-ß1 group, cell proliferation, the expression of α-SMA, the concentrations of HA, IV-C and LN in culture supernatant, the number of autophages, the expressions of Beclin-1 and LC3-II, the ratio of LC3-II/LC3-I in HSC2-T6 cells in TGF-ß1 group were decreased significantly, and the expression of p-mTOR, the ratio of p-mTOR/mTOR and expression of p62 protein were increased significantly in TGF-ß1 + propofol group (All P＜0.05). Conclusion: Propofol inhibits the activation of hepatic stellate cells induced by TGF-beta 1, and its mechanism involves the mTOR-autophagy pathway.

The MyD88 inhibitor TJ-M2010-2 suppresses proliferation, migration and invasion of breast cancer cells by regulating MyD88/GSK-3ß and MyD88/NF-κB signalling pathways.

MyD88 has been implicated in the tumourigenesis, metastasis and recurrence of breast cancer (BC). Here we utilized TJ-M2010-2 (TJ), an inhibitor of MyD88 homodimerimerization, and siMyD88 to suppress the function of MyD88 in MCF-7 and MDA-MB-231 cells. BC cells were treated in vitro and xenografted into nude mice to generate a model in vivo. TJ inhibited BC cell growth by impeding proliferation rather than by promoting apoptosis in vitro. Additionally, TJ and siMyD88 significantly attenuated cell migration and invasion, inhibited EMT-like progression and reduced cytokine (IL-6, IL-8, TGF-ß1 and TNF-α) secretion induced by LPS. In vivo, TJ significantly hindered tumour growth in mice. Notably, TJ also decreased the secretion of IL-6, IL-8, TGF-ß1, and TNF-α and M2 macrophage infiltration in the tumour microenvironment. The expression of MyD88, TRAF6, NF-κB p65, Snail, MMP-2, MMP-9, p-GSK-3ß and p-Akt was significantly downregulated by TJ in BC cells and tumour tissues. Collectively, these results suggest that a MyD88 inhibitor (TJ) may be a promising therapeutic modality for treating BC patients.

Intraductal Therapy in Breast Cancer: Current Status and Future Prospective.

With our improved understanding of the biological behavior of breast cancer, minimally invasive intervention is urgently needed for personalized treatment of early disease. Intraductal therapy is one such minimally invasive approach. With the help of appropriate tools, technologies using the intraductal means of entering the ducts may be used both to diagnose and treat lesions in the mammary duct system with less trauma and at the same time avoid systemic toxicity. Traditional agents such as those targeting pathways, endocrine therapy, immunotherapy, or gene therapy can be used alone or combined with other new technologies, such as nanomaterials, through the intraductal route. Additionally, relevant mammary tumor models in rodents which reflect changes in the tumor microenvironment will help deepen our understanding of their biological behavior and heterogeneity. This article reviews the current status and future prospects of intraductal therapy in breast cancer, with emphasis on ductal carcinoma in situ.