Design and Synthesis of Cytotoxic Water-Soluble Rocaglaol Derivatives against HEL Cells by Inhibiting Fli-1.

Rocaglaol, embedding a cyclopenta[b]benzofuran scaffold, was isolated mainly from the plants of Aglaia and exhibited nanomolar level antitumor activity. However, the drug-like properties of these compounds are poor. To improve the physicochemical properties of rocaglaol, 36 nitrogen-containing phenyl-substituted rocaglaol derivatives were designed and synthesized. These derivatives were tested for the inhibitory effects on three tumor cell lines, HEL, MDA-231, and SW480, using the MTT assay. Among them, 22 derivatives exhibited good cytotoxic activities with IC50 values between 0.11 ± 0.07 and 0.88 ± 0.02 µM. Fourteen derivatives exhibited stronger cytotoxicity than the positive control, adriamycin. In particular, a water-soluble derivative revealed selective cytotoxic effects on HEL cells (IC50 = 0.19 ± 0.01 µM). This compound could induce G1 cell cycle arrest and apoptosis in HEL cells. Western blot assays suggested that the water-soluble derivative could downregulate the expression of the marker proteins of apoptosis, PARP, caspase-3, and caspase-9, thus inducing apoptosis. Further CETSA and Western blot studies implied that this water-soluble derivative might be an inhibitor of friend leukemia integration 1 (Fli-1). This water-soluble derivative may serve as a potential antileukemia agent by suppressing the expression of Fli-1.

CST3 alleviates bilirubin-induced neurocytes' damage by promoting autophagy.

High concentrations of unconjugated bilirubin (UCB) have toxic effects. The aim of our study was to find a way to elevate UCB tolerance or inhibit its toxicity in neurocytes. It has been reported that cystatin C (CST3) concentrations have a significant positive correlation with total bilirubin (TB) levels and a negative correlation with albumin levels. In addition, CST3 can directly bind UCB, decrease human umbilical vein endothelial cells' permeability, improve blood-brain barrier integrity after ischemic brain injury in mice, and induce autophagy. We hypothesized that CST3 could increase the solubility of UCB, decrease permeability of neurocytes, induce autophagy of neurocytes, and alleviate bilirubin-induced damage. To verify our hypothesis, we measured TB and conjugated bilirubin levels, and the permeability and autophagy of neurocytes treated with UCB and CST3. Our findings suggest that CST3 can protect against UCB-induced damage in neurocytes and that autophagy played an important role in this process.

Targeted Energy Metabolomics Combined with Spatial Metabolomics Study on the Efficacy of Guhong Injection Against Cerebral Ischemia Reperfusion.

Optimizing the metabolic phenotype to improve cerebral function is critical for treatment of cerebral ischemia-reperfusion (I/R) injury. Guhong injection (GHI), which comprised safflower extract and aceglutamide, is widely prescribed in Chinese medicine for the treatment of cerebrovascular diseases. In this study, a combination of LC-QQQ-MS and MALDI-MSI were utilized to explore tissue-specific metabolic alterations in the brain of I/R, as well as to evaluate the therapeutic effect of GHI. Pharmacological evaluation demonstrated that GHI can significantly improve infarction rate, neurological deficit, cerebral blood flow, and neuronal damage in I/R rats. Based on LC-QQQ-MS, 23 energy metabolites were found to be significantly altered in the I/R group compared to the sham group (P < 0.05). After GHI treatment, 12 metabolites, including G6P, TPP, NAD, citrate, succinate, malate, ATP, GTP, GDP, ADP, NADP, and FMN showed a significant tendency of returning to baseline values (P < 0.05). Based on MALDI-MSI, 4 metabolites in glycolysis and TCA, 4 metabolites in nucleic acid metabolism, 4 amino acid metabolites, and 6 metabolites were discovered and compared between the different groups in the four special regions of cortex, hippocampus, hypothalamus, and striatum. Parts of these were found to have significant changes after I/R in the special brain region, and were regulated by GHI. The study provides comprehensive and detailed information for specific metabolic reprogramming of brain tissue in rats with I/R, and the therapeutic effect of GHI. Schema describing the discovery strategies of integrated LC-MS and MALDI-MSI to identify cerebral ischemia reperfusion metabolic reprogramming and GHI therapeutic effects.

Bionic Structure Inspired by Tree Frogs to Enhance Damping Performance.

Magnetic fluid shock absorbers (MFSAs) have been successfully utilized to eliminate microvibrations of flexible spacecraft structures. The method of enhancing the damping efficiency of MFSAs has always been a critical issue. To address this, we drew inspiration from the tree frog's toe pads, which exhibit strong friction due to their unique surface structure. Using 3D printing, we integrated bionic textures copied from tree frog's toe pad surfaces onto MFSAs, which is the first time to combine bionic design and MFSAs. Additionally, this is also the first time that surface textures have been applied to MFSAs. However, we also had to consider practical engineering applications and manufacturing convenience, so we modified the shape of bionic textures. To do so, we used an edge extraction algorithm for image processing and obtained recognition results. After thorough consideration, we chose hexagon as the shape of surface textures instead of bionic textures. For theoretical analysis, a magnetic field-flow field coupling dynamic model for MFSAs was built for the first time to simulate the magnetic fluid (MF) flow in one oscillation cycle. Using this model, the flow rate contours of the MF were obtained. It was observed that textures cause vortexes to form in the MF layer, which produced an additional velocity field. This increased the shear rate, ultimately leading to an increase in flow resistance. Finally, we conducted vibration reduction experiments and estimated damping characteristics of the proposed MFSAs to prove the effectiveness of both bionic texture and hexagon surface textures. Fortunately, we concluded that hexagon surface textures not only improve the damping efficiency of MFSAs but also require less MF mass.

A Time-Domain Signal Processing Algorithm for Data-Driven Drive-by Inspection Methods: An Experimental Study.

Constructional material deterioration and member damage can cause changes in the dynamic characteristics of bridge structures, and such changes can be tracked in the responses of passing vehicles via the vehicle-bridge interaction (VBI). Though data-driven methods have shown promising results in damage inspection for drive-by methods, there is still much room for improvement in their performance. Given this background, this paper proposes a novel time-domain signal processing algorithm for the raw vehicle acceleration data of data-driven drive-by inspection methods. To achieve the best data processing performance, an optimizing strategy is designed to automatically search for the optimal parameters, tuning the algorithm. The proposed method intentionally overcomes the difficulties in the application of drive-by methods, such as measurement noise, speed variance, and enormous data volumes. Meanwhile, the use of this method can greatly improve the accuracy and efficiency of Machine Learning (ML) models in vehicle-based damage detection. It consists of a filtering process to denoise the data, a pooling process to reduce data redundancy, and an optimizing procedure to maximize algorithm performance. A dataset is obtained to validate the proposed algorithm through laboratory experiments with a scale truck model and a steel beam. The results show that, compared to using raw data, the present algorithm can increase the average accuracy by 12.2-15.0%, and the average efficiency by 35.7-96.7% for different damaged cases and ML models. Additionally, the functions of filtering and pooling operations, the influence of window function parameters, as well as the performance of different sensor locations, are also investigated in the paper. The goal is to present a signal processing algorithm for data-driven drive-by inspection methods to improve their detection performance of bridge damage caused by material deterioration or structural change.

Investigation of Frequency-Domain Dimension Reduction for A2M-Based Bridge Damage Detection Using Accelerations of Moving Vehicles.

Recent decades have witnessed a rise in interest in bridge health monitoring utilizing the vibrations of passing vehicles. However, existing studies commonly rely on constant speeds or tuning vehicular parameters, making their methods challenging to be used in practical engineering applications. Additionally, recent studies on the data-driven approach usually need labeled data for damage scenarios. Still, getting these labels in engineering is difficult or even impractical because the bridge is typically in a healthy state. This paper proposes a novel, damaged-label-free, machine-learning-based, indirect bridge-health monitoring method named the assumption accuracy method (A2M). Initially, the raw frequency responses of the vehicle are employed to train a classifier, and K-folder cross-validation accuracy scores are then used to calculate a threshold to specify the bridge's health state. Compared to merely focusing on low-band frequency responses (0-50 Hz), utilizing full-band vehicle responses can significantly improve the accuracy, meaning that the bridge's dynamic information exists in the higher frequency ranges and can contribute to detecting bridge damage. However, raw frequency responses are generally in a high-dimensional space, and the number of features is much greater than that of samples. To represent the frequency responses via latent representations in a low-dimension space, appropriate dimension-reduction techniques are therefore, needed. It was found that principal component analysis (PCA) and Mel-frequency cepstral coefficients (MFCCs) are suitable for the aforementioned issue, and MFCCs are more damage-sensitive. When the bridge is in a healthy condition, the accuracy values obtained using MFCCs are primarily dispersed around 0.5, but following the occurrence of damage, they increased significantly to 0.89-1.0 in this study.

Exosome-derived GTF2H2 from Huh7 cells can inhibit endothelial cell viability, migration, tube formation, and permeability.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related morbidity and mortality worldwide. Given that HCC is an extraordinarily heterogeneous malignant disease, finding an effective therapeutic strategy for treating it has been difficult. Because of the importance of angiogenesis in tumorigenesis, targeting the more homogenous HCC endothelial cells may be a better therapeutic strategy. In a unpublished manuscript, we found that the expression levels of vascular endothelial growth factor receptor 2 (VEGFR2) and matrix metalloproteinase 2/9 (MMP2/9) were reduced in human HCC tissues that overexpressed DNA damage repair gene general transcription factor II subunit H2 (GTF2H2). This suggested that GTF2H2 may have an inhibitory effect on angiogenesis. Therefore, we hypothesized that GTF2H2 acts as an anti-angiogenesis gene. However, our results showed that GTF2H2 overexpression had no effect on endothelial cell viability, migration, or permeability. To our surprise, treating human umbilical vein endothelial cells (HUVECs) with the culture medium of Huh 7 cells overexpressing GTF2H2 could inhibit their viability, migration, and permeability. We then isolated the culture medium into exosomes and other components from the culture medium. Only GTF2H2-enriched exosomes could inhibit the viability, migration, tube formation, and permeability of HUVECs. Our results suggest that overexpressing GTF2H2 had no effect on HUVECs, while GTF2H2 enriched exosomes from Huh7 cells could inhibit HUVEC phenotypes such as proliferation and migration. Therefore, GTF2H2-enriched exosomes can possibly be utilized as a novel drug for treating HCC and also serve as a potential molecular target for inhibiting tumor angiogenesis.

Prognostic Nomograms for Hospital Survival and Transplant-Free Survival of Patients with Hepatorenal Syndrome: A Retrospective Cohort Study.

Hepatorenal syndrome (HRS) is a life-threatening complication of cirrhosis with a poor prognosis. To develop novel and effective nomograms which could numerically predict both the hospital survival and transplant-free survival of HRS, we retrospectively enrolled a cohort of 149 patients. A backward stepwise method based on the smallest Akaike information criterion value was applied to select the covariates to be included in the Cox proportional hazards models. The Harrell C-index, area under the receiver operating characteristic curve (AUC), Brier score, and Kaplan-Meier curves with the log-rank test were used to assess nomograms. The bootstrapping method with 1000 resamples was performed for internal validation. The nomogram predicting hospital survival included prothrombin activity, HRS clinical pattern, Child-Pugh class, and baseline serum creatinine. The C-index was 0.72 (95% confidence interval (CI), 0.65-0.78), and the adjusted C-index was 0.72 (95% CI, 0.66-0.79). The nomogram predicting transplant-free survival included sex, prothrombin activity, HRS clinical pattern, model for end-stage liver disease-Na score, and peak serum creatinine. The C-index of the nomogram was 0.74 (95% CI, 0.69-0.79), and the adjusted C-index was 0.74 (95% CI, 0.68-0.79). The AUC and Brier score at 15, 30, and 45 days calculated from the hospital survival nomogram and those at 6, 12, and 18 months calculated from the transplant-free survival nomogram revealed good predictive ability. The two models can be used to identify patients at high risk of HRS and promote early intervention treatment.

Antibiotics in elderly Chinese population and their relations with hypertension and pulse pressure.

Although antibiotic exposure in the general population has been well documented by a biomonitoring approach, epidemiologic data on the relationships between urinary antibiotic burden in the elderly with blood pressure (BP) are still lacking. The current study revealed thirty-four antibiotics in urine specimens from 990 elderly patients in Lu'an City, China, with detection frequencies ranging from 0.2 to 35.5%. Among the elderly, the prevalence of hypertension was 72.0%, and 12 antibiotics were detected in more than 10% of individuals with hypertension. The elderly with hypertension had the maximum daily exposure (5450.45 µg/kg/day) to fluoroquinolones (FQs). Multiple linear regression analyses revealed significant associations of BP and pulse pressure (PP) with exposure to specific antibiotics. The estimated ß values (95% confidence interval) of associations with systolic blood pressure (SBP) in the right arm were 4.42 (1.15, 7.69) for FQs, 4.26 (0.52, 8.01) for the preferred as human antibiotics (PHAs), and 3.48 (0.20, 6.77) for the mixtures (FQs + tetracyclines [TCs] (tertile 3 vs. tertile 1)), respectively. Increased concentrations of TCs were associated with decreased diastolic BP (DBP; tertile 3: -1.75 [-3.39, -0.12]) for the right arm. Higher levels of FQs (tertile 3: 4.28 [1.02, 7.54]), PHAs (tertile 3: 4.25 [0.49, 8.01]), and FQs + TCs (tertile 3: 3.99 [0.71, 7.26]) were associated with increased SBP, and an increase in DBP for FQs (tertile 3: 1.82 [0.22, 3.42]) was shown in the left arm. Also, higher urinary concentrations of FQs (tertile 3: 3.18 [0.53, 5.82]), PHAs (tertile 3: 3.42 [0.40, 6.45]), and FQs + TCs (tertile 3: 3.06 [0.40, 5.72]) were related to increased PP, whereas a decline in PP for TCs (tertile 2: -2.93 [-5.60, -0.25]) in the right arm. And increased concentrations of penicillin V (tertile 3: 5.31 [1.53, 9.10]) and FQs + TCs (tertile 3: 2.84 [0.19, 5.49]) were related to higher PP in the left arm. By utilizing restricted cubic splines, our current study revealed a potential nonlinear dose-response association between FQ exposure and hypertension risk. In conclusion, this investigation is the first to present antibiotic exposure using a biomonitoring approach, and informs understanding of impacts of antibiotic residues, as emerging hazardous pollutants, on the hypertension risk in the elderly.

Endothelium-dependent vasorelaxant effects of praeruptorin a in isolated rat thoracic aorta.

Praeruptorin A (PA) is a natural coumarin compound from the roots of Radix Peucedani and is commonly used in the treatment of certain respiratory diseases and hypertension. Although previous studies identified relaxant effects of PA on tracheal and arterial preparations, little is known about its vasodilative effects and underlying mechanisms. Here, an organ bath system and tension recording methods were used to prepare and analyze isolated rat thoracic aorta artery rings. Aorta artery rings were pre-contracted with phenylephrine and then incubated with PA, and the possible mechanism of relaxation was investigated by adding inhibitors of nitric oxide synthase (NG-nitro-L-arginine methyl ester, L-NAME), endothelial nitric oxide synthase (L-NG-nitroarginine, L-NNA), cyclooxygenase (indomethacin), guanylyl cyclase (1 H-[1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one, ODQ), and KCa channels (tetraethylammonium, TEA). Our study showed that PA-induced vasodilation was blocked by L-NAME, L-NNA, and ODQ, while CaCl2-induced vasoconstriction was countered by PA. Thus, PA may exert a vasodilatory effect by influencing the amounts of endothelium-derived relaxing factors through endothelial-dependent NO-cGMP and prostacyclin pathways (such as NO and prostacyclin 2). In the rat thoracic aorta, PA reduces vasoconstriction by inhibiting Ca2+ inflow.

Profilin 2 and Endothelial Exosomal Profilin 2 Promote Angiogenesis and Myocardial Infarction Repair in Mice.

Cardiovascular diseases (CVD) are the leading cause of death worldwide, wherein myocardial infarction (MI) is the most dangerous one. Promoting angiogenesis is a prospective strategy to alleviate MI. Our previous study indicated that profilin 2 (PFN2) may be a novel target associated with angiogenesis. Further results showed higher levels of serum PFN2 and exosomal PFN2 in patients, mice, and pigs with MI. In this study, we explored whether PFN2 and endothelial cell (EC)-derived exosomal PFN2 could increase angiogenesis and be beneficial for the treatment of MI. Serum PFN2, exosomes, and exosomal PFN2 were elevated in rats with MI. PFN2 and exosomes from PFN2-overexpressing ECs (OE-exo) enhanced EC proliferation, migration, and tube formation ability. OE-exo also significantly increased the vessel number in zebrafish and protected the ECs from inflammatory injury. Moreover, OE-exo-treated mice with MI showed improvement in motor ability, ejection fraction, left ventricular shortening fraction, and left ventricular mass, as well as increased vessel numbers in the MI location, and decreased infarction volume. Mechanistically, PI3K might be the upstream regulator of PFN2, while ERK might be the downstream regulator in the PI3K-PFN2-ERK axis. Taken together, our findings demonstrate that PFN2 and exosomal PFN2 promote EC proliferation, migration, and tube formation through the PI3K-PFN2-ERK axis. Exosomal PFN2 may be a valuable target in the repair of MI injury via angiogenesis.

Identification of potential modifier genes in Chinese patients with Wilson disease.

The mutations in modifier genes may contribute to some inherited diseases including Wilson disease (WD). This study was designed to identify potential modifier genes that contribute to WD. A total of 10 WD patients with single or no heterozygous ATP7B mutations were recruited for whole-exome sequencing (WES). Five hundred and thirteen candidate genes, of which the genetic variants present in at least two patients, were identified. In order to clarify which proteins might be involved in copper transfer or metabolism processes, the isobaric tags for relative and absolute quantitation (iTRAQ) was performed to identify the differentially expressed proteins between normal and CuSO4-treated cell lines. Thirteen genes/proteins were identified by both WES and iTRAQ, indicating that disease-causing variants of these genes may actually contribute to the aberrant copper ion accumulation. Additionally, the c.86C > T (p.S29L) mutation in the SLC31A2 gene (coding CTR2) has a relative higher frequency in our cohort of WD patients (6/191) than reported (0.0024 in gnomAD database) in our healthy donors (0/109), and CTR2S29L leads to increased intracellular Cu concentration and Cu-induced apoptosis in cultured cell lines. In conclusion, the WES and iTRAQ approaches successfully identified several disease-causing variants in potential modifier genes that may be involved in the WD phenotype.

Effect of single tube sections on the structural safety of Chinese solar greenhouse skeletons.

In recent years, the use of single-tube skeletons for the construction of Chinese solar greenhouses has increased. As a consequence, during the selection of the construction materials, the safety of these structures has become an important issue. The single tube section has various forms, but there is no scientific theory to guide the selection process. To the best of our knowledge, the scientific analysis of the impact of single pipe cross section on the safety of greenhouse skeleton has not been addressed so far. In this context, the finite element analysis software was used to calculate and analyze the stress elements, displacement of round tube, Ω tube, elliptic tube and square tube under the same load conditions. We used the Chinese Standard values as a reference and analyzed structural features of different sizes and thicknesses of the greenhouse steel skeleton sections under non-uniform snow load. The results showed that, under the same load condition, the maximum stress in the four skeleton materials was all located at the connection of the transverse tension bar and the front roof. In addition, under same load condition, the greenhouse skeleton with elliptic tube presented the smallest cross-sectional displacement between the different materials tested. The effect of increasing the size of the greenhouse frame was better than that of increasing the greenhouse material thickness. All this work will provide theoretical guidance to the material selection of this structure.

Characterization and clinical evaluation of microsatellite instability and loss of heterozygosity within tumor-related genes in colorectal cancer.

BACKGROUND: Microsatellite instability (MSI) is a biomarker for better outcomes in colorectal cancer (CRC). However, this conclusion is controversial. In addition, MSs can be a useful marker for loss of heterozygosity (LOH) of genes, but this finding has not been well studied. Here, we aimed to clarify the predictive value of MSI/LOH within tumor-related genes in CRC. METHODS: We detected MSI/LOH of MSs in tumor-related genes and the Bethesda (B5) panel by STR scanning and cloning/sequencing. We further analyzed the relationship between MSI/LOH status and clinical features or outcomes by Pearson's Chi-square test, Fisher's exact test and the Kaplan-Meier method. RESULTS: The findings indicated that the MSI rates of B5 loci were all higher than those of loci in tumor-related genes. Interestingly, MSI/LOH of 2 loci in the B5 panel and 12 loci in tumor-related genes were associated with poorer outcomes, while MSI/LOH of the B5 panel failed to predict outcomes in CRC. MSI of BAT25, MSI/LOH of BAT26 and MSI of the B5 panel showed closer relationships with mucinous carcinoma. In addition, LOH-H of the B5 panel was associated with increased lymphatic metastasis. CONCLUSIONS: In summary, MSI/LOH of certain loci or the whole panel of B5 is related to clinical features, and several loci within tumor-related genes showed prognostic value in the outcomes of CRC.

Role of tight junction-associated MARVEL protein marvelD3 in migration and epithelial-mesenchymal transition of hepatocellular carcinoma.

MarvelD3, a recently identified tight junction membrane protein, could be associated with hepatocellular carcinoma (HCC). We aimed to investigate the role of marvelD3 in Epithelial-Mesenchymal Transition (EMT) and migration of HCC and explore the underlying molecular mechanisms. First, we assessed marvlD3 expression in HCC and normal liver tissues and found loss of marvelD3 expression was significantly correlated with the occurrence and TNM stage of HCC. Second, we detected that marvelD3 was downregulated in HCC cells with transforming growth factor ß1 and snail/slug-induced EMT. Finally, we analyzed expression of marvelD3 protein was significantly associated with EMT and the NF-κB signaling pathway. Our study demonstrated that MarvelD3 inhibited EMT and migration of HCC cells along with inhibiting NF-κB signaling pathway.Abbreviations:HCC, Hepatocellular carcinoma; TJ, Tight junction; MARVEL, MAL and related proteins for vesicle trafficking and membrane link; EMT, Epithelial-mesenchymal transition; NF-κB, Nuclear factor kappa B; TAMPs, Tight junction-associated marvel proteins; TGF-ß1, Transforming growth factor-ß1; MMP9, matrix metallopeptidase 9; RT-PCR, Real-time PCR; IHC, Immunohistochemistry; IF, Immunofluorescence.

[Construction of model for multidimensional evaluation of value and risk of Chinese patent medicine].

It is the core of the development for Chinese patent medicine enterprises to cultivate large varieties of Chinese patent medicine, and the selection of potential "seed" products is the prerequisite for the cultivation strategy. By constructing the evaluation model from multiple dimensions of value and risk, we can conduct specialized evaluation of Chinese patent medicines to effectively, professionally and objectively select the "seed" products with large variety cultivation potential. In this paper, the establishment of a multidimensional evaluation system would be discussed from the aspects of drug naming and prescription composition, safety risk and supply guarantee of raw materials and medicinal materials, competition situation, access to policy catalogue, scientific and technological support, clinical evidence and recognition, systematical and standardized collection of information on product instructions, quality standards, policy catalogue, scientific and technological literature, market competition and clinical application of Chinese patent medicines. Through the objective evaluation index and the range of objective index, the multi-dimensional evaluation model on values and risks of Chinese patent medicine products was discussed. Based on this model, a batch of Chinese patent medicine products can be quickly and comprehensively analyzed, and quantitative comparison can be formed among different types and fields of products. According to the evaluation results of the model and the comprehensive evaluation of experts, high-quality "seed" products can be selec-ted, laying a solid foundation for the next step of large variety cultivation. With use of this model, we can further clarify the external competitive advantages and internal priority levels of each product, and provide support for enterprises to optimize product structure and improve product strategic layout.

Study on the yielding behaviors of ferrofluids: a very shear thinning phenomenon.

The yielding behaviors of the ferrofluids are vital for many applications. However, previous studies have mainly focused on the magnetoviscous effect under relatively high shear rates and rarely involved the yielding process of ferrofluids under very low shear rates. In this study, ferrofluid samples of different particle volume concentrations were prepared and their shear thinning behaviors within a wide shear stress range were systematically studied under various magnetic field strengths and temperatures. The very shear thinning phenomenon of ferrofluids was first observed and its microscopic mechanism was analyzed. A precipitous fall-off stage as the mark of yielding appeared between the low shear and high shear plateaus in the viscosity curves of ferrofluids. The precipitous fall-off stage in the viscosity curves became steeper with the increase of the magnetic field strength or decrease in the temperature. For ferrofluids with relatively low particle volume concentrations, the high viscosity limit under the low shear region disappeared when temperature exceeded a certain value and was interpreted as the disappearance of the equilibrium columnar structures under high Brownian thermal interaction level. A composite Ellis model was proved to be suitable for the fitting of different types of yield stresses and a structural number, Sn was proposed for the dimensionless analysis of the shear thinning behaviors of ferrofluids. The findings in this study contribute to a better understanding of the microscopic mechanism of yielding behaviors of ferrofluids and also provide guidance for many practical applications.

[Analysis of patent data of Panax notoginseng and enlightenment of industrial development].

In order to find the trends in Panax notoginseng industries of China, a combination of data analysis and empirical analysis was applied to analyze the application of global P. notoginseng patents, the innovation field, the distribution of patent assets, the patent citation network, the distribution of enterprises, the talent team, the competition and cooperation situation based on the financial big data platform of intellectual property industry. From the perspective of industrial technology hotspots, the clinical application of P. notoginseng is becoming more and more widespread, and its clinical treatment field is further expanding. From the perspective of industrial fields, the P. notoginseng industry has gradually expanded from the traditional Chinese medicine field to food, cosmetics, beverages, tea and other daily consumer goods. From the perspective of patent quality, the average maintenance life of P. notoginseng patents of China is lower than the global level, and the value and quality of patents need to be further improved. And the quality of P. notoginseng of China related patent applications has gradually improved in recent years. We analyzed the technology, capital, and talent issues of P. notoginseng industry of China, and summarized and forecasted the status and trends of P. notoginseng industry development of China. It is considered that scientific and technological innovation has become the core engine for the development of the P. notoginseng industry and intellectual property, especially patent protection, escorted the sustainable development of the P. notoginseng industry. Based on the above analysis, several suggestions were put forward to promote the high-quality development of the P. notoginseng industry. It should strengthen scientific and technological support, especially the need for a large number of high-quality scientific and technological output, expand multi-party cooperation, build a high-level technological innovation platform for the P. notoginseng industry, guide long-term capital to continuously and stably invest, and help the P. notoginseng industry to revitalize.

eEF1A2 exacerbated insulin resistance in male skeletal muscle via PKCß and ER stress.

Recent studies raise the possibility that eukaryotic translation elongation factor 1 alpha (eEF1A) may play a role in metabolism. One isoform, eEF1A2, is specifically expressed in skeletal muscle, heart and brain. It regulates translation elongation and signal transduction. Nonetheless, eEF1A2's function in skeletal muscle glucose metabolism remains unclear. In the present study, suppression subtractive hybridisation showed a decrease in Eef1a2 transcripts in the skeletal muscle of diabetic Mongolian gerbils. This was confirmed at mRNA and protein levels in hyperglycaemic gerbils, and in db/db and high-fat diet-fed mice. Further, this downregulation was independent of Eef1a2 promoter methylation. Interestingly, adeno-associated virus-mediated eEF1A2 overexpression in skeletal muscle aggravated fasting hyperglycaemia, hyperinsulinaemia and glucose intolerance in male diabetic gerbils but not in female gerbil models. The overexpression of eEF1A2 in skeletal muscle also resulted in promoted serum glucose levels and insulin resistance in male db/db mice. Up- and downregulation of eEF1A2 by lentiviral vector transfection confirmed its inhibitory effect on insulin-stimulated glucose uptake and signalling transduction in C2C12 myotubes with palmitate (PA)-induced insulin resistance. Furthermore, eEF1A2 bound PKCß and increased its activation in the cytoplasm, whereas suppression of PKCß by an inhibitor attenuated eEF1A2-mediated impairment of insulin sensitivity in insulin-resistant myotubes. Endoplasmic reticulum (ER) stress was elevated by eEF1A2, whereas suppression of ER stress or JNK partially restored insulin sensitivity in PA-treated myotubes. Additionally, eEF1A2 inhibited lipogenesis and lipid utilisation in insulin-resistant skeletal muscle. Collectively, we demonstrated that eEF1A2 exacerbates insulin resistance in male murine skeletal muscle via PKCß and ER stress.

Rapamycin attenuates the paraquat-induced pulmonary fibrosis through activating Nrf2 pathway.

Oxidative stress is a key regulator of idiopathic pulmonary fibrosis. Paraquat (PQ)-induced pulmonary fibrosis seriously endangers people's health. Rapamycin has been reported to alleviate PQ-induced pulmonary fibrosis, but its underlying mechanism is unclear. The nuclear factor E2-related factor 2 (Nrf2) plays an important regulatory role in the antioxidant therapy of PQ-induced pulmonary fibrosis. In this study, we tried to confirm that rapamycin attenuates PQ-induced pulmonary fibrosis by regulating Nrf2 pathway. In vivo, we proved that rapamycin could inhibit the degree of PQ-induced oxidant stress as well as enhanced the expression of Nrf2. In vitro, rapamycin decreased the upregulated effects of cell death and apoptosis, fibrosis-related factors expression and fibroblast-to-myofibroblast transformation by PQ treatment. In vivo, rapamycin treatment reduced fibrosis degree and the expression of fibrosis-related factors in lung tissues of rat treated PQ. Furthermore, we also found that Nrf2 knockdown reduced the inhibitory effect of rapamycin on PQ-induced pulmonary fibrosis, as well as decreased Nrf2 transfer from the cytoplasm into the nucleus. Our findings demonstrated that the protective effect of rapamycin is associated with the activation of the Nrf2 pathway in pulmonary fibrosis induced by PQ poisoning.