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Recent advancements in RNA therapeutics highlight the critical need for precision gene delivery systems that target specific organs and cells. Lipid nanoparticles (LNPs) have emerged as key vectors in delivering mRNA and siRNA, offering protection against enzymatic degradation, enabling targeted delivery and cellular uptake, and facilitating RNA cargo release into the cytosol. This review discusses the development and optimization of organ- and cell-specific LNPs, focusing on their design, mechanisms of action, and therapeutic applications. We explore innovations such as DNA/RNA barcoding, which facilitates high-throughput screening and precise adjustments in formulations. We address major challenges, including improving endosomal escape, minimizing off-target effects, and enhancing delivery efficiencies. Notable clinical trials and recent FDA approvals illustrate the practical applications and future potential of LNP-based RNA therapies. Our findings suggest that while considerable progress has been made, continued research is essential to resolve existing limitations and bridge the gap between pre-clinical and clinical evaluation of the safety and efficacy of RNA therapeutics. This review highlights the dynamic progress in LNP research. It outlines a roadmap for future advancements in RNA-based precision medicine.
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The structures of three 1:1 cocrystal forms of etoricoxib {ETR; systematic name: 5-chloro-2-(6-methylpyridin-3-yl)-3-[4-(methylsulfonyl)phenyl]pyridine, C18H15ClN2O2S} have been synthesized and characterized by single-crystal X-ray diffraction; these are etoricoxib-benzoic acid (1/1), C18H15ClN2O2S·C7H6O2 (ETR-Bz), etoricoxib-4-fluorobenzoic acid (1/1), C18H15ClN2O2S·C7H5FO2 (ETR-PFB), and etoricoxib-4-nitrobenzoic acid (1/1), C18H15ClN2O2S·C7H5NO4 (ETR-PNB). Powder X-ray diffraction and thermal differential scanning calorimetry-thermogravimetry (DSC-TG) techniques were also used to characterize these multicomponent systems. Due to the influence of the corresponding acids, ETR shows different conformations. Furthermore, the energetic contributions of the supramolecular motifs have been established by energy framework studies of the stabilizing interaction forces and are consistent with the thermal stability of the cocrystals.
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Recent research has shown that membrane trafficking plays an important role in canonical Wnt signaling through sequestration of the ß-catenin destruction complex inside multivesicular bodies (MVBs) and lysosomes. In this study, we introduce Ouabain, an inhibitor of the Na,K-ATPase pump that establishes electric potentials across membranes, as a potent inhibitor of Wnt signaling. We find that Na,K-ATPase levels are elevated in advanced colon carcinoma, that this enzyme is elevated in cancer cells with constitutively activated Wnt pathway and is activated by GSK3 inhibitors that increase macropinocytosis. Ouabain blocks macropinocytosis, which is an essential step in Wnt signaling, probably explaining the strong effects of Ouabain on this pathway. In Xenopus embryos, brief Ouabain treatment at the 32-cell stage, critical for the earliest Wnt signal in development-inhibited brains, could be reversed by treatment with Lithium chloride, a Wnt mimic. Inhibiting membrane trafficking may provide a way of targeting Wnt-driven cancers.
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Neoplasias del Colon , Pinocitosis , ATPasa Intercambiadora de Sodio-Potasio , Vía de Señalización Wnt , Animales , Humanos , Línea Celular Tumoral , Neoplasias del Colon/metabolismo , Neoplasias del Colon/etiología , Ouabaína/farmacología , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , XenopusRESUMEN
FERMT2 has been identified as a participant in integrin-linked kinase signaling pathways, influencing epithelial-mesenchymal transition and thereby affecting tumor initiation, progression, and invasion. While the character of FERMT2 in the tumor microenvironment (TME) as well as its implications for immunotherapy remain unclear. Thus, we conducted a comprehensive analysis to assess the prognostic significance of FERMT2 using Kaplan-Meier analysis. In addition, we employed enrichment analysis to uncover potential underlying molecular mechanisms. Using "Immunedeconv" package, we evaluated the immune characteristics of FERMT2 within TME. Furthermore, we determined the expression levels of FERMT2 in various cell types within TME, based on single-cell sequencing data. To confirm the co-expression of FERMT2 and markers of cancer-associated fibroblasts (CAFs), we performed multiplex immunofluorescence staining on tissue paraffin sections across various cancer types. Our analysis disclosed a significant correlation between elevated FERMT2 expression and unfavorable prognosis in specific cancer types. Furthermore, we identified a strong correlation between FERMT2 expression and diverse immune-related factors, including immune checkpoint molecules, immune cell infiltration, microsatellite instability (MSI), and tumor mutational burden (TMB). Additionally, there was a significant correlation between FERMT2 expression and immune-related pathways, particularly those associated with activating, migrating, and promoting the growth of fibroblasts in diverse cancer types. Interestingly, we observed consistent co-expression of FERMT2 in both malignant tumor cells and stromal cells, particularly within CAFs. Notably, our findings also indicated that FERMT2, in particular, exhibited elevated expression levels within tumor tissues and co-expressed with α-SMA in CAFs based on the multiplex immunofluorescence staining results.
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Introduction: Salvia L., representing the largest genus within the mint family, is noted for its global distribution of approximately 1000 species, with East Asia, and particularly China, recognized as a critical center of diversity for the genus. Methods: Our research was conducted through extensive fieldwork in Guidong County, Hunan Province, China, where we identified a previously undescribed species of Salvia. The identification process involved detailed morphological observations, phylogenetic analyses, and plastid genomics. Results: The newly discovered species, Salvia guidongensis, exhibits unique characteristics not commonly observed in the East Asian lineage of Salvia, including dual floral colors within natural populations-either pale purple or pale yellow. Morphologically, while it shares similarities with members of sect. Glutinaria, S. guidongensis is distinct in its floral morphology, stature, and specific foliar traits. Phylogenetic analysis places S. guidongensis in a unique clade within the East Asian lineage of Salvia, suggesting it may serve as an important evolutionary link. Additionally, we explored the plastome features of S. guidongensis, comparing them with those of closely related species. Discussion: The discovery of S. guidongensis not only entriches the taxonomic tapestry of Salvia but also provides critical insights into the biogeography and evolutionary pathways of the genus in East Asia. By integrating morphological and molecular data, we validate the novel status of S. guidongensis and highlight its significance in bridging taxonomic and evolutionary gaps within Sect. Glutinaria of Salvia.
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Discovering new ligands for enhanced drug uptake and delivery has been the core interest of the drug delivery field. This study capitalizes on the natural "eat-me" signal of calreticulin (CRT), proposing a novel strategy for functionalizing liposomes to improve cellular uptake. CRT is presented on the surfaces of apoptotic cells, and it plays a crucial role in immunogenic cell death (ICD). This is because it is essential for antigen uptake via low-density lipoprotein (LDL) receptor-mediated phagocytosis. Inspired by this mechanism, we interrogated CRT's "eat-me" feature using CRT-derived peptides to functionalize liposomes. We studied liposomal formulation stability, properties, cellular uptake, toxicity, and intracellular trafficking in dendritic cells. We identified key peptide fragments of CRT, specifically from the hydrophilic P-domain, that are compatible with liposomal formulations. Contrary to the more hydrophobic N-domain peptides, the P-domain peptides induced significantly higher liposomal uptake in DC2.4 dendritic cells than cationic DOTAP and anionic DPPG liposomes without inducing toxicity. The P-domain-derived peptides led to enhanced liposomal uptake into DC2.4 dendritic cells compared to the standard DPPC liposomes. The uptake can be partially blocked by the receptor-associated protein (RAP). Upon internalization, P-domain-peptide-decorated liposomes showed higher co-localization with lysosomes compared to the standard DPPC liposomes. Our findings illuminate CRT's operational role and identify P-domain peptides as promising agents for developing biomimetic drug delivery systems that can potentially replicate CRT's "eat-me" function.
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Calreticulina , Liposomas , Liposomas/química , Péptidos/química , Sistemas de Liberación de Medicamentos , Células DendríticasRESUMEN
Purpose@#Patients with advanced biliary tract cancer (BTC) have a poor survival. We aim to evaluate the efficacy and safety of nab-paclitaxel plus gemcitabine and cisplatin regimen in Chinese advanced BTC patients. @*Materials and Methods@#Eligible patients with locally advanced or metastatic BTC administrated intravenous 100 mg/m2 nab-paclitaxel, 800 mg/m2 gemcitabine, and 25 mg/m2 cisplatin every 3 weeks. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS) and adverse events, while exploratory endpoint was the association of biomarkers with efficacy. @*Results@#After the median follow-up of 25.0 months, the median PFS and OS of 34 enrolled patients were 7.1 months (95% confidence interval [CI], 5.4 to 13.7) and 16.4 months (95% CI, 10.9 to 23.6), respectively. The most common treatment-related adverse events at ≥ 3 grade were neutropenia (26.5%) and leukopenia (26.5%). Survival analyses demonstrated that carcinoembryonic antigen (CEA) levels could monitor patients’ survival outcomes. A significant increase in the number of infiltrating CD4+ cells (p=0.008) and a decrease in programmed death-1–positive (PD-1+) cells (p=0.032) were observed in the response patients. @*Conclusion@#In advanced BTC patients, nab-paclitaxel plus gemcitabine and cisplatin regimen showed therapeutic potential. Potential prognostic factors of CEA levels, number of CD4+ cells and PD-1+ cells may help us maximize the efficacy benefit.
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In recent years, combining different types of therapy has emerged as an advanced strategy for cancer treatment. In these combination therapies, oral delivery of anticancer drugs is more convenient and compliant. This study developed an irinotecan/rapamycin-loaded oral lecithin-based self-nanoemulsifying nanoemulsion preconcentrate (LBSNENPir/ra) and evaluated its synergistic combination effects on pancreatic cancer. LBSNENP loaded with irinotecan and rapamycin at a ratio of 1:1 (LBSNENPir10/ra10) had a better drug release profile and smaller particle size (<200 nm) than the drug powder. Moreover, LBSNENPir10/ra10 exhibited a strong synergistic effect (combination index [CI] < 1.0) in cell viability and combination effect studies. In the tumor inhibition study, the antitumor activity of LBSNENPir10/ra10/sily20 against MIA PaCa-2 (a human pancreatic cancer cell line) was significantly increased compared with the other groups. When administered with rapamycin and silymarin, the area under the curve and the maximum concentration of irinotecan significantly improved compared with the control. We successfully developed an irinotecan/rapamycin-loaded oral self-nanoemulsifying nanoemulsion system to achieve treatment efficacy for pancreatic cancer.
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Amino acids are the basic building blocks of protein that are very important to the nutrition and health of humans and animals, and widely used in feed, food, medicine and daily chemicals. At present, amino acids are mainly produced from renewable raw materials by microbial fermentation, forming one of the important pillar industries of biomanufacturing in China. Amino acid-producing strains are mostly developed through random mutagenesis- and metabolic engineering-enabled strain breeding combined with strain screening. One of the key limitations to further improvement of production level is the lack of efficient, rapid, and accurate strain screening methods. Therefore, the development of high-throughput screening methods for amino acid strains is very important for the mining of key functional elements and the creation and screening of hyper-producing strains. This paper reviews the design of amino acid biosensors and their applications in the high-throughput evolution and screening of functional elements and hyper-producing strains, and the dynamic regulation of metabolic pathways. The challenges of existing amino acid biosensors and strategies for biosensor optimization are discussed. Finally, the importance of developing biosensors for amino acid derivatives is prospected.
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Animales , Humanos , Aminoácidos , Técnicas Biosensibles , Ingeniería Metabólica , Ensayos Analíticos de Alto Rendimiento , ChinaRESUMEN
Background: Erectile dysfunction (ED) mainly affects men over 40 years of age and is a common clinical condition. In addition to hypertension and diabetes, environment, and lifestyle are also significantly associated with erectile dysfunction. The relationship between dietary trace metal intake and ED has not been studied. Materials and methods: Data on participants were obtained from the National Health and Nutrition Examination Survey for this study, and those with incomplete information on clinical variables were excluded. Dose-response curve analysis was used to investigate the relationship between dietary trace metal intake and ED prevalence. Multivariate logistic regression analysis was used to adjust for confounders to further investigate the relationship between dietary trace metal intake and ED prevalence. 1:1 propensity score matching (PSM) was performed to adjust for differences between clinical variables for data reanalysis to confirm the reliability of the results. Results: A total of 3,745 individuals were included in the study, including 1096 ED patients and 2,649 participants without ED. Dietary intake of trace metals (Mg, Zn, Cu, and Se) was significantly higher in participants without ED than in ED patients (all P < 0.001). Dose-response curve analysis showed a significant negative association between these dietary metal intakes and ED prevalence (all P < 0.001). Multivariate logistic regression analysis adjusted for confounders (age, education, BMI, annual household income, hypertension, diabetes, marital status, race, and current health status) revealed that increased dietary metal intake reduced the odds ratio of ED. 1:1 PSM reanalysis further confirmed the validity of the results. Conclusion: Increasing dietary intake of trace metals (magnesium, zinc, copper, and selenium) within the upper limit is beneficial in reducing the prevalence of ED.
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Objective: This study aims to clinically investigate and compare the therapeutic effects and treatment cycle between traditional direct bonding and OrthGuide computer-aided indirect bonding in orthodontic treatment. Methods: Forty patients treated at the Department of Orthodontics, Beijing Rytime Dental Hospital between July 1, 2016, and December 31, 2019, were included. The patients were divided into a control group (n = 20, traditional direct bonding) and a test group (n = 20, OrthGuide computer-aided indirect bonding). The American Board of Orthodontics (ABO) measurement was performed on patients using Uceph cephalometric analysis software to compare intragroup and intergroup differences, and the treatment cycles of all patients were recorded. Results: After treatment, U1-NA (mm), â U1-SN (°), LL-EP (mm), and UL-EP (mm) in the control group were significantly lower than before treatment, and there was no significant difference in other ABO measurement indexes, while the test group showed no marked difference in all ABO measurements between pre- and posttreatment. Further, intergroup comparison showed no significant difference in ABO measurements in pre- and posttreatment between the two groups. The test group had a shorter treatment cycle than the control group, with an average treatment cycle of 21.20 ± 7.14 months in the control group and 17.17 ± 4.16 months in the test group. Conclusion: There was no significant difference in the therapeutic effects between the direct and indirect bonding techniques. However, OrthGuide computer-assisted indirect bonding demonstrated a significantly shorter treatment cycle and might be more efficient than traditional direct bonding.
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Computadores , Programas Informáticos , HumanosRESUMEN
In this study, PEGylated poly (lactide-co-glycolide) (PLGA) thermosensitive composite hydrogels (DTgels) loaded with bispecific anti-cluster of differentiation 3 (CD3) scFv T-cell/anti-epidermal growth factor receptor (EGFR) Fab engager (BiTEE) were subcutaneously (s.c.) injected for the in situ formation of a drug deposit to resolve limitations of the clinical application of the BiTEE of a short half-life and potential side effects. Three kinds of DTgels prepared with different ratios of methoxy poly (ethylene glycol) (mPEG)-PLGA (diblock copolymer, DP) and PLGA-PEG-PLGA (triblock copolymer, TP) were designated DTgel-1, DTgel-2, and DTgel-2S. All three DTgel formulations showed thermosensitive properties with a sol-gel transition temperature at 28-34 °C, which is suitable for an injection. An in vitro release study showed that all DTgel formulations loaded with stabilized BiTEE extended the release of the BiTEE for up to 7 days. In an animal pharmacokinetics study, an s.c. injection of BiTEE/DTgel-1, BiTEE/DTgel-2, or BiTEE/DTgel-2S respectively prolonged the half-life of the BiTEE by 3.5-, 2.0-, and 2.2-fold compared to an intravenous injection of the BiTEE solution. Simultaneously, BiTEE/DTgel formulations showed almost no proinflammatory cytokine release in mice injected with T cells after s.c. administration. Results of an animal antitumor (MDA-MB-231) study indicated that an s.c. injection of the BiTEE/DTgel formulations significantly improved the antitumor efficacy compared to an intravenous (i.v.) or s.c. injection of the BiTEE solution. Moreover, BiTEE/DTgel formulations led to enhanced T-cell recruitment to solid-tumor sites. In conclusion, the in situ formation of injectable PEGylated PLGA thermosensitive hydrogels loaded with the BiTEE was successfully carried out to increase its half-life, maintain a constant blood level within therapeutic windows, and enhance T-cell recruitment to solid-tumor sites resulting in exceptional treatment efficacy.
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Portadores de Fármacos , Polietilenglicoles , Animales , Diferenciación Celular , Hidrogeles , Ratones , Poliésteres , TemperaturaRESUMEN
OBJECTIVE: The purpose of this meta-analysis was to study the prognostic effects of androgen receptor splicing variant 7 (AR-V7) on metastatic castration-resistant prostate cancer (mCRPC) under different treatment options (chemotherapy, hormone therapy). METHODS: We conducted a systematic search of PubMed, EMBASE and Cochrane databases for clinical studies up to June 4, 2021, and used prostate-specific antigen (PSA) progression free-survival (PSA-PFS), radiologic PFS (r-PFS), overall survival (OS) and PSA response rate (PSA RR) as the main endpoints. Subgroup analyses were conducted based on the source of the specimens. STATA v.15 software was used for data analysis. RESULTS: Twenty-one studies were included in this meta-analysis, with a total of 1578 samples. In the abiraterone (AA)/enzalutamide (E) treatment group, AR-V7 positive patients had worse PSA-PFS (hazard ratio [HR] = 3.40; 95% confidence interval [95%CI] 2.56-4.51; P < 0.05) and worse r-PFS (HR = 2.69; 95%CI 1.70-4.24; P < 0.05) and OS (HR = 3.02; 95%CI 1.73-5.30; P < 0.05). Multivariate Cox regression results showed that AR-V7 positive status was an independent risk factor for OS in the AA/E treatment group. In the taxane treatment group, AR-V7-positive and negative patients had similar PSA-PFS (HR = 0.87; 95%CI 0.46-1.63; P = 0.657), r-PFS (HR = 1.01; 95%CI 0.53-1.96; P = 0.965) and OS (HR = 1.50; 95%CI 0.89-2.52; P = 0.127). For AR-V7-positive patients, the difference in OS between taxane and AA/E treatment was not statistically significant (HR = 1.03; 95%CI 0.52-2.06; P = 0.930). However, multivariate Cox regression results suggested that for AR-V7-positive patients, taxane therapy was a protective factor for OS (HR = 0.35; 95%CI 0.20-0.60; P < 0.05). CONCLUSION: The expression of AR-V7 indicates a poor prognosis and is an independent risk factor for OS in AA/E-treated mCRPC patients. However, AR-V7 positive status does not play the same role in taxane-treated patients. In addition, compared to AA/E, taxane treatment is a protective factor for OS in AR-V7-positive patients. AR-V7 may thus be an effective biomarker for treatment prognosis in patients with mCRPC.
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Empalme Alternativo , Biomarcadores de Tumor , Neoplasias de la Próstata Resistentes a la Castración/etiología , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Isoformas de ARN , Receptores Androgénicos/genética , Humanos , Masculino , Pronóstico , Modelos de Riesgos Proporcionales , Neoplasias de la Próstata Resistentes a la Castración/diagnósticoRESUMEN
Environmental pollutants, such as bisphenol A (BPA) have recently been implicated in the development of adverse birth outcomes. However, the underlying teratogenic mechanisms remain unclear. We investigated the effects of BPA on the migration and invasion of human primary extravillous trophoblast HTR-8/SVneo cells. Our results indicated that BPA reduced cell migration and invasion. Moreover, it altered the ratio of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) by downregulating MMP-2 and MMP-9, and upregulating TIMP-1 and TIMP-2. Furthermore, BPA suppressed integrin ß1, integrin α5, and vimentin. Interestingly, BPA-induced invasion was partially restored by G15, a membrane G-protein-coupled estrogen receptor 30 antagonist. We further revealed that 42 proteins were differentially expressed by mass spectrometry analysis, which could be divided into three categories based on gene ontology including biological process, cellular component, and molecular function. These results suggest that BPA reduces HTR-8/SVneo cell migration and invasion by downregulating MMP-2 and MMP-9, up-regulating TIMP-1 and TIMP-2, and suppressing adhesion molecules.
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Extracellular matrix (ECM) hydrogel can create a favorable regenerative microenvironment and act as a promising dressing for accelerating the healing of diabetic wound. In this study, a simple and effective decellularization technique was developed and optimized to obtain acellular extracellular matrix (aECM) from porcine skin. It was found that decellularization at 30% formic acid for 72 h effectively decellularized porcine skin while retaining >75% collagen and ~37% GAG in the aECM with no presence of nuclei of cellular remnants. aECM hydrogel was fabricated by digesting aECM with pepsin in various acidic solutions (0.1 N HCl, glycolic acid (GA) and 2-pyrrolidone-5-carboxylic acid (PCA)) and then treated with a pH-controlled neutralization and temperature-controlled gelation procedure. Based on physical characterizations, including SDS-PAGE, rheological analysis and SEM analysis, aECMHCl hydrogels fabricated at 25 mg/mL in 0.1 N HCl were selected. Four polymeric ECM-mimic hydrogels, including sacchachitin (SC), hyaluronic acid (HA) and chitosan (CS) and three composite hydrogels of combining SC either with aECMHCl,25 (aECMHCl/SC), HA (HA/SC) or CS (SC/CS) were prepared and evaluated for WS-1 cell viability and wound-healing effectiveness. Cell viability study confirmed that no hydrogel dressings possessed any toxicity at all concentrations examined and ECMHCl, HA and ECMHCl/SC at higher concentrations (>0.05%) induced statistically significant proliferation. Diabetic wound healing study and histological examinations revealed that ECMHCl/SC hydrogel was observed to synergistically accelerate wound healing and ultimately stimulated the growth of hair follicles and sweat glands in the healing wound indicating the wound had healed as functional tissues. The results support the great potential of this newly produced ECMHCl/SC composite hydrogel for healing and regeneration of diabetic wounds.
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Objective:To explore the mechanism of Shaoyaotang in the treatment of ulcerative colitis (UC) based on toll-like receptor 4 (TLR4)/nuclear factor kappaB (NF-κB) signaling pathway. Method:A total of 50 Wistar rats were selected, including half male and half female. The damp-heat UC rat model was replicated by the methods of the combination of diseases and syndromes and the combination of 2, 4, 6-nitrobenzene sulfonic acid (TNBS) and ethanol. After the successful modeling, the model rats were randomly divided into model group, salazulesulfonate group, and low, medium and high-dose Shaoyaotang groups, and 10 rats (half male and half female) were selected as the blank control group. Low, medium and high-dose Shaoyaotang groups were given 6, 12, 24 g·kg-1 by gavage, and salazonyl arsenic group was given 1 g·kg-1 by gavage. Blank control group was given the equal volume of normal saline for 21 consecutive days. Colon samples were collected after the last administration, and the expressions of TLR4, NF-κB p65 and IL-6 mRNA in colon tissues were detected by fluorescent quantitative polymerase chain reaction (Real-time PCR), and the expressions of TLR4, NF-κB p65 and IL-6 protein in colon tissues were detected by Western blot. Result:Compared with the blank control group, the relative expressions of TLR4, NF-κB p65, IL-6 mRNA and protein in the model group were significantly increased (P<0.05). Compared with the model group, the expression levels of TLR4, NF-κB p65 and IL-6 mRNA and protein in the salazopyridine group and Shaoyaotang groups were significantly decreased (P<0.05). Conclusion:Shaoyaotang can inhibit the development of UC by regulating the expressions of TLR4, NF-κB p65 and IL-6 mRNA and proteins in the TLR4/NF-κB pathway.
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Objective To explore the protective effect of ginsenoside Rb1 on the myocardial ischemia / reperfusion (I / R) injury in rats in vitro. Methods Totally 60 adult male SD rats were randomly divided into 6 groups:sham group,I / R group,ginsenosde Rb1 pretreatment groups(at the doses of 1 μmol / L,5 μmol / L,10 μmol / L and 20 μmol / L,respectively), 10 in each group. The Langendorff perfusion system was used to establish I / R model. The Lab Chart electrophysiological system was used to monitor real-time heart function by monitoring heart rate (HR), left ventricular development pressure (LVDP) and left ventricular development pressure (± dp / dtmax). TTC staining method was used to measure myocardial infarct size. The Western blotting were used to assay Beclin 1, LC3, p62 and Lamp 2 expression, respectively. The immunohistochemistry were used to assay Beclin 1 expression. Results Ginsenoside Rbl of all the four different concent rations improved the decrease of LVDP and ± dp / dtmax arising from myocardial I / R injury. Meanwhile, ginsenoside Rbl significantly decreased the area of cardial infarction. Ginsenoside Rb1 (10 μmol / L) precondition group protected the heart most significantly (P<0. 05). The expression of Beclin 1 with I / R increased significantly in the cytoplasm of cardiomyocytes. Moreover, Beclin 1 expression decreased after addition pretreatment with ginsenoside Rb1 (10 μmol / L) (P < 0. 05). Compared with sham group, we found that the autophagic flux was impaired in I / R group which the expression of Beclin 1, LC3 and p62 increased significantly, as well as the expression of Lamp 2 decreased significantly. On the other hand, pretreatment with ginsenoside Rb1 (10 μmol / L) could reverse impaired autophagic flux (P < 0. 05). Conclusion Ginsenoside Rbl demonstrates pharmacological preconditioning effect and protects against myocardial I / R injury by improving damaged-autophagy flux, the dose of 10 μmol / L precondition protectes the heart most significantly.
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Conventional optofluidic lens usually has only one interface, which means that the zoom range is small, and the ability to correct aberrations is poor. In this paper, we propose a hybrid driving variable-focus optofluidic lens. It has one water-oil interface shifted by an applied voltage and one tunable Polydimethylsiloxane (PDMS) lens deformed by pumping liquid in or out of the cavity. The proposed lens combines the advantages of electrowetting lens and mechanical lens. Therefore, it can provide a large focal length tuning range with good image quality. The shortest positive and negative focal length are â¼6.02â mm and â¼-11.15â mm, respectively. The maximum resolution of our liquid lens can be reached 18 lp/mm. We also designed and fabricated a zoom system using the hybrid driving variable-focus optofluidic lens. In the experiment, the zoom range of the system is 14â mmâ¼30â mm and the zoom ratio is â¼2.14× without any mechanical moving parts. Its applications for zoom telescope system and zoom microscope and so on are foreseeable.
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The output synchronization and H∞ output synchronization problems for multiweighted complex network are discussed in this paper. First, we analyze the output synchronization of multiweighted complex network by exploiting Lyapunov functional and Barbalat's lemma. In addition, some nodes- and edges-based pinning control strategies are developed to ensure the output synchronization of multiweighted complex network. Similarly, the H∞ output synchronization problem of multiweighted complex network is also discussed. Finally, two numerical examples are presented to verify the correctness of the obtained results.