A bioinspired heterostructured nanochannel based on dendrimer-gold network and aluminum oxide arrays for sensitive detection of miRNA.

BACKGROUND: MicroRNAs, as oncogenes or tumor suppressors, enable to up or down-regulate gene expression during tumorigenesis. The detection of miRNAs with high sensitivity is crucial for the early diagnosis of cancer. Inspired by biological ion channels, artificial nanochannels are considered as an excellent biosensing platform with relatively high sensitivity and stability. The current nanochannel biosensors are mainly based on homogeneous membranes, and their monotonous structure and functionality limit its further development. Therefore, it is necessary to develop a heterostructured nanochannel with high ionic current rectification to achieve highly sensitive miRNA detection. RESULTS: In this work, an asymmetric heterostructured nanochannel constructed from dendrimer-gold nanoparticles network and anodic aluminum oxide are designed through an interfacial super-assembly method, which can regulate ion transport and achieve sensitive detection of target miRNA. The symmetry breaking is demonstrated to endow the heterostructured nanochannels with an outstanding ionic current rectification performance. Arising from the change of surface charges in the nanochannels triggered by DNA cascade signal amplification in solution, the proposed heterogeneous nanochannels exhibits excellent DNA-regulated ionic current response. Relying on the nucleic acid's hybridization and configuration transformation, the target miRNA-122 associated with liver cancer can be indirectly quantified with a detection limit of 1 fM and a wide dynamic range from 1 fM to 10 pM. The correlation fitting coefficient R2 of the calibration curve can reach to 0.996. The experimental results show that the method has a good recovery rate (98%-105 %) in synthetic samples. SIGNIFICANCE: This study reveals how the surface charge density of nanochannels regulate the ionic current response in the heterostructured nanochannels. The designed heterogeneous nanochannels not only possess high ionic current rectification property, but also enable to induce superior transport performance by the variation of surface chemistry. The proposed biosensor is promising for applications in early diagnosis of cancers, life science research, and single-entity electrochemical detection.

Strained few-layer MoS2 with atomic copper and selectively exposed in-plane sulfur vacancies for CO2 hydrogenation to methanol.

In-plane sulfur vacancies (Sv) in molybdenum disulfide (MoS2) were newly unveiled for CO2 hydrogenation to methanol, whereas edge Sv were found to facilitate methane formation. Thus, selective exposure and activation of basal plane is crucial for methanol synthesis. Here, we report a mesoporous silica-encapsulated MoS2 catalysts with fullerene-like structure and atomic copper (Cu/MoS2@SiO2). The main approach is based on a physically constrained topologic conversion of molybdenum dioxide (MoO2) to MoS2 within silica. The spherical curvature enables the generation of strain and Sv in inert basal plane. More importantly, fullerene-like structure of few-layer MoS2 can selectively expose in-plane Sv and reduce the exposure of edge Sv. After promotion by atomic copper, the resultant Cu/MoS2@SiO2 exhibits stable specific methanol yield of 6.11 molMeOH molMo-1 h-1 with methanol selectivity of 72.5% at 260 °C, much superior to its counterparts lacking the fullerene-like structure and copper decoration. The reaction mechanism and promoting role of copper are investigated by in-situ DRIFTS and in-situ XAS. Theoretical calculations demonstrate that the compressive strain facilitates Sv formation and CO2 hydrogenation, while tensile strain accelerates the regeneration of active sites, rationalizing the critical role of strain.

[Site-directed mutagenesis enhances the activity of benzylidene acetone synthase of polyketide synthase from Polygonum cuspidatum].

Polygonum cuspidatum polyketide synthase 1 (PcPKS1) has the catalytic activity of chalcone synthase (CHS) and benzylidene acetone synthase (BAS), which can catalyze the production of polyketides naringenin chalcone and benzylidene acetone, and then catalyze the synthesis of flavonoids or benzylidene acetone. In this study, three amino acid sites (Thr133, Ser134, Ser33) that may affect the function of PcPKS1 were identified by analyzing the sequences of PcPKS1, the BAS from Rheum palmatum and the CHS from Arabidopsis thaliana, as well as the conformation of the catalytic site of the enzyme. Molecular modification of PcPKS1 was carried out by site-directed mutagenesis, and two mutants were successfully obtained. The in vitro enzymatic reactions were carried out, and the differences in activity were detected by high performance liquid chromatography (HPLC). Finally, mutants T133LS134A and S339V with bifunctional activity were obtained. In addition to bifunctional activities of BAS and CHS, the modified PcPKS1 had much higher BAS activity than that of the wild type PcPKS1 under the conditions of pH 7.0 and pH 9.0, respectively. It provides a theoretical basis for future use of PcPKS1 in genetic engineering to regulate the biosynthesis of flavonoids and raspberry ketones.

Roles and mechanism of IL-11 in vascular diseases.

Vascular diseases are the leading cause of morbidity and mortality worldwide. Therefore, effective treatment strategies that can reduce the risk of vascular diseases are urgently needed. The relationship between Interleukin-11 (IL-11) and development of vascular diseases has gained increasing attention. IL-11, a target for therapeutic research, was initially thought to participate in stimulating platelet production. Additional research concluded that IL-11 is effective in treating several vascular diseases. However, the function and mechanism of IL-11 in these diseases remain unknown. This review summarizes IL-11 expression, function, and signal transduction mechanism. This study also focuses on the role of IL-11 in coronary artery disease, hypertension, pulmonary hypertension, cerebrovascular disease, aortic disease, and other vascular diseases and its potential as a therapeutic target. Consequently, this study provides new insight into the clinical diagnosis and treatment of vascular diseases.

Metagenomic analysis of the relationship between the microorganisms and the volatiles' development in the wines during spontaneous fermentation from the eastern foothills of the Ningxia Helan mountains in China.

BACKGROUND: The natural fermentation of multispecies microbial communities is responsible for unique flavors of winery regions of the eastern foothills of the Ningxia Helan Mountains in China. However, the participation of different microorganisms in the metabolic network for the development of important flavor substances is not clearly defined. Microbial population and diversity on different fermentation phases of Ningxia wine were analyzed by metagenomic sequencing approach. RESULTS: Gas chromatography-mass spectrometry and ion chromatography were used to identify flavor components, and 13 esters, 13 alcohols, nine aldehydes and seven ketones were detected in volatile substances with odor activity values > 1, and eight organic acids were detected as important flavor components in young wine. Thus, 52 238 predicted protein-coding genes from 24 genera were identified in the Kyoto Encyclopedia of Genes and Genomes level 2 pathways of global and overview maps, and the genes were primarily involved in amino acid metabolism and carbohydrate metabolism. Major microbial genera (Saccharomyces, Tatumella, Hanseniaspora, Lactobacillus, and Lachancea) were closely related to self-characteristic compound metabolism and further contributed to wine flavor. CONCLUSION: This study clarifies the different metabolic roles of microorganisms in flavor formation during Ningxia wine spontaneous fermentation. Saccharomyces, dominant fungi involved in glycolysis and pyruvate metabolism, produces not only ethanol but also two important precursors, pyruvate and acetyl-CoA, which are necessary for the tricarboxylic acid cycle, fatty acid metabolism, amino acid metabolism, and flavor formation. Lactobacillus and Lachancea, dominant bacteria involved in lactic acid metabolism. Tatumella, dominant bacteria involved in amino acid metabolism, fatty acid metabolism, and acetic acid metabolism to produce esters in the Shizuishan City region samples. These findings provide insights into the use of local functional strains to generate unique flavor formation, as well as improved stability and quality, in wine production. © 2023 Society of Chemical Industry.

Retrograde percutaneous coronary intervention of chronic total occlusion via discontinuous septal channels.

OBJECTIVES: The study aims to investigate the safety and feasibility of retrograde CTO intervention via collateral connection grade 0 (CC-0) septal channel and to identify predictors of collateral tracking failure. BACKGROUND: Guidewire crossing a collateral channel is a critical step for successful retrograde percutaneous coronary intervention (PCI) of chronic total occlusion (CTO). METHODS: Retrograde PCI was attempted in 122 cases of CTO with CC-0 septal collaterals from December 2018 to May 2021. A hydrophilic polymer coating guidewire was used for crossing all intended CC-0 collaterals. A multivariable logistic regression analysis was performed to identify the predictors of guidewire tracking failure via the CC-0 collaterals. RESULTS: Successful guidewire tracking via CC-0 septal channel was achieved in 98 (80.3%) of 122 cases. The independent predictors of CC-0 septal channel guidewire tracking failure included well-developed non-septal collateral (OR: 5.297, 95% CI: 1.107-25.353, p = 0.037) and the ratio length of posterior descending artery (PDA) versus the distance of PDA ostium to cardiac apex ≤2/3 (OR: 3.970, 95% CI: 1.454-10.835, p = 0.007). Collateral perforation, target vessel perforation, and cardiac tamponade occurred in 5 (4.1%), 3 (2.5%), and 6 (4.9%) cases, respectively. There were no complications requiring emergency cardiac surgery or revascularization of nontarget vessel. CONCLUSIONS: Retrograde PCI via CC-0 septal channels with a hydrophilic polymer-coated guidewire is feasible and safe in patients with CTO. Well-developed nonseptal collaterals and short PDA length influence the procedure success and the risk of guidewire tracking failure via CC-0 septal channels.

Enhancement of antibacterial properties and biocompatibility of Ti6Al4V by graphene oxide/strontium nanocomposite electrodepositing.

Ti6Al4V is a widely used orthopedic implant material in clinics. Due to its poor antibacterial properties, surface modification is required to prevent peri-implantation infection. However, chemical linkers used for surface modification have generally been reported to have detrimental effects on cell growth. In this work, by optimizing parameters related to electrodeposition, a composite structural coating with graphene oxide (GO) compact films in the inner layer and 35 nm diameter strontium (Sr) nanoparticles in the outer layer was constructed on the surface of Ti6Al4V without using substance harmful to bone marrow mesenchymal stem cells (BMSCs) growth. The antibacterial properties of Ti6Al4V are enhanced by the controlled release of Sr ions and incomplete masking of the GO surface, showing excellent antibacterial activity against Staphylococcus aureus in bacterial culture assays. The biomimetic GO/Sr coating has a reduced roughness of the implant surface and a water contact angle of 44.1°, improving the adhesion, proliferation and differentiation of BMSCs. Observations of synovial tissue and fluid in the joint in an implantation model of rabbit knee also point to the superior anti-infective properties of the novel GO/Sr coating. In summary, the novel GO/Sr nanocomposite coating on the surface of Ti6Al4V effectively prevents surface colonization of Staphylococcus aureus and eliminates local infections in vitro and in vivo.

Early vascular healing after neXt-generation drug-eluting stent implantation in Patients with non-ST Elevation acute Coronary syndrome based on optical coherence Tomography guidance and evaluation (EXPECT): study protocol for a randomized controlled trial.

Background: There is limited evidence about vessel wall healing response following implantation of next-generation drug-eluting stents (DES) in patients admitted with a non-ST elevation acute coronary syndrome (NSTE-ACS). Cumulative data indicate that optical coherence tomography (OCT) imaging can optimize percutaneous coronary intervention results and expedite stent endothelialization in the general population but there is lack of data in NSTE-ACS patients. Methods: The EXPECT study is an investigator-initiated, prospective, randomized trial to assess early vascular healing response following next-generation DES implantation in patients admitted with NSTE-ACS based on OCT guidance and evaluation. Sixty patients are randomized at 1:1:1 ratio to OCT-guided percutaneous coronary intervention (PCI) with 3-month follow-up OCT imaging (O3 group, n = 20), to angiography-guided PCI with 3-month follow-up OCT imaging (A3 group, n = 20) and to angiography-guided PCI with 6-month follow-up OCT imaging (A6 group, n = 20). The primary endpoint of the study is stent strut coverage rate at 3- or 6- month follow-up in the studied groups. The secondary endpoints of the study include OCT imaging endpoints, clinical endpoints, and molecular biology endpoints at the different time points. The clinical endpoints comprised of major cardiovascular adverse events and individual components. The molecular biology endpoints comprised of lipid levels and the levels of inflammatory indicators. Discussion: The findings of the EXPECT study are anticipated to provide novel insights into vessel wall healing in NSTE-ACS population following implantation of next-generation DES, underscore the value of OCT imaging in expediting strut coverage in this setting, and explore the potential of an early discontinuation of dual antiplatelet therapy (DAPT) in this population. Clinical Trial Registration: ClinicalTrials.gov, NCT04375319.

Anti-Inflammatory Activity of Panax notoginseng Flower Saponins Quantified Using LC/MS/MS.

Panax notoginseng (Burk) F. H. Chen is a traditional Chinese medicinal and edible plant. However, Panax notoginseng flower (PNF) is rarely used. Therefore, the purpose of this study was to explore the main saponins and the anti-inflammatory bioactivity of PNF saponins (PNFS). We explored the regulation of cyclooxygenase 2 (COX-2), a key mediator of inflammatory pathways, in human keratinocyte cells treated with PNFS. A cell model of UVB-irradiation-induced inflammation was established to determine the influence of PNFS on inflammatory factors and their relationship with LL-37 expression. An enzyme-linked immunosorbent assay and Western blotting analysis were used to detect the production of inflammatory factors and LL37. Finally, liquid chromatography-tandem mass spectrometry was employed to quantify the main active components (ginsenosides Rb1, Rb2, Rb3, Rc, Rd, Re, Rg1, and notoginsenoside R1) in PNF. The results show that PNFS substantially inhibited COX-2 activity and downregulated the production of inflammatory factors, indicating that they can be used to reduce skin inflammation. PNFS also increased the expression of LL-37. The contents of ginsenosides Rb1, Rb2, Rb3, Rc, and Rd in PNF were much higher than those of Rg1, and notoginsenoside R1. This paper provides data in support of the application of PNF in cosmetics.

A novel vaccine targeting ß1-adrenergic receptor.

Beta-blockers are widely used in the treatment of hypertension, heart failure and ischemic heart disease. However, unstandardized medication results in diverse clinical outcomes in patients. The main causes are unattained optimal doses, insufficient follow-up and patients' poor adherence. To improve the medication inadequacy, our team developed a novel therapeutic vaccine targeting ß1-adrenergic receptor (ß1-AR). The ß1-AR vaccine named ABRQß-006 was prepared by chemical conjugation of a screened ß1-AR peptide with Qß virus like particle (VLP). The antihypertensive, anti-remodeling and cardio-protective effects of ß1-AR vaccine were evaluated in different animal models. The ABRQß-006 vaccine was immunogenic that induced high titers of antibodies against ß1-AR epitope peptide. In the NG-nitro-L-arginine methyl ester (L-NAME) + Sprague Dawley (SD) hypertension model, ABRQß-006 lowered systolic blood pressure about 10 mmHg and attenuated vascular remodeling, myocardial hypertrophy and perivascular fibrosis. In the pressure-overload transverse aortic constriction (TAC) model, ABRQß-006 significantly improved cardiac function, decreased myocardial hypertrophy, perivascular fibrosis and vascular remodeling. In the myocardial infarction (MI) model, ABRQß-006 effectively improved cardiac remodeling, reduced cardiac fibrosis and inflammatory infiltration, which was superior to metoprolol. Moreover, no significant immune-mediated damage was observed in immunized animals. The ABRQß-006 vaccine targeting ß1-AR showed the effects on hypertension and heart rate control, myocardial remodeling inhibition and cardiac function protection. These effects could be differentiated in different types of diseases with diverse pathogenesis. ABRQß-006 could be a novel and promising method for the treatment of hypertension and heart failure with different etiologies.

Recent Progress of Surface-Enhanced Raman Spectroscopy for Bacteria Detection.

There are various pathogenic bacteria in the surrounding living environment, which not only pose a great threat to human health but also bring huge losses to economic development. Conventional methods for bacteria detection are usually time-consuming, complicated and labor-intensive, and cannot meet the growing demands for on-site and rapid analyses. Sensitive, rapid and effective methods for pathogenic bacteria detection are necessary for environmental monitoring, food safety and infectious bacteria diagnosis. Recently, benefiting from its advantages of rapidity and high sensitivity, surface-enhanced Raman spectroscopy (SERS) has attracted significant attention in the field of bacteria detection and identification as well as drug susceptibility testing. Here, we comprehensively reviewed the latest advances in SERS technology in the field of bacteria analysis. Firstly, the mechanism of SERS detection and the fabrication of the SERS substrate were briefly introduced. Secondly, the label-free SERS applied for the identification of bacteria species was summarized in detail. Thirdly, various SERS tags for the high-sensitivity detection of bacteria were also discussed. Moreover, we emphasized the application prospects of microfluidic SERS chips in antimicrobial susceptibility testing (AST). In the end, we gave an outlook on the future development and trends of SERS in point-of-care diagnoses of bacterial infections.

Ultrasound-Guided Transversus Abdominis Plane Block in Treating Abdominal Skin Tension Pain After Kyphosis Surgery: A Pilot Study in Enhanced Recovery After Surgery Setting.

BACKGROUND: The postsurgical management of patients with ankylosing spondylitis is often only focused on the incision pain, and the pain caused by abdominal skin traction is paid little attention. OBJECTIVES: To explore the effectiveness of ultrasound-guided transversus abdominis plane block (TAPB) in treating abdominal skin tension pain after kyphosis surgery. STUDY DESIGN: Randomized controlled trial. SETTING: This prospective study consecutively enrolled patients scheduled to undergo kyphosis correction surgery at the Department of Orthopedics of Xijing Hospital from March 2021 to December 2021. METHODS: The patients were randomized 1:1 to the TAPB and control groups. The Visual Analog Scale (VAS) for abdominal pain, Bruggrmann Comfort Scale (BCS), abdominal skin tension blisters, bed rest duration, length of hospitalization, and the use of patient-controlled analgesia pumps (PCAPs) were compared. The primary endpoint was pain alleviation at 24 hours after surgery. RESULTS: Thirty-one patients were enrolled, without differences between the 2 groups regarding age, body mass index, preoperative kyphosis severity, operation duration, and blood loss. The TAPB group (n = 16) had lower abdominal VAS scores than the control group (n = 15) at 2, 4, 6, 8, and 12 hours after surgery (P < 0.05). The TAPB group had higher BCS scores than the control group at 4, 6, 8, and 12 hours after surgery (P < 0.05). The TAPB group used PCAPs less frequently than the control group after surgery (P < 0.001). The incidence of tension blisters in the TAPB group was numerically lower than that of the control group, but the difference was not statistically significant (18.8% vs 33.3%, P > 0.05). LIMITATIONS: The sample size of this study is small and a single-center study, there might be data bias. CONCLUSIONS: In the first 24 hours after severe kyphosis surgery, TAPB can reduce the pain from abdominal skin tension and increase the comfort scores, but its effects on tension blisters remain to be further studied.

Vaccine Targeting Alpha 1D-Adrenergic Receptor Improved Metabolic Syndrome in Mice.

PURPOSE: Metabolic syndrome (MetS) is a complex chronic disease that includes obesity and hypertension, with rising evidence demonstrating that sympathetic nervous system (SNS) activation plays a key role. Our team designed a therapeutic vaccine called ADRQß-004 targeting the α1D-adrenergic receptor (α1D-AR). This study was performed to investigate whether the ADRQß-004 vaccine improves MetS by modulating SNS activity. METHODS: C57BL/6N mice were fed a high-fat diet (HFD) and Nω-nitro-L-arginine methyl ester (L-NAME) combination diet for 18 weeks to elicit MetS. The MetS mice were subcutaneously immunized with the ADRQß-004 vaccine four times to evaluate the therapeutic efficacy in obesity and hypertension and other associated abnormalities related to MetS by conducting echocardiographic, histological, and biochemical analyses. RESULTS: The ADRQß-004 vaccine induced strong antibody production and maintained a high anti-ADR-004 antibody titer in MetS mice. The ADRQß-004 vaccine improved obesity (P < 0.001) and decreased systolic blood pressure (P < 0.001). Improvements in dysregulated glucose homeostasis and dyslipidemia resulting from the ADRQß-004 vaccine were also confirmed. Furthermore, the ADRQß-004 vaccine attenuated cardiovascular functional (P = 0.015) and structural changes (P < 0.001), decreased fat accumulation (P = 0.012) and inflammation (P = 0.050) in the epididymal white adipose tissue, and alleviated hepatic steatosis (P = 0.043) involved in MetS. Moreover, the ADRQß-004 vaccine improved systematic and visceral organs SNS activities in the MetS. CONCLUSION: This study demonstrated for the first time that the ADRQß-004 vaccine targeting α1D-AR improved obesity, hypertension, dyslipidemia, and dysglycemia, and further reduced end-organ damage, which may provide new motivation for MetS research.

Clinical outcomes of percutaneous coronary intervention for de novo lesions in small coronary arteries: A systematic review and network meta-analysis.

Background: Percutaneous coronary intervention (PCI) has a well-established role in revascularization for coronary artery disease. We performed network meta-analysis to provide evidence on optimal intervention strategies for de novo lesions in small coronary arteries. Materials and methods: Enrolled studies were randomized clinical trials that compared different intervention strategies [balloon angioplasty (BA), biolimus-coated balloon (BCB), bare-metal stent (BMS), new-generation drug-eluting stent (New-DES), older generation sirolimus-eluting stent (Old-SES), paclitaxel-coated balloon (PCB), and paclitaxel-eluting stent (PES)] for de novo lesions in small coronary arteries. The primary outcome was major adverse cardiac events (MACE). Results: A total of 23 randomized clinical trials comparing seven intervention devices were analyzed. In terms of the primary outcome, New-DES was the intervention device with the best efficacy [surface under the cumulative ranking curve (SUCRA), 89.1%; mean rank, 1.7], and the Old-SES [risk ratio (RR), 1.09; 95% confidence interval (CI), 0.45-2.64] and PCB (RR, 1.40; 95% CI, 0.72-2.74) secondary to New-DES, but there was no statistically significant difference between these three intervention devices. All DES and PCB were superior to BMS and BA for MACE in both primary and sensitivity analysis. For secondary outcomes, there was no association between all-cause mortality and myocardial infarction (MI) with any intervention strategy, and additionally, the findings of target lesion revascularization (TLR) were similar to the primary outcomes. Conclusion: Paclitaxel-coated balloon yielded similar outcomes to New-DES for de novo lesions in small coronary arteries. Therefore, this network meta-analysis may provide potential support for PCB as a feasible, effective, and safe alternative intervention strategy for the revascularization of small coronary arteries. Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO/#recordDetails], identifier [CRD42022338433].

Single-cell transcriptomic analysis reveals differential cell subpopulations and distinct phenotype transition in normal and dissected ascending aorta.

BACKGROUND: Acute thoracic aortic dissection (ATAD) is a fatal condition characterized by tear of intima, formation of false lumen and rupture of aorta. However, the subpopulations of normal and dissected aorta remain less studied. METHODS: Single-cell RNA sequencing was performed including 5 patients with ATAD and 4 healthy controls. Immunohistochemistry and immunofluorescence were used to verify the findings. RESULTS: We got 8 cell types from human ascending aorta and identified 50 subpopulations including vascular smooth muscle cells (VSMCs), endothelial cells, fibroblasts, neutrophils, monocytes and macrophages. Six transmembrane epithelial antigen of prostate 4 metalloreductase (STEAP4) was identified as a new marker of synthetic VSMCs. CytoTRACE identified subpopulations with higher differentiation potential in specified cell types including synthetic VSMCs, enolase 1+ fibroblasts and myeloid-derived neutrophils. Synthetic VSMCs-derived C-X-C motif chemokine ligand 12 (CXCL12) might interact with neutrophils and fibroblasts via C-X-C motif chemokine receptor 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3), respectively, which might recruit neutrophils and induce transdifferentitation of fibroblasts into synthetic VSMCs. CONCLUSION: We characterized signatures of different cell types in normal and dissected human ascending aorta and identified a new marker for isolation of synthetic VSMCs. Moreover, we proposed a potential mechanism that synthetic VSMCs might interact with neutrophils and fibroblasts via CXCL12-CXCR4/ACKR3 axis whereby deteriorating the progression of ATAD, which might provide new insights to better understand the development and progression of ATAD.

A microfluidic-based SERS biosensor with multifunctional nanosurface immobilized nanoparticles for sensitive detection of MicroRNA.

Developing sensitive and miniaturized biosensors for the detection of microRNAs (miRNAs) is highly desirable due to their association with early cancer diagnosis and prognosis. Here, a new microfluidic-based biosensor, combined with multifunctional nanosurface and DSN-assisted target recycle amplification strategy, is designed for the detection of miRNA-21. The design of nanosurface includes gold nanoparticles on porous anodic aluminum oxide (AAO) for surface enhanced Raman scattering (SERS) substrate, AuMBA@Ag core-shell nanoparticles for SERS nanotags and single-stranded DNA (ssDNA) in between for miRNA capture and nanotags immobilization. When the target miRNA is present near the nanosurface, it will be captured by ssDNA via hybridization reaction. Then, triggered by the DSN-assisted target recycle process, the freshly formed DNA/miRNA heteroduplexes are cleaved by DSN enzyme into DNA fragments and single-strand miRNA. The SERS nanotags are also dissociated from the nanosurface, leading to decrease of SERS signal. The cleaved target miRNA can be captured and SERS nanotags are released again in the next cycle, resulting in amplification of detection signal. To improve the accuracy of this biosensor, the functionalized AAO membrane is subdivided into two groups - AAO/Au array linked with encoded core-shell SERS nanotags acting as a reactor and primary detector and AAO/Au@Ag array serving as a collector and secondary detector for the dissociative SERS nanotags from the reactor. The decrease of SERS signal in primary detector and increase of signal in secondary detector ensures the accuracy and it is called dual-SERS detection strategy. The detection of miRNA-21 can be achieved with only 30 µL sample and 10 µL enzyme and a wide linear range of 10 fM∼10 nM is obtained. In addition, the microfluidic dual-SERS detection strategy can greatly reduce the possibility of false positive or false negative in single detection mode and it can be applied to the simultaneous detection of multiple miRNAs via integrating different probes.

Patient-derived microphysiological model identifies the therapeutic potential of metformin for thoracic aortic aneurysm.

BACKGROUND: Thoracic aortic aneurysm (TAA) is the permanent dilation of the thoracic aortic wall that predisposes patients to lethal events such as aortic dissection or rupture, for which effective medical therapy remains scarce. Human-relevant microphysiological models serve as a promising tool in drug screening and discovery. METHODS: We developed a dynamic, rhythmically stretching, three-dimensional microphysiological model. Using patient-derived human aortic smooth muscle cells (HAoSMCs), we tested the biological features of the model and compared them with native aortic tissues. Drug testing was performed on the individualized TAA models, and the potentially effective drug was further tested using ß-aminopropionitrile-treated mice and retrospective clinical data. FINDINGS: The HAoSMCs on the model recapitulated the expressions of many TAA-related genes in tissue. Phenotypic switching and mitochondrial dysfunction, two disease hallmarks of TAA, were highlighted on the microphysiological model: the TAA-derived HAoSMCs exhibited lower alpha-smooth muscle actin expression, lower mitochondrial membrane potential, lower oxygen consumption rate and higher superoxide accumulation than control cells, while these differences were not evidently reflected in two-dimensional culture flasks. Model-based drug testing demonstrated that metformin partially recovered contractile phenotype and mitochondrial function in TAA patients' cells. Mouse experiment and clinical investigations also demonstrated better preserved aortic microstructure, higher nicotinamide adenine dinucleotide level and lower aortic diameter with metformin treatment. INTERPRETATION: These findings support the application of this human-relevant microphysiological model in studying personalized disease characteristics and facilitating drug discovery for TAA. Metformin may regulate contractile phenotypes and metabolic dysfunctions in diseased HAoSMCs and limit aortic dilation. FUNDING: This work was supported by grants from National Key R&D Program of China (2018YFC1005002), National Natural Science Foundation of China (82070482, 81771971, 81772007, 51927805, and 21734003), the Science and Technology Commission of Shanghai Municipality (20ZR1411700, 18ZR1407000, 17JC1400200, and 20YF1406900), Shanghai Municipal Science and Technology Major Project (2017SHZDZX01), and Shanghai Municipal Education Commission (Innovation Program 2017-01-07-00-07-E00027). Y.S.Z. was not supported by any of these funds; instead, the Brigham Research Institute is acknowledged.

Cardioprotective Effects and Possible Mechanisms of Luteolin for Myocardial Ischemia-Reperfusion Injury: A Systematic Review and Meta-Analysis of Preclinical Evidence.

Background: At present, effective clinical therapies for myocardial ischemia-reperfusion injury (MIRI) are lacking. We investigated if luteolin conferred cardioprotective effects against MIRI and elucidated the potential underlying mechanisms. Method: Four databases were searched for preclinical studies of luteolin for the treatment of MIRI. The primary outcomes were myocardial infarct size (IS) and intracardiac hemodynamics. The second outcomes were representative indicators of apoptosis, oxidative stress, and inflammatory. The Stata and RevMan software packages were utilized for data analysis. Results: Luteolin administration was confirmed to reduce IS and ameliorate hemodynamics as compared to the control groups (p < 0.01). IS had decreased by 2.50%, 2.14%, 2.54% in three subgroups. Amelioration of hemodynamics was apparent in two different myocardial infarct models (model of left anterior descending branch ligation and model of global heart ischemia), as left ventricular systolic pressure improved by 21.62 and 35.40 mmHg respectively, left ventricular end-diastolic pressure decreased by 7.79 and 4.73 mmHg respectively, maximum rate of left ventricular pressure rise increased by 737.48 and 750.47 mmHg/s respectively, and maximum rate of left ventricular pressure decrease increased by 605.66 and 790.64 mmHg/s respectively. Apoptosis of cardiomyocytes also significantly decreased, as indicated by thelevels of MDA, an oxidative stress product, and expression of the inflammatory factor TNF-α (p < 0.001). Conclusion: Pooling of the data demonstrated that luteolin exerts cardioprotective effects against MIRI through different signaling pathways. As possible mechanisms, luteolin exerts anti-apoptosis, anti-oxidation, and anti-inflammation effects against MIRI.

Microencapsulation protects the biological activity of sea buckthorn seed oil.

Introduction: Sea buckthorn (Hippophae rhamnoides) seed oil is rich in unsaturated fatty acids, and is thus susceptible to oxidation and rancidity. Microencapsulation technology allows the effective protection of active substances, thereby prolonging the deterioration time and shelf life. Methods: In this study, H. rhamnoides microcapsules were prepared using a spray-drying method, and the microencapsulation parameters were optimized. The morphological characteristics, structural parameters, and stability of the microcapsules were determined using scanning electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, and oil oxidation stability testing. Results: Based on encapsulation efficiency (EE, %) and the particle size (D50) of the microcapsules, the optimal preparation conditions were characterized as a wall material consisting of soy protein isolate and soybean polysaccharide (2:3), a wall concentration of 15%, a core-to-wall ratio of 1:3, and an inlet temperature of 160°C. Under these optimal conditions, the encapsulation efficiency was 95.30 ± 2.67%, with a yield of 57.03 ± 3.71% and a particle size of 7.96 ± 1.04 µm. Discussion: Furthermore, the effectiveness of microencapsulation in protecting the biological activity of H. rhamnoides seed oil was confirmed by an antioxidation test. Thus, the results of this study showcase the successful microencapsulation of H. rhamnoides seed oil, thereby significantly improving its stability.