Antiplatelet effects of the CEACAM1-derived peptide QDTT.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) restricts platelet activation via platelet collagen receptor GPVI/FcRγ-chain. In this study, screening against collagen-induced platelet aggregation was performed to identify functional CEACAM1 extracellular domain fragments. CEACAM1 fragments, including Ala-substituted peptides, were synthesized. Platelet assays were conducted on healthy donor samples for aggregation, cytotoxicity, adhesion, spreading, and secretion. Mice were used for tail bleeding and FeCl3-induced thrombosis experiments. Clot retraction was assessed using platelet-rich plasma. Extracellular segments of CEACAM1 and A1 domain-derived peptide QDTT were identified, while N, A2, and B domains showed no involvement. QDTT inhibited platelet aggregation. Ala substitution for essential amino acids (Asp139, Thr141, Tyr142, Trp144, and Trp145) in the QDTT sequence abrogated collagen-induced aggregation inhibition. QDTT also suppressed platelet secretion and "inside-out" GP IIb/IIIa activation by convulxin, along with inhibiting PI3K/Akt pathways. QDTT curtailed FeCl3-induced mesenteric thrombosis without significantly prolonging bleeding time, implying the potential of CEACAM1 A1 domain against platelet activation without raising bleeding risk, thus paving the way for novel antiplatelet drugs.

What is the context? The study focuses on Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and its role in platelet activation, particularly through the GPVI/FcRγ-chain pathway.The research aims to identify specific fragments of CEACAM1's extracellular domain that could restrict platelet activation, without increasing bleeding risk.What is new? The researchers identified a peptide called QDTT derived from the A1 domain of CEACAM1's extracellular segment. This peptide demonstrated the ability to inhibit platelet aggregation, secretion, and GP IIb/IIIa activation.The study also revealed that specific amino acids within the QDTT sequence were essential for its inhibitory effects on collagen-induced aggregation.What is the impact? The findings suggest that the A1 domain-derived peptide QDTT from CEACAM1 could serve as a potential basis for developing novel antiplatelet drugs. This peptide effectively limits platelet activation and aggregation without significantly prolonging bleeding time, indicating a promising approach to managing thrombosis and related disorders while minimizing bleeding risks.

Rationale and design of a comparison of angiography-derived fractional flow reserve-guided and intravascular ultrasound-guided intervention strategy for clinical outcomes in patients with coronary artery disease: a randomised controlled trial (FLAVOUR II).

INTRODUCTION: Percutaneous coronary intervention (PCI) guided by coronary angiography-derived fractional flow reserve (FFR) or intravascular ultrasound (IVUS) has shown improved clinical outcomes compared with angiography-only-guided PCI. In patients with intermediate stenoses, FFR resulted in fewer coronary interventions and was non-inferior to IVUS with respect to clinical outcomes. However, whether this finding can be applied to angiography-derived FFR in significant coronary artery disease (CAD) remains unclear. METHOD AND ANALYSIS: The comparison of angiography-derived FFR-guided and IVUS-guided intervention strategies for clinical outcomes in patients with coronary artery disease (FLAVOUR II) trial is a multicentre, prospective, randomised controlled trial. A total of 1872 patients with angiographically significant CAD (stenoses of at least 50% as estimated visually through angiography) in a major epicardial coronary artery will be randomised 1:1 to receive either angiography-derived FFR-guided or IVUS-guided PCI. Patients will be treated with second-generation drug-eluting stent according to the predefined criteria for revascularisation: angiography-derived FFR≤0.8 and minimal lumen area (MLA)≤3 mm2 or 3 mm270%. The primary endpoint is a composite of all-cause death, myocardial infarction and revascularisation at 12 months after randomisation. We will test the non-inferiority of the angiography-derived FFR-guided strategy compared with the IVUS-guided decision for PCI and the stent optimisation strategy.The FLAVOUR II trial will provide new insights into optimal evaluation and treatment strategies for patients with CAD. ETHICS AND DISSEMINATION: FLAVOUR II was approved by the institutional review board at each participating site (The Second Affiliated Hospital of Zhejiang University School of Medicine Approval No: 2020LSYD410) and will be conducted in line with the Declaration of Helsinki. Informed consent would be obtained from each patient before their participation. The study results will be submitted to a scientific journal. TRIAL REGISTRATION NUMBER: NCT04397211.

Luteolin inhibits GPVI-mediated platelet activation, oxidative stress, and thrombosis.

Introduction: Luteolin inhibits platelet activation and thrombus formation, but the mechanisms are unclear. This study investigated the effects of luteolin on GPVI-mediated platelet activation in vitro and explored the effect of luteolin on thrombosis, coagulation, and platelet production in vivo. Methods: Washed human platelets were used for aggregation, membrane protein expression, ATP, Ca2+, and LDH release, platelet adhesion/spreading, and clot retraction experiments. Washed human platelets were used to detect collagen and convulxin-induced reactive oxygen species production and endogenous antioxidant effects. C57BL/6 male mice were used for ferric chloride-induced mesenteric thrombosis, collagen-epinephrine induced acute pulmonary embolism, tail bleeding, coagulation function, and luteolin toxicity experiments. The interaction between luteolin and GPVI was analyzed using solid phase binding assay and surface plasmon resonance (SPR). Results: Luteolin inhibited collagen- and convulxin-mediated platelet aggregation, adhesion, and release. Luteolin inhibited collagen- and convulxin-induced platelet ROS production and increased platelet endogenous antioxidant capacity. Luteolin reduced convulxin-induced activation of ITAM and MAPK signaling molecules. Molecular docking simulation showed that luteolin forms hydrogen bonds with GPVI. The solid phase binding assay showed that luteolin inhibited the interaction between collagen and GPVI. Surface plasmon resonance showed that luteolin bonded GPVI. Luteolin inhibited integrin αIIbß3-mediated platelet activation. Luteolin inhibited mesenteric artery thrombosis and collagen- adrenergic-induced pulmonary thrombosis in mice. Luteolin decreased oxidative stress in vivo. Luteolin did not affect coagulation, hemostasis, or platelet production in mice. Discussion: Luteolin may be an effective and safe antiplatelet agent target for GPVI. A new mechanism (decreased oxidative stress) for the anti-platelet activity of luteolin has been identified.

Improved Catalytic Performance toward Selective Oxidation of Benzyl Alcohols Originated from New Open-Framework Copper Molybdovanadate with a Unique V/Mo Ratio.

A new organic-inorganic hybrid open-framework molybdovanadate with mixed-valences of vanadium (V4+ /V5+ =4/3) and molybdenum (Mo5+ /Mo6+ =8/2) cations has been synthesized. The complex possesses the unique V/Mo ratio (7/10), fascinating 8-C topological network and 1D 4-MR channels (7.793 Å×6.699 Å). Importantly, its catalytic activities for the selective oxidation of benzyl alcohol to benzaldehyde (oxidant: H2 O2 , 30 wt %) have been well evaluated. The results indicated that it exhibited improved catalytic activities (conv.: 96.8 %) compared with the catalyst (Cpyr)5 PV2 Mo5 W5 O40 [conv.: 88.51 %, Cpyr=(C16 H32 C5 H4 N)+ )], high recyclability and structural stability. Moreover, the conversions and selectivities (conv.: 82.4-92.5 %; sele.: 91.5-95.7 %) of the substrates containing electron donating groups (-OH, -CH3 , -OCH3 and -Cl) were significantly higher than those of the substrate containing electron withdrawing group (-NO2 ) (conv. 67.4 %; sele.: 80.8 %). This is due to the fact that the -NO2 with a large Hammett substituent constant is not conducive to the generation of transition state products. The studies revealed the complex could act as a highly efficient heterogeneous catalyst in selective oxidation of benzyl alcohols.

Identification of immune-related hub genes and miRNA-mRNA pairs involved in immune infiltration in human septic cardiomyopathy by bioinformatics analysis.

Abstract: Septic cardiomyopathy (SCM) is a serious complication caused by sepsis that will further exacerbate the patient's prognosis. However, immune-related genes (IRGs) and their molecular mechanism during septic cardiomyopathy are largely unknown. Therefore, our study aims to explore the immune-related hub genes (IRHGs) and immune-related miRNA-mRNA pairs with potential biological regulation in SCM by means of bioinformatics analysis and experimental validation. Method: Firstly, screen differentially expressed mRNAs (DE-mRNAs) from the dataset GSE79962, and construct a PPI network of DE-mRNAs. Secondly, the hub genes of SCM were identified from the PPI network and the hub genes were overlapped with immune cell marker genes (ICMGs) to further obtain IRHGs in SCM. In addition, receiver operating characteristic (ROC) curve analysis was also performed in this process to determine the disease diagnostic capability of IRHGs. Finally, the crucial miRNA-IRHG regulatory network of IRHGs was predicted and constructed by bioinformatic methods. Real-time quantitative reverse transcription-PCR (qRT-PCR) and dataset GSE72380 were used to validate the expression of the key miRNA-IRHG axis. Result: The results of immune infiltration showed that neutrophils, Th17 cells, Tfh cells, and central memory cells in SCM had more infiltration than the control group; A total of 2 IRHGs were obtained by crossing the hub gene with the ICMGs, and the IRHGs were validated by dataset and qRT-PCR. Ultimately, we obtained the IRHG in SCM: THBS1. The ROC curve results of THBS1 showed that the area under the curve (AUC) was 0.909. Finally, the miR-222-3p/THBS1 axis regulatory network was constructed. Conclusion: In summary, we propose that THBS1 may be a key IRHG, and can serve as a biomarker for the diagnosis of SCM; in addition, the immune-related regulatory network miR-222-3p/THBS1 may be involved in the regulation of the pathogenesis of SCM and may serve as a promising candidate for SCM therapy.

A highly efficient heterogeneous catalyst for selective oxidation of sulfides derived from an open-framework copper borovanadate containing a unique crown-shaped anion.

A novel 3D open-framework copper borovanadate with a unique crown-shaped anion [(VIVO)8(VVO)4B32O64(OH)8]12- and the largest ratio of Cu2+/borovanadate anions (6/1) has been successfully synthesized and systematically studied. The compound not only possesses high stability in a wide pH range of 3.2-10.8 (DMF solution), but also exhibits excellent catalytic activities for selective oxidation of sulfides.

Comparative analysis of left atrial appendage closure efficacy and outcomes by CHA2DS2-VASc score group in patients with non-valvular atrial fibrillation.

Background: Higher CHA2DS2-VASc score is associated with an increased risk of adverse cardio-cerebrovascular events in patients with non-valvular atrial fibrillation (NVAF), regardless of oral anticoagulation (OAC) status. However, whether this association still exists in patients undergoing left atrial appendage closure (LAAC) is unknown. We evaluated the impact of CHA2DS2-VASc score on LAAC efficacy and outcomes. Methods: A total of 401 consecutive patients undergoing LAAC were included and divided into 3 groups based on CHA2DS2-VASc score (0-2, 3-4, and ≥5). Baseline characteristics, periprocedural complications, and long-term outcomes were collected and compared across all groups. Results: There were no significant differences in implantation success, periprocedural complications, and long-term outcomes across all score groups. Kaplan-Meier estimation showed that the cumulative ratio of freedom from all-cause mortality (P = 0.146), cardiovascular mortality (P = 0.519), and non-cardiovascular mortality (P = 0.168) did not differ significantly by CHA2DS2-VASc score group. LAAC decreased the risks of thromboembolism and major bleeding, resulting in a relative risk reduction (RRR) of 82.4% (P < 0.001) and 66.7% (P < 0.001) compared with expected risks in the overall cohort, respectively. Subgroup analysis indicated that observed risks of thromboembolism and major bleeding were significantly lower than the expected risks in score 3-4 and score ≥5 groups, respectively. The level of RRR increased with CHA2DS2-VASc score (P < 0.001 for trend) for thromboembolism but not for major bleeding (P = 0.2729 for trend). Conclusion: Patients with higher CHA2DS2-VASc score did not experience worse outcomes, which may be partly attributed to more benefits provided by LAAC intervention in such patients compared to those with a low score.

Effect of Evodiamine on Collagen-Induced Platelet Activation and Thrombosis.

Evodia rutaecarpa has multiple pharmacological effects and is widely used in the prevention and treatment of migraine, diabetes, cardiovascular disease, cancer, and other chronic diseases; however, the pharmacological effects of its active compound evodiamine (Evo) have not been thoroughly investigated. The purpose of this study was to investigate the effects of Evo on antiplatelet activation and thrombosis. We discovered that Evo effectively inhibited collagen-induced platelet activation but had no effect on platelet aggregation caused by activators such as thrombin, ADP, and U46619. Second, we found that Evo effectively inhibited the release of platelet granules induced by collagen. Finally, evodiamine inhibits the transduction of the SFKs/Syk/Akt/PLCγ2 activation pathway in platelets. According to in vivo studies, Evo significantly prolonged the mesenteric thromboembolism induced by ferric chloride and had no discernible effect on the coagulation function of mice. In conclusion, the antiplatelet and thrombotic effects of Evo discovered in this study provide an experimental basis for the investigation of the pharmacological mechanisms of Evo and the development of antiplatelet drugs.

Coupling of Silk Fibroin Nanofibrils Enzymatic Membrane with Ultra-Thin PtNPs/Graphene Film to Acquire Long and Stable On-Skin Sweat Glucose and Lactate Sensing.

The applications of enzymatic biosensors are largely limited by their relatively poor stability and short lifespan. Herein, a bio-active porous enzymatic nanofiber (PEN) membrane composed of silk fibroin nanofibrils (SFNFs) and enzymes is developed to effectively retain the enzymes in the 3D space. The 3D functional scaffolds formed by SFNFs can immobilize enzymes and provide a large surface area for molecular/ion diffusion and biochemical reactions. The PEN membrane is subsequently attached to an ultra-thin PtNPs/graphene (Pt-G) nanocomposite film to facilitate the electron transport between the enzymes and electrodes, permitting highly effective glucose and lactate sensing with long and stable performance. The as-assembled glucose and lactate sensors demonstrate high sensitivity, good cyclic reproducibility, and in particular long-term stability of up to 25 and 23.6 h, respectively. These glucose sensors have a working life that is ≈1.25-times longer than that of the best available sensors reported so far. Moreover, a wearable platform based on the sensors is developed for real-time analysis of sweat during outdoor exercising to transmit signals to a mobile handset. The high sensitivity, comfort and long-term stability of the device can benefit for long-term in-line surveillance of physiological conditions.

Serum exosomal microRNA-146a as a novel diagnostic biomarker for acute coronary syndrome.

BACKGROUND: Circulating microRNAs (miRNAs) have emerged as potential biomarkers for cardiovascular diseases. However, few studies have focused on the role of exosomal miRNAs in acute coronary syndrome (ACS). The purpose of this study was to explore weather serum exosomal microRNA-146a (exo-miR-146a) could be used as a novel diagnostic biomarker for ACS and to investigate its relationship with inflammatory response. METHODS: A total of 63 ACS patients and 25 patients with normal coronary arteries (Control) were enrolled respectively. The serum exosomes were isolated and then identified by transmission electron microscopy (TEM), western blot, and nanoparticle tracking analysis (NTA). The expression levels of exo-miR-146a in serum were detected by real-time quantitative polymerase chain reaction (RT-qPCR) and the expression levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in serum were assessed by enzyme-linked immunosorbent assay (ELISA). Spearman's correlation analysis was used to appraise the potential factors related to serum exo-miR-146a and receiver operating characteristic (ROC) curve analysis was applied for predicting the accuracy of ACS via the area under curve (AUC). RESULTS: Exosomes isolated from serum were of typical cup-like shape, with 50-150 nm diameter, and expressed CD9, CD63, CD81, and HSP70. The expression levels of serum exo-miR-146a, IL-1ß, IL-6, and TNF-α were significantly increased in ACS patients compared with the control group, Spearman's correlation analysis indicated that exo-miR-146a expression was markedly positively correlated with IL-1ß, IL-6, and TNF-α. The ROC curve analyses revealed that exo-miR-146a could distinguish ACS patients from their normal controls. CONCLUSIONS: The serum exo-miR-146a may be used as a novel diagnostic biomarker for ACS patients, and it is also associated with inflammatory response.

Biomimetic Salinity Power Generation Based on Silk Fibroin Ion-Exchange Membranes.

Powering implanted medical devices (IMDs) is a long-term challenge since their use in biological environments requires a long-term and stable supply of power and a biocompatible and biodegradable battery system. Here, silk fibroin-based ion-exchange membranes are developed using bionics principles for reverse electrodialysis devices (REDs). Silk fibroin nanofibril (SNF) membranes are negatively and positively modified, resulting in strong cation and anion selectivity that regulates ion diffusion to generate electric power. These oppositely charged SNF membranes are assembled with Ag/AgCl electrodes into a multicompartment RED. By filling them with 10 and 0.001 mM NaCl solutions, a maximum output power density of 0.59 mW/m2 at an external loading resistance of 66 kΩ is obtained. In addition, 10 pairs of SNF membranes produce a considerable voltage of 1.58 V. This work is a proof of concept that key components of battery systems can be fabricated with protein materials. Combined with the emergence of water-based battery technologies, the findings in this study provide insights for the construction of tissue-integrated batteries for the next generation of IMDs.

A capacitive humidity sensor based on all-protein embedded with gold nanoparticles @ carbon composite for human respiration detection.

Wool and silk fiber are the most extensive resources of protein fibers and have been used in the textile field for many years. The extracted biocompatible proteins are more and more widely used in flexible devices, sensors, tissue engineering, etc. Here, a fully biomaterial based flexible humidity sensor has been successfully fabricated for the first time. Interdigital electrodes of humidity sensor are printed on a transparent sensor substrate made of silk protein by inkjet printing. The humidity sensitive material is gold nanoparticles hosted nitrogen doped carbon (AuNPs@NC), which is fabricated by in situ dispersion of gold nanoparticles in a wool keratin assisted porous carbon precursor. The best treatment condition of the sensitive materials is obtained by comparing the sensitivity of humidity response. Moreover, the as-prepared biocompatible flexible sensor was successfully used to detect human respiration.

Left Atrial Appendage Closure Yields Favorable Cardio- and Cerebrovascular Outcomes in Patients With Non-valvular Atrial Fibrillation and Prior Stroke.

Introduction: Patients with non-valvular atrial fibrillation (NVAF) and previous stroke are at significantly higher risk of stroke recurrence. Data on the efficacy of left atrial appendage closure (LAAC) on these patients is limited. The aim of this study was to investigate the differences of LAAC efficacy on long-term cardio- and cerebrovascular outcomes in NVAF patients with vs. without prior stroke. Methods: Three hundred and seventy consecutive NVAF patients who underwent LAAC were enrolled and divided into stroke and non-stroke groups based on history of previous stroke. Endpoints, such as thromboembolism, major bleeding, and mortality post-LAAC, were followed up among groups. Results: Patients in the stroke group had higher mean CHA2DS2-VASc and HAS-BLED scores compared to the non-stroke group (5.1 vs. 3.6 and 4.1 vs. 3.4, both P < 0.001, respectively). Over a median follow-up of 2.2 years, there were no significant differences in incidence rates of thromboembolism, device-related thrombus (DRT), major bleeding, and combined efficacy endpoints between the two groups. In both stroke and non-stroke groups, LAAC decreased the risk of thromboembolism [relative risk reduction (RRR) 87.5%, P = 0.034, and 74.6%, P = 0.004, respectively] and major bleeding (RRR 68.8%, P = 0.034, and 68.6%, P = 0.007, respectively) compared with predicted risk. The RRR in thromboembolism was greater in patients with vs. without prior stroke (OR 2.45, 95% CI: 1.20-5.12, P = 0.016). The incidence rates of all-cause mortality and non-cardiovascular death were similar between the two groups, but the risks of cardiovascular death post-LAAC both before (1.4% vs. 8.1%, respectively, P = 0.038) and after adjustment for confounding factors (P = 0.048) were significantly decreased in the stroke group. Conclusions: Patients with vs. without prior stroke did not exhibit a worse clinical prognosis after LAAC. LAAC may provide an increased benefit in cardio-cerebrovascular outcomes in patients with previous stroke compared to those without previous stroke. Further research is necessary to evaluate the efficacy of LAAC in this field.

Tailoring NiCoAl layered double hydroxide nanosheets for assembly of high-performance asymmetric supercapacitors.

NiCoAl layered double hydroxide nanosheets (NiCoAl-LDHNs) were prepared by a one-step solvothermal method. The shape and size of the obtained nanosheets are optimized by adjusting the solvothermal time and the molar concentration ratio of Ni2+/Co2+ to obtain the electrode material with the best performance. When the solvothermal time is 9 h and the molar concentration ratio of Ni2+/Co2+ is 1:1, NiCoAl-LDHNs has the best morphology and electrochemical performance. When assembled into a supercapacitor, NiCoAl-LDHN-9 has a high specific capacitance of 1228.5 F g-1 at 1 A g-1. As the current density is increased to 20 A g-1, the specific capacitance is 1001.8 F g-1, which still has a high capacitance retention of 81.6%. When NiCoAl-LDHN-9 was assembled into an asymmetric supercapacitor, NiCoAl-LDHN-9//AC has a specific capacitance of 102.1 F g-1 at 0.5 A g-1. The asymmetric supercapacitor devices also show excellent electrochemical performance in terms of energy density (35.9 Wh kg-1 at 225.8 W kg-1), power density (4.8 kW kg-1 at 22.2 Wh kg-1) and cycle life (capacitance retention rate after 10,000 cycles is 87.1%). Those results indicate that NiCoAl-LDHN have the potential to be promising electrode materials for high performance supercapacitors.

Flexible and disposable gold nanoparticles-N-doped carbon-modified electrochemical sensor for simultaneous detection of dopamine and uric acid.

Catalytic and electrocatalytic applications of supported metal nanoparticles are hindered due to an aggregation of metal nanoparticles and catalytic leaching under harsh operations. Hence, stable and leaching free catalysts with high surface area are extremely desirable but also challenging. Here we report a gold nanoparticles-hosted mesoporous nitrogen doped carbon matrix, which is prepared using bovine serum albumin (BSA) through calcination. BSA plays three roles in this process as a reducing agent, capping agent and carbon precursor, hence the protocol exhibits economic and sustainable. Gold nanoparticles at N-doped BSA carbon (AuNPs@NBSAC)-modified three-electrode strip-based flexible sensor system has been developed, which displayed effective, sensitive and selective for simultaneous detection of uric acid (UA) and dopamine (DA). The AuNPs@NBSAC-modified sensor showed an excellent response toward DA with a linear response throughout the concentration range from 1 to 50 µM and a detection limit of 0.05 µM. It also exhibited an excellent response toward UA, with a wide detection range from 5 to 200 µM as well as a detection limit of 0.1 µM. The findings suggest that the AuNPs@NBSAC nanohybrid reveals promising applications and can be considered as potential electrode materials for development of electrochemical biosensors.

A TiS2/Celgard separator as an efficient polysulfide shuttling inhibitor for high-performance lithium-sulfur batteries.

The rapid capacity loss caused by the shuttling effect of polysulfides is one of the great challenges of Li-S batteries. In this work, we adopted a simple solid-phase sintering method to synthesize titanium disulfide (TiS2) and further demonstrated it as a superior modifier of separators for Li-S batteries. Two commonly adopted modification processes of separators, including vacuum filtration (VF) and slurry casting (SC) have been used to prepare TiS2/Celgard separators. TiS2-VF/Celgard can better restrain the polysulfide shuttling effect compared with TiS2-SC/Celgard. A TiS2-VF/Celgard-based Li-S battery has a reversible capacity of 771.6 mA h g-1, with a capacity retention of 645.6 mA h g-1 after 500 cycles at 2.0 C, corresponding to a capacity fading rate of ∼0.033% per cycle. This study has shown the potential of TiS2 as a multifunctional modifier of separators for high performance and long cycle life Li-S batteries.

Programing Performance of Silk Fibroin Superstrong Scaffolds by Mesoscopic Regulation among Hierarchical Structures.

To design higher-strength natural scaffold materials, wool keratin (WK) rich in α-helix structures is used as a well-defined foreign substrate, which induces the formation of ß-crystallites in silk fibroin (SF). Consequently, the macroscopic properties of silk materials (such as the rheological properties of SF hydrogels and the mechanical properties of stents) can be manipulated by governing the change in the hierarchical mesoscopic structure of silk materials. In this work, by monitoring the structure and morphology in the SF gel process, the mechanism of the effect of keratin on SF network formation was speculated, which was further used to design ultra-high-strength protein scaffolds. It has been confirmed that WK accelerates the gelation of SF by reducing the multistep nucleation barrier and increasing the primary nucleation sites, and then establishing a high-density SF domain network. The modulus of the protein composite scaffold prepared by this facile strategy can reach 11.55 MPa, and the MC-3T3 cells can grow well on the scaffold surface. The results suggest that freeze-dried biocompatible SF-based scaffolds are potential candidates for bone tissue engineering.

Efficacy of tolvaptan for fluid management after cardiovascular surgery: A systematic review and meta-analysis of randomized control trials.

The purpose of this study was to systematically search the literature and analyze evidence from randomized controlled trials (RCTs) comparing tolvaptan with conventional diuretics for postoperative fluid management in cardiac surgery patients. An electronic search of PubMed, Scopus, BioMed Central, CENTRAL (Cochrane Central Register of Controlled Trials) and Google scholar databases was carried out up to 1st December 2019. Four RCTs were included. Tolvaptan was co-administered with conventional diuretics in all the studies. The mean postoperative urine output was significantly greater in patients receiving tolvaptan as compared to controls (MD=0.39; 95% CI: 0.17 to 0.61; P=0.006, I2=48%). Body weight of patients on tolvaptan returned to pre-operative levels significantly earlier (MD=-1.57; 95% CI: -2.48 to -0.66; P=0.007, I2=50%). There was statistical significant difference in the highest postoperative serum sodium levels (MD=2.34; 95% CI: -1.65 to 3.03; p<0.00001, I2=0%), lowest serum sodium levels (MD=2.05; 95% CI: 1.41 to 2.68; p<0.00001, I2=0%) and mean serum sodium levels (MD=1.69; 95% CI: 0.98 to 2.40; p<0.00001, I2=0%) between the tolvaptan and control groups. Lowest serum potassium was significantly higher with tolvaptan as compared to the control group (MD=0.10; 95% CI: 0.01 to 0.18; P=0.03, I2=19%). There was no significant difference in the length of ICU stay or incidence of arrhythmias between the two groups. The quality of the included studies was not high. Within the limitations of our study, our results indicate that co-administration of tolvaptan with low dose of conventional diuretics significantly increases urine output while maintaining electrolyte balance in postoperative cardiac surgery patients. Faster return of body weight to pre-operative levels is evident with tolvaptan. Further high-quality RCTs are required to confirm this evidence.

CEACAM1 Inhibited IκB-α/NF-κB Signal Pathway Via Targeting MMP-9/TIMP-1 Axis in Diabetic Atherosclerosis.

Atherosclerosis (AS) is the most common and serious complication in type 2 diabetes mellitus (T2DM). Recent studies have emphasized that inflammation is the main cause of atherosclerosis. Studies have shown that carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1) regulates the expression of matrix metallopeptidase 9 (MMP-9) after ischemic stroke to reduce inflammation. The aim of this study was to elucidate potential molecular mechanism of CEACAM1 on the inflammatory response in atherosclerosis. The serum levels of CEACAM1, MMP-9, and tissue inhibitors of metalloproteinase 1 (TIMP-1) in T2DM patients and healthy control was detected. The results showed that the levels of CEACAM1 and TIMP-1 were significantly decreased, and the levels of MMP-9 were significantly higher than those in the control group. Moreover, we also observed the effect of CEACAM1 on atherosclerosis in T2DM rats. Hematoxylin & eosin (HE) staining and oil red staining showed that CEACAM1 recombinant protein reduced intima-media thickness and the area of atherosclerotic plaques. To further explore the molecular mechanism of CEACAM1 regulating MMP-9/TIMP-1, we conducted experiments in rat aorta vascular endothelial cells and rat aorta smooth muscle cells. The result showed that CEACAM1 inhibits inflammatory response via MMP-9/TIMP-1 axis. Taken together, CEACAM1 attenuates diabetic atherosclerosis by inhibition of IκB/NF-κB signal pathway via MMP-9/TIMP-1 axis, which indicate that CEACAM1 is potentially amenable to therapeutic manipulation for clinical application in atherosclerosis in T2DM.

Meso-Reconstruction of Wool Keratin 3D "Molecular Springs" for Tunable Ultra-Sensitive and Highly Recovery Strain Sensors.

Wool keratin (WK) consists of a large number of α-helices, which are just like many molecular-scale springs. Herein, the construction of 3D WK molecular spring networks are reported by cross-linking individual WK molecules via a Michael addition reaction. The as-prepared springs display a superior recovery capability with unusual nonlinear elasticity, very low dissipative energy, and turntable elastic constant achieved by adjusting the chemical crosslinking density of WK networks. Owing to these unique characteristics, the 3D WK networks based flexible strain sensors reveal a high sensitivity, broad sensing ranges, and extremely long and stable performance. While normal highly sensible strain sensors, obtained by highly sophisticated surface or bulk patterning, often exhibit a relatively narrow range of measurements and limited life cycles. Such the WK mediated sensing materials have widespread applications in wearable electronics, such as detection and tracking of different human motions, and even discern voice during speaking.