Sirolimus-eluting iron bioresorbable scaffold versus cobalt-chromium everolimus-eluting stents in patients with coronary artery disease: Rationale and design of the IRONMAN-II trial.

BACKGROUND: The previous first-in-human study established the preliminary safety and effectiveness of the novel thin-strut iron bioresorbable scaffold (IBS). The current study aims to directly compare the imaging and physiological efficacy, and clinical outcomes of IBS with contemporary metallic drug-eluting stents (DES). METHODS: A total of 518 patients were randomly allocated to treatment with IBS (257 patients) or metallic DES (261 patients) from 36 centers in China. The study is powered to test noninferiority of the IBS compared with the metallic everolimus-eluting stent in terms of the primary endpoint of in-segment late lumen loss at 2 years, and major secondary endpoints including 2-year quantitative flow ratio and cross-sectional mean flow area measured by optical coherence tomography (OCT) (limited to the OCT subgroup, 25 patients in each group). CONCLUSION: This will be the first powered randomized trial investigating the safety and efficacy of the novel thin-strut IBS compared to a contemporary metallic DES. The findings will provide valuable evidence for future research of this kind and the application of metallic bioresorbable scaffolds.

Biomechanics of annulus fibrosus: Elastic fiber simplification and degenerative impact on damage initiation and propagation.

This study addresses three primary objectives related to lumbar intervertebral disc (IVD) biomechanics under ramping quasi-static loading conditions. First, we explore the conditions justifying the simplification of axisymmetric elastic fiber families into single fiber bundles through discretized strain energy functions. Simulations reveal that a concentration factor exceeding 10 allows for a consistent deviation below 10% between simplified and non-simplified responses. Second, we investigate the impact of elastic fibers on the physiological stiffness in IVDs, revealing minimal influence on biological motions but significant effects on degeneration. Lastly, we examine the initiation and progression of annulus fibrosus (AF) damage. Our findings confirm the validity of simplifying elastic fiber families and underscore the necessity of considering elastic fiber damage in biomechanical studies of AF tissues. Elastic fibers contribute to increased biaxial stretch stiffness, and their damage significantly affects the loading capacity of the inner AF. Additionally, degeneration significantly alters the susceptibility to damage in the AF, with specific regions exhibiting higher vulnerability. Damage tends to extend circumferentially and radially, emphasizing the regional variations in collagen and elastic fiber properties. This study offers useful insights for refining biomechanical models, paving the way for a more comprehensive understanding of IVD responses and potential clinical implications.

Multi-parameter design of triply periodic minimal surface scaffolds: from geometry optimization to biomechanical simulation.

This study introduces a multi-parameter design methodology to create triply periodic minimal surface (TPMS) scaffolds with predefined geometric characteristics. The level-set constant and unit cell lengths are systematically correlated with targeted porosity and minimum pore sizes. Network and sheet scaffolds featuring diamond, gyroid, and primitive level-set structures are generated. Three radially graded schemes are applied to each of the six scaffold type, accommodating radial variations in porosity and pore sizes. Computer simulations are conducted to assess the biomechanical performance of 18 scaffold models. Results disclose that diamond and gyroid scaffolds exhibit more expansive design ranges than primitive counterparts. While primitive scaffolds display the highest Young's modulus and permeability, their lower yield strength and mesenchymal stem cell (MSC) adhesion render them unsuitable for bone scaffolds. Gyroid scaffolds demonstrate superior mechanical and permeability performances, albeit with slightly lower MSC adhesion than diamond scaffolds. Sheet scaffolds, characterized by more uniform material distribution, exhibit superior mechanical performance in various directions, despite slightly lower permeability. The higher specific surface area of sheet scaffolds contributes to elevated MSC adhesion. The stimulus factor analysis also revealed the superior differentiation potential of sheet scaffolds over network ones. The diamond sheet type demonstrated the optimal differentiation. Introducing radial gradations enhances axial mechanical performance at the expense of radial mechanical performance. Radially decreasing porosity displays the highest permeability, MSC adhesion, and differentiation capability, aligning with the structural characteristics of human bones. This study underscores the crucial need to balance diverse biomechanical properties of TPMS scaffolds for bone tissue engineering.

Protective effects of sinomenine against dextran sulfate sodium-induced ulcerative colitis in rats via alteration of HO-1/Nrf2 and inflammatory pathway.

BACKGROUND: Dextran Sulfate Sodium (DSS) induces ulcerative colitis (UC), a type of inflammatory bowel disease (IBD) that leads to inflammation, swelling, and ulcers in the large intestine. The aim of this experimental study is to examine how sinomenine, a plant-derived alkaloid, can prevent or reduce the damage caused by DSS in the colon and rectum of rats. MATERIAL AND METHODS: Induction of ulcerative colitis (UC) in rats was achieved by orally administering a 2% Dextran Sulfate Sodium (DSS) solution, while the rats concurrently received oral administrations of sinomenine and sulfasalazine. The food, water intake was estimated. The body weight, disease activity index (DAI), colon length and spleen index estimated. Antioxidant, cytokines, inflammatory parameters and mRNA expression were estimated. The composition of gut microbiota was analyzed at both the phylum and genus levels in the fecal samples obtained from all groups of rats. RESULTS: Sinomenine treatment enhanced the body weight, colon length and reduced the DAI, spleen index. Sinomenine treatment remarkably suppressed the level of NO, MPO, ICAM-1, and VCAM-1 along with alteration of antioxidant parameters such as SOD, CAT, GPx, GR and MDA. Sinomenine treatment also decreased the cytokines like TNF-α, IL-1, IL-1ß, IL-6, IL-10, IL-17, IL-18 in the serum and colon tissue; inflammatory parameters viz., PAF, COX-2, PGE2, iNOS, NF-κB; matrix metalloproteinases level such as MMP-1 and MMP-2. Sinomenine significantly (P < 0.001) enhanced the level of HO-1 and Nrf2. Sinomenine altered the mRNA expression of RIP1, RIP3, DRP3, NLRP3, IL-1ß, caspase-1 and IL-18. Sinomenine remarkably altered the relative abundance of gut microbiota like firmicutes, Bacteroidetes, F/B ratio, Verrucomicrobia, and Actinobacteria. CONCLUSION: The results clearly indicate that sinomenine demonstrated a protective effect against DSS-induced inflammation, potentially through the modulation of inflammatory pathways and gut microbiota.

Comparing the osteogenesis outcomes of different lumbar interbody fusions (A/O/X/T/PLIF) by evaluating their mechano-driven fusion processes.

BACKGROUND: In lumbar interbody fusion (LIF), achieving proper fusion status requires osteogenesis to occur in the disc space. Current LIF techniques, including anterior, oblique, lateral, transforaminal, and posterior LIF (A/O/X/T/PLIF), may result in varying osteogenesis outcomes due to differences in biomechanical characteristics. METHODS: A mechano-regulation algorithm was developed to predict the fusion processes of A/O/X/T/PLIF based on finite element modeling and iterative evaluations of the mechanobiological activities of mesenchymal stem cells (MSCs) and their differentiated cells (osteoblasts, chondrocytes, and fibroblasts). Fusion occurred in the grafting region, and each differentiated cell type generated the corresponding tissue proportional to its concentration. The corresponding osteogenesis volume was calculated by multiplying the osteoblast concentration by the grafting volume. RESULTS: TLIF and ALIF achieved markedly greater osteogenesis volumes than did PLIF and O/XLIF (5.46, 5.12, 4.26, and 3.15 cm3, respectively). Grafting volume and cage size were the main factors influencing the osteogenesis outcome in patients treated with LIF. A large grafting volume allowed more osteoblasts (bone tissues) to be accommodated in the disc space. A small cage size reduced the cage/endplate ratio and therefore decreased the stiffness of the LIF. This led to a larger osteogenesis region to promote osteoblastic differentiation of MSCs and osteoblast proliferation (bone regeneration), which subsequently increased the bone fraction in the grafting space. CONCLUSION: TLIF and ALIF produced more favorable biomechanical environments for osteogenesis than did PLIF and O/XLIF. A small cage and a large grafting volume improve osteogenesis by facilitating osteogenesis-related cell activities driven by mechanical forces.

Integrated evaluation of biomechanical and biological properties of the biomimetic structural bone scaffold: Biomechanics, simulation analysis, and osteogenesis.

A porous structure is essential for bone implants because it increases the bone ingrowth space and improves mechanical and biological properties. The biomimetically designed porous Voronoi scaffold can reconstruct the structure and function of cancellous bone; however, its comprehensive properties need to be investigated further. In this study, algorithms based on scaling factors were used to design the Voronoi scaffolds. Classic approaches, such as computer-aided design and the implicit surface method, have been used to design Diamond, Gyroid, and I-WP scaffolds as controls. All scaffolds were prepared by selective laser melting of titanium alloys and three-dimensional printing. Mechanical tests, finite element analysis, and in vitro and in vivo experiments were performed to investigate the biomechanical, cytologic, and osteogenic performance of the scaffolds, while computational fluid dynamics simulations were used to explore the underlying mechanisms. Diamond scaffolds have a better loading capacity, and the mechanical behaviors and fluid flow of Voronoi scaffolds are similar to those of the human trabecular bone. Cells showed more proliferation and distribution on the Diamond and Voronoi scaffolds and exhibited evident differentiation on Gyroid and Voronoi scaffolds. Bone formation was apparent on the inner part of the Gyroid, the outer part of the I-WP, and the entire Diamond and Voronoi scaffolds. The hydrodynamic properties and stimulus response of cells influenced by the porous structure account for the varied biological performance of the scaffolds. The Voronoi scaffolds with bionic mechanical behavior and an appropriate hydrodynamic response exhibit evident cell growth and osteogenesis, making them preferable for porous structural bone implants.

Comprehensive modeling of annulus fibrosus: From biphasic refined characterization to damage accumulation under viscous loading.

The annulus fibrosus (AF), a permeable, hydrated, and fiber-reinforced soft tissue, exhibits complex responses influenced by fluid pressure, osmotic pressure, and structural mechanics. Existing models struggle to comprehensively represent these intricate interactions and the heterogeneous solid responses within the AF. Additionally, the mechanisms driving differential damage accumulation between non-degenerative and degenerative intervertebral discs remain poorly understood. In this study, we introduce a biphasic-swelling damage model for the AF. We conceptually develop and rigorously validate this model through tissue-level tests employing various loading modes, consistently aligning model predictions with experimental data. Leveraging parametric geometric algorithms and custom Python scripts, we construct models simulating both non-degenerative and degenerative discs. Following calibration, we subject these models to viscous loading protocols. Our findings reveal the posterior AF's susceptibility to damage, contingent upon loading rate and water content. We elucidate the underlying mechanisms by examining the temporal evolution of fluid pressure, osmotic pressure, and the regionally dependent fiber network. This research presents a highly accurate model of the AF, providing valuable insights into disc damage. Future research endeavors should expand this model to incorporate ionic transport and diffusion, enabling a more profound exploration of intervertebral disc mechanobiology. This comprehensive model contributes to a better understanding of AF behavior and may inform therapeutic strategies for disc-related pathologies. STATEMENT OF SIGNIFICANCE: This research presents a comprehensive model of the annulus fibrosus (AF), a crucial component of the intervertebral disc that provides structural support and resists deformation. The study introduces a biphasic-swelling damage model for the AF and validates it through tissue-level tests. The model accounts for fluid pressure, osmotic pressure, and matrix mechanics, providing a more accurate representation of the AF's behavior. The study also investigates the differential damage accumulation between non-degenerative and degenerative discs, shedding light on the mechanisms driving disc degeneration. The findings have significant implications for medical treatments and interventions, as they highlight the posterior AF's susceptibility to damage. This research is of great interest to readers interested in biomechanics, tissue engineering, and medical treatments for disc degeneration.

Fabrication of Nickel/Zinc Oxide Nanocomposites from Citrus sinensis Extract Prompts Apoptosis Through Impeding JAK/STAT3 Signaling in Gastric Cancer.

In this study, we sought to fabricate nickel/zinc oxide nanocomposites utilizing Citrus sinensis (C. sinensis) peel extract (CS-Ni/ZnO NCs) and investigate their ability to impede the JAK/STAT3 signaling pathway in gastric cancer AGS cells. Different methods, including UV-Vis spectral analysis, FT-IR, XRD, FE-SEM, EDAX, DLS, and zeta potential, were used to characterize the fabricated CS-Ni/ZnO NCs. By measuring ROS, MMP, and apoptotic cell death using the appropriate fluorescence describing procedures, the anticancer potential of CS-Ni/ZnO NCs was examined against AGS cells. The synthesized CS-Ni/ZnO NCs displayed a rod structure with a diameter of 74.76 nm. The cytotoxicity assay showed that the CS-Ni/ZnO NCs diminished the viability of the AGS cells in a dosage-dependent manner. Results from the fluorescence probe assay showed that the CS-Ni/ZnO NCs caused apoptosis in AGS cells. JAK/STAT-3 over expressions thought to expand the transcriptional regulation of proliferation and anti-apoptosis. Hence, inhibition of JAK/STAT-3 expression is considered a crucial target for impeding the expansion of gastric cancer proliferation. The JAK/STAT3 signaling cascade was successfully blocked by CS-Ni/ZnO NCs treatment, which also started the apoptotic pathway in the AGS cells. The findings conclude that CS-Ni/ZnO NCs might serve as a promising chemo-preventive agent for treating GC. Nickel/Zinc oxide nanocomposites were synthesized using C. sinensis peel extract (CS-Ni/ZnO NCs) and characterized by UV-Vis, XRD, FTIR, and TEM to confirm the nanoparticles. CS-Ni/ZnO NCs induce the overproduction of ROS-mediated MMP alteration and apoptosis features in AGS gastric cancer cells. CS-Ni/ZnO NCs inhibited the JAK/STAT3 signaling, thereby suppressing the proliferation and inducing apoptosis in gastric cancer cells.

On the identification of the ultra-structural organization of elastic fibers and their effects on the integrity of annulus fibrosus.

Due to the complicated structure of the elastic fiber network in annulus fibrosus, existing in-silico studies either simplified or just overlooked its distribution pattern. Nonetheless, experimental and simulation results have proven that elastic fibers are of great importance to maintaining the structural integrity of annulus fibrosus and therefore to ensuring the load-bearing ability of intervertebral discs. Such needs call for a fine model. This work aims at developing a biphasic annulus fibrosus model by incorporating the accurate distribution pattern of collagen and elastic fibers. Both the structural parameters and intrinsic mechanical parameters were successfully identified using single lamella and inter-lamella microscopy anatomy and micromechanical testing data. The proposed model was then used to implement finite element simulations on various anterior and posterolateral multi-lamellae annulus fibrosus specimens. In general, simulation results agree well with available experimental and simulation data. On this basis, the effects of elastic fibers on the integrity of annulus fibrosus were further investigated. It was found that elastic fibers significantly influence the free swelling, radial stretching and circumferential shear performances of annulus fibrosus. Nonetheless, no significant effects were found for the circumferential stretching capability. The proposed biphasic model considers for the first time the distribution characteristics of elastic fibers at two scales, including both the principal orientations of all fiber families and the detailed distribution pattern within each family. Better understandings on the functions of collagen and elastic fibers can therefore be realized. To further enhance its prediction capability, the current model can be extended in the future by taking the fiber-matrix interaction as well as progressive damages into consideration.

Quantitative flow ratio as a continuous predictor of myocardial infarction.

BACKGROUND: The quantitative flow ratio (QFR) identifies functionally ischaemic lesions that may benefit more from percutaneous coronary intervention (PCI) than from medical therapy. AIMS: This study investigated the association between QFR and myocardial infarction (MI) as affected by PCI versus medical therapy. METHODS: All vessels requiring measurement (reference diameter ≥2.5 mm and existence of at least one stenotic lesion with diameter stenosis of 50-90%) in the FAVOR III China (5,564 vessels) and PANDA-III trials (4,471 vessels) were screened and analysed for offline QFR. The present study reported clinical outcomes on a per-vessel level. Interaction between vessel treatment and QFR as a continuous variable was evaluated for the threshold of 2-year MI estimated by Cox proportional hazards model. RESULTS: Compared with medical therapy at 2 years, PCI reduced the MI risk in vessels with a QFR ≤0.80 (3.0% vs 4.6%) but increased the MI risk in vessels with a QFR>0.80 (3.6% vs 1.2%). Additionally, continuous QFR showed an inverse association with spontaneous MI (hazard ratio [HR] 0.89, 95% confidence interval [CI]: 0.79-0.99; p=0.04) that was reduced by PCI compared to medical therapy (HR 0.26, 95% CI: 0.17-0.40; p<0.0001). The interaction indicated a net benefit for PCI over medical therapy to reduce total MI beginning at QFR ≤0.64. CONCLUSIONS: The present study demonstrated a continuous, inverse relationship between the QFR value of a vessel and its subsequent risk for MI, and PCI, compared to medical therapy, reduced this risk beginning at a QFR value of 0.64. These novel findings provide physicians with an angiographic tool for optimising vessel selection for PCI.

First-in-human evaluation of a novel ultrathin sirolimus-eluting iron bioresorbable scaffold: 3-year outcomes of the IBS-FIM trial.

BACKGROUND: The first-generation polymeric bioresorbable scaffolds resulted in higher than acceptable 3-year rates of device-related adverse outcomes. AIMS: We aimed to assess the intermediate-term safety and performance of a novel ultrathin-strut sirolimus-eluting iron bioresorbable scaffold (IBS) in non-complex coronary lesions. METHODS: The prospective, single-arm, open-label IBS first-in-human study enrolled 45 patients, each with a single de novo lesion. Enrolled patients were randomly assigned to 2 follow-up cohorts. Angiographic and imaging follow-up with intravascular ultrasound and optical coherence tomography (OCT) were conducted at 6 and 24 months in cohort 1 (n=30) and at 12 and 36 months in cohort 2 (n=15). Clinical follow-up was conducted at 1, 6 and 12 months, and annually thereafter up to 5 years. The coprimary outcomes were target lesion failure (TLF) and angiographic late lumen loss (LLL) at 6 months. RESULTS: A total of 45 patients were enrolled between April 2018 and January 2019. The mean age was 53.2 years, 77.8% were male, and 26.7% had diabetes. The TLF rates were 2.2% at 6 months and 6.7% at 3 years, which in all cases were due to clinically indicated target lesion revascularisation. No deaths, myocardial infarctions or stent thromboses occurred during 3-year follow-up. In-scaffold LLL was 0.33±0.27 mm at 6 months and 0.37±0.57 mm at 3 years. By OCT, the proportion of covered struts was 99.8% at 6 months and 100% after 1 year. The 3-year strut absorption rate was 95.4%. CONCLUSIONS: In this first-in-human experience, an ultrathin IBS was safe and effective for the treatment of de novo non-complex coronary lesions up to 3-year follow-up.

A swelling-based biphasic analysis on the quasi-static biomechanical behaviors of healthy and degenerative intervertebral discs.

BACKGROUND AND OBJECTIVE: The degeneration of intervertebral discs is significantly dependent of the changes in tissue composition ratio and tissue structure. Up to the present, the effects of degeneration on the quasi-static biomechanical responses of discs have not been well understood. The goal of this study is to quantitatively analyze the quasi-static responses of healthy and degenerative discs. METHODS: Four biphasic swelling-based finite element models are developed and quantitatively validated. Four quasi-static test protocols, including the free-swelling, slow-ramp, creep and stress-relaxation, are implemented. The double Voigt and double Maxwell models are further used to extract the immediate (or residual), short-term and long-term responses of these tests. RESULTS: Simulation results show that both the swelling-induced pressure in the nucleus pulposus and the initial modulus decrease with degeneration. In the free-swelling test of discs possessing healthy cartilage endplates, simulation results show that over 80% of the total strain is contributed by the short-term response. The long-term response is dominant for discs with degenerated permeability in cartilage endplates. For the creep test, over 50% of the deformation is contributed by the long-term response. In the stress-relaxation test, the long-term stress contribution occupies approximately 31% of total response and is independent of degeneration. Both the residual and short-term responses vary monotonically with degeneration. In addition, both the glycosaminoglycan content and permeability affect the engineering equilibrium time constants of the rheologic models, in which the determining factor is the permeability. CONCLUSIONS: The content of glycosaminoglycan in intervertebral soft tissues and the permeability of cartilage endplates are two critical factors that affect the fluid-dependent viscoelastic responses of intervertebral discs. The component proportions of the fluid-dependent viscoelastic responses depend also strongly on test protocols. In the slow-ramp test, the glycosaminoglycan content is responsible for the changes of the initial modulus. Since existing computational models simulate disc degenerations only by altering disc height, boundary conditions and material stiffness, the current work highlights the significance of biochemical composition and cartilage endplates permeability in the biomechanical behaviors of degenerated discs.

Distribution of microplastics in different tissues of major commercial catches in different functional areas of the South Yellow Sea.

The microplastic (MP) pollution in different tissues of six commercial catches, including (Miichthys miiuy, Eleutheronema tetradactylum, Collichthys lucidus, Mugil cephalus, Portunus trituberculatus and Exopalaemon carinicauda) in Haizhou Bay (nori farming area), Yancheng offshore (wind power construction area) and the Nantong marine ranch area of the South Yellow Sea was investigated. MPs are ubiquitous in commercial catches; the average abundance of MPs is 5.19 ± 3.64 items/individual. There are significant differences in the level of MP pollution in commercial catches among functional sea areas. The level of MP pollution in commercial catches in Haizhou Bay and Yancheng offshore is higher than that in the Nantong marine ranch areas. This difference may be related to intense anthropogenic activities such as engineering construction and mariculture. In addition to the presence in digestive tract, MPs in the skin and gills of fish and in the gills of shrimp and crabs cannot be ignored. The main shape, color and material of MPs are fiber, black-gray and celluloid (CP), respectively. Since commercial catches are consumed by humans, the potential risks of MPs in these catches to human health and marine ecology are of concern.

Roles of irregularity of pore morphology in osteogenesis of Voronoi scaffolds: From the perspectives of MSC adhesion and mechano-regulated osteoblast differentiation.

Bone scaffolds designed based on the Voronoi-tessellation algorithm have been increasingly studied owing to their structural similarity with natural cancellous bone. The irregularity of pore morphology (IPM) influences the osteogenesis efficiency of Voronoi scaffolds since it may alter the static and hydromechanical microenvironments for the initial adhesion and mechano-regulated osteoblast differentiation (MrOD) of mesenchymal stem cells (MSCs). In this work, animal experiments were conducted to explore the relationship between IPM and osteogenesis efficiency in Voronoi scaffolds. A computational fluid dynamics (CFD) analysis based on discrete phase models was performed to predict the efficiency of MSC adhesion in different IPMs. Another combined finite element and CFD analysis based on the mechano-regulation algorithm was performed to predict the influence of IPM on the MrOD of the adhesive MSCs. The results showed that the osteogenesis efficiency of the Voronoi scaffolds increased as the IPM rose from low to moderate and then dropped as the IPM further rose. Same trends were also found in the MSC adhesion and MrOD, which caused by the changes of strain tensors on the strut surface and the tortuosity and fluid velocity of the fluid pathway. Moderate IPM induced the highest osteogenesis efficiency owing to its highest efficiencies of MSC adhesion and MrOD. This work identified the optimal IPM for the osteogenesis of Voronoi scaffolds and clarified its biomechanical mechanisms from the adhesion and mechano-regulated differentiation of MSCs, which is of great importance for guiding Voronoi scaffold design when it is used for bone defect repair.

Coupling Quantum Random Walks with Long- and Short-Term Memory for High Pixel Image Encryption Schemes.

This paper proposes an encryption scheme for high pixel density images. Based on the application of the quantum random walk algorithm, the long short-term memory (LSTM) can effectively solve the problem of low efficiency of the quantum random walk algorithm in generating large-scale pseudorandom matrices, and further improve the statistical properties of the pseudorandom matrices required for encryption. The LSTM is then divided into columns and fed into the LSTM in order for training. Due to the randomness of the input matrix, the LSTM cannot be trained effectively, so the output matrix is predicted to be highly random. The LSTM prediction matrix of the same size as the key matrix is generated based on the pixel density of the image to be encrypted, which can effectively complete the encryption of the image. In the statistical performance test, the proposed encryption scheme achieves an average information entropy of 7.9992, an average number of pixels changed rate (NPCR) of 99.6231%, an average uniform average change intensity (UACI) of 33.6029%, and an average correlation of 0.0032. Finally, various noise simulation tests are also conducted to verify its robustness in real-world applications where common noise and attack interference are encountered.

Disruption of phosphate metabolism and sterol transport-related genes conferring yeast resistance to vanillin and rapid ethanol production.

Vanillin is a potent growth-inhibiting factor in Saccharomyces cerevisiae during lignocellulose biorefineries. Here, a haploid gene-deletion library was screened to search for vanillin-tolerant mutants and explain the possible tolerance mechanisms. Twenty-two deletion mutants were identified. The deleted genes in these mutants were involved in phosphate and inositol polyphosphate metabolism and intracellular sterol transport. Activation of the phosphate signaling pathway is not conducive to yeast against the pressure of vanillin. Furthermore, the findings indicate the role of inositol polyphosphates in altering vanillin tolerance by regulating phosphate metabolism. Meanwhile, reducing the transport of sterols from the plasma membrane enhanced tolerance to vanillin. In the presence of vanillin, the representative yeast deletions, pho84Δ and lam3Δ, showed good growth performance and promoted rapid ethanol production. Overall, this study identifies robust yeast strain alternatives for ethanol fermentation of cellulose and provides guidance for further genomic reconstruction of yeast strains.

Integrated Bioinformatics-Based Identification of Ferroptosis-Related Genes in Carotid Atherosclerosis.

Background: Ferroptosis, a type of cell death caused by phospholipid peroxidation, has lately been linked to the onset and development of numerous illnesses. Numerous investigations have demonstrated the close relationship between lipid peroxidation and carotid atherosclerosis. In order to get new knowledge for targeted therapy, bioinformatics analysis was employed in this study to discover the probable ferroptosis-related genes of carotid atherosclerosis. Methods: The GSE43292 gene expression dataset was downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed ferroptosis-related genes were screened by R software and then analyzed by protein-protein interaction (PPI) network, differential gene correlation analysis, Kyoto Encyclopedia of Gene and Genome (KEGG) pathway, and Gene Ontology (GO) terminology enrichment analysis to explore the functional role. Result: In samples of atherosclerosis, we found 33 ferroptosis genes that were differentially expressed, including 21 upregulated genes and 12 downregulated genes. These differentially elevated genes were mainly connected to the ferroptosis and glutathione metabolism pathways, according to GO and KEGG enrichment analysis. We also discovered 10 hub genes and 2 important modules through the analysis of the PPI network and the creation of key modules. Conclusion: The current findings imply that the carotid atherosclerosis phenomenon involves ferroptosis, and 10 important genes associated to ferroptosis may play a role in the development of carotid atherosclerosis. This study offered a novel approach to future research on the carotid atherosclerosis pathogenic processes and treatment targets.

Performance Evaluation of an Octadecyltrimethyl Ammonium Chloride-Dimethyl Silicone Oil as a Waterproof Locking Agent in Low-Permeability Reservoirs.

Low porosity and permeability of oil and gas reservoirs make it difficult to develop these resources. To address these problems, we developed and evaluated a novel, environmentally friendly waterproof locking agent, which was prepared using dimethyl silicone oil and octadecyltrimethylammonium chloride and characterized by Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and particle size measurement. The waterproof locking performance of the agent was evaluated in a low-permeability reservoir using surface tension and contact angle measurements, and thermodynamic calculations were performed. The average particle size or median diameter (D 50) of a 1% mother liquor was 325 nm at 20 °C and 470.8 nm at 70 °C. The contact angle of clean water on the core surface increased from 10 to 110°. At 70 °C, the surface tension of water was reduced to 24 mN·m-1, indicating good waterproof locking performance. The interaction parameters were calculated in accordance with the Langmuir adsorption theory. The increase in temperature from 20 to 70 °C reduced Γmax from 4.59 × 10-6 to 1.36 × 10-6 mol·m-2 and ΔG θ from -40.93 to -56.54 kJ·mol-1. Thus, the adsorption behavior of the developed locking agent is believed to improve the productivity of oil wells.

A First-in-Human Study of the Bioheart Sirolimus-Eluting Bioresorbable Vascular Scaffold in Patients with Coronary Artery Disease: Two-Year Clinical and Imaging Outcomes.

INTRODUCTION: Newer generation bioresorbable scaffolds (BRSs) with thinner struts and improved deliverability are expected to enhance safety and efficacy profiles. Bioheart (Bio-Heart, Shanghai, China) BRS is constructed from a PLLA (poly-l-lactic acid) backbone coated with a PDLLA (poly D-l-lactic acid) layer eluting sirolimus. We report 2-year serial intracoronary imaging findings. METHODS: In this first-in-human study, 46 patients with single de novo lesions in native coronary vessels (vessel size 3.0-3.75 mm, lesion length ≤ 25 mm) were enrolled at a single institution. Baseline intravascular ultrasound (IVUS) and post-implantation IVUS and optical coherence tomography (OCT) examinations were mandatory. After successful implantations of BRS, the 46 patients were randomized to two different follow-up cohorts in a 2:1 ratio. Thirty patients in cohort 1 had to undergo angiography, IVUS, and OCT follow-ups at 6 and 24 months, respectively. The 16 patients in cohort 2 underwent the same types of imaging follow-ups at 12 and 36 months, respectively. Clinical follow-ups were scheduled uniformly in both cohorts at 1, 6, and 12 months and annually up to 5 years for all patients. RESULTS: Between August and November 2016, a total of 54 patients were assessed. However, 8 patients could not meet all the inclusion criteria; thus, the remaining 46 patients (age 57.5 ± 8.7 years, 34.8% female, 50.0% with unstable angina, 26.1% diabetics) with 46 target lesions were enrolled in this study. All patients in both cohorts were required to complete clinical follow-up uniformly and regularly. In cohort 1, one patient had definite scaffold thrombosis within 6 months of follow-up; thus, after 6 months, cohort 1 had 96.7% patients . Imaging follow-up was available in 24 patients, and in-scaffold late loss was 0.44 ± 0.47 mm; intracoronary imaging confirmed the late loss was mainly due to to neointimal hyperplasia, but not scaffold recoil. CONCLUSIONS: Serial 2-year clinical and imaging follow-up results confirmed the preliminary safety and efficacy of Bioheart BRS for treatment of simple coronary lesions.

A finite element study on the effects of follower load on the continuous biomechanical responses of subaxial cervical spine.

In spine biomechanics, follower loads are used to mimic the in vivo muscle forces acting on a human spine. However, the effects of the follower load on the continuous biomechanical responses of the subaxial cervical spines (C2-T1) have not been systematically clarified. This study aims at investigating the follower load effects on the continuous biomechanical responses of C2-T1. A nonlinear finite element model is reconstructed and validated for C2-T1. Six levels follower loads are considered along the follower load path that is optimized through a novel range of motion-based method. A moment up to 2 Nm is subsequently superimposed to produce motions in three anatomical planes. The continuous biomechanical responses, including the range of motion, facet joint force, intradiscal pressure and flexibility are evaluated for each motion segment. In the sagittal plane, the change of the overall range of motion arising from the follower loads is less than 6%. In the other two anatomical planes, both the magnitude and shape of the rotation-moment curves change with follower loads. At the neutral position, over 50% decrease in flexibility occurs as the follower load increases from zero to 250 N. In all three anatomical planes, over 50% and 30% decreases in flexibility occur in the first 0.5 Nm for small (≤100 N) and large (≥150 N) follower loads, respectively. Moreover, follower loads tend to increase both the facet joint forces and the intradiscal pressures. The shape of the intradiscal pressure-moment curves changes from nonlinear to roughly linear with increased follower load, especially in the coronal and transverse planes. The results obtained in this work provide a comprehensive understanding on the effects of follower load on the continuous biomechanical responses of the C2-T1.