Engineering Nanosensitizer to Remodel the TME for Hypoimmunogenic "Cold"-"Hot" Tumor Transformations.

α-PD-L1 therapy has shown encouraging results at harnessing the immune system to combat cancer. However, the treatment effect is relatively low due to the dense extracellular matrix (ECM) and tumor immunosuppressive microenvironment (TIME). Therefore, an ultrasound (US)-responsive nanosensitizer (URNS) is engineered to deliver losartan (LST) and polyethylenimine (PEI) to remolde the TME, driving "cold"-"hot" tumor transformation and enhancing the sensitivity of α-PD-L1 therapy. In the tumor site, noninvasive US can make MTNP generate ROS, which cleave ROS-sensitive bonds to dissociate MTNPtK@LST-PEI, shedding PEI and releasing LST from mesoporous spheres. The results demonstrated that URNS combined with α-PD-L1 therapy effectively inhibited tumor growth with an inhibition rate as high as 90%, which was 1.7-fold higher than that of the α-PD-L1 treatment in vivo. In summary, the URNS improves the sensitivity of α-PD-L1 therapy by remodeling the TME, which provides promising insights for optimizing cancer immunotherapy.

TRIUMPH: phase II trial of rucaparib monotherapy in patients with metastatic hormone-sensitive prostate cancer harboring germline homologous recombination repair gene mutations.

BACKGROUND: The activity of PARP inhibitors (PARPi) in patients with homologous recombination repair (HRR) mutations and metastatic castration-resistant prostate cancer has been established. We hypothesized that the benefit of PARPi can be maintained in the absence of androgen deprivation therapy (ADT) in an HRR-mutated population. We report the results of a phase II clinical trial of rucaparib monotherapy in patients with metastatic hormone-sensitive prostate cancer (mHSPC). METHODS: This was a multi-center, single-arm phase II trial (NCT03413995) for patients with asymptomatic, mHSPC. Patients were required to have a pathogenic germline mutation in an HRR gene for eligibility. All patients received rucaparib 600 mg by mouth twice daily, without androgen deprivation. The primary endpoint was a confirmed PSA50 response rate. RESULTS: Twelve patients were enrolled, 7 with a BRCA1/2 mutation and 5 with a CHEK2 mutation. The confirmed PSA50 response rate to rucaparib was 41.7% (N = 5/12, 95% CI: 15.2-72.3%, one-sided P = .81 against the 50% null), which did not meet the pre-specified efficacy boundary to enroll additional patients. In patients with measurable disease, the objective response rate was 60% (N = 3/5), all with a BRCA2 mutation. The median radiographic progression-free survival on rucaparib was estimated at 12.0 months (95% CI: 8.0-NR months). The majority of adverse events were grade ≤2, and expected. CONCLUSION: Rucaparib can induce clinical responses in a biomarker-selected metastatic prostate cancer population without concurrent ADT. However, the pre-specified efficacy threshold was not met, and enrolment was truncated. Although durable responses were observed in a subset of patients, further study of PARPi treatment without ADT in mHSPC is unlikely to change clinical practice.

Natural Underwater Bioadhesive Offering Cohesion Modulation via Hydrogen Bond Disruptor: A Highly Injectable and in Vivo Stable Remedy for Gastric Ulcer Resolution.

Injectable bioadhesives are attractive for managing gastric ulcers through minimally invasive procedures. However, the formidable challenge is to develop bioadhesives that exhibit high injectability, rapidly adhere to lesion tissues with fast gelation, provide reliable protection in the harsh gastric environment, and simultaneously ensure stringent standards of biocompatibility. Here, a natural bioadhesive with tunable cohesion is developed based on the facile and controllable gelation between silk fibroin and tannic acid. By incorporating a hydrogen bond disruptor (urea or guanidine hydrochloride), the inherent network within the bioadhesive is disturbed, inducing a transition to a fluidic state for smooth injection (injection force <5 N). Upon injection, the fluidic bioadhesive thoroughly wets tissues, while the rapid diffusion of the disruptor triggers instantaneous in situ gelation. This orchestrated process fosters the formed bioadhesive with durable wet tissue affinity and mechanical properties that harmonize with gastric tissues, thereby bestowing long-lasting protection for ulcer healing, as evidenced through in vitro and in vivo verification. Moreover, it can be conveniently stored (≥3 m) postdehydration. This work presents a promising strategy for designing highly injectable bioadhesives utilizing natural feedstocks, avoiding any safety risks associated with synthetic materials or nonphysiological gelation conditions, and offering the potential for minimally invasive application.

CLPs-miR-103a-2-5p inhibits proliferation and promotes cell apoptosis in AML cells by targeting LILRB3 and Nrf2/HO-1 axis, regulating CD8 + T cell response.

BACKGROUND: LILRB3, a member of the leukocyte immunoglobulin-like receptor B (LILRB) family, has immunosuppressive functions and directly regulates cancer development, which indicates that LILRB3 is an attractive target for cancer diagnosis and therapy. Novel therapeutic treatments for acute myeloid leukemia (AML) are urgent and important, and RNA therapeutics including microRNAs (miRNAs) could be an effective option. Here, we investigate the role of dysregulated miRNA targeting LILRB3 in the AML microenvironment. METHODS: Potential miRNAs binding to the 3'-untranslated region (3'-UTR) of the LILRB3 mRNA were predicted by bioinformatics websites. Then, we screened miRNAs targeting LILRB3 by quantitative real-time PCR, and the dual luciferase reporter assay. The expression of LILRB3 and microRNA (miR)-103a-2-5p in AML were determined and then their interactions were also analyzed. In vitro, the effects of miR-103a-2-5p were determined by CCK8, colony formation assay, and transwell assay, while cell apoptosis and cell cycle were analyzed by flow cytometry. Cationic liposomes (CLPs) were used for the delivery of miR-103a-2-5p in the AML mouse model, which was to validate the potential roles of miR-103a-2-5p in vivo. RESULTS: LILRB3 was upregulated in AML cells while miR-103a-2-5p was dramatically downregulated. Thus, a negative correlation was found between them. MiR-103a-2-5p directly targeted LILRB3 in AML cells. Overexpressed miR-103a-2-5p significantly suppressed the mRNA and protein levels of LILRB3, thereby inhibiting AML cell growth and reducing CD8 + T cell apoptosis. In addition, overexpressed miR-103a-2-5p reduced both the relative expression of Nrf2/HO-1 pathway-related proteins and the ratio of GSH/ROS, leading to the excessive intracellular ROS that may promote AML cell apoptosis. In the mouse model, the delivery of miR-103a-2-5p through CLPs could inhibit tumor growth. CONCLUSIONS: MiR-103a-2-5p serves as a tumor suppressor that could inhibit AML cell proliferation and promote their apoptosis by downregulating LILRB3 expression, suppressing the Nrf2/HO-1 axis, and reducing the ratio of GSH/ROS. Besides, our findings indicate that miR-103a-2-5p may enhance the CD8 + T cell response by inhibiting LILRB3 expression. Therefore, the delivery of miR-103a-2-5p through CLPs could be useful for the treatment of AML.

Stoichiometric microplastics models in natural and laboratory environments.

Microplastics pose a severe threat to marine ecosystems; however, relevant mathematical modeling and analysis are lacking. This paper formulates two stoichiometric producer-grazer models to investigate the interactive effects of microplastics, nutrients, and light on population dynamics under different settings. One model incorporates optimal microplastic uptake and foraging behavior based on nutrient availability for natural settings, while the other model does not include foraging in laboratory settings. We establish the well-posedness of the models and examine their long-term behaviors. Our results reveal that in natural environments, producers and grazers exhibit higher sensitivity to microplastics, and the system may demonstrate bistability or tristability. Moreover, the influences of microplastics, nutrients, and light intensity are highly intertwined. The presence of microplastics amplifies the constraints on grazer growth related to food quality and quantity imposed by extreme light intensities, while elevated phosphorus input enhances the system's resistance to intense light conditions. Furthermore, higher environmental microplastic levels do not always imply elevated microplastic body burdens in organisms, as organisms are also influenced by nutrients and light. We also find that grazers are more vulnerable to microplastics, compared to producers. If producers can utilize microplastics for growth, the system displays significantly greater resilience to microplastics.

Polyacetylene-Based Asymmetric Bicyclic Polymer by Blocking-Cyclization Technique.

A rare asymmetric bicyclic polymer containing different length of conjugated polyacetylene segments is synthesized by metathesis cyclopolymerization-mediated blocking-cyclization technique. The size of each single ring differs from each other, and the unique cyclic polymer topology is controlled by adjusting the feed ratio of monofunctional monomer to catalyst. The topological difference between linear and bicyclic polymers is confirmed by several techniques, and the visualized morphology of asymmetric bicyclic polymer is directly observed without tedious post-modification process. The photoelectric and thermal properties of polymers are investigated. This work expands the pathway for the derivation of cyclic polymers, and such unique topological structure enriches the diversity of cyclic polymer classes.

One-step enrichment and stepwise elution of glycoproteins and phosphoproteins by hydrophilic Ti4+-immobilized dendrimer poly(glycidyl methacrylate) microparticles functionalized with polyethylenimine and phytic acid.

Glycosylation and phosphorylation rank as paramount post-translational modifications, and their analysis heavily relies on enrichment techniques. In this work, a facile approach was developed for the one-step simultaneous enrichment and stepwise elution of glycoproteins and phosphoproteins. The core of this approach was the application of the novel titanium (IV) ion immobilized poly(glycidyl methacrylate) microparticles functionalized with dendrimer polyethylenimine and phytic acid. The microparticles possessed dual enrichment capabilities due to their abundant titanium ions and hydroxyl groups on the surface. They demonstrate rapid adsorption equilibrium (within 30 min) and exceptional adsorption capacity for ß-casein (1107.7 mg/g) and horseradish peroxidase (438.6 mg/g), surpassing that of bovine serum albumin (91.7 mg/g). Furthermore, sodium dodecyl sulfate-polyacrylamide gel electrophoresis was conducted to validate the enrichment capability. Experimental results across various biological samples, including standard protein mixtures, non-fat milk, and human serum, demonstrated the remarkable ability of these microparticles to enrich low-abundance glycoproteins and phosphoproteins from biological samples.

A prospective study on maternal periodontal diseases and neonatal adverse outcomes.

OBJECTIVE: It is evident that periodontitis is linked to various adverse pregnancy outcomes. This prospective study explored the potential link of maternal periodontal diseases to neonatal adverse outcomes. MATERIALS AND METHODS: A total of 193 generally healthy females in their third trimester (34-36 weeks) of pregnancy were enrolled. All subjects received full-mouth periodontal assessment, and the periodontal inflamed surface area (PISA) was calculated. Demographic data, lifestyles and anthropometric measurements of the neonates (e.g., body length and head circumference) were recorded. Herein, small-for-gestational age (SGA) referred to gender- and age-adjusted birth weight below the 10th percentile in line with the standard reference. Multivariable logistic regression analysis and restricted cubic spline were performed for examining the association of periodontal parameters with SGA.  Results: There were 8.3% (16/193) of neonates with SGA. Significantly positive correlation existed between the percentage of tooth sites with increased probing depth and an elevated risk of SGA (OR: 1.052; P < 0.05). Yet, the PISA was positively associated with the risk of SGA (OR: 1.002; P < 0.05) as well. No significant link occurred between maternal periodontal status and other neonatal outcome measures. CONCLUSION: Within the limitations of this study, the findings suggest that there could be a link between maternal periodontal diseases and neonatal adverse outcomes like SGA. Further investigation is required to clarify the current findings and potential implications for promoting maternal oral/periodontal health and newborn health.

Development of a spermine lipid for transient antibody expression.

Transient expression is the only way to quickly obtain a small scale of antibodies for biomedical research and therapeutic evaluation. The agents for transfecting the suspension cells, e.g. PEI or commercial agents, either lack efficiency or excessively expensive. Herein, a novel spermine-based lipid was developed and fabricated into a cationic liposome for antibody expression. This new transfection agent, designated as sperminoliposome, is feasible, cheap, and highly effective to produce antibodies. Compared to PEI, a 3 times higher yield of antibody was obtained by sperminoliposome during the transient expression of cetuximab in suspension 293F cells. Characterizations confirmed that the expressed antibody is fully functional and eligible for further research. Our study provides an effective tool for the rapid production of antibodies economically and feasibly.

Cotransport of microplastics and sulfanilamide antibiotics in groundwater: The impact of MP/SA ratio and aquifer media.

The aim of this study was to investigate the effects of the aquifer media, structure type, and initial concentration ratio of contaminants on the cotransport behavior of microplastics (MPs) and sulfanilamide antibiotics (SAs) through a series of one-dimensional column experiments in groundwater. Under a single suspension system, the relative mass recovery rates of fine sand, medium sand, and coarse sand were 25.65%, 37.50%, and 57.91%, respectively. The breakthrough curve of MPs showed a weak and slow upward trend, indicating that the migration of MPs in aqueous media is mainly blocked by the surface. The migration results of different structure type on SAs (ST, SM, SM2, SMX) in a single suspension system indicated that the deposition rate coefficients (kc) of the four SAs were 1.23 × 10-1, 9.09 × 10-2, 1.11 × 10-1, and 8.87 × 10-2. Under a binary suspension system (MPs:ST = 1:1), the maximum effluent concentration (MEC) of MPs in fine sand, medium sand, and coarse sand increased to 0.52, 0.64, and 0.88, respectively, and the relative mass recovery rates of ST were 22.79%, 23.59%, 20.25%. This results show that the coexistence of MPs and SAs significantly promotes the migration of MPs and inhibits that of SAs. It is mainly because of their carrier action, adsorption sites and additional deposit sites for MPs through SAs pre-deposition on media. When the initial concentration ratio was 2:1, the particles had the highest Zeta potential (-48.3 mV) and the highest potential barrier (3200 kBT), leading to the formation of complex aggregates (MPs-SAs-MPs) owing to the aggregation of colloidal MPs. The increase in the volume and number of MPs-SAs co-aggregates on the surface of the media as the initial concentration of MPs increases, which was mainly due to the disappearance of surface blocking effect and the occurrence of filtering maturation effect.

Behavioral and brain- transcriptomic synchronization between the two opponents of a fighting pair of the fish Betta splendens.

Conspecific male animals fight for resources such as food and mating opportunities but typically stop fighting after assessing their relative fighting abilities to avoid serious injuries. Physiologically, how the fighting behavior is controlled remains unknown. Using the fighting fish Betta splendens, we studied behavioral and brain-transcriptomic changes during the fight between the two opponents. At the behavioral level, surface-breathing, and biting/striking occurred only during intervals between mouth-locking. Eventually, the behaviors of the two opponents became synchronized, with each pair showing a unique behavioral pattern. At the physiological level, we examined the expression patterns of 23,306 brain transcripts using RNA-sequencing data from brains of fighting pairs after a 20-min (D20) and a 60-min (D60) fight. The two opponents in each D60 fighting pair showed a strong gene expression correlation, whereas those in D20 fighting pairs showed a weak correlation. Moreover, each fighting pair in the D60 group showed pair-specific gene expression patterns in a grade of membership analysis (GoM) and were grouped as a pair in the heatmap clustering. The observed pair-specific individualization in brain-transcriptomic synchronization (PIBS) suggested that this synchronization provides a physiological basis for the behavioral synchronization. An analysis using the synchronized genes in fighting pairs of the D60 group found genes enriched for ion transport, synaptic function, and learning and memory. Brain-transcriptomic synchronization could be a general phenomenon and may provide a new cornerstone with which to investigate coordinating and sustaining social interactions between two interacting partners of vertebrates.

An application framework of 3D assessment image registration accuracy and untouched surface area in canal instrumentation laboratory research with micro-computed tomography.

OBJECTIVES: The purpose of this study was to develop a customized framework for evaluating the registration accuracy of four registration techniques and measuring the untouched surface area of canal instrumentation by visually inspecting and calculating the overlapping area of the surfaces. METHODS: Twenty-one mandibular incisors were scanned by micro-computed tomography before and after instrumentation. Elastix registration, surface registration, manual registration, and DataViewer registration techniques were used to align the pre- and post-operative datasets. The customized MeVisLab framework was created to investigate the registration accuracy by visual inspection and calculating overlapping areas. The canal surfaces were imported into the same framework to measure the untouched surface area and the consistence test was validated. The correlation between registration accuracy and untouched surface area was analyzed. RESULTS: There is a statistically significant difference between manual registration and automatic registration (P < 0.05). There is no statistical difference between the two untouched surface measure methods (P > 0.05). The partial correlation coefficients for the untouched surface area and registration accuracy were 0.45 (P < 0.05). CONCLUSIONS: This application framework based on free customizable software, allows a new method to measure registration accuracy and untouched surface area in an efficient and sensitive way. The application of a precise registration method would improve the quality of micro-CT canal instrumentation studies. CLINICAL RELEVANCE: This study developed a customized framework based on free software for evaluating the registration accuracy of different registration techniques and measuring the untouched surface area of canal instrumentation could help researchers to improve the quality of micro-CT studies of canal instrumentation.

Guided Wave Ultrasonic Testing for Crack Detection in Polyethylene Pipes: Laboratory Experiments and Numerical Modeling.

The use of guided wave-based Ultrasonic Testing (UT) for monitoring Polyethylene (PE) pipes is mostly restricted to detecting defects in welded zones, despite its diversified success in monitoring metallic pipes. PE's viscoelastic behavior and semi-crystalline structure make it prone to crack formation under extreme loads and environmental factors, which is a leading cause of pipeline failure. This state-of-the-art study aims to demonstrate the potential of UT for detecting cracks in non-welded regions of natural gas PE pipes. Laboratory experiments were conducted using a UT system consisting of low-cost piezoceramic transducers assembled in a pitch-catch configuration. The amplitude of the transmitted wave was analyzed to study wave interaction with cracks of different geometries. The frequency of the inspecting signal was optimized through wave dispersion and attenuation analysis, guiding the selection of third- and fourth- order longitudinal modes for the study. The findings revealed that cracks with lengths equal to or greater than the wavelength of the interacting mode were more easily detectable, while smaller crack lengths required greater crack depths for detection. However, there were potential limitations in the proposed technique related to crack orientation. These insights were validated using a finite element-based numerical model, confirming the potential of UT for detecting cracks in PE pipes.

Stiff Shape Memory Polymers for High-Resolution Reconfigurable Nanophotonics.

Reconfigurable metamaterials require constituent nanostructures to demonstrate switching of shapes with external stimuli. Yet, a longstanding challenge is in overcoming stiction caused by van der Waals forces in the deformed configuration, which impedes shape recovery. Here, we introduce stiff shape memory polymers. This designer material has a storage modulus of ∼5.2 GPa at room temperature and ∼90 MPa in the rubbery state at 150 °C, 1 order of magnitude higher than those in previous reports. Nanopillars with diameters of ∼400 nm and an aspect ratio as high as ∼10 were printed by two-photon lithography. Experimentally, we observe shape recovery as collapsed and touching structures overcome stiction to stand back up. We develop a theoretical model to explain the recoverability of these sub-micrometer structures. Reconfigurable structural color prints with a resolution of 21150 dots per inch and holograms are demonstrated, indicating potential applications of the stiff shape memory polymers in high-resolution reconfigurable nanophotonics.

Impact of separate concentrations of polyethylene microplastics on the ability of pollutants removal during the operation of constructed wetland-microbial fuel cell.

Microplastics (MPs) in water pose a great threat to the ecological environment, but the impact of MPs on constructed wetland microbial fuel cells (CW-MFCs) has not been studied, so in order to fill the research gap and enrich the research in the field of microplastics, a 360-day experiment was designed to determine the operating status of CW-MFCs at different concentrations (0, 10, 100 and 1000 µg/L) polyethylene microplastics (PE-MPs) at different times, focusing on the changes of the CW-MFCs' ability to handle pollutants, power production performance and microbial composition. The results showed that with the accumulation of PE-MPs, the removal effect of COD and TP did not change significantly, and that the removal rate was maintained at around 90% and 77.9% respectively, within 120 d of operation. What's more, the denitrification efficiency increased (from 4.1% to 19.6%), but with the passage of time, it decreased significantly (from 7.16% to 31.9%) at the end of the experiment, while oxygen mass transfer rate was significantly increased. Further analysis showed that the accumulation of PE-MPs did not affect the current power density significantly with the changes of time and concentration, but the accumulation of PE-MPs would inhibit the exogenous electrical biofilm and increase the internal resistance, thereby affecting the electrochemical performance of the system. In addition, the results of microbial PCA showed that the composition and the activity of the microorganisms were changed under the action of PE-MPs, that the microbial community in CW-MFC showed a dose effect on the input of PE-MPs, and that the relative abundance of nitrifying bacteria with time was significantly affected by PE-MPs concentration. The relative abundance of denitrifying bacteria decreased over time, but PE-MPs promoted the reproduction of denitrifying bacteria, which was consistent with the changes in nitrification and denitrification rates. The removal modes of EP-MPs by CW-MFC include the adsorption and the electrochemical degradation, with two isothermal adsorption models of Langmuir and Freundlich being constructed in the experiment, and the electrochemical degradation process of EP-MPs being simulated. In summary, the results show that the accumulation of PE-MPs can induce a series of changes in substrate, microbial species and activity of CW-MFCs, which in turn affects the pollutant removal efficiency and power generation performance during its operation.

Machine Learning-Assisted Pattern Recognition of Amyloid Beta Aggregates with Fluorescent Conjugated Polymers and Graphite Oxide Electrostatic Complexes.

Five fluorescent positively charged poly(para-aryleneethynylene) (P1-P5) were designed to construct electrostatic complexes C1-C5 with negatively charged graphene oxide (GO). The fluorescence of conjugated polymers was quenched by the quencher GO. Three electrostatic complexes were enough to distinguish between 12 proteins with 100% accuracy. Furthermore, using these sensor arrays, we could identify the levels of Aß40 and Aß42 aggregates (monomers, oligomers, and fibrils) via employing machine learning algorithms, making it an attractive strategy for early diagnosis of Alzheimer's disease.

Structural insight and engineering of a plastic degrading hydrolase Ple629.

Polyethylene terephthalate (PET) is one of the most abundantly produced synthetic polyesters. The vast number of waste plastics including PET has challenged the waste management sector while also posing a serious threat to the environment due to improper littering. Recently, enzymatic PET degradation has been shown to be a viable option for a circular plastic economy, which can mitigate the plastic pollution. While protein engineering studies on specific PET degradation enzymes such as leaf-branch compost cutinase (LCC), Thermobifida sp. cutinases and Ideonella sakaiensis PETase (IsPETase) have been extensively published, other homologous PET degrading enzymes have received less attention. Ple629 is a polyester hydrolase identified from marine microbial consortium having activity on PET and the bioplastic polybutylene adipate terephthalate (PBAT). In order to explore its catalytic mechanism and improve its potential for PET hydrolysis, we solved its crystal structure in complex with a PET monomer analogue, and validated its structural and mechanistic similarity to known PET hydrolases. By structural comparisons, we identified some hot spot positions described in previous research on protein engineering of PET hydrolases. We substitute these amino acid residues in Ple629, and obtained variants with improved activity and thermo-stability. The most promising variant D226A/S279A exhibited a more than 5.5-fold improved activity on PET nanoparticles than the wild-type enzyme, suggesting its potential applicability in the biotechnological plastic recycling.

Hybrid Nanofibrous Composites with Anisotropic Mechanics and Architecture for Tendon/Ligament Repair and Regeneration.

Rupture of tendons and ligaments (T/L) is a major clinical challenge due to T/L possess anisotropic mechanical properties and hierarchical structures. Here, to imitate these characteristics, an approach is presented by fabricating hybrid nanofibrous composites. First, hybrid fiber-reinforced yarns are fabricated via successively electrospinning poly(L-lactide-co-ε-caprolactone) (PLCL) and gelatin (Ge) nanofibers onto polyethylene terephthalate (PET) fibers to improve biodurability and biocompatibility. Then, by comparing different manufacturing methods, the knitted structure succeeds in simulating anisotropic mechanical properties, even being stronger than natural ligaments, and possessing comfort compliance superior to clinically used ligament advanced reinforcement system (LARS) ligament. Moreover, after inoculation with tendon-derived stem cells and transplantation in vivo, hybrid nanofibrous composites are integrated with native tendons to guide surrounding tissue ingrowth due to the highly interconnected and porous structure. The knitted hybrid nanofibrous composites are also ligamentized and remodeled in vivo to promote tendon regeneration. Specifically, after the use of optimized anisotropic hybrid nanofibrous composites to repair tendon, the deposition of tendon-associated extracellular matrix proteins is more significant. Thus, this study indicates a strategy of manufacturing anisotropic hybrid nanofibrous composites with superior mechanical properties and good histocompatibility for clinical reconstruction.

Heat-Stimuli Shape Memory Effect of Poly (ε-Caprolactone)-Cellulose Acetate Composite Tubular Scaffolds.

Small-diameter artery disease is the most common clinical occurrence, necessitating the development of small-diameter artificial blood vessels. In this study, seven types of poly(-caprolactone)-cellulose acetate (PCL-CA) composite nanofiber membranes were prepared with different proportions of PCL and CA. The adhesion and growth of Mc3t3-e1 cells were considered to confirm the in vitro cytocompatibility of PCL-CA membranes. A smooth stainless-steel mandrel with a diameter of 4 mm was used to roll up the prepared nanofiber membranes to produce the tubular scaffold with 50 °C hot water. The tubular scaffolds were subjected to axial and circumferential tensile tests. The mechanical performance of the PCL-CA tubular scaffold could be improved by increasing the layers. In addition, the burst pressure (BP) of the tubular scaffolds was increased with the layers, and the BPs of six-layer (2380 ± 36.8 mmHg) and eight-layer (3720 ± 80.5 mmHg) tubular scaffolds were much higher than that of the human saphenous vein (2000 mmHg). The compression shape memory performances of the PCL-CA tubular scaffold with different layers were also investigated to simulate and analyze the contraction and expansion of tubular scaffolds. The experimental results showed that the compression strain of the tubular scaffold in the diameter direction reached 35%, and the ultimate shape recovery rate reached 87%. However, the shape fixity rate and shape recovery rate increased, demonstrating that the optimum number of layers can improve the compression shape memory performance of the tubular scaffold. The results of this study, including comprehensive morphological and mechanical properties and cytocompatibility, indicated the potential applicability of PCL-CA tubular scaffolds as tissue engineering grafts.

Successful percutaneous left atrial appendage occlusion for atrial fibrillation in a patient with mirror-image dextrocardia: a case report.

BACKGROUND: Dextrocardia is a rare congenital condition (1/10,000-12,000) and AF is uncommon (1-2%). Therefore, the occurrence of the two conditions is rare. Percutaneous left atrial appendage occlusion (LAAO) is a treatment to prevent atrial fibrillation (AF)-associated thromboembolic events. CASE PRESENTATION: An 85-year-old female with known situs inversus totalis, persistent AF, and stroke was treated with oral anticoagulation, but she was suffering from constant gingival bleeding. Her CHA2DS2VASc score was 6 points (abnormal, ≥ 2), and her HAS-BLED score was 4 points (abnormal, ≥ 3). The transthoracic echocardiography (TTE) demonstrated left atrial (LA) enlargement (46 mm) and 50% of ejection fraction. She underwent percutaneous LAAO for stroke recurrence prevention using a Watchman occluder. The operation was successful but with technical differences compared with a standard case because of the dextrocardia. CONCLUSION: This is the first reported case of a percutaneous LAAO in situs inversus dextrocardia. This case indicates the feasibility of LAAO in congenital cardiac malposition combined with AF.