Assessment and phenotypic identification of millet germplasm (Setaria italica L.) in Liaoning, China.

Aims: This study evaluated millet germplasms in Liaoning Province to support the collection, preservation and innovation of millet germplasm resources. Methods: The study was conducted from 2018 to 2020, involved the selection of 105 millet germplasm resources from the Germplasm Bank of the Liaoning Academy of Agricultural Sciences (LAAS), the observation and recording of 31 traits, and the application of multivariate analysis methods to assess phenotypic diversity. Results: From the diversity analysis and correlation analysis, it was found that the tested traits had abundant diversity and complex correlations among them. Principal component analysis (PCA) comprehensively analyzed all quantitative traits and extracted seven principal components. Grey relational analysis (GRA) highlighted the varied contributions of different traits to yield. Through systematic cluster analysis (SCA), the resources were categorized into six groups at Euclidean distance of 17.09. K-mean cluster analysis determined the distribution interval and central value of each trait, then identified resources with desirable traits. Conclusion: The results revealed resources that possess characteristics such as upthrow seedling leaves, more tillers and branches, larger and well-formed ears, and lodging resistance prefer to higher grain yield. It was also discovered that the subear internode length (SIL) could be an indicator for maturity selection. Four specific resources, namely, Dungu No. 1, Xiao-li-xiang, Basen Shengu, and Yuhuanggu No. 1, were identified for further breeding and practical applications.

ß-Cyclodextrin enhanced bioavailability of petroleum hydrocarbons in industrially contaminated soil: A phytoremediation field study.

Low remediation efficiency due to low bioavailability is a primary restrictive factor for phytoremediation applications. Specifically, this investigation examines whether Suaeda heteroptera Kitagawa (S. heteroptera) can be used in combination with ß-cyclodextrin (ß-CD) to remediate contaminated site. The study was conducted on the growth response of S. heteroptera, bioavailability and dissipation of petroleum hydrocarbons (PHs) in soil under the influence of ß-CD Our preliminary studies confirmed that ß-CD is effective in increasing the biomass and height of plants. The presence of ß-CD could dramatically elevate polycyclic aromatic hydrocarbons (PAHs) and n-alkanes in S. heteroptera. Moreover, a remarkable positive correlation between PHs levels in roots with the dosage of ß-CD and a negative correlation between the PHs levels in roots with KOW of PHs have been observed. The dissipation of n-alkanes was estimated to be 38.73-62.27%, and the dissipation of PAHs was 36.59-60.10%. In addition, the dissipation behavior of n-alkanes and PAHs was well agreement with the first-order kinetic model. These results display that applying ß-CD accelerated the desorption process of PHs from soil and promoted the absorption process of PHs onto the root epidermis. The enhancement of phytoremediation was achieved by increasing the bioavailability of PHs.

There has been an increasing concern regarding soil contamination by petroleum hydrocarbons (PHs) released by industrial activities. The study attempted to investigate how ß-CD affects the phytoremediation of PHs-contaminated sites. The findings of this study offer an environmentally friendly and cost-effective method of phytoremediating industrially contaminated sites using ß-CD enhanced-phytoremediation.

Effect of Implanted Capsular Tension Ring on Postoperative Refractive Shift: A Systematic Review and Meta-Analysis.

BACKGROUND: The capsular tension ring is a novel assistant tool for cataract surgery; however, controversy exists in its co-implantation. The potential for hyperopic or myopic shift resulting from the co-implantation of the capsular tension ring and intraocular lens remains unclear. This study aimed to determine the postoperative refractive prediction error and the direction of refractive shift in cataract patients who underwent capsular tension ring co-implantation. METHODS: We conducted a systematic review and meta-analysis,searching electronic databases for studies of individuals diagnosed with cataracts receiving surgery with or without capsular tension ring implantation. Systematic searches were performed based on five databases: PubMed, Cochrane Library, Web of Science, Medline, and China National Knowledge Infrastructure. The primary outcome was the mean arithmetic refractive prediction error. Secondary outcomes were mean absolute refractive prediction error and the number of eyes within a certain refractive prediction error range. We applied a fixed-effectsmodel to pool effect sizes across trials using weighted mean differences (WMD) and risk ratios (RR) with their 95% confidence intervals (95% CI). Statistical heterogeneity scores were assessed with the I2statistic. RESULTS: A total of 407 affected eyes were included in eight independent clinical studies. Meta-analysis suggested significant differences both in short-term (≤1 month) co-implantation (WMD = 0.16, p < .001, 95% CI: -0.13 ~ 0.19) and long-term (≥3 months) co-implantation between the capsular tension ring co-implantation group and the control group (WMD = 0.19, p < .001, 95% CI: 0.15 ~ 0.23). However, no significant difference was observed in the high myopia subgroup whether capsular tension ring co-implantation (WMD = 0.03, p = .083, 95% CI: -0.27 ~ 0.34). Heterogeneity was not found among the studies. CONCLUSION: Compared to simple intraocular lens implantation, capsular tension ring co-implantation is more susceptible to developing hyperopic shifts in non-myopic cataract patients, probably related to anterior chamber depth. It requires careful consideration by clinicians when determining the target diopter preoperatively. However, interpretation is limited, because there is a lack of studies available for analysis. There still needs to be additional studies to expand the evidence base.

Advancing Energy Sustainability Through Solar-to-Fuel Technologies: From Materials to Devices and Systems.

To achieve carbon neutrality and sustainable development, innovative solar-to-fuel systems have been designed through the integration of solar energy harvesting and electrochemical devices. Over the last decade, there have been notable advancements in enhancing the efficiency and durability of these solar-to-fuel systems. Despite the advancements, there remains significant potential for further improvements in the performance of systems. Enhancements can be achieved by optimizing electrochemical catalysts, advancing the manufacturing technologies of photovoltaics and electrochemical cells, and refining the overall design of these systems. In the realm of catalyst optimization, the effectiveness of materials can be significantly improved through active site engineering and strategic use of functional groups. Similarly, the performance of electrochemical devices can be enhanced by incorporating specific additives into electrolytes and optimizing gas diffusion electrodes. Improvements in solar harvesting devices are achievable through efficient passivant and self-assembled monolayers, which enhance the overall quality and efficiency of these systems. Additionally, optimizing the energy conversion efficiency involves the strategic use of DC converters, photoelectrodes, and redox media. This review aims to provide a comprehensive overview of the advancements in solar-powered electrochemical energy conversion systems, laying a solid foundation for future research and development in the field of energy sustainability.

Effects of transcranial direct current stimulation on different cognitive domains in Alzheimer's disease: a meta-study.

BACKGROUND: Numerous studies have investigated the potential effects of transcranial direct current stimulation (tDCS) on improving symptoms related to Alzheimer's disease (AD). However, these studies have produced inconsistent results, leading to a need for further investigation. METHODS: A comprehensive search was conducted, including articles published from the initial availability date to 5 April 2024. The extracted study data were analyzed using STATA 12.0 software. The standard mean difference (SMD) and a 95% confidence interval (CI) were calculated to assess the effects of tDCS. RESULTS: A total of 18 studies assessing the effects of tDCS on AD were included in the study. The study revealed that tDCS has an immediate positive impact on general cognitive, executive, language, and visuospatial function. However, the study did not observe any other significant effect of tDCS treatment on improvements in brain function, including long-term effects on general cognitive, attention, language, and memory function, as well as immediate effects on attention and memory function. CONCLUSIONS: In conclusion, the study suggests that tDCS may be a promising intervention for improving the cognitive function of patients with AD. However, given the complex and multifactorial nature of AD, further well-designed studies with larger sample sizes are necessary to clarify the effectiveness of tDCS and determine the optimal combination of tDCS parameters.

Aged polystyrene microplastics exposure affects apoptosis via inducing mitochondrial dysfunction and oxidative stress in early life of zebrafish.

In recent years, the toxic effects of microplastics (MPs) on aquatic organisms have been increasingly recognized. However, the developmental toxicity and underlying mechanisms of photoaged MPs at environmental concentrations remain unclear. Therefore, the photodegradation of pristine polystyrene (P-PS) under UV irradiation was used to investigate, as well as the developmental toxicity and underlying mechanisms of zebrafish (Danio rerio) exposed to P-PS and aged polystyrene (A-PS) at environmentally relevant concentrations (0.1-100 µg/L). Mortality, heart rate, body length, and tail coiling frequency of zebrafish larvae were the developmental toxicity endpoints. A-PS had increased crystallinity, the introduction of new functional groups, and higher oxygen content after UV-photoaging. The toxicity results showed that exposure to A-PS resulted in more adverse developmental toxicity than exposure to P-PS. Exposure to A-PS induced oxidative damage, as evidenced by elevated production of reactive oxygen species (ROS) and DNA damage, and led to decreased mitochondrial membrane potential (MMP) and causes the release of cytochrome c (cyt c) from the mitochondria. The caspase-3/-9 activation signaling pathways may cause developmental toxicity via mitochondrial apoptosis. Significant changes in the expression of genes were further explored linking with oxidative stress, mitochondria dysfunctions and apoptosis pathways following A-PS exposure. These findings underscore the importance of addressing the environmental applications of aged MPs and call for further research to mitigate their potential risks on aquatic ecosystems and human health.

Emergent normal fluid in the superconducting ground state of overdoped cuprates.

The microscopic mechanism for the disappearance of superconductivity in overdoped cuprates is still under heated debate. Here we use scanning tunneling spectroscopy to investigate the evolution of quasiparticle interference phenomenon in Bi2Sr2CuO6+δ over a wide range of hole densities. We find that when the system enters the overdoped regime, a peculiar quasiparticle interference wavevector with arc-like pattern starts to emerge even at zero bias, and its intensity grows with increasing doping level. Its energy dispersion is incompatible with the octet model for d-wave superconductivity, but is highly consistent with the scattering interference of gapless normal carriers. The gapless quasiparticles are mainly located near the antinodes and are independent of temperature, consistent with the disorder scattering mechanism. We propose that a branch of normal fluid emerges from the pair-breaking scattering between flat antinodal bands in the quantum ground state, which is the primary cause for the reduction of superfluid density and suppression of superconductivity in overdoped cuprates.

Structural, physicochemical, and digestive properties of enzymatic debranched rice starch modified by phenolic compounds with varying structures.

The physicochemical properties of starch and phenolic acid (PA) complexes largely depend on the effect of non-covalent interactions on the microstructure of starch. However, whether there are differences and commonalities in the interactions between various types of PAs and starch remains unclear. The physicochemical properties and digestive characteristics of the complexes were investigated by pre-gelatinization of 16 structurally different PAs and pullulanase-modified rice starches screened. FT-IR and XRD results revealed that PA complexed with debranched rice starch (DRS) through hydrogen bonding and hydrophobic interaction. Benzoic/phenylacetic acid with polyhydroxy groups could enter the helical cavities of the starch chains to promote the formation of V-shaped crystals, and cinnamic acid with p-hydroxyl structure acted between starch chains in a bridging manner, both of which increased the relative crystallinity of DRS, with DRS-ellagic acid increasing to 20.03 %. The digestion and hydrolysis results indicated that the acidification and methoxylation of PA synergistically decreased the enzyme activity leading to a decrease in the digestibility of the complexes, and the resistant starch content of the DRS-vanillic acid complexes increased from 28.27 % to 71.67 %. Therefore, the selection of structurally appropriate PAs can be used for the targeted preparation of starch-based foods and materials.

Effects of Transport Duration and Pre-Transport Fasting on Blood Biochemistry in Dorper × Mongolian Sheep.

Transport is a high-risk time for sheep, especially if the distances are long and sheep are fasted for a long time beforehand. Two experiments were conducted to compare transport durations of 1 hour (1 h) and 3 hours (3 h) and the effects of feeding before transport using Dorper × Mongolian sheep, which are typical of the region and may be tolerant of the high temperatures in the Inner Mongolian summer. Thirty 4-month-old male sheep were randomly divided into two treatment groups, with 15 sheep/treatment in each experiment, to evaluate the effects on blood biochemical indicators, stress hormone levels, rectal temperatures, and antioxidant status of lambs in summer. In Experiment 1, the levels of triglycerides and free fatty acids after 3 h transport were significantly lower than after 1 h transport (p < 0.05). The levels of thyroxine and malondialdehyde in blood were greater after 3 h transport than 1 h transport (p < 0.05). Creatine kinase levels after 3 h transport tended to be lower than after 1 h transport (p = 0.051). In Experiment 2, the levels of urea and superoxide dismutase in the group fasted pre-transport was significantly lower than those of the group fed pre-transport (p < 0.05). The serum cortisol level in the pre-transport fed group was higher compared to the group fed pre-transport (p = 0.04). Total antioxidant capacity in the pre-transport fasted group tended to be lower compared to that in the pre-transport fed group (p < 0.0001). We conclude that the reduction in nutritional status of sheep transported for longer and without feed pre-transport suggests that transporting sheep in hot conditions in northern China after fasting for a long period should be restricted. However, a decrease in the stress induced by transport following fasting is worthy of further study.

Tumor-derived extracellular vesicles as a biomarker for breast cancer diagnosis and metastasis monitoring.

It is imperative to explore biomarkers that are both precise and readily accessible in the comprehensive management of breast cancer. A multicenter cohort, including 512 breast cancer patients and 198 nonneoplastic individuals, was recruited to detect the level of tumor-derived extracellular vesicles using our method based on dual DNA tetrahedral nanostructures. The level of tumor-derived extracellular vesicles was significantly higher in newly diagnosed breast cancer patients than in nonneoplastic individuals at a cutoff value of 3.58 U/µL. For postoperative metastasis monitoring, the level of tumor-derived extracellular vesicles was significantly higher in breast cancer patients with metastasis than in those without metastasis at a cutoff value of 3.91 U/µL. Its efficacy of diagnosis and metastasis monitoring was superior to traditional tumor markers. Elevated level of tumor-derived extracellular vesicles served as a predictive biomarker for diagnosis and metastasis monitoring in breast cancer patients.

Development of pharmacological immunoregulatory anti-cancer therapeutics: current mechanistic studies and clinical opportunities.

Immunotherapy represented by anti-PD-(L)1 and anti-CTLA-4 inhibitors has revolutionized cancer treatment, but challenges related to resistance and toxicity still remain. Due to the advancement of immuno-oncology, an increasing number of novel immunoregulatory targets and mechanisms are being revealed, with relevant therapies promising to improve clinical immunotherapy in the foreseeable future. Therefore, comprehending the larger picture is important. In this review, we analyze and summarize the current landscape of preclinical and translational mechanistic research, drug development, and clinical trials that brought about next-generation pharmacological immunoregulatory anti-cancer agents and drug candidates beyond classical immune checkpoint inhibitors. Along with further clarification of cancer immunobiology and advances in antibody engineering, agents targeting additional inhibitory immune checkpoints, including LAG-3, TIM-3, TIGIT, CD47, and B7 family members are becoming an important part of cancer immunotherapy research and discovery, as are structurally and functionally optimized novel anti-PD-(L)1 and anti-CTLA-4 agents and agonists of co-stimulatory molecules of T cells. Exemplified by bispecific T cell engagers, newly emerging bi-specific and multi-specific antibodies targeting immunoregulatory molecules can provide considerable clinical benefits. Next-generation agents also include immune epigenetic drugs and cytokine-based therapeutics. Cell therapies, cancer vaccines, and oncolytic viruses are not covered in this review. This comprehensive review might aid in further development and the fastest possible clinical adoption of effective immuno-oncology modalities for the benefit of patients.

Uptake, biotransformation and physiological response of TBBPA derivatives in Helianthus annus.

Tetrabromobisphenol A (TBBPA) and its derivatives are widely used as brominated flame retardants. Because of their high production and wide environment distribution, TBBPA derivatives have increased considerable concern. Previous studies have primarily focused on TBBPA, with limited information available on its derivative. In this study, we investigated the uptake, biotransformation and physiological response of two derivatives, Tetrabromobisphenol A bis(allyl ether) (TBBPA BAE) and Tetrabromobisphenol A bis(2,3-dibromopropylether) (TBBPA BDBPE), in Helianthus annus (H. annus) through a short-term hydroponic assay. The results revealed that H. annus could absorb TBBPA BAE and TBBPA BDBPE from solution, with removal efficiencies of 98.33 ± 0.5% and 98.49 ± 1.56% after 10 days, respectively, which followed first-order kinetics. TBBPA BAE was absorbed, translocated and accumulated while TBBPA BDBPE couldn't be translocated upward due to its high hydrophobicity and low solubility. The concentrations of TBBPA derivatives in plants peaked within 72 h, and then decreased. We identified twelve metabolites resulting from ether bond breakage, debromination, and hydroxylation in H. annus. The high-level TBBPA BAE suppressed the growth and increased malondialdehyde (MDA) content of H. annus, while TBBPA BDBPE didn't pose a negative effect on H. annus. TBBPA BAE and TBBPA BDBPE increased the activity of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), with higher levels of these enzymes activity found in high concentration treatments. Contrastingly, TBBPA BAE exhibited higher toxicity than TBBPA BDBPE, as indicated by greater antioxidant enzyme activity. The findings of this study develop better understanding of biotransformation mechanisms of TBBPA derivatives in plants, contributing to the assessment of the environmental and human health impacts of these contaminants.

Molecular design, construction and analgesic mechanism insights into the novel transdermal fusion peptide ANTP-BgNPB.

Toad venom, a traditional Chinese medicine, exhibits remarkable medicinal properties of significant therapeutic value. The peptides present within toad venom possess a wide range of biological functions, yet the neuropeptide B (NPB) and it modification requires further exploration to comprehensively understand its mechanisms of action and potential applications. In this study, a fusion peptide, ANTP-BgNPB, was designed to possess better analgesic properties through the transdermal modification of BgNPB. After optimizing the conditions, the expression of ANTP-BgNPB was successfully induced. The molecular dynamics simulations suggested that the modified protein exhibited improved stability and receptor binding affinity compared to its unmodified form. The analysis of the active site of ANTP-BgNPB and the verification of mutants revealed that GLN3, SER38, and ARG42 were crucial for the protein's recognition and binding with G protein-coupled receptor 7 (GPR7). Moreover, experiments conducted on mice using the hot plate and acetic acid twist body models demonstrated that ANTP-BgNPB was effective in transdermal analgesia. These findings represent significant progress in the development of transdermal delivery medications and could have a significant impact on pain management.

Highly efficient Mn2+, Mg2+, and NH4+ recovery from electrolytic manganese residue via leaching, solvent extraction, coprecipitation, and atmospheric oxidation.

Electrolytic manganese residue (EMR), a solid waste generated during electrolytic manganese production, exhibits substantial leaching toxicity owing to its elevated levels of soluble Mn2+ and NH4+. The leaching and recovery of valuable metal ions and NH4+ from EMR are key to the hazard-free treatment and resource utilization of EMR. In this study, two-stage countercurrent leaching with water was used to leach Mn2+, Mg2+, and NH4+ from EMR. Subsequently, two-stage countercurrent extraction was conducted using α-hydroxy-2-ethylhexyl phosphinic acid (α-H-2-EHA) as an extractant to enrich Mn2+, and Mg2+, and NH4+ were recovered via coprecipitation. Based on the calculations for a single leaching-extraction process, the recoveries of Mn2+, Mg2+, and NH4+ ions exceeded 80%, 99%, and 90%, respectively. In addition, high-purity Mn3O4 with an Mn content of 71.61% and struvite were produced. This process represents a win-win strategy that facilitates the hazard-free treatment of EMR while simultaneously recovering valuable Mn2+, Mg2+, and NH4+ resources from waste. Thus, this study provides a novel approach to the hazard-free and resourceful management of solid waste. ENVIRONMENTAL IMPLICATION: Electrolytic manganese residue (EMR), a solid waste generated during electrolytic manganese production, poses significant environmental risks due to its soluble heavy metals and ammonia nitrogen content. Efforts have been made to address this issue, but there has been no mature industrial application due to cost or processing capacity constraints. In this work, solvent extraction was first used to enrich Mn2+ from EMR leachate, and a novel α­hydroxy­2­ethylhexyl phosphinic acid was used as extractant. High purity Mn3O4 and struvite was synthesized through this process. The win­win strategy offers a novel approach for the hazard­free and resourceful utilization of solid waste.

Phenotypic and genomic insights into mutant with high nattokinase-producing activity induced by carbon ion beam irradiation of Bacillus subtilis.

Nattokinase (NK) is found in fermented foods and has high fibrinolytic activity, which makes it promising for biological applications. In this study, a mutant strain (Bacillus subtilis ZT-S1, 5529.56 ± 183.59 U/mL) with high NK-producing activity was obtained using 12C6+ heavy ion beam mutagenesis for the first time. The surface morphology of B. subtilis is also altered by changes in functional groups caused by heavy ion beams. Furthermore, B. subtilis ZT-S1 required more carbon and nitrogen sources and reached stabilization phase later. Comparative genome analysis revealed that most of the mutant implicated genes (oppA, appA, kinA, spoIIP) were related to spore formation. And the affected rpoA is related to the synthesis of the NK-coding gene aprE. In addition, the B. subtilis ZT-S1 obtained by mutagenesis had good genetic stability. This study further explores the factors affecting NK activity and provides a promising microbial resource for NK production in commercial applications.

Advancing Slim-Hole Drilling Accuracy: A C-I-WOA-CNN Approach for Temperature-Compensated Pressure Measurements.

This paper presents a novel method to improve drill pressure measurement accuracy in slim-hole drilling within the petroleum industry, a sector often plagued by extreme conditions that compromise data integrity. We introduce a temperature compensation model based on a Chaotic-Initiated Adaptive Whale Optimization Algorithm (C-I-WOA) for optimizing Convolutional Neural Networks (CNNs), dubbed the C-I-WOA-CNN model. This approach enhances the Whale Optimization Algorithm (WOA) initialization through chaotic mapping, boosts the population diversity, and features an adaptive weight recalibration mechanism for an improved global search and local optimization. Our results reveal that the C-I-WOA-CNN model significantly outperforms traditional CNNs in its convergence speed, global searching, and local exploitation capabilities, reducing the average absolute percentage error in pressure parameter predictions from 1.9089% to 0.86504%, thereby providing a dependable solution for correcting temperature-induced measurement errors in downhole settings.

The dissipation of organophosphate esters mediated by ryegrass root exudate oxalic acid in soil: Analysis of enzymes activities, microorganism.

Complex rhizoremediation is the main mechanism of phytoremediation in organic-contaminated soil. Low molecular weight organic acids (LMWOAs) in root exudates have been shown to increase the bioavailability of contaminants and are essential for promoting the dissipation of contaminants. The effects of root exudates on the dissipation of organophosphate esters (OPEs) in soil are unclear. Consequently, we studied the combined effects of root exudates, soil enzymes and microorganisms on OPEs (tri (1-chloro-2-propyl) phosphate (TCPP) and triphenyl phosphate (TPP)) dissipation through pot experiments. Oxalic acid (OA) was confirmed to be the main component of LMWOAs in root exudates of ryegrass. The existence of OA increased the dissipation rate of OPEs by 6.04%-25.50%. Catalase and dehydrogenase activities were firstly activated and then inhibited in soil. While, urease activity was activated and alkaline phosphatase activity was inhibited during the exposure period. More bacteria enrichment (e.g., Sphingomonas, Pseudomonas, Flavisolibacter, Pontibacter, Methylophilus and Massilia) improved the biodegradation of OPEs. In addition, the transformation paths of OPEs hydrolysis and methylation under the action of root exudates were observed. This study provided theoretical insights into reducing the pollution risk of OPEs in the soil.

Silk fibroin and hydroxypropyl cellulose composite injectable hydrogel-containing extracellular vesicles for myocardial infarction repair.

Extracellular vesicles (EVs) have been recognized as one of the promising specific drugs for myocardial infarction (MI) prognosis. Nevertheless, low intramyocardial retention of EVs remains a major impediment to their clinical application. In this study, we developed a silk fibroin/hydroxypropyl cellulose (SF/HPC) composite hydrogel combined with AC16 cell-derived EVs targeted modification by folic acid for the treatment of acute myocardial infarction repair. EVs were functionalized by distearoylphosphatidyl ethanolamine-polyethylene glycol (DSPE-PEG-FA) via noncovalent interaction for targeting and accelerating myocardial infarction repair.In vitro, cytocompatibility analyses revealed that the as-prepared hydrogels had excellent cell viability by MTT assay and the functionalized EVs had higher cell migration by scratch assay.In vivo, the composite hydrogels can promote myocardial tissue repair effects by delaying the process of myocardial fibrosis and promoting angiogenesis of infarct area in MI rat model.

Release of exosomes from injectable silk fibroin and alginate composite hydrogel for treatment of myocardial infarction.

Myocardial infarction (MI) is considered as a significant cause of death globally. Exosomes (EXOs) are essential for intercellular communication and pathophysiology of several cardiovascular diseases. Nevertheless, the short half-life and rapid clearance of EXOs leads to a lack of therapeutic doses delivered to the lesioned area. Therefore, an injectable silk fibroin and alginate (SF/Alg) composite hydrogel was developed to bind folate receptor-targeted EXOs (FA-EXOs) derived from H9C2 cells for the therapy of myocardial injury following myocardial infarction-ischemia/reperfusion (MI-I/R). The resulting composite exhibits a variety of properties, including adjustable gelation kinetics, shear-thinning injectability, soft and dynamic stability that adapts to the heartbeat, and outstanding cytocompatibility. After injected into the damaged rat heart, administration of SF/Alg + FA-EXOs significantly enhanced cardiac function as demonstrated by improved ejection fraction, fractional shortening and decreased fibrosis area. The results of real-time PCR and immunofluorescence staining show a remarkable up-regulation in the expression of proteins (CD31) and genes (VWF and Serca2a) related to the heart. Conversely, expression of fibrosis-related genes (TGF-ß1) decreased significantly. Therefore, the obtained SF/Alg + FA-EXOs system remarkably enhanced the intercellular interactions, promoted cell proliferation and angiogenesis, and achieved an outstanding therapeutic effect on MI.

The role of COVID-19 vaccines in preventing post-COVID-19 thromboembolic and cardiovascular complications.

OBJECTIVE: To study the association between COVID-19 vaccination and the risk of post-COVID-19 cardiac and thromboembolic complications. METHODS: We conducted a staggered cohort study based on national vaccination campaigns using electronic health records from the UK, Spain and Estonia. Vaccine rollout was grouped into four stages with predefined enrolment periods. Each stage included all individuals eligible for vaccination, with no previous SARS-CoV-2 infection or COVID-19 vaccine at the start date. Vaccination status was used as a time-varying exposure. Outcomes included heart failure (HF), venous thromboembolism (VTE) and arterial thrombosis/thromboembolism (ATE) recorded in four time windows after SARS-CoV-2 infection: 0-30, 31-90, 91-180 and 181-365 days. Propensity score overlap weighting and empirical calibration were used to minimise observed and unobserved confounding, respectively.Fine-Gray models estimated subdistribution hazard ratios (sHR). Random effect meta-analyses were conducted across staggered cohorts and databases. RESULTS: The study included 10.17 million vaccinated and 10.39 million unvaccinated people. Vaccination was associated with reduced risks of acute (30-day) and post-acute COVID-19 VTE, ATE and HF: for example, meta-analytic sHR of 0.22 (95% CI 0.17 to 0.29), 0.53 (0.44 to 0.63) and 0.45 (0.38 to 0.53), respectively, for 0-30 days after SARS-CoV-2 infection, while in the 91-180 days sHR were 0.53 (0.40 to 0.70), 0.72 (0.58 to 0.88) and 0.61 (0.51 to 0.73), respectively. CONCLUSIONS: COVID-19 vaccination reduced the risk of post-COVID-19 cardiac and thromboembolic outcomes. These effects were more pronounced for acute COVID-19 outcomes, consistent with known reductions in disease severity following breakthrough versus unvaccinated SARS-CoV-2 infection.