A Reactive Oxygen Species Scavenging and O2 Generating Injectable Hydrogel for Myocardial Infarction Treatment In vivo.

The excessive reactive oxygen species (ROS) and hypoxia deteriorate the inflammation-related diseases such as myocardial infarction (MI), and thereby deter the normal tissue repair and recovery and further lead to severe fibrosis and malfunction of tissues and organs. In particular, the MI has become one of the leading causes of death nowadays. In this study, a novel type of injectable hydrogel with dual functions of ROS scavenging and O2 generating is fabricated for MI treatment in vivo. The hydrogel is formed within 3 s from the synthetic ROS-cleavable hyperbranched polymers and methacrylate hyaluronic acid (HA-MA) under UV-irradiation. Addition of biocompatible and applicable catalase in vivo enables the further transition of H2 O2 , a major type of ROS, to O2 and H2 O. Results of rat MI model demonstrate that this hydrogel can significantly remove excessive ROS, inhibit cell apoptosis, increase M2/M1 macrophage ratio, promote angiogenesis, reduce infarcted area, and improve cardiac functions. With the appropriate degradation rate, simple structure and composition without cell seeding, and very excellent MI therapeutic effect, this ROS scavenging and O2 generating hydrogel has a great promise to be applied clinically.

A study of best practices in promoting sustainable urbanization in China.

In the past twenty years, various sustainable urban development policies and methods had been implemented within China, such that sustainable urbanization is now more widely accepted. Some of these policies and methods have been found to be successful in improving the sustainability of cities in China. Those practices can be defined as the best practices of sustainable urbanization, which can provide useful references for future urban developments. However, few existing studies examine how to learn from these best practices. Combining the methods of content analysis and social network analysis, this paper conducts a comprehensive study on 150 best practices of sustainable urbanization in China. The methods and outcomes of the 150 best practices are identified. The research findings demonstrate the statistics of categories, methods and outcomes of the 150 best practices and the main adopted methods. The achieved outcomes in different regions of China are also presented.

The feasibility of concentrated rural settlement in a context of post-disaster reconstruction: a study of China.

There is growing appreciation of the use of concentrated rural settlement as an effective means of implementing infrastructure projects and helping to achieve sustainable development in rural areas. This occurs in China through the exchange of rural residential land for urban construction. However, this policy has not been effective under normal circumstances (called development-driven conditions) as frequently farmers are reluctant to accept such an exchange. By contrast, in a time of disaster, such as after the 2008 earthquake in Sichuan Province, China, rural victims have accepted this policy of rural residential land exchange. Employing game theory, this paper identifies the reasons for the different outcomes and it contends that the implementation of concentrated rural settlement practice under disaster-induced conditions is more effective than its introduction under development-driven conditions. The results of the analysis indicate that, in China, concentrated rural settlement is feasible in a context of post-disaster reconstruction.

A Sequential Dual Functional Supramolecular Hydrogel with Promoted Drug Release to Scavenge ROS and Stabilize HIF-1α for Myocardial Infarction Treatment.

Myocardial infarction (MI) has a characteristic inflammatory microenvironment due to the overproduction of reactive oxygen species (ROS) and causes the extraordinary deposition of collagen and thereby fibrosis. An on-demand adaptive drug releasing hydrogel is designed to modulate the inflammatory microenvironment and inhibit cardiac fibroblasts (CFs) proliferation post MI by scavenging the overproduced ROS and releasing 1,4-dihydrophenonthrolin-4-one-3-carboxylic acid (DPCA) to maintain the expression of hypoxia-inducible factor 1α (HIF-1α). DPCA is prefabricated to a prodrug linked with disulfide bond (DPCA-S-S-OH). The DPCA-S-S-OH and carboxylated calixarene (CSAC4A) are grafted onto the backbone of methacrylated hyaluronic acid (HAMA) to obtain HAMA-S-S-DPCA and HAMA-CA, respectively, which are further reacted to form a dual network hydrogel (R+ /DPCA(CA)) with covalent linking and host-guest interaction between DPCA and CSAC4A. The ROS-triggered hydrolysis of ester bond and subsequently sustaining release of DPCA from the cavity of CSAC4A jointly cause the constant expression of HIF-1α, which significantly restricts the CFs proliferation, leading to suppressed fibrosis and promoted heart repair.

ROS-responsive drug-releasing injectable microgels for ameliorating myocardial infarction.

Despite of the recent advances in regulatory T cell (Treg) therapy, a limited number of available cells and specificity at the desired tissue site have severely compromised their efficacy. Herein, an injectable drug-releasing (MTK-TK-drug) microgel system in response to in situ stimulation by reactive oxygen species (ROS) was constructed with a coaxial capillary microfluidic system and UV curing. The spherical microgels with a size of 150 µm were obtained. The MTK-TK-drug microgels efficiently converted the pro-inflammatory Th17 cells into anti-inflammatory regulatory T cells (Treg) cells in vitro, and the ROS-scavenging materials synergistically enhanced the effect by modulating the inflammation microenvironment. Thus, the microgels significantly reduced cardiomyocyte apoptosis and decreased the inflammatory response in the early stages of post-myocardial infarction (MI) in vivo, thereby reducing fibrosis, promoting vascularization, and preserving cardiac function. Overall, our results indicate that the MTK-TK-drug microgels can attenuate the inflammatory response and improve MI therapeutic effects in vivo.

A systematic analysis and review of soil organic carbon stocks in urban greenspaces.

Urban greenspaces typically refer to urban wetland, urban forest and urban turfgrass. They play a critical role in carbon sequestration by absorbing carbon from the atmosphere; however, their capacity to retain and store carbon in the form of soil organic carbon (SOC) varies significantly. This study provides a systematic analysis and review on the capacity of different urban greenspace types in retaining and storing SOC in 30 cm soil depth on a global scale. Data came from 78 publications on the subject of SOC stocks, covering different countries and climate zones. Overall, urban greenspace types exerted significant influences on the spatial pattern of SOC stocks, with the highest value of 18.86 ± 11.57 kg m-2 (mean ± standard deviation) in urban wetland, followed by urban forest (6.50 ± 3.65 kg m-2), while the lowest mean value of 4.24 ± 3.28 kg m-2 was recorded in urban turfgrass soil. Soil organic carbon stocks in each urban greenspace type were significantly affected by climate zones, management/environmental settings, and selected soil properties (i.e. soil bulk density, pH and clay content). Furthermore, our analysis showed a significantly negative correlation between SOC stocks and human footprint in urban wetland, but a significantly positive relationship in urban forest and urban turfgrass. A positive correlation between SOC stocks and human footprint indicates that increased human activity and development can enhance SOC stocks through effective management and green infrastructure. Conversely, a negative correlation suggests that improper management of human activities can degrade SOC stocks. This highlights the need for sustainable practices to maintain or enhance SOC accumulation in urban greenspaces.

Enhancing miR-19a/b induced cardiomyocyte proliferation in infarcted hearts by alleviating oxidant stress and controlling miR-19 release.

Fully restoring the lost population of cardiomyocytes and heart function remains the greatest challenge in cardiac repair post myocardial infarction. In this study, a pioneered highly ROS-eliminating hydrogel was designed to enhance miR-19a/b induced cardiomyocyte proliferation by lowering the oxidative stress and continuously releasing miR-19a/b in infarcted myocardium in situ. In vivo lineage tracing revealed that ∼20.47 % of adult cardiomyocytes at the injected sites underwent cell division in MI mice. In MI pig the infarcted size was significantly reduced from 40 % to 18 %, and thereby marked improvement of cardiac function and increased muscle mass. Most importantly, our treatment solved the challenge of animal death--all the treated pigs managed to live until their hearts were harvested at day 50. Therefore, our strategy provides clinical conversion advantages and safety for healing damaged hearts and restoring heart function post MI, which will be a powerful tool to battle cardiovascular diseases in patients.

Shape-recovery of implanted shape-memory devices remotely triggered via image-guided ultrasound heating.

Shape-memory materials hold great potential to impart medical devices with functionalities useful during implantation, locomotion, drug delivery, and removal. However, their clinical translation is limited by a lack of non-invasive and precise methods to trigger and control the shape recovery, especially for devices implanted in deep tissues. In this study, the application of image-guided high-intensity focused ultrasound (HIFU) heating is tested. Magnetic resonance-guided HIFU triggered shape-recovery of a device made of polyurethane urea while monitoring its temperature by magnetic resonance thermometry. Deformation of the polyurethane urea in a live canine bladder (5 cm deep) is achieved with 8 seconds of ultrasound-guided HIFU with millimeter resolution energy focus. Tissue sections show no hyperthermic tissue injury. A conceptual application in ureteral stent shape-recovery reduces removal resistance. In conclusion, image-guided HIFU demonstrates deep energy penetration, safety and speed.

Exploring the effect of human capital on carbon emissions: evidences from 125 countries.

Human capital (HC) plays a crucial role in economic growth, and also has a considerable effect on environmental performance, including carbon emissions (CEs). Existing studies have drawn inconsistent conclusions on whether and how HC affects CEs, and most of them conduct case studies of a certain country or several countries with similar economic backgrounds. In order to accurately determine the effect and the influence mechanism of HC on CEs, this research conducted an empirical study by applying econometric method and the panel data of 125 countries over the period 2000-2019. The empirical results indicate that there is an inverted U-shaped nexus between HC and CEs of full sample countries, revealing that HC will increase CEs before turning point and decrease CEs after turning point. From a heterogeneity perspective, this inverted U-shaped nexus only exists in high and upper-middle income countries, while is not supported in low and lower-middle income countries. This study further disclosed that HC can affect CEs by the mediating effects of labor productivity, energy intensity, and industrial structure from a macro perspective. Specifically, HC will increase CEs by promoting labor productivity, while decrease CEs by reducing energy intensity and the proportion of secondary industry. These results can provide important references for governments of different countries to make tailored carbon reduction policies according to the mitigation effect of HC on CEs.

Analysis on the synchronized development between urbanization process and eco-efficiency through the sustainability lens.

Urbanization and eco-efficiency are two interactive systems, contributing to sustainable urban development jointly. However, the synchronized development between them has not received sufficient attention. In light of this gap, this paper conducts an analysis on seeking the synchronized development between sustainable urbanization and eco-efficiency in the context of China. The aim of this study is to uncover the spatial and temporal performance of the synchronized relationship between urbanization process (UP) and eco-efficiency (EE) in a sample of 255 Chinese cities. To this end, entropy method, super efficiency SBM and coupling coordination degree model are employed to conduct the research analysis, covering the period of 2005 to 2019. The findings of this study reveal that (1) there is about 97% of the surveyed cities that exhibit a moderate level of coupling coordination between urbanization process and eco-efficiency (CC-UE). (2) Spatial disparities in the performance of CC-UE are evident, with cities in South and Southeast China demonstrating better CC-UE performance than their counterparts. However, this disparity has been gradually diminishing in recent years. (3) Local perspective presented an evident spatial autocorrelation within the 255 cities analyzed. These research findings provide valuable insights not only for the policy-makers and practitioners to adopt measures for achieving a synchronized development between urbanization process and eco-efficiency in the Chinese context, but also for further studies on sustainable development in the international context.

Influencing factors of falls among older adults in Chinese retirement institutions: A systematic review and meta-analysis.

BACKGROUND: The incidence of falling has always been high among the elderly, and it was easy to cause injuries to the elderly and seriously affect their quality of life. There were many studies have been conducted on risk factors affecting the fall of the elderly, but the results widely, retirement institutions as a gathering place for the elderly, there was currently no comprehensive analysis of the factors related to elderly falls in pension institutions. This study aimed to explore the influencing factors of falls among older adults in Chinese nursing homes. METHODS: Chinese and English databases were searched for literature published from database inception to 5 April 2023 on the influencing factors of falls among older adults in Chinese nursing homes. Two reviewers independently screened articles, extracted data, and assessed the quality of the included studies. Meta-analysis was performed using RevMan 5.4 software. RESULTS: Eleven studies involving 3503 participants were included in the meta-analysis. The pooled estimate of falls among older adults in Chinese nursing homes was 32% [95% confidence interval (95%CI) (24.0%, 39.0%)]. The main influencing factors for falls among older adults in Chinese nursing homes were age (Odds Ratio (OR) = 1.53), gender (OR = 5.50), visual impairment (OR = 2.30), sedative-hypnotics (OR = 2.36), fear of falling (OR = 2.95), hypertension (OR = 3.72), static balance (OR = 2.02), three or more chronic diseases (OR = 5.63), cognitive status (OR = 2.64), walking aid use (OR = 1.98), fall-related chronic diseases (OR = 2.48), self-awareness of abilities (OR = 2.43), and frequent reminders for fall prevention (OR = 0.10). CONCLUSION: Falls among older adults in Chinese nursing homes were common, and there were many influencing factors. Timely screening and intervention should be implemented to reduce the adverse consequences of falls on older adults. TRIAL REGISTRATION: Registration number: CRD42023421099.

Simplified α2-macroglobulin as a TNF-α inhibitor for inflammation alleviation in osteoarthritis and myocardial infarction therapy.

Tumor necrosis factor α (TNF-α) is a leading proinflammatory cytokine as the master regulator of inflammation in chronic inflammation diseases. Although TNF-α antagonists such as small molecules and peptides are in development, comparable effectiveness in TNF-α neutralization is hardly achieved only with TNF-α capture. In this study, simplified α2-macroglobulin (SM) as a novel TNF-α inhibitor was fabricated to relieve inflammation response by TNF-α capture and internalization with lysosomal degradation. SM was prepared by conjugating a TNF-α-targeting peptide with a receptor binding domain (RBD) derived from α2-macroglobulin through a synthetic biology strategy. SM exhibited effective capture and bioactivity inhibition of TNF-α. Improved endocytosis of TNF-α into lysosomes was observed with SM in macrophages. Even challenged with LPS/IFNγ, the macrophages showed relieved inflammation response with SM treatment. When administrated in chronic inflammation injury in vivo, SM achieved comparable therapeutic efficacy with Infliximab, showing ameliorated cartilage degeneration with relieved inflammation in osteoarthritis (OA) and preserved cardiac function with mitigated myocardium injury in myocardial infarction (MI). These results suggest that SM functioning in TNF-α capture-internalization mechanism might be promising therapeutic alternatives of TNF-α antibodies.

Real-Time Objective Evaluation of the Ischemic Stroke through pH-Responsive Fluorescence Imaging.

A rapid and comprehensive assessment of ischemic stroke (IS) is critical for clinicians to take the most appropriate treatment. Currently, IS assessment is mainly carried out by computed tomography and magnetic resonance imaging in combination with observing the clinical symptoms and inquiring about contraindications. However, they cannot diagnose pathological conditions and judge the microenvironment in real-time. Near-infrared fluorescence imaging has advantages for IS imaging, such as high sensitivity, high spatiotemporal resolution, and straightforward real-time operation. Herein, a pH-responsive fluorescent liposomal probe (BOD@Lip) is prepared for in vivo real-time visualization of the degree of IS based on the different acid microenvironments in the progression of the disease. The fluorescence imaging with BOD@Lip shows the degree of IS, and the correlation between fluorescence signals and the neurological deficit scores is established for the first time. This work provides a new method to objectively evaluate the degree of IS through a visualized route and a new insight into the relationship between the acidic microenvironment and the progression of IS.

In vivo self-assembled shape-memory polyurethane for minimally invasive delivery and therapy.

Advanced elastomers are highly in demand for the fabrication of medical devices for minimally invasive surgery (MIS). Herein, a shape memory and self-healing polyurethane (PCLUSe) composed of semi-crystalline poly(ε-caprolactone) (PCL) segments and interchangeable and antioxidative diselenide bonds was designed and synthesized. The excellent shape memory of PCLUSe contributed to the smooth MIS operation, leading to less surgical wounds than in the case of sternotomy. The diselenide bonds of PCLUSe contributed to the rapid self-healing under 405 nm irradiation within 60 s, and the alleviation of tissue oxidation post injury. After being delivered through a 10 mm diameter trocar onto a beating canine heart by MIS, two shape-recovered PCLUSe films self-assembled (self-healing) into a larger single patch (20 × 10 × 0.2 mm3) under the trigger of laser irradiation in situ, which could efficiently overcome the limited-size problem within MIS and meet a larger treatment area. The diselenide bonds in the PCLUSe cardiac patches protected the myocardium under oxidative stress post myocardial infarction (MI), and significantly maintained the cardiac functions.

A biodegradable, flexible photonic patch for in vivo phototherapy.

Diagnostic and therapeutic illumination on internal organs and tissues with high controllability and adaptability in terms of spectrum, area, depth, and intensity remains a major challenge. Here, we present a flexible, biodegradable photonic device called iCarP with a micrometer scale air gap between a refractive polyester patch and the embedded removable tapered optical fiber. ICarP combines the advantages of light diffraction by the tapered optical fiber, dual refractions in the air gap, and reflection inside the patch to obtain a bulb-like illumination, guiding light towards target tissue. We show that iCarP achieves large area, high intensity, wide spectrum, continuous or pulsatile, deeply penetrating illumination without puncturing the target tissues and demonstrate that it supports phototherapies with different photosensitizers. We find that the photonic device is compatible with thoracoscopy-based minimally invasive implantation onto beating hearts. These initial results show that iCarP could be a safe, precise and widely applicable device suitable for internal organs and tissue illumination and associated diagnosis and therapy.

Implantable Thermal Therapeutic Device with Precise Temperature Control Enabled by Foldable Electronics and Heat-Insulating Pads.

Thermal therapy has continued to attract the attention of researchers and clinicians due to its important applications in tumor ablation, wound management, and drug release. The lack of precise temperature control capability in traditional thermal treatment may cause the decrease of therapeutic effect and thermal damage to normal tissues. Here, we report an implantable thermal therapeutic device (ITTD), which offers precise closed loop heating, in situ temperature monitoring, and thermal protection. The ITTD features a multifunctional foldable electronics device wrapped on a heat-insulating composite pad. Experimental and numerical studies reveal the fundamental aspects of the design, fabrication, and operation of the ITTD. In vivo experiments of the ITTD in thermal ablation for antitumor demonstrate that the proposed ITTD is capable of controlling the ablation temperature precisely in real time with a precision of at least 0.7°C and providing effective thermal protection to normal tissues. This proof-of-concept research creates a promising route to develop ITTD with precise temperature control capability, which is highly desired in thermal therapy and other disease diagnosis and treatments.

A hyaluronic acid/platelet-rich plasma hydrogel containing MnO2 nanozymes efficiently alleviates osteoarthritis in vivo.

The osteoarthritis (OA) symptoms cannot be fully remedied by using only a single functional component because of its complex pathogenesis. Herein, a MnO2 nanozyme-encapsulated hydrogel was fabricated via dispersing bovine serum albumin (BSA)-MnO2 (BM) nanoparticles (NPs) into a hyaluronic acid (HA)/platelet-rich plasma (PRP) gel network crosslinked by Schiff base reaction. Due to the self-healing and pH-responsive properties of Schiff base bonds, the hydrogel not only functioned as viscosupplementation but also exhibited pH-responsive release of BM NPs and growth factors in PRP. The BM NPs could attenuate the severe oxidative stress, and the PRP could promote chondrocyte proliferation. In a rat OA model, the HA/PRP/BM hydrogel markedly suppressed cartilage matrix degradation. Both the in vitro and in vivo studies showed that this novel hydrogel platform could inhibit the development of osteoarthritis through a synergetic effect of mechanical dissipation, depressing inflammation, facilitating cartilage repair, and thus has essential application prospects in OA treatment.

A Load-Carrier Perspective Method for Evaluating Land Resources Carrying Capacity.

If land resources are forced to withstand greater populations than they are able to withstand, irreversible damage to the land resources system will happen in a specific region. This challenge highlights the urgency of appropriately evaluating the land resources carrying capacity (LRCC). A proper level of the capacity can ensure that land resources demands imposed by human activities are at a reasonable level. There is a need for a proper evaluation method for assessing LRCC. This study presents a new evaluation method from a load-carrier perspective for assessing LRCC by examining the relationships between the pressure caused by human activities and the supply capacity of land resources. In developing this method, a land resources system is determined by two primary components, namely carrier and load. The compositions of carrier and load are determined by applying the theory of multifunctional land use. A case demonstration is conducted to show the application of the method. The main findings can be drawn from this study as follows. Firstly, a "load-carrier" perspective method is requested for evaluating the regional LRCC, and it is effective in obtaining the value of LRCC in the demonstration case. Secondly, the composition of land resources carriers and loads embodied in the load-carrier perspective method is determined by using the theory of multifunctional land use. Thirdly, the case results suggest that seven regions are overloaded in LRCC and the other two regions are approaching the limitation of LRCC among nine county-level administration regions in Chongqing. This study contributes to the development of literature in the field of LRCC. The application of the "load-carrier" perspective method can help local governments in the case study regions make policies to ensure that land resources demands imposed by human activities are under control at a reasonable level.

Alleviating Oxidative Injury of Myocardial Infarction by a Fibrous Polyurethane Patch with Condensed ROS-Scavenging Backbone Units.

Excessive reactive oxygen species (ROS) generated after myocardial infarction (MI) result in the oxidative injury in myocardium. Implantation of antioxidant biomaterials, without the use of any type of drugs, is very appealing for clinical translation, leading to the great demand of novel biomaterials with high efficiency of ROS elimination. In this study, a segmented polyurethane (PFTU) with a high density of ROS-scavenging backbone units is synthesized by the reaction of poly(thioketal) dithiol (PTK) and poly(propylene fumarate) diol (PPF) (soft segments), thioketal diamine (chain extender), and 1,6-hexamethylene diisocyanate (HDI). Its chemical structure is verified by gel permeation chromatography (GPC), 1 H nuclear magnetic resonance (1 H NMR) spectroscopy, and Fourier transform infrared (FTIR) spectroscopy. The electrospun composite PFTU/gelatin (PFTU/Gt) fibrous patches show good antioxidation capacity and ROS-responsive degradation in vitro. Implantation of the PFTU/gelatin patches on the heart tissue surface in MI rats consistently decreases the ROS level, membrane peroxidation, and cell apoptosis at the earlier stage, which are not observed in the non-ROS-responsive polyurethane patch. Inflammation and fibrosis are also reduced in the PFTU/gelatin-treated hearts, resulting in the reduced left ventricular remodeling and better cardiac functions postimplantation for 28 d.

Scalable Milk-Derived Whey Protein Hydrogel as an Implantable Biomaterial.

There are limited naturally derived protein biomaterials for the available medical implants. High cost, low yield, and batch-to-batch inconsistency, as well as intrinsically differing bioactivity in some of the proteins, make them less beneficial as common implant materials compared to their synthetic counterparts. Here, we present a milk-derived whey protein isolate (WPI) as a new kind of natural protein-based biomaterial for medical implants. The WPI was methacrylated at 100 g bench scale, >95% conversion, and 90% yield to generate a photo-cross-linkable material. WPI-MA was further processed into injectable hydrogels, monodispersed microspheres, and patterned scaffolds with photo-cross-linking-based advanced processing methods including microfluidics and 3D printing. In vivo evaluation of the WPI-MA hydrogels showed promising biocompatibility and degradability. Intramyocardial implantation of injectable WPI-MA hydrogels in a model of myocardial infarction attenuated the pathological changes in the left ventricle. Our results indicate a possible therapeutic value of WPI-based biomaterials and give rise to a potential collaboration between the dairy industry and the production of medical therapeutics.