Adaptive enzyme-responsive self-assembling multivalent apelin ligands for targeted myocardial infarction therapy.

Microvascular dysfunction following myocardial infarction exacerbates coronary flow obstruction and impairs the preservation of ventricular function. The apelinergic system, known for its pleiotropic effects on improving vascular function and repairing ischemic myocardium, has emerged as a promising therapeutic target for myocardial infarction. Despite its potential, the natural apelin peptide has an extremely short circulating half-life. Current apelin analogs have limited receptor binding efficacy and poor targeting, which restricts their clinical applications. In this study, we utilized an enzyme-responsive peptide self-assembly technique to develop an enzyme-responsive small molecule peptide that adapts to the expression levels of matrix metalloproteinases in myocardial infarction lesions. This peptide is engineered to respond to the high concentration of matrix metalloproteinases in the lesion area, allowing for precise and abundant presentation of the apelin motif. The changes in hydrophobicity allow the apelin motif to self-assemble into a supramolecular multivalent peptide ligand-SAMP. This self-assembly behavior not only prolongs the residence time of apelin in the myocardial infarction lesion but also enhances the receptor-ligand interaction through increased receptor binding affinity due to multivalency. Studies have demonstrated that SAMP significantly promotes angiogenesis after ischemia, reduces cardiomyocyte apoptosis, and improves cardiac function. This novel therapeutic strategy offers a new approach to restoring coronary microvascular function and improving damaged myocardium after myocardial infarction.

Respiratory characterization of a humanized Duchenne muscular dystrophy mouse model.

Duchenne muscular dystrophy (DMD) is the most common X-linked disease. DMD is caused by a lack of dystrophin, a critical structural protein in striated muscle. Dystrophin deficiency leads to inflammation, fibrosis, and muscle atrophy. Boys with DMD have progressive muscle weakness within the diaphragm that results in respiratory failure in the 2nd or 3rd decade of life. The most common DMD mouse model - the mdx mouse - is not sufficient for evaluating genetic medicines that specifically target the human DMD (hDMD) gene sequence. Therefore, a novel transgenic mouse carrying the hDMD gene with an exon 52 deletion was created (hDMDΔ52;mdx). We characterized the respiratory function and pathology in this model using whole body plethysmography, histology, and immunohistochemistry. At 6-months-old, hDMDΔ52;mdx mice have reduced maximal respiration, neuromuscular junction pathology, and fibrosis throughout the diaphragm, which worsens at 12-months-old. In conclusion, the hDMDΔ52;mdx exhibits moderate respiratory pathology, and serves as a relevant animal model to study the impact of novel genetic therapies, including gene editing, on respiratory function.

Comparison of the effect of tea shoots during different seasons in Arma chinensis (Hemiptera: Pentatomidae) reared on Ectropis grisescens (Lepidoptera: Geometridae) pupae.

In this study, we compared the growth, development, and fecundity of Arma chinensis (Fallou) reared on pupae of the geometrid Ectropis grisescens Warren fed on tea shoots during different seasons of the year. The raw data on life history were analyzed using the age-stage, 2-sex life table. When reared on spring or winter geometrid pupae, the duration of the immature stage of A. chinensis was significantly longer than in those produced during the summer or autumn. The survival rate of immature A. chinensis reared on autumn geometrid pupae was significantly lower compared to other treatments. Reproductive diapause was observed in adult A. chinensis reared on winter geometrid pupae. The adult preoviposition period (APOP), total preoviposition period (TPOP), and total longevity were significantly longer in A. chinensis reared on winter pupae than in the other treatments. The fecundity of A. chinensis reared on spring geometrid pupae was significantly lower than in the other treatments. The higher intrinsic rate of increase of the A. chinensis reared on summer pupae (r = 0.0966 day-1) and autumn pupae (r = 0.0983 day-1) resulted in higher fecundity, shorter immature duration, and shorter TPOP compared to the winter and spring populations. These findings can be utilized to enhance and sustain biological control of E. grisescens in tea plantations.

Mrc1+ macrophage-derived IGF1 mitigates crystal nephropathy by promoting renal tubule cell proliferation via the AKT/Rb signaling pathway.

Rationale: The present understanding of the cellular characteristics and communications in crystal nephropathy is limited. Here, molecular and cellular studies combined with single-cell RNA sequencing (scRNA-seq) were performed to investigate the changes in cell components and their interactions in glyoxylate-induced crystallized kidneys to provide promising treatments for crystal nephropathy. Methods: The transcriptomes of single cells from mouse kidneys treated with glyoxylate for 0, 1, 4, or 7 days were analyzed via 10× Genomics, and the single cells were clustered and characterized by the Seurat pipeline. The potential cellular interactions between specific cell types were explored by CellChat. Molecular and cellular findings related to macrophage-to-epithelium crosstalk were validated in sodium oxalate (NaOx)-induced renal tubular epithelial cell injury in vitro and in glyoxylate-induced crystal nephropathy in vivo. Results: Our established scRNA atlas of glyoxylate-induced crystalline nephropathy contained 15 cell populations with more than 40000 single cells, including relatively stable tubular cells of different segments, proliferating and injured proximal tubular cells, T cells, B cells, and myeloid and mesenchymal cells. In this study, we found that Mrc1+ macrophages, as a subtype of myeloid cells, increased in both the number and percentage within the myeloid population as crystal-induced injury progresses, and distinctly express IGF1, which induces the activation of a signal pathway to dominate a significant information flow towards injured and proliferating tubule cells. IGF1 promoted the repair of damaged tubular epithelial cells induced by NaOx in vitro, as well as the repair of damaged tubular epithelial cells and the recovery of disease outcomes in glyoxylate-induced nephrolithic mice in vivo. Conclusion: After constructing a cellular atlas of glyoxylate-induced crystal nephropathy, we found that IGF1 derived from Mrc1+ macrophages attenuated crystal nephropathy through promoting renal tubule cell proliferation via the AKT/Rb signaling pathway. These findings could lead to the identification of potential therapeutic targets for the treatment of crystal nephropathy.

Structure-Property Relationships of Hydrogel-based Atmospheric Water Harvesting Systems.

Atmospheric water harvesting (AWH) is considered one of the promising technologies to alleviate the uneven-distribution of water resources and water scarcity in arid regions of the world. Hydrogel-based AWH materials are currently attracting increasing attention due to their low cost, high energy efficiency and simple preparation. However, there is a knowledge gap in the screening of hydrogel-based AWH materials in terms of structure-property relationships, which may increase the cost of trial and error in research and fabrication. In this study, we synthesised a variety of hydrogel-based AWH materials, characterized their physochemcial properties visualized the electrostatic potential of polymer chains, and ultimately established the structure-property-application relationships of polymeric AWH materials. Poly(2-acrylamido-2-methyl-1-propanesulfonic acid) (PAMPS) hydrogel is able to achieve an excellent water adsorption capacity of 0.62 g g-1 and a high water desorption efficiency of more than 90 % in relatively low-moderate humidity environments, which is regarded as one of the polymer materials with potential for future AWH applications.

Electrospun nanofiber membranes for rapid liver hemostasis via N-alkylated chitosan doped chitosan/PEO.

The ideal hemostatic agents should be able to stop bleeding quickly and avoid secondary bleeding caused by adhesion with blood clots during dressing change. Herein, a hydrophobic electrospun nanofiber membrane was prepared for achieving hemostasis, rationally targeting both attributes, via doping N-alkylated chitosan (N-CS) grafted with octadecyl into chitosan/polyethylene oxide (PEO). In vitro and in vivo coagulation tests showed that CPNs doped with small amounts of N-CS (CPN31) could significantly shorten hemostasis time and promote the formation of more stable and stronger blood clots. In particular, the whole blood clotting time of CPN31 (58.8 ± 2.2 s) was significantly lower than that of chitosan/PEO (CPN0) nanofiber membrane (67 ± 3.5 s) and the medical sterile gauze (86.7 ± 0.6 s). Furthermore, due to the hemophobic nature of CPNs, blood wetting of the dressing was severely limited and blood can coagulated at the site of liver injury in rats, thus reducing blood loss and allowing rapid removal of the dressing without triggering secondary hemorrhage. The CPN31 exhibited excellent hemostasis properties, easy to remove, blood compatibility, biocompatibility and promoting fibroblast proliferation properties. This hydrophobic CPNs is a promising biological adhesive for hemorrhage control.

Spiral grass inspired eco-friendly zein fibrous membrane for multi-efficient air purification.

Air pollution, one of the severest threats to public health, may lead to cardiovascular and respiratory illnesses. In order to cope with the deteriorating air pollutant, there is an increasing demand for filters with high purification efficiency, but it's tough to strike a balance between efficiency and resistance. Fabricating an eco-friendly fibrous filter which can capture both PM2.5 and gaseous chemical hazards with high efficiency but under ultra-low resistance is a long-term challenge. Herein, inspired by the interesting ribbon shape of spiral grass, a green and robust 3D nonwoven membrane with controllable hierarchical structure made of self-curved zein nanofibers modified by zeolitic imidazolate framework-8 (ZIF-8) via bi-solvent electrospinning and fumigation welding method was fabricated. The obtained ZIF-8 modified zein membranes showed extraordinary overall performance with high PM2.5 removal efficiency (99.04 %) at a low stress drop (54.87 Pa), first-rate formaldehyde removal efficiency (98.8 %) and excellent photocatalytic antibacterial. In addition, the relatively weak mechanical properties of zein fibrous membranes have been improved via solvent fumigation welding of the joint zein fibers. This study provides a green and convenient insight to the manufacturing of environmentally-friendly zein fibrous membranes with high filtration efficiency, low air resistance and high formaldehyde removal for sustainable air remediation.

Risk factors associated with indoor transmission during home quarantine of COVID-19 patients.

Purpose: The study aimed to identify potential risk factors for family transmission and to provide precautionary guidelines for the general public during novel Coronavirus disease 2019 (COVID-19) waves. Methods: A retrospective cohort study with numerous COVID-19 patients recruited was conducted in Shanghai. Epidemiological data including transmission details, demographics, vaccination status, symptoms, comorbidities, antigen test, living environment, residential ventilation, disinfection and medical treatment of each participant were collected and risk factors for family transmission were determined. Results: A total of 2,334 COVID-19 patients participated. Compared with non-cohabitation infected patients, cohabitated ones were younger (p = 0.019), more commonly unvaccinated (p = 0.048) or exposed to infections (p < 0.001), and had higher rates of symptoms (p = 0.003) or shared living room (p < 0.001). Risk factors analysis showed that the 2019-nCov antigen positive (OR = 1.86, 95%CI 1.40-2.48, p < 0.001), symptoms development (OR = 1.86, 95%CI 1.34-2.58, p < 0.001), direct contact exposure (OR = 1.47, 95%CI 1.09-1.96, p = 0.010) were independent risk factors for the cohabitant transmission of COVID-19, and a separate room with a separate toilet could reduce the risk of family transmission (OR = 0.62, 95%CI 0.41-0.92, p = 0.018). Conclusion: Patients showing negative 2019-nCov antigen tests, being asymptomatic, living in a separate room with a separate toilet, or actively avoiding direct contact with cohabitants were at low risk of family transmission, and the study recommended that avoiding direct contact and residential disinfection could reduce the risk of all cohabitants within the same house being infected with COVID-19.

Flexible and Transparent Ceramic Nanocomposite for Laboratory X-ray Imaging of Micrometer Resolution.

Transparent nanocomposites have attracted considerable attention in many areas including X-ray imaging, wearable electronics, and volumetric display. However, both the transparency and the flexibility were largely jeopardized by the loading content of functional nanoparticles (NPs), posing a major challenge to material engineering. Herein, an ultra-high-loading-ceramic nanocomposite film was fabricated by a blade-coating technique. The film exhibited a high transparency over ∼89% in the whole visible region even with a fluoride-ceramic content up to ∼83 wt %. Based on a real-time investigation on the formation process of the film, the refractive-index difference between the nanoparticles and matrix was identified as the dominating factor to transparency. The transmittance spectra based on Rayleigh scattering theory were simulated to screen both nanoparticle radius and loading content, leading to the discovery of a transparency zone for film making. As a proof-of-concept experiment, the transparent film was used as an X-ray scintillation screen, which exhibited a comparable light yield to that of LYSO owing to the mitigated self-absorption effect. The homemade imager demonstrated a spatial resolution of 122 lp/mm, representing a record resolution of 4.1 µm for laboratory X-ray photography. Our work not only provided an experimental procedure to make high-loading functional films but also demonstrated a theoretical model to guide the search for gradients of transparent composites.

Trap-tuning in afterglow perovskite crystals through alkali metal ion doping.

Herein, we report a trap-tuning strategy involving alkali metal ions of Li+ and K+, which enabled a fine tuning of afterglow traps at 250 K. Through Li+/K+ doping, a red afterglow from Cs2AgInCl6:Mn was activated at room temperature, which was extended up to 3600 s at low temperature. Thermoluminescence measurement revealed a shallow trap at ∼0.50 eV below the conduction band, which could be shifted up- and down-ward by dopant species.

Airway acidification impaired host defense against Pseudomonas aeruginosa infection by promoting type 1 interferon ß response.

Airway microenvironment played an important role in the progression of chronic respiratory disease. Here we showed that standardized pondus hydrogenii (pH) of exhaled breath condensate (EBC) of bronchiectasis patients was significantly lower than that of controls and was significantly correlated with bronchiectasis severity index (BSI) scores and disease prognosis. EBC pH was lower in severe patients than that in mild and moderate patients. Besides, acidic microenvironment deteriorated Pseudomonas aeruginosa (P. aeruginosa) pulmonary infection in mice models. Mechanistically, acidic microenvironment increased P. aeruginosa outer membrane vesicles (PA_OMVs) released and boosted it induced the activation of interferon regulatory factor3 (IRF3)-interferonß (IFN-ß) signalling pathway, ultimately compromised the anti-bacteria immunity. Targeted knockout of IRF3 or type 1 interferon receptor (IFNAR1) alleviated lung damage and lethality of mice after P. aeruginosa infection that aggravated by acidic microenvironment. Together, these findings identified airway acidification impaired host resistance to P. aeruginosa infection by enhancing it induced the activation of IRF3-IFN-ß signalling pathway. Standardized EBC pH may be a useful biomarker of disease severity and a potential therapeutic target for the refractory P. aeruginosa infection. The study also provided one more reference parameter for drug selection and new drug discovery for bronchiectasis.

Combined toxicity of polystyrene microplastics and ammonium perfluorooctanoate to Daphnia magna: Mediation of intestinal blockage.

Microplastics (MPs) have worldwide accumulated in aquatic environments and coexisted with various water contaminants including perfluorinated compounds (PFCs) that are frequently detected. The adverse effects of individual MPs or PFCs on aquatic organisms have been extensively reported; however, the combined toxicity of MPs and PFCs remains unknown. This study evaluated the combined toxicity of MPs [pristine and aged polystyrene (PS)] and a PFC [ammonium perfluorooctanoate (APFO)] to Daphnia magna under different concentration ratios by three classic methods: toxicity unit, additive index, and mixed toxicity index. The adsorption kinetics of APFO on MPs, aggregation of MPs in exposure medium, MP gut fullness of daphnids, intestinal histology, and lipid peroxidation were analyzed to reveal the mechanism underlying the combined toxicity. Our results showed that the combined toxic modes varied with the concentration ratios of MPs to APFO (antagonism at 4:1 and 1:4, synergism at 3:1, 1:2, and 1:3, and partial addition/antagonism at 2:1 and 1:1 for pristine PS + APFO; antagonism at all ratios except partial addition/antagonism at 3:1 and 1:3 for aged PS + APFO), which could be attributed to the alteration of MP aggregation and thus MP gut fullness in the daphnids. The combined toxicity was further confirmed to occur in the daphnid's gut, which was reflected in physiological and biochemical responses mediated by intestinal blockage. Observable intestinal damages under co-exposures at µg•L-1 levels indicated the risks from future long-term exposure to MPs and PFCs in aquatic environments. This work demonstrates the necessity of assessing combined toxicity with different concentration ratios and provides new insights into the potential risks of MPs in aquatic environments.

In-situ sludge reduction performance and mechanism in an anoxic/aerobic process coupled with alternating aerobic/anaerobic side-stream reactor.

Activated sludge process with anaerobic side-stream reactors (SR) in the sludge recirculation can achieve in-situ sludge reduction, but sludge reduction efficiency is limited with the low hydraulic retention time (HRT) of SR. An anoxic/aerobic (AO) process, AO coupled with anaerobic SR and AO coupled with alternating aerobic/anaerobic side-stream reactor (AO-OASR) were operated to investigate enhancing effects of alternative aerobic and anaerobic condition (AltOA) in SR on sludge reduction and pollutants removal performance. The AltOA was firstly proposed into SR with a low HRT during the long-term continuous operation. The results showed that AO-OASR presented a lower effluent COD concentration (29.6%) with no adverse effect on nitrogen removal, compared to AO, owing to the intensified refractory carbon reuse in the mainstream aerobic tank. The sludge yield in AO-OASR (0.240 g SS/g COD) was 39.7% lower than that in AO. The OASR accelerated sludge lysis and particle organic matter hydrolysis due to the weakened network strength of flocs, leading to an enhanced increase (17.3 mg/L) of dissolved organic matter (DOM), especially for the fraction of molecular weight (MW) < 25 kDa. The OASR reduced the adenosine triphosphate (ATP) content for heterotrophic anabolism in the mainstream reactor by 42.9%, compared to the ASR. MW < 25 kDa of DOM caused the disturbance of oxidative phosphorylation with a decreasing ATP synthase activity under high-level electronic transport system, leading to ATP dissipation. The cooperation interaction of predator (norank_Chitinophagales), hydrolytic/fermentative bacteria (unclassified_Bacteroidia and Delftia), and slow grower (Trichococcus) played a key role in improving the sludge reduction and carbon reuse in AO-OASR. The results provided an efficient and cost-saving technology for sludge reduction with modified SR under low HRT, which is meaningful to overcome the present bottleneck of deficient reduction efficiency for application in wastewater treatment plants.