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Abstract Acute kidney injury (AKI) is a clinical syndrome characterized by a rapid decline in renal function, and is associated with a high risk of death. Many pathological changes happen in the process of AKI, including crucial alterations to oxidative stress levels. Numerous efforts have thus been made to develop effective medicines to scavenge excess reactive oxygen species (ROS). However, researchers have encountered several significant challenges, including unspecific biodistribution, high biotoxicity, and in vivo instability. To address these problems, engineered nanoparticles have been developed to target oxidative stress and treat AKI. This review thoroughly discusses the methods that empower nanodrugs to specifically target the glomerular filtration barrier and presents the latest achievements in engineering novel ROS‐scavenging nanodrugs in clustered sections. The analysis of each study's breakthroughs and imperfections visualizes the progress made in developing effective nanodrugs with specific biodistribution and oxidative stress‐targeting capabilities. This review fills the blank of a comprehensive outline over current progress in applying nanotechnology to treat AKI, providing potential insights for further research.

Abstract An ideal implant needs to have the ability to coordinate the foreign body response and tissue regeneration. Here, Hydrogenated‐silicon nanosheets (H‐Si NSs) with favorable biodegradability are integrated and functionalized into a β‐tricalcium phosphate scaffold (H‐Si TCP) for bone defect healing. H‐Si TCP can greatly improve bone regeneration through osteoimmunomodulation‐guided biodegradation in vivo. The spatiotemporal regulation of degradation products replenishes sufficient nutrients step by step for the entire process of bone repair. Extracellular and intracellular reactive oxygen species (ROS) are first downregulated by reaction with H‐Si NSs, followed by marked M2 polarization, remodeling the micro‐environment timely for immune‐bone regeneration. The release of primary reaction products awakened bone marrow mesenchymal stem cells (BMSCs), which are converted into osteoblasts anchored on scaffolds. Subsequently, biomineralization is promoted by the final degradation products. The intrinsic ROS‐responsive, immunoregulatory, and osteo‐promotive capability of 2D H‐Si NSs makes such composite H‐Si TCP scaffold a highly potential alternative for the treatment of critical bone defect.

Abstract PROteolysis TArgeting Chimeras (PROTACs) are an emerging class of promising therapeutic modalities that selectively degrade intracellular proteins of interest by hijacking the ubiquitin‐proteasome system. However, the lack of techniques to efficiently transport these degraders to targeted cells and consequently the potential toxicity of PROTACs limit their clinical applications. Here, a strategy of nanoengineered PROTACs, that is, Nano‐PROTACs, is reported, which improves the bioavailability of PROTACs and maximizes their capacity to therapeutically degrade intracellular oncogenic proteins for tumor therapy. The Nano‐PROTACs are developed by encapsulating PROTACs in glutathione (GSH)‐responsive poly(disulfide amide) polymeric (PDSA) nanoparticles and show that ARV@PDSA Nano‐PROTAC, nanoengineered BRD4 degrader ARV‐771, improves BRD4 protein degradation and decreases the downstream oncogene c‐Myc expression. Benefiting from the GSH‐scavenging ability to amply the c‐Myc‐related ferroptosis and cell cycle arrest, this ARV@PDSA Nano‐PROTACs strategy shows superior anti‐tumor efficacy with a low dose administration and good biocompatibility in vivo. The findings reveal the potential of the Nano‐PROTACs strategy to treat a broad range of diseases by dismantling associated pathogenic proteins.

Looking retrospectively at the development of humanity, vaccination is an unprecedented medical landmark that saves lives by harnessing the human immune system. During the ongoing coronavirus disease 2019 (COVID-19) pandemic, vaccination is still the most effective defense modality. The successful clinical application of the lipid nanoparticle-based Pfizer/BioNTech and Moderna mRNA COVID-19 vaccines highlights promising future of nanotechnology in vaccine development. Compared with conventional vaccines, nanovaccines are supposed to have advantages in lymph node accumulation, antigen assembly, and antigen presentation; they also have, unique pathogen biomimicry properties because of well-organized combination of multiple immune factors. Beyond infectious diseases, vaccine nanotechnology also exhibits considerable potential for cancer treatment. The ultimate goal of cancer vaccines is to fully mobilize the potency of the immune system as a living therapeutic to recognize tumor antigens and eliminate tumor cells, and nanotechnologies have the requisite properties to realize this goal. In this review, we summarize the recent advances in vaccine nanotechnology from infectious disease prevention to cancer immunotherapy and highlight the different types of materials, mechanisms, administration methods, as well as future perspectives.

Abstract Abnormal iron metabolism, mitochondrial dysfunction and the derived oxidative damage are the main pathogeneses of Friedrich's ataxia (FRDA), a single-gene inherited recessive neurodegenerative disease characterized by progressive cerebellar and sensory ataxia. This disease is caused by frataxin (FXN) mutation, which reduces FXN expression and impairs iron sulfur cluster biogenesis. To date, there is no effective therapy to treat this condition. Curcumin is proposed harboring excellent ability to resist oxidative stress through Nrf2 activation and its newly found ability to chelate iron. However, its limitation is its poor water solubility and permeability. Here, we synthesized slow-release nanoparticles (NPs) by loading curcumin (Cur) into silk fibroin (SF) to form NPs with an average size of 150 nm (Cur@SF NPs), which exhibited satisfactory therapeutic effects on the improvement of FRDA manifestation in lymphoblasts (1 μM) derived from FRDA patients and in YG8R mice (150 mg/kg/5 days). Cur@SF NPs not only removed iron from the heart and diminished oxidative stress in general but also potentiate iron-sulfur cluster biogenesis, which compensates FXN deficiency to improve the morphology and function of mitochondria. Cur@SF NPs showed a significant advantage in neuron and myocardial function, thereby improving FRDA mouse behavior scores. These data encourage us to propose that Cur@SF NPs are a promising therapeutic compound in the application of FRDA disease. Graphical Abstract

Abstract Ionizing radiation (IR) poses a growing threat to human health, and thus ideal radioprotectors with high efficacy and low toxicity still receive widespread attention in radiation medicine. Despite significant progress made in conventional radioprotectants, high toxicity, and low bioavailability still discourage their application. Fortunately, the rapidly evolving nanomaterial technology furnishes reliable tools to address these bottlenecks, opening up the cutting‐edge nano‐radioprotective medicine, among which the intrinsic nano‐radioprotectants characterized by high efficacy, low toxicity, and prolonged blood retention duration, represent the most extensively studied class in this area. Herein, we made the systematic review on this topic, and discussed more specific types of radioprotective nanomaterials and more general clusters of the extensive nano‐radioprotectants. In this review, we mainly focused on the development, design innovations, applications, challenges, and prospects of the intrinsic antiradiation nanomedicines, and presented a comprehensive overview, in‐depth analysis as well as an updated understanding of the latest advances in this topic. We hope that this review will promote the interdisciplinarity across radiation medicine and nanotechnology and stimulate further valuable studies in this promising field.

In this study, a two-compartment biofilm reactor was designed for iturin A production. The biofilm reactor consists of a stirred-tank fermentor containing exclusively suspended cells and a packing column where the biofilm is attached. Polyester fiber with sphere shape and rough surfaces was chosen as the carrier of biofilm in packing column. Batch, fed-batch, and repeated-batch fermentation using Bacillus velezensis ND in the biofilm reactor were studied. Compared to conventional suspended cell fermentations, the productivity of iturin A in batch and fed-batch biofilm fermentation were increased by 66.7% and 63.3%, respectively. Maximum itutin A concentration of 6.8 ± 0.1 g/L and productivity of 46.9 ± 0.2 mg/L/h were obtained in fed-batch biofilm fermentation. Repeated-batch fermentation showed high stability, with almost same profile as batch fermentation. After a step-wise temperature control strategy was introduced in the biofilm reactor, productivity of iturin A was increased by 131.9% compared to suspended cell reactor. This superior performance of biofilm reactor confirms that it has great potential in industrial production of iturin A.

Vegetation is a crucial component of any ecosystem and to preserve the health and stability of grassland ecosystems, species diversity is important. The primary form of grassland use globally is livestock grazing, hence many studies focus on how plant diversity is affected by the grazing intensity, differential use of grazing time and livestock species. Nevertheless, the impact of the grazing time on plant diversity remains largely unexplored. We performed a field survey on the winter pastures in alpine meadows of the Qinghai-Tibetan Plateau (QTP) to examine the effects of grazing time on the vegetation traits. Livestock species, grazing stocking rates and the initiation time of the grazing were similar, but termination times of the grazing differed. The grazing termination time has a significant effect on most of the vegetation traits in the winter pastures. The vegetation height, above-ground biomass, and the Graminoids biomass was negatively related to the grazing termination time in the winter pastures. In contrast, vegetation cover and plant diversity initially increased and subsequently decreased again as the grazing termination time was extended. An extension of the grazing time did not have any effect on the biomass of forbs. Our study is the first to investigate the effects of grazing during the regrowth period on vegetation traits and imply that the plant diversity is mediated by the grazing termination time during the regrowth period in winter pastures. These findings could be used to improve the guidelines for livestock grazing management and policies of summer and winter pasture grazing of family pastures on the QTP from the perspective of plant diversity protection.

Current-sensing topology with multi resistors in series has limitations in improving the dynamic range of current acquisition, so a sensing topology with multi resistors in parallel is proposed. The overcurrent state of a parallel shunt circuit cannot be latched, resulting in protection hiccups. A dual threshold-detection circuit is designed to achieve protection state latching and self-recovery. The rectified mean circuit is applied for overcurrent magnitude detection and its validity is proved. But the delay and ripple of the output waveform of the rectified mean circuit may also cause protection hiccups. Combining Fourier series representation, Fourier transform and inverse transform, the time domain expressions of the output of the rectified mean circuit for three common waveforms are obtained. Furthermore, the estimation formulas for the residual ripple amplitude of the three waveforms are derived. In an experiment, the protection hiccup issue in parallel sensing topology was eliminated, while the time constants and hysteresis ratios of the protection circuits were properly set according to theoretical calculation results. With five parallel sensing resistors, the ratio of the maximum to minimum range of the single current channel reaches 1.28×104, which is higher than counterparts with multiple series sensing resistors. The advantages of parallel sensing topology in improving dynamic range are confirmed.

Abstract In the field of nanomedicine, there is a tendency of matching designed nanomaterials with a suitable type of orthotopic cancer model, not just a casual subcutaneous one. Under this condition, knowing the specific features of the chosen cancer model is the priority, then introducing a proper therapy strategy using designed nanomaterials. Here, the Fenton chemistry is combined with zinc peroxide nanoparticles in the treatment of orthotopic liver cancer which has a “chemical factory” including that liver is the main place for iron storage, metabolism, and also the main metabolic sites for the majority of ingested substances, guaranteeing customized and enhanced chemodynamic therapy and normal liver cells protection as well. The good results in vitro and in vivo can set an inspiring example for exploring and utilizing suitable nanomaterials in corresponding cancer models, ensuring well‐fitness of nanomaterials for disease and satisfactory therapeutic effect.

Messenger RNA (mRNA)-based therapeutics are transforming the landscapes of medicine, yet targeted delivery of mRNA to specific cell types while minimizing off-target accumulation remains challenging for mRNA-mediated therapy. In this study, we report an innovative design of a cationic lipid- and hyaluronic acid-based, dual-targeted mRNA nanoformulation that can display the desirable stability and efficiently transfect the targeted proteins into lung tissues. More importantly, the optimized dual-targeted mRNA nanoparticles (NPs) can not only accumulate primarily in lung tumor cells and inflammatory macrophages after inhalation delivery but also efficiently express any desirable proteins (e.g., p53 tumor suppressor for therapy, as well as luciferase and green fluorescence protein for imaging as examples in this study) and achieve efficacious lung tissue transfection in vivo. Overall, our findings provide proof-of-principle evidence for the design and use of dual-targeted mRNA NPs in homing to specific cell types to up-regulate target proteins in lung tissues, which may hold great potential for the future development of mRNA-based inhaled medicines or vaccines in treating various lung-related diseases. [ABSTRACT FROM AUTHOR]

The complexity of online narratives and their important influence on events, attitudes, and emotions in society make visible certain limitations in the explication of such narratives found in traditional narrative theory. Their generative mechanism provides the logical starting point for understanding online communication. Event correlatives, text assemblage and specific texts, as the organic structure of online narratives, shape the intertextual existence and dynamic accumulation of the online text. A universal multidirectional co-construction forms around event correlatives and between specific texts and the pre-text, post-text and synchronous text within the text assemblage, while the textual object, the communicating subject and the online group communication context together build up the interpretive system of online narrative meanings. The generative mechanism and vitality of online narratives not only provide guarantees for the active nature of online communication, but also become a huge variable in social development, profoundly influencing social communication and even our way of thinking. [ABSTRACT FROM AUTHOR]