Controlled-release hydrogel loaded with magnesium-based nanoflowers synergize immunomodulation and cartilage regeneration in tendon-bone healing.

Tendon-bone interface injuries pose a significant challenge in tissue regeneration, necessitating innovative approaches. Hydrogels with integrated supportive features and controlled release of therapeutic agents have emerged as promising candidates for the treatment of such injuries. In this study, we aimed to develop a temperature-sensitive composite hydrogel capable of providing sustained release of magnesium ions (Mg2+). We synthesized magnesium-Procyanidin coordinated metal polyphenol nanoparticles (Mg-PC) through a self-assembly process and integrated them into a two-component hydrogel. The hydrogel was composed of dopamine-modified hyaluronic acid (Dop-HA) and F127. To ensure controlled release and mitigate the "burst release" effect of Mg2+, we covalently crosslinked the Mg-PC nanoparticles through coordination bonds with the catechol moiety within the hydrogel. This crosslinking strategy extended the release window of Mg2+ concentrations for up to 56 days. The resulting hydrogel (Mg-PC@Dop-HA/F127) exhibited favorable properties, including injectability, thermosensitivity and shape adaptability, making it suitable for injection and adaptation to irregularly shaped supraspinatus implantation sites. Furthermore, the hydrogel sustained the release of Mg2+ and Procyanidins, which attracted mesenchymal stem and progenitor cells, alleviated inflammation, and promoted macrophage polarization towards the M2 phenotype. Additionally, it enhanced collagen synthesis and mineralization, facilitating the repair of the tendon-bone interface. By incorporating multilevel metal phenolic networks (MPN) to control ion release, these hybridized hydrogels can be customized for various biomedical applications.

Emerging Co-Assembled and Sustained Released Natural Medicinal Nanoparticles for Multitarget Therapy of Choroidal Neovascularization.

Age-related macular degeneration (AMD) disease has become a worldwide senile disease, and frequent intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) is the mainstream treatment in the clinic, which is associated with sight-threatening complications. Herein, nintedanib, an inhibitor of angiogenesis, and lutein, a potent antioxidant, can co-assemble into nanoparticles through multiple noncovalent interactions. Interestingly, the co-assembled lutein/nintedanib nanoparticles (L/N NPs) exhibit significantly improved stability and achieve long-term sustained release of two drugs for at least two months in mice. Interestingly, in rabbit eyeball with a more complete barrier system, the L/N NPs still successfully distribute in the retina and choroid for a month. In the laser-induced mouse choroidal neovascularization model, the L/N NPs after a minimally invasive subconjunctival administration can successfully inhibit angiogenesis and achieve comparable and even better therapeutic results to that of standard intravitreal injection of anti-VEGF. Therefore, the subconjunctival injection of L/N NPs with long-term sustained drug release behavior represents a promising and innovative strategy for AMD treatment. Such minimally invasive administration together with the ability to effectively inhibit angiogenesis reduce inflammation and counteract oxidative stress and holds great potential for improving patient outcomes and quality of life in those suffering from this debilitating eye condition.

Rspo2 exacerbates rheumatoid arthritis by targeting aggressive phenotype of fibroblast-like synoviocytes and disrupting chondrocyte homeostasis via Wnt/ß-catenin pathway.

BACKGROUND: The aggressive phenotype of fibroblast-like synoviocytes (FLS) has been identified as a contributing factor to the exacerbation of rheumatoid arthritis (RA) through the promotion of synovitis and cartilage damage. Regrettably, there is currently no effective therapeutic intervention available to address this issue. Recent research has shed light on the crucial regulatory role of R-spondin-2 (Rspo2) in cellular proliferation, cartilage degradation, and tumorigenesis. However, the specific impact of Rspo2 on RA remains poorly understood. We aim to investigate the function and mechanism of Rspo2 in regulating the aggressive phenotype of FLS and maintaining chondrocyte homeostasis in the context of RA. METHODS: The expression of Rspo2 in knee joint synovium and cartilage were detected in RA mice with antigen-induced arthritis (AIA) and RA patients. Recombinant mouse Rspo2 (rmRspo2), Rspo2 neutralizing antibody (Rspo2-NAb), and recombinant mouse DKK1 (rmDKK1, a potent inhibitor of Wnt signaling pathway) were used to explore the role and mechanism of Rspo2 in the progression of RA, specifically in relation to the aggressive phenotype of FLS and chondrocyte homeostasis, both in vivo and in vitro. RESULTS: We indicated that Rspo2 expression was upregulated both in synovium and articular cartilage as RA progressed in RA mice and RA patients. Increased Rspo2 upregulated the expression of leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), as the ligand for Rspo2, and ß-catenin in FLS and chondrocytes. Subsequent investigations revealed that intra-articular administration of rmRspo2 caused striking progressive synovitis and articular cartilage destruction to exacerbate RA progress in mice. Conversely, neutralization of Rspo2 or inhibition of the Wnt/ß-catenin pathway effectively alleviated experimental RA development. Moreover, Rspo2 facilitated FLS aggressive phenotype and disrupted chondrocyte homeostasis primarily through activating Wnt/ß-catenin pathway, which were effectively alleviated by Rspo2-NAb or rmDKK1. CONCLUSIONS: Our data confirmed a critical role of Rspo2 in enhancing the aggressive phenotype of FLS and disrupting chondrocyte homeostasis through the Wnt/ß-catenin pathway in the context of RA. Furthermore, the results indicated that intra-articular administration of Rspo2 neutralizing antibody or recombinant DKK1 might represent a promising therapeutic strategy for the treatment of RA.

Liquid metal microspheres with an eddy-thermal effect for magnetic hyperthermia-enhanced cancer embolization-immunotherapy.

Patients with hepatocellular carcinoma (HCC) display poor prognosis because HCC involves a high rate of metastasis and regrowth. Herein, we present an effective strategy to treat HCC using magnetic hyperthermia therapy (MHT)-enhanced cancer immunotherapy combined with transcatheter arterial embolization (TAE). Uniform liquid metal microspheres (LM MSs) obtained by microfluidic technology with powerful eddy-thermal effects could be used as both MHT and TAE agents for effective cancer therapy. The eddy-thermal effect of LM MSs demonstrated effective MHT, whereas LM MS-induced MHT boosted the immune system, promoted immune cell infiltration, and further stimulated powerful immune responses to suppress the growth of distant tumors, together with immune checkpoint blockade therapy. Furthermore, LM MS-lipiodol dispersion displayed excellent efficacy of the combined MHT-TAE in the orthotopic rabbit liver cancer model. Our work not only highlighted that LM MSs could act as effective MHT agents to achieve MHT-enhanced immunotherapy but also presented the significant promise of combining MHT with TAE for the efficient treatment of large orthotopic liver tumors.

Mo2C promoted electrocatalysis of the Pt/Mo2C (C) heterostructure for a superior hydrogen evolution reaction.

Constructing a unique electrochemical interface to enhance the catalytic capacity of Pt-based catalysts is indispensable for wider application of the hydrogen evolution reaction (HER). Herein, platinum-analogous molybdenum carbide (Mo2C) was combined with a lower content of Pt to construct the Pt/Mo2C (C) heterostructure via a solid-phase method, using ammonium molybdate as the precursor. Vulcan-C served as a support to promote the distribution of the Pt and Mo2C heterostructure, and cooperative effects between Pt and the Mo2C heterostructure contributed to the significantly improved catalytic capacity of Pt. The obtained Pt/Mo2C (C) exhibits superior HER activity and enhanced long-term durability in the acidic medium, with a low overpotential of 38 mV at 10 mA cm-2 and a low Tafel slope of 24 mV dec-1. In particular, a drastically enhanced amount of H2 production can be achieved (6837.28 mmol h-1 g-1). This facile approach not only provides a new pathway for constructing novel heterostructures but also gives an insight into the design of cost-effective Pt-based materials for an efficient HER.

Microneedle Patches Loaded with Nanovesicles for Glucose Transporter-Mediated Insulin Delivery.

Glucose-responsive insulin delivery systems that mimic insulin secretion activity in the pancreas show great potential to improve clinical therapeutic outcomes for people with type 1 and advanced type 2 diabetes. Here, we report a glucose-responsive insulin delivery microneedle (MN) array patch that is loaded with red blood cell (RBC) vesicles or liposome nanoparticles containing glucose transporters (GLUTs) bound with glucosamine-modified insulin (Glu-Insulin). In hyperglycemic conditions, high concentrations of glucose in interstitial fluid can replace Glu-Insulin via a competitive interaction with GLUT, leading to a quick release of Glu-Insulin and subsequent regulation of blood glucose (BG) levels in vivo. To prolong the effective glucose-responsive insulin release from MNs, additional free Glu-Insulin, which serves as "stored insulin", is loaded after RBC vesicles or liposome nanoparticles bound with Glu-Insulin. In the streptozotocin (STZ)-induced type 1 diabetic mouse model, this smart GLUT-based insulin patch can effectively control BG levels without causing hypoglycemia.

Disulfiram loaded calcium phosphate nanoparticles for enhanced cancer immunotherapy.

Considering the huge cost and long test periods required for new drug development, repurposing drugs that have already been applied in the clinic as new cancer treatment candidates represents an attractive alternative. Disulfiram (DSF) was originally used to treat alcoholism and has proven to have anticancer effects with the coadministration of copper ions (Cu2+). However, the limited water-solubility of DSF and systemic toxicity induced by exogenous Cu2+ hinder its practical application. Herein, we constructed pH-responsive lipid-coated calcium phosphate nanoparticles (LCP NPs) co-loaded with Cu2+ and DSF. After intravenous injection, those nanoparticles with long blood half-life preferentially accumulate in tumors, followed by the degradation of nanoparticles in response to the acidic tumor microenvironment, subsequently releasing Cu2+ and DSF to generate cytotoxic metabolite DTC-Copper complex, bis(diethyldithiocarbamate)-copper (CuET) for tumor treatment. In addition to direct cytotoxicity, the active metabolite CuET could effectively induce immunogenic cell death (ICD) of cancer cells to regulate the immunosuppressive tumor microenvironment, contributing to enhanced immune checkpoint blockade (ICB) therapy in triggering systemic immune responses. This work thus demonstrates the great promises of repurposing the old drug DSF as a new ICD inducer with nano-formulation, to achieve improved synergetic tumor-responsive therapy with low side effects.

Microfluidic Production of Zwitterion Coating Microcapsules with Low Foreign Body Reactions for Improved Islet Transplantation.

Islet transplantation is a promising strategy for type 1 diabetes mellitus (T1DM) treatment, whereas implanted-associated foreign body reaction (FBR) usually induces the necrosis of transplanted islets and leads to the failure of glycemic control. Benefiting from the excellent anti-biofouling property of zwitterionic materials and their successful application in macroscopic implanted devices, microcapsules with zwitterionic coatings may be promising candidates for islet encapsulation. Herein, a series of zwitterion-coated core-shell microcapsules is fabricated (including carboxybetaine methacrylate [CBMA]-coated gelatin methacrylate [GelMA] [CBMA-GelMA], sulfobetaine methacrylate [SBMA]-coated GelMA [SBMA-GelMA], and phosphorylcholine methacrylate [MPC]-coated GelMA [MPC-GelMA]) by one-step photopolymerization of inner GelMA and outer zwitterionic monomers via a handmade two-fluid microfluidic device and it is demonstrated that they can effectively prevent protein adsorption, cell adhesion, and inflammation in vitro. Interestingly, the zwitterionic microcapsules successfully resist FBR in C57BL/6 mice after intraperitoneal implantation for up to 4 months. After successfully encapsulating xenogeneic rat islets in the SBMA-GelMA microcapsules, sustained normoglycemia is further validated in streptozotocin (STZ)-induced mice for up to 3 months. The zwitterion-modified microcapsule using a microfluidic device may represent a platform for cell encapsulation treatment for T1DM and other hormone-deficient diseases.

Heavy haze pollution during the COVID-19 lockdown in the Beijing-Tianjin-Hebei region, China.

To investigate the characteristics of particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5) and its chemical compositions in the Beijing-Tianjin-Hebei (BTH) region of China during the novel coronavirus disease (COVID-19) lockdown, the ground-based data of PM2.5, trace gases, water-soluble inorganic ions, and organic and elemental carbon were analyzed in three typical cities (Beijing, Tianjin, and Baoding) in the BTH region of China from 5-15 February 2020. The PM2.5 source apportionment was established by combining the weather research and forecasting model and comprehensive air quality model with extensions (WRF-CAMx). The results showed that the maximum daily PM2.5 concentration reached the heavy pollution level (>150 µg/m3) in the above three cities. The sum concentration of SO42-, NO3- and NH4+ played a dominant position in PM2.5 chemical compositions of Beijing, Tianjin, and Baoding; secondary transformation of gaseous pollutants contributed significantly to PM2.5 generation, and the secondary transformation was enhanced as the increased PM2.5 concentrations. The results of WRF-CAMx showed obviously inter-transport of PM2.5 in the BTH region; the contribution of transportation source decreased significantly than previous reports in Beijing, Tianjin, and Baoding during the COVID-19 lockdown; but the contribution of industrial and residential emission sources increased significantly with the increase of PM2.5 concentration, and industry emission sources contributed the most to PM2.5 concentrations. Therefore, control policies should be devoted to reducing industrial emissions and regional joint control strategies to mitigate haze pollution.

ControlVAE: Tuning, Analytical Properties, and Performance Analysis.

This paper reviews the novel concept of a controllable variational autoencoder (ControlVAE), discusses its parameter tuning to meet application needs, derives its key analytic properties, and offers useful extensions and applications. ControlVAE is a new variational autoencoder (VAE) framework that combines automatic control theory with the basic VAE to stabilize the KL-divergence of VAE models to a specified value. It leverages a non-linear PI controller, a variant of the proportional-integral-derivative (PID) controller, to dynamically tune the weight of the KL-divergence term in the evidence lower bound (ELBO) using the output KL-divergence as feedback. This allows us to precisely control the KL-divergence to a desired value (set point) that is effective in avoiding posterior collapse and learning disentangled representations. While prior work developed alternative techniques for controlling the KL divergence, we show that our PI controller has better stability properties and thus better convergence, thereby producing better disentangled representations from finite training data. In order to improve the ELBO of ControlVAE over that of the regular VAE, we provide a simplified theoretical analysis to inform the choice of set point for the KL-divergence of ControlVAE. We evaluate the proposed method on three tasks: image generation, language modeling, and disentangled representation learning. The results show that ControlVAE can achieve much better reconstruction quality than the other methods for comparable disentanglement. On the language modeling task, our method can avoid posterior collapse (KL vanishing) and improve the diversity of generated text. Moreover, it can change the optimization trajectory, improving the ELBO and the reconstruction quality for image generation.

Equipping Cancer Cell Membrane Vesicles with Functional DNA as a Targeted Vaccine for Cancer Immunotherapy.

By inducing tumor-specific immune responses, tumor vaccines have recently aroused great research interest. Herein, we design a targeted nanovaccine by equipping cell membrane vesicles (CMVs) harvested from tumor cells with functional DNA including CpG oligonucleotide, an agonist for toll-like receptor 9, as well as an aptamer targeting the dendritic cell (DC)-specific intercellular adhesion molecule (ICAM)-3 grabbing nonintegrin (DC-SIGN) receptor overexpressed on DCs. Such DNA-modified CMVs could target DCs and further stimulate their maturation. Notably, our nanovaccines could trigger robust antitumor immune responses to effective delay the tumor growth. Moreover, the combination of CMV-based nanovaccines with an immune checkpoint blockade could result in improved therapeutic responses by eliminating the majority of the tumors as well as long-term immune memory to prevent tumor recurrence. Therefore, by simply assembling functional DNA on CMVs harvested from tumor cells, we propose a general platform of DC-targeted personalized cancer vaccines for effective and specific cancer immunotherapy.

CaCO3 -Encapuslated Microspheres for Enhanced Transhepatic Arterial Embolization Treatment of Hepatocellular Carcinoma.

Transcatheter arterial embolization (TAE) is an extensively applied treatment method for hepatocellular carcinoma (HCC). However, the worsened tumor microenvironment (TME, e.g., reduced pH post-TAE) may result in unsatisfactory therapeutic outcome. Herein, a new kind of embolic agent, calcium carbonate encapsulated alginate microspheres (CaCO3 -ALG MSs) are synthesized. Such CaCO3 -ALG MSs are able to neutralize the tumor pH owing to the reaction of CaCO3 with protons, which would not affect the overall morphology of microspheres after decomposition of CaCO3 . TAE treatment with CaCO3 -ALG MSs is then conducted in an orthotopic rat liver cancer model. 18 F-Fluorodeoxyglucose micropositron emission tomography/computed tomography imaging is conducted post-TAE and discovered that intra-arterial injection of CaCO3 -ALG MSs shows obvious enhanced therapeutic outcome compared to the same treatment with bare ALG MSs or the clinically used lipiodol. Further studies including analysis of immune cells in tumors, cytokine assays, and bioinformatics analysis all verify the reverse of immunosuppressive TME toward a more immunosupportive one after TAE with CaCO3 -ALG MSs. The research not only presents a new CaCO3 -containing embolic agent for enhanced TAE treatment of HCC but also highlights a clinically meaningful approach to improve cancer treatment via tumor pH neutralization.

Transmucosal Delivery of Self-Assembling Photosensitizer-Nitazoxanide Nanocomplexes with Fluorinated Chitosan for Instillation-Based Photodynamic Therapy of Orthotopic Bladder Tumors.

Theoretically, on account of improved local bioavailability of photosensitizers and attenuated systemic phototoxicity, intravesical instillation-based photodynamic therapy (PDT) for bladder cancer (BCa) would demonstrate significant advantages in comparison with the intravenous route. Actually, the low transmucosal efficiency, hypoxia regulation deficiency, as well as the biosafety risks of intravesical drug agents all have greatly limited the clinical development of instillation-based PDT for BCa. Herein, based on our recent findings on bladder intravesical vectors and photodynamic treatment, we explore and find that the conventional antiparasitic agent nitazoxanide (NTZ) by mixing with chlorine e6 (Ce6) conjugated human serum albumin (HSA), HSA-Ce6, is capable of forming self-assembled HSA-Ce6/NTZ nanoparticles (NPs). Then, the HSA-Ce6/NTZ complexes further fabricate with fluorinated chitosan (FCS), the synthesized transmucosal carrier, to form a biocompatible nanoscale system HSA-Ce6/NTZ/FCS NPs, which exhibit remarkably improved transmucosal delivery and uptake capacities compared with HSA-Ce6/NTZ alone or non-fluorinated HSA-Ce6/NTZ/CS NPs. Meanwhile, due to the metabolic regulation of tumor cells by NTZ, the tumor hypoxia could be efficaciously ameliorated to further favor PDT. This work represents a new photosensitizer nanomedicine formulation for the perfection of PDT performance through the modulation of tumor hypoxia by clinically approved agents. Thus, intravesical instillation of HSA-Ce6/NTZ/FCS NPs with favorable biocompatibility, followed by cystoscope-mediated PDT, could achieve a dramatically improved therapeutic effect to ablate orthotopic bladder tumors.

TCP/PLGA composite scaffold loaded rapamycin in situ enhances lumbar fusion by regulating osteoblast and osteoclast activity.

The purpose of this study was to develop a novel ß-tricalcium phosphate (TCP)/poly (D,L-lactic-co-glycolic acid) (PLGA) composite scaffold loaded with rapamycin that can regulate the activity of osteoblasts and osteoclasts for lumbar fusion. The TCP/PLGA composite scaffold was fabricated by cryogenic three-dimensional printing techniques and then loaded with rapamycin in situ. The structural surface morphology of the composite scaffold was tested with scanning electron microscope. To evaluate the biocompatibility of the composite scaffold in vitro, bone marrow mesenchymal stem cells (BMSCs) were cultured on the TCP/PLGA composite scaffold slide and tested with Live/Dead Viability Kit. The effect of rapamycin on osteoclast and osteoblast was studied with staining and Western blotting. The in vitro results showed that the rapamycin-loaded TCP/PLGA composite scaffold showed good biocompatibility with BMSC and released rapamycin obviously promoted the osteoblast differentiation and mineralization. In vivo study, the TCP/PLGA composite scaffold loaded with rapamycin were implanted in lumbar fusion model and study with micro-computed tomography scanning, hematoxylin-eosin, Masson, and immune-histological staining, to evaluate the effect of rapamycin on bone fusion. The in vivo results demonstrated that rapamycin-loaded TCP/PLGA composite scaffold could enhance bone formation by regulating osteoblast and osteoclast activity, respectively. In this study, the TCP/PLGA composite scaffold loaded with rapamycin was confirmed to provide great compatibility and improved performance in lumbar fusion by regulating osteoblastic and osteoclastic activity and would be a promising composite biomaterial for bone tissue engineering.

Localized cocktail chemoimmunotherapy after in situ gelation to trigger robust systemic antitumor immune responses.

Currently, there is a huge demand to develop chemoimmunotherapy with reduced systemic toxicity and potent efficacy to combat late-stage cancers with spreading metastases. Here, we report several "cocktail" therapeutic formulations by mixing immunogenic cell death (ICD)-inducing chemotherapeutics and immune adjuvants together with alginate (ALG) for localized chemoimmunotherapy. Immune checkpoint blockade (ICB) antibody may be either included into this cocktail for local injection or used via conventional intravenous injection. After injection of such cocktail into a solid tumor, in-situ gelation of ALG would lead to local retention and sustained release of therapeutics to reduce systemic toxicity. The chemotherapy-induced ICD with the help of immune adjuvant would trigger tumor-specific immune responses, which are further amplified by ICB to elicit potent systemic antitumor immune responses in destructing local tumors, eliminating metastases and inhibiting cancer recurrence. Our strategy of combining clinically used agents for tumor-localized cocktail chemoimmunotherapy possesses great potential for clinical translation.

Fluorinated Chitosan To Enhance Transmucosal Delivery of Sonosensitizer-Conjugated Catalase for Sonodynamic Bladder Cancer Treatment Post-intravesical Instillation.

Sonodynamic therapy (SDT) is a noninvasive ultrasound-triggered therapeutic strategy for site-specific treatment of tumors with great depth penetration. The design of nano-sonosensitizers suitable for SDT treatment of bladder cancer (BCa) post-intravesical instillation has not yet been reported. Herein, a transmucosal oxygen-self-production SDT nanoplatform is developed to achieve highly efficient SDT against BCa. In this system, fluorinated chitosan (FCS) is synthesized as a highly effective nontoxic transmucosal delivery carrier to assemble with meso-tetra(4-carboxyphenyl)porphine-conjugated catalase (CAT-TCPP). The formed CAT-TCPP/FCS nanoparticles after intravesical instillation into the bladder cavity exhibit excellent transmucosal and intratumoral penetration capacities and could efficiently relieve hypoxia in tumor tissues by the catalase-catalyzed O2 generation from tumor endogenous H2O2 to further improve the therapeutic efficacy of SDT to ablate orthotopic bladder tumors under ultrasound. Our work presents a nano-sonosensitizer formulation with FCS to enhance transmucosal delivery and intratumoral diffusion and CAT to improve tumor oxygenation, promising for instillation-based SDT to treat bladder tumors without the concern of systemic toxicity.

Comparison of four different types of planetary boundary layer heights during a haze episode in Beijing.

The planetary boundary layer (PBL) height mainly determines the environmental capacity for the diffusion of atmospheric pollutants, and has always been a hot issue in the study of air pollution. However, there still remains great uncertainty, partly because different PBL heights definitions and the PBL heights are obtained by various measurement instruments. Pollutants are the substances emitted, different from the atmospheric background physical properties such as wind, temperature and turbulence flux that always exist even without pollution. It is very important to distinguish PBL heights obtained from wind, temperature, turbulence quantities and the concentration of pollutants. In this paper, we express the PBL heights determined on the above four parameters as Hu, Hθ, Ht and Hc respectively, and compare them during a heave haze pollution process in Beijing using observation data and simulation results. The comparison results show that: (1) Hθ, namely the inversion layer height, decreased from approximately 1250 m to 450 m from 26 to 30 December, resulting in deteriorating pollution situation. Hc, calculated by lidar and characterizes the maximum depth of vertical diffusion of particulates, also dropped below 500 m, and on the whole, the values of Hc estimated by gradient method and Hθ were in good agreement; (2) Generally, Hc was relatively lower than Hθ and Hu, despite a high bias caused by the existence of the residual layer, multilayer aerosol structure, or lower inversion; (3) Ht estimated from turbulence quantities simulated by WRF model mainly approximated Hu, Hθ and Hc in the daytime during haze pollution, however for the nocturnal boundary layer height in the winter, Ht was seriously underestimated. The averaged PBL heights according to the pollution level showed that Hc, Hθ, Hu and Ht differed greatly on clean days, and the maximum PBL height Hu exceeded 1400 m. On clean days, the inversion intensities observed were lower, so the blocking effect of the inversion layer to pollutant diffusion was not strong enough, Hθ (886 m) deviated from Hc (1111 m). However, Hc and Ht were very close, approximately 1100 m. The decrease of PBL height led to heavy pollution, Hc, Hθ and Ht were almost 700 m. Hu was slightly higher and reduced by about 450 m during heavy pollution. The detailed analyses and comparisons of the PBL height from different variables can help improve the rational application of different methods in the determination of PBL height.

Mitochondria-targeting Au nanoclusters enhance radiosensitivity of cancer cells.

Radiotherapy is an important technology for the clinical treatment of cancer, but the patients suffer from the severe side effects after exposure to radiation. There is an urgent need to develop theranostic agents with excellent imaging capability and effective radiosensitization in order to minimize X-ray irradiation. Herein, we report an approach to synthesize peptide-templated Au nanoclusters (AuNCs) for theranostic radiosensitization. A new peptide (CCYKFR) is designed for the preparation of AuNCs with uniform size distribution and fluorescence (656 nm) of high photostability. CCYKFR-AuNCs feature highly efficient targeting/accumulation on mitochondria after endocytosis. With a series of experiments, we demonstrate that CCYKFR-AuNCs irradiated by 4 Gy X-rays can introduce a burst of mitoROS and severe DNA damage leading to cancer cell death. This study presents an important strategy to design theranostic nanomaterials with improved radiosensitization for the development of new anti-cancer therapies.