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Extracellular vesicles (EVs) are efficient natural vehicles for intercellular communication and are under extensive investigation for the delivery of diverse therapeutics including small molecule drugs, nucleic acids, and proteins. To understand the mechanisms behind the biological activities of EVs and develop EV therapeutics, it's fundamental to track EVs and engineer EVs in a customized manner. In this study, we identified, using single-vesicle flow cytometry and microscopy, the lipid DOPE (dioleoyl phosphatidyl ethanolamine) as an efficient anchor for isolated EVs. Notably, DOPE associated with EVs quickly, and the products remained stable under several challenging conditions. Moreover, conjugating fluorophores, receptor-targeting peptides or albumin-binding molecules with DOPE enabled tracking the cellular uptake, enhanceing the cellular uptake or extending the circulation time in mice of engineered EVs , respectively. Taken together, this study reports an efficient lipid anchor for exogenous engineering of EVs and further showcases its versatility for the functionalization of EVs. [Display omitted] • DOPE outperforms the benchmark cholesterol in exogenous engineering of EVs. • DOPE-engineered EVs retain high stability at common storage conditions. • Different moieties can be conjugated with DOPE and displayed on EV surface. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are promising carriers for the delivery of a variety of chemical and biological drugs. However, their efficacy is limited by the lack of cellular specificity. Available methods to improve the tissue specificity of EVs predominantly rely on surface display of proteins and peptides, largely overlooking the dense glycocalyx that constitutes the outermost layer of EVs. In the present study, we report a reconfigurable glycoengineering strategy that can endogenously display glycans of interest on EV surface. Briefly, EV producer cells are genetically engineered to co‐express a glycosylation domain (GD) inserted into the large extracellular loop of CD63 (a well‐studied EV scaffold protein) and fucosyltransferase VII (FUT7) or IX (FUT9), so that the engineered EVs display the glycan of interest. Through this strategy, we showcase surface display of two types of glycan ligands, sialyl Lewis X (sLeX) and Lewis X, on EVs and achieve high specificity towards activated endothelial cells and dendritic cells, respectively. Moreover, the endothelial cell‐targeting properties of sLeX‐EVs were combined with the intrinsic therapeutic effects of mesenchymal stem cells (MSCs), leading to enhanced attenuation of endothelial damage. In summary, this study presents a reconfigurable glycoengineering strategy to produce EVs with strong cellular specificity and highlights the glycocalyx as an exploitable trait for engineering EVs. [ABSTRACT FROM AUTHOR]

Multi-focus image fusion technology is wildly used in the digital photography, and also be considered as a pre-task of other high level vision tasks. The main purpose is producing an all-in-focus image from multiple partly focused sources accurately, naturally and efficiently. Nowadays, transformer models have achieved great success in numerous vision-related tasks, and its powerful attention modeling ability brings significant possibilities for focus property detection. To make multi-focus image fusion technology even further, in this paper, a novel multi-focus image fusion method using interactive transformer and asymmetric soft sharing is proposed. First, for taking the transformer's advantages in global context modeling and improve its limitations in diversity and efficiency, a locally-enhanced interactive approach is devised. More specifically, it used cross-scale and cross-domain computation strategy to overcome the transformer's certain limitations when comes to domain-specific task, and simultaneously alleviate the insufficient local feature perception and redundant computational cost of existing approach. Second, to cope with the problems of fusion image distortion and artifacts, the proposed method adopts a multi-task learning strategy with asymmetric soft sharing. It predicts the fusion images and decision maps at the same time for avoiding image distortion and further obtaining natural fusion effect. Experimental results reveal that, the proposed method reaches promising focus property detection performance and high-fidelity fusion results. Moreover, when compared with other state-of-the-art methods on five multi-focus image datasets, it is more prominent in both qualitative and quantitative analysis as well as efficiency. The source code is available at https://github.com/zwy0913/MFFT. • An interactive transformer architecture is proposed for both cross-scale feature integration and cross-domain information sharing. • A strategy simultaneously execute generative and discriminative task is exploited for both high fidelity and natural fusion result. • A more objective and comprehensive rank-based efficiency evaluation approach is devised for better efficiency comparison. • Experimental result reveal that proposed method reaches state-of-the-art in fusion performance as well as efficiency. [ABSTRACT FROM AUTHOR]

Selenocompounds (SeCs) are promising therapeutic agents for a wide range of diseases including cancer. The treatment results are heterogeneous and dependent on both the chemical species and the concentration of SeCs. Moreover, the mechanisms of action are poorly revealed, which most probably is due to the detection methods where the quantification is based on the total selenium as an element. To understand the mechanisms underlying the heterogeneous cytotoxicity of SeCs and to determine their pharmacokinetics, we investigated selenium speciation of six SeCs representing different categories using liquid chromatography-mass spectrometry (LC-MS) and X-ray absorption spectroscopy (XAS) and the cytotoxicity using leukemic cells. SeCs cytotoxicity was correlated with albumin binding degree as revealed by LC-MS and XAS. Further analysis corroborated the covalent binding between selenol intermediates of SeCs and albumin thiols. On basis of the Se-S model, pharmacokinetic properties of four SeCs were for the first time profiled. In summary, we have shown that cytotoxic SeCs could spontaneously transform into selenol intermediates that immediately react with albumin thiols through Se-S bond. The heterogeneous albumin binding degree may predict the variability in cytotoxicity. The present knowledge will also guide further kinetic and mechanistic investigations in both experimental and clinical settings. [ABSTRACT FROM AUTHOR]

Abnormal levels of reactive oxygen species (ROS) and the hypoxic microenvironment within bone defects are important factors that impede bone repair processes. Herein, an innovative ultrasound‐modulatable hydrogel platform with selenoprotein‐mediated antioxidant effects to promote bone injury repair is presented. This hydrogel platform encapsulates oxygen‐enriched selene‐incorporated thin‐shell silicon within methacrylate gelatin (O2‐PSSG). The resultant construct orchestrates the modulation of the bone‐defect microenvironment, thereby expediting the course of bone regeneration. Ultrasound (US) is used to regulate the pore size of the hydrogel to release selenium‐containing nanoparticles and promote the in situ synthesis of efficient intracellular selenoproteins and hydrogen peroxide consumption. As expected, O2‐PSSG rapidly releases selenocystine ([Sec]2) under US control to scavenge reactive oxygen species and maintain the homeostasis of bone marrow mesenchymal stem cells (BMSCs). Over time, the action of the system by selenoprotein increases the activation of Wnt/β‐catenin pathways and promotes the differentiation of BMSCs. Consequently, O2‐PSSG potentiates the antioxidant proficiency of BMSCs both in vitro and in vivo, alleviates hypoxic environments, promotes osteogenic differentiation, and expedites cranial bone repair in rat models. In summary, this study suggests that the designed and constructed US‐responsive antioxidant hydrogel is a promising prospective strategy for addressing bone defects and fostering bone regeneration. [ABSTRACT FROM AUTHOR]

Myeloid-derived suppressor cells (MDSCs) accumulate in tumor-bearing hosts and play a key role in the suppression of the innate and adaptive immunity. Chemotherapeutic strategies have been developed to deplete or deactivate MDSCs in different tumor models. The pyrimidine analog, 5-fluorouracil (5-FU) is found to reduce the tumor size by depleting MDSCs. Here, we asked whether the purine analog, fludarabine (Flu), could exert similar effects. Employing a lymphoma model, we demonstrated that in mice with advanced tumors (where MDSC-induced suppression was present), treatment with a single low-dose Flu (25, 50, 100 mg/kg) elevated the numbers of splenic MDSCs and serum arginase activity, and simultaneously, increased the tumor growth (only the highest dose). On the other hand, in mice with palpable tumors (where the MDSC-induced suppression was in progress), treatment with Flu had no significant effects on the tumor growth or the number of splenic MDSCs. In contrast to Flu, treatment with low-dose 5-FU, irrespective of tumor stage, caused tumor regression which coincided with significant reductions in the numbers of splenic MDSCs and blood neutrophils, but increases in the ratios of splenic CD4 + T and CD8 + T cells to suppressive MDSCs. Finally, in healthy mice (where MDSC-induced immuosuppression did not exist), 5-FU, but not Flu induced significant decreases in the number of myeloid cells in the bone marrow, naturally occurring splenic MDSCs and thymocytes. In conclusion, Flu exacerbates MDSC-induced immunosuppression in a tumor stage-dependent manner, whereas 5-FU alleviates the suppressive effects of MDSC at all stages of tumor development. [ABSTRACT FROM AUTHOR]

For the air quality data collection, a great potential is offered by unmanned aerial vehicles (UAV) with spatial and temporal resolutions. The fast scientific development has enabled the class production of UAVs cost effective in which civilian applications are serviced. A modular UAV-based platform design and development are the objectives of this study. The system comprises of five modules like the UAV, the ground station, sensors, data acquisition (DA) module, and the data fusion (DF) module. With adequate flight time, UAV platform can fly on pathways which are predetermined as shown by the results of data collection missions. The high precision data and air quality are collected through the system simultaneously. In a real manner, they are integrated and visualized. The UAV system power consumption is measured on ground and flight. The consumed current reached about 30 A when the UAV was in the air regardless the speed. [ABSTRACT FROM AUTHOR]

The aim of this work was to maximize the tumor targetability of biocompatible hyaluronan ( HA) by construction of a novel nanocarrier, using HA as the single material. HA was prefunctionalized with active amino groups, desolvated by acetone, and cross-linked by glutaraldehyde. The process was further optimized with regard to yield, stability, and particle size. The cytotoxicity of HA nanospheres ( HA- NPs) was evaluated by thiazolyl blue tetrazolium bromide and reactive oxygen species assays. A549 cells and H22-bearing Kunming mice were employed to characterize the tumor targeting of fluorescein isothiocyanate-conjugated HA- NPs. Nanospheres prepared according to the optimal formulation were characterized by a maximum yield (90%), high stability over 7 days, regular spheres (97.42 nm in diameter), and negative charge (−32.7 mV in zeta potential). In vitro results revealed that HA- NPs had little cytotoxicity and efficiently accumulated into A549 cells in a HA-dependent manner. Following systemic administration in mice, HA- NPs selectively accumulated in the tumor as demonstrated by the frozen section examination and flow cytometry analysis. In conclusion, this work successfully prepared HA- NPs and explored their potential applications for tumor targeting in terms of safety and efficacy. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:1529-1537, 2014 [ABSTRACT FROM AUTHOR]

N-acetylcysteine amide (NACA) is the amide derivative of N-acetylcysteine (NAC) that is rapidly converted to NAC after systemic administration. It has emerged as a promising thiol antioxidant for multiple indications; however, the pharmacokinetic property is yet unclear due to lack of an accurate quantification method. The present investigation aimed to develop an analytical method for simultaneous quantification of NACA and NAC in plasma. A new reagent (2-(methylsulfonyl)-5-phenyl-1,3,4-oxadiazole, MPOZ) was introduced for thiol stabilization during sample processing and storage. Further, we utilized tris (2-carboxyethyl) phosphine (TCEP) to reduce the oxidized forms of NACA and NAC. After derivatization, NACA-MPOZ and NAC-MPOZ were quantified using liquid chromatography–mass spectrometry (LC-MS). The new method was validated and found to have high specificity, linearity, accuracy, precision, and recovery for the quantification of NACA and NAC in plasma. Furthermore, the formed derivatives of NACA and NAC were stable for 48 h under different conditions. The method was utilized in pharmacokinetic study which showed that the bioavailability of NACA is significantly higher than NAC (67% and 15%, respectively). The pharmacokinetic of NACA obeyed a two-compartment open model. The glutathione (GSH)-replenishing capacity was found to be three to four-fold higher after the administration of NACA compared to that observed after the administration of NAC. In conclusion, the present method is simple, robust and reproducible, and can be utilized in both experimental and clinical studies. NACA might be considered as a prodrug for NAC. Furthermore, this is the first report describing the pharmacokinetics and bioavailability of NACA in mouse. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Selenocompounds (SeCs) are well-known nutrients and promising candidates for cancer therapy; however, treatment efficacy is very heterogeneous and the mechanism of action is not fully understood. Several SeCs have been reported to have albumin-binding ability, which is an important factor in determining the treatment efficacy of drugs. In the present investigation, we hypothesized that extracellular albumin might orchestrate SeCs efficacy. Four SeCs representing distinct categories were selected to investigate their cytotoxicity, cellular uptake, and species transformation. Concomitant treatment of albumin greatly decreased cytotoxicity and cellular uptake of SeCs. Using both X-ray absorption spectroscopy and hyphenated mass spectrometry, we confirmed the formation of macromolecular conjugates between SeCs and albumin. Although the conjugate was still internalized, possibly via albumin scavenger receptors expressed on the cell surface, the uptake was strongly inhibited by excess albumin. In summary, the present investigation established the importance of extracellular albumin binding in determining SeCs cytotoxicity. Due to the fact that albumin content is higher in humans and animals than in cell cultures, and varies among many patient categories, our results are believed to have high translational impact and clinical implications. [ABSTRACT FROM AUTHOR]

In the article "Selenoprotein-Regulated Hydrogel for Ultrasound-Controlled Microenvironment Remodeling to Promote Bone Defect Repair," Hongmei Liu, Tianfeng Chen, and their colleagues introduce an innovative hydrogel platform that can be controlled by ultrasound to promote the repair of bone injuries. The hydrogel contains a thin-shell silicon incorporated with selene and oxygen, which is released under ultrasound control. This process helps to remodel the microenvironment of bone defects by addressing hypoxia and high levels of reactive oxygen species. The researchers believe that this hydrogel platform shows promising potential for promoting bone regeneration. [Extracted from the article]

Background: The Core Outcome Measures in Effectiveness Trials (COMET) working group proposed core outcome sets (COS) to address the heterogeneity in outcome measures in clinical studies. According to the recommendations of COMET, performing systematic reviews (SRs) usually was the first step for COS development. However, the SRs that serve as a basis for COS are not specifically appraised by organizations such as COMET regarding their quality. Here, we investigated the status of SRs related to development of COS and evaluated their methodological quality. Methods: We conducted a search on PubMed to identify SRs related to COS development published from inception to May 2022. We qualitatively summarized the disease included in SR topics, and the studies included in the SRs. We evaluated the methodological quality of the SRs using AMSTAR 2.0 and compared the overall quality of SRs with and without protocols using the Mann-Whitney U test. Results: We included 175 SRs from 23 different countries or regions, and they mainly focused on five diseases: musculoskeletal system or connective tissue disease (n = 19, 10.86%), injury, poisoning, or certain other consequences of external causes (n = 18, 10.29%), digestive system disease (n = 16, 9.14%), nervous system disease (n = 15, 8.57%), and genitourinary system disease (n = 15, 8.57%). Although 88.00% of SRs included randomized controlled trials (RCTs), only a few SRs (23.38%) employed appropriate tools to assess the risk of bias in RCTs. The assessment results on the basis of AMSTAR 2.0 indicated that most SRs (93.71%) were rated as ‘’critically low’’ to ‘’low’’ in terms of overall confidence. The overall confidence of SRs with protocols was significantly higher than that without protocols (P <.001). Compared to the SRs with protocols on Core Outcome Measures in Effectiveness Trials (COMET), SRs with protocols on PROSPERO were of better overall confidence (P =.017). Conclusion: The overall quality of published SRs regarding COS development was poor. Our findings emphasize the need for researchers to carefully select the disease topic and strictly adhere to the requirements of optimal methodology when conducting a SR for the establishment of a COS. [ABSTRACT FROM AUTHOR]

Gas chimneys are key pathways for geofluid vertical migration; therefore, deciphering their formation and evolution is crucial for hydrocarbon exploration and geohazard risk assessment. However, the influences of ambient conditions (e.g. bathymetry, tectonics, sediment supply flux) on gas chimney development have not been thoroughly investigated. Using high‐resolution 3D seismic data, we have identified 59 gas chimneys beneath the Shenhu Slope (a gas hydrate test production area on the northern South China Sea margin), 35 of which intersect faults. Above fault interfaces, internal seismic structures are dominated by chaotic discontinuous reflections. Internal structures below interfaces display more continuous reflections, which are also apparent in gas chimneys, not intersecting faults. A higher degree of chaotic or discontinuous seismic reflections may indicate more fragmented networks. This may occur due to increased fluid flow along faults and concomitant fluid overpressure. The present‐day undulating seafloor comprises the inter‐canyon (IT) region, intra‐canyon (IN) region and flat slope (FD) region downstream of canyons. Gas chimneys beneath IT and IN regions exhibit elongated elliptical shapes in the plane, with the long axis azimuth (sub‐) parallel to the main strike of canyons. Chimneys beneath the IT region have larger heights than those beneath the IN and FD regions. Thicker sediment in the IT region corresponds to a higher overburden pressure, which may induce stronger overpressure in the subsurface reservoir region. This overpressure may promote chimneys gathering in the IT region. Canyons' main directions are likely to limit hydraulic fracturing due to maximum gradient boundaries between overlying sediment stress fields. This study provides insights into gas chimney distribution, morphology and structure evolution in relation to bathymetry and fault conditions. It contributes to an improved understanding of how geofluids migrate in marginal ocean basins. [ABSTRACT FROM AUTHOR]

Abstract A missed abortion (MA) is an in-utero death of the embryo or fetus before the 20th week of gestation with retained products of conception. In order to discover novel biomarkers for MA, a 1H NMR spectroscopy-based metabolomics approach was applied to detect human MA serum metabolic profiles. Serum samples were obtained from patients with MA (n = 15) and healthy controls (n = 9) for study. The NOESYPR1D spectrum combined with multi-variate pattern recognition analysis was used to cluster the groups and establish a disease-specific metabolites phenotype. Principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) models were capable of distinguishing MA patients from healthy subjects. The results revealed that 24 metabolites altered in MA patients compared with the control population. Metabolomic pathway analysis demonstrated that alanine, aspartate and glutamate metabolism, citrate cycle (TCA cycle), taurine and hypotaurine metabolism were significantly altered in MA. The results indicated that serum NMR-based metabolomic profiling method is sensitive and specific enough to distinguish MA and from healthy controls, this method could be developed as a clinically useful diagnostic tool for MA. The finding from the MA serum metabolic profiling shed a new light on further understanding of MA disease mechanisms. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) have shown promise as potential therapeutics for the treatment of various diseases. However, their rapid clearance after administration could be a limitation in certain therapeutic settings. To solve this, an engineering strategy is employed to decorate albumin onto the surface of the EVs through surface display of albumin binding domains (ABDs). ABDs were either included in the extracellular loops of select EV‐enriched tetraspanins (CD63, CD9 and CD81) or directly fused to the extracellular terminal of single transmembrane EV‐sorting domains, such as Lamp2B. These engineered EVs exert robust binding capacity to human serum albumins (HSA) in vitro and mouse serum albumins (MSA) after injection in mice. By binding to MSA, circulating time of EVs dramatically increases after different routes of injection in different strains of mice. Moreover, these engineered EVs show considerable lymph node (LN) and solid tumour accumulation, which can be utilized when using EVs for immunomodulation, cancer‐ and/or immunotherapy. The increased circulation time of EVs may also be important when combined with tissue‐specific targeting ligands and could provide significant benefit for their therapeutic use in a variety of disease indications. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) play a key role in many physiological and pathophysiological processes and hold great potential for therapeutic and diagnostic use. Despite significant advances within the last decade, the key issue of EV storage stability remains unresolved and under investigated. Here, we aimed to identify storage conditions stabilizing EVs and comprehensively compared the impact of various storage buffer formulations at different temperatures on EVs derived from different cellular sources for up to 2 years. EV features including concentration, diameter, surface protein profile and nucleic acid contents were assessed by complementary methods, and engineered EVs containing fluorophores or functionalized surface proteins were utilized to compare cellular uptake and ligand binding. We show that storing EVs in PBS over time leads to drastically reduced recovery particularly for pure EV samples at all temperatures tested, starting already within days. We further report that using PBS as diluent was found to result in severely reduced EV recovery rates already within minutes. Several of the tested new buffer conditions largely prevented the observed effects, the lead candidate being PBS supplemented with human albumin and trehalose (PBS‐HAT). We report that PBS‐HAT buffer facilitates clearly improved short‐term and long‐term EV preservation for samples stored at ‐80°C, stability throughout several freeze‐thaw cycles, and drastically improved EV recovery when using a diluent for EV samples for downstream applications. [ABSTRACT FROM AUTHOR]

Objectives. To investigate the mechanism of the protective effect of Zishenwan on pyelonephritis rats. Methods. In the rat model of pyelonephritis, protective effects of Zishenwan, the content of secretory immunoglobulin A (SIg A), and interleukins were detected by ELISA. The expressions of TLR4-NFκB pathway were detected by Western blot in renal and urinary tract mucosa. The protective effect and influence on TLR4-NFκB pathway of Zishenwan were studied. Results. Zishenwan protected rats from pyelonephritis which related to the increase of SIgA, the regulation of interleukins, and the inhibition of TLR4-NFκB pathway. Serum containing Zishenwan can significantly decrease LPS-induced expression of TLR4, MyD88, and NFκB in vitro. And the inhibition of TLR4 signal by Zishenwan related to the degradation of TRAF3 and TRAF6. Conclusions. Zishenwan protected rats from urinary tract infection by clearance of bacteria and decrease of tissue damage. 20S proteasomes mediated the degradation of TRAF3 which is important to the decrease of tissue damage from Zishenwan. [ABSTRACT FROM AUTHOR]

Purpose: In absence of direct comparison randomized controlled trials (RCTs), indirect comparison was conducted to evaluate the efficacy and safety of thrombopoietin-receptor agonists (TPO-RAs) in treatment of adult immune thrombocytopenia (ITP). Methods: We searched PubMed, Embase and Cochrane Library, Clinical Trials.gov, China National Knowledge Infrastructure, and Chinese Biomedical Literature Database from their earliest records to May 2017. RCTs comparing the TPO-RAs with placebo in adult ITP were included. Primary outcomes were the overall response rate. Secondary outcomes included safety, durable response, overall or clinically significant bleeding, and the proportion of patients receiving rescue medication. Results: Nine randomized placebo-controlled trials (786 participants) were included in this systematic review. Overall response [Risk Ratio(RR) = 0.59, 95%Confidence Interval(CI): 0.24–1.45], the incidence of adverse events (RR = 0.98, 95%CI: 0.79–1.21), durable response (RR = 0.47, 95%CI: 0.08–2.81), the incidence of overall bleeding (RR = 1.15, 95%CI: 0.52–2.57) and clinically significant bleeding (RR = 1.09, 95%CI: 0.37–3.24), and the proportion of patients receiving rescue treatment (RR = 0.95, 95%CI: 0.47–1.90) were similar between eltrombopag and romiplostim. Conclusions: Eltrombopag and romiplostim might be in efficacy and safety for adult ITP, however, physicians should still take into account drug cost and comorbidities of the specific patient while making decisions on the treatment of ITP with TPO-RAs. Registration: PROSPERO International Prospective Register of Systematic Review (PROSPERO 2017: ). [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Although chemotherapy is the primary means in colorectal cancer treatment, it is burdenerd by adverse drug effects. Drug-resistance is one of the most important challenges for chemotherapy and epithelial-mesenchymal transition (EMT) plays critical role in the development of drug resistance. Aims: The aim of this study was to investigate the mechanisms underlying the effect of astragaloside IV (AS-IV) on miR-134 expression, EMT and chemotherapeutic sensitivity in CRC. Methods: Cell proliferation, transfection assay, western blot, real-time PCR, cell migration and invasion assay and luciferase reporter assay were used to detect the effects of AS-IV on CRC. Results: AS-IV significantly inhibited CRC cell migration and invasion by inducing miR-134 expression. Moreover, AS-IV and miR-134 increased the sensitivity of CRC tumors to oxaliplatin (OXA) chemotherapy. cAMP responsive elementbinding protein 1 (CREB1), which was required for CRC cells migration, invasion and drug sensitivity, was significantly down-regulated by AS-IV. Conclusions: Our results indicated that AS-IV inhibited CRC EMT by inducing miR-134 expression which significantly down-regulated the CREB1 signaling pathway, and therefore increased the sensitivity to chemotherapy. Our findings provided new insight into the mechanisms of chemotherapy-resistant CRC, and may open new therapeutic options in the treatment of this devastating disease. [ABSTRACT FROM AUTHOR]

We report the studies on origin of peroxidase-like activity for gold nanoparticles, as well as the impact from morphology and surface charge of nanoparticles. For this purpose, we have synthesized hollow gold nanospheres (HAuNS) and gold nanorods (AuNR) with different morphology and surface chemistry to investigate their influence on the catalytic activity. We found that citrate-capped HAuNS show catalyzing efficiency in oxidation reaction of 3,3′,5,5′-tetramethylbenzidine (TMB) by hydrogen peroxide (H 2 O 2 ) and it is superior to that of cetyltrimethylammonium bromide (CTAB)-capped AuNR. The kinetics of catalytic activities from HAuNS and AuNR were respectively studied under varied temperatures. The results indicated that surface chemistry rather than morphology of nanoparticles plays an important role in the catalytic reaction of substrate. Furthermore, influencing factors such as pH, amount of nanoparticle and H 2 O 2 concentration were also investigated on HAuNS-catalyzed system. The great impact of nanoparticle surface properties on catalytic reactions makes a paradigm in constructing nanozymes as peroxidase mimic for sensing application. [ABSTRACT FROM AUTHOR]

As reported previously, large numbers of neutrophils appear in the circulation during tumor development. However, the relationship between these cells and myeloid-derived suppressor cells (MDSCs), as well as their susceptibility to myelosuppressive drugs have not been yet investigated. Here, we employed a lymphoma model to characterize tumor-associated circulating neutrophils, including their sensitivity to 5-fluorouracil (5-FU), busulfan (Bu) or treosulfan (Treo). Tumor-bearing mice exhibited pronounced elevations in the numbers of splenic MDSCs and circulating neutrophils, MDSCs, and granulocytic-MDSCs (G-MDSCs). Although these cells were not affected by 5-FU at a dose of 17 mg/kg, 50 and 100 mg/kg were equally effective in causing dramatic tumor regression, normalizing neutrophil number, and significantly reducing the numbers of splenic MDSCs, B cells, and bone marrow myeloid cells. Treatment with Bu (10, 30 or 60 mg/kg) only reduced the number of circulating neutrophils, with no effects on these other parameters. At a concentration of 500 mg/kg, Treo was ineffective, whereas, doses of 1500 and 3000 mg/kg comparably reduced the tumor size as well as the numbers of circulatory neutrophils and bone marrow myeloid cells. Finally, in comparison to 5-FU alone, a combined treatment with low-dose 5-FU and Treo resulted in a more pronounced reduction in the numbers of circulatory neutrophils and bone marrow myeloid cells, together with longer survival time. We conclude that tumor-associated circulatory neutrophils represent blood MDSCs/G-MDSCs that are highly sensitive to 5-FU and Treo, but not Bu. Moreover, the efficacy of 5-FU can be potentiated by Treo. [ABSTRACT FROM AUTHOR]

• Onset of acute graft-versus-host disease (aGVHD) induces kidney injury. • aGVHD-induced kidney injury involves up-regulation of renal NGAL protein. • aGVHD-induced kidney injury involves accumulation of lysosomes in proximal tubules. • aGVHD-induced kidney injury involves down-regulation of renal αKlotho. • aGVHD-induced kidney injury involves increases in circulatory Fgf23. Acute graft-versus-host disease (aGVHD) and kidney injury are the major complications after allogeneic hematopoietic stem cell transplantation (HSCT). Although the underlying mechanisms for the development of these complications are not yet fully understood, it has been proposed that emergence of aGVHD contributes to the development of kidney injury after HSCT. We have shown previously that aGVHD targets the kidney in a biphasic manner: at the onset, inflammatory genes are up-regulated, while when aGVHD becomes established, donor lymphocytes infiltrate the kidney. Here, we characterize renal manifestations at the onset of aGVHD. Mice receiving allogeneic bone marrow and spleen cells displayed symptoms of aGVHD and elevated serum levels of tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) within 4 days. There was concurrent kidney injury with the following characteristics: (1) elevated expression of the kidney injury biomarker, neutrophil gelatinase-associated lipocalin (NGAL), (2) accumulation of hetero-lysosomes in proximal tubule epithelial cells, and (3) reductions in αKlotho mRNA and protein and increased serum levels of fibroblast growth factor 23 (Fgf23), phosphate and urea. This situation resembled acute renal injury caused by bacterial lipopolysaccharide. We conclude that the onset of aGVHD is associated with kidney injury involving down-regulation of αKlotho, a sight that may inspire novel therapeutic approaches. [ABSTRACT FROM AUTHOR]