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[Display omitted] • X-ray-activatable hitchhiking polymer nanodrugs can cross the blood–brain barrier via neutrophil hitchhiking. • Polymer nanodrugs enable X-ray-activatable ferroptosis and immunization activation for rejecting orthotopic glioma. • Polymer nanodrug-mediated ferroptosis synergized with antitumor immune response to reject orthotopic glioma. While various tactics have been adopted to treat glioma, the clinical therapeutic efficacy of glioma is still poor due to its aggressiveness, blood–brain barrier (BBB), drug resistance and highly immunosuppressive microenvironment. We herein present X-ray-activatable hitchhiking polymer nanodrugs (HPN FcN) that can enable controlled ferroptosis and immunization for rejecting orthotopic glioma. HPN FcN are formed via loading a newly synthesized ferroptosis-inducing ferrocene prodrug and an immunotherapeutic drug (NLG919) into reactive oxygen species (ROS)-responsive semiconducting polymer nanosystems with surface embellishment of a neutrophil targeting ligand. We found that neutrophil-targeted HPN FcN could achieve effective delivery into the orthotopic glioma sites via acrossing BBB. Low-dose X-ray irradiation of HPN FcN resulted in the generation of ROS by semiconducting polymer, which not only activated the ferrocene prodrug to cause ferroptosis, but also wrecked the ROS-responsive nanosystems to on-demand deliver NLG919. Moreover, the ferroptosis effect triggered immunogenic cell death (ICD) to promote immunization, which synergized with the NLG919-based blockade for reinforcing antitumor immune response. Such a precise and effective therapeutic strategy could observably reject orthotopic glioma without significant side effects. This study demonstrates the superiorities of HPN FcN for glioma treatment via neutrophil-mediated effective delivery and X-ray-activatable therapeutic actions of ferroptosis and immunization. [ABSTRACT FROM AUTHOR]

[Display omitted] • X-ray-activatable hitchhiking polymer nanodrugs can cross the blood–brain barrier via neutrophil hitchhiking. • Polymer nanodrugs enable X-ray-activatable ferroptosis and immunization activation for rejecting orthotopic glioma. • Polymer nanodrug-mediated ferroptosis synergized with antitumor immune response to reject orthotopic glioma. While various tactics have been adopted to treat glioma, the clinical therapeutic efficacy of glioma is still poor due to its aggressiveness, blood–brain barrier (BBB), drug resistance and highly immunosuppressive microenvironment. We herein present X-ray-activatable hitchhiking polymer nanodrugs (HPN FcN) that can enable controlled ferroptosis and immunization for rejecting orthotopic glioma. HPN FcN are formed via loading a newly synthesized ferroptosis-inducing ferrocene prodrug and an immunotherapeutic drug (NLG919) into reactive oxygen species (ROS)-responsive semiconducting polymer nanosystems with surface embellishment of a neutrophil targeting ligand. We found that neutrophil-targeted HPN FcN could achieve effective delivery into the orthotopic glioma sites via acrossing BBB. Low-dose X-ray irradiation of HPN FcN resulted in the generation of ROS by semiconducting polymer, which not only activated the ferrocene prodrug to cause ferroptosis, but also wrecked the ROS-responsive nanosystems to on-demand deliver NLG919. Moreover, the ferroptosis effect triggered immunogenic cell death (ICD) to promote immunization, which synergized with the NLG919-based blockade for reinforcing antitumor immune response. Such a precise and effective therapeutic strategy could observably reject orthotopic glioma without significant side effects. This study demonstrates the superiorities of HPN FcN for glioma treatment via neutrophil-mediated effective delivery and X-ray-activatable therapeutic actions of ferroptosis and immunization. [ABSTRACT FROM AUTHOR]

A specific surface-enhanced Raman scattering (SERS) assay for dopamine (DA) based on an azo derivatization reaction is proposed for the first time by preparation of p-aminothiophenol (PATP)-modified composite SERS substrate, composed of metal–organic framework (MIL-101) decorated with Au and Ag nanoparticles. As the result, the SERS method for detection of the azo reaction between PATP and DA exhibits superior sensitivity, selectivity, and stability. A reasonable linearity in the range 10−6 to 10−10 mol∙L−1 is achieved, and the limit of detection is 1.2 × 10−12 mol∙L−1. The reactive SERS assay is free from interference in complex physiological fluid. The feasibility of the proposed SERS method for the detection of DA levels in fetal bovine serum (FBS) samples and human serum samples is validated by HPLC–MS methods, displaying promising application potential in early disease diagnosis. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is one of the deadliest primary brain tumors, but its diagnosis and curative therapy still remain a big challenge. Herein, neutrophil‐targeting semiconducting polymer nanotheranostics (SSPNiNO) is reported for second near‐infrared (NIR‐II) fluorescence imaging‐guided trimodal therapy of orthotopic glioblastoma in mouse models. The SSPNiNO are formed based on two semiconducting polymers acting as NIR‐II fluorescence probe as well as photothermal conversion agent, respectively. A thermal‐responsive nitric oxide (NO) donor and an adenosine 2A receptor (A2AR) inhibitor are co‐integrated into SSPNiNO to enable trimodal therapeutic actions. SSPNiNO are surface attached with a neutrophil‐targeting ligand to mediate their effective delivery into orthotopic GBM sites via a "Trojan Horse" manner, enabling high‐sensitive NIR‐II fluorescence imaging. Upon NIR‐II light illumination, SSPNiNO effectively generates heat via NIR‐II photothermal effect, which not only kills tumor cells and induces immunogenic cell death (ICD), but also triggers controlled NO release to strengthen tumor ICD. Additionally, the encapsulated A2AR inhibitor can modulate immunosuppressive tumor microenvironment by blocking adenosine‐A2AR pathway, which further boosts the antitumor immunological effect to observably suppress the orthotopic GBM progression. This study can provide a multifunctional theranostic nanoplatform with cumulative therapeutic actions for NIR‐II fluorescence imaging‐guided effective GBM treatment. [ABSTRACT FROM AUTHOR]

[Display omitted] • Au nanoparticles loaded on MOF-199 (Au NPs/MOF-199) present high SERS effect. • Au NPs/MOF-199 with long-term storage stability benefits real application. • Au NPs/MOF-199-based SERS assay is used to detect cancer biomarker 5-HIAA. 5-Hydroxyindole-3-acetic acid (5-HIAA) is regarded as a biomarker for diagnosis of carcinoid tumors, and it is of great significance to developing a precision assay for monitoring 5-HIAA levels. In this work, gold nanoparticles loading on the surface of MOF-199 (Au NPs/MOF-199) is prepared to propose a surface enhanced Raman scattering (SERS) assay for 5-HIAA. When 4-mercaptopyridine (4-MPy) is used as a SERS probe, on Au NPs/MOF-199, limit of detection (LOD) at 10−9 mol/L can be achieved. In addition, Au NPs/MOF-199 substrate with good preparation reproducibility shows long-term storage stability at 4 °C. Under optimal condition, the Au NPs/MOF-199-based SERS method is applied to determine 5-HIAA in serum. The concentration linear range is from 10−9 to 10−5 mol/L and LOD is of 6.40 × 10−11 mol/L. Much importantly, Au NPs/MOF-199 substrate exhibits specific response toward 5-HIAA against other metabolites in the serum due to the capturing selectivity from porous MOF-199. The recoveries obtained on spiked human serum samples locate in the span from 94.30% to 106.00% with RSD of 4.01–7.43%. Au NPs/MOF-199-based SERS sensing strategy is a promising avenue for on-field monitoring biomedical species for clinic diagnosis purpose. [ABSTRACT FROM AUTHOR]

Bone metastasis is a type of metastatic tumors that involves the spreads of malignant tumor cells into skeleton, and its diagnosis and treatment remain a big challenge due to the unique tumor microenvironment. We herein develop osteoclast and tumor cell dual‐targeting biomimetic semiconducting polymer nanocomposites (SPFeNOC) for amplified theranostics of bone metastasis. SPFeNOC contain semiconducting polymer and iron oxide (Fe3O4) nanoparticles inside core and surface camouflaged hybrid membrane of cancer cells and osteoclasts. The hybrid membrane camouflage enables their targeting to both metastatic tumor cells and osteoclasts in bone metastasis through homologous targeting mechanism, thus achieving an enhanced nanoparticle accumulation in tumors. The semiconducting polymer mediates near‐infrared (NIR) fluorescence imaging and sonodynamic therapy (SDT), and Fe3O4 nanoparticles are used for magnetic resonance (MR) imaging and chemodynamic therapy (CDT). Because both cancer cells and osteoclasts are killed synchronously via the combinational action of SDT and CDT, the vicious cycle in bone metastasis is broken to realize high antitumor efficacy. Therefore, 4T1 breast cancer‐based bone metastasis can be effectively detected and cured by using SPFeNOC as dual‐targeting theranostic nanoagents. This study provides an unusual biomimetic nanoplatform that simultaneously targets osteoclasts and cancer cells for amplified theranostics of bone metastasis. [ABSTRACT FROM AUTHOR]

Bone metastasis is a type of metastatic tumors that involves the spreads of malignant tumor cells into skeleton, and its diagnosis and treatment remain a big challenge due to the unique tumor microenvironment. We herein develop osteoclast and tumor cell dual‐targeting biomimetic semiconducting polymer nanocomposites (SPFeNOC) for amplified theranostics of bone metastasis. SPFeNOC contain semiconducting polymer and iron oxide (Fe3O4) nanoparticles inside core and surface camouflaged hybrid membrane of cancer cells and osteoclasts. The hybrid membrane camouflage enables their targeting to both metastatic tumor cells and osteoclasts in bone metastasis through homologous targeting mechanism, thus achieving an enhanced nanoparticle accumulation in tumors. The semiconducting polymer mediates near‐infrared (NIR) fluorescence imaging and sonodynamic therapy (SDT), and Fe3O4 nanoparticles are used for magnetic resonance (MR) imaging and chemodynamic therapy (CDT). Because both cancer cells and osteoclasts are killed synchronously via the combinational action of SDT and CDT, the vicious cycle in bone metastasis is broken to realize high antitumor efficacy. Therefore, 4T1 breast cancer‐based bone metastasis can be effectively detected and cured by using SPFeNOC as dual‐targeting theranostic nanoagents. This study provides an unusual biomimetic nanoplatform that simultaneously targets osteoclasts and cancer cells for amplified theranostics of bone metastasis. [ABSTRACT FROM AUTHOR]

[Display omitted] • Magnetic Au/Cys-Fe 3 O 4 /MIL-101is synthesized for the detection of parathion-methyl. • The stable SERS substrate shows high enhancement for Raman scattering. • The detection sensitivity is further promoted by magnetically induced effect. • Such SERS substrate is used for selective detection for parathion-methyl in juice. Parathion-methyl (PTM) as one of organophosphate insecticides was once widely used to control pests on rice, cotton and other crops. Recently, due to high toxicity to people, PTM has been prohibited in vegetable and fruit production process but illegal abuse of PTM occasionally happens in some areas. Conventional detection methods for PTM suffer from cumbersome sample pretreatment or insufficient sensitivity. In this work, we rationally prepare metal organic framework MIL-101 decorated with Au nanoparticles and cysteine modified Fe 3 O 4 (designated as /Cys-Fe 3 O 4 /MIL-101) as magnetic surface enhanced Raman scattering (SERS) substrate. Benefiting the magnetically induced improvement effect, by using Au/Cys-Fe 3 O 4 /MIL-101, the SERS method exhibits superior sensitivity and detection reproducibility, which is successfully used to detect PTM residue in juice. The limit of detection for PTM at 5 ppb in juice is reached with a good linearity ranging from 10−11 to 10-7 M, meeting the requirement of the European Union Standard. [ABSTRACT FROM AUTHOR]

Laser interstitial thermal therapy (LITT), which ablates diseased brain tissues via hyperthermia, has offered novel treatment approach for epilepsy; however, the current LITT protocols still lack ablation selectivity and disease‐modifying efficacy. A second near‐infrared (NIR‐II) activatable nitric oxide (NO) releasing nanoactuator is reported here for photothermal combinational modulation of epileptogenic focus. The nanoactuator is prepared by conjugating NO donor S‐nitrosoglutathione (GSNO) onto polydopamine‐coated gold (Au) nanoparticles (NPs), which shows excellent photothermal conversion capability and controlled NO‐releasing property upon illumination in the NIR‐II window. Both in vitro and in vivo study demonstrate that the nanoactuator could exert stronger cell killing effects as compared to its counterpart. Furthermore, the NIR‐II‐activated NO release could inhibit P‐gp expression by regulating NF‐κb pathway, resulting in reprogramming of epileptogenic microenvironment. This study thus offers a novel regulating strategy for the treatment of drug‐resistant epilepsy. [ABSTRACT FROM AUTHOR]

A highly sensitive triple-amplification assay for the detection of microRNA (miRNA) let-7a is reported in this work. The assay relies on the formation of magnetic two-dimensional DNA/Fe3O4 nanosheet networks initiated by the target miRNA-associated hybridization chain reaction. The Fe3O4 nanosheets in the DNA/Fe3O4 networks display peroxidase-like catalytic activity towards a colorimetric reaction, thereby producing a highly sensitive signal for the quantification of let-7a. Under optimal conditions, the assay achieved a detection limit of 13 aM at a signal-to-noise ratio of 3 and a linear calibration plot between 0.05 fM and 12 nM. Successful attempts were made in the quantification of let-7a in serum samples. [ABSTRACT FROM AUTHOR]

Picric acid (PA) has a severe environmental risk and security problem owing to its unstable property and high toxic. On-field selective and sensitive detection of trace PA is also a challenging task. PA molecules due to poor affinity to surface of noble metal nanoparticles are hardly detectable by surface-enhanced Raman scattering (SERS) method. In this work, silver shell and gold core nanoparticles with inositol hexaphosphate inner gap (Au@IP 6 @AgNPs) is prepared and then two-dimension (2D) substrate at the ITO surface (designated as ITO-Au@IP 6 @Ag) is formed via self-assembly. For capturing PA, we firstly modify creatinine (CRN) molecules onto the ITO-Au@IP 6 @Ag designated as ITO-Au@IP 6 @Ag@CRN to construct a specific SERS chip for PA, taking advantage of Jaffe reaction between PA and CRN. The generated Jaffe Complex has the greater Raman scattering section with respect to PA. Therefore, such chip-based SERS array for PA shows a good sensitivity and selectivity and the limit of detection at 3.9 × 10−11 mol/L could be reached. As real applications, the ITO-Au@IP 6 @Ag@CRN chips have been used for identification of PA in environmental samples such as clothing, envelope, and luggage, and determination of trace PA (~10−7 mol/L) in lake water. It demonstrates a promising perspective for on-site detection of the explosive for public security. [Display omitted] • Creatinine modified ITO-Au@IP 6 @Ag as a SERS chip for picric acid (PA) is made. • Based on Jaffe reaction, the SERS chip is used to detect trace PA selectively. • As applications, SERS chip-based inspection of PA residues in environmental samples is performed. [ABSTRACT FROM AUTHOR]

[Display omitted] • Gold core and silver shell substrate with inositol hexaphosphate inner gap is prepared. • Ag@IP 6 @AuNPs substrate generates great surface plasmon resonance hot spots. • The stable Ag@IP 6 @AuNPs substrate is used for SERS detection of trace Penicillin G in milk. The abuse of Penicillin G (PG) in the feeds of livestock resulted in health risk for human being via the food chain. It is urged to develop the rapid and sensitive method for monitoring PG residue in food products. In this work, silver shell was formed on the core gold nanoparticles protected with inositol hexaphosphate (IP 6), designated as Ag@IP 6 @AuNPs, which is used as surface enhanced Raman scattering (SERS) substrate. Thanks to the presence of IP 6 between silver shell and core gold, Ag@IP 6 @AuNPs show high storage stability. The great surface plasmon resonance of hot spot field generated in the molecular gap between core-shell extends to nanoparticle surface results in synergistic enhancement of Raman scattering effect. Ag@IP 6 @AuNPs-based SERS assay is employed to successfully detect trace PG residue in milk with a wide linear quantitative range from 10−5 to 10-11 mol/L and the limit of detection at 10-12 mol/L. The sensitivity of such Raman protocol meets the requirement for the maximum residue limit (MRL, 4 μg/kg or 1.2 × 10−8 mol/L) of PG in milk products set by the European Union. Additionally, the detection recoveries in the range from 92.18 % to 101.4 % mean the acceptable robustness of such SERS method. The proposed SERS method could be advanced to realize the on-field determination of PG in milk for guarantee of food safety. [ABSTRACT FROM AUTHOR]

A novel and low-cost DNAzyme, Ni/Fe layered double hydroxide (LDH) nanosheet/G-quadruplex (without hemin) with enhanced peroxidase-mimic activity was designed. The catalytic mechanism was investigated. The detection of Cu(II) in actual serum samples could be realized sensitively via this efficient DNAzyme-based method. [ABSTRACT FROM AUTHOR]

Objective: Detecting brain abnormalities in clinical high-risk populations before the onset of psychosis is important for tracking pathological pathways and for identifying possible intervention strategies that may impede or prevent the onset of psychotic disorders. Co-occurring cellular and extracellular white matter alterations have previously been implicated after a first psychotic episode. The authors investigated whether or not cellular and extracellular alterations are already present in a predominantly medication-naive cohort of clinical high-risk individuals experiencing attenuated psychotic symptoms.Methods: Fifty individuals at clinical high risk, of whom 40 were never medicated, were compared with 50 healthy control subjects, group-matched for age, gender, and parental socioeconomic status. 3-T multishell diffusion MRI data were obtained to estimate free-water imaging white matter measures, including fractional anisotropy of cellular tissue (FAT) and the volume fraction of extracellular free water (FW).Results: Significantly lower FAT was observed in the clinical high-risk group compared with the healthy control group, but no statistically significant FW alterations were observed between groups. Lower FAT in the clinical high-risk group was significantly associated with a decline in Global Assessment of Functioning Scale (GAF) score compared with highest GAF score in the previous 12 months.Conclusions: Cellular but not extracellular alterations characterized the clinical high-risk group, especially in those who experienced a decline in functioning. These cellular changes suggest an early deficit that possibly reflects a predisposition to develop attenuated psychotic symptoms. In contrast, extracellular alterations were not observed in this clinical high-risk sample, suggesting that previously reported extracellular abnormalities may reflect an acute response to psychosis, which plays a more prominent role closer to or at onset of psychosis. [ABSTRACT FROM AUTHOR]

This work reports that the magnetically oriented porous hydrogel installed on the glove sensor is first time constructed as a wearable solidoid sensing platform for on-site chemical contamination evaluation. Such hydrogels with uniform porous distribution and highly tunable anisotropic MWCNT-Fe 3 O 4 strips act as the electrochemical cell and medium of analyte diffusion to enhance the permeability and effectively speed electrolyte ion diffusion. The MWCNT-Fe 3 O 4 strips doped in the three-dimensional rigid hydrogel exhibit a quick recovery from compressive strength within 2 min. The hydrogel could be easily and tightly assembled onto the wearable glove sensor by using a magnet, improving the stability and sensitivity of the sensing platform. The wearable glove sensor is successfully applied for rapid detection (< 5 min) of trace Cd2+ in tea, rice, and soil. [Display omitted] • Magnetically oriented hydrogel is prepared to realize wearable electrochemical solid sensing. • Magnetic porous hydrogel has excellent conductivity and mechanical performance. • The wearable sensing platform is used to monitor Cd2+ in tea, soil, and rice powder. • Swipe sampling method is introduced to pretreat the solid samples on-field. Developing wearable sensors to determine chemical contamination in solidoid is currently a great challenge. Hydrogels with polymeric networks have been employed as electrochemical cells and media to realize wearable solidoid sensing. However, it is still a hard task to enable hydrogel to simultaneously possess effective mass transfer, mechanical robustness as well as easy and tight adhesion to sensing electrodes. Routinely, a hydrogel with improved adhesion to the electrode surface by introducing additives may deteriorate the mass transfer capability. Increasing the porosity of hydrogel could enhance mass diffusion but sacrifices mechanical robustness. Herein, a composite hydrogel is achieved by embedding magnetic oriented MWCNT-Fe 3 O 4 strips in porous agarose (MMFPA), which exhibits enhanced permeability and speeding diffusion of electrolyte ions. Moreover, the orientation in order and strip-like MWCNT-Fe 3 O 4 three-dimensional composites improve the compressive strength of hydrogel, which could recover back within 2 min in water after removal of pressure. Such magnetic hydrogel is beneficial to be assembled to the wearable glove sensor by using magnets to achieve a stable and compact sensing platform. As the application example, the resultant wearable sensing protocol is successfully utilized to monitor Cd2+ trace residues in rice, tea, and soil with an affordable response as low as 0.112 mg/kg and rapid signal acquisition (<5 min). It paves an attractive, accessible, and effective way to on-site evaluate solidoid Cd2+ level for forewarning food safety and environmental risk. [ABSTRACT FROM AUTHOR]

Glutathione, referred to as GSH, abnormal physiologic level of GSH is an indication to some neurodegenerative diseases and cancers. A measurement of cellular GSH calls for rapid, sensitive, and selective methods. In this work, we rationally design and prepare Au@MnO 2 core-shell composite nanoparticles combining with tetramethylbenzidine (TMB) molecules to determine intracellular GSH by Surface enhanced Raman scattering (SERS) technique. MnO 2 plays multifunctional roles in the method, including the participation in catalyzing TMB to molecules form dimer charge-transfer complex (CTC) which own a great SERS signal reporter. With the addition of GSH, the MnO 2 will be dissolving detaching CTC molecules from the surface of Au@MnO 2 and resulting in a signal-off off SERS response and indirect and sensitive detection of GSH could be realized. The limit of detection of GSH by SERS method is as low as 0.1 μmol/L and a good linear relationship of GSH is found in the range from 0.5 to 30 μmol/L. Au@MnO 2 -SERS assay is successfully applied to detect cellular GSH, which is validated by using Enzyme-linked-immunoassay-based Kit. The Au@MnO 2 -SERS protocol has promising potential for clinical application. [ABSTRACT FROM AUTHOR]

Youth football players may incur hundreds of repetitive head impacts (RHI) in one season. Our recent research suggests that exposure to RHI during a critical neurodevelopmental period prior to age 12 may lead to greater later-life mood, behavioral, and cognitive impairments. Here, we examine the relationship between age of first exposure (AFE) to RHI through tackle football and later-life corpus callosum (CC) microstructure using magnetic resonance diffusion tensor imaging (DTI). Forty retired National Football League (NFL) players, ages 40-65, were matched by age and divided into two groups based on their AFE to tackle football: before age 12 or at age 12 or older. Participants underwent DTI on a 3 Tesla Siemens (TIM-Verio) magnet. The whole CC and five subregions were defined and seeded using deterministic tractography. Dependent measures were fractional anisotropy (FA), trace, axial diffusivity, and radial diffusivity. Results showed that former NFL players in the AFE <12 group had significantly lower FA in anterior three CC regions and higher radial diffusivity in the most anterior CC region than those in the AFE ≥12 group. This is the first study to find a relationship between AFE to RHI and later-life CC microstructure. These results suggest that incurring RHI during critical periods of CC development may disrupt neurodevelopmental processes, including myelination, resulting in altered CC microstructure. [ABSTRACT FROM AUTHOR]

CODAS syndrome is a multi-system developmental disorder characterized by cerebral, ocular, dental, auricular, and skeletal anomalies. Using whole-exome and Sanger sequencing, we identified four LONP1 mutations inherited as homozygous or compound-heterozygous combinations among ten individuals with CODAS syndrome. The individuals come from three different ancestral backgrounds (Amish-Swiss from United States, n = 8; Mennonite-German from Canada, n = 1; mixed European from Canada, n = 1). LONP1 encodes Lon protease, a homohexameric enzyme that mediates protein quality control, respiratory-complex assembly, gene expression, and stress responses in mitochondria. All four pathogenic amino acid substitutions cluster within the AAA + domain at residues near the ATP-binding pocket. In biochemical assays, pathogenic Lon proteins show substrate-specific defects in ATP-dependent proteolysis. When expressed recombinantly in cells, all altered Lon proteins localize to mitochondria. The Old Order Amish Lon variant ( LONP1 c.2161C>G[p.Arg721Gly]) homo-oligomerizes poorly in vitro. Lymphoblastoid cell lines generated from affected children have (1) swollen mitochondria with electron-dense inclusions and abnormal inner-membrane morphology; (2) aggregated MT-CO2, the mtDNA-encoded subunit II of cytochrome c oxidase; and (3) reduced spare respiratory capacity, leading to impaired mitochondrial proteostasis and function. CODAS syndrome is a distinct, autosomal-recessive, developmental disorder associated with dysfunction of the mitochondrial Lon protease. [ABSTRACT FROM AUTHOR]