GLUT1 mediates bronchial epithelial E-cadherin disruption in TDI-induced steroid-insensitive asthma.

OBJECTIVE: Down-regulation of bronchial epithelial E-cadherin is an important of feature of severe asthma, including steroid-insensitive asthma. Yet, the mechanisms involved in E-cadherin disruption are not fully understood. This study was aimed to investigate the role of glucose transporter 1 (GLUT1) in dysregulation of E-cadherin in toluene diisocyanate (TDI)-induced steroid-insensitive asthma. METHODS: A murine model of steroid-insensitive asthma was established by TDI sensitization and aerosol inhalation. Selective GLUT1 antagonists WZB117 and BAY876 were given to BALB/c mice after airway challenge. In vitro, primary human bronchial epithelial cells (HBECs) cultured in an airway-liquid interface (ALI) were exposed to TDI. RESULTS: TDI exposure markedly up-regulated GLUT1 in murine lungs and HBECs. Pharmacological inhibition of GLUT1 with BAY876 decreased airway hyperresponsiveness, neutrophil and eosinophil accumulation, as well as type 2 inflammation in vivo. Besides, the TDI-induced down-regulated expression of full-length E-cadherin was also partly recovered, accompanied by inhibited secretion of soluble E-cadherin (sE-cadherin). WZB117 also exhibited mild therapeutic effects, though not significant. In vitro, treatment with GLUT1 inhibitor relieved the TDI-induced disruption of E-cadherin in HBECs. CONCLUSIONS: Taken together, our data demonstrated that GLUT1 modulates bronchial epithelial E-cadherin dysfunction production in TDI-induced steroid-insensitive asthma.

Ferroptosis contributes to airway epithelial E-cadherin disruption in a mixed granulocytic asthma mouse model.

Aberrant expression of airway epithelial E-cadherin is a key feature of asthma, yet the underlying mechanisms are largely unknown. Ferroptosis is a novel form of regulated cell death involved in asthma pathogenesis. This study was aimed to evaluate the role of ferroptosis and to investigate whether ferroptosis mediates E-cadherin disruption in mixed granulocyte asthma (MGA). Two murine models of MGA were established using toluene diisocyanate (TDI) or ovalbumin with Complete Freund's Adjuvant (OVA/CFA). Specific antagonists of ferroptosis, including Liproxstatin-1 (Lip-1) and Ferrostatin-1 (Fer-1) were given to the mice. The allergen-exposed mice displayed markedly shrunk mitochondria in the airway epithelia, with decreased volume and denser staining accompanied by down-regulated GPX4 as well as up-regulated FTH1 and malondialdehyde, which are markers of ferroptosis. Decreased pulmonary expression of E-cadherin was also observed, with profound loss of membrane E-cadherin in the airway epithelia, as well as increased secretion of sE-cadherin. Treatment with Lip-1 not only showed potent protective effects against the allergen-induced airway hyperresponsiveness and inflammatory responses, but also rescued airway epithelial E-cadherin expression and inhibited the release of sE-cadherin. Taken together, our data demonstrated that ferroptosis mediates airway epithelial E-cadherin dysfunction in MGA.

GLUT1 mediates the release of HMGB1 from airway epithelial cells in mixed granulocytic asthma.

Asthma is quite heterogenous and can be categorized as eosinophilic, mixed granulocytic (presence of both eosinophils and neutrophils in the airways) and neutrophilic. Clinically, mixed granulocytic asthma (MGA) often tends to be severe and requires large doses of corticosteroids. High mobility group box 1 (HMGB1) is one of the epithelium-derived alarmins that contributes to type 2 inflammation and asthma. This study was aimed to investigate the role of glucose transporter 1 (GLUT1) in modulation of airway epithelial HMGB1 production in MGA. Induced sputum and bronchial biopsy specimens were obtained from healthy subjects and asthma patients. BALB/c mice, the airway epithelial cell line BEAS-2B, or primary human bronchial epithelial cells (HBECs) were immunized with allergens. Intracellular and extracellular HMGB1 were both detected. The role of GLUT1 was assessed by using a pharmacological antagonist BAY876. MGA patients have a significant higher sputum HMGB1 level than the health and subjects with other inflammatory phenotypes. Nuclear-to-cytoplasmic translocation of HMGB1 was also observed in the bronchial epithelia. Allergen exposure markedly induced GLUT1 expression in murine lungs and cultured epithelial cells. Pharmacological antagonism of GLUT1 with BAY876 dramatically decreased airway hyperresponsiveness, neutrophil and eosinophil accumulation, as well as type 2 inflammation in murine models of MGA. Besides, the allergen-induced up-regulation of HMGB1 was also partly recovered by BAY876, accompanied by inhibited secretion into the airway lumen. In vitro, treatment with BAY876 relieved the allergen-induced over-expression and secretion of HMGB1 in airway epithelia. Taken together, our data indicated that GLUT1 mediates bronchial epithelial HMGB1 release in MGA.

GLUT1 contributes to impaired epithelial tight junction in the late phase of acute lung injury.

Dysfunction of epithelial barrier is crucial for the development of acute lung injury (ALI). This study was aimed to evaluate the role of glucose transporter 1 (GLUT1) in dysregulation of epithelial tight junction in ALI. GLUT1 was inhibited with specific antagonists WZB117 or BAY876 to see the effects on epithelial tight junction in a well-established LPS-induced mouse ALI model as well as in vitro cultured epithelial cells. Pharmacological inhibition of GLUT1 with WZB117 at either a low or high dose had no effects on lung injury and inflammation 24 h after LPS challenge, but significantly decreased the pulmonary inflammatory responses induced by LPS at 72 h with a high dose, which was verified by treatment with BAY876. WZB117 or BAY876 also recovered the expression of epithelial tight junction proteins ZO-1 and occludin. In cultured BEAS-2B and A549 cells, LPS induced increased GLUT1 expression, accompanied by decreased expression of tight junction protein ZO-1 and occludin. Blockade of GLUT1 restored LPS-induced disruption of ZO-1 and occludin in BEAS-2B rather than A549. Taken together, our results showed that GLUT1 is responsible for dysfunction of epithelial tight junctions in the late phase of LPS-induced ALI.

Mechanical stretch promotes apoptosis and impedes ciliogenesis of primary human airway basal stem cells.

BACKGROUND: Airway basal stem cells (ABSCs) have self-renewal and differentiation abilities. Although an abnormal mechanical environment related to chronic airway disease (CAD) can cause ABSC dysfunction, it remains unclear how mechanical stretch regulates the behavior and structure of ABSCs. Here, we explored the effect of mechanical stretch on primary human ABSCs. METHODS: Primary human ABSCs were isolated from healthy volunteers. A Flexcell FX-5000 Tension system was used to mimic the pathological airway mechanical stretch conditions of patients with CAD. ABSCs were stretched for 12, 24, or 48 h with 20% elongation. We first performed bulk RNA sequencing to identify the most predominantly changed genes and pathways. Next, apoptosis of stretched ABSCs was detected with Annexin V-FITC/PI staining and a caspase 3 activity assay. Proliferation of stretched ABSCs was assessed by measuring MKI67 mRNA expression and cell cycle dynamics. Immunofluorescence and hematoxylin-eosin staining were used to demonstrate the differentiation state of ABSCs at the air-liquid interface. RESULTS: Compared with unstretched control cells, apoptosis and caspase 3 activation of ABSCs stretched for 48 h were significantly increased (p < 0.0001; p < 0.0001, respectively), and MKI67 mRNA levels were decreased (p < 0.0001). In addition, a significant increase in the G0/G1 population (20.2%, p < 0.001) and a significant decrease in S-phase cells (21.1%, p < 0.0001) were observed. The ratio of Krt5+ ABSCs was significantly higher (32.38% vs. 48.71%, p = 0.0037) following stretching, while the ratio of Ac-tub+ cells was significantly lower (37.64% vs. 21.29%, p < 0.001). Moreover, compared with the control, the expression of NKX2-1 was upregulated significantly after stretching (14.06% vs. 39.51%, p < 0.0001). RNA sequencing showed 285 differentially expressed genes, among which 140 were upregulated and 145 were downregulated, revealing that DDIAS, BIRC5, TGFBI, and NKX2-1 may be involved in the function of primary human ABSCs during mechanical stretch. There was no apparent difference between stretching ABSCs for 24 and 48 h compared with the control. CONCLUSIONS: Pathological stretching induces apoptosis of ABSCs, inhibits their proliferation, and disrupts cilia cell differentiation. These features may be related to abnormal regeneration and repair observed after airway epithelium injury in patients with CAD.

Long-term efficacy and safety of the Dumon stent for treatment of benign airway stenosis.

BACKGROUND: The long-term efficacy of the Dumon stent in the treatment of benign airway stenosis is unclear. OBJECTIVE: The objective of this study was to evaluate the long-term efficacy and safety of the Dumon stent in patients with benign airway stenosis. METHODS: We retrospectively reviewed patients with benign airway stenosis who were treated with a Dumon stent at the First Affiliated Hospital of Guangzhou Medical University between March 2014 and October 2021. We included patients with successful removal of silicone stents after implantation. The clinical data and information on bronchoscopic interventional procedures and related complications were collected and analyzed. RESULTS: Ninety-nine patients with benign airway stenosis were included. The stent was placed mainly in the trachea (44.4%) and left main bronchus (43.4%). The main type of stenosis was post-tuberculosis bronchial stenosis (57.6%). The overall cure rate was 60.6%. Stent-related complications included retention of secretions (70.7%), granuloma formation (67.7%), stent angulation (21.2%), and stent migration (12.1%). The stent was less effective for left main bronchus stenosis (p = 0.012). Multivariate logistic regression analysis identified that stent placement for more than 13 months, a stent-intervention number of ⩽ 1 predicted a favorable outcome. CONCLUSION: The efficacy and safety of the Dumon stent for benign airway stenosis need improvement. The stent is less effective for left main bronchus stenosis; regular follow-up is required in such cases. Stent placement for > 13 months and no more than once stent intervention within a 6-month period were associated with a favorable outcome.

Microorganism-Templated Nanoarchitectonics of Hollow TiO2-SiO2 Microspheres with Enhanced Photocatalytic Activity for Degradation of Methyl Orange.

In this study, hollow SiO2 microspheres were synthesized by the hydrolysis of tetraethyl orthosilicate (TEOS) according to the Stober process, in which Pichia pastoris GS 115 cells were served as biological templates. The influence of the preprocessing method, the TEOS concentration, the ratio of water to ethanol, and the aging time on the morphology of microspheres was investigated and the optimal conditions were identified. Based on this, TiO2-SiO2 microspheres were prepared by the hydrothermal process. The structures and physicochemical properties of TiO2-SiO2 photocatalysts were systematically characterized and discussed. The photocatalytic activity for the degradation of methyl orange (MO) at room temperature under Xe arc lamp acting as simulated sunlight was explored. The result showed that the as-prepared TiO2-SiO2 microspheres exhibited a good photocatalytic performance.

BMP-2 and VEGF-A modRNAs in collagen scaffold synergistically drive bone repair through osteogenic and angiogenic pathways.

Bone has a remarkable potential for self-healing and repair, yet several injury types are non-healing even after surgical or non-surgical treatment. Regenerative therapies that induce bone repair or improve the rate of recovery are being intensely investigated. Here, we probed the potential of bone marrow stem cells (BMSCs) engineered with chemically modified mRNAs (modRNA) encoding the hBMP-2 and VEGF-A gene to therapeutically heal bone. Induction of osteogenesis from modRNA-treated BMSCs was confirmed by expression profiles of osteogenic related markers and the presence of mineralization deposits. To test for therapeutic efficacy, a collagen scaffold inoculated with modRNA-treated BMSCs was explored in an in vivo skull defect model. We show that hBMP-2 and VEGF-A modRNAs synergistically drive osteogenic and angiogenic programs resulting in superior healing properties. This study exploits chemically modified mRNAs, together with biomaterials, as a potential approach for the clinical treatment of bone injury and defects.

Application of computer-assisted navigation in treating congenital maxillomandibular syngnathia: A case report.

BACKGROUND: Congenital maxillomandibular syngnathia is an extremely rare disorder characterized by craniofacial malformations and inability to open the mouth adequately, which leads to problems with feeding, swallowing, and breathing as well as temporomandibular joint ankylosis. The main goal of the surgery is to release the ankylosis, establish functioning mandible, and prevent re-fusion. However, surgical procedures for this disease are rarely reported. CASE SUMMARY: Here, we report a 7-mo-old girl with bilateral maxillomandibular syngnathia. The patient presented with difficulty in feeding, breathing, sounding, and swallowing and had developmental dysplasia. For treatment, we performed bone isolation by computer-assisted navigation and used silicone to fix the wound surface to prevent refusion of bone. To our knowledge, this is the only syngnathia case in the literature treated using computer-assisted navigation. With the guidance of precise navigation, we were able to minimize operation time by at least one hour, the patient's blood vessels, nerves, and tooth germs were well protected, and excessive bleeding was avoided. After six weeks, the patient showed improvement in mouth opening and no major issues of feeding. CONCLUSION: Application of computer-assisted navigation can significantly improve accuracy, effectiveness, and surgical safety in correcting congenital maxillomandibular syngnathia.

[Simultaneous rapid determination of 12 anti-allergic chemical drugs in Chinese traditional patent medicine and health food by supercritical fluid chromatography tandem mass spectrometry with solid phase extraction].

An analytical method was developed for simultaneous rapid determination of 12 anti-allergic chemical drugs in Chinese traditional patent medicine and health food by supercritical fluid chromatography tandem mass spectrometry with solid phase extraction (SPE-SFC-MS/MS). Samples were extracted with methanol by sonification and then purified by Oasis mixed-model cation exchange SPE. The extracts were separated on a Waters Trefoil CEL1 (150 mm×3.0 mm, 2.5 µ m) column with a mobile phase consisting of carbon dioxide-methanol containing 0.1% (v/v) ammonia water in a gradient elution mode, at a flow rate of 1.2 mL/min. The column temperature was 45℃ and the back pressure was 12.4×106 Pa. The whole analysis was completed in 10 min. The 12 anti-allergic chemical drugs were detected by an electrospray ion source in positive or negative modes with a multiple reaction monitoring (MRM) mode. The calibration curves of the 12 anti-allergic chemical drugs showed good linearities in the range of 5-250 µ g/L with the correlation coefficients (r) ≥ 0.998. The limits of detection (LODs) were 0.141-0.262 µ g/L, and the limits of quantification (LOQs) were 0.703-1.308 µ g/L. The recoveries of the 12 anti-allergic chemical drugs at spiked levels of 10, 20 and 100 µ g/L were in the range of 76.1%-112.5%, and the relative standard deviations (RSDs) were 1.1%-8.3% (n=6). The method is simple, sensitive and reliable. It has been successfully used for the detection of illegally added anti-allergic chemical drugs in Chinese traditional patent medicine and health food.

Complete genome sequence of the first bluetongue virus serotype 7 isolate from China: evidence for entry of African-lineage strains and reassortment between the introduced and native strains.

Bluetongue virus (BTV) mainly infects sheep but can be transmitted to other domestic and wild ruminants, resulting in a considerable financial burden and trade restriction. Our understanding of the origin, movement, and distribution of BTV has been hindered by the fact that this virus has a segmented genome with the possibility of reassortment, the existence of 27 identified serotypes, and a lack of complete sequences of viruses isolated from different parts of the world. BTV serotype 7 is one of the prevalent BTV serotypes in Asia. Nonetheless, no complete genomic sequence of an Asian isolate of this serotype is available. In an effort to understand the molecular epidemiology of BTV infection in China, for the first time, we report here the complete genome sequence of a BTV serotype 7 strain, GDST008, which was isolated in 2014 in China. This sequence also represents the first complete genome sequence of a BTV serotype 7 from Asia and the third one in the world. Sequence analysis suggests that GDST008 consists of segments from BTV viruses of African lineage as well as those from China. Together, these results improve our understanding of the origin, emergence/re-emergence, and movement of BTV and thus can be applied in the development of vaccines and diagnostics.

Bio-inspired synthesis of metal nanomaterials and applications.

This critical review focuses on recent advances in the bio-inspired synthesis of metal nanomaterials (MNMs) using microorganisms, viruses, plants, proteins and DNA molecules as well as their applications in various fields. Prospects in the design of bio-inspired MNMs for novel applications are also discussed.

Design of functional nanoparticles and assemblies for theranostic applications.

Nanostructured materials have found increasing applications in medical therapies and diagnostics (theranostics). The main challenge is the ability to impart the nanomaterials with structurally tailored functional properties which can effectively target biomolecules but also provide signatures for effective detection. The harnessing of functional nanoparticles and assemblies serves as a powerful strategy for the creation of the structurally tailored multifunctional properties. This article highlights some of the important design strategies in recent investigation of metals (especially gold and silver), and magnetically functionalized nanoparticles, and molecularly assembled or biomolecularly conjugated nanoparticles with tunable optical, spectroscopic, magnetic, and electrical properties for applications in several areas of potential theranostic interests. Examples include colorimetric detection of amino acids and small peptides, surface-enhanced Raman scattering detection of biomolecular recognition of proteins and DNAs, delivery in cell transfection and bacteria inactivation, and chemiresistive detection of breath biomarkers. A major emphasis is placed on understanding how the control of the nanostructures and the molecular and biomolecular interactions impact these biofunctional properties, which has important implications for bottom-up designs of theranostic materials.

Facile fabrication of Pd nanoparticle/Pichia pastoris catalysts through adsorption-reduction method: a study into effect of chemical pretreatment.

Based on rapid adsorption and incomplete reduction in Pd (II) ions by yeast, Pichia pastoris (P. pastoris) GS115, the effects of pretreatment on adsorption and reduction of Pd (II) ions and the catalytic properties of Pd NP/P. pastoris catalysts were studied. Interestingly, the results showed that the adsorption ability of the cells for Pd (II) ions was greatly enhanced after they were pretreated with aqueous HCl, aqueous NaOH and methylation of amino group. For the reduction in the adsorbed Pd (II) ions, more slow reduction rates by pretreated P. pastoris cells were displayed compared with the cells without pretreatment. Using the reduction of 4-nitrophenol as a model reaction, the Pd NP/P. pastoris catalysts based on the cells after pretreatment with aqueous HCl, aqueous NaOH and methylation of amino group exhibited higher stability than the unpretreated cells. The enhanced stability of the Pd catalysts can be attributed to smaller Pd NPs, better dispersion of the Pd NPs, and stronger binding forces of the pretreated P. pastoris for preparing the Pd NPs. This work exemplifies enhancing the stability of Pd catalysts through pretreatments.

The zoonotic risk of Ancylostoma ceylanicum isolated from stray dogs and cats in Guangzhou, South China.

Canine and feline hookworm infection is endemic in many countries with zoonotic transmission representing a potentially significant public health concern. However, there is limited data available on the zoonotic transmission of canine and feline hookworms in China. This study was conducted to evaluate the zoonotic risk of Ancylostoma ceylanicum isolated from stray dogs and cats in Guangzhou, south China. Primer pairs CAF/CAR were designed to amplify complete ITS sequences of obtained A. ceylanicum. The results were compared with fourteen ITS reference sequences of human-derived A. ceylanicum registered in GenBank, and phylogenetic trees were established by using NJ and ML methods. The sequence similarity of three dog-derived and five cat-derived A. ceylanicum with fourteen human-derived A. ceylanicum were 96.8%~100% and 97.8%~100%, respectively. Phylogenetic analysis placed A. ceylanicum isolated from dogs and cats in the same group with A. ceylanicum human isolates. Due to the ability of A. ceylanicum to cause a patent infection in humans, the zoonotic risk arising from dog and cat reservoirs to communities in this region should be determined.

Molecular identification of Ancylostoma caninum isolated from cats in southern China based on complete ITS sequence.

Ancylostoma caninum is a blood-feeding parasitic intestinal nematode which infects dogs, cats, and other mammals throughout the world. A highly sensitive and species-specific PCR-RFLP technique was utilised to detect the prevalence of A. caninum in cats in Guangzhou, southern China. Of the 102 fecal samples examined, the prevalence of A. caninum in cats was 95.1% and 83.3% using PCR-RFLP and microscopy, respectively. Among them, the prevalence of single hookworm infection with A. caninum was 54.90%, while mixed infections with both A. caninum and A. ceylanicum were 40.20%. Comparative analysis of three complete ITS sequences obtained from cat-derived A. caninum showed the same length (738 bp) as that of dog-derived A. caninum. However, the sequence variation range was 98.6%-100%, where only one cat isolate (M63) showed 100% sequence similarity in comparison with two dog-derived A. caninum isolates (AM850106, EU159416) in the same studied area. The phylogenetic tree revealed A. caninum derived from both cats and dogs in single cluster. Results suggest that cats could be the main host of A. caninum in China, which may cause cross-infection between dogs and cats in the same area.

Quantitative nucleation and growth kinetics of gold nanoparticles via model-assisted dynamic spectroscopic approach.

Lacking of quantitative experimental data and/or kinetic models that could mathematically depict the redox chemistry and the crystallization issue, bottom-to-up formation kinetics of gold nanoparticles (GNPs) remains a challenge. We measured the dynamic regime of GNPs synthesized by l-ascorbic acid (representing a chemical approach) and/or foliar aqueous extract (a biogenic approach) via in situ spectroscopic characterization and established a redox-crystallization model which allows quantitative and separate parameterization of the nucleation and growth processes. The main results were simplified as the following aspects: (I) an efficient approach, i.e., the dynamic in situ spectroscopic characterization assisted with the redox-crystallization model, was established for quantitative analysis of the overall formation kinetics of GNPs in solution; (II) formation of GNPs by the chemical and the biogenic approaches experienced a slow nucleation stage followed by a growth stage which behaved as a mixed-order reaction, and different from the chemical approach, the biogenic method involved heterogeneous nucleation; (III) also, biosynthesis of flaky GNPs was a kinetic-controlled process favored by relatively slow redox chemistry; and (IV) though GNPs formation consists of two aspects, namely the redox chemistry and the crystallization issue, the latter was the rate-determining event that controls the dynamic regime of the whole physicochemical process.

DNA assembly and enzymatic cutting in solutions: a gold nanoparticle based SERS detection strategy.

The ability to monitor biomolecular recognition such as DNA hybridization and enzymatic reactivity in solutions with high sensitivity is important for developing effective bioassay strategies. Surface enhanced Raman scattering (SERS) based on use of solid substrates to produce the SERS effect for the detection often requires substrate preparation which is ineffective for rapid monitoring. This report describes a new strategy exploiting a gold nanoparticle (AuNP) based interparticle "hot-spot" for SERS monitoring of DNA mediated assembly and enzyme induced cleavage of the assembly in solution phase. The DNAs consist of two different complementary DNA strands with a thiol modification for attachment to AuNPs of selected sizes. In a solution containing AuNPs conjugated with one of the single-stranded (ss) DNA and other AuNPs labeled with a Raman reporter molecule, 4-mercaptobenzoic acid (MBA), the introduction of the complementary DNA strand leads to a linkage of the two types of AuNPs, producing double-stranded (ds) DNA-AuNP assembly (ds-DNA-AuNPs) with an interparticle "hot-spot" for SERS detection of the diagnostic bands of the reporter. Upon introducing a restriction enzyme (e.g. MspI) into the ds-DNA-AuNP assembly solution, the removal of the interparticle "hot-spot" due to restriction enzyme cleavage of the ds-DNA leads to a decrease of the SERS signals. While the detailed cleavage process may depend on the reaction time and the amount of enzyme, the viability of using gold nanoparticle "hot-spot" based SERS monitoring of DNA assembly and enzyme cleavage is clearly demonstrated, which has important implications for developing new strategies for bioassays.

Bifunctional nanoparticles for SERS monitoring and magnetic intervention of assembly and enzyme cutting of DNAs.

The ability to harness the nanoscale structural properties is essential for the exploration of functional properties of nanomaterials. This report demonstrates a novel strategy exploring bifunctional nanoparticles for spectroscopic detection and magnetic intervention of DNA assembly, disassembly, and enzyme cutting processes in a solution phase. In contrast to existing single-function based approaches, this strategy exploits magnetic MnZn ferrite nanoparticles decorated with gold or silver on the surface to retain adequate magnetization while producing sufficient plasmonic resonance features to impart surface-enhanced Raman scattering (SERS) functions. The decoration of MnZn ferrite nanoparticles with Au or Ag (MZF/Au or MZF/Ag) was achieved by thermally activated deposition of Au or Ag atoms/nanoparticles on MZF nanoparticles. Upon interparticle double-stranded DNA linkage of the MZF/Au (or MZF/Ag) nanoparticles with gold nanoparticles labeled with a Raman reporter, the resulting interparticle "hot spots" are shown to enable real time SERS monitoring of the DNA assembly, disassembly, or enzyme cutting processes, where the magnetic component provides an effective means for intervention of the biomolecular processes in the solution. The unique bifunctional combination of the SERS "hot spots" and the magnetic separation capability serves as the first example of bifunctional nanoprobes for biomolecular recognition and intervention.