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Abstract In recent years, wearable sensor devices with exceptional portability and the ability to continuously monitor physiological signals in real time have played increasingly prominent roles in the fields of disease diagnosis and health management. This transformation has been largely facilitated by materials science and micro/nano-processing technologies. However, as this technology continues to evolve, the demand for multifunctionality and flexibility in wearable devices has become increasingly urgent, thereby highlighting the problem of stable and sustainable miniaturized power supplies. Here, we comprehensively review the current mainstream energy technologies for powering wearable sensors, including batteries, supercapacitors, solar cells, biofuel cells, thermoelectric generators, radio frequency energy harvesters, and kinetic energy harvesters, as well as hybrid power systems that integrate multiple energy conversion modes. In addition, we consider the energy conversion mechanisms, fundamental characteristics, and typical application cases of these energy sources across various fields. In particular, we focus on the crucial roles of different materials, such as nanomaterials and nano-processing techniques, for enhancing the performance of devices. Finally, the challenges that affect power supplies for wearable electronic products and their future developmental trends are discussed in order to provide valuable references and insights for researchers in related fields. Graphic Abstract

In recent years, the deep integration of basic research and clinical translational research of nanotechnology and oncology has led to the emergence of a new branch, namely integrated nano-oncology. This is an emerging and important interdisciplinary field, which plays an irreplaceable role in the diagnosis, treatment, early warning, monitoring and prevention of tumors, and has become a new interdisciplinary frontier. Here main advances of integrated nano-oncology was reviewed, mainly included controlled preparation of nanomaterials, ultra-sensitive detection of tumor biomarkers, multi-functional nanoimaging probes and integrated diagnosis and treatment technology, innovative nano drugs and nano drug delivery system, DNA nanotechnology, RNA nanotechnology, nano self-assembly technology, nanosensors, intelligent nanorobots, nanotherapeutic machines. The terms, concepts, trends and challenges are also discussed with the aim of promoting the application of nanotechnology in integrated oncology and solving the scientific and key technical problems in basic and clinical translational research of cancer.

Summary: Background: The use of mesenchymal stem cells (MSCs) has recently emerged as a promising new therapeutic strategy for many diseases including perianal fistulizing Crohn’s disease (CD). Whether hUC-MSCs can promote the healing of luminal ulcer in CD has not been studied so far. Methods: The model of TNBS-induced colitis in rats was used to confirm the efficacy of hUC-MSCs in the treatment of CD. Then, seventeen CD patients refractory to or unsuitable for currently available therapies were enrolled and received once submucosal local injection through colonoscopy combined with once intravenous drip on the next day. All patients received a 24-week follow-up. Clinical and laboratory assessments were monitored at baseline, week 4, 8, 12, and 24. Endoscopic evaluations were conducted at baseline and week 12. Mucosal specimens were obtained at the margin of lesions by endoscopy biopsies and used for RNA sequencing. Two hUC-MSCs co-culture systems were established in vitro, one with the mucosa specimens and the other with M1 macrophages induced from THP1. The expressions of genes representing inflammation (TNFα, IL-6, and IL-1β) and intestinal barrier function (ZO1, CLAUDIN1, and CDH1) were tested by RT-PCR. Findings: hUC-MSCs treatment increased body weight and decreased disease activity index (DAI), colon macroscopic damage index (CMDI), and histopathological score (HPS) of rats with TNBS-induced colitis. The results of the clinical study also showed that this mode of hUC-MSCs application was associated with regression of intestinal ulceration. Eight patients (47%) got endoscopic responses (SES-CD improvement of ≥50% from baseline) and three patients (17.65%) got mucosal healing (SES-CD is zero), with a parallel improvement of clinical and laboratory parameters without serious adverse events. RNA sequencing showed hUC-MSCs therapy was associated with an upregulation of transcripts linked to intestinal epithelial barrier integrity and a downregulation of inflammatory signaling pathways in the intestinal mucosa, especially the TNF signaling pathway, IL-17 signaling pathway, and TLR signaling pathway. RNA expression of intestinal epithelial tight junction protein (ZO1, CLAUDIN1, and CDH1), and the RNA expression of major intestinal inflammatory factors in CD (IL-1β, IL-6, and TNFα, p

Abstract The aging population and the prevalence of infectious diseases have impacted the traditional medical order, significantly increasing the burden on healthcare and adversely affecting the socio‐economic system. Medical sensors based on artificial intelligence (AI) provide new ideas for modern medical data collection to monitor the health status of individuals and environmental changes. Meanwhile, with the aid of AI algorithms, the big data processing capabilities of sensor systems have been greatly improved, further realizing early predictions and timely diagnoses. In this paper, a brief overview is offered on the development status of AI‐enabled medical sensors for off‐body detection, near‐body monitoring, disease prediction, and clinical decision support system, and the ongoing challenges and future prospects to move from concept to implementation are discussed. In the foreseeable future, breakthroughs in the combination of medical sensors and AI algorithms are expected to pave the way for early detection and clinical decision support and improve the accuracy and efficiency for disease diagnosis.

Since the nanomaterial has become one of the most popular topics, gold nanomaterials have always been a research hotspot. Gold nanostars (GNSs) as one of the formations of the gold nanoparticles has stepped on the stage due to its remarkable property. By using Turkevich method, Brust method, seeded growth method and seedless-based method with proper and specific modification, GNSs could be produced for different requirements. These GNSs present various properties under a proper modification: high physical and chemical stability, high biocompatibility and the ability of modification easily. Such enormous properties and the surface plasmon resonance of GNSs could be used for various-potential applications such as surface-enhanced Raman scattering (SERS) detection, in vivo diseases detection and therapy, drug delivery and release and so on. All these indicate that GNS is a valuable material in biological, phenomenological and optical researches.

Abstract Background There have been reports of increased glutamate pyruvate transaminase 2 (GPT2) expression in certain cancers including breast cancer. Although the role of GPT2 as a metabolic enzyme is well understood in breast cancer progression, little is known about the other roles of GPT2, especially exosomal GPT2. Methods BT549 and BT474 Cells were cultured and their exosomes were isolated by using ultracentrifugation. Cells migrated through the membrane were stained with crystal violet, and then were observed by microscope. Total RNA was extracted from culture cells and transcribed into cDNA, quantitative real‐time RT‐PCR was used to detect mRNA expression of ICAM1, VCAM1, and MMP9 using SYBR Green qPCR Mix with a 7500 Fast Real‐time PCR system. Western blot was used to detect the gene expression of p‐lkBa and TSG101 and GPT2 in breast cancer cells. Immunohistochemistry was used to detect the protein expression of GPT2 and BTRC in cancer cells, animal models loaded with metastasis breast cancer cells were established via tail vein injections. Interaction between GPT2 and BTRC in breast cancer cells was investigated via Co‐immunoprecipitation. Results GPT2 was up‐regulated in TNBC. Exosomes were isolated effectively from TNBC cells, and confirmed that GPT2 was overexpressed inexosomes. QRT‐PCR showed that mRNA expression levels of ICAM1, VCAM1, and MMP9 in TNBC were high. Exosomal GPT2 derived from TNBC enhanced migration and invasion of breast cancer via in vitro cell experiment and in vivo animal model experiment. Exosomal GPT2 binds with BTRC to degrade p‐lkBa, and improved metastasis of breast cancer cells. Conclusion We demonstrated that GPT2 was upregulated in TNBC as well as in exosomes derived from triple‐negative breast cancer (TNBC) cells. GPT2 expression was associated with the malignancy of breast cancer and promoted metastasis of breast cancer cells. Moreover, exosomal GPT2 derived from TNBC cells was verified to increase the capacity of breast cancer cells to metastasize through activating beta‐transducin repeat containing E3 ubiquitin protein ligase (BTRC). This suggested that exosomal GPT2 may be useful for breast cancer patients as a potential biomarker and treatment target.

Abstract In this research, we design and implement a small, convenient, and noninvasive paper-based microfluidic sweat sensor that can simultaneously detect multiple key biomarkers in human sweat. The origami structure of the chip includes colorimetric and electrochemical sensing regions. Different colorimetric sensing regions are modified with specific chromogenic reagents to selectively identify glucose, lactate, uric acid, and magnesium ions in sweat, as well as the pH value. The regions of electrochemical sensing detect cortisol in sweat by molecular imprinting. The entire chip is composed of hydrophilically and hydrophobically treated filter paper, and 3D microfluidic channels are constructed by using folding paper. The thread-based channels formed after the hydrophilic and hydrophobic modifications are used to control the rate of sweat flow, which in turn can be used to control the sequence of reactions in the differently developing colored regions to ensure that signals of the best color can be captured simultaneously by the colorimetric sensing regions. Finally, the results of on-body experiments verify the reliability of the proposed sweat sensor and its potential for the noninvasive identification of a variety of sweat biomarkers.

Objective: Although great progress has been made in the field of siRNA gene therapy, safe, efficient, and targeted delivery of siRNA are still major challenges in siRNA therapeutics. Methods: We developed an up-conversion nanoparticle-based nanocage system. This system protected the siRNA from being degraded by nucleases in organisms and selectively delivered the siRNAs to the tumor sites, due to modifications of targeted molecules on the surfaces of nanocages and local inhalation. Results: The siRNAs delivered by the up-conversion nanoparticle nanocages were protected from degradation in transit to the tumor sites, where they accumulated. Compared with the passive target and control groups, the up-conversion nanoparticles based on the nanocage system showed a tumor suppressive effect after approximately 3 weeks of treatment. Conclusions: The up-conversion nanoparticle nanocages efficiently delivered vascular endothelial growth factor siRNAs to tumor sites. Mice with lung tumors treated with tumors targeting up-conversion nanoparticle nanocages showed steady body weight changes, high tumor inhibition ratios, and longer survival times.

COVID-19 is caused by severe acute respiratory SARS-CoV-2. Regardless of the availability of treatment strategies for COVID-19, effective therapy will remain essential. A promising approach to tackle the SARS-CoV-2 could be small interfering (si) RNAs. Here we designed the small hairpin RNA (named as shRNA688) for targeting the prepared 813 bp Est of the S protein genes (Delta). The conserved and mutated regions of the S protein genes from the genomes of the SARS-CoV-2 variants in the public database were analyzed. A 813 bp fragment encoding the most part of the RBD and partial downstream RBD of the S protein was cloned into the upstream red florescent protein gene (RFP) as a fusing gene in the pCMV-S-Protein RBD-Est-RFP plasmid for expressing a potential target for RNAi. The double stranded of the DNA encoding for shRNA688 was constructed in the downstream human H1 promoter of the plasmid in which CMV promoter drives enhanced green fluorescent protein (EGFP) marker gene expression. These two kinds of the constructed plasmids were co-transfected into HEK293T via Lipofectamine 2000. The degradation of the transcripts of the SARS-CoV-2 S protein fusing gene expressed in the transfected HEK293T treated by RNAi was analyzed by RT-qPCR with a specific probe of the targeted SARS-CoV-2 S protein gene transcripts. Our results showed that shRNA688 targeting the conserved region of the S protein genes could effectively reduce the transcripts of the S protein genes. This study provides a cell model and technical support for the research and development of the broad-spectrum small nucleic acid RNAi drugs against SARS-CoV-2 or the RNAi drugs for the other hazard viruses which cause human diseases.

Abstract Passive and label-free microfluidic devices have no complex external accessories or detection-interfering label particles. These devices are now widely used in medical and bioresearch applications, including cell focusing and cell separation. Geometric structure plays the most essential role when designing a passive and label-free microfluidic chip. An exquisitely designed geometric structure can change particle trajectories and improve chip performance. However, the geometric design principles of passive and label-free microfluidics have not been comprehensively acknowledged. Here, we review the geometric innovations of several microfluidic schemes, including deterministic lateral displacement (DLD), inertial microfluidics (IMF), and viscoelastic microfluidics (VEM), and summarize the most creative innovations and design principles of passive and label-free microfluidics. We aim to provide a guideline for researchers who have an interest in geometric innovations of passive label-free microfluidics.

Abstract User-interactive electronic skin (e-skin) that could convert mechanical stimuli into distinguishable outputs displays tremendous potential for wearable devices and health care applications. However, the existing devices have the disadvantages such as complex integration procedure and lack of the intuitive signal display function. Here, we present a bioinspired user-interactive e-skin, which is simple in structure and can synchronously achieve digital electrical response and optical visualization upon external mechanical stimulus. The e-skin comprises a conductive layer with a carbon nanotubes/cellulose nanofibers/MXene nanohybrid network featuring remarkable electromechanical behaviors, and a stretchable elastomer layer, which is composed of silicone rubber and thermochromic pigments. Furthermore, the conductive nanohybrid network with outstanding Joule heating performance can generate controllable thermal energy under voltage input and then achieve the dynamic coloration of silicone-based elastomer. Especially, such an innovative fusion strategy of digital data and visual images enables the e-skin to monitor human activities with evermore intuition and accuracy. The simple design philosophy and reliable operation of the demonstrated e-skin are expected to provide an ideal platform for next-generation flexible electronics.

Effective and specific diagnostic imaging of brain glioma remains a challenge. Magnetic nanoparticles are actively being developed as contrast agents for diagnosis of tumor. In this work, we developed the targeted magnetic nanoparticles as T1-positive magnetic resonance imaging (MRI) contrast agents. Zn-doped Fe3O4 NPs were synthesized by solvothermal method, coated with liposome and conjugated to a tumor-penetrating peptide (RGERPPR). The effect of zinc doping on the magnetic properties of Fe3O4 nanoparticles was studied. Zn0.4Fe2.6O4-PEG nanoparticles exhibited T1 MR contrast enhancement. Cytotoxicity assay indicated that nanoparticles have good biocompatibility and low toxicity. And the in vitro cellular uptake assays on U87 cells confirmed that the conjugation of RGERPPR increased the uptake of the Zn0.4Fe2.6O4 NPs. In vivo MR imaging showed the contrast enhance of U87 brain glioma in rat model after injection.

In recent years, a huge extent of data that contains hidden information is collected by the health care industries. Deep Neural Networks (DNN) have been employed to obtain appropriate decisions and effective results. The obtained results have been validated using confusion matrix and region of interest. In this work, we have used fourteen parameters for the prediction of cardiovascular disease (CVD) of 303 volunteers. The proposed predictive technique predicts that the chance for prediction of the risk level of cardiovascular disease. In this work, the prediction method using deep neural networks showed the highest accuracy. Our proposed method has outperformed the existing methods and can be combined with multimedia technology.

The real-time monitoring of food freshness in refrigerators is of significant importance in detecting potential food spoiling and preventing serious health issues. One method that is commonly reported and has received substantial attention is the discrimination of food freshness via the tracking of volatile molecules. Nevertheless, the ambient environment of low temperature (normally below 4 °C) and high humidity (90% R.H.), as well as poor selectivity in sensing gas species remain the challenge. In this research, an integrated smart gas-tracking device is designed and fabricated. By applying pump voltage on the yttria-stabilized zirconia (YSZ) membrane, the oxygen concentration in the testing chamber can be manually tailored. Due to the working principle of the sensor following the mixed potential behavior, distinct differences in sensitivity and selectivity are observed for the sensor that operated at different oxygen concentrations. Typically, the sensor gives satisfactory selectivity to H2S, NH3, and C2H5OH at the oxygen concentrations of 10%, 30%, and 40%, respectively. In addition, an acceptable response/recovery rate (within 24 s) is also confirmed. Finally, a refrigerator prototype that includes the smart gas sensor is built, and satisfactory performance in discriminating food freshness status of fresh or semi-fresh is verified for the proposed refrigerator prototype. In conclusion, these aforementioned promising results suggest that the proposed integrated smart gas sensor could be a potential candidate for alarming food spoilage.

Restoring skin integrity after wound infection remains a tougher health challenge due to the uncontrolled antibiotic-resistant pathogens caused by antibiotic abuse. Herein, an injectable hydrogel with dual antibacterial and anti-inflammatory activities composed of gold nanoclusters (GNCs) and carbomer (CBM) is developed for wound dressing to overcome multidrug-resistant infection. Firstly, both experimental investigations and molecular dynamics simulation validate the protonation state of 6-mercaptohexanoic acid (MHA) ligands play an important role in its antibacterial action of GNCs. The self-organizing GNCs-CBM composite hydrogel is then spontaneously cross-linked by the dimeric hydrogen bonds (H-bonds) between the MHA ligands and the acrylic acid groups of CBM. Benefitting from the dimeric H-bonds, the hydrogel becomes thickening enough as an ideal wound dressing and the GNCs exist in the hydrogel with a high protonation level that contributes to the enhanced bactericidal function. In all, by combining bactericidal and immunomodulatory actions, the GNCs-CBM hydrogel demonstrated excellent synergy in accelerating wound healing in animal infection models. Hence, the dimeric H-bonds strengthening strategy makes the GNCs-CBM hydrogel hold great potential as a safe and effective dressing for treating infected wounds.

The novel coronavirus pneumonia, a global pandemic disease named as coronavirus disease 2019, has caused enormous losses on the health and economies of people all over the world, while there is still a lack of quick and sensitive diagnostic method and effective therapy. Developing rapid diagnostic method for coronavirus disease 2019 has become exceptional urgent. Herein we report a rapid diagnostic method for the novel coronavirus through monitoring the volatile biomarkers in human exhaled breath. The breath volatile biomarkers are derived from the metabolism of novel coronavirus, including acetoin, 2,4,6-trimethylpyridine, 3-methyl tridecane, tetradecane, isooctyl alcohol, pentadecane, hexadecane, 1-methylene-1H-indene. By comparing the types and concentrations of the volatile biomarkers in human exhaled breath combined with SERS sensor, we could distinguish between the healthy person and the patients with coronavirus disease 2019. This work confirms that various volatile organic compounds metabolized by novel coronavirus can be employed for rapidly screening of patients with coronavirus disease 2019, and has broad application prospects in the prevention and control of the epidemic.

Abstract Biological applications of nanomaterials as delivery carriers have been embedded in traditional biomedical research for decades. Despite lagging behind, recent significant breakthroughs in the use of nanocarriers as tools for plant biotechnology have created great interest. In this Perspective, we review the outstanding recent works in nanocarrier‐mediated plant transformation and its agricultural applications. We analyze the chemical and physical properties of nanocarriers determining their uptake efficiency and transport throughout the plant body.

Abstract Since the ferromagnetic (Fe3O4) nanoparticles were firstly reported to exert enzyme-like activity in 2007, extensive research progress in nanozymes has been made with deep investigation of diverse nanozymes and rapid development of related nanotechnologies. As promising alternatives for natural enzymes, nanozymes have broadened the way toward clinical medicine, food safety, environmental monitoring, and chemical production. The past decade has witnessed the rapid development of metal- and metal oxide-based nanozymes owing to their remarkable physicochemical properties in parallel with low cost, high stability, and easy storage. It is widely known that the deep study of catalytic activities and mechanism sheds significant influence on the applications of nanozymes. This review digs into the characteristics and intrinsic properties of metal- and metal oxide-based nanozymes, especially emphasizing their catalytic mechanism and recent applications in biological analysis, relieving inflammation, antibacterial, and cancer therapy. We also conclude the present challenges and provide insights into the future research of nanozymes constituted of metal and metal oxide nanomaterials.

Objective: The aim of the study was to use a network pharmacological method to examine the mechanism of Guishao-Liujun decoction against gastric cancer (GC).Methods: The traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) and the Traditional Chinese Medicine Integrated Database (TCMID) were used to obtain the chemical composition and targets of all the drugs of Guishao-Liujun decoction, and the targets of GC were screened using GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. The obtained targets were imported into Cytoscape 3.7.2 software by using the R language to take the intersection for a Venn analysis to construct active ingredient target networks, and they were imported into the STRING database to construct protein–protein interaction (PPI) networks, with the BisoGenet plugin in Cytoscape 3.7.2 being used for analyzing network topology. On the potential target of Guishao-Liujun decoction for GC, gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed using the R-language bioconductor platform, and the outcomes were imported into Cytoscape 3.7.2 software to obtain the KEGG network map. The core targets were docked with the active components by the macromolecular docking software application AutoDock Vina.Results: A total of 243 chemical components and 1,448 disease targets including 127 intersecting targets were discovered. AKT1, TP53, and GO functional analysis were mainly associated with ubiquitination and oxidase reduction activity. In GC treatment, the KEGG analysis revealed that Guishao-Liujun decoction mainly acted through the tumor necrosis factor (TNF), interleukin 17 (IL-17), and cancer-related signaling pathways, with the best binding performance with TP53, as indicated by the outcomes of macromolecular docking.Conclusion: In the treatment of GC, Guishao-Liujun decoction works with a variety of components and targets, establishing the groundwork for further research into its mechanism of action.

Titanium dioxide nanoparticles (TiO2 NPs) are one of the main sources of the nanoparticulate matter exposure to humans. Although several studies have demonstrated their potential toxic effects, the real nature of the correlation between NP properties and their interaction with biological targets is still far from being fully elucidated. Here, engineered TiO2 NPs with various geometries (bipyramids, plates, and rods) have been prepared, characterized and intravenously administered in healthy mice. Parameters such as biodistribution, accumulation, and toxicity have been assessed in the lungs and liver. Our data show that the organ accumulation of TiO2 NPs, measured by ICP-MS, is quite low, and this is only partially and transiently affected by the NP geometries. The long-lasting permanence is exclusively restricted to the lungs. Here, bipyramids and plates show a higher accumulation, and interestingly, rod-shaped NPs are the most toxic, leading to histopathological pulmonary alterations. In addition, they are also able to induce a transient increase in serum markers related to hepatocellular injury. These results indicate that rods, more than bipyramidal and spherical geometries, lead to a stronger and more severe biological effect. Overall, small physico-chemical differences can dramatically modify both accumulation and safety.

Abstract Deep learning is an emerging tool, which is regularly used for disease diagnosis in the medical field. A new research direction has been developed for the detection of early-stage gastric cancer. The computer-aided diagnosis (CAD) systems reduce the mortality rate due to their effectiveness. In this study, we proposed a new method for feature extraction using a stacked sparse autoencoder to extract the discriminative features from the unlabeled data of breath samples. A Softmax classifier was then integrated to the proposed method of feature extraction, to classify gastric cancer from the breath samples. Precisely, we identified fifty peaks in each spectrum to distinguish the EGC, AGC, and healthy persons. This CAD system reduces the distance between the input and output by learning the features and preserve the structure of the input data set of breath samples. The features were extracted from the unlabeled data of the breath samples. After the completion of unsupervised training, autoencoders with Softmax classifier were cascaded to develop a deep stacked sparse autoencoder neural network. In last, fine-tuning of the developed neural network was carried out with labeled training data to make the model more reliable and repeatable. The proposed deep stacked sparse autoencoder neural network architecture exhibits excellent results, with an overall accuracy of 98.7% for advanced gastric cancer classification and 97.3% for early gastric cancer detection using breath analysis. Moreover, the developed model produces an excellent result for recall, precision, and f score value, making it suitable for clinical application.

Abstract Background Gene and chemical therapy has become one of the rising stars in the field of molecular medicine during the last two decades. However, there are still numerous challenges in the development of efficient, targeted, and safe delivery systems that can avoid siRNA degradation and reduce the toxicity and adverse effects of chemotherapy medicine. Results In this paper, a highly efficient AS1411 aptamer modified, dsDNA and MMP-2 cleavable peptide-fabricated gold nanocage vehicle, which could load doxorubicin hydrochloride (DOX) and siRNAs to achieve a combination of tumor responsive genetic therapy, chemotherapy, and photothermal treatment is presented. Our results show that this combined treatment achieved targeted gene silencing and tumor inhibition. After nearly one month of treatment with DOX-loaded Au-siRNA-PAA-AS1411 nanoparticles with one dose every three days in mice, a synergistic effect promoting the eradication of long-lived tumors was observed along with an increased survival rate of mice. The combined genetic, chemotherapeutic, and photothermal treatment group exhibited more than 90% tumor inhibition ratio (tumor signal) and a ~ 67% survival rate compared with a 30% tumor inhibition ratio and a 0% survival rate in the passive genetic treatment group. Conclusions The development of nanocarriers with double-stranded DNA and MMP-2 cleavable peptides provides a new strategy for the combined delivery of gene and chemotherapy medicine. Au-siRNA-PAA-AS1411 exerts high anticancer activities on lung cancer, indicating immense potentials for clinical application.

Highlights A standalone-like smart device that can remotely track the variation of air pollutants in a power-saving way is created; Metal–organic framework-derived hollow polyhedral ZnO was successfully synthesized, allowing the created smart device to be highly selective and to sensitively track the variation of NO2 concentration; A novel photoluminescence-enhanced Li-Fi telecommunication technique is proposed, offering the created smart device with the capability of long distance wireless communication. Abstract Remote tracking the variation of air quality in an effective way will be highly helpful to decrease the health risk of human short- and long-term exposures to air pollution. However, high power consumption and poor sensing performance remain the concerned issues, thereby limiting the scale-up in deploying air quality tracking networks. Herein, we report a standalone-like smart device that can remotely track the variation of air pollutants in a power-saving way. Brevity, the created smart device demonstrated satisfactory selectivity (against six kinds of representative exhaust gases or air pollutants), desirable response magnitude (164–100 ppm), and acceptable response/recovery rate (52.0/50.5 s), as well as linear response relationship to NO2. After aging for 2 weeks, the created device exhibited relatively stable sensing performance more than 3 months. Moreover, a photoluminescence-enhanced light fidelity (Li-Fi) telecommunication technique is proposed and the Li-Fi communication distance is significantly extended. Conclusively, our reported standalone-like smart device would sever as a powerful sensing platform to construct high-performance and low-power consumption air quality wireless sensor networks and to prevent air pollutant-induced diseases via a more effective and low-cost approach.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a public health emergency of international concern. Real-time reverse transcription-polymerase chain reaction (RT-PCR) is widely used as the gold standard method for the diagnosis of SARS-CoV-2 infection. However, the reliability of current real-time RT-PCR assays is questioned due to some false-negative reports. In this study, we improved the real-time RT-PCR method based on three target regions (ORF1ab, E, and N) of SARS-CoV-2. Results showed that real-time RT-PCR assays herein could complete detection within one hour after viral RNA preparation and had high sensitivity down to 5 copies of viral RNA. In addition, six clinical specimens were detected to evaluate the availability of this method. Among them, four samples were 3-plex SARS-CoV-2 positive and two were negative by real-time RT-PCR. The sensitivity was 100% (4/4), and specificity was 100% (2/2). These results demonstrate that we develop a rapid and high-sensitive real-time RT-PCR method for SARS-CoV-2 detection, which will be a powerful tool for COVID-19 identification and for monitoring suspected patients.

The new coronavirus SARS-CoV-2 has become a global pandemic, which has had a huge impact on the lives of people around the world and has caused huge impacts and losses on global economic development. To now, there is still no effective drug or therapy against coronavirus. A large number of studies have shown that vaccines are the ultimate weapon to eliminate major infectious diseases. The development of new vaccines against new coronaviruses is the best way to prevent new coronavirus infections. In this study, we developed a new vaccine against the new coronavirus by combining our self-developed nano adjuvant loaded with carnosine graphene oxide adjuvant with loaded with CpG molecule and RBD protein antigen. Our results showed that this vaccine can produce high titer anti-SARS-CoV-2 RBD antibody neutralizing SARS-CoV-2 in mice within 2 weeks.

To combat the COVID-19 pandemic, serologic lateral flow immunoassays are required to facilitate accurate diagnosis of SARS-CoV-2 infection and confirmation of molecular results. This study evaluated sensitivity of two different designs of colloidal gold serologic tests (antigen based total antibody test and antibody based IgG test) by using residual serum samples from patients who were evaluated for SARS-CoV-2 infection status by polymerase chain reaction (PCR). The results showed 100% specificity for both tests, while when testing of 16 positive patients, the data showed 90% sensitivity for total antibody test and 30% for IgG test. This study demonstrates high diagnostic accuracy for anti-SARS-CoV-2 total antibody tests and will facilitate further development and selection of serological assays.

The novel coronavirus disease (COVID-19) is breaking out and spreading rapidly around the world. There is an urgent need for an accurate and rapid detection method to quickly find infected patients and asymptomatic carriers in order to prevent the spread of the severe acute respiratory syndrome coronavirus [SARS-CoV-2]. In this paper, we designed a test strip which used the principle of double antigen sandwich. Fe3O4 magnetic nanobeads are firstly coupled with specific antibodies, and the S protein of the new coronavirus is used as the coating antigen to capture specific antibodies against the new coronavirus, which is used to detect the virus nucleoprotein of specific antibodies in clinical samples. At the same time, Fe3O4 magnetic nanobeads have unique magnetic properties, which can be used to generate different types of detection signals and simplify the detection process. These results can be judged by color changes and magnetic changes at the test and control lines. Compared with the traditional method, this test strip of Fe3O4 magnetic nanobeads has high sensitivity and can qualitatively detect samples within 15 minutes. The magnetic performance of the magnetic nanobeads can be used to improve the sensitivity of the strip in our further research and product development.

The SARS-CoV-2 isothermal amplification detection kits based on loop-mediated isothermal amplification (LAMP) were developed and evaluated on three types samples of SARS-CoV-2. The kits included enzyme reaction mixtures and chromogenic agents. After the isothermal amplification reactions were completed, the reaction results were judged by using the chromogenic agents to determine whether SARS-CoV-2 exists in the samples to be tested. The detection kits have the advantages of convenient operation, fast detection speed and high sensitivity up to 1 copy of virus particles per reaction, which can speed up the detection speed of suspected cases, and avoid the missing detection problems caused by the low detection sensitivity.

Gasdermin E (GSDME) is one of the executors of pyroptosis, a type of programmed lytic cell death, which can be triggered by caspase-3 activation upon stimulation. Silenced GSDME expression due to promoter hypermethylation is associated with gastric cancer (GC), which is confirmed in the present study by bioinformatics analysis and methylation-specific PCR (MSP) test of GC cell lines and clinical samples. GC cell lines and mouse xenograft models were used to investigate the pyroptosis-inducing effect of the common cholesterol-depleting, drug simvastatin (SIM), allied with upregulating GSDME expression by doxycycline (DOX)- inducible Tet-on system or DNA methyltransferase inhibitor 5-Aza-2′-deoxycytidine (5-Aza-CdR). Cell viability assessment and xenograft tumour growth demonstrated that the tumour inhibition effects of SIM can be enhanced by elevated GSDME expression. Morphological examinations and assays measuring lactate dehydrogenase (LDH) release and caspase-3/GSDME protein cleavage underlined the stimulation of pyroptosis as an important mechanism. Using short hairpin RNA (shRNA) knockdown of caspase-3 or GSDME, and caspase-3-specific inhibitors, we provided evidence of the requirement of caspase-3/GSDME in the pyroptosis process triggered by SIM. We conclude that reactivating GSDME expression and thereby inducing cancer cell-specific pyroptosis could be a potential therapeutic strategy against GC.

Highlights MnO2@Ce6 nanoprobes-loaded-iPS cells (iPS-MnO2@Ce6) were developed for enhanced photodynamic and immunotherapy against cancer. Under the guidance of multi-mode real-time imaging, iPS-MnO2@Ce6 achieved an enhanced photodynamic therapeutic effect and stimulated a strong anti-tumor immune response in the tumor-bearing mouse. Abstract How to trigger strong anti-tumor immune responses has become a focus for tumor therapy. Here, we report the human-induced pluripotent stem cells (iPSs) to deliver MnO2@Ce6 nanoprobes into tumors for simultaneous photodynamic therapy (PDT) and enhanced immunotherapy. Ce6 photosensitizer was attached on manganese dioxide (MnO2) nanoparticles, and resultant MnO2@Ce6 nanoprobes were delivered into mitomycin-treated iPSs to form iPS-MnO2@Ce6 nanoprobes. The iPS-MnO2@Ce6 actively targeted in vivo tumors, the acidic microenvironment triggered interaction between MnO2 and H2O2, released large quantities of oxygen, alleviated hypoxia in tumor. Upon PDT, singlet oxygen formed, broken iPSs released tumor-shared antigens, which evoked an intensive innate and adaptive immune response against the tumor, improving dendritic cells matured, effector T cells, and natural killer cells were activated. Meanwhile, regulatory T cells were reduced, and then the immune response induced by iPS-MnO2@Ce6 was markedly stronger than the immune reaction induced by MnO2@Ce6 (P

Machine learning techniques are widely used for the diagnosis of cancers. In this study, we proposed a classification and prediction system for the diagnosis of gastric cancer based on saliva samples. Gastric cancer (GC) is classified into early gastric cancer (EGC) and advanced gastric cancer (AGC). The diagnosis of GC at an early stage will improve the survival rate. Computer-aided diagnostic (CAD) systems can assist the radiologists in the diagnosis of EGC. 220 saliva samples were collected from the non-cancerous and gastric cancerous persons and analyzed using high-performance liquid chromatography-mass spectrometry (HPLC-MS). Fourteen amino acid biomarkers were sufficient to distinguish the persons from malignant to benign and were observed in the saliva samples with dominant peaks. We used the support vector machine (SVM) for binary classification. The processed Raman dataset was used to train and test the developed model. SVM based neural networks were established using different kernels, which produced different results. Accuracy, specificity, sensitivity, and receiver operating characteristics (ROC) were used to evaluate the proposed classification model, along with mean average error (MAE), mean square Error (MSE), sum average error (SAE), and sum square error (SSE). We achieved an overall accuracy of 97.18%, specificity of 97.44%, and sensitivity of 96.88% for the proposed method. This established method owns the prospect of clinical translation.

Abstract Point-of-care testing (POCT) is widely used for early diagnosis and monitoring of diseases. Lateral flow assay (LFA) is a successfully commercial tool for POCT. However, LFA often suffers from a lack of quantification and analytical sensitivity. To solve these drawbacks, we have previously developed a thermal LFA using plasmonic gold nanoparticles for thermal contrast into a portable device. Although this methodology significantly improves the analytical sensitivity compared with conventional visual detection, quantification problems are still remaining. In this study, we optimized the operating conditions for the device using conduction and radiation thermal sensing modes allowing the quantification of LFA. The limit of detection of the strips merely containing nanoparticles was decreased by 5-fold (conduction mode) and 12-fold (radiation mode) compared to traditional visual detection. The effect of the ambient temperature was studied for both methods of detection showing that the radiation mode was more affected by the ambient temperature than the conduction mode. To validate the thermal sensing method, human chorionic gonadotropin (HCG) biomarker was quantified using our LFA strips, obtaining a detection limit of 2.8 mIU/mL when using the radiation method of detection.

ObjectiveTo construct a novel nanoplatform GNS@CaCO3/Ce6-NK by loading the CaCO3-coated gold nanostars (GNSs) with Chlorin e6 molecules (Ce6) into human peripheral blood mononuclear cells (PBMCs)-derived NK cells for tumor targeted therapy.MethodsGNS@CaCO3/Ce6 nanoparticles were prepared and characterized by TEM and UV-vis. The cell surface markers and cytokines secretion of NK cells before and after loading the GNS@CaCO3/Ce6 nanoparticles were detected by Flow Cytometry (FCM) and ELISA. Effects of the GNS@CaCO3/Ce6-NK cells on A549 cancer cells was determined by FCM and CCK-8. Intracellular fluorescent signals of GNS@CaCO3/Ce6-NK cells were detected via Confocal laser scanning microscopic (CLSM) and FCM at different time points. Intracellular ROS generation of GNS@CaCO3/Ce6-NK cells under laser irradiation were examined by FCM. The distribution of GNS@CaCO3/Ce6-NK in A549 tumor-bearing mice were observed by fluorescence imaging and PA imaging. The combination therapy of GNS@CaCO3/Ce6-NK under laser irradiation were investigated on tumor-bearing mice.ResultsThe coated CaCO3 shell on the surface of GNSs exhibited prominent delivery and protection effect of Ce6 during the cellular uptake process. The as-prepared multifunctional GNS@CaCO3/Ce6-NK cells possessed bimodal functions of fluorescence imaging and photoacoustic imaging. The as-prepared multifunctional GNS@CaCO3/Ce6-NK cells could actively target tumor tissues with the enhanced photothermal/photodynamic therapy and immunotherapy.ConclusionsThe GNS@CaCO3/Ce6-NK shows effective tumor-targeting ability and prominent therapeutic efficacy toward lung cancer A549 tumor-bearing mice. Through fully utilizing the features of GNSs and NK cells, this new nanoplatform provides a new synergistic strategy for enhanced photothermal/photodynamic therapy and immunotherapy in the field of anticancer development in the near future.

ObjectiveSuppression of bromodomain and extra terminal (BET) proteins has a bright prospect to treat MYC-driven tumors. Bromodomain containing 4 (BRD4) is one of the BET proteins. ARV-825, consisting of a BRD4 inhibitor conjugated with a cereblon ligand using proteolysis-targeting chimera (PROTAC) technology, was proven to decrease the tumor growth effectively and continuously. Nevertheless, the efficacy and mechanisms of ARV-825 in gastric cancer are still poorly understood.MethodsCell counting kit 8 assay, lentivirus infection, Western blotting analysis, Annexin V/propidium iodide (PI) staining, RNA sequencing, a xenograft model, and immunohistochemistry were used to assess the efficacy of ARV-825 in cell level and animal model.ResultsThe messenger RNA (mRNA) expression of BRD4 in gastric cancer raised significantly than those in normal tissues, which suggested poor outcome of patients with gastric cancer. ARV-825 displayed higher anticancer efficiency in gastric cancer cells than OTX015 and JQ1. ARV-825 could inhibit cell growth, inducing cell cycle block and apoptosis in vitro. ARV-825 induced degradation of BRD4, BRD2, BRD3, c-MYC, and polo-like kinase 1 (PLK1) proteins in four gastric cancer cell lines. In addition, cleavage of caspase 3 and poly-ADP-ribose polymerase (PARP) was elevated. Knockdown or overexpression CRBN could increase or decrease, respectively, the ARV-825 IC50 of gastric cancer cells. ARV-825 reduced MYC and PLK1 expression in gastric cancer cells. ARV-825 treatment significantly reduced tumor growth without toxic side effects and downregulated the expression of BRD4 in vivo.ConclusionsHigh mRNA expression of BRD4 in gastric cancer indicated poor prognosis. ARV-825, a BRD4 inhibitor, could effectively suppress the growth and elevate the apoptosis of gastric cancer cells via transcription downregulation of c-MYC and PLK1. These results implied that ARV-825 could be a good therapeutic strategy to treat gastric cancer.

Exosomal miRNAs (EmiRs) can be used for prediction of gastric cancer (GC) development. Supposedly, both plasma and urinary microRNAs can also be potential biomarkers for screening, but the diagnostic values of EmiRs in blood and urine are not fully studied. We here collected both types of samples from GC patients and healthy individuals and conducted miRNA sequencing to identify key members of EmiRs in GC. The exosomes samples derived from blood and urine were collected from 3 healthy individuals and 7 GC patients. Differentially expressed miRNAs (DEmiRNAs) were acquired, ontology enrichment analysis and Protein-protein Interaction (PPI) enrichment analysis were performed. There were 8 DEmiRNAs in the serum and 3 DEmiRNAs in the urine. For GC patients, there were three up-regulated DEmiRNAs (hsa-miR-130b-3p, hsa-miR-151a-3p and hsa-miR-15b-3p) in the serum exosomes, and one up-regulated DEmiRNA (hsa-miR-1246) in the urinary exosomes. Using miRNA target prediction databases, we found 418 common targets of hsa-miR-15b-3p, 35 common targets of hsa-miR-151a-3p, 117 common targets of hsa-miR-130b-3p, and 357 common targets of hsa-miR-1246. Some commonly enriched ontology terms were found, including GO BP terms like cell surface receptor signaling pathway involved in cell-cell signaling, positive regulation of catabolic process, morphogenesis of an epithelium, and GO CC terms perinuclear region of cytoplasm. The PPI network show some key nodes, including TAOK1, CMTM6, SCN3A, WASF3, IGF1, CNOT7, GABRG1, PRKD1. Together, this study provided an integrative analysis of expression profile of key circulating exosomal microRNAs. Four key exosomal miRNAs (hsa-miR-130b-3p, hsa-miR-151a-3p and hsa-miR-15b-3p) and the interaction network or enrichments based on their targets (TAOK1, CMTM6, SCN3A, WASF3, IGF1, CNOT7, GABRG1, PRKD1) may provide a reference of the molecular mechanisms in the GC development.

Abstract Up to date, the way in which metal nanoparticles are cleared in vivo has yet to be elucidated well. Herein, we report a novel intestinal goblet cell-mediated in vivo clearance pathway to remove metal nanoparticles. Typical metal nanoparticles such as triangular silver nanoplates, magnetic nanoparticles, gold nanorods, and gold nanoclusters were selected as representative examples. These metal nanoparticles were prepared, characterized, and injected via tail vein into a mice model with common bile duct (CBD) ligation. The feces and urines were collected for 7 days to be followed by the sacrifice of the mice and collection of the intestinal and gastric tissues for further analysis. The results showed that all four selected metal nanoparticles were located inside the goblet cells (GCs) of the whole intestinal tissue and were excreted into the gut lumen through the secretion of intestinal GC. Moreover, triangular silver nanoplates and gold nanorods were located inside the gastric parietal cells (PCs). Importantly, nanoparticles did not cause obvious pathological changes in intestinal tissues. In this study, we confirmed that the blood corpuscles are involved in the GCs secretion pathway. Furthermore, we found that the secretion of nanoparticles from intestinal GCs and PCs is accelerated by diarrhea induced via Chinese herbs. In conclusion, metal nanoparticles such as triangular silver nanoplates, magnetic nanoparticles, gold nanorods, and gold nanoclusters can be cleaned away by intestinal GCs and PCs. This novel pathway of in vivo clearance of metal nanoparticles has a great potential for future applications such as new drug design and development, nanoparticle-based labeling and in vivo tracking, and biosafety evaluation of in vivo nanoparticles.

Abstract How to fabricate scale low-cost microfluidic device for detection of biomarkers owns a great requirement. Herein, it is for the first time reported that a new microfluidic device based on bonding polydimethylsiloxane microfluidic channels onto the substrate of a screen-printed electrode with coating glass solution was fabricated for electrochemical sensing of prostate-specific antigen (PSA). Compared to traditional microfabrication processes, this method is simple, fast, low cost, and also suitable for mass production. The prepared screen-printed electrode-based microfluidic device (CASPE-MFD) was used for the detection of the PSA in human serum. The prepared CASPE-MFD had a detection limit of 0.84 pg/mL (25.8 fM) and a good linearity with PSA concentration ranging from 0.001 to 10 ng/mL, which showed a great promise platform toward the development of miniaturized, low-cost electrochemical microfluidic device for use in human health, environmental monitoring, and other applications.

Abstract The use of magnetic nanoparticle (MNP)-labeled immunochromatography test strips (ICTSs) is very important for point-of-care testing (POCT). However, common diagnostic methods cannot accurately analyze the weak magnetic signal from ICTSs, limiting the applications of POCT. In this study, an ultrasensitive multiplex biosensor was designed to overcome the limitations of capturing and normalization of the weak magnetic signal from MNPs on ICTSs. A machine learning model for sandwich assays was constructed and used to classify weakly positive and negative samples, which significantly enhanced the specificity and sensitivity. The potential clinical application was evaluated by detecting 50 human chorionic gonadotropin (HCG) samples and 59 myocardial infarction serum samples. The quantitative range for HCG was 1–1000 mIU mL−1 and the ideal detection limit was 0.014 mIU mL−1, which was well below the clinical threshold. Quantitative detection results of multiplex cardiac markers showed good linear correlations with standard values. The proposed multiplex assay can be readily adapted for identifying other biomolecules and also be used in other applications such as environmental monitoring, food analysis, and national security.

Circulating tumor cells (CTCs) are the cancer cells that circulate in the peripheral blood after escaping from the original or metastatic tumors. CTCs could be used as non-invasive source of clinical information in early diagnosis of cancer and evaluation of cancer development. In recent years, CTC research has become a hotspot field wherein many novel CTC detection technologies based on microfluidics have been developed. Great advances have been made that exhibit obvious technical advantages, but cannot yet satisfy the current clinical requirements. In this study, we review the main advances in isolation and detection methods of CTC based on microfluidics research over several years, propose five technical indicators for evaluating these methods, and explore the application prospects. We also discuss the concepts, issues, approaches, advantages, limitations, and challenges with an aim of stimulating a broader interest in developing microfluidics-based CTC detection technology.

Abstract The Cas13a system has great potential in RNA interference and molecular diagnostic fields. However, lacking guidelines for crRNA design hinders practical applications of the Cas13a system in RNA editing and single nucleotide polymorphism identification. This study posits that crRNAs with hairpin spacers improve the specificity of CRISPR/Cas13a system (termed hs‐CRISPR). Gibbs free energy analysis suggests that the hairpin‐spacer crRNAs (hs‐crRNAs) suppress Cas13a's affinity to off‐target RNA. A hepatitis B virus DNA genotyping platform is established to further validate the high‐specificity of hs‐CRISPR/Cas13a system. Compared to ordinary crRNA, hs‐crRNAs increase the specificity by threefold without sacrificing the sensitivity of the CRISPR/Cas13a system. Furthermore, the mechanism of the Cas13a/hs‐crRNA/target RNA composition is elucidated with theoretical simulations. This work builds on the fundamental understanding of Cas13a activation and offers significant improvements for the rational design of crRNA for the CRISPR/Cas13a system.

Effectively capturing and sensitively detecting cancer cells are critical to clinical diagnosis and cancer therapy. In this work, we prepared gold nanostar-decorated graphene oxide (GO-AuNSs) nanocomposites using a ultraviolet (UV)-induced strategy, and then modified them with a layer of bio-complex rBSA-FA (coupled reduced bovine serum albumin with folic acid) to generate GO-AuNSs@rBSA-FA nanocomposites. Herein, the application of GO and AuNSs not only strengthened the conductivity of the sensing platform but also guaranteed nanocomposites with biocompatible performance. Moreover, the adopted rBSA-FA layer could effectively enhance the stability and specificity towards gastric cancer cells (MGC-803). According to a systemic construction procedure, a novel electrochemical cytosensor based on GO-AuNSs@rBSA-FA was fabricated for MGC-803 cell detection. With the assistance of cyclic voltammetry (CV) and differential pulse voltammetry (DPV), the cytosensor reached a detection limit of 100 cell/mL in a wide linear range of 3 × 102~7 × 106 cell/mL towards MGC-803 cells. The good electrochemical characteristics for the cancer cell analysis indicate a promising prospect of this electrochemical cytosensor in clinical cancer diagnosis.

Abstract Background Cryptococcus neoformans is an encapsulated yeast. There is still little quick and effective solution for the diagnosis or treatment of C. neoformans infection at an early stage in clinical. Antibody-conjugated silica-modified gold nanorods (GNR-SiO2-Ab) can conjugate C. neoformans selectively. It may provide a possibility for treatment of cryptococcosis safely and effectively. Methods Gold nanorods (GNRs) were synthesized according to the seed-mediated template-assisted protocol. Anti-C. neoformans antibody was covalently anchored on the surface of GNRs with silane coupling agent. In vitro computer tomography imaging was performed to explore the diagnostic effect of the GNR-SiO2-Ab. The viability of cells was evaluated to confirm the photo-thermal therapy effect of GNR-SiO2-Ab combined with near-infrared (NIR) laser light. Results GNR-SiO2-Ab has a potential application as a positive X-ray/CT imaging contrast agent. An antibody can induce a much greater aggregation of GNRs by binding to the surface of C. neoformans cells resulting in a much higher attenuation values than ever. After irradiation, C. neoformans cells suffered photo-thermal damages and the normal structure of cells were destroyed. The viability of cells reduced significantly compared to the untreated cells. Conclusions Our work confirmed that antibody-conjugated silica-modified gold nanorods could enhance X-ray attenuation of C. neoformans cells in CT images. And immune GNRs, which were mediated by antibodies, could increase the effects of NIR-induced photo-thermal therapy in C. neoformans cells.

Development of safe, efficient nanocomplex for targeted imaging and therapy of cancer stem cells in brain glioma has become a great challenge. Herein, a low-density lipoprotein receptor-related protein and a RNA aptamer bound CD133 were used as dual-targeting ligands to prepare dual-modified cationic liposomes (DP-CLPs) loaded with survivin siRNA and paclitaxel (DP-CLPs–PTX–siRNA) for actively targeting imaging and treating CD133+ glioma stem cells after passing through the blood–brain barrier. After being administrated with DP-CLPs–PTX–siRNA nanocomplex, DP-CLPs showed a persistent target ability to bind glioma cells and brain microvascular endothelial cells (BCECs) and to deliver drugs (PTX/siRNA) to CD133+ glioma stem cells. Prepared DP-CLPs–PTX–siRNA nanocomplex showed very low cytotoxicity to BCECs, but induced selectively apoptosis of CD133+ glioma stem cells, and improved CD133+ glioma stem cells' differentiation into non-stem-cell lineages, also markedly inhibited tumorigenesis, induced CD133+ glioma cell apoptosis in intracranial glioma tumor-bearing nude mice and improved survival rates. In conclusion, prepared DP-CLPs–PTX–siRNA nanocomplex selectively induced CD133+ glioma stem cell apoptosis in vitro and in vivo exhibits great potential for targeted imaging and therapy of brain glioma stem cells.