UV-assisted synthesis of ultra-small GO-Austar for efficient PTT therapeutic architectonic construction.

Conventional Au nanomaterial synthesis typically necessitates the involvement of extensive surfactants and reducing agents, leading to a certain amount of chemical waste and biological toxicity. In this study, we innovatively employed ultra-small graphene oxide as a reducing agent and surfactant for the in situ generation of small Au nanoparticles under ultraviolet irradiation (UV) at ambient conditions. After ultra-small GO-Au seeds were successfully synthesized, we fabricated small star-like Au nanoparticles on the surface of GO, in which GO effectively prevented Austar from aggregation. To further use GO-Austar for cancer PTT therapy, through the modification of reduced human serum albumin-folic acid conjugate (rHSA-FA) and loading IR780, the final probe GO-Austar@rHSA-FA@IR780 was prepared. The prepared probe showed excellent biocompatibility and superb phototoxicity towards MGC-803 cells in vitro. In vivo, the final probe dramatically increased tumor temperature up to 58.6 °C after 5 minutes of irradiation by an 808 nm laser, significantly inhibiting tumor growth and nearly eradicating subcutaneous tumors in mice. This research provides a novel and simple method for the synthesis of GO-Au nanocomposites, showcasing significant potential in biological applications.

hUC-MSCs therapy for Crohn's disease: efficacy in TNBS-induced colitis in rats and pilot clinical study.

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-1ß) 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-1ß, IL-6, and TNFα, p < 0.001 for all) were improved significantly. Moreover, hUC-MSCs could attenuate the polarization of M1 macrophage induced from THP1, thereby decreasing the mRNA expression of IL-1ß, IL-6, and TNFα significantly (p < 0.05 for all). TSG-6 expression was evaluated in hUC-MSCs culture supernatant after treatment with TNFα, IFNγ, and LPS for 48 h. And hUC-MSCs could inhibit the phosphorylation of JAK/STAT1 in the intestinal mucosa of CD patients. INTERPRETATION: hUC-MSCs transplantation alleviated TNBS-induced colitis in rats. In this pilot clinical study, preliminary data suggested that this approach to administering hUC-MSCs might have potential for clinical efficacy and manageable safety in treating refractory CD, potentially providing hope for better outcomes. No serious adverse events were observed. FUNDING: This work was funded by General Program of National Natural Science Foundation of China (Grant No. 82270639), the Scientific research project of Shanghai Municipal Health Committee (Grant No. 202240001), Specialty Feature Construction Project of Shanghai Pudong New Area Health Commission (Grant No. PWZzb2022-05), Shanghai East Hospital Youth Research and Cultivation Foundation program (Grant No. DFPY2022015), Peak Disciplines (Type IV) of Institutions of Higher Learning in Shanghai, Technology Development Project of Pudong Science, Technology and Economic Commission of Shanghai (Grant No. PKJ2021-Y08), Key Disciplines Group Construction Project of Shanghai Pudong New Area Health Commission (Grant No. PWZxq2022-06), Medical discipline Construction Project of Pudong Health Committee of Shanghai (Grant No. PWYgf2021-02) and National Natural Science Foundation of China (Grant No. 82300604).

An ingestible near-infrared fluorescence capsule endoscopy for specific gastrointestinal diagnoses.

Early diagnosis of gastrointestinal (GI) diseases is important to effectively prevent carcinogenesis. Capsule endoscopy (CE) can address the pain caused by wired endoscopy in GI diagnosis. However, existing CE approaches have difficulty effectively diagnosing lesions that do not exhibit obvious morphological changes. In addition, the current CE cannot achieve wireless energy supply and attitude control at the same time. Here, we successfully developed a novel near-infrared fluorescence capsule endoscopy (NIFCE) that can stimulate and capture near-infrared (NIR) fluorescence images to specifically identify subtle mucosal microlesions and submucosal lesions while capturing conventional white light (WL) images to detect lesions with significant morphological changes. Furthermore, we constructed the first synergetic system that simultaneously enables multi-attitude control in NIFCE and supplies long-term power, thus addressing the issue of excessive power consumption caused by the NIFCE emitting near-infrared light (NIRL). We performed in vivo experiments to verify that the NIFCE can specifically "light up" tumors while sparing normal tissues by synergizing with probes actively aggregated in tumors, thus realizing specific detection and penetration. The prototype NIFCE system represents a significant step forward in the field of CE and shows great potential in efficiently achieving early targeted diagnosis of various GI diseases.

Erythrocyte Membrane Camouflaged Nanotheranostics for Optical Molecular Imaging-Escorted Self-Oxygenation Photodynamic Therapy.

Hypoxic tumor microenvironment (TME) hampers the application of oxygen (O2 )-dependent photodynamic therapy (PDT) in solid tumors. To address this problem, a biomimetic nanotheranostics (named MMCC@EM) is developed for optical molecular imaging-escorted self-oxygenation PDT. MMCC@EM is synthesized by encapsulating chlorin e6 (Ce6) and catalase (CAT) in metal-organic framework (MOF) nanoparticles with erythrocyte membrane (EM) camouflage. Based on the biomimetic properties of EM, MMCC@EM efficiently accumulates in tumor tissues. The enriched MMCC@EM achieves TME-activatable drug release, thereby releasing CAT and Ce6, and this process can be monitored through fluorescence (FL) imaging. In addition, endogenous hydrogen peroxide (H2 O2 ) will be decomposed by CAT to produce O2 , which can be reflected by the measurement of intratumoral oxygen concentration using photoacoustic (PA) imaging. Such self-oxygenation nanotheranostics effectively mitigate tumor hypoxia and improve the generation of singlet oxygen (1 O2 ). The 1 O2 disrupts mitochondrial function and triggers caspase-3-mediated cellular apoptosis. Furthermore, MMCC@EM triggers immunogenic cell death (ICD) effect, leading to an increased infiltration of cytotoxic T lymphocytes (CTLs) into tumor tissues. As a result, MMCC@EM exhibits good therapeutic effects in 4T1-tumor bearing mice under the navigation of FL/PA duplex imaging.

Aß-Aggregation-Generated Blue Autofluorescence Illuminates Senile Plaques as well as Complex Blood and Vascular Pathologies in Alzheimer's Disease.

Senile plaque blue autofluorescence was discovered around 40 years ago, however, its impact on Alzheimer's disease (AD) pathology has not been fully examined. We analyzed senile plaques with immunohistochemistry and fluorescence imaging on AD brain sections and also Aß aggregation in vitro. In DAPI or Hoechst staining, the nuclear blue fluorescence could only be correctly assigned after subtracting the blue plaque autofluorescence. The flower-like structures wrapping dense-core blue fluorescence formed by cathepsin D staining could not be considered central-nucleated neurons with defective lysosomes since there was no nuclear staining in the plaque core when the blue autofluorescence was subtracted. Both Aß self-oligomers and Aß/hemoglobin heterocomplexes generated blue autofluorescence. The Aß amyloid blue autofluorescence not only labels senile plaques but also illustrates red cell aggregation, hemolysis, cerebral amyloid angiopathy, vascular plaques, vascular adhesions, and microaneurysms. In summary, we conclude that Aß-aggregation-generated blue autofluorescence is an excellent multi-amyloidosis marker in Alzheimer's disease.

Artificial intelligence in theranostics of gastric cancer, a review.

Gastric cancer (GC) is one of the commonest cancers with high morbidity and mortality in the world. How to realize precise diagnosis and therapy of GC owns great clinical requirement. In recent years, artificial intelligence (AI) has been actively explored to apply to early diagnosis and treatment and prognosis of gastric carcinoma. Herein, we review recent advance of AI in early screening, diagnosis, therapy and prognosis of stomach carcinoma. Especially AI combined with breath screening early GC system improved 97.4 % of early GC diagnosis ratio, AI model on stomach cancer diagnosis system of saliva biomarkers obtained an overall accuracy of 97.18 %, specificity of 97.44 %, and sensitivity of 96.88 %. We also discuss concept, issues, approaches and challenges of AI applied in stomach cancer. This review provides a comprehensive view and roadmap for readers working in this field, with the aim of pushing application of AI in theranostics of stomach cancer to increase the early discovery ratio and curative ratio of GC patients.

Application of near-infrared fluorescence imaging in theranostics of gastrointestinal tumors.

Gastrointestinal cancers have become an important cause of cancer-related death in humans. Improving the early diagnosis rate of gastrointestinal tumors and improving the effect of surgical treatment can significantly improve the survival rate of patients. The conventional diagnostic method is high-definition white-light endoscopy, which often leads to missed diagnosis. For surgical treatment, intraoperative tumor localization and post-operative anastomotic state evaluation play important roles in the effect of surgical treatment. As a new imaging method, near-infrared fluorescence imaging (NIRFI) has its unique advantages in the diagnosis and auxiliary surgical treatment of gastrointestinal tumors due to its high sensitivity and the ability to image deep tissues. In this review, we focus on the latest advances of NIRFI technology applied in early diagnosis of gastrointestinal tumors, identification of tumor margins, identification of lymph nodes, and assessment of anastomotic leakage. In addition, we summarize the advances of NIRFI systems such as macro imaging and micro imaging systems, and also clearly describe the application process of NIRFI from system to clinical application, and look into the prospect of NIRFI applied in the theranostics of gastrointestinal tumors.

Integrated Smart Gas Tracking Device with Artificially Tailored Selectivity for Real-Time Monitoring Food Freshness.

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.

Confining Prepared Ultrasmall Nanozymes Loading ATO for Lung Cancer Catalytic Therapy/Immunotherapy.

Nanozymes with inherent enzyme-mimicking catalytic properties combat malignant tumor progression via catalytic therapy, while the therapeutic efficacy still needs to be improved. In this work, ultrasmall platinum nanozymes (nPt) in a confined domain of a wormlike pore channel in gold nanobipyramidal-mesoporous silica dioxide nanocomposites, producing nanozyme carriers AP-mSi with photoenhanced peroxidase ability, are innovatively synthesized. Afterward, based on the prepared AP-mSi, a lung-cancer nanozymes probe (AP-HAI) is ingeniously produced by removing the SiO2 template, modifying human serum albumin, and loading atovaquone molecules (ATO) as well as IR780. Under NIR light irradiation, inner AuP and IR780 collaborate for photothermal process, thus facilitating the peroxidase-like catalytic process of H2 O2 . Additionally, loaded ATO, a cell respiration inhibitor, can impair tumor respiration metabolism and cause oxygen retention, hence enhancing IR780's photodynamic therapy (PDT) effectiveness. As a result, IR780's PDT and nPt nanozymes' photoenhanced peroxidase-like ability endow probes a high ROS productivity, eliciting antitumor immune responses to destroy tumor tissue. Systematic studies reveal that the obvious reactive oxygen species (ROS) generation is obtained by the strategy of using nPt nanozymes and reducing oxygen consumption by ATO, which in turn enables lung-cancer synergetic catalytic therapy/immunogenic-cell-death-based immunotherapy. The results of this work would provide theoretical justification for the practical use of photoenhanced nanozyme probes.

Exosomal GPT2 derived from triple-negative breast cancer cells promotes metastasis by activating BTRC.

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.

Exploring Purification Methods of Exosomes from Different Biological Samples.

Objective: Exosomes were extracted from a variety of biological samples using several different purification processes, and our goal was to determine which method and sample were the most effective for exosome extraction. Methods: We used ExoQuick-TC combined with ultrafiltration to separate and purify exosomes from the supernatant of gastric cancer cells, while we used the ExoQuick kit and ultracentrifugation to purify exosomes from human serum samples. Furthermore, exosomes were isolated and purified from human urine samples by diafiltration and from postparturition human breast milk samples by the filtration-polyethylene glycol precipitation method. The isolated exosomes were morphologically analyzed using a transmission electron microscope, the particle size was measured by NanoSight, and the protein content was analyzed by western blotting. Results: The isolated exosomes showed an obvious cup holder shape, with a clear outline and typical exosome morphological characteristics. The sizes of exosomes derived from gastric cancer cell supernatant, serum, urine, and milk were 65.8 ± 26.9 nm, 87.6 ± 50.9 nm, 197.5 ± 55.2 nm, and 184.1 ± 68.7 nm, respectively. Western blot results showed that CD9 and TSG101 on the exosomes were expressed to varying degrees based on the exosome source. Exosome abundance was higher in the serum, urine, and breast milk than in the supernatant. It is suggested that its exosomes can be extracted to obtain an excellent potential biological source of exosomes. Conclusion: In this study, the extraction and separation methods of foreign bodies from different biological samples were obtained, and it was found that human breast milk was a potential excellent material for administration because of its high abundance.

From Conventional to Microfluidic: Progress in Extracellular Vesicle Separation and Individual Characterization.

Extracellular vesicles (EVs) are nanoscale membrane vesicles, which contain a wide variety of cargo such as proteins, miRNAs, and lipids. A growing body of evidence suggests that EVs are promising biomarkers for disease diagnosis and therapeutic strategies. Although the excellent clinical value, their use in personalized healthcare practice is not yet feasible due to their highly heterogeneous nature. Taking the difficulty of isolation and the small size of EVs into account, the characterization of EVs at a single-particle level is both imperative and challenging. In a bid to address this critical point, more research has been directed into a microfluidic platform because of its inherent advantages in sensitivity, specificity, and throughput. This review discusses the biogenesis and heterogeneity of EVs and takes a broad view of state-of-the-art advances in microfluidics-based EV research, including not only EV separation, but also the single EV characterization of biophysical detection and biochemical analysis. To highlight the advantages of microfluidic techniques, conventional technologies are included for comparison. The current status of artificial intelligence (AI) for single EV characterization is then presented. Furthermore, the challenges and prospects of microfluidics and its combination with AI applications in single EV characterization are also discussed. In the foreseeable future, recent breakthroughs in microfluidic platforms are expected to pave the way for single EV analysis and improve applications for precision medicine.

Structure design mechanisms and inflammatory disease applications of nanozymes.

Nanozymes are artificial enzymes with high catalytic activity, low cost, and good biocompatibility, and have received ever-increasing attention in recent years. Various inorganic and organic nanoparticles have been found to exhibit enzyme-like activities and are used as nanozymes for diverse biomedical applications ranging from tumor imaging and therapeutics to detection. However, their further clinical applications are hindered by the potential toxicity and long-term retention of nanomaterials in vivo. Clarifying the catalytic mechanism of nanozymes and identifying the key factors responsible for their behavior can guide the design of nanozyme structure, enlighten the ways to improve their enzyme-like activities, and minimize the dosage of nanozymes, leading to reduced toxicity to the human body for a real biomedical application prospect. In particular, inflammation occurring in numerous diseases is closely related to reactive oxygen species, and the active oxygen scavenging ability of nanozymes potentially exerts excellent therapeutic effects on inflammatory diseases. In this review, we systematically summarize the structure-activity relationship of nanozymes, including regulation strategies for size and morphology, surface structure, and composition. Based on the structure-activity mechanisms, a series of chemically designed nanozymes developed to target various inflammatory diseases are briefly summarized.

Electrochemical Biosensor Based on l-Arginine and rGO-AuNSs Deposited on the Electrode Combined with DNA Probes for Ultrasensitive Detection of the Gastric Cancer-Related PIK3CA Gene of ctDNA.

Gene biomarkers of circulating tumor DNA (ctDNA) in liquid biopsies have been explored for use in the precise diagnosis of tumors. There is a great clinical need to realize the ultrasensitive detection of gene biomarkers in ctDNA. Here we reported that an ultrasensitive label-free biosensor was developed for the detection of the gastric cancer-related PIK3CA gene of ctDNA in peripheral blood. The polymeric l-arginine and graphene oxide-wrapped gold nanostars (rGO-AuNSs) were prepared and deposited on the glass electrode. The capturing DNA probes for the PIK3CA gene were prepared and successfully immobilized on the rGO-AuNS-modified electrode surface via π-π interaction among the rGO-AuNS composites and DNA probes. The resultant electrochemical sensor was effectively applied to detect the PIK3CA gene of ctDNA via the hybridization between the capturing DNA probe and ctDNA, the result of which showed that the biosensor exhibited desirable sensitivity, stability, and a wider dynamic response in a ctDNA concentration range from 1.0 × 10-20 to 1.0 × 10-10 M (R2 = 0.997). Moreover, the low limit of detection of 1.0 × 10-20 M (S/N = 3) indicates the biosensor owns satisfactory detection sensitivity. Fourteen PIK3CA genes and two PIK3CA gene mutations were detected in 60 clinical ctDNA samples of gastric cancer patients by using the developed biosensor. In conclusion, this ultrasensitive label-free electrochemical biosensor possesses a significant application prospect in the detection of the PIK3CA gene in ctDNA and in early screening for gastric cancer in the near future.

Recent developments of sonodynamic therapy in antibacterial application.

The rapid emergence of pathogenic bacteria poses a serious threat to global health. Notably, traditional antibiotic therapies suffer from the risk of strengthening bacterial drug resistance. Sonodynamic therapy (SDT) combining sonosensitizers and low-intensity ultrasound (US) has broadened the way towards treating drug-resistant bacteria. The allure of this therapy emerges from the capacity to focus the US energy on bacterial infection sites buried deep in tissues, locally activating the sonosensitizers to produce cytotoxic reactive oxygen species (ROS) with the ability to induce bacterial death. The past decade has witnessed the rapid development of antibacterial SDT owing to their excellent penetration, favorable biocompatibility and specific targeting ability. This review summarizes available sonosensitizers for antibacterial SDT, and digs into innovative biotechnologies to improve SDT efficiency, such as enhancing the targeting ability of sonosensitizers, image-guided assisted SDT, improvement of hypoxia and combination of SDT with other therapies. Finally, we conclude with the present challenges and provide insights into the future research of antibacterial SDT.

Enzyme-like copper-encapsulating magnetic nanoassemblies for switchable T1-weighted MRI and potentiating chemo-/photo-dynamic therapy.

Photodynamic therapy (PDT) has become a promising cancer treatment due to in situ generation of cytotoxic reactive oxygen (ROS); however, it remains limited by the hypoxia of tumor microenvironment (TME) and penetration depth of laser. Herein, we developed a kind of GSH-/H2O2-responsive copper-encapsulating magnetic nanoassemblies (MNSs) for switchable T1-weighted magnetic resonance imaging (MRI) and enzyme-like activity potentiating PDT of cancer. MNSs were rationally constructed using the chelation effect of copper ions (Cu2+) with polyacrylic acid-coated ultrasmall iron oxide nanoparticles (UIONPs). After uptake by tumor cells, the incorporated Cu2+ of MNSs was reduced to Cu+ through the intracellular GSH, which resulted in the disassembly of MNSs accompanied by the "silenced" MR signal shifting to a positive state. Sequentially, the generated Cu+ manifested peroxidase-like activity, catalyzing local H2O2 in TME to cytotoxic ·OH for chemodynamic therapy. Furthermore, Cu2+ and UIONPs could decompose H2O2 to O2, thus providing extra oxygen necessary for enhancing the PDT effect of photosensitizer IR-780. Finally, IR-780-loading MNSs (MNSs@IR-780) under laser irradiation significantly inhibited tumor growth and prolonged the survival of gastric MGC-803 tumor-bearing mice. Therefore, this study provides a versatile nanoplatform as a tumor-responsive theragnostic agent. STATEMENT OF SIGNIFICANCE: Tumor hypoxia and penetration depth of laser severely hindered the PDT of cancer. Valence-convertible metal ions (VCMI, e.g., Cu2+/Cu+, Fe3+/Fe2+) have been reported as Fenton-like agents disintegrating H2O2 to O2 to enhance PDT. Tumor-delivery of VCMI is of essential importance for in situ triggering of a Fenton-like reaction. We thereby developed magnetic nanoassemblies (MNSs) to encapsulate Cu2+ and load photosensitizer (IR-780). Stimulated by GSH and H2O2, MNSs performed catalase/peroxidase-like activity that provided extra O2 for PDT and catalyzed H2O2 to ·OH for CDT. Consequently, IR-780-loading MNSs under laser irradiation significantly inhibit the tumor growth due to effective tumor delivery of Cu2+ and IR-780. This study might offer a feasible nanoplatform for tumor-delivery of metal ions and drugs.

Topology optimization based deterministic lateral displacement array design for cell separation.

Circulating tumor cell (CTC) can be used to guide cancer theranostics. How to isolate efficiently CTCs from blood owns great clinical requirement. Deterministic lateral displacement (DLD) is a pillar-array-based effective passive microfluidic method to separate cells based on their sizes. DLD is a potential CTC isolation tool. Pillar shape is one of the key priorities in DLD array design. Altered zigzag mode is a normally undesired phenomenon that leads zigzag particles away from flow direction. This work makes use of the altered zigzag mode to manipulate zigzag particles for the first time, and developed a novel DLD chip with topology optimized pillar shape and a wide DLD channel. The novel designing method based on topology optimization (TO) greatly increases lateral displacement of different sized cells, meanwhile demonstrates its universality and expansibility. The proposed structure has the ability to shorten the device and to manipulate cells flexibly. Bead experiment has been applied to determine the critical diameter of the DLD array. Numerical, bead and cell experiment have been carried out to verify the separation efficiency of the structure. The TO-based wide DLD channel promotes the separation efficiency.

Point-of-care biochemical assays using electrochemical technologies: approaches, applications, and opportunities.

Against the backdrop of hidden symptoms of diseases and limited medical resources of their investigation, in vitro diagnosis has become a popular mode of real-time healthcare monitoring. Electrochemical biosensors have considerable potential for use in wearable products since they can consistently monitor the physiological information of the patient. This review classifies and briefly compares commonly available electrochemical biosensors and the techniques of detection used. Following this, the authors focus on recent studies and applications of various types of sensors based on a variety of methods to detect common compounds and cancer biomarkers in humans. The primary gaps in research are discussed and strategies for improvement are proposed along the dimensions of hardware and software. The work here provides new guidelines for advanced research on and a wider scope of applications of electrochemical biosensors to in vitro diagnosis.

Network-Based Pharmacological Study on the Mechanism of Guishao-Liujun Decoction in the Treatment of Gastric Cancer.

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.

Two-Photon Nanoprobe for NIR-II Imaging of Tumour and Biosafety Evaluation.

How to develop near-infrared second window (NIR-II, 1000-1700 nm) fluorescent nanoprobes with a uniform size, strong fluorescence signal and good biosafety owns great clinical requirement. Herein we reported that a two photon fluorescent nanoprobe was developed via encapsulating NIR-II-fluorescent molecules into DSPE-PEG, which was effectively endocytosized by cancer cells, and achieved strong NIR-II fluorescence imaging in cancer cells and cancer cell-beard mice models. Prepared NIR-II-fluorescent nanoprobe exhibited rapid metabolism and excellent biocompatibility. In conclusion, the prepared two photon nanoprobe owns good biosafety, and clinical translational prospect in NIR-II fluorescent imaging of tumour in vivo in near future.