Search

ObjectiveThe circulating tumor cells (CTCs) could be captured by the peptide functionalized magnetic nanoparticles (Pep@MNP) detection system in pancreatic ductal adenocarcinoma (PDAC). CTCs and the CXCR4 expression were detected to explore their clinical significance. The CXCR4+ CTCs, this is highly metastatic-prone stem cell-like subsets of CTCs (HM-CTCs), were found to be associated with the early recurrence and metastasis of PDAC.MethodsCTCs were captured by Pep@MNP. CTCs were identified via immunofluorescence with CD45, cytokeratin antibodies, and the CXCR4 positive CTCs were assigned to be HM-CTCs.ResultsThe over-expression of CXCR4 could promote the migration of pancreatic cancer cell in vitro and in vivo. In peripheral blood (PB), CTCs were detected positive in 79.0% of all patients (49/62, 9 (0–71)/2mL), among which 63.3% patients (31/49, 3 (0–23)/2mL) were HM-CTCs positive. In portal vein blood (PVB), CTCs were positive in 77.5% of patients (31/40, 10 (0–40)/2mL), and 67.7% of which (21/31, 4 (0–15)/2mL) were HM-CTCs positive CTCs enumeration could be used as diagnostic biomarker of pancreatic cancer (AUC = 0.862), and the combination of CTCs positive and CA19–9 increase shows improved diagnostic accuracy (AUC = 0.963). in addition, PVB HM-CTCs were more accurate to predict the early recurrence and liver metastasis than PB HM-CTCs (AUC 0.825 vs. 0.787 and 0.827 vs. 0.809, respectively).ConclusionsThe CTCs identified by Pep@MNP detection system could be used as diagnostic and prognostic biomarkers of PDAC patients. We identified and defined the CXCR4 over-expressed CTC subpopulation as highly metastatic-prone CTCs, which was proved to identify patients who were prone to suffering from early recurrence and metastasis.

Overcoming resistance to apoptosis is a major challenge in cancer therapy. Recent research has shown that manipulating mitochondria, the organelles critical for energy metabolism in tumor cells, can increase the effectiveness of photodynamic therapy and trigger apoptosis in tumor cells. However, there is currently insufficient research and effective methods to exploit mitochondrial damage to induce apoptosis in tumor cells and improve the effectiveness of photodynamic therapy. In this study, we present a novel nanomedicine delivery and therapeutic system called PyroFPSH, which utilizes a nanozymes-modified metal-organic framework as a carrier. PyroFPSH exhibits remarkable multienzyme-like activities, including glutathione peroxidase (GPx) and catalase (CAT) mimicry, allowing it to overcome apoptosis resistance, reduce endogenous glutathione levels, and continuously generate reactive oxygen species (ROS). In addition, PyroFPSH can serve as a carrier for the targeted delivery of sulfasalazine, a drug that can induce mitochondrial depolarization in tumor cells, thereby reducing oxygen consumption and energy supply in the mitochondria of tumor cells and weakening resistance to other synergistic treatment approaches. Our experimental results highlight the potential of PyroFPSH as a versatile nanoplatform in cancer treatment. This study expands the biomedical applications of nanomaterials as platforms and enables the integration of various novel therapeutic strategies to synergistically improve tumor therapy. It deepens our understanding of multienzyme-mimicking active nanocarriers and mitochondrial damage through photodynamic therapy. Future research can further explore the potential of PyroFPSH in clinical cancer treatment and improve its drug loading capacity, biocompatibility and targeting specificity. In summary, PyroFPSH represents a promising therapeutic approach that can provide new insights and possibilities for cancer treatment.

Liquid biopsy has received increasing attention as a new disease detection modality because of its noninvasive, simple sampling, and reproducible assay advantages. Among the markers of liquid biopsy, extracellular vesicles (EVs) are considered as promising disease biomarkers because they contain a large amount of biological information and have a significant role in physiological activities. The emergence and progression of some of these diseases are associated with miRNAs carried by EVs (EV‐miRNAs). Therefore, high‐sensitive detection of EV‐miRNAs is essential in clinical applications. A growing number of strategies, including biosensors, in situ detection methods, and microfluidics have been developed for the detection of EV‐miRNA and have been applied in the diagnosis of diseases such as cancer. This review summarizes the probes, signal amplification, and detection methods for EV‐miRNA detection, as well as the application of membrane fusion‐based in situ detection and integrated microfluidic chips for EV‐miRNA detection. The challenges of these materials and techniques in clinical diagnostic applications are also discussed.

AlGaN-based LEDs are promising for many applications in deep ultraviolet fields, especially for water-purification projects, air sterilization, fluorescence sensing, etc. However, in order to realize these potentials, it is critical to understand the factors that influence the optical and electrical properties of the device. In this work, AlxGa1−xN (x = 0.24, 0.34, 0.47) epilayers grown on c-plane patterned sapphire substrate with GaN template by the metal organic chemical vapor deposition (MOCVD). It is demonstrated that the increase of the aluminum content leads to the deterioration of the surface morphology and crystal quality of the AlGaN epitaxial layer. The dislocation densities of AlxGa1−xN epilayers were determined from symmetric and asymmetric planes of the ω-scan rocking curve and the minimum value is 1.01 × 109 cm−2. The (101¯5) plane reciprocal space mapping was employed to measure the in-plane strain of the AlxGa1−xN layers grown on GaN. The surface barrier heights of the AlxGa1−xN samples derived from XPS are 1.57, 1.65, and 1.75 eV, respectively. The results of the bandgap obtained by PL spectroscopy are in good accordance with those of XRD. The Hall mobility and sheet electron concentration of the samples are successfully determined by preparing simple indium sphere electrodes.

Abstract Extracellular vesicles (EVs) are natural vehicles carrying and transferring bioactive molecules for intercellular communication and play key roles in physiological and pathological processes. EVs are promising biomarkers for disease diagnosis due to their rich biological information and minimally invasive sampling. In this review, we summarize the current methods for isolating EVs from the body fluids and the techniques for analyzing EVs’ biomolecules including the proteins, nucleic acids, and lipids. The advantages, feasibility, and challenges of EV‐based in vitro diagnosis toward clinical application are discussed. Finally, an outlook on the marketing and routine clinical application of EV‐based in vitro diagnosis is provided.

The high-quality aluminum nitride (AlN) epilayer is the key factor that directly affects the performance of semiconductor deep-ultraviolet (DUV) photoelectronic devices. In this work, to investigate the influence of thickness on the quality of the AlN epilayer, two AlN-thick epi-film samples were grown on c-plane sapphire substrates. The optical and structural characteristics of AlN films are meticulously examined by using high-resolution X-ray diffraction (HR-XRD), scanning electron microscopy (SEM), a dual-beam ultraviolet-visible spectrophotometer, and spectroscopic ellipsometry (SE). It has been found that the quality of AlN can be controlled by adjusting the AlN film thickness. The phenomenon, in which the thicker AlNn film exhibits lower dislocations than the thinner one, demonstrates that thick AlN epitaxial samples can work as a strain relief layer and, in the meantime, help significantly bend the dislocations and decrease total dislocation density with the thicker epi-film. The Urbach’s binding energy and optical bandgap (Eg) derived by optical transmission (OT) and SE depend on crystallite size, crystalline alignment, and film thickness, which are in good agreement with XRD and SEM results. It is concluded that under the treatment of thickening film, the essence of crystal quality is improved. The bandgap energies of AlN samples obtained from SE possess larger values and higher accuracy than those extracted from OT. The Bose–Einstein relation is used to demonstrate the bandgap variation with temperature, and it is indicated that the thermal stability of bandgap energy can be improved with an increase in film thickness. It is revealed that when the thickness increases to micrometer order, the thickness has little effect on the change of Eg with temperature.

Chronic myeloid leukemia (CML) is recognized as a classic clonal myeloproliferative disorder. Given the limited treatment options for CML patients in the accelerated phase (AP) and blast phase (BP), there is an evident need to develop new therapeutic strategies. This has the potential to improve outcomes for individuals in the advanced stages of CML. A promising therapeutic target is Wilms’ tumor 1 (WT1), which is highly expressed in BP-CML cells and plays a crucial role in CML progression. In this study, a chemically synthesized nucleus-targeting WT1 antagonistic peptide termed WIP2W was identified. The therapeutic implications of both the peptide and its micellar formulation, M—WIP2W, were evaluated in WT1+ BP-CML cell lines and in mice. The findings indicate that WIP2W can bind specifically to the WT1 protein, inducing cell cycle arrest and notable cytotoxicity in WT1+ BP-CML cells. Moreover, subcutaneous injections of M—WIP2W were observed to significantly enhance intra-tumoral accumulation and to effectively inhibit tumor growth. Thus, WIP2W stands out as a potent and selective WT1 inhibitor, and the M—WIP2W nanoformulation appears promising for the therapeutic treatment of refractory CML as well as other WT1-overexpressing malignant cancers.

The conventional two-dimensional (2D) tumor cell lines in Petri dishes have played an important role in revealing the molecular biological mechanism of lung cancer. However, they cannot adequately recapitulate the complex biological systems and clinical outcomes of lung cancer. The three-dimensional (3D) cell culture enables the possible 3D cell interactions and the complex 3D systems with co-culture of different cells mimicking the tumor microenvironments (TME). In this regard, patient-derived models, mainly patient-derived tumor xenograft (PDX) and patient-derived organoids discussed hereby, are with higher biological fidelity of lung cancer, and regarded as more faithful preclinical models. The significant Hallmarks of Cancer is believed to be the most comprehensive coverage of current research on tumor biological characteristics. Therefore, this review aims to present and discuss the application of different patient-derived lung cancer models from molecular mechanisms to clinical translation with regards to the dimensions of different hallmarks, and to look to the prospects of these patient-derived lung cancer models.

Abstract Acute myeloid leukemia (AML) is a common malignant heterogeneous hematopoietic disease with very low average 5-year survival rate due to the refractory feature and high rate of relapse. CD123 is highly expressed on multiple types of AML cells, especially leukemia stem cells, and closely associated with the poor prognosis of AML. Aiming to meet the urgent demand to targeted therapeutics for the refractory AML patients, herein we synthesize a CD123 antagonistic peptide (PO-6) loaded in nanomicelles (mPO-6), and investigated its therapeutic effect and pharmacokinetics on a lab-established refractory AML mice model (AE & CKITD816V). It is shown that the PO-6 can effectively bind to the CD123+ AML cells and the micellar formulation mPO-6 increases the dissolution stability and the specific binding capacity. When injected intravenously, mPO-6 significantly prolongs the survival of the refractory AML mice by interfering CD123/IL-3 axis, evidenced by the down regulation of phosphorylation of STAT5 and PI3K/AKT and the inhibition of activated NF-κB in the nucleus, as well as by the analysis results of next generation RNA-sequencing (RNA-seq) with the bone marrow of the AML mice. The antagonistic effect leads to the significantly reduction of AML cells infiltration in the bone marrow of the AML mice. In conclusion, mPO-6 could provide a potent antagonistic therapeutic approach for targeted treatment of AML.

BackgroundWe sought to explore the impact of changing treatment strategy based on circulating tumor cells (CTC) on postoperative survival of breast cancer.MethodsWe retrospectively analyzed records of patients who underwent surgery for early-stage breast cancer at Beijing Friendship Hospital from January 2016 to January 2018 and regularly underwent CTC examination after surgery. During the regular examination and CTC monitoring, the patients with positive CTC results and without distant metastasis had their treatment regimen changed.ResultsOf 109 patients who received CTC examination regularly after surgery, 61 (56.0%) were CTC-positive during postoperative follow-up, including 33 ER or PR-positive, and 28 ER and PR-negative patients. Of the 33 ER or PR-positive patients, 20 changed endocrine therapy drugs. Compared with those without replacement, those with changed endocrine therapy strategy had higher CTC clearance rates (90.0% vs. 53.8%, p=0.04) and significantly lower CTC-positive values (1.70 ± 1.72 vs. 0.62 ± 0.65, p = 0.04). Among the 28 patients who were CTC positive and ER and PR-negative, 11 used capecitabine. Compared with non-users, the capecitabine users had higher CTC clearance rates (100.0% vs. 52.9%, p=0.01) and more significant decrease in CTC-positive values (2.09 ± 1.14 vs. 0.82 ± 1.67, p=0.04). Disease-free survival (DFS) at 1, 3, and 5 years was significantly longer in those who changed treatment than in those who did not (respectively, 96.6% vs. 89.6%, 92.8% vs. 56.9%, 69.0% vs. 47.8%, p

Efficacy of anti-human epidermal growth factor receptor 2 (HER2) treatment is impacted by tissue-based evaluation bias due to tumor heterogeneity and dynamic changes of HER2 in breast cancer. Circulating tumor cell (CTC)-based HER2 phenotyping provides integral and real-time assessment, benefiting accurate HER2 diagnosis. This study developed a semi-quantitative fluorescent evaluation system of HER2 immunostaining on CTCs by peptide-functionalized magnetic nanoparticles (Pep@MNPs) and immunocytochemistry (ICC). 52 newly-diagnosed advanced breast cancer patients were enrolled for blood samples before and/or after first-line treatment, including 24 patients who were diagnosed with HER2+ tumors and treated with anti-HER2 drugs. We enumerated CTCs and assessed levels of HER2 expression on CTCs in 2.0 ml whole blood. Enumerating CTCs at baseline could distinguish cancer patients (sensitivity, 69.2%; specificity, 100%). 80.8% (42/52) of patients had at least one CTCs before therapy. Patients with

BackgroundNeoadjuvant therapy is a standard treatment for patients with large, nonmetastatic breast cancer and may allow breast-conserving surgery after tumor downsizing while decreasing the risk of subsequent relapse. Dynamic changes of circulation tumor cells (CTCs) have a role in predicting treatment efficacy of breast cancer. However, the relationship between CTC enumeration before neoadjuvant therapy and pathologic complete response rate is still uncertain.MethodsThe study was exploratory. A total of 50 breast cancer patients were enrolled in a phase II clinical study of neoadjuvant therapy for HER-2-positive early breast cancer. They were enrolled for blood draws before and after neoadjuvant therapy. We used two methods (CellSearch and TUMORFISH) to detect CTCs. We compared the sensitivity of the two systems and investigated the correlation of the enumeration on baseline CTCs with the diagnosis, prognosis, and efficacy of neoadjuvant therapy of the patients with HER-2-positive early breast cancer. We also explored the dynamic change of CTCs after neoadjuvant therapy.ResultsThe sensitivity of TUMORFISHER (27/50) method was significantly higher than that of the CellSearch system (15/50, p=0.008). The CTC numbers detected by the two detection systems were not significantly correlated with lymph node status, clinical stage, ki-67 level and hormone receptor status. Patients with ≥1 CTC before neoadjuvant therapy measured by the TUMORFISHER system had a significant high pCR rate (74.1% vs. 39.1%, p = 0.013); whereas, there was no predictive effect on pCR by CellSearch system (73.3% vs. 51.4%, p = 0.15). Patients with a decrease in CTCs enumeration after neoadjuvant therapy were more likely to achieve pCR than those with no change or increase in CTCs enumeration (87.5% vs 50.0%, p = 0.015) by the TUMORFISHER method. Unfortunately, there was no predictive value of CTCs enumeration for EFS before and after neoadjuvant therapy by two methods.ConclusionsOur study demonstrates that the new CTCs detection method TUMORFISHER system has a higher checkout rate in early breast cancer than the CellSearch system, and shows the opportunity of CTC enumeration as a novel assistant biomarker to predict the response of neoadjuvant therapy in patients with HER-2-positive early breast cancer.

Summary: Immunogenic cell death (ICD) in malignant cells can decrease tumor burden and activate antitumor immune response to obtain lasting antitumor immunity, leading to the elimination of distant metastases and prevention of recurrence. Here, we reveal that ppM1 peptide is capable of forming irreparable transmembrane pores on tumor cell membrane, leading to ICD which we name poroptosis. Poroptosis is directly dependent on cell membrane nanopores regardless of the upstream signaling of cell death. ppM1-induced poroptosis was characterized by the sustained release of intracellular LDH. This unique feature is distinct from other well-characterized types of acute necrosis induced by freezing-thawing (F/T) and detergents, which leads to the burst release of intracellular LDH. Our results suggested that steady transmembrane-nanopore-mediated subacute cell death played a vital role in subsequent activated immunity that transforms to an antitumor immune microenvironment. Selectively generating poroptosis in cancer cell could be a promise strategy for cancer therapy.

The applications of three-dimensional materials combined with two-dimensional materials are attractive for constructing high-performance electronic and photoelectronic devices because of their remarkable electronic and optical properties. However, traditional preparation methods usually involve mechanical transfer, which has a complicated process and cannot avoid contamination. In this work, chemical vapor deposition was proposed to vertically synthesize self-assembly oriented hexagonal boron nitride on gallium nitride directly. The material composition, crystalline quality and orientation were investigated using multiple characterization methods. Thermal conductivity was found to be enhanced twofold in the h-BN incorporated sample by using the optothermal Raman technique. A vertical-ordered (VO)h-BN/GaN heterojunction photodetector was produced based on the synthesis. The photodetector exhibited a high ultraviolet photoresponsivity of up to 1970.7 mA/W, and detectivity up to 2.6 × 1013 Jones, and was stable in harsh high temperature conditions. Our work provides a new synthesis method to prepare h-BN on GaN-based materials directly, and a novel vertically oriented structure of VO-h-BN/GaN heterojunction, which has great application potential in optoelectronic devices.

Recently, female breast cancer (BC) has surpassed lung cancer to occupy the first place of the most commonly diagnosed cancer. The unsatisfactory prognosis of endocrine therapy for breast cancer might be attributed to the discordance in estrogen receptor (ER) status between primary tumors and corresponding metastases, as well as temporal and spatial receptor status heterogeneity at point-in-time between biopsy and treatment. The purpose of this study was to evaluate the prognostic and predictive value of ER status in circulating tumor cells (CTCs) in BC patients. We analyzed ER expression on CTCs isolated using the Pep@MNPs method in 2.0 ml of blood samples from 70 patients with BC and 67 female controls. The predictive and prognostic value of ER expression in CTCs and immunohistochemistry results of biopsies for progression-free survival (PFS) and overall survival (OS) of patients in response to therapies were assessed. The detection rate for CTCs was 95.71% (67/70 patients), with a median of 8 CTCs within 2 ml of peripheral venous blood (PVB). A concordance of 76.56% in ER status between CTCs and corresponding primary tumor and 69.23% between CTCs and corresponding metastases was observed. We also found that patients with ER-positive CTCs (CTC ER+) had longer PFS and OS than those without ER-positive CTCs (CTC ER-). Our findings suggested that ER status in CTCs of BC patients may provide valuable predictive and prognostic insights into endocrine therapies, although further evaluation in larger prospective trials is required.

Bulk aluminum nitride (AlN) crystals with different polarities were grown by physical vapor transport (PVT). The structural, surface, and optical properties of m-plane and c-plane AlN crystals were comparatively studied by using high-resolution X-ray diffraction (HR-XRD), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy. Temperature-dependent Raman measurements showed that the Raman shift and the full width at half maximum (FWHM) of the E2 (high) phonon mode of the m-plane AlN crystal were larger than those of the c-plane AlN crystal, which would be correlated with the residual stress and defects in the AlN samples, respectively. Moreover, the phonon lifetime of the Raman-active modes largely decayed and its line width gradually broadened with the increase in temperature. The phonon lifetime of the Raman TO-phonon mode was changed less than that of the LO-phonon mode with temperature in the two crystals. It should be noted that the influence of inhomogeneous impurity phonon scattering on the phonon lifetime and the contribution to the Raman shift came from thermal expansion at a higher temperature. In addition, the trend of stress with increasing 1000/temperature was similar for the two AlN samples. As the temperature increased from 80 K to ~870 K, there was a temperature at which the biaxial stress of the samples transformed from compressive to tensile stress, while their certain temperature was different.

Abstract The nanomechanical properties of tumor‐derived small extracellular vesicles (sEVs) are essential to cancer progression. Here, nanoindentation is utilized on atomic force microscopy (AFM) to quantitatively investigate the nanomechanical properties of human breast cancer cell‐derived sEVs at single vesicle level and explore their relationship with tumor malignancy and vesicle size. It is demonstrated that the stiffness of the sEVs results from the combined contribution of the bending modulus and osmotic pressure of the sEVs. The stiffness and osmotic pressure increase with increasing malignancy of the sEVs and decrease with increasing size of the sEVs. The bending modulus decreases with increasing malignancy of the sEVs and is lower in smaller sEVs. This study builds relationship between the nanomechanical signature of the sEV and tumor malignancy, adding information for better understanding cancer mechanobiology.

The high crystal quality and low dislocation densities of aluminum nitride (AlN) grown on flat and nano-patterned sapphire substrate that are synthesized by the metal-organic chemical vapor deposition (MOCVD) method are essential for the realization of high-efficiency deep ultraviolet light-emitting diodes. The micro-strains of 0.18 × 10−3 cm−2 for flat substrate AlN and 0.11 × 10−3 cm−2 for nano-patterned substrate AlN are obtained by X-ray diffractometer (XRD). The screw and edge dislocation densities of samples are determined by XRD and transmission electron microscope (TEM), and the results indicate that the nano-patterned substrates are effective in reducing the threading dislocation density. The mechanism of the variation of the threading dislocation in AlN films grown on flat and nano-patterned substrates is investigated comparatively. The etch pit density (EPD) determined by preferential chemical etching is about 1.04 × 108 cm−2 for AlN grown on a nano-patterned substrate, which is slightly smaller than the results obtained by XRD and TEM investigation. Three types of etch pits with different sizes are all revealed on the AlN surface using the hot KOH etching method.

Extracellular vesicles (EVs) are nanoscale vesicles secreted by most types of cells as natural vehicles to transfer molecular information between cells. Due to their low toxicity and high biocompatibility, EVs have attracted increasing attention as drug delivery systems. Many studies have demonstrated that EV-loaded nucleic acids, including RNA-based nucleic acid drugs and CRISPR/Cas gene-editing systems, can alter gene expressions and functions of recipient cells for cancer gene therapy. Here in this review, we discuss the advantages and challenges of EV-based nucleic acid delivery systems in cancer therapy. We summarize the techniques and methods to increase EV yield, enhance nucleic acid loading efficiency, extend circulation time, and improve targeted delivery, as well as their applications in gene therapy and combination with other cancer therapies. Finally, we discuss the current status, challenges, and prospects of EVs as a therapeutic tool for the clinical application of nucleic acid drugs.

Receptor-targeting peptides have been extensively pursued for improving binding specificity and effective accumulation of drugs at the site of interest, and have remained challenging for extensive research efforts relating to chemotherapy in cancer treatments. By chemically linking a ligand of interest to drug-loaded nanocarriers, active targeting systems could be constructed. Peptide-functionalized nanostructures have been extensively pursued for biomedical applications, including drug delivery, biological imaging, liquid biopsy, and targeted therapies, and widely recognized as candidates of novel therapeutics due to their high specificity, well biocompatibility, and easy availability. We will endeavor to review a variety of strategies that have been demonstrated for improving receptor-specificity of the drug-loaded nanoscale structures using peptide ligands targeting tumor-related receptors. The effort could illustrate that the synergism of nano-sized structures with receptor-targeting peptides could lead to enrichment of biofunctions of nanostructures.

Abstract Multifunctional nanoplatforms for imaging‐guided synergistic antitumor treatment are highly desirable in biomedical applications. However, anticancer treatment is largely affected by the pre‐existing hypoxic tumor microenvironment (TME), which not only causes the resistance of the tumors to photodynamic therapy (PDT), but also promotes tumorigenesis and tumor progression. Here, a continuous O2 self‐enriched nanoplatform is constructed for multimodal imaging‐guided synergistic phototherapy based on octahedral gold nanoshells (GNSs), which are constructed by a more facile and straightforward one‐step method using platinum (Pt) nanozyme‐decorated metal–organic frameworks (MOF) as the inner template. The Pt‐decorated MOF@GNSs (PtMGs) are further functionalized with human serum albumin‐chelated gadolinium (HSA‐Gd, HGd) and loaded with indocyanine green (ICG) (ICG‐PtMGs@HGd) to achieve a synergistic PDT/PTT effect and fluorescence (FL)/multispectral optoacoustic tomography (MSOT)/X‐ray computed tomography (CT)/magnetic resonance (MR) imaging. The Pt‐decorated nanoplatform endows remarkable catalase‐like behavior and facilitates the continuous decomposition of the endogenous H2O2 into O2 to enhance the PDT effect under hypoxic TME. HSA modification enhances the biocompatibility and tumor‐targeting ability of the nanocomposites. This TME‐responsive and O2 self‐supplement nanoparticle holds great potential as a multifunctional theranostic nanoplatform for the multimodal imaging‐guided synergistic phototherapy of solid tumors.

Small extracellular vesicles (sEVs) carry molecular information from their source cells and are desired biomarkers for cancer diagnosis. We establish a machine learning-assisted dual-marker detection method to analyze the expression of epidermal growth factor receptor (EGFR) and C-X-C chemokine receptor 4 (CXCR4) in serum sEVs for the diagnosis and prognosis prediction of non-small cell lung cancer (NSCLC). We find that the serum sEV EGFR and CXCR4 are significantly higher in advanced stage NSCLC (A/NSCLC) patients compared to early stage NSCLC (E/NSCLC) patients and the healthy donors (HDs). A receiver operating characteristic curve (ROC) analysis demonstrates that the combination of EGFR and CXCR4 in serum sEVs as an efficient diagnostic index and malignant degree indicator for NSCLC. Machine learning further shows a diagnostic accuracy of 97.4% for the training cohort and 91.7% for the validation cohort based on the combinational marker. Moreover, this machine leaning-assisted serum sEV analysis successfully predicts the possibility of tumor relapse in three NSCLC patients by comparing their serum sEVs before and three days after surgery. This study provides an intelligent serum sEV-based assay for the diagnosis and prognosis prediction of NSCLC, and will benefit the precision management of NSCLC.

Surface plasmon (SP) enhancement of photoluminescence (PL) from a green-emitting InGaN/GaN quantum well (QW) using nanoparticles (NPs) made of different metals and their combinations was investigated. The NPs were formed by annealing the metal films in N2 followed by rapid cooling. Four-fold enhancement in PL intensity was achieved using random metal NPs made of Cu on Mg (Cu-Mg) double metal film that was more than two folds of the enhancement observed by AgNPs. Reversing the order of metal film deposition (Mg on Cu) resulted in much lower PL intensity due to significantly different NPs size distribution as the given annealing conditions did not cause homogeneous alloying of the two metals. The results pave the way for the application of NPs of relatively low-cost unconventional metals and their combinations in the SP enhancement of LEDs.

A small Boron ion (B-ion) dose of 5 × 1014 cm−2 was implanted in a GaN epilayer at an energy of 50 keV, and the sample was subjected to high-temperature rapid thermal annealing (RTA). The resonant Raman spectrum (RRS) showed a strong characteristic of a photoluminescence (PL) emission peak associated with GaN before B-ion implantation and RTA treatment. The PL signal decreased significantly after the B-ion implantation and RTA treatment. The analysis of temperature-dependent Raman spectroscopy data indicated the activation of two transitions in B-ion-implanted GaN in different temperature ranges with activation energies of 66 and 116 meV. The transition energies were estimated in the range of 3.357–3.449 eV through calculations. This paper introduces a calculation method that can be used to calculate the activation and transition energies, and it further highlights the strong influence of B-ion implantation on the luminesce of GaN.

Most chiral molecules and structures in living organisms exist as single enantiomers, but why? Here, the authors investigated surface-mediated homochirality on the single-molecule level and show that it can be triggered by the chirality unbalance of two adsorption configuration monomers.

Misfolding and abnormal aggregation of β-amyloid peptide is associated with the onset and progress of Alzheimer's disease (AD). Therefore, modulating β-amyloid aggregation is critical for the treatment of AD. Herein, we studied the regulatory effects and mechanism of graphene quantum dots (GQDs) on 1–42 β-amyloid (Aβ1–42) aggregation. GQDs displayed significant regulatory effects on the aggregation of Aβ1–42 peptide as detected by thioflavin T (ThT) assay. Then, the changes of confirmations and structures induced by GQDs on the Aβ1–42 aggregation were monitored by circular dichroism (CD), dynamic light scattering (DLS) and transmission electron microscope (TEM). The in vitro cytotoxicity experiments further demonstrated the feasibility of GQDs on the regulation of Aβ1–42 aggregation. Meanwhile, the structural changes of a Aβ1–42/GQDs mixture in different pH revealed that electrostatic interaction was the major driving force in the co-assembly process of Aβ1–42 and GQDs. The proposed mechanism of the regulatory effects of GQDs on the Aβ1–42 aggregation was also deduced reasonably. This work not only demonstrated the potential feasibility of GQDs as therapeutic drug for AD but also clarified the regulatory mechanism of GQDs on the Aβ1–42 aggregation.

Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a slow process, partly due to the difficulty of delivering drugs effectively. Nanoparticles, with their targeted delivery capabilities, biocompatibility, and enhanced bioavailability over conventional drugs, are garnering attention for spinal cord injury treatment. This review explores the current mechanisms and shortcomings of existing treatments, highlighting the benefits and progress of nanoparticle-based approaches. We detail nanoparticle delivery methods for spinal cord injury, including local and intravenous injections, oral delivery, and biomaterial-assisted implantation, alongside strategies such as drug loading and surface modification. The discussion extends to how nanoparticles aid in reducing oxidative stress, dampening inflammation, fostering neural regeneration, and promoting angiogenesis. We summarize the use of various types of nanoparticles for treating spinal cord injuries, including metallic, polymeric, protein-based, inorganic non-metallic, and lipid nanoparticles. We also discuss the challenges faced, such as biosafety, effectiveness in humans, precise dosage control, standardization of production and characterization, immune responses, and targeted delivery in vivo. Additionally, we explore future directions, such as improving biosafety, standardizing manufacturing and characterization processes, and advancing human trials. Nanoparticles have shown considerable progress in targeted delivery and enhancing treatment efficacy for spinal cord injuries, presenting significant potential for clinical use and drug development.

Background: Tumor PD-L1 levels have predictive value in PD-1/PD-L1 checkpoint blockade therapies, yet biopsies can only provide baseline information. Whether PD-L1 expression on circulating tumor cells (CTCs) could serve as an alternative biomarker is of great interest. Design: We established an immunofluorescence assay for semi-quantitative assessment of the PD-L1 expression levels on CTCs with four categories (PD-L1negative, PD-L1low, PD-L1medium and PD-L1high). 35 patients with different advanced gastrointestinal tumors were enrolled in a phase 1 trial of a PD-1 inhibitor, IBI308. The CTC numeration and the PD-L1 expression levels were analyzed. Results: Prior the treatment of IBI308, 97% (34/35) patients had CTCs, ranging from1 to 70 (median 7). 74% (26/35) had PD-L1positive CTCs, and 60% (21/35) had at least one PD-L1high CTCs. The disease control (DC) rate in PD-L1high patients (48%) is much higher than the others (14%). The group with at least 20% abundance of PD-L1high CTCs had even higher DC rate of 64% (9/14), with only 14% DC rate for the rest (3/21). We also observed that the count changes of total CTC, PD-L1postive CTC and PD-L1high CTC correlate quite well with disease outcome (P

Cancer is the leading cause of death worldwide, and metastasis is the main attribute to cancer death. CXCR4 and its natural ligand CXCL12 have been known to play a critical role in tumorigenesis, angiogenesis and metastasis. Therefore, designing a new CXCR4 antagonist to prevent tumor metastasis will be of great significance. Herein, a novel chemically synthesized peptide (E5) that has an ability to target CXCR4/CXCL12 axis was loaded in micelle glycol-phosphatidylethanolamine (PEG-PE) block copolymer to form micelle-encapsulated E5 (M-E5). We demonstrated that M-E5 exhibited higher affinity for CXCR4-overexpressing MCF-7 and HepG2 tumor cells as compared to free E5, and efficiently inhibited the tumor cells migration. Mechanistic studies implied that PEG-PE micelle can encapsulate E5 and improve E5 targeting efficiency for CXCR4 by accumulating E5 on the tumor cell membrane. Furthermore, through encapsulation of chemotherapeutic drug doxorubicin (Dox) in PEG-PE micelle, we proved that PEG-PE micelle could serve as a co-carrier for both E5 and Dox (M-E5-Dox). M-E5 enhanced the efficiency of Dox by down-regulating the phosphorylation level of Akt, Erk and p38/MAPK proteins. In conclusion, PEG-PE micelle demonstrated a promising delivery system for E5, and M-E5 is expected to be a potential therapeutic agent that will help to improve the clinical benefits in current therapies used for solid tumors.

Purple membranes (PM) of the bacteria Halobacterium salinarum are a unique natural membrane where bacteriorhodopsin (BR) can convert photon energy and pump protons. Elucidating the electronic properties of biomembranes is critical for revealing biological mechanisms and developing new devices. We report here the electric properties of PMs studied by using multi-functional electric force microscopy (EFM) at the nanoscale. The topography, surface potential, and dielectric capacity of PMs were imaged and quantitatively measured in parallel. Two orientations of PMs were identified by EFM because of its high resolution in differentiating electrical characteristics. The extracellular (EC) sides were more negative than the cytoplasmic (CP) side by 8 mV. The direction of potential difference may facilitate movement of protons across the membrane and thus play important roles in proton pumping. Unlike the side-dependent surface potentials observed in PM, the EFM capacitive response was independent of the side and was measured to be at a dC/dz value of ~5.25 nF/m. Furthermore, by modification of PM with de novo peptides based on peptide-protein interaction, directional oriented PM assembly on silicon substrate was obtained for technical devices. This work develops a new method for studying membrane nanoelectronics and exploring the bioelectric application at the nanoscale.