Establishing an accurate, simple, and rapid serodiagnosis method aiming for specific cancer antigens is critically important for the clinical diagnosis, therapy, and prognostication of cancer. ...Currently, surface-enhanced Raman scattering (SERS) readout techniques challenge fluorescent-based detection methods in terms of both optical stability and more importantly multiple detection capability, which become more desirable for clinical diagnostics. We thus started using an interference-free mixing SERS emission (m-SERS) readout to simultaneously indicate, for the first time, three specific liver cancer antigens, including α-fetoprotein (AFP), carcinoembryonic antigen (CEA), and ferritin (FER), even in one clinical serum sample. Here, three triple bonds (CN and CC) coded SERS tags contribute separate SERS emissions located at 2105, 2159, and 2227 cm–1, respectively; must have one-to-one correspondence from AFP, to FER, to CEA, In the process of detection, the mature double antibody sandwich allows the formation of microscale core–satellite assembly structure between a magnetic bead (MB) and single SERS tags, and therefore a pure and single SERS emission can be observed under the routine excitation laser spot. Because of the action of magnetic force, the uniform 3D packing of SERS tags absorbed MBs will in contrast generate a so-called m-SERS signals. With the help of enrichment and separation by MBs, the proposed m-SERS immunoassay provides an extremely rapid, sensitive, and accurate solution for multiplex detection of antigens or other biomarkers. Herein, the limit of detection (LOD) for simultaneous m-SERS detection of AFP, CEA, and FER was 0.15, 20, and 4 pg/mL, respectively. As expected for 39 clinical serum samples, simultaneous detection of ternary specific antigens can significantly improve the accuracy of liver cancer diagnosis.
Abstract Black phosphorus (BP) nanostructures such as nanosheets and nanoparticles have attracted considerable attention in recent years due to their unique properties and great potential in various ...physical, chemical, and biological fields. In this article, water-soluble and biocompatible PEGylated BP nanoparticles with a high yield were prepared by one-pot solventless high energy mechanical milling technique. The resultant BP nanoparticles can efficiently convert near infrared (NIR) light into heat, and exhibit excellent photostability, which makes them suitable as a novel nanotheranostic agent for photoacoustic (PA) imaging and photothermal therapy of cancer. The in-vitro results demonstrate the excellent biocompatibility of PEGylated BP nanoparticles, which can be used for photothermal ablation of cancer cells under irradiation with NIR light. The in-vivo PA images demonstrate that these BP nanoparticles can be efficiently accumulated in tumors through the enhanced permeability retention effect. The resultant BP nanoparticles can be further utilized for photothermal ablation of tumors by irradiation with NIR light. The tumor-bearing mice were completely recovered after photothermal treatment with BP nanoparticles, in comparison with mice from control groups. Our research highlights the great potential of PEGylated BP nanoparticles in detection and treatment of cancer.
•Conduct a series of experiments and simulations on cracking process of the brittle sandstone specimens with different shapes of holes.•Analyze the effect of the shape of hole on the uniaxial ...compression strength and failure behavior of brittle sandstone by experiment.•Reveal the crack evolution mechanism of brittle sandstone containing different shapes of holes by force distribution.
Defects, such as joints, fissures and holes, are common in natural rocks. These pre-existing defects have significant effects on the mechanical properties of rock masses. Researchers have performed several studies on jointed or fissured rocks; however, rock specimens with one hole of different shapes have not been studied systematically. In this research, the mechanical properties and cracking behaviors of specimens with a hole under uniaxial compressive loading are explored through laboratory experiments. The corresponding numerical simulations using two-dimensional particle flow code (PFC2D) are conducted and the force field distribution before and during cracking, which is significant for exposing the cracking mechanism but hard to be measured in laboratory tests, were captured. The results demonstrate that the shape of hole has a considerable impact on the uniaxial compression strength and failure mode but minimal effects on the elastic modulus. The force field distribution before crack initiation varies with the shape of the pre-existing hole, and differences primarily exist in the configuration of the pure tension triangle and the low force region. During compressive loading, the crack initiation and propagation are influenced by the force field distribution, which will be affected by the newly formed cracks in return. The macro-cracks, generated in the specimens with a hole under compression, can be assigned to two categories: tension-induced cracks and compression-induced cracks. The former type of crack is typically thin and comparatively orderly, and it generally propagates along the maximum loading direction. The latter type of crack is relatively disorderly and thick, and it typically forms from the coalescence of several short but thick cracks. The compression-induced crack is a mixture of tension and shear cracks whereas the tension-induced crack is a pure tension crack.
Inorganic nanoparticles as a versatile nanoplatform have been broadly applied in the diagnosis and treatment of cancers due to their inherent superior physicochemical properties (including magnetic, ...thermal, optical, and catalytic performance) and excellent functions (e.g., imaging, targeted delivery, and controlled release of drugs) through surface functional modification or ingredient dopant. However, in practical biological applications, inorganic nanomaterials are relatively difficult to degrade and excrete, which induces a long residence time in living organisms and thus may cause adverse effects, such as inflammation and tissue cysts. Therefore, the development of biodegradable inorganic nanomaterials is of great significance for their biomedical application. This Review will focus on the recent advances of degradable inorganic nanoparticles for cancer theranostics with highlight on the degradation mechanism, aiming to offer an in-depth understanding of degradation behavior and related biomedical applications. Finally, key challenges and guidelines will be discussed to explore biodegradable inorganic nanomaterials with minimized toxicity issues, facilitating their potential clinical translation in cancer diagnosis and treatment.
Surface-enhanced Raman scattering (SERS) and magnetic resonance imaging (MRI)-guided phototherapy are new breakthroughs in cancer therapeutics due to their complementary advantages, such as enhanced ...imaging spatial resolution and depth. Herein, we synthesized monodispersed Prussian blue-encapsulated gold nanoparticles (Au@PB NPs), in which the plasmonic gold core plus coordination polymer of cyanide (Ctriple bond, length as m-dashN) and iron ions coincidently become a superexcellent contrast agent for both MRI and zero-background SERS imaging. PB, as a signal source for MR and SERS, can be easily assembled onto single Au NPs, of which iron ions possess high relaxation efficiency for in vivo MRI, e.g., the longitudinal and transversal relaxation efficiency values are 0.86 mM-1 s-1 (r1) and 5.42 mM-1 s-1 (r2), respectively. Furthermore, with the help of the plasmonic enhancement of the gold core, the Ctriple bond, length as m-dashN groups exhibit a specific, strong, and stable (3S) SERS emission in the Raman-silent region (1800-2800 cm-1), allowing accurate in vivo imaging at the single or even subcellular level. More importantly, PB has remarkable absorption properties in the near infrared region, and can be used as a photosensitizer for photothermal (PT) and photodynamic (PD) therapy simultaneously. Hence, the ideal integration of a plasmonic Au core and PB shell into a single monodispersed MR-guided NP, with zero-background SERS signals, is an important candidate for both tumor navigation and in situ PT/PD treatment guided by SERS/MR dual-mode imaging.
The expression of gp350 facilitates the recognition of EBV by the human immune system and initiates the complement pathway and antibody-dependent cell-mediated cytotoxicity (ADCC) to eliminate the EB ...virus. 11 Excessive inflammatory reactions, especially in a microenvironment that results from nonresolving inflammation, may lead to DNA breakage, increase the probability of mutation and induce cell proliferation, which may eventually lead to carcinogenesis. 2 Moreover, through the downregulation of the expression of c-Jun (AP1 transcription factor), LTF can inhibit the transcriptional activation of c-Jun by the AKT pathway kinase PDK1, which downregulates the activity of the AKT pathway and inhibits the growth of NPC cells through downstream AKT signaling. 15 LTF can also inhibit PDK1 and then inhibit AKT phosphorylation and membrane translocation, which leads to the inhibition of tumor cell proliferation, invasion and metastasis through the PDK1/AKT pathway.
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•Plant-inspired TiO2/C hybrids with controllable morphologies have been fabricated.•The oxidized Ti3C2Tx MXene was employed as the support of TiO2 crystals and carbon.•The obtained ...TiO2/C hybrids demonstrate tunable electrorheological (ER) performances.•The design principle is generally applicable to other metal (M) oxides/C systems.
Well defined morphology of titanium dioxide/carbon (TiO2/C) hybrids provides intriguing physical chemical properties, thus, they are attractive for broadly specific applications. However, the conventional wisdom of rational design of TiO2/C hybrids has not been satisfactorily investigated especially in nanostructure mainly due to the heterogeneous interface barriers between TiO2 and carbon. Herein, we present a completely novel yet generalized approach for the fabrication of TiO2/C hybrids with tunable bio-inspired shapes (e.g., grape-like, echeveria-like, albizia-like, bamboo-type, chestnut-like, etc.) based on a versatile solvothermal technique. To reduce interfacial barriers between TiO2 and carbon layers, the TiO2 nanoparticles are firstly decorated on the conductive carbon layers via an in-situ CO2 oxidation of Ti3C2Tx MXene (c-TiO2/C). The TiO2 arrays are heteroepitaxially grown on the c-TiO2/C substrate, which serves simultaneously as the TiO2 crystal seeds and carbon sources. A series of bio-inspired TiO2/C hybrids with desired constituent nano-units (including nanoplates, nanorods, nanoribbons, and nanowires) are facilely achieved via simply tuning the amounts and calcination temperatures of c-TiO2/C along with the hydrothermal time. More interestingly, the introduction of lithium ions can split the TiO2 arrays into small pieces, which is highly beneficial for the design of TiO2/C hybrids with preferred architectures. A detailed growth mechanism of the achieved TiO2/C hybrids is also proposed. Additionally, these TiO2/C hybrids provide valuable applications in many fields, such as sensing, catalysis and energy storage. Take the electro-responsive activity as an example, the achieved TiO2/C hybrids with tailored morphologies demonstrate tunable electro-rheological (ER) performances. The design principle is generally applicable to other metal (M) oxides/C systems, which will provide excellent opportunities for designing advanced material systems with widespread multifunctional applications.
Rheumatoid arthritis has a significant impact on the life quality, but current pharmacological therapies have limitations. As a result, there is growing interest in exploring the potential of natural ...plant components to intervene in the development of rheumatoid arthritis. Resveratrol, a natural polyphenol and one of the main active components of the Chinese herbal medicine Polygonum cuspidatum, has emerged as a promising candidate for this purpose. In the present study, we investigated the role and mechanism of resveratrol in inhibiting inflammatory response in rat primary fibroblast-like synoviocytes. Tumor necrosis factor (TNF)-α was used to establish a model of inflammation, the Sirtuin1 selective inhibitor Selisistat (EX527) was used to inhibit Sirtuin1 activity, and small interfering RNA was used to silence cortistatin expression. The results showed that pre-treatment with resveratrol could time- and dose-dependently inhibit TNF-α induced cellular interleukin (IL)-1β and IL-6 secretion, and upregulate Sirtuin1 and cortistatin mRNA and protein expression in the range of 48 h, 100 µM. Selisistat (EX527) could attenuate resveratrol inhibited inflammatory response and upregulated cortistatin expression. Silencing cortistatin expression attenuated the effect of resveratrol on inhibiting inflammatory response, but did not affect its effect on upregulating Sirtuin1 expression. In conclusion, resveratrol effectively inhibited the TNF-α induced inflammatory response in fibroblast-like synoviocytes by a mechanism involving the Sirtuin1/cortistatin pathway.
To ascertain if preoperative short-term radiotherapy followed by chemotherapy is not inferior to a standard schedule of long-term chemoradiotherapy in patients with locally advanced rectal cancer.
...Patients with distal or middle-third, clinical primary tumor stage 3-4 and/or regional lymph node-positive rectal cancer were randomly assigned (1:1) to short-term radiotherapy (25 Gy in five fractions over 1 week) followed by four cycles of chemotherapy (total neoadjuvant therapy TNT) or chemoradiotherapy (50 Gy in 25 fractions over 5 weeks, concurrently with capecitabine chemoradiotherapy; CRT). Total mesorectal excision was undertaken 6-8 weeks after preoperative treatment, with two additional cycles of CAPOX (intravenous oxaliplatin 130 mg/m
, once a day on day 1 and capecitabine 1,000 mg/m
, twice a day from days 1 to 14) in the TNT group and six cycles of CAPOX in the CRT group. The primary end point was 3-year disease-free survival (DFS).
Between August 2015 and August 2018, a total of 599 patients were randomly assigned to receive TNT (n = 302) or CRT (n = 297). At a median follow-up of 35.0 months, 3-year DFS was 64.5% and 62.3% in TNT and CRT groups, respectively (hazard ratio, 0.883; one-sided 95% CI, not applicable to 1.11;
< .001 for noninferiority). There was no significant difference in metastasis-free survival or locoregional recurrence, but the TNT group had better 3-year overall survival than the CRT group (86.5%
75.1%;
= .033). Treatment effects on DFS and overall survival were similar regardless of prognostic factors. The prevalence of acute grade III-V toxicities during preoperative treatment was 26.5% in the TNT group versus 12.6% in the CRT group (
< .001).
Short-term radiotherapy with preoperative chemotherapy followed by surgery was efficacious with acceptable toxicity and could be used as an alternative to CRT for locally advanced rectal cancer.
Diabetic ulcers (DUs) appearing as chronic wounds are difficult to heal due to the oxidative stress in the wound microenvironment and their high susceptibility to bacterial infection. A routine ...treatment combining surgical debridement with anti‐infection therapy is widely used for treating DUs in the clinic, but hardly offers a satisfying wound healing outcome. It is known that a long‐term antibiotic treatment may also lead to the drug resistance of pathogens. To address these challenges, new strategies combining both reactive oxygen species (ROS) scavenging and bacterial sterilization have been proposed for fighting against DUs. Following this idea, oxygen deficient molybdenum‐based nanodots (MoO3−X) for healing the DUs are reported. The ROS scavenging ability of MoO3−X nanodots is investigated and the antibacterial property of the nanodots is also demonstrated. The systematic cell and animal experimental results indicate that the MoO3−X nanodots can effectively reduce inflammation, promote epithelial cell regeneration, accelerate angiogenesis, and facilitate DUs recovery. Most importantly, they present excellent capacity to diminish infection of methicillin‐resistant Staphylococcus aureus, manifesting the potent application prospect of MoO3−X nanodots for diabetic wound therapy.
Diabetic ulcer wounds are difficult to heal because of excessive ROS generation, and susceptibility to infection by bacteria. In this work, a type of simple MoO3−X nanodots integrated the functions of excellent ROS scavenging and broad‐spectrum bacteria‐killing is introduced. Importantly, the nanodots can effectively accelerate drug‐resistant bacteria infected diabetic wound healing.
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