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Background Fluorescence imaging as the beacon for optical navigation has wildly developed in preclinical studies due to its prominent advantages, including noninvasiveness and superior temporal resolution. However, the traditional optical methods based on ultraviolet (UV, 200–400 nm) and visible light (Vis, 400–650 nm) limited by their low penetration, signal-to-noise ratio, and high background auto-fluorescence interference. Therefore, the development of near-infrared-II (NIR-II 1000–1700 nm) nanoprobe attracted significant attentions toward in vivo imaging. Regrettably, most of the NIR-II fluorescence probes, especially for inorganic NPs, were hardly excreted from the reticuloendothelial system (RES), yielding the anonymous long-term circulatory safety issue. Results Here, we develop a facile strategy for the fabrication of Nd3+-doped rare-earth core–shell nanoparticles (Nd-RENPs), NaGdF4:5%Nd@NaLuF4, with strong emission in the NIR-II window. What’s more, the Nd-RENPs could be quickly eliminated from the hepatobiliary pathway, reducing the potential risk with the long-term retention in the RES. Further, the Nd-RENPs are successfully utilized for NIR-II in vivo imaging and magnetic resonance imaging (MRI) contrast agents, enabling the precise detection of breast cancer. Conclusions The rationally designed Nd-RENPs nanoprobes manifest rapid-clearance property revealing the potential application toward the noninvasive preoperative imaging of tumor lesions and real-time intra-operative supervision. Graphical abstract

Background Few studies focused on the functional outcomes of patients at 3 months after receiving intravenous thrombolysis, anticoagulation, or antiplatelet therapy within 4.5 h of onset of the cardiogenic cerebral embolism (CCE) subtype. Methods The purpose of this retrospective study was to analyse the clinical data of patients with acute CCE and compare the 3-month functional prognoses of patients after administration of different antithrombotic therapies within 4.5 h of stroke onset. A total of 335 patients with CCE hospitalized in our institution were included in this study. The patients were stratified according to the hyperacute treatment received, and baseline clinical and laboratory data were analysed. A 3-month modified Rankin scale (mRS) score of 0–2 was defined as an excellent functional outcome. Results A total of 335 patients were divided into thrombolytic (n = 78), anticoagulant (n = 88), and antiplatelet therapy groups (n = 169). A total of 164 patients had a good prognosis at 3 months (mRS ≤ 2). After adjustments were made for age and National Institute of Health Stroke Scale (NIHSS) score, each group comprised 38 patients, and there were no significant differences in sex composition, complications, lesion characteristics, or Oxfordshire Community Stroke Project (OSCP) classification among the three groups. The plasma D-dimer level (µg/ml) in the thrombolytic group was significantly higher than those in the anticoagulant and antiplatelet groups [3.07 (1.50,5.62), 1.33 (0.95,1.89), 1.61 (0.76,2.96), P P = 0.025]. A total of 47 patients (41.2 %) had an mRS score of ≤ 2 at 3 months, and 23 patients died (20.2 %). There was no significant difference in the proportion of patients with a good prognosis or the mortality rate among the three groups (P = 0.363, P = 0.683). Conclusions Thrombolytic therapy is effective at improving short-term and 3-month prognoses. Anticoagulant therapy may be a safe and effective treatment option for patients with the cardiac stroke subtype who fail to receive intravenous recombinant tissue plasminogen activator (r-tPA) thrombolysis within 4.5 h in addition to antiplatelet therapy, as recommended by the guidelines.

With a 5-year overall survival of approximately 20%, lung cancer has always been the number one cancer-specific killer all over the world. As a fusion of positron emission computed tomography (PET) and computed tomography (CT), PET/CT has revolutionized cancer imaging over the past 20 years. In this review, we focused on the optimization of the function of 18F-flurodeoxyglucose (FDG)-PET/CT in diagnosis, prognostic prediction and therapy management of lung cancers by computer programs. FDG-PET/CT has demonstrated a surprising role in development of therapeutic biomarkers, prediction of therapeutic responses and long-term survival, which could be conducive to solving existing dilemmas. Meanwhile, novel tracers and optimized procedures are also developed to control the quality and improve the effect of PET/CT. With the continuous development of some new imaging agents and their clinical applications, application value of PET/CT has broad prospects in this area.

Two-dimensional (2D) nanomaterials have shown promising potential in a wide range of biomedical applications. Nevertheless, the rapid advances in this field recently have also evoked growing concer...

Antibacterial agents are an important tool in the prevention of bacterial infections. Inorganic materials are attractive due to their high stability under a variety of conditions compared to organic antibacterial agents. Herein tungsten oxide nanodots (WO3-x), synthesized by a simple one-pot synthetic approach, were found to exhibit strong antibacterial capabilities. The analyses with colony-forming units (CFU) showed an excellent antibacterial activity of WO3-x against both Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) strains. The scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images revealed clear damages to the bacterial cell membranes, which was further confirmed by molecular dynamics simulations. Additionally, exposure to simulated sunlight was found to further increase the germicidal activity of WO3-x nanodots, a 30 min exposure to sunlight combined with 50 μg/mL WO3-x nanodots showed a 70% decrease in E. coli viability compared to without exposure. Electron spin resonance spectroscopy (ESR) was used to elucidate the underlying mechanism of this photocatalytic activity through the generation of hydroxyl radical species. The cell counting kit-8 (CCK-8) and the live/dead assay were further employed to evaluate the cytotoxicity of WO3-x nanodots on eukaryotic cells, which demonstrated their general biocompatibility. In summary, our results suggest WO3-x nanodots have considerable potential in antibacterial applications, while also being biocompatible at large.

Purpose: The main objective is to investigate the protective effect of camel milk (CM) on radiation-induced intestinal injury. Methods: The C57BL/6 J mice in 2 experiments were assigned into control group (Con), irradiation group (IR), and CM+irradiation group (CM+IR). After receiving the CM via gavage for 14 days, the mice in the first experiment were exposed to 6 Gy X-ray whole body irradiation, and survival rate was compared among the groups. Mice in the second experiment were exposed to 4 Gy irradiation and sacrificed at day 7. The small intestines were collected to examine the histopathological changes and to determine the anti-oxidative index and HMGB1/TLR4 inflammatory pathway. Fasting blood was used to measure serum pro-inflammatory factors. Results: Compared with the IR group, the survival time was prolonged, and survival rate was increased in the CM+IR group. CM increased levels of SOD and GSH and decreased MDA in the jejunum. Furthermore, intestinal protein expression of HMGB1/TLR4 pathway (TLR4, NF-κB, and HMGB1) was up-regulated by CM intervention. CM decreased the serum levels of TNF-α and IL-1β and increased IL-10 level. Conclusions: CM extended the survival time and had a protective effect against radiation-induced jejunum injury by regulation of antioxidant capacity and HMGB1/TLR4/NF-κB/MyD88 inflammatory signaling pathway.

Purpose and Methods: To investigate the doses of total body (TBI) and whole abdominal irradiation (WAI) induced lethal intestinal injury, healthy C57BL/6 J mice were divided randomly into 7 groups: control group; 6, 7, and 8 Gy TBI groups; and 5, 10, and 15 Gy WAI groups. The survival length, general conditions, body weight, daily food and water intake of the mice and the histopathological changes of small intestine were observed. Results: Lethal injury among C57BL/6 J mice was caused by ≥6 Gy TBI and 15 Gy WAI. Their body weight and food intake decreased, the structure of their small intestinal villi was destroyed, and the number of surviving crypts per circumference of the jejunum decreased in ≥6 Gy TBI groups and 15 Gy WAI group. The mice in the 10 Gy WAI group significantly lost weight within 5 days but recovered slowly thereafter. They also had poor appetite and reversibly damaged intestinal mucosa. Conclusions: Nonlethal intestinal injury could be induced by 10 Gy WAI, whereas lethal intestinal injury could be triggered by ≥6 Gy TBI and >15 Gy WAI in mice. Our results provided a basis for establishing radiation-induced intestinal injury models with C57BL/6 J mice.

Boron nitride (BN) nanosheets have emerged as promising nanomaterials in a wide range of biomedical applications. Despite extensive studies on these bio-nano interfacial systems, the underlying molecular mechanisms remain elusive. In this study, we used hemolysis assays and morphology observations to demonstrate for the first time that BN nanosheets can cause damages to the red-blood-cell membranes, leading to significant hemolysis. Further molecular dynamics simulations revealed that BN nanosheets can penetrate into the cell membrane and also extract considerable amount of phospholipid molecules directly from the lipid bilayer. The potential of mean force calculations then showed that their penetration effect was thermodynamically favorable due to the strong attractive van der Waals interactions between BN nanosheets and phospholipids. Overall, these findings provided valuable insights into the interaction of BN nanosheets with cell membranes at the atomic level, which can help future de novo design of BN-based nanodevices with better biocompatibility.

The antibacterial activities of tungsten disulfide (WS2) nanosheets against two representative bacterial strains: Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) were evaluated by colony-forming unit (CFU) studies. The WS2 samples demonstrate a time and concentration dependent antibacterial activity (retardation of bacterial growth) for both bacterial strains. Morphology analyses reveal that WS2 nanosheets adhere to the bacterial surfaces, resulting in robust inhibition of cell proliferation once a bacterium is fully covered with this nanomaterial. More importantly, the intimate contact of WS2 nanosheets with a bacterium cell membrane can cause serious damage to the membrane integrity, and subsequently the cell death. On the other hand, the reactive oxygen species (ROS) generated by WS2 nanosheets are found to be modest regardless of the WS2 concentration, which is contradictory to the case of its structural analogue, MoS2, where ROS also play a significant role in its antibacterial activity. Taken together, our findings provide a detailed understanding of the antibacterial mechanism of WS2 nanosheets, which might help promote their potential applications in biomedical fields.

Antibacterial agents are an important tool in the prevention of bacterial infections. Inorganic materials are attractive due to their high stability under a variety of conditions compared to organic antibacterial agents. Herein tungsten oxide nanodots (WO3-X), synthesized by a simple one-pot synthetic approach, was found to exhibit efficient antibacterial capabilities. The analyses with colony-forming units (CFU) showed excellent antibacterial activity of WO3-Xagainst both gram-negativeE. coli(Escherichia coli) and gram-positiveS. aureus (Staphylococcus aureus) strains. The scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images revealed clear damage to the bacterial cell membranes, which was further confirmed by molecular dynamics simulations. Additionally, exposure to simulated sunlight was found to further increase germicidal activity of WO3-Xnanodots – a 30-minute exposure to sunlight (combining 50 μg/mL WO3-Xnanodots) showed a 70% decrease inE. coliviability compared to without exposure. Electron spin resonance spectroscopy (ESR) was used to elucidate the underlying mechanism of this photocatalytic activity through the generation of hydroxyl radical species. Cell counting kit-8 (CCK-8) and the live/dead assay were further employed to evaluate the cytotoxicity of WO3-Xnanodots on eukaryotic cells, which demonstrated their general biocompatibility. In all, our results suggest WO3-Xnanodots have considerable potential in antibacterial applications, while also being biocompatible at large.

Ultrasmall biocompatible WO3 - x nanodots with an outstanding X-ray radiation sensitization effect are prepared, and demonstrated to be applicable for multi-modality tumor imaging through computed tomography and photoacoustic imaging (PAI), and effective cancer treatment combining both photothermal therapy and radiation therapy.

Multiple drugs in combinatory therapy can improve the treatment of cancer due to their efficient reduction of multidrug resistance (MDR) of tumor cells. In this paper, we first synthesized a reduction-sensitive dextran-ss-camptothecin (Dex-ss-CPT, or Dex-CPT) prodrug conjugated by a disulfide bond, and a pH-responsive dextran-hyd-doxorubicin (Dex-hyd-DOX, or Dex-DOX) prodrug linked with an acid-cleavable hydrazone group. The chemical structures of the intermediate polymers and polymeric prodrugs have been fully characterized by 1H NMR, FT-IR, UV-Vis and HPLC analyses, respectively. Both prodrugs could self-assemble into uniform particles in aqueous solution. Subsequently, in vitro synergistic drug release of the two prodrugs was studied by methyl thiazolyl tetrazolium (MTT) assay. The reduction of a disulfide linker generates a thiol intermediate that is followed by intramolecular cyclization and the cleavage of the neighboring carbonate bridge, thus releasing native CPT molecules from the Dex-ss-CPT micelles. Similarly, the pH-sensitive hydrazone bond is broken under intracellular acidic conditions and the DOX parent drug is released from the Dex-hyd-DOX micelles. Finally, in vivo pharmacokinetics and biodistribution were investigated via intravenous administration with various formulations to treat 4T1 tumor-bearing mice. Meanwhile, the antitumor activity was also studied. This work demonstrates an effective anti-cancer prodrug design platform, which is expected to be useful for the treatment of various tumors.

Many recent studies have shown that the way nanoparticles interact with cells and biological molecules can vary greatly in the serum-containing or serum-free culture medium. However, the underlying molecular mechanisms of how the so-called "protein corona" formed in serum medium affects nanoparticles' biological responses are still largely unresolved. Thus, it is critical to understand how absorbed proteins on the surfaces of nanoparticles alter their biological effects. In this work, we have demonstrated with both experimental and theoretical approaches that protein BSA coating can mitigate the cytotoxicity of graphene oxide (GO) by reducing its cell membrane penetration. Our cell viability and cellular uptake experiments showed that protein corona decreased cellular uptake of GO, thus significantly mitigating the potential cytotoxicity of GO. The electron microscopy images also confirmed that protein corona reduced the cellular morphological damage by limiting GO penetration into the cell membrane. Further molecular dynamics (MD) simulations validated the experimental results and revealed that the adsorbed BSA in effect weakened the interaction between the phospholipids and graphene surface due to a reduction of the available surface area plus an unfavorable steric effect, thus significantly reducing the graphene penetration and lipid bilayer damaging. These findings provide new insights into the underlying molecular mechanism of this important graphene protein corona interaction with cell membranes, and should have implications in future development of graphene-based biomedical applications.

The widespread use of nanomaterials, such as carbon based 2D nanomaterials, in biomedical applications, has been accompanied by a growing concern on their biocompatibility, and in particular, on how they may affect the integrity of cell membranes. Herein, the interactions between C2 N, a novel 2D nanomaterial, and human red blood cell membranes are explored using a combined experimental and theoretical approach. The experimental microscopies show that C2 N exerts a negligible hemolysis effect on the blood cells with a superior compatibility to their cell membranes, when compared with the control system, reduced graphene oxide (rGO), which is found to be highly hemolytic. The molecular dynamics simulations further reveal the underlying molecular mechanisms, which indicate that C2 N prefers to be adsorbed flat on the water-membrane interface. Interaction energy analyses demonstrate the crucial role of Coulombic contributions, originating from the unique electrostatic potential surface of C2 N, in preventing C2 N from penetrating into cell membranes. These findings indicate a high compatibility of C2 N with cell membranes, which may provide useful foundation for the future exploration of this 2D nanomaterial in related biomedical applications.

Epigallocatechingallate (EGCG) is a major bioactive component of green tea and is associated with health benefits against multiple diseases including cancer. As an indicator of hepatocellular carcinoma (HCC), high levels of α-fetal protein (AFP) are related to malignant differentiation and poor prognosis of cancer cells. In this study, EGCG can effectively reduce AFP secretion and simultaneously induce AFP aggregation in human HCC HepG2 cells. EGCG-stimulated autophagy induces the degradation of AFP aggregates in HepG2 cells. Furthermore, we thoroughly studied the underlying molecular mechanisms behind EGCG-stimulated autophagy by using large-scale all-atom molecular dynamics simulations, which revealed a novel molecular mechanism. EGCG directly interacts with LC3-I protein, readily exposing the pivotal Gly-120 site of the latter to other important binding partners such as 1,2-distearoyl-sn-glycero-3-phosphoethanolamine and promoting the synthesis of LC3-II, a characteristic autophagosomal marker. Our results suggest that EGCG is critical in regulating AFP secretion and in modulating autophagic activities of HepG2 cells, providing a molecular basis for potentially preventing and treating HCC.