Reactive oxygen species (ROS) can be used not only as a therapeutic agent for chemodynamic therapy (CDT), but also as a stimulus to activate release of antitumor drugs, achieving enhanced efficacy ...through the combination of CDT and chemotherapy. Here we report a pH/ROS dual‐responsive nanomedicine consisting of β‐lapachone (Lap), a pH‐responsive polymer, and a ROS‐responsive polyprodrug. In the intracellular acidic environment, the nanomedicine can realize pH‐triggered disassembly. The released Lap can efficiently generate hydrogen peroxide, which will be further converted into highly toxic hydroxyl radicals via the Fenton reaction. Subsequently, through ROS‐induced cleavage of thioketal linker, doxorubicin is released from the polyprodrug. In vivo results indicate that the cascade of ROS generation and antitumor‐drug release can effectively inhibit tumor growth. This design of nanomedicine with cascade reactions offers a promising strategy to enhance antitumor efficacy.
Cascade reactions: A nanomedicine that consists of a pH‐responsive polymer and polyprodrug, which is responsive to reactive oxygen species (ROS), has been developed. This nanomedicine can achieve enhanced antitumor efficacy by the cascade of ROS generation and drug release, which is promising for chemo/chemodynamic combination cancer therapy.
The combination of chemotherapeutic drugs and reactive oxygen species (ROS) is a promising strategy to achieve improved anticancer effect. Herein, a nanomedicine (LaCIONPs) that can achieve ...tumor‐specific chemotherapeutic drug release and ROS generation is developed for cancer chemo/chemodynamic combination therapy. The LaCIONPs are constructed by encapsulation of iron oxide nanoparticles (IONPs) and β‐lapachone (La) in nanostructure assembled by hydrogen peroxide (H2O2)‐responsive polyprodrug and pH‐responsive polymer. Through the enhanced permeability and retention effect, the nanosized LaCIONPs can accumulate in tumor tissue. After the LaCIONPs are internalized by tumor cells, the structure of LaCIONPs is disintegrated in acidic intracellular environment, leading to rapid release of La and iron ions. Then the released La generates massive H2O2 through tumor specific catalysis. On the one hand, H2O2 further reacts with iron ions to produce highly toxic hydroxyl radicals for chemodynamic therapy. On the other hand, H2O2 also activates the release of camptothecin from the polyprodrug for chemotherapy. The potent antitumor effect of the LaCIONPs is demonstrated by both in vitro and in vivo results. Therefore, the LaCIONP is a promising nanomedicine for tumor‐specific chemo/chemodynamic combination therapy.
A pH and hydrogen peroxide (H2O2) dual‐responsive nanomedicine is developed for tumor‐specific chemo/chemodynamic combination therapy. Once the nanomedicines enter cancer cells through endocytosis, their structure is disintegrated, resulting in rapid release of β‐lapachone and iron ions. The β‐lapachone generates H2O2 inside cells, which further produces highly toxic hydroxyl radicals through the Fenton reaction and activates chemotherapeutic drug release.
Long nanopore reads are advantageous in de novo genome assembly. However, nanopore reads usually have broad error distribution and high-error-rate subsequences. Existing error correction tools cannot ...correct nanopore reads efficiently and effectively. Most methods trim high-error-rate subsequences during error correction, which reduces both the length of the reads and contiguity of the final assembly. Here, we develop an error correction, and de novo assembly tool designed to overcome complex errors in nanopore reads. We propose an adaptive read selection and two-step progressive method to quickly correct nanopore reads to high accuracy. We introduce a two-stage assembler to utilize the full length of nanopore reads. Our tool achieves superior performance in both error correction and de novo assembling nanopore reads. It requires only 8122 hours to assemble a 35X coverage human genome and achieves a 2.47-fold improvement in NG50. Furthermore, our assembly of the human WERI cell line shows an NG50 of 22 Mbp. The high-quality assembly of nanopore reads can significantly reduce false positives in structure variation detection.
Activatable imaging probes are promising to achieve increased signal‐to‐noise ratio for accurate tumor diagnosis and treatment monitoring. Magnetic resonance imaging (MRI) is a noninvasive imaging ...technique with excellent anatomic spatial resolution and unlimited tissue penetration depth. However, most of the activatable MRI contrast agents suffer from metal ion‐associated potential long‐term toxicity, which may limit their bioapplications and clinical translation. Herein, an activatable MRI agent with efficient MRI performance and high safety is developed for drug (doxorubicin) loading and tumor signal amplification. The agent is based on pH‐responsive polymer and gadolinium metallofullerene (GMF). This GMF‐based contrast agent shows high relaxivity and low risk of gadolinium ion release. At physiological pH, both GMF and drug molecules are encapsulated into the hydrophobic core of nanoparticles formed by the pH‐responsive polymer and shielded from the aqueous environment, resulting in relatively low longitudinal relativity and slow drug release. However, in acidic tumor microenvironment, the hydrophobic‐to‐hydrophilic conversion of the pH‐responsive polymer leads to amplified MR signal and rapid drug release simultaneously. These results suggest that the prepared activatable MRI contrast agent holds great promise for tumor detection and monitoring of drug release.
An activatable magnetic resonance imaging contrast agent, which is based on gadolinium metallofullerene and pH‐responsive polymer, is developed for tumor detection and drug delivery. Once the agent reaches the tumor area, the pH‐responsive polymer allows activation of magnetic resonance contrast and drug release (ON state). Therefore, the agent can be used for tumor signal‐amplification and monitoring of drug release.
Hierarchical porosity and functionalization help to fully make use of metal–organic frameworks (MOFs) for their diverse applications. Herein, a simple strategy is reported to construct hierarchically ...porous MOFs through a competitive coordination method using tetrafluoroborate (M(BF4)x, where M is metal site) as both functional sites and etching agents. The resulting MOFs have in situ formed defect‐mesopores and functional sites without sacrificing their structure stability. The formation mechanism of the defect‐mesopores is elucidated by a combination of experimental and first‐principles calculation method, indicating the general feasibility of this new approach. Compared with the original microporous counterparts, the new hierarchical MOFs exhibit superior adsorption for the bulky dye molecules and catalytic performance for the CO2 conversion attributed to their specific hierarchical pore structures.
A simple and novel strategy is reported to fabricate a series of hierarchically porous metal–organic frameworks through the competitive coordination method. The formation mechanism of defect‐mesopores is elucidated by a combination of experimental and first‐principles calculation methods. Furthermore, the adsorption and catalytic advantage over the original microporous counterparts is also demonstrated attributed to their specific hierarchical pore structures.
Since December 2019, novel coronavirus infected pneumonia emerged in Wuhan city and rapidly spread throughout China. In severe novel coronavirus pneumonia cases, the number of platelets, their ...dynamic changes during the treatment, platelet‐to‐lymphocyte ratio (PLR) were a concern. We sought to describe the platelet feature of these cases. Single‐center case series of the 30 hospitalized patients with confirmed coronavirus disease (COVID)‐19 in Huizhou municipal central hospital from January 2020 to February 2020 were retrospectively analyzed. Demographic, clinical, blood routine results, other laboratory results, and treatment data were collected and analyzed. Outcomes of severe patients and nonsevere patients were compared. Univariate analysis showed that: age, platelet peaks, and PLR at peak platelet were the influencing factors in severe patients, multivariate analysis showed that the PLR value at peak platelet during treatment was an independent influencing factor in severe patients. The average hospitalization day of patients with platelet peaks during treatment was longer than those without platelet peaks (P < .05). The average age of patients with platelet peaks during treatment was older than those without platelet peaks (P < .05). The patients with significantly elevated platelets during treatment had longer average hospitalization days. And the higher PLR of patients during treatment had longer average hospitalization days. Single‐center case series of the 30 hospitalized patients with confirmed COVID‐19 in Huizhou Municipal Central Hospital, presumed that the number of platelets and their dynamic changes during the treatment may have a suggestion on the severity and prognosis of the disease. The patient with markedly elevated platelets and longer average hospitalization days may be related to the cytokine storm. The PLR of patients means the degree of cytokine storm, which might provide a new indicator in the monitoring in patients with COVID‐19.
Zeolite Beta single crystals with intracrystalline hierarchical porosity at macro‐, meso‐, and micro‐length scales can effectively overcome the diffusion limitations in the conversion of bulky ...molecules. However, the construction of large zeolite Beta single crystals with such porosity is a challenge. We report herein the synthesis of hierarchically ordered macro‐mesoporous single‐crystalline zeolite Beta (OMMS‐Beta) with a rare micron‐scale crystal size by an in situ bottom‐up confined zeolite crystallization strategy. The fully interconnected intracrystalline macro‐meso‐microporous hierarchy and the micron‐sized single‐crystalline nature of OMMS‐Beta lead to improved accessibility to active sites and outstanding (hydro)thermal stability. Higher catalytic performances in gas‐phase and liquid‐phase acid‐catalyzed reactions involving bulky molecules are obtained compared to commercial Beta and nanosized Beta zeolites. The strategy has been extended to the synthesis of other zeolitic materials, including ZSM‐5, TS‐1, and SAPO‐34.
An in situ bottom‐up confined zeolite crystallization strategy is developed to construct micron‐sized hierarchically ordered macro‐mesoporous single‐crystalline zeolite Beta with improved accessibility to active sites and outstanding (hydro)thermal stability for both gas‐phase and liquid‐phase acid‐catalyzed reactions of bulky molecules.
The diverse expression pattern of CD36 reflects its multiple cellular functions. However, the roles of CD36 in colorectal cancer (CRC) remain unknown. Here, we discover that CD36 expression is ...progressively decreased from adenomas to carcinomas. CD36 loss predicts poor survival of CRC patients. In CRC cells, CD36 acts as a tumor suppressor and inhibits aerobic glycolysis in vitro and in vivo. Mechanically, CD36-Glypcian 4 (GPC4) interaction could promote the proteasome-dependent ubiquitination of GPC4, followed by inhibition of β-catenin/c-myc signaling and suppression of downstream glycolytic target genes GLUT1, HK2, PKM2 and LDHA. Moreover, disruption of CD36 in inflammation-induced CRC model as well as Apc
mice model significantly increased colorectal tumorigenesis. Our results reveal a CD36-GPC4-β-catenin-c-myc signaling axis that regulates glycolysis in CRC development and may provide an intervention strategy for CRC prevention.
Three‐dimensionally ordered macroporous (3DOM) structures have been widely utilized to largely enhance a photocatalytic activity. However, the common nanoparticles‐constructed 3DOM photocatalysts ...possess numerous grain boundaries, unavoidably leading to a fast recombination of photogenerated electrons and holes. Herein, for the first time, a hierarchically two‐dimensional (2D) meso‐microporous perovskite nanosheet‐constructed 3DOM CaTiO3 to significantly reduce the grain boundaries is designed and fabricated. Using carbon quantum dots (CQDs) as a metal‐free co‐catalyst, the 3DOM CQDs‐CaTiO3 exhibits an outstanding photocatalytic activity for hydrogen generation of 0.13 mmol h−1 (20 mg photocatalyst) with remarkable apparent quantum efficiency (QAY) of 14.55% at 365 nm monochromatic light. This unprecedented performance is endowed by the synergy of a macro‐meso‐microporosity architecture, a large surface area, enhanced light harvesting, and improved charge carriers separation and transport. Density functional theory calculations and finite difference time‐domain simulations further reveal the mechanism behind the enhanced separation of photogenerated electrons and holes. The present work demonstrates a trial on rationally designing meso‐microporous nanosheet‐constructed 3DOM perovskites for solar driven hydrogen production.
A perovskite meso‐microporous nanosheet‐constructed 3DOM CaTiO3 decorated with CQDs is designed for remarkable photocatalytic hydrogen production in a noble‐metal free system. The as‐synthesized composite exhibits extremely enhanced photocatalytic activity owing to the easy mass transfer by the synergistic effect of macro‐meso‐microporosity, large surface area, enhanced light harvesting, and improved separation of charge carriers.
Cognitive dysfunction is a common postoperative neurological complication in patients undergoing valve replacement surgery. This study aimed to compare the effects of sevoflurane versus ...propofol‐based total intravenous anesthesia on the incidence of cognitive dysfunction following valve replacement surgery. This multicenter, randomized, controlled double‐blinded study was conducted in three teaching hospitals in China. Patients receiving on‐pump valve replacement surgery were enrolled. Stratified block randomization was used to randomly assign patients 1:1 to receive sevoflurane (1.0–1.5 MAC) or propofol (2.0–3.0 mg/kg/h) for anesthesia maintenance. The primary outcome was the incidence of cognitive dysfunction assessed by four cognitive tests before, as well as 7–14 days after surgery. Patients were randomly assigned to receive sevoflurane anesthesia (n = 144) or propofol‐based total intravenous anesthesia (n = 145). The incidence of postoperative cognitive dysfunction in the sevoflurane anesthesia group (31.9%) was significantly lower than that in the total intravenous anesthesia group (43.4%; relative risk 0.61, 95% confidence interval CI: 0.38–0.97, p = 0.044). There was no difference in the incidence of delirium between patients receiving sevoflurane and total intravenous anesthesia (27.8% 35/144 vs. 25.9% 35/145, 1.10, 95% CI: 0.64 to 1.90, p = 0.736). There was a significant difference in the Katz Index on day 3 after surgery (3 0.9) vs. 3 (1.0, 0.095, 95% CI: 0.05 to 0.43, p = 0.012). No difference was observed in other outcomes between the two groups. For patients undergoing on‐pump valve replacement surgery, sevoflurane anesthesia had a smaller effect on cognitive function and independence in daily life activities compared with propofol anesthesia.
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