"Multi-in-One" Yolk-Shell Structured Nanoplatform Inducing Pyroptosis and Antitumor Immune Response Through Cascade Reactions.

Pyroptosis, a new mode of regulatory cell death, holds a promising prospect in tumor therapy. The occurrence of pyroptosis can trigger the release of damage-associated molecular patterns (DAMPs) and activate the antitumor immune response. Moreover, enhancing intracellular reactive oxygen species (ROS) generation can effectively induce pyroptosis. Herein, an integrated nanoplatform (hCZAG) based on zeolitic imidazolate framework-8 (ZIF-8) with Cu2+ and Zn2+ as active nodes and glucose oxidase (GOx) loading is constructed to evoke pyroptosis. GOx can effectively elevate intracellular hydrogen peroxide (H2O2) levels to regulate the unfavorable tumor microenvironment (TME). Cu2+ can be reduced to Cu+ by endogenous overexpressed GSH and both Cu2+ and Cu+ can exert Fenton-like activity to promote ROS generation and amplify oxidative stress. In addition, the accumulation of Cu2+ leads to the aggregation of lipoylated dihydrolipoamide S-acetyltransferase (DLAT), thus resulting in cuproptosis. Notably, the outburst of ROS induced by hCZAG activates Caspase-1 proteins, leads to the cleavage of gasdermin D (GSDMD), and induces pyroptosis. Pyroptosis further elicits an adaptive immune response, leading to immunogenic cell death (ICD). This study provides effective strategies for triggering pyroptosis-mediated immunotherapy and achieving improved therapeutic effects.

Tumor Microenvironment Specific Regulation Ca-Fe-Nanospheres for Ferroptosis-Promoted Domino Synergistic Therapy and Tumor Immune Response.

Reactive oxygen species (ROS)-mediated emerging treatments exhibit unique advantages in cancer therapy in recent years. While the efficacy of ROS-involved tumor therapy is greatly restricted by complex tumor microenvironment (TME). Herein, a dual-metal CaO2@CDs-Fe (CCF) nanosphere, with TME response and regulation capabilities, are proposed to improve ROS lethal power by a multiple cascade synergistic therapeutic strategy with domino effect. In response to weak acidic TME, CCF will decompose, accompanied with intracellular Ca2+ upregulated and abundant H2O2 and O2 produced to reverse antitherapeutic TME. Then the exposed CF cores can act as both Fenton agent and sonosensitizer to generate excessive ROS in the regulated TME for enhanced synergistic CDT/SDT. In combination with calcium overloading, the augmented ROS induced oxidative stress will cause more severe mitochondrial damage and cellular apoptosis. Furthermore, CCF can also reduce GPX4 expression and enlarge the lipid peroxidation, causing ferroptosis and apoptosis in parallel. These signals of damage will finally initiate damage-associated molecular patterns to activate immune response and to realize excellent antitumor effect. This outstanding domino ROS/calcium loading synergistic effect endows CCF with excellent anticancer effect to efficiently eliminate tumor by apoptosis/ferroptosis/ICD both in vitro and in vivo.

Antisocial peer exclusion does not eliminate the effectiveness of prosocial peer exclusion in structured populations.

While prosocial exclusion has been proposed as a mechanism to maintain cooperation in one-shot social dilemma games, the evolution of prosocial peer exclusion in response to the threat of antisocial peer exclusion, particularly in structured populations, remains insufficiently understood. In this study, we employ an extended spatial public goods game to investigate the evolution of prosocial peer exclusion and its impact on cooperation in the presence of both prosocial and antisocial peer exclusion. Our model encompasses four primary strategies: traditional cooperation and defection, prosocial peer exclusion targeting defectors, and antisocial peer exclusion targeting cooperators. Our findings illuminate that the presence of antisocial peer exclusion significantly disrupts network reciprocity and suppresses cooperation. However, when coexisting with prosocial peer exclusion, it does not undermine the latter's efficacy in upholding cooperation, except in scenarios with low exclusion costs Unlike the cooperation-sustaining cyclic dominance pattern observed in the exclusive presence of prosocial peer exclusion, the co-presence of prosocial and antisocial peer exclusion gives rise to more intricate pathways for maintaining cooperation. These pathways include cyclic dominance involving traditional cooperation, prosocial peer exclusion, and antisocial peer exclusion, or a similar pattern involving traditional defection and the two exclusion strategies, or even cyclic dominance among all four strategies. In essence, our study enhances the theoretical framework concerning the effectiveness of the prosocial exclusion strategy, contributing to a more comprehensive understanding of its dynamics.

AuPt-Loaded Cu-Doped Polydopamine Nanocomposites with Multienzyme-Mimic Activities for Dual-Modal Imaging-Guided and Cuproptosis-Enhanced Photothermal/Nanocatalytic Therapy.

Nanocatalytic therapy (NCT) has made great achievements in tumor treatments due to its remarkable enzyme-like activities and high specificity. Nevertheless, the limited types of nanozymes and undesirable tumor microenvironments (TME) greatly weaken the therapeutic efficiency. Developing a combination therapy integrating NCT and other strategies is of great significance for optimal treatment outcomes. Herein, a AuPt-loaded Cu-doped polydopamine nanocomposite (AuPt@Cu-PDA) with multiple enzyme-like activities was rationally designed, which integrated photothermal therapy (PTT) and NCT. The peroxidase (POD)-like activity of AuPt@Cu-PDA can catalyze hydrogen peroxide (H2O2) into ·OH, and the catalase (CAT)-mimic activity can decompose H2O2 into O2 to alleviate hypoxia of TME, and O2 can be further converted into toxic ·O2- by its oxidase (OXD)-mimic activity. In addition, Cu2+ in AuPt@Cu-PDA can effectively consume GSH overexpressed in tumor cells. The boosting of reactive oxygen species (ROS) and glutathione (GSH) depletion can lead to severe oxidative stress, which can be enhanced by its excellent photothermal performance. Most importantly, the accumulation of Cu2+ can disrupt copper homeostasis, promote the aggregation of lipoylated dihydrolipoamide S-acetyltransferase (DLAT), disrupt the mitochondrial tricarboxylic acid (TCA) cycle, and finally result in cuproptosis. Collectively, photothermal and photoacoustic imaging (PTI/PAI)-guided cuproptosis-enhanced NCT/PTT can be achieved. This work may expand the application of nanozymes in synergistic therapy and provide new insights into cuproptosis-related therapeutic strategies.

Establishment and validation of a delirium prediction model for neurosurgery patients in intensive care.

BACKGROUND: Neurosurgical intensive care unit patients are at high risk for delirium. A risk prediction model could help the staff screen for patients at high risk for delirium. On the basis of this risk, preventive measures could be taken to reduce the undesired effects of delirium. OBJECTIVES: To establish a delirium prediction model for neurosurgical intensive care unit patients and to verify the sensitivity and specificity of this model. DESIGN: A prospective, observational, single-centre study. METHODS: Data were collected from a total of 310 patients admitted to the neurosurgery intensive care unit between January 2017 and February 2018. A risk factor prediction model was then created using multivariate logistic regression. Further data were collected from another 60 patients between March 2018 and June 2018 to validate the model. RESULTS: The model consisted of six predictors, namely, cognitive dysfunction on admission, fever, hypoalbuminaemia, abnormal liver function, sedative use four or more times, and physical restraint. The area under the curve of the model was 0.80, with sensitivity and specificity of 0.68 and 0.83, respectively. CONCLUSIONS: This study established a delirium prediction model for neurosurgical intensive care unit patients, which we believe would help focused prevention of delirium in intensive care unit patients.

Biocompatible Ag2S quantum dots for highly sensitive detection of copper ions.

A simple aqueous approach for synthesizing biocompatible red and near-infrared (NIR) emitting Ag2S quantum dots (QDs) at low temperature without a required oxygen-free process has been developed. The fluorescence of the obtained red emitting Ag2S QDs could be selectively quenched by Cu2+. Based on this, a novel Ag2S QD based fluorescent sensor for highly selective and sensitive detection of Cu2+ was developed. This method showed a low limit of detection (LOD) of 27.6 nM for Cu2+ sensing in a wide linear range concentration of 25 nM-10 µM. The quenching mechanism was discussed by the time-resolved photoluminescence, absorption spectra, TEM and energy-dispersive X-ray (EDX) results. Cation exchange of Ag2S QDs between Cu(ii) and Ag(i), and dynamic quenching due to excited state electron transfer from Ag2S QDs to Cu2+ were considered to be the quenching mechanism. Furthermore, to understand the interaction between Ag2S QDs and Cu2+, the thermodynamic process was investigated by means of isothermal titration calorimetry (ITC). The values of ΔH, ΔS and ΔG were calculated from the ITC results to be -79.43 kJ mol-1, -142.18 J K-1 mol-1 and -37.06 kJ mol-1, respectively. The Ag2S QD based Cu2+ detection had advantages of nontoxicity, fast response, high sensitivity and selectivity, wide linear range and easy preparation.

Protective Effect of Eckol against Acute Hepatic Injury Induced by Carbon Tetrachloride in Mice.

Several in vitro studies have shown the potential hepatoprotective properties of eckol, a natural phlorotannin derived from the brown alga. However, the in vivo hepatoprotective potential of eckol has not been determined. In this study, we performed an in vivo study to investigate the protective effect of eckol and its possible mechanisms on the carbon tetrachloride (CCl4)-induced acute liver injury model in mice. Results revealed that eckol pre-treatment at the dose of 0.5 and 1.0 mg/kg/day for 7 days significantly suppressed the CCl4-induced increases of alanine transaminase (ALT) and aspartate aminotransferase (AST) levels in serum and meliorated morphological liver injury. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) analysis showed that the number of positive apoptotic hepatocytes in the eckol-treated group was lower than that in the CCl4 model group. Western blotting analysis also demonstrated the enhanced expression of bcl-2 and suppressed expression of cleaved caspase-3 by eckol. The CCl4-induced oxidative stress in liver was significantly ameliorated by eckol, which was characterized by reduced malondialdehyde (MDA) formations, and enhanced superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities and glutathione (GSH) content. Moreover, the CCl4-induced elevations of pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6 were markedly suppressed in the eckol-treated group. However, eckol enhanced the level of IL-10, a potent anti-inflammatory cytokine, and recruited CD11c⁺ dendritic cells into the liver tissues of CCl4-treated mice. These results indicated that eckol has the protective effect on CCl4-induced acute liver injury via multiple mechanisms including anti-apoptosis, anti-oxidation, anti-inflammation and immune regulation.

Risk factors for the incidence of delirium in cerebrovascular patients in a Neurosurgery Intensive Care Unit: A prospective study.

AIMS AND OBJECTIVES: To explore the incidence of delirium in cerebrovascular patients admitted in our Neurosurgery Intensive Care Unit and analyse the risk factors leading to delirium. BACKGROUND: Delirium is one of the most common mental disorders in general hospitals, but the incidence of different kinds of diseases and studies varies. Cerebrovascular patients in our Neurosurgery Intensive Care Unit are high-risk groups for delirium; identifying risk factors for delirium and taking early interventions are crucial for patient prognosis. DESIGN: A prospective study. METHODS: A convenience sampling method was used to collect data from 128 patients in the Neurosurgery Intensive Care Unit of Xuanwu Hospital, Capital Medical University, Beijing, China, between May 2016-January 2017. Researchers used Confusion Assessment Method for the Intensive Care Unit (Chinese version) to assess each patient's delirium statement twice a day at regular times. We also collected other independent data variables and followed up the short-term clinical outcomes daily. RESULTS: On the basis of Confusion Assessment Method for the Intensive Care Unit evaluation, patients were divided into a delirium group and a nondelirium group. The prevalence of delirium among the 128 patients was 42.2%. Multivariate analysis showed that severity of illness, fever, the use of physical restraints and sleep deprivation were independent predictors of delirium in cerebrovascular patients in the Neurosurgery Intensive Care Unit. CONCLUSIONS: Cerebrovascular patients in the Neurosurgery Intensive Care Unit with a critical condition, fever or use of physical restraints or experiencing sleep deprivation were more prone to delirium. RELEVANCE TO CLINICAL PRACTICE: Cerebrovascular patients in the Neurosurgery Intensive Care Unit showed a high incidence of delirium. There are many risk factors leading to delirium, some of which are independent predictors of intensive care delirium. Patients with delirium will suffer various adverse effects upon their short-term clinical outcomes. Therefore, nurses should pay close attention to changes in a patient's mental state and learn about the risk factors associated with delirium, in order to be able to take early measures to prevent delirium.

Comparison of the occurrence of antibiotic residues in two rural ponds: implication for ecopharmacovigilance.

As a well-accepted drug-administration strategy for the minimization of environmental risks posed by pharmaceutical residues, ecopharmacovigilance (EPV) needs to guard against and control the pharmaceutical pollution sources. However, the underlying routes by which pharmaceuticals reach the environment vary significantly under different scenes, so it is necessary to implement different EPV measures in different backgrounds. This study detected the occurrence of antibiotic residues in two ponds within a Chinese rural community; assessed their ecological risks; compared and analyzed the geographic and demographic information, as well as the antibiotic-related anthropogenic behaviors of residents living around ponds, in order to trace the main entrances of antibiotics into the water environment; and then propose the EPV measures according to rural conditions. The results showed that the pollution degree of antibiotic residues was different between two studied ponds, which was manifested by the different antibiotic types and levels in water samples. And the possible main sources of antibiotic pollution in the studied rural water environment might include the application of human excretions and animal manures as fertilizers on the farmland, antibiotic use and inappropriate disposal in the clinic, and the direct disposal of the leftover antibiotics. From the perspective of drug administration, we then identified some suggestions on EPV measures which could be taken under existing rural conditions, including encouraging eco-directed sustainable prescribing of antibiotics in human and animals, improving take-back collection of unused antibiotics, building monitoring mechanism for antibiotic residues in the natural environment, identifying high-priority antibiotic residues, and implementing targeted EPV.

Characteristics and management of domestic waste in the rural area of Southwest China.

With its rapid development, the rural area of Southwest China has been puzzled by the waste management problem, especially for increasing solid waste and water pollution from the domestic waste. Therefore, in order to efficiently and effectively manage the domestic waste in the rural area of Southwest China, 22 villages were selected randomly to analyse the characteristics of domestic waste, the influence factors of characteristics and resident's willingness of participation in domestic waste management by questionnaires, field samplings and laboratory tests. The results of the rural area of Southwest China indicated that the generation of domestic waste was 178 g d(-1) per capita and it was mainly composed of kitchen waste, inert waste, plastics and paper with a total proportion of 81.98%. The waste bulk density, moisture, ash, combustible and lower calorific value were 107 kg m(-3), 37.04%, 25.73%, 37.23% and 8008 kJ kg(-1), respectively. These characteristics were influenced by the topography, the distance from towns or cities, the villagers' ethnicities and income sources to some extent. Moreover, the distance of 50-800 m between each collection facility and the disposal fee of around ¥5.00 per household per month could be accepted. The working hours of participation in waste management is suggested as 5 hours per day with the income of ¥1000 per capita per month. Based on the outcome of this survey, a waste management system consisting of classified collection, centralised treatment and decentralised treatment was proposed. It is important to ensure financial viability and practical considerations of this system.

Occurrence of pentachlorophenol in surface water from the upper to lower reaches of the Yangtze River and treated water in Wuhan, China.

Pentachlorophenol (PCP), a persistent organic pollutant, has been banned in many countries, but it is still used in China as a wood preservative, molluscicide, or reagent for fish-pond cleaning, which may pose risks to the ecosystem and humans. However, data on the occurrence of PCP in the environment are scarce in the recent decade. The Yangtze River was regarded as a priority area of PCP pollution according to previous documents. This study aimed to examine the spatial distribution of PCP in the Yangtze River water, the differences in dry and wet seasons, the ecological risk for aquatic organisms, and its removal efficiency in tap water treatment plants. The river water samples (n = 144) were collected from the upper, middle, and lower reaches across ten provinces (or municipalities) in December 2020 and June 2021, respectively. PCP was detected in 88.9% of all the samples, ranging from

Metal-amplified sonodynamic therapy of Ti-based chitosan-polyvinyl alcohol hybrid hydrogel dressing against subcutaneous Staphylococcus aureus infection.

Ultrasound (US)-mediated sonodynamic therapy (SDT) has received extensive attention in pathogen elimination for non-invasiveness and high spatial and temporal accuracy. Considering that hydrogel can provide a healing-friendly environment for wounds, in this work, hybrid hydrogels are constructed by embedding Ag doped TiO2 nanoparticles in chitosan-polyvinyl alcohol hydrogels for enhanced sonodynamic antibacterial therapy. With metal silver doped, TiO2 nanoparticles sonosensitivity is improved to generate more reactive oxygen species (ROS), which endows hybrid hydrogels with high-efficient antibacterial properties. In vivo results show that hybrid hydrogel dressing can prevent infection and promote wound closure within 2 days. The healing ratio excess 95 % with no pus produced at the end of treatment. The therapeutic mechanism was identified that heterojunction formed in Ag doped TiO2 facilitates the separation of charge carriers under US irradiation, leading to elevating ROS generation. The generated ROS promote hybrid hydrogels sonodynamic antibacterial therapeutic efficacy to thoroughly eliminate pathogen via disrupting bacterial cell membrane integrity, decreasing membrane fluidity and increasing membrane permeability. Besides, biofilm formation could be effectively inhibited. This work developed a hybrid hydrogel with amplified SDT effect for wound healing, which is expected to provide inspiration of hybrid hydrogels design and Ti-based nanomaterials sonosensitivity enhancement.

Associations of maternal exposure to 2,4-dichlorophenoxyacetic acid during early pregnancy with steroid hormones among one-month-old infants.

BACKGROUND: Exposure to 2,4-dichlorophenoxyacetic acid (2,4-D), a widely used hormonal herbicide, may disrupt steroid hormone homeostasis. However, evidence from population-based studies is limited, especially for one-month-old infants whose steroid hormones are in a state of adjustment to extrauterine life and can be important indicators of endocrine development. This study aimed to explore the associations between maternal 2,4-D exposure during early pregnancy and infant steroid hormone levels. METHODS: The 885 mother-infant pairs were from a birth cohort in Wuhan, China. Maternal exposure to 2,4-D was determined in urine samples from early pregnancy, and nine steroid hormones were determined in infant urine. The associations of maternal 2,4-D exposure with infant steroid hormones and their product-to-precursor ratios were estimated based on generalized linear models, and bioinformatic analysis was conducted with public databases to explore the potential mechanisms involved. RESULTS: The detection frequency of 2,4-D was 99.32 %, and the detection frequency of steroid hormones ranged from 98.42 % to 100.00 %. After adjusting for covariates, an interquartile range increase in 2,4-D concentrations was associated with a 7.84 % decrease in 11-deoxycortisol (95 % confidence interval, CI: -14.12 %, -1.10 %), an 8.09 % decrease in corticosterone (95 % CI: -14.56 %, -1.14 %), an 8.67 % decrease in cortisol (95 % CI: -14.43 %, -2.52 %), a 13.00 % decrease in cortisone (95 % CI: -20.64 %, -4.62 %), and an 11.17 % decrease in aldosterone (95 % CI: -19.62 %, -1.83 %). Maternal 2,4-D was also associated with lower infant cortisol/17α-OH-progesterone, cortisol/pregnenolone, and aldosterone/pregnenolone ratios. In bioinformatic analysis, pathways/biological processes related to steroid hormone synthesis and secretion were enriched from target genes of 2,4-D exposure. CONCLUSIONS: Maternal urinary 2,4-D during early pregnancy was associated with lower infant urinary 11-deoxycortisol, corticosterone, cortisol, cortisone, and aldosterone, reflecting that 2,4-D exposure may interfere with infant steroid hormone homeostasis. Further efforts are still needed to study the relevant health effects of exposure to 2,4-D, particularly for vulnerable populations.

Trihalomethanes in global drinking water: Distributions, risk assessments, and attributable disease burden of bladder cancer.

This study aimed to assess the global spatiotemporal variations of trihalomethanes (THMs) in drinking water, evaluate their cancer and non-cancer risks, and THM-attributable bladder cancer burden. THM concentrations in drinking water around fifty years on a global scale were integrated. Health risks were assessed using Monte Carlo simulations and attributable bladder cancer burden was estimated by comparative risk assessment methodology. The results showed that global mean THM concentrations in drinking water significantly decreased from 78.37 µg/L (1973-1983) to 51.99 µg/L (1984-2004) and to 21.90 µg/L (after 2004). The lifestage-integrative cancer risk and hazard index of THMs through all exposure pathways were acceptable with the average level of 6.45 × 10-5 and 7.63 × 10-2, respectively. The global attributable disability adjusted of life years (DALYs) and the age-standardized DALYs rate (ASDR) dropped by 16% and 56% from 1990-1994 to 2015-2019, respectively. A big decline in the attributable ASDR was observed in the United Kingdom (62%) and the United States (27%), while China experienced a nearly 3-fold increase due to the expanded water supply coverage and increased life expectancy. However, China also benefited from the spread of chlorination, which helped reduce nearly 90% of unsafe-water-caused mortality from 1998 to 2018.

Nanomaterials-Involved Tumor-Associated Macrophages' Reprogramming for Antitumor Therapy.

Tumor-associated macrophages (TAMs) play pivotal roles in tumor development. As primary contents of tumor environment (TME), TAMs secrete inflammation-related substances to regulate tumoral occurrence and development. There are two kinds of TAMs: the tumoricidal M1-like TAMs and protumoral M2-like TAMs. Reprogramming TAMs from immunosuppressive M2 to immunocompetent M1 phenotype is considered a feasible way to improve immunotherapeutic efficiency. Notably, nanomaterials show great potential for biomedical fields due to their controllable structures and properties. There are many types of nanomaterials that exhibit great regulatory activities for TAMs' reprogramming. In this review, the recent progress of nanomaterials-involved TAMs' reprogramming is comprehensively discussed. The various nanomaterials for TAMs' reprogramming and the reprogramming strategies are summarized and introduced. Additionally, the challenges and perspectives of TAMs' reprogramming for efficient therapy are discussed, aiming to provide inspiration for TAMs' regulator design and promote the development of TAMs-mediated immunotherapy.

A keratin 15 containing stem cell population from the hair follicle contributes to squamous papilloma development in the mouse.

The multistage model of nonmelanoma skin carcinogenesis has contributed significantly to our understanding of epithelial cancer in general. We used the Krt1-15CrePR1;R26R transgenic mouse to determine the contribution of keratin 15+ cells from the hair follicle to skin tumor development by following the labeled progeny of the keratin 15 expressing cells into papillomas. We present three novel observations. First, we found that keratin 15 expressing cells contribute to most of the papillomas by 20 weeks of promotion. Second, in contrast to the transient behavior of labeled keratin 15-derived progeny in skin wound healing, keratin 15 progeny persist in papillomas, and some malignancies for many months following transient induction of the reporter gene. Third, papillomas have surprising heterogeneity not only in their cellular composition, but also in their expression of the codon 61 signature Ha-ras mutation with approximately 30% of keratin 15-derived regions expressing the mutation. Together, these results demonstrate that keratin 15 expressing cells of the hair follicle contribute to cutaneous papillomas with long term persistence and a subset of which express the Ha-ras signature mutation characteristic of initiated cells.

MXenes Functionalized with Macrocyclic Hosts: From Molecular Design to Applications.

Two-dimensional (2D) MXene has aroused wide attention for its excellent physical and chemical properties. The interlayer engineering formed by layer-by-layer stacking of MXene nanosheets can be employed for molecular sieving and water purification by incorporating specific groups onto the exterior surface of MXene. Macrocyclic hosts exhibiting unique structural features and recognition ability can construct smart devices for external stimuli with reversible features between macrocycles and guests. On that basis, macrocyclic hosts can be anchored to MXene to provide numerous insights into their compositions and intercalation states. In this review, the MXene prepared based on macrocyclic hosts from molecular design to applications is highlighted. Various MXenes functionalized with macrocyclic hosts are empowered in functional membrane (including water purification, organic solvent nanofiltration, and electromagnetic shielding), photocatalysis, sensing, and adsorption (interactions with specific guest). Hopefully, this review can bring new inspiration to the design of multifunctional MXene-based materials and improving its practical applications.

Inhibition mechanism of human insulin fibrillation by Bodipy carbon polymer dots and photothermal defibrillation effect of Bodipy carbon polymer dots modified by ThT.

Fibrillation process of human insulin (HI) is closely related to type 2 diabetes (T2D). In the present work, Carbon Polymer Dots (CPDs) was synthesized by Bodipy to control the process of insulin fibrillation. The inhibition process of insulin fibrillation with the existence of CPDs was completed investigated. The hydrophobic interaction of CPDs and insulin was used to inhibit the change of insulin's secondary structure in the lag phase and growth period. ThT fluorescence analysis and transmission electron microscopy (TEM) characterization of the CPDs were used to explore the kinetics of insulin fibrillation and regulation process by CPDs. Isothermal titration calorimetry (ITC) was applied to explore the regulatory mechanism by CPDs at all stages of the insulin fibrillation process. ThT was used to complete the chemical modification of CPDs by Friedel-Crafts alkylation, which made the CPDs maintain the characteristics of photothermal effect and also obtain the ability to bind specifically to the fibers. Finally, the process of defibrillation of human insulin fibers under the Near-infrared light's irradiation was realized. In this work, we clarified the mechanism of the regulation process by Bodipy CPDs and made CPDs able to defibrillate the insulin fibers by chemical modification.

Recent strategies of carbon dot-based nanodrugs for enhanced emerging antitumor modalities.

Nanomaterial-based cancer therapy has recently emerged as a new therapeutic modality with the advantages of minimal invasiveness and negligible normal tissue toxicity over traditional cancer treatments. However, the complex microenvironment and self-protective mechanisms of tumors have suppressed the therapeutic effect of emerging antitumor modalities, which seriously hindered the transformation of these modalities to clinical settings. Due to the excellent biocompatibility, unique physicochemical properties and easy surface modification, carbon dots, as promising nanomaterials in the biomedical field, can effectively improve the therapeutic effect of emerging antitumor modalities as multifunctional nanoplatforms. In this review, the mechanism and limitations of emerging therapeutic modalities are described. Further, the recent advances related to carbon dot-based nanoplatforms in overcoming the therapeutic barriers of various emerging therapies are systematically summarized. Finally, the prospects and potential obstacles for the clinical translation of carbon dot-based nanoplatforms in tumor therapy are also discussed. This review is expected to provide a reference for nanomaterial design and its development for the efficacy enhancement of emerging therapeutic modalities.

Cu-Doped black phosphorus quantum dots as multifunctional Fenton nanocatalyst for boosting synergistically enhanced H2O2-guided and photothermal chemodynamic cancer therapy.

Chemodynamic therapy (CDT) is a cancer treatment that converts endogenous H2O2 into hydroxyl radicals (˙OH) through Fenton reaction to destroy cancer cells. However, there are still some challenges in accelerating the Fenton reaction of CDT and improving the biodegradability of nanocatalysts. Herein, a multifunctional biomimetic BPQDs-Cu@GOD (BCG) Fenton nanocatalyst for boosting synergistically enhanced H2O2-guided and photothermal CDT of cancer is reported. Cu2+ in BCG can be reduced to Cu+ by black phosphorus quantum dots (BPQDs), triggering a Cu+-mediated Fenton-like reaction to degrade H2O2 and generate abundant ˙OH for cancer CDT. The loaded glucose oxidase (GOD) can consume the glucose in the tumor to produce abundant H2O2 for Fenton-like reaction. In addition, Cu2+ in BCG can react with GSH in tumor cells to alleviate the antioxidant capacity of tumor tissues, further improving the CDT efficacy. Furthermore, the photothermal performance of BPQDs can be enhanced by capturing Cu2+, improving the photoacoustic imaging and photothermal therapy (PTT) functions. More importantly, the enhanced photothermal performance can rapidly accelerate the Fenton-like reaction under NIR irradiation. Finally, Cu2+ can accelerate the degradation of BPQDs, which can reduce the retention of reagents. As a novel multifunctional biocompatible Fenton nanocatalyst, BCG have great potential in cancer therapy.