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Abstract Nanobodies (Nbs), the smallest antigen-binding fragments with high stability and affinity derived from the variable domain of naturally occurring heavy-chain-only antibodies in camelids, have been shown as an efficient way to improve the specificity to tumors for photodynamic therapy (PDT). Nonetheless, the rapid clearance of Nbs in vivo restricts the accumulation and retention of the photosensitizer at the tumor site causing insufficient therapeutic outcome, especially in large-volume tumors. Herein, we develop photodynamic conjugates, MNB-Pyra Nbs, through site-specific conjugation between 7D12 Nbs and type I photosensitizer MNB-Pyra (morpholine-modified nile blue structure connected to pyrazolinone) in a 1:2 ratio. The photosensitizers with long-term retention can be released at the tumor site by reactive oxygen species cleavage after illumination, accompanied with fluorescence recovery for self-reporting the occurrence of PDT. Ultimately, a single dose of MNB-Pyra Nbs demonstrate highly effective tumor suppression with high biosafety in the large-volume tumor models after three rounds of PDT. This nanobody conjugate provides a paradigm for the design of precise long-time retention photosensitizers and is expected to promote the development of PDT.

Abstract The integration of robust photon‐absorption capacity, high reactive oxygen species yields and photothermal conversion efficiency (PCE) into a single phototheranostic nano‐agents is ideal but rarely reported. This study employed a dual‐acceptor engineering strategy utilizing isoindigo and selenium‐substituted [1,2,5]thiadiazolo[3,4‐c]pyridine to augment the molar extinction coefficient and spin‐orbit coupling effect, respectively, resulting in a substantial enhancement of photon‐absorption ability and non‐radiative decay energy‐release process of donor‐acceptor type phototherapy molecules. As the optimal phototherapy agent, IID‐PSe exhibited a high molar extinction coefficient two times that of photosensitizer, excellent 1O2 yield (15%) and PCE (34%), exhibiting great potential for phototherapy. After encapsulating with DSPE‐PEG2000, IID‐PSe NPs showed excellent anti‐tumor phototherapy ability both in vitro and in vivo. This work provides an effective idea for designing high‐performance photosensitive dyes with high efficiency phototherapy output.

Abstract Therapeutic cancer vaccines fail to produce satisfactory outcomes against solid tumors since vaccine‐induced anti‐tumor immunity is significantly hampered by immunosuppression. Generating an in situ cancer vaccine targeting immunological cold tumor microenvironment (TME) appears attractive. Here, a type of free‐field based whole‐body ultrasound (US)‐driven nanovaccines are constructed, named G5‐CHC‐R, by conjugating the sonosensitizer, Chenghai chlorin (CHC) and the immunomodulator, resiquimod (R848) on top of a super small‐sized dendrimeric nanoscaffold. Once entering tumors, R848 can be cleaved from a hypoxia‐sensitive linker, thus modifying the TME via converting macrophage phenotypes. The animals bearing orthotopic pancreatic cancer with intestinal metastasis and breast cancer with lung metastasis are treated with G5‐CHC‐R under a free‐field based whole‐body US system. Benefit from the deep penetration capacity and highly spatiotemporal selectiveness, G5‐CHC‐R triggered by US represented a superior alternative for noninvasive irradiation of deep‐seated tumors and magnification of local immune responses via driving mass release of tumor antigens and “cold‐warm‐hot” three‐state transformation of TME. In addition to irradiating primary tumors, a robust adaptive anti‐tumor immunity is potentiated, leading to successful induction of systemic tumor suppression. The sono‐nanovaccines with good biocompatibility posed wide applicability to a broad spectrum of tumors, revealing immeasurable potential for translational research in oncology.

Fuzzy-ball fluid is a two-phase fluid composed of fuzzy-ball and base fluid. It can enhance oil recovery by approximately 30% after water flooding and polymer flooding, which has been demonstrated in laboratory experiments and field applications. However, the EOR mechanism of fuzzy-ball fluid still needs further research. In this study, the microstructure of fuzzy-ball was observed using optical and cryo-scanning electron microscopy. The EOR mechanism of fuzzy-ball fluid was investigated by the microscopic glass etching model experiment and inter-molecular force calculation. EOR contribution ratio of three parts of fuzzy-ball was evaluated by the single core flooding experiment. Results showed that fuzzy-ball was further subdivided into fuzzy-ball structure and floss structure. Correspondingly, the EOR effects of fuzzy-ball fluid were mainly divided into three parts: (a) base fluid. Emulsification was the main way for base fluid to enhance oil recovery; (b) fuzzy-ball structure. According to the distribution characteristics of residual oil, the EOR mechanisms of fuzzy-ball structure were mainly as follows: wedging displacement for membranous oil, squeezing-carrying mechanism for columnar oil, and extruding-squeezing mechanism for blind-end oil; (c) floss structure. Floss structure enhanced oil recovery mainly through entanglement and carrying mechanism. Moreover, the EOR contribution ratio of base fluid, fuzzy-ball structure, and floss structure are 18.35%, 50.94%, and 30.71%, respectively. This study elucidates the EOR mechanism of fuzzy-ball fluid and provides guidance for its subsequent field application and performance improvement.

Abstract Pentamethyl cyanine dyes are promising fluorophores for fluorescence sensing and imaging. However, advanced biomedical applications require enhanced control of their excited‐state properties. Herein, a synthetic approach for attaching aryl substituents at the C2’ position of the thio‐pentamethine cyanine (TCy5) dye structure is reported for the first time. C2’‐aryl substitution enables the regulation of both the twisted intramolecular charge transfer (TICT) and photoinduced electron transfer (PET) mechanisms to be regulated in the excited state. Modulation of these mechanisms allows the design of a nitroreductase‐activatable TCy5 fluorophore for hypoxic tumor photodynamic therapy and fluorescence imaging. These C2’‐aryl TCy5 dyes provide a tunable platform for engineering cyanine dyes tailored to sophisticated biological applications, such as photodynamic therapy.

Power cable conductor ampacity directly correlates with conductor temperature. Traditional thermocouple measurement fails to ensure real-time monitoring, risking cable operation. Leveraging Raman scattering principles, this study establishes a method for continuous surface temperature detection of long-distance power cables using distributed fiber optics. This approach surpasses OTDR-based measurement in speed and reliability, offering superior online monitoring for cable systems, suitable for widespread adoption.

Pyroptosis, a unique lytic programmed cell death, inspired tempting implications as potent anti-tumor strategy in pertinent to its potentials in stimulating anti-tumor immunity for eradication of primary tumors and metastasis. Nonetheless, rare therapeutics have been reported to successfully stimulate pyroptosis. In view of the intimate participation of reactive oxygen species (ROS) in stimulating pyroptosis, we attempted to devise a spectrum of well-defined subcellular organelle (including mitochondria, lysosomes and endoplasmic reticulum)-targeting photosensitizers with the aim of precisely localizing ROS (produced from photosensitizers) at the subcellular compartments and explore their potentials in urging pyroptosis and immunogenic cell death (ICD). The subsequent investigations revealed varied degrees of pyroptosis upon photodynamic therapy (PDT) towards cancerous cells, as supported by not only observation of the distinctive morphological and mechanistic characteristics of pyroptosis, but for the first-time explicit validation from comprehensive RNA-Seq analysis. Furthermore, in vivo anti-tumor PDT could exert eradication of the primary tumors, more importantly suppressed the distant tumor and metastatic tumor growth through an abscopal effect, approving the acquirement of specific anti-tumor immunity as a consequence of pyroptosis. Hence, pyroptosis was concluded unprecedently by our proposed organelles-targeting PDT strategy and explicitly delineated with molecular insights into its occurrence and the consequent ICD.

Abstract Research on the anti‐jamming target detection for pulsed Doppler (PD) radar is intensively important to the normal work of radar in complicated and volatile electromagnetic environments. Generally, traditional anti‐jamming target detection methods involve several stages, each one of these stages is based on a model. Due to the issues of poor flexibility caused by multi‐stage processing and model mismatch caused by model‐based methods, the detection performance will be severely decreased. Therefore, a new target detection scheme for PD radar in an Interrupted‐Sampling Repeater Jamming (ISRJ) environment is proposed, which is a dual‐driven method of model and data. This innovative solution first achieves energy accumulation on the Doppler channel by a model‐driven method, then proposes a series of preprocessing methods to process radar signals to adapt to a data‐driven Convolutional Neural Network (CNN) detector. Finally, a CNN detector structure is proposed. The effectiveness of this novel scheme is demonstrated by a series of performance and visualisation experiments.

Type I photodynamic therapy (PDT) sensitizers show good hypoxia tolerance but only few strategies are available for the design of purely organic Type I photosensitizers (PS). Here, the authors use biotinylation as design strategy to obtain PS-Biotin sensitizers with high efficiency for the generation of superoxide anion radicals and singlet oxygen.

Abstract PEGylation of nano‐drug delivery systems (NDDSs) has been investigated to overcome the side effect of conventional chemotherapy including improving pharmacokinetics by prolonging drug circulation, reducing immune clearance and premature drug leakage. Although, PEGylation of NDDSs can also disturb the tumor penetration and cellular uptake with the diameter enhancement. Therefore, in this work, we constitute a light‐triggered dePEGylation strategy, which results in the decrease of diameter of the pH‐responsive hydroxyapatite drug nanocarriers (DOX@HAP‐PEG) for enhanced cellular uptake and tumor penetration. Under light irradiation (650 nm), PEG chains can be availably separated from the nanocarrier by cleaving the Cy linker. Moreover, the cellular uptake of DOX@HAP‐PEG and DOX@HAP‐PEG+L (DOX@HAP‐PEG under light irradiation) are explored against MCF‐7, Hela, and HepG2 cancer cells. The results show that the cellular uptake of DOX@HAP‐PEG is lower than that of DOX@HAP‐PEG+L. In addition, in 3D tumor model, DOX@HAP‐PEG+L can better penetrate into the cell spheroid than DOX@HAP‐PEG, which is demonstrated by the accumulated fluorescence signals in the cell spheroid.

Abstract Upconverted reactive oxygen species (ROS) photosensitization with one‐photon excitation mode is a promising tactic to elongate the excitation wavelengths of photosensitive dyes to near‐infrared (NIR) light region without the requirement of coherent high‐intensity light sources. However, the photosensitization efficiencies are still finite by the unilateral improvement of excited‐state intersystem crossing (ISC) via heavy‐atom‐effect, since the upconverted efficiency also plays a decisive role in upconverted photosensitization. Herein, a NIR light initiated one‐photon upconversion heavy‐atom‐free small molecule system is reported. The meso‐rotatable anthracene in pentamethine cyanine (Cy5) is demonstrated to enrich the populations in high vibrational–rotational energy levels and subsequently improve the hot‐band absorption (HBA) efficiency. Moreover, the spin–orbit charge transfer intersystem crossing (SOCT‐ISC) caused by electron donated anthracene can further amplify the triplet yield. Benefiting from the above two aspects, the 1O2 generation significantly increases with over 2‐fold improved performance compared with heavy‐atom‐modified method under upconverted light excitation, which obtains efficient in vivo phototheranostic results and provides new opportunities for other applications such as photocatalysis and fine chemical synthesis.

Abstract Hepatitis B virus (HBV) infection remains a major health issue worldwide and the leading cause of cirrhosis and hepatocellular carcinoma (HCC). It has been reported previously that HBV invasion can extensively alter transcriptome, the proteome of exosomes and host cell lipid rafts. The impact of HBV on host proteins through regulating their global post-translational modifications (PTMs), however, is not well studied. Viruses have been reported to exploit cellular processes by enhancing or inhibiting the ubiquitination of specific substrates. Nevertheless, host cell physiology in terms of global proteome and ubiquitylome has not been addressed yet. Here by using HBV-integrated HepG2.2.15 model cell line we first report that HBV significantly modify the host global ubiquitylome. As currently the most widely used HBV cell culture model, HepG2.2.15 can be cultivated for multiple generations for protein labeling, and can replicate HBV, express HBV proteins and secrete complete HBV Dane particles, which makes it a suitable cell line for ubiquitylome analysis to study HBV replication, hepatocyte immune response and HBV-related HCC progression. Our previous experimental results showed that the total ubiquitination level of HepG2.2.15 cell line was significantly higher than that of the corresponding parental HepG2 cell line. By performing a Ubiscan quantification analysis based on stable isotope labeling of amino acids in cell culture (SILAC) of HepG2.2.15 and HepG2 cell lines, we identified a total of 7188 proteins and the protein levels of nearly 19% of them were changed over 2-folds. We further identified 3798 ubiquitinated Lys sites in 1476 host proteins with altered ubiquitination in response to HBV. Our results also showed that the global proteome and ubiquitylome were negatively correlated, indicating that ubiquitination might be involved in the degradation of host proteins upon HBV integration. We first demonstrated the ubiquitination change of VAMP3, VAMP8, DNAJB6, RAB8A, LYN, VDAC2, OTULIN, SLC1A4, SLC1A5, HGS and TOLLIP. In addition, we described 5 novel host factors SLC1A4, SLC1A5, EIF4A1, TOLLIP and BRCC36 that efficiently reduced the amounts of secreted HBsAg and HBeAg. Overall, the HBV-mediated host proteome and ubiquitylome change we reported will provide a valuable resource for further investigation of HBV pathogenesis and host-virus interaction networks.

Abstract In flexible electronics, appropriate inlaid structures for stress dispersion to avoid excessive deformation that can break chemical bonds are lacking, which greatly hinders the fabrication of super‐foldable composite materials capable of sustaining numerous times of true‐folding. Here, mimicking the microstructures of both cuit cocoon possessing super‐flexible property and Mimosa leaf featuring reversible scatheless folding, super‐foldable C‐web/FeOOH‐nanocone (SFCFe) conductive nanocomposites are prepared, which display cone‐arrays on fiber structures similar to Mimosa leaf, as well as non‐crosslinked junctions, slidable nanofibers, separable layers, and compressible network like cuit cocoon. Remarkably, the SFCFe can undergo over 100 000 times of repeated true‐folding without structural damage or electrical conductivity degradation. The mechanism underlying this super‐foldable performance is further investigated by real‐time scanning electron microscopy folding characterization and finite‐element simulations. The results indicate its self‐adaptive stress‐dispersion mechanism originating from multilevel biomimetic structures. Notably, the SFCFe demonstrates its prospect as a super‐foldable anode electrode for aqueous batteries, which shows not only high capacities and satisfactory cycling stability, but also completely coincident cyclic voltammetry and galvanostatic charge–discharge curves throughout the 100 000 times of true‐folding. This work reports a mechanical design considering the self‐adaptive stress dispersion mechanism, which can realize a scatheless super‐foldable electrode for soft‐matter electronics.

Abstract Background Carbon nanoparticles (CNPs) have been reported to boost plant growth, while the mechanism that CNPs enhanced potassium uptake for plant growth has not been reported so far. Results In this study, the function that CNPs promoted potassium uptake in BY-2 cells was established and the potassium accumulated in cells had a significant correlation with the fresh biomass of BY-2 cells. The K+ accumulation in cells increased with the increasing concentration of CNPs. The K+ influx reached high level after treatment with CNPs and was significantly higher than that of the control group and the negative group treated with K+ channels blocker, tetraethylammonium chloride (TEA+). The K+ accumulation was not reduced in the presence of CNPs inhibitors. In the presence of potassium channel blocker TEA+ or CNPs inhibitors, the NKT1 gene expression was changed compared with the control group. The CNPs were found to preferentially transport K+ than other cations determined by rectification of ion current assay (RIC) in a conical nanocapillary. Conclusions These results indicated that CNPs upregulated potassium gene expression to enhance K+ accumulation in BY-2 cells. Moreover, it was speculated that the CNPs simulated protein of ion channels via bulk of carboxyl for K+ permeating. These findings will provide support for improving plant growth by carbon nanoparticles.

Abstract The synergistic combination of chemotherapy and photodynamic therapy has attracted considerable attention for its enhanced antitumoral effects; however, it remains challenging to successfully delivery photosensitizers and anticancer drugs while minimizing drug leakage at off‐target sites. A red‐light‐activatable metallopolymer, Poly(Ru/PTX), is synthesized for combined chemo‐photodynamic therapy. The polymer has a biodegradable backbone that contains a photosensitizer Ru complex and the anticancer drug paclitaxel (PTX) via a singlet oxygen (1O2) cleavable linker. The polymer self‐assembles into nanoparticles, which can efficiently accumulate at the tumor sites during blood circulation. The distribution of the therapeutic agents is synchronized because the Ru complex and PTX are covalently conjugate to the polymer, and off‐target toxicity during circulation is also mostly avoided. Red light irradiation at the tumor directly cleaves the Ru complex and produces 1O2 for photodynamic therapy. Sequentially, the generated 1O2 triggers the breakage of the linker to release the PTX for chemotherapy. Therefore, this novel sequential dual‐model release strategy creates a synergistic chemo‐photodynamic therapy while minimizing drug leakage. This study offers a new platform to develop smart delivery systems for the on‐demand release of therapeutic agents in vivo.

Angle-only sensors cannot provide range information of targets and in order to determine accurate position of a signal source, one can connect distributed passive sensors with communication links and implement a fusion algorithm to estimate target position. To measure moving targets with sensors on moving platforms, most of existing algorithms resort to the filtering method. In this paper, we present two fusion algorithms to estimate both the position and velocity of moving target with distributed angle-only sensors in motion. The first algorithm is termed as the gross least square (LS) algorithm, which takes all observations from distributed sensors together to form an estimate of the position and velocity and thus needs a huge communication cost and a huge computation cost. The second algorithm is termed as the linear LS algorithm, which approximates locations of sensors, locations of targets, and angle-only measures for each sensor by linear models and thus does not need each local sensors to transmit raw data of angle-only observations, resulting in a lower communication cost between sensors and then a lower computation cost at the fusion center. Based on the second algorithm, a truncated LS algorithm, which estimates the target velocity through an average operation, is also presented. Numerical results indicate that the gross LS algorithm, without linear approximation operation, often benefits from more observations, whereas the linear LS algorithm and the truncated LS algorithm, both bear lower communication and computation costs, may endure performance loss if the observations are collected in a long period such that the linear approximation model becomes mismatch.

Land use transition and its eco-environmental effects are important research topics. Its essence is the process that human activities exert interference to the ecological environment in the process of social and economic development, and the ecosystem resists interference and recovers and adapts to interference. The article starts from the transition of land use dominant morphology and takes ecological resilience as the breakthrough point. Based on four periods of land use data, this article studied the spatio-temporal evolution of land use and ecological resilience and the response of ecological resilience to land use transition in China from 1990 to 2020. The results showed as follows: (1) During the study period, the construction land in China continued to increase, and the forest land, grassland, and farmland showed a fluctuating trend. (2) The spatial distribution pattern of ecological resilience showed the characteristics of “high in the southeast and low in the northwest”. The mean value and total value of ecological resilience in the region decreased first and then increased, taking 2010 as the dividing line. The difference in ecological resilience increased first and then decreased. (3) Ecological land and construction land are the main types of land that affect the changes in ecological resilience. The higher the proportion of ecological lands such as forest land, grassland, and waters, the smaller the variable coefficient of ecological resilience. The higher the proportion of construction land, the greater the difference in ecosystem elasticity among different types of areas.

In this study, we innovatively use sulphoaluminate cement slurry and its additives as a fracturing fluid system for supercritical CO2 graphene-permeable cement stone (referred to hereafter as the SCGPCS) fracturing without sand. Utilizing small fluid volumes, small displacement and small pump pressure, we obtain the success of the first field test in an extra-low desorption pressure coal seam. Laboratory experiments have proven that sulphoaluminate cement is suitable as base cements for the SCGPCS system due to their rapid setting and fast hardening characteristics. The reaction of sodium carbonate + aluminum sulfate system and sodium bicarbonate + aluminum sulfate system will generate precipitation to block the internal pore structure of cement stone, leading to a decrease in permeability. Calcium hypochlorite (1.5 wt.%) + urea (0.6 wt.%) system is preferred as a gas-generating agent system for SCGPCS. Sand (30 wt.%) with 300–425 μm particle size is preferred as a structural strength substance for SCGPCS. Graphene poly-gel (referred to hereafter as the GPG) has a high FCI and good CO2 foam stability. GPG (6.0 wt.%) is preferred as a foam stabilizer for SCGPCS. The thickening time of graphene–foam–cement slurry is 138 min at 50 °C, with long pumping time, normal thickening curve and excellent performance. The SCGPCS has a corrosion rate of 11.25 mpy in the formation water and can be stable in the formation. Acid is more corrosive to SCGPCS, and it can be used to improve the permeability of SCGPCS. Field tests have proven that SCGPCS fracturing injected 33 m3 of fluid, of which 27 m3 entered the formation. Graphene–foam–cement slurry was injected into the formation through the casing for 13 m3, with a displacement of 0.4–0.6 m3/min and tubing pressure 8–13 MPa. The formation was fractured with a fracturing crack half-length of 71.58 m, a supported fracturing crack half-length of 56.95 m, and a supported fracturing crack permeability of 56.265 mD.

Abstract Activity‐based approaches for designing AIEgens possess prominent advantages including high selectivity, sensitivity, and signal‐to‐noise ratio, and they have received more attention in recent years. Excellent activatable AIE probes have been reported for detecting toxic substances, imaging intracellular active molecules/biomolecules, as well as monitoring the activity of overexpressed enzymes in cancers. Moreover, the majority of activatable theranostic AIEgens can be specifically triggered in cancer cells and can kill these cells under light irradiation, while they have no distinct effect on normal cells, demonstrating satisfactory therapeutic selectivity that is superior to that of traditional chemotherapy. Thus, in this review, we systematically summarized the development of activatable AIE bioprobes in recent years from molecular design principles to biological applications. The challenges of activatable AIE probes and the corresponding solutions are described. We hope that the information provided in this review will facilitate the design of more activatable AIE probes to promote practical application of corresponding AIEgens.

Triple-negative breast cancer (TNBC) is more aggressive and has poorer prognosis compared to other subtypes of breast cancer. Epithelial-to-mesenchymal transition (EMT) is a process in which epithelial cells transform into mesenchymal-like cells capable of migration, invasion, and metastasis. Recently, we have demonstrated that lovastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor and a lipid-lowering drug, could inhibit stemness properties of cancer stem cells (CSCs) derived from TNBC cell in vitro and in vivo. This study is aimed at investigating whether lovastatin inhibits TNBC CSCs by inhibiting EMT and suppressing metastasis and the mechanism involved. In the present study, we found that lovastatin dysregulated lysine succinylation of cytoskeleton-associated proteins in CSCs derived from TNBC MDA-MB-231 cell. Lovastatin inhibited EMT as demonstrated by down-regulation of the protein levels of Vimentin and Twist in MDA-MB-231 CSCs in vitro and vivo and by reversal of TGF-β1-induced morphological change in MCF10A cells. Lovastatin also inhibited the migration of MDA-MB-231 CSCs. The disruption of cytoskeleton in TNBC CSCs by lovastatin was demonstrated by the reduction of the number of pseudopodia and the relocation of F-actin cytoskeleton. Combination of lovastatin with doxorubicin synergistically inhibited liver metastasis of MDA-MB-231 CSCs. Bioinformatics analysis revealed that higher expression levels of cytoskeleton-associated genes were characteristic of TNBC and predicted survival outcomes in breast cancer patients. These data suggested that lovastatin could inhibit the EMT and metastasis of TNBC CSCs in vitro and in vivo through dysregulation of cytoskeleton-associated proteins.

Lipid droplets (LDs), an extremely important cellular organelle, are responsible for the storage of neutral lipids in multiple biological processes, which could be a potential target site for photodynamic therapy (PDT) of cancer. Herein, a lipid droplet–targeted photosensitizer (BODSeI) is developed, allowing for fluorescence imaging–guided PDT. Owing to the location of lipid droplets, BODSeI demonstrates enhanced PDT efficiency with an extremely low IC50 value (around 125 nM). Besides, BODSeI shows good biocompatibility and high photostability. Therefore, BODSeI is promising for droplet-location PDT, which may trigger wide interest for exploring the pathway of lipid droplet–location PDT.

Abstract Uremia has been a rapidly increasing health problem in China. Hemodialysis (HD) is the main renal replacement therapy for uremia. The results of large-scale clinical trials have shown that the HD pattern is crucial for long-term prognosis of maintenance hemodialysis (MHD) in uremic patients. Plasma metabolism is very important for revealing the biological insights linked to the therapeutic effects of the HD pattern on uremia. Alteration of plasma metabolites in uremic patients in response to HD therapy has been reported. However, HD-pattern-dependent changes in plasma metabolites remain poorly understood. To this end, a capillary electrophoresis-time of flight mass spectrometry (CE-TOF/MS)-based metabolomics method was performed to systemically study the differences between HD and high flux hemodialysis (HFD) on plasma metabolite changes in patients. Three hundred and one plasma samples from three independent human cohorts (i.e., healthy controls, patients with pre-HD/post-HD, and patients with pre-HFD/post-HFD) were used in this study. Metabolites significantly changed (p

Abstract Targeted drug delivery systems (TDDSs) provide a promising approach to overcome the side effect of traditional chemotherapy by specific tumor targeting and drug release. Hyaluronan (HA), as a selective CD44 targeting group, has been widely used in TDDSs for chemotherapy. However, different molecular weight HAs would demonstrate different binding ability to CD44, which may result in different therapeutic effects. Herein, a silica/hydroxyapatite (MSNs/HAP) hybrid carrier loaded with anticancer drug doxorubicin (DOX) (DOX@MSNs/HAP) is fabricated. HA and oligo HA (oHA) are coated onto the nanoparticles (HA‐DOX@MSNs/HAP, oHA‐DOX@MSNs/HAP), respectively, to investigate their performance in tumor targeting ability. oHA‐DOX@MSNs/HAP shows much higher efficiency cellular uptake and drug release in tumor regions due to more effective CD44 targeting of oHA. Thus, the anticancer effect of oHA‐DOX@MSNs/HAP is significantly enhanced compared to HA‐DOX@MSNs/HAP, as demonstrated in a tumor‐bearing mouse model. This study may enable the rational design of nanodrug systems for future tumor‐targeted chemotherapy.

For the precision resection, development of near-infrared (NIR) fluorescent probe based on specificity identification tumor-associated enzyme for lighting-up the tumor area, is urgent in the field of diagnosis and treatment. Overexpression of γ-glutamyltranspeptidase, one of the cell-membrane enzymes, known as a biomarker is concerned with the growth and progression of ovarian, liver, colon and breast cancer compared to normal tissue. In this work, a remarkable enzyme-activated NIR fluorescent probe NIR-SN-GGT was proposed and synthesized including two moieties: a NIR dicyanoisophorone core as signal reporter unit; γ-glutamyl group as the specificity identification site. In the presence of γ-GGT, probe NIR-SN-GGT was transformed into NIR-SN-NH2, the recovery of Intramolecular Charge Transfer (ICT), liberating the NIR fluorescence signal, which was firstly employed to distinguish tumor tissue and normal tissues via simple “spraying” manner, greatly promoting the possibility of precise excision. Furthermore, combined with magnetic resonance imaging by T2 weight mode, tumor transplanted BABL/c mice could be also lit up for first time by NIR fluorescence probe having a large stokes, which demonstrated that probe NIR-SN-GGT would be a useful tool for assisting surgeon to diagnose and remove tumor in clinical practice.

Formaldehyde (FA), a highly reactive carbonyl species, plays significant role in physiological and pathological functions. However, elevated FA will lead to cognitive impairments, memory loss and various neurodegenerative diseases due to its potent DNA and protein cross-linking mechanisms. In this work, a fluorescence probe, BD-CHO, based on benz-2-oxa-1, 3- diazole (BD) skeleton, was designed and synthesized for detection of FA via Aza-Cope reaction with high selectivity and large Stokes shifts (about 118 nm). BD-CHO was successfully applied to monitor the changes FA level in living cells, and kidney tissues of mice. Importantly it was the first time that BD-CHO was used for visualizing exogenous FA changes in Daphnia magna through fluorescence microscopy, demonstrating its potential application for studies of biological processes associated with FA.

Modifying chitosan (CS) with polyethylenimine (PEI) grafts is an effective way to improve its gene transfection performance. However, it is still a challenge to conduct the grafting with fine control and high efficiency, particularly for the modification of water-insoluble CS. Herein, a novel method to graft CS with PEI (1.8 kDa, PEI-1.8) was developed by using ionic liquid 1-butyl-3-methyl imidazolium acetate ([BMIM]Ac) as a reaction solvent, water-insoluble CS as a reaction substrate and 1,1-carbonyldiimidazole (CDI) as a linking agent. The grafting reaction was greatly accelerated and the reaction time was largely shortened to 4 h by taking advantages of the good solubility of CS, the enhanced nucleophilicity of amino groups and the preferential stability of the activated complexes in the ionic liquid. The chitosan-graft-polyethylenimine (CS-g-PEI) products were characterized by 1H NMR, FTIR and GPC. PEI-1.8 was quantitatively grafted to CS through urea linkages, and the grafting degree (GD) was conveniently tuned by varying the molar ratios of PEI-1.8 to D-glucosamine units of CS in the range of 9.0 × 10(-3) to 9.0 × 10(-2). Compared with CS, the synthesized CS-g-PEI copolymers showed higher pDNA-binding affinity, which increased with the GD as shown in Agarose gel electrophoresis. The dynamic light scattering (DLS) experiment demonstrated that the CS-g-PEI/pDNA polyplexes had suitable particle sizes and proper ζ-potentials for cell transfection. The CS-g-PEI copolymer with a medium GD of 4.5% conferred the best gene transfection, with the efficiency 44 times of CS and 38 times of PEI-1.8 in HEp-2 cells. The cytotoxicity of CS-g-PEI was tested and found nearly as low as that of CS and much lower than that of PEI.

This study describes H2O2-activated photosensitizer nanoparticles (ICyHD NPs), which inhibit histone deacetylase via binding Zn2+ to induce ferroptosis and upregulate the intracellular O2, thus resulting in enhanced photodynamic therapeutic effect. ICyHD NPs exert strong antitumor effects on mice and have improved the therapeutic precision via observing the increase in cellular fluorescence. [ABSTRACT FROM AUTHOR]

Aerobic photooxidation in the aqueous phase is a promising field, but it faces the challenge of water-induced photocatalyst deactivation. In this work, we prepared three TADF-based photocatalysts with enhanced hydrophobicity to protect the excited state against water. Efficient aerobic photooxidation of sulfides into sulfoxides was realized in water owing to their extended triplet state lifetimes. The recyclability and oxidation mechanism of the photocatalyst were also discussed. [ABSTRACT FROM AUTHOR]

Photon-controlled pyroptosis activation (PhotoPyro) is a promising technique for cancer immunotherapy due to its noninvasive nature, precise control, and ease of operation. Here, we report that biomolecular photoredox catalysis in cells might be an important mechanism underlying PhotoPyro. Our findings reveal that the photocatalyst lutetium texaphyrin (MLu) facilitates rapid and direct photoredox oxidation of nicotinamide adenine dinucleotide, nicotinamide adenine dinucleotide phosphate, and various amino acids, thereby triggering pyroptosis through the caspase 3/GSDME pathway. This mechanism is distinct from the well-established role of MLu as a photodynamic therapy sensitizer in cells. Two analogs of MLu, bearing different coordinated central metal cations, were also explored as controls. The first control, gadolinium texaphyrin (MGd), is a weak photocatalyst but generates reactive oxygen species (ROS) efficiently. The second control, manganese texaphyrin (MMn), is ineffective as both a photocatalyst and a ROS generator. Neither MGd nor MMn was found to trigger pyroptosis under the conditions where MLu was active. Even in the presence of a ROS scavenger, treating MDA-MB-231 cells with MLu at concentrations as low as 50 nM still allows for pyroptosis photo-activation. The present findings highlight how biomolecular photoredox catalysis could contribute to pyroptosis activation by mechanisms largely independent of ROS. [ABSTRACT FROM AUTHOR]