Higher GSH Content Research Articles

Fabrication and characterization of dual-responsive nanocarriers for effective drug delivery and synergistic chem-photothermal effects

Multifunctional drug delivery systems (DDS) with simultaneous multimodal therapeutic and stimuli-responsive capabilities are recently of considerable interest. Herein, a versatile DDS capable of glutathione (GSH)/pH responsivity was engineered for the effective drug delivery and chemo-photothermal synergistic effects. Polydopamine (PDA) and polyethylene glycol (PEG) were coated on the surface of degradable dendritic mesoporous silica nanoparticles (DDMSNs) to construct the dual-responsive and photothermal nanoplatform, coined as DDMSNs-DOX-PDA-PEG. The developed nanocarriers presented excellent GSH/pH responsivity due to PDA coating and tetrasulfide bonds imbedded in DDMSNs can be broken under in low pH and high GSH concentration environment, implementing the controlled drug release. Specifically, the DDS showed better stability, biocompatibility and photothermal properties owning to the modification of PDA and PEG, and the nanocarriers performed an efficient cell uptake and significant tumor permeability efficiency. Furthermore, upon near-infrared laser irradiation, the cyto-inhibition for 4T1 cells was enhanced evidently via a synergism of chemo-photothermal treatment. Therefore, the proposed DDMSNs-DOX-PDA-PEG has great potential as DDS for effective drug delivery and the synergistic treatment of chemo-photothermal therapy. As expected, the developed strategy provides a facile alternative for fabricating multifunctional DDS for tumor therapy.

Tumor microenvironment enhanced NIR II fluorescence imaging for tumor precise surgery navigation via tetrasulfide mesoporous silica-coated Nd-based rare-earth nanocrystals.

In vivo fluorescent imaging by using the new contrast agents emitted at short-wavelength infrared region (NIR II, 1000–1700 ​nm) presents an unprecedent advantages in imaging sensitivity and spatial resolution over traditional near-infrared (NIR) light. Recently, Nd-based rare-earth nanocrystals have attracted considerable attention due to the high quantum yield (∼40%) of their emission at NIR II. However, undesirable capture by reticuloendothelial system to bring strong background signal is unsatisfying for tumor discrimination. Here, GSH-sensitive tetrasulfide bond incorporated mesoporous silica shell has entrusted onto Nd-based down-conversion nanocrystals (DCNPs) surface to totally quench the fluorescence of DCNPs. After RGD conjugation on the silica surface, the NIR II contrast agents could actively target to liver tumors. Then tetrasulfide bonds can be broken during the silica framework decomposing in cytoplasm under high GSH concentration to result in NIR II fluorescence explosive recover. Benefiting from this specific response under tumor microenvironment, the NIR II signal in other organs was markedly reduced, while the signal-to-background ratio is prominently enhanced in tumors. Then, solid liver tumors were successfully resected under the guidance of our GSH responsive NIR II fluorescent imaging with no recurrence after 20-day of surgery. Meanwhile, by combining with the ignorable side effects, the Nd-based nanoprobes vastly improved the imaging resolution of tumor margin, opening a paradigm of NIR II fluorescent imaging-guided surgery.

Dietary Protein Modifies Hepatic Glycolipid Metabolism, Intestinal Immune Response, and Resistance to Streptococcus agalactiae of Genetically Improved Farmed Tilapia (GIFT: Oreochromis niloticus) Exposed to High Temperature

The present study investigates the effects of dietary protein levels on glucolipid metabolism, immune function, and resistance to Streptococcus agalactiae of genetically improved farmed tilapia (GIFT) exposed to high temperature. Six practical diets were prepared to feed 360 fish (initial weight 43.78 ± 0.12 g) with graded protein levels (26.45%, 29.28%, 31.69%, 33.68%, 36.18%, and 38.75% dry matter). The results showed that 26.45% dietary protein significantly improved glycolysis by increasing PK mRNA levels, while the 29.28% and 31.69% dietary protein levels promoted gluconeogenesis by increasing PEPCK and G6Pase mRNA levels. For lipid metabolism, 26.45% dietary protein enhanced lipid synthesis by increasing PPAR-γ, SREBP1c, and FAS mRNA levels, while 31.69% dietary protein enhanced the level of lipolysis by increasing the PPAR-α and CPT1 mRNA levels. The highest plasma TG and TC contents were observed in the 29.28% and 31.69% dietary protein groups, respectively. In terms of antioxidants and immunity, the 31.69% dietary protein level activated the expression levels of HSP90 mRNA, thus increasing the expression levels of antioxidant-related genes (CAT, SOD, and GPx), and upregulating the anti-inflammatory factor IL-10 mRNA levels. In addition, regarding the antioxidant enzymes, the highest GSH content was found in the 29.28% dietary protein group, while the 31.69% dietary protein group had the maximum GSH-Px activity. The lowest plasma ALT and AST activities were observed in the 31.69% dietary protein group. Ultimately, the survival rate of juvenile GIFT fed 31.69% dietary protein was highest after a Streptococcus agalactiae challenge. Overall, 29.28–31.69% dietary protein was recommended in the diet of GIFT in a high-temperature environment.

Exogenous tryptophan application improves cadmium tolerance and inhibits cadmium upward transport in broccoli (Brassica oleracea var. italica)

Cadmium (Cd) pollution not only reduces crop yields, but also threatens human health and food safety. It is of great significance for agricultural production to improve plant Cd resistance and reduce Cd accumulation. In Arabidopsis, tryptophan (Trp) has been found to play a role in Cd resistance. However, studies on the role of exogenous Trp on Cd tolerance in crops are limited. Here, we report that exogenous Trp application can effectively alleviate biomass decline induced by Cd stress and inhibit Cd transport from roots to shoots in Brassica oleracea var. italica (broccoli). Compared to Cd stress alone, the fresh weight of shoots and roots of B. oleracea seedlings treated with Cd and Trp increased by 25 and 120%, respectively, and the Cd content in shoots decreased by 51.6%. In combination with physiological indices and transcriptome analysis, we preliminarily explored the mechanism of Trp alleviating Cd stress and affecting Cd transport. Trp inhibited Cd-induced indole-3-acetic acid (IAA) conjugation, thereby providing enough free IAA to sustain growth under Cd stress; Trp inhibited the indolic glucosinolate (IGS) biosynthesis induced by Cd. Considering that the synthesis of IGS consumes glutathione (GSH) as a sulfur donor, the inhibition of Trp in IGS synthesis may be conducive to maintaining a high GSH content to be against Cd stress. Consistent with this, we found that GSH content under Cd stress with Trp application was higher than that of Cd alone. In addition to alleviating the damage caused by Cd, Trp can also inhibit the upward transport of Cd from roots to shoots, possibly by repressing the expression of HMA4, which encodes a transporter responsible for the xylem loading and Cd upward transport.

A novel carbon-nanodots-based theranostic nano-drug delivery system for mitochondria-targeted imaging and glutathione-activated delivering camptothecin

Chemotherapy is severely limited by continuously decreased therapeutic efficacy and uncontrolled side effects on normal tissue, which can be improved by constructing a nanoparticle-based drug delivery system (DDS). Nevertheless, no studies have reported on DDS-based on carbon-nanodots (CNDs), combining subcellular organelle-targeted imaging/drug delivery, high drug loading content, and glutathione (GSH)-sensitive drug release into one system. Herein, the as-fabricated CNDs can be covalently conjugated with a mitochondria-targeting ligand (triphenylphosphine, TPP), a smart GSH-responsive disulfide linker (S-S), and the anticancer drug (camptothecin, CPT) to initially prepare a theranostic nano-DDS (TPP-CNDs-S-CPT) with the drug loading efficiency of 64.6 wt%. Owing to excellent water dispersibility, superior fluorescence properties, satisfactory cell permeability, and favorable biocompatibility, TPP-CNDs-S-CPT was successfully used for intracellular mitochondrial-targeted imaging in vitro. High intracellular GSH concentrations in tumor cells caused the cleavage of S-S, resulting in concomitant activation and release of CPT, as well as significant fluorescence enhancement. In vivo, TPP-CNDs-S-CPT exhibited lower biological toxicity and even higher tumor-activatable performance than free CPT, as well as specific cancer therapy with few side effects. The mitochondria-targeted ability and the precise drug-release in tumor make TPP-CNDs-S-CPT a hopeful chemotherapy prodrug, providing significant theoretical basis and data support for in-depth understanding and exploration of chemotherapeutic DDS-based on CNDs.

A glutathione activatable bioprobe for detection of hepatocellular carcinoma cells in peripheral blood via carbohydrate-protein interaction

Due to high recurrence and metastasis rates leading to high mortality of hepatocellular carcinoma (HCC), detection of HCC circulating tumor cells (HCC-CTCs), which are regarded as an HCC blood marker, holds great significance in HCC early diagnosis, metastasis evolution, and prognosis. However, current existing circulating tumor cell (CTC) detection methods require multiple steps, and have low accuracy due to extremely rare CTCs in peripheral blood (PB). Thus, a simple and sensitive HCC-CTCs detection method is urgently needed. Here, a glutathione (GSH) activatable bioprobe (LacCC) targeting HCC cells was first developed through coordinating copper ions (Cu2+) to lactose modified coumarin derivative (LacC). Owing to the carbohydrate-protein interaction between lactose group and asialoglycoprotein receptors (ASGPRs) overexpressed on the membrane of HCC cells, LacCC displays selectivity towards HCC cells. The fluorescence of LacCC recovers rapidly within 2 min upon demetallation by high concentration of GSH in HCC cells. In simulated PB samples, as low as 10 HepG2 cells were detected via CLSM after removing red blood cells (RBCs) and culturing with LacCC. By coupling with flow cytometry, LacCC can achieve quantitative detection of HCC cells with low detection limit (LOD) of 3 cells per sample. Thus, this bioprobe possessing ASGPRs targetability and fast GSH responsiveness shows ultrasensitive detectability towards HCC cells in PB, which may have the potential for simple yet highly sensitive HCC-CTCs detection.

Galactosed and Reduction-Responsive Nanoparticles Assembled from Trimethylchitosan-Camptothecin Conjugates for Enhanced Hepatocellular Carcinoma Therapy.

The targeted delivery of drugs to tumor cells and prevention of premature release before reaching the target is one of the key challenges to developing nanomedicines. In this paper, galactose decorated trimethyl chitosan (GT)–camptothecin (CPT) prodrug nanoparticles (GT-ss-CPT NPs) were prepared from GT-CPT conjugates linked by dithiodipropionic acid. The obtained GT-ss-CPT NPs were spherical with a particle size of 184.1 nm. GT-ss-CPT NPs displayed low drug release under physiological conditions, whereas efficient drug release was triggered by high GSH concentration. GT-ss-CPT NPs exhibited a higher antitumor effect both in vitro and in vivo than the free drug counterpart. More importantly, GT-ss-CPT NPs reduced the high systematic toxicity of CPT to tumor-bearing mice. In summary, GT-ss-CPT NPs can not only inhibit the premature release of CPT but also have a great potential for targeted hepatocellular carcinoma chemotherapy.

Biomimetic smart mesoporous carbon nanozyme as a dual-GSH depletion agent and O2 generator for enhanced photodynamic therapy

Photodynamic therapy (PDT) has been thriving in the theranostics of cancer in recent years. However, due to a series of problems such as high concentration of GSH and insufficient O2 partial pressure in the tumor micro-environment, it is difficult to achieve the desired therapeutic effects with single PDT. Mesoporous carbon (MC-COOH) has been widely used in photothermal therapy (PTT) due to its high photothermal conversion efficiency and drug loading. In addition, we have discovered that MC-COOH owned high-efficiency glutathione oxidase-like activity for intracellular lasting GSH consumption. Hence, a smart mesoporous carbon nanozyme (CCM) was designed as a dual-GSH depletion agent and O2 generator combined with PTT to overcome the dilemma of PDT. MnO2-doped carbon nanozyme (MC-Mn) was developed as the photothermal vehicles for the efficient loading of photosensitizer (Ce6). Subsequently, 4T1 membrane-coated nanozyme (Ce6/CCM) was constructed to achieve homologous targeting capability. The carbon nanozyme owned the sustained dual-GSH depletion function through MC-COOH and MnO2, which greatly destroyed the antioxidant system of the tumor. Meanwhile, MnO2 could produce affluent O2 in the presence of H2O2, thereby alleviating the hypoxic state of tumor tissues and further promoting the generation of ROS. In addition, the novel carbon nanozyme was designed as photoacoustic imaging (PAI) agent and magnetic resonance imaging (MRI) contrast for real-time imaging during tumor therapy. In summary, this work showed that the biomimetic carbon nanozyme could be used as dual-GSH depletion agent and O2 generator for dual-mode imaging-guided PTT-PDT. Statement of significance- MC-COOH with highly efficient GSH-OXD activity was first discovered and applied in PDT.- MnO2 acted as an O2 generator and GSH depletion agent to enhance PDT.- The tumor-targeting ability of the nanozyme was improved by cell membrane camouflage.- CCM nanozyme possesses both PAI and MRI dual-mode imaging modalities to guide PDT/PTT.

Synthesis of Dual-Response MnO2 Nanospheres as Multifunctional Drug Carriers

Recently, hollow structures have attracted much attention due to their high specific surface area, clear interior space, low density and good permeability. Among them, manganese dioxide (MnO2) hollow structure has also been widely studied for catalysis, drug delivery and energy storage. Based on the characteristics of low pH and high GSH concentration in tumor microenvironment, it is possible to develop an intelligent drug delivery system with pH/GSH response based on hollow mesoporous MnO2 nanospheres. In addition, the excellent physical and chemical properties of MnO2 nanomaterials provide conditions for its synergistic photothermal therapy. For example, Mn2+ released after manganese dioxide reacts with GSH can enhance T1-MAGNETIC resonance (MR) imaging. Meanwhile, manganese dioxide can also react with H2O2 in tumor microenvironment to release oxygen and alleviate tumor hypoxia. In order to prevent drug loss during delivery, a GSH-responsive hollow mesoporous manganese dioxide microsphere was selected as the drug carrier in this paper, and a series of studies were carried out on the performance of the carrier. Hollow mesoporous MnO2 nanospheres with particle size below 100 nm were prepared by hydrothermal method, and their response to tumor microenvironment was simulated in vitro. It has been proved that hollow mesoporous MnO2 nanospheres can be desorbed at low pH and GSH response, and can be used to deliver drugs or photothermal agents, as well as for collaborative cancer imaging and treatment.

Local delivery of tumor‐targeting nano‐micelles harboring GSH‐responsive drug release to improve antitumor efficiency

AbstractIncreasing the accumulation of therapeutics in tumor site and improving the bioavailability of delivered drug are vital strategies to enhance chemotherapy efficiency as well as reduce side effects. Herein, we report an injectable hydrogel system to locally deliver tumor‐targeting nano‐micelles with GSH‐responsive drug release to improve antitumor efficiency. Amphiphilic polymers with different functions were designed and successfully synthesized. Then, the prepared polymers self‐assembled into nano‐micelles (PPR‐NP), which exhibited tumor cell targeting and GSH‐responsive drug release behavior. Furthermore, we constructed an injectable hydrogel system composed of the nano‐micelles (PPR‐NP@α‐CDgel). Peritumorally administrated to tumor site, PPR‐NP@α‐CDgel sustainedly released PPR‐NP around tumor site in situ, which were specifically taken up by tumor cells and rapidly released loaded paclitaxel in responsible to the high concentration of GSH in tumor cell, thus effectively inhibiting tumor growth. Synergized by the multitargeting effect, the present system could effectively improve the bioavailability of antineoplastic drug and enhance the antitumor efficiency, holding potential for solid tumor therapy.

Comparative study on the oxidative stress of commercially important fish species from localities with different ecological conditions along the Bulgarian Black Sea coast

The aim of the present study was to perform a pilot assessment and analysis of the oxidative stress (OS) level in four commercially important fish species (round goby, red mullet, sprat and horse mackerel) from different localities of the Bulgarian Black Sea coast. The fish were sampled during trawl selectivity experiments. The OS level in the fish was assessed by measuring lipid peroxidation (LPO), glutathione concentration (GSH), activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST), as well as acetylcholine esterase (AChE) in gills and liver. Round goby and red mullet caught in the Nessebar Bay showed clear signs of OS with the highest levels of LPO and GST activities, accompanied by the lowest AChE activities in both liver and gills. On the contrary, round goby caught near Maslen Nos (a region with good ecological conditions) were least affected by OS with low LPO and high GSH concentrations and SOD activity. There were no significant differences in the OS bioindicators of horse mackerel from the different localities. Sprat caught in Nessebar Bay, compared to those caught from the other localities, showed presence of OS indicated by lower GSH levels and relatively higher CAT, GPx and GST activities, accompanied by low AChE activity in gills. It can be concluded that round goby and red mullet were more vulnerable to OS induced by marine environmental factors than the horse mackerel and sprat. However, their antioxidant defense system allows them to tolerate and adapt to the environment of their habitats. Further studies are needed for the assessment of OS in important fish species in the Bulgarian part of the Black Sea.

Glutathione depletion and photosensitizer activation augments efficacy of tumor photodynamic immunotherapy

Photodynamic therapy (PDT) is a novel and promising clinical therapy, that is proven these years to be able to induce immunogenicity of tumor cells and activate anti-tumor immunity. However, its application is constrained by the upregulated glutathione (GSH) concentration in tumor cells, coupled with aggregation-caused quenching (ACQ) effect which impedes activation of photosensitizers, thereby hindering the production of reactive oxygen species (ROS) and lowering efficacy. Here, we developed a drug delivery system PSSP, containing a poly(disulfide) (PSS) frame with high disulfide content and Pheophorbide a (Ppa) for laser-induced photodynamic immunotherapy. The PSS bond responded well and effectively depleted high GSH content to a certain degree, under high GSH levels in tumor cells. Moreover, Ppa maintained a hydrophobic property and exhibited excellent performance when bonded with albumin in tumor cells. Taken together, our findings indicated that the PSSP drug delivery system circumvented the shortcomings of abundant GSH in tumor cells and ACQ of photosensitizers, effectively activated the photosensitizer, and elicited more powerful PDT effects, thereby inducing more efficient immunogenic cell death (ICD) effect, and consequently strongly activating immunity to eliminate tumor cells.

Red and Near-Infrared Fluorescent Probe for Distinguishing Cysteine and Homocysteine through Single-Wavelength Excitation with Distinctly Dual Emissions.

Small-molecule biothiols, including cysteine (Cys), homocysteine (Hcy), and glutathione (GSH), participate in various pathological and physiological processes. It is still a challenge to simultaneously distinguish Cys and Hcy because of their similar structures and reactivities, as well as the interference from the high intramolecular concentration of GSH. Herein, a novel fluorescent probe, CySI, based on cyanine and thioester was developed to differentiate Cys and Hcy through a single-wavelength excitation and two distinctly separated emission channels. The probe exhibited a turn-on fluorescence response to Cys at both 625 nm (the red channel) and 740 nm (the near-infrared channel) but only showed fluorescence turn-on to Hcy at 740 nm (the near-infrared channel) and no fluorescent response to GSH. With the aid of built-in self-calibration of single excitation and dual emissions, simultaneous discriminative determinations of Cys and Hcy were realized through red and near-infrared channels. CySI exhibited excellent selectivity toward Cys and Hcy with a fast response. This probe was further exploited to visualize exogenous Cys and Hcy in cells through dual emission channels under one excitation. Moreover, it could efficiently target mitochondria and was applied to monitor the endogenous Cys fluctuations independently in mitochondria through the red emission channel.

Glutathione-sensitive IPI-549 nanoparticles synergized with photodynamic Chlorin e6 for the treatment of breast cancer

We combined phosphoinositol-3-kinin inhibitor IPI-549 and photodynamic Chlorin e6 (Ce6) on carboxymethyl chitosan to develop a novel drug delivery nanoparticle (NP) system (Ce6/CMCS-DSP-IPI549) and evaluate its glutathione (GSH) sensitivity and targeting ability for breast cancer treatment. The NPs were spherical with a uniform size of 218.8 nm, a stable structure over 7 days. The maximum encapsulation efficiency was 64.42%, and NPs drug loading was 8.05%. The NPs released drugs within tumor cells due to their high GSH concentration, while they maintained structural integrity in normal cells, which have low GSH concentration. The cumulative release rates of IPI-549 and Ce6 at 108 h were 70.67% and 40.35% (at GSH 10 mM) and 8.11% and 2.71% (at GSH 2 μM), respectively. The NPs showed a strong inhibitory effect on 4T1 cells yet did not affect human umbilical vein endothelial cells (HUVECs). After irradiation by a 660 nm infrared laser for 72 h, the survival rate of 4T1 cells was 15.51%. Cellular uptake studies indicated that the NPs could accurately release drugs into tumor cells. In addition, the NPs had a good photodynamic effect and promoted the release of reactive oxygen species to damage tumor cells. Overall, the combination therapy of IPI-549 and Ce6 is safe and effective, and may provide a new avenue for the treatment of breast cancer.

A Smart Near-Infrared Carbon Dot-Metal Organic Framework Assemblies for Tumor Microenvironment-Activated Cancer Imaging and Chemodynamic-Photothermal Combined Therapy.

Tumor microenvironment (TME)-activated cancer imaging and therapy is a key to achieving accurate diagnosis and treatment of cancer and reducing the side effects. Herein, smart near-infrared carbon dot-metal organic framework MIL-100 (Fe) assemblies are constructed to achieve TME-activated cancer imaging and chemodynamic-photothermal combined therapy. First, a near-infrared emission carbon dot (RCDs) is developed using glutathione (GSH) as the precursor. Then, the RCDs@MIL-100 self-assemblies are obtained using RCDs, FeCl3 , and trimesic acid solutions as raw materials. After the RCDs@MIL-100 enters the TME, a high concentration of GSH reduces Fe3+ to Fe2+ and drains the GSH, triggering the collapse of RCDs@MIL-100 skeleton and the release of RCDs and Fe2+ , at which time the RCDs fluorescence is restored and in an "on" state to illuminate the tumor cells, which achieved cancer imaging. The released Fe2+ reacts with H2 O2 in the TME to form highly reactive hydroxyl radicals (•OH) by Fenton reaction, which achieves the chemodynamic therapy of tumors. Thus, efficient synergistic chemodynamic-photothermal dual mode therapy is achieved under fluorescence imaging guidance with TME response.

Aggregation Turns BODIPY Fluorophores into Photosensitizers: Reversibly Switching Intersystem Crossing On and Off for Smart Photodynamic Therapy

Aggregation Turns BODIPY Fluorophores into Photosensitizers: Reversibly Switching Intersystem Crossing On and Off for Smart Photodynamic Therapy

Addition of Reduced Glutathione (GSH) to Freezing Medium Reduces Intracellular ROS Levels in Donkey Sperm.

In donkeys, the use of frozen-thawed sperm for artificial insemination (AI) leads to low fertility rates. Furthermore, donkey sperm produce a large amount of reactive oxygen species (ROS), and post-AI inflammation induces the formation of neutrophil extracellular traps (NETosis), which further generates many more ROS. These high ROS levels may induce lipid peroxidation in the sperm plasma membrane, thus affecting its integrity. Enzymatic and non-enzymatic antioxidants, mainly found in the seminal plasma (SP), are responsible for maintaining the redox balance. However, this fluid is removed prior to cryopreservation, thereby exposing sperm cells to further oxidative stress. The exogenous addition of antioxidants to the freezing medium can reduce the detrimental effects caused by ROS generation. Therefore, the aim of this study was to evaluate how the addition of different reduced glutathione (GSH) concentrations (control, 2 mM, 4 mM, 6 mM, 8 mM, and 10 mM) to fresh sperm affect their cryotolerance. Total and progressive motility, kinematic parameters and motile sperm subpopulations were significantly (p < 0.05) different from the control in treatments containing 8 mM and 10 mM GSH, but not at lower concentrations. Plasma and acrosome membrane integrity, mitochondrial membrane potential (MMP) and intracellular superoxide levels (O2−) were not affected (p > 0.05) by any GSH concentration. Interestingly, however, the addition of 8 mM or 10 mM GSH reduced (p < 0.05) the percentages of viable sperm with high overall ROS levels compared to the control. In conclusion, frozen-thawed donkey sperm are able to tolerate high GSH concentrations, which differs from what has been observed in other species. This antioxidant capacity suggests that ROS could be important during post-AI and that the impact of using exogenous antioxidants like GSH to improve the sperm resilience to freeze-thawing is limited in this species.

Construction multifunctional nanozyme for synergistic catalytic therapy and phototherapy based on controllable performance

Advances in nanozyme involve an efficient catalytic process, which has demonstrated great potential in tumor therapy. The key to improving catalytic therapy is to solve the limitation of the tumor microenvironment on Fenton reaction. In this work, Prussian blue nanoparticles doped with different rare earth ions (Yb3+, Gd3+, Tm3+) were screened to perform synergistic of photothermalandcatalytictumortherapy. The optimized catalytic performance can be further enhanced through photothermal effect to maximize the Fenton reaction to solve the limitation of the tumor microenvironment. Yb-PB, with the optimal photothermal and catalytic performance, was screened out. In order to avoid the scavenging effect of glutathione (GSH) on ·OH in tumor cells and the reaction with a bit H2O2 in normal cells, GSH targeted polydopamine (PDA) was wrapped on the surface of Yb-PB to obtain Yb-PB@PDA. It was found that enough hydroxyl radicals (·OH) can be generated even if at high GSH concentration and the NIR irradiation can help produce more ·OH. Cell fluorescence imaging (FOI) and in vivo magnetic resonance imaging (MRI) experiments showed the potential application in FOI/MRI dual-mode imaging guided therapy. In vivo anti-tumor experiments showed that Yb-PB@PDA has a satisfactory anti-cancer effect through the combined effect of catalytic/photothermal therapy. Thus, a multifunctional nanozyme for tumor therapy is constructed.

The effects of various organic fertilizers with or without adsorbents on the productivity, antioxidant status and immune responses of Nile tilapia raised in cement ponds

The present study investigated the role of fish sludge (FS) as an organic fertilizer in fish ponds alone or in combined with some industrial wastes such as sawdust (SD) and sugar beet pulp (SBP) and their influences on productivity, blood biochemistry, antioxidant and immune status of Nile tilapia compared to the well-known fertilizer cow dung. Fish were distributed into the following experimental groups: control group (with no fertilizers); CD group (cow dung fertilized group); FS group (fish sludge fertilized group); FS + SD (fertilized with fish sludge combined with sawdust); FS + SBP group (fertilized with fish sludge combined with sugar beet pulp) in 3 replicates ponds per each. Fish raised in ponds fertilized with FS + SD, FS, and FS + SBP respectively, recorded higher final weight (FW), weight gain (WG), specific growth rate (SGR), and protein efficiency ratio (PER) values and the lowest feed conversion ratio (FCR) values when compared to the control group. Fish raised in CD fertilized ponds showed significantly higher alanine aminotransferase (ALT) levels. While, FS + SD group had the highest GSH content followed by FS and FS + SBP groups. The catalase (CAT) activity was also significantly higher in FS, FS + SD and FS + SB groups compared to control and CD groups. FS significantly reduced the Malondialdehyde (MDA) content than control and CD groups and a more significant reduction was recorded in FS + SD and FS + SBP groups. The highest total antioxidant activity (TAC) was recorded in the FS + SBP group. The results also showed that FS + SBP followed by FS + SD obtained the highest Alternative Complement pathway (ACH50) activity. FS, FS + SD and FS + SBP groups showed significantly higher lysozyme activity than the CD group. All added fertilizers significantly increased the NBT value compared to the control group. In conclusion, fish sludge showed a more promising property as an organic fertilizer in fish ponds than cow dung, particularly in the presence of adequate water purifying material such as sawdust or sugar beet pulp.

Nano-Drug Design Based on the Physiological Properties of Glutathione.

Glutathione (GSH) is involved in and regulates important physiological functions of the body as an essential antioxidant. GSH plays an important role in anti-oxidation, detoxification, anti-aging, enhancing immunity and anti-tumor activity. Herein, based on the physiological properties of GSH in different diseases, mainly including the strong reducibility of GSH, high GSH content in tumor cells, and the NADPH depletion when GSSH is reduced to GSH, we extensively report the design principles, effect, and potential problems of various nano-drugs in diabetes, cancer, nervous system diseases, fluorescent probes, imaging, and food. These studies make full use of the physiological and pathological value of GSH and develop excellent design methods of nano-drugs related to GSH, which shows important scientific significance and prominent application value for the related diseases research that GSH participates in or responds to.