Sono-responsive smart nanoliposomes for precise and rapid hemostasis application.

Massive hemorrhage caused by injuries and surgical procedures is a major challenge in emergency medical scenarios. Conventional means of hemostasis often fail to rapidly and efficiently control bleeding, especially in inaccessible locations. Herein, a type of smart nanoliposome with ultrasonic responsiveness, loaded with thrombin (thrombin@liposome, named TNL) was developed to serve as an efficient and rapid hemostatic agent. Firstly, the hydrophilic cavities of the liposomes were loaded onto the sono-sensitive agent protoporphyrin. Secondly, a singlet oxygen-sensitive chemical bond was connected with the hydrophobic and hydrophilic ends of liposomes in a chemical bond manner. Finally, based on the host guest effect between ultrasound and the sono-sensitizer, singlet oxygen is continuously generated, which breaks the hydrophobic and hydrophilic ends of liposome fragments, causing spatial collapse of the TNL structure, swiftly releases thrombin loaded in the hydrophilic capsule cavity, thereby achieving accurate and rapid local hemostasis (resulted in a reduction of approximately 67% in bleeding in the rat hemorrhage model). More importantly, after thorough assessments of biocompatibility and biodegradability, it has been confirmed that TNL possesses excellent biosafety, providing a new avenue for efficient and precise hemostasis.

Novel Sulfoximine Derivatives Containing Cyanoguanidine and Nitroguanidine Moieties: Design, Synthesis, and Bioactivities.

A total of 32 novel sulfoximines bearing cyanoguanidine and nitroguanidine moieties were designed and synthesized by a rational molecule design strategy. The bioactivities of the title compounds were evaluated and the results revealed that some of the target compounds possessed excellent antifungal activities against six agricultural fungi, including Sclerotinia sclerotiorum, Fusarium graminearum, Phytophthora capsici, Botrytis cinerea, Rhizoctonia solani, and Pyricularia grisea. Among them, compounds 8e1 and 8e4 exhibited significant efficacy against P. grisea with EC50 values of 2.72 and 2.98 µg/mL, respectively, which were much higher than that of commercial fungicides boscalid (47.95 µg/mL). Interestingly, in vivo assays determined compound 8e1 possessed outstanding activity against S. sclerotiorum with protective and curative effectiveness of 98 and 95.6% at 50 µg/mL, which were comparable to those of boscalid (93.2, 91.9%). The further preliminary mechanism investigation disclosed that compound 8e1 could damage the structure of the cell membrane of S. sclerotiorum, increase its permeability, and suppress its growth. Overall, the findings enhanced that these novel sulfoximine derivatives could be potential lead compounds for the development of new fungicides.

The Complete Genome Sequence of Bacillus toyonensis Cbmb3 with Polyvinyl Chloride-Degrading Properties.

The accumulation of high amounts of plastic waste in the environment has raised ecological and health concerns, particularly in croplands, and biological degradation presents a promising approach for the sustainable treatment of this issue. In this study, a polyvinyl chloride (PVC)-degrading bacterium was isolated from farmland soil samples attached to waste plastic, utilizing PVC as the sole carbon source. The circular chromosome of the strain Cbmb3, with a length of 5,768,926 bp, was subsequently sequenced. The average GC content was determined to be 35.45%, and a total of 5835 open reading frames were identified. The strain Cbmb3 was designated as Bacillus toyonensis based on phylogenomic analyses and genomic characteristics. The bioinformatic analysis of the Cbmb3 genome revealed putative genes encoding essential enzymes involved in PVC degradation. Additionally, the potential genomic characteristics associated with phytoprobiotic effects, such as the synthesis of indole acetic acid and secondary metabolite synthesis, were also revealed. Overall, the present study provides the first complete genome of Bacillus toyonensis with PVC-degrading properties, suggesting that Cbmb3 is a potential strain for PVC bioremediation and application.

Porous Se@SiO2 nanospheres alleviate diabetic retinopathy by inhibiting excess lipid peroxidation and inflammation.

BACKGROUND: Lipid peroxidation is a characteristic metabolic manifestation of diabetic retinopathy (DR) that causes inflammation, eventually leading to severe retinal vascular abnormalities. Selenium (Se) can directly or indirectly scavenge intracellular free radicals. Due to the narrow distinction between Se's effective and toxic doses, porous Se@SiO2 nanospheres have been developed to control the release of Se. They exert strong antioxidant and anti-inflammatory effects. METHODS: The effect of anti-lipid peroxidation and anti-inflammatory effects of porous Se@SiO2 nanospheres on diabetic mice were assessed by detecting the level of Malondialdehyde (MDA), glutathione peroxidase 4 (GPX4), decreased reduced/oxidized glutathione (GSH/GSSG) ratio, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL) -1ß of the retina. To further examine the protective effect of porous Se@SiO2 nanospheres on the retinal vasculopathy of diabetic mice, retinal acellular capillary, the expression of tight junction proteins, and blood-retinal barrier destruction was observed. Finally, we validated the GPX4 as the target of porous Se@SiO2 nanospheres via decreased expression of GPX4 and detected the level of MDA, GSH/GSSG, TNF-α, IFN-γ, IL -1ß, wound healing assay, and tube formation in high glucose (HG) cultured Human retinal microvascular endothelial cells (HRMECs). RESULTS: The porous Se@SiO2 nanospheres reduced the level of MDA, TNF-α, IFN-γ, and IL -1ß, while increasing the level of GPX4 and GSH/GSSG in diabetic mice. Therefore, porous Se@SiO2 nanospheres reduced the number of retinal acellular capillaries, depletion of tight junction proteins, and vascular leakage in diabetic mice. Further, we identified GPX4 as the target of porous Se@SiO2 nanospheres as GPX4 inhibition reduced the repression effect of anti-lipid peroxidation, anti-inflammatory, and protective effects of endothelial cell dysfunction of porous Se@SiO2 nanospheres in HG-cultured HRMECs. CONCLUSION: Porous Se@SiO2 nanospheres effectively attenuated retinal vasculopathy in diabetic mice via inhibiting excess lipid peroxidation and inflammation by target GPX4, suggesting their potential as therapeutic agents for DR.

Genipin inhibits proliferation of gastric cancer cells by inducing ferroptosis: an integrated study of network pharmacology and bioinformatics study.

Ferroptosis has been demonstrated to suppress cancer development and is targeted for cancer therapy. Genipin, an iridoid constituent in Gardeniae Fructus, has been reported to exert anti-cancer abilities. However, whether genipin could induce ferroptosis remains unclear. The purpose of this study is to explore the anti-gastric cancer (GC) effects of genipin by inducing ferroptosis and to identify the potential targets. CCK-8 and colony formation assays were performed to evaluate the anti-GC effects of genipin. Flowcytometry and western blot were used to indicate ferroptosis-inducing ability of genipin. The potential targets of genipin were analyzed by network pharmacology, screened using UALCAN and KM-plotter database and evaluated by molecular docking. The results showed that genipin inhibited cell viability and proliferation of GC cells. Genipin treatment decreased levels of GPX4 and SLC7A11, induced accumulation of lipid peroxidation intracellularly and led to ferroptosis in GC cells. Network pharmacology analysis identified that lipid- and ROS-related pathways involved in ferroptosis ranked high among genipin-GC common targets. Data from UALCAN and KM-plotter database demonstrated that expression levels of ferroptosis-related targets, including AURKA, BCAT2, DHODH, and GPI, increased in GC tissues and the higher levels of the above four targets were related to tumor stage, tumor grade, and poor prognosis. Among these four targets, AURKA, BCAT2, and DHODH were confirmed by molecular docking with binding energies less than - 5. Taken together, our study demonstrates that genipin could exert anti-GC ability by inducing ferroptosis and provides evidence for the potential application of genipin in GC treatment.

Nanocatalytic theranostics with intracellular mutual promotion for ferroptosis and chemo-photothermal therapy.

The reactive oxygen species (ROS) produced through the Fenton reaction, induces lipid peroxide (LPO), causing cellular structural damage and ultimately triggering ferroptosis. However, the generation of ROS in the tumor microenvironment (TME) is limited by the catalytic efficiency of the Fenton reaction. Herein, a novel hollow mesoporous silica nanoparticle (HMSN) combined with multi-metal sulfide-doped mesoporous silica nanocatalyzers (NCs) was developed, namely MxSy-HMSN NCs (M represents Cu Mn and Fe, S denotes sulfur). The MxSy-HMSN can dramatically enhanced the ferroptosis by: (1) facilitating the conversion of H2O2 to ·OH through Fenton or Fenton-like reactions through co-catalysis; (2) weakening ROS scavenging systems by depleting the over expressed glutathione (GSH) in TME; (3) providing exceptional photothermal therapy to augment ferroptosis. The MxSy-HMSN can also act as smart cargos for anticancer drug-doxorubicin (DOX). The release of DOX is responsive to GSH/pH/Near-infrared Light (NIR) irradiation at the tumor lesion, significantly improving therapeutic outcomes while minimizing side effects. Additionally, the MxSy-HMSN has demonstrated excellent magnetic resonance imaging (MRI) potential. This smart MxSy-HMSN offer a synergetic approach combining ferroptosis with chemo-photothermal therapy and magnetic resonance imaging (MRI) diagnose, which could be an informative guideline for the design of future NCs.

Combining Porous Se@SiO2 Nanocomposites and dECM Enhances the Myogenic Differentiation of Adipose-Derived Stem Cells.

Background: Volumetric Muscle Loss (VML) denotes the traumatic loss of skeletal muscle, a condition that can result in chronic functional impairment and even disability. While the body can naturally repair injured skeletal muscle within a limited scope, patients experiencing local and severe muscle loss due to VML surpass the compensatory capacity of the muscle itself. Currently, clinical treatments for VML are constrained and demonstrate minimal efficacy. Selenium, a recognized antioxidant, plays a crucial role in regulating cell differentiation, anti-inflammatory responses, and various other physiological functions. Methods: We engineered a porous Se@SiO2 nanocomposite (SeNPs) with the purpose of releasing selenium continuously and gradually. This nanocomposite was subsequently combined with a decellularized extracellular matrix (dECM) to explore their collaborative protective and stimulatory effects on the myogenic differentiation of adipose-derived mesenchymal stem cells (ADSCs). The influence of dECM and NPs on the myogenic level, reactive oxygen species (ROS) production, and mitochondrial respiratory chain (MRC) activity of ADSCs was evaluated using Western Blot, ELISA, and Immunofluorescence assay. Results: Our findings demonstrate that the concurrent application of SeNPs and dECM effectively mitigates the apoptosis and intracellular ROS levels in ADSCs. Furthermore, the combination of dECM with SeNPs significantly upregulated the expression of key myogenic markers, including MYOD, MYOG, Desmin, and myosin heavy chain in ADSCs. Notably, this combination also led to an increase in both the number of mitochondria and the respiratory chain activity in ADSCs. Conclusion: The concurrent application of SeNPs and dECM effectively diminishes ROS production, boosts mitochondrial function, and stimulates the myogenic differentiation of ADSCs. This study lays the groundwork for future treatments of VML utilizing the combination of SeNPs and dECM.

A pH-responsive ZC-QPP hydrogel for synergistic antibacterial and antioxidant treatment to enhance wound healing.

The problems of bacterial resistance and high oxidation level severely limit wound healing. Therefore, we constructed a multifunctional platform of chitosan quaternary ammonium salts (QCS)/polyvinyl alcohol (PVA)/polyethylene glycol (PEG) hydrogels (QPP) loaded with ZnO@CeO2 (ZC-QPP). Firstly, the hydrogel was co-cross-linked by hydrogen and borate ester bonds, which allows easy adherence to a tissue surface for offering a protective barrier and moist environment for wounds. The chitosan quaternary ammonium salts due to their amino groups have inherent antibacterial properties to induce bacterial death. In response to the acidic conditions of the bacterial infection microenvironment, the borate ester bonds in the QPP hydrogel break and the ZC NCs dispersed in the hydrogel are released. The gradual dissociation of Zn2+ under acidic conditions can directly damage bacterial membranes. The wound site of bacterial infection always causes overexpression of reactive oxygen species (ROS) levels, often leading to inflammation and preventing rapid wound repair. CeO2 can eliminate excess ROS to reduce the inflammatory response. From in vitro and in vivo results, the high biosafety of the ZC-QPP hydrogel has demonstrated excellent antibacterial and antioxidant performance to enhance wound healing. Therefore, the ZC-QPP hydrogel opens a method to develop multifunctional synergistic therapeutic platforms combining enzyme-like nanomaterials with hydrogels for synergistic antibacterial and antioxidant treatment to promote wound healing.

Solubility determination, dissolution properties and solid transformation of resmetirom (form A) in heptane and seven alcohols.

In this work, the solubility of resmetirom (form A) was initially measured in heptane and seven alcohol solvents by gravimetric methods. Then, the transformation temperature between form A and ethanol solvate was determined at 333.76 K. Subsequently, some commonly used models were applied to fit the solubility data, and it was found that the modified Apelblat equation and the Jouyban-Acree-van't Hoff (J-A-V) model achieved the highest correlation accuracy for those in mono-solvents and heptane + propanol, respectively. And the average relative deviation (ARD) values of models were less than 0.5%, indicating a good agreement with the experimental results. Additionally, through density functional theory calculation and the analysis of solvent parameters, it was observed that hydrogen-bonding played primary roles in the dissolution process of resmetirom. The multiple factors such as the polarity of solvent, active site interaction, the molecular size and free volume all affect the solubility of resmetirom. Furthermore, by comparing the experimental and simulated infrared spectra of form A and two alcohol solvates, five characteristic bands were selected for quantification. Partial least squares regression (PLSR), a multivariate statistical analysis method, was used to extract quantitative information. The quantitative analysis model was established based on specific wavelength intervals, which were associated with inter-molecular interactions. Combined with PLSR, a new high-precision quantitative method was established to study the solid transformation process between form A and solvates. From 303.15 to 323.15 K, the rate of transformation from form A to methanol solvate or ethanol solvate was decreased with increasing temperature, revealing that the transformation process was driven by the solubility difference between form A and solvates under the studied conditions. This research will definitely afford necessary solubility data and solvent selection for the design of the crystallization process of resmetirom (form A) in industry, and provide basic data for the production of resmetirom (form A) in the pharmaceutical industry.

Molecular targets and mechanisms involved in the action of Banxia Shumi decoction in insomnia treatment.

Insomnia is a common sleep-wake rhythm disorder, which is closely associated with the occurrence of many serious diseases. Recent researches suggest that circadian rhythms play an important role in regulating sleep duration and sleep quality. Banxia Shumi decoction (BSXM) is a well-known Chinese formula used to treat insomnia in China. However, the overall molecular mechanism behind this therapeutic effect has not yet been fully elucidated. This study aimed to identify the molecular targets and mechanisms involved in the action of BSXM during the treatment of insomnia. Using network pharmacology and molecular docking methods, we investigated the molecular targets and underlying mechanisms of action of BSXM in insomnia therapy. We identified 8 active compounds from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and the traditional Chinese medicine integrative database that corresponded to 26 target genes involved in insomnia treatment. The compound-differentially expressed genes of the BXSM network indicated that cavidine and gondoic acid could potentially become key components of drugs used for insomnia treatment. Further analysis revealed that GSK3B, MAPK14, IGF1R, CCL5, and BCL2L11 were core targets significantly associated with the circadian clock. Pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes revealed that epidermal growth factor receptor tyrosine kinase inhibitor resistance was the most prominently enriched pathway for BSXM in the insomnia treatment. The forkhead box O signaling pathway was also found to be significantly enriched. These targets were validated using the Gene Expression Omnibus dataset. Molecular docking studies were performed to confirm the binding of cavidine and gondoic acid to the identified core targets. To our knowledge, our study confirmed for the first time that the multi-component, multi-target, and multi-pathway characteristics of BXSM may be the potential mechanism for treating insomnia with respect to the circadian clock gene. The results of this study provided theoretical guidance for researchers to further explore its mechanism of action.

Biodegradable nanomaterials for diagnosis and therapy of tumors.

Although degradable nanomaterials have been widely designed and applied for cancer bioimaging and various cancer treatments, few reviews of biodegradable nanomaterials have been reported. Herein, we have summarized the representative research advances of biodegradable nanomaterials with respect to the mechanism of degradation and their application in tumor imaging and therapy. First, four kinds of tumor microenvironment (TME) responsive degradation are presented, including pH, glutathione (GSH), hypoxia and matrix metalloproteinase (MMP) responsive degradation. Second, external stimulation degradation is summarized briefly. Next, we have outlined the applications of nanomaterials in bioimaging. Finally, we have focused on some typical examples of biodegradable nanomaterials in radiotherapy (RT), photothermal therapy (PTT), starvation therapy, photodynamic therapy (PDT), chemotherapy, chemodynamic therapy (CDT), sonodynamic therapy (SDT), gene therapy, immunotherapy and combination therapy.

Menthone Exerts its Antimicrobial Activity Against Methicillin Resistant Staphylococcus aureus by Affecting Cell Membrane Properties and Lipid Profile.

Objective: The characteristic constituents of essential oils from aromatic plants have been widely applied as antimicrobial agents in the last decades. However, their mechanisms of action remain obscure, especially from the metabolic perspective. The aim of the study was to explore the antimicrobial effect and mechanism of menthone, a main component of peppermint oil, against methicillin resistant Staphylococcus aureus (MRSA). Methods: An integrated approach including the microbiology and the high-coverage lipidomics was applied. The changes of membrane properties were studies by the fluorescence and electron microscopical observations. The lipid profile was analyzed by ultra-high performance liquid chromatography coupled with quadruple Exactive mass spectrometry (UHPLC-QE-MS). The lipid-related key targets which were associated with the inhibitory effect of menthone against MRSA, were studied by network analysis and molecular docking. Results: Menthone exhibited antibacterial activities against MRSA, with minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of 3,540 and 7,080 µg/mL, respectively. The membrane potential and membrane integrity upon menthone treatment were observed to change strikingly. Further, lipids fingerprinting identified 136 significantly differential lipid species in MRSA cells exposed to menthone at subinhibitory level of 0.1× MIC. These metabolites span 30 important lipid classes belonging to glycerophospholipids, glycolipids, and sphingolipids. Lastly, the correlations of these altered lipids, as well as the potential metabolic pathways and targets associated with menthone treatment were deciphered preliminarily. Conclusion: Menthone had potent antibacterial effect on MRSA, and the mechanism of action involved the alteration of membrane structural components and corresponding properties. The interactions of identified key lipid species and their biological functions need to be further determined and verified, for the development of novel antimicrobial strategies against MRSA.

Oxidized low-density lipoprotein induces M2-type differentiation of macrophages to promote the protracted progression of atherosclerotic inflammation in high-fat diet-fed ApoE -/- mice.

In this study, the significance of oxidized low-density lipoprotein (ox-LDL) in promoting the progression of atherosclerosis was investigated by inducing the differentiation of macrophages into the M2 subtype within a high-fat diet-induced ApoE -/- mouse model. The study also evaluated the effects of ß2-AR agonists and blockers on this process. Ox-LDL was found to have significantly promoted the differentiation of macrophages into the M2 type and induced related functional alterations. Furthermore, it activated the pyroptosis pathway and encouraged the release of lactate dehydrogenase. The administration of ß2-AR agonists intensified these processes, while ß2-AR blockers had the opposite effect. In animal experiments, the model group displayed elevated numbers of M2-type macrophages beneath the aortic root intima, an increased rate of plaque destruction, and the formation of atherosclerotic plaques compared to the control group. The SAL (Salbutamol) group exhibited even more severe plaque development than the model group. Conversely, the ICI (ICI118551) group demonstrated M2-type macrophage levels comparable to the control group, with a higher plaque destruction rate than controls but significantly lower than the model group, and no atherosclerotic plaques. These findings suggest that ox-LDL promoted the differentiation of recruited monocytes into M2-type macrophages, leading to a shift in the inflammatory response from M1 to M2 macrophages. This alteration resulted in the persistence of atherosclerotic inflammation, as M2-type macrophages were prone to cell membrane rupture (such as pyroptosis), contributing to the continuous recruitment of circulating monocytes and heightened inflammatory reactions within atherosclerotic plaques. Consequently, this process fueled the progression of atherosclerosis.

Immunogenic cell death-related classifications in breast cancer identify precise immunotherapy biomarkers and enable prognostic stratification.

Background: Immunogenic cell death (ICD) remodels the tumor immune microenvironment, plays an inherent role in tumor cell apoptosis, and promotes durable protective antitumor immunity. Currently, appropriate biomarker-based ICD immunotherapy for breast cancer (BC) is under active exploration. Methods: To determine the potential link between ICD genes and the clinical risk of BC, TCGA-BC was used as the training set and GSE58812 was used as the validation set. Gene expression, consistent clustering, enrichment analysis, and mutation omics analyses were performed to analyze the potential biological pathways of ICD genes involved in BC. Furthermore, a risk and prognosis model of ICD was constructed to evaluate the correlation between risk grade and immune infiltration, clinical stage, and survival prognosis. Results: We identified two ICD-related subtypes by consistent clustering and found that the C2 subtype was associated with good survival prognosis, abundant immune cell infiltration, and high activity of immune biological processes. Based on this, we constructed and validated an ICD risk and prognosis model of BC, including ATG5, HSP90AA1, PIK3CA, EIF2AK3, MYD88, IL1R1, and CD8A. This model can effectively predict the survival rate of patients with BC and is negatively correlated with the immune microenvironment and clinical stage. Conclusion: This study provides new insights into the role of ICD in BC. The novel classification risk model based on ICD in BC established in this study can aid in estimating the potential prognosis of patients with BC and the clinical outcomes of immunotherapy and postulates targets that are more useful in comprehensive treatment strategies.

Porous Se@SiO2 nanoparticles improve oxidative injury to promote muscle regeneration via modulating mitochondria.

Background: Acute skeletal muscle injuries are common among physical or sports traumas. The excessive oxidative stress at the site of injury impairs muscle regeneration. The authors have recently developed porous Se@SiO2 nanoparticles (NPs) with antioxidant properties. Methods: The protective effects were evaluated by cell proliferation, myogenic differentiation and mitochondrial activity. Then, the therapeutic effect was investigated in a cardiotoxin-induced muscle injury rat model. Results: Porous Se@SiO2 NPs significantly protected the morphological and functional stability of mitochondria, thus protecting satellite cells from H2O2-induced damage to cell proliferation and myogenic differentiation. In the rat model, intervention with porous Se@SiO2 NPs promoted muscle regeneration. Conclusion: This study reveals the application potential of porous Se@SiO2 NPs in skeletal muscle diseases related to mitochondrial dysfunction.

Muscle injuries are very common in daily life and in sports. When a muscle is injured, the local response inhibits the regeneration and differentiation of stem cells inside the muscle, thus hindering muscle regeneration. The authors have recently developed a nanoparticle with the ability to protect muscle stem cell function, promote stem cell proliferation and differentiation and facilitate muscle regeneration after skeletal muscle injury in rats. Thus, this study reveals the potential of porous Se@SiO₂ nanoparticles in skeletal muscle diseases associated with mitochondrial dysfunction.

Integrated Analysis of Gut Microbiome and Lipid Metabolism in Mice Infected with Carbapenem-Resistant Enterobacteriaceae.

The disturbance in gut microbiota composition and metabolism has been implicated in the process of pathogenic bacteria infection. However, the characteristics of the microbiota and the metabolic interaction of commensals−host during pathogen invasion remain more than vague. In this study, the potential associations of gut microbes with disturbed lipid metabolism in mice upon carbapenem-resistant Escherichia coli (CRE) infection were explored by the biochemical and multi-omics approaches including metagenomics, metabolomics and lipidomics, and then the key metabolites−reaction−enzyme−gene interaction network was constructed. Results showed that intestinal Erysipelotrichaceae family was strongly associated with the hepatic total cholesterol and HDL-cholesterol, as well as a few sera and fecal metabolites involved in lipid metabolism such as 24, 25-dihydrolanosterol. A high-coverage lipidomic analysis further demonstrated that a total of 529 lipid molecules was significantly enriched and 520 were depleted in the liver of mice infected with CRE. Among them, 35 lipid species showed high correlations (|r| > 0.8 and p < 0.05) with the Erysipelotrichaceae family, including phosphatidylglycerol (42:2), phosphatidylglycerol (42:3), phosphatidylglycerol (38:5), phosphatidylcholine (42:4), ceramide (d17:1/16:0), ceramide (d18:1/16:0) and diacylglycerol (20:2), with correlation coefficients higher than 0.9. In conclusion, the systematic multi-omics study improved the understanding of the complicated connection between the microbiota and the host during pathogen invasion, which thereby is expected to lead to the future discovery and establishment of novel control strategies for CRE infection.

Application of Hydrogels as Carrier in Tumor Therapy: A Review.

Cancer is one of the most intractable diseases in the world because of its high recurrence rate, high metastasis rate and high lethality rate. Traditional chemotherapy, radiotherapy and surgery have unsatisfactory therapeutic effects and cause many severe side effects at the same time. Hydrogel is a new type of biomaterial with the advantages of good biocompatibility and easy degradation, which can be used as a carrier of functional nanomaterials for tumor therapy. Herein, we represent the progress of hydrogels with different skeletons and their application as carrier in tumor treatment. The hydrogels are listed as polyethylene glycol-based hydrogels, chitosan-based hydrogels, peptide-based hydrogels, hyaluronic acid-based hydrogels, steroid-based hydrogels and other hydrogels by skeletons, and their properties, modifications and toxicities were introduced. Some representative applications of combined hydrogels with nanomaterial for chemotherapy, photodynamic therapy, photothermal therapy, sonodynamic therapy, chemodynamic therapy and synergistic therapy are highlighted.

Tumor microenvironment responsive theranostic agent for enhanced chemo/chemodynamic/photothermal therapy.

The specific characteristics of the tumor microenvironment (TME) and monotherapy always lead to poor therapy effects for tumors. Hereby, we have developed a smart multifunctional theranostic agent-SSMID (Se@SiO2@MnO2-ICG/DOX) nanocomposites (NCs) that could intelligently respond to the TME for enhanced chemotherapy/photothermal/chemodynamic therapy guided by magnetic resonance imaging (MRI). The SSMID NCs were composed of indocyanine green (ICG) and doxorubicin hydrochloride (DOX) co-loaded porous Se@SiO2 @MnO2. Under the specific conditions of the TME (slightly acidic, H2O2 and GSH overexpression), the MnO2 NPs were specifically decomposed and then SSMID released Mn2+, DOX and Se, which played roles in chemodynamic therapy (CDT), chemotherapy, protecting normal tissues and inhibiting tumor cells by modulating reactive oxygen species (ROS), respectively. MnO2 reacted with glutathione (GSH) and H2O2 to generate O2 and Mn2+, which alleviated tumor hypoxia to improve chemotherapy and depleted GSH to enhance oxidative stress for chemodynamic therapy. More importantly, SSMID NCs could simultaneously exert the photothermal therapy (PTT) effect with near-infrared laser irradiation and promote the release of Mn2+ and DOX to achieve enhanced chemotherapy/chemodynamic therapy. In addition, the released Mn2+ could be used as a T1-weighted MRI contrast agent to monitor tumor location. The SSMID NCs exhibited a pronounced tumor growth inhibitory effect and promising biological safety, which develop a new method to rationally design nano-theranostic agents with enhanced performance for anti-tumor.

Using Amphiphilic Polymer Micelles as the Templates of Antisolvent Crystallization to Produce Drug Nanocrystals.

Biocompatible and biodegradable amphiphilic polymeric micelles (PLA-CMCS-g-OA) were prepared by surface grafting of oleic acid and polylactic acid onto carboxymethyl chitosan and were used as templates for the crystallization of camptothecin. The camptothecin (CPT) nanocrystals prepared by the novel micelle-templated antisolvent crystallization (mt-ASC) method demonstrated higher crystallinity, narrower particle size distribution, and slower release characteristic than those prepared by conventional antisolvent crystallization (c-ASC) using a high initial concentration and fast addition rate. In particular, the CPT release behavior of mt-ASC products in phosphate buffer solutions presented a pH-responsive characteristic with the increasing release rate of CPT under lower pH conditions. This work confirmed that amphiphilic nanomicelle-templated crystallization was an effective method for preparing drug nanocrystals.

Fine mapping of QFlw-5B, a major QTL for flag leaf width in common wheat (Triticum aestivum L.).

KEY MESSAGE: A major stable QTL for flag leaf width was narrowed down to 2.5 Mb region containing two predicated putative candidate genes, and its effects on yield-related traits was characterized. Flag leaf width (FLW) is important to production in wheat. In a previous study, a major quantitative trait locus for FLW (QFlw-5B) was detected on chromosome 5B, within an interval of 6.5 cM flanked by the markers of XwPt-9103 and Xbarc142, using a mapping population of recombinant inbred lines derived from a cross between Kenong9204 (KN9204) and Jing411 (J411) (denoted as KJ-RILs). The aim of this study was to fine map QFlw-5B and characterize its genetic effects on yield-related traits. Multiple near-isogenic lines (NILs) were developed using one residual heterozygous line for QFlw-5B. Five recombinants for QFlw-5B were identified, and its location was narrowed to a 2.5 Mb region based on combined phenotypic and genotypic data analysis. This region contained 27 predicted genes, two of which were considered as the most likely candidate genes for QFlw-5B. The FLW of NIL-KN9204 was significantly higher than that of NIL-J411 across all the tested environments. Meanwhile, significant increases in plant height, grain width and 1000-grain weight were observed in NIL-KN9204 compared with that in NIL-J411. These results indicate that QFlw-5B has great potential for marker-assisted selection in wheat breeding programs designed to improve both plant architecture and yield. This study also provides a basis for the map-based cloning of QFlw-5B.