One-pot bottom-up fabrication of biocompatible PEGylated WS2 nanoparticles for CT-guided photothermal therapy of tumors in vivo.

BACKGROUND: Tungsten disulfide (WS2), which enjoyed a good potential to be a promising clinical theranostic agent for cancer treatment, is still subject to the tedious synthesis procedure. METHODS: Here, we reported a one-pot 'bottom-up' hydrothermal strategy for the fabrication of PEGylated WS2 nanoparticles (NPs). The WS2-PEG nanoparticles were characterized systematically. The CT imaging and photothermal therapy against tumor as well as biosafety in vitro and in vivo were also investigated. RESULTS: The obtained WS2-PEG NPs enjoyed obvious merits of good solubility and favorable photothermal performance. WS2-PEG NPs exhibited desirable photothermal ablation ability against cancer cells and cancer cell-bearing mice in vitro and in vivo. MTT assay and histological analysis demonstrated the low cytotoxicity and biotoxicity of WS2-PEG NPs, providing a valid biosafety guarantee for the coming biomedical applications. In addition, thanks to the obvious X-ray attenuation of W atom, the WS2-PEG NPs can also be served as a favorable contrast agent for CT imaging of tumors. CONCLUSION: WS2-PEG NPs has enjoyed a good potential to be a promising clinical CT-guided photothermal therapeutic agent against cancers.

[Effects of Wine-processing on Rhei Radix et Rhizoma on Upper-energizer Disease and Effects on Activities of Energy Metabolism Enzymes in Liver].

OBJECTIVE: To compare the effects of crude and wine-processed Rhei Radix et Rhizoma on upper-energizer disease and hepatic energy metabolism in mice. METHODS: The streptococcal pneumonia rats model and acetic acid burning mouth ulcers rats model were established and randomly divided into three groups: model group, crude Rhei Radix et Rhizoma group and wine-processed Rhei Radix et Rhizoma group. The pathologic changes were observed after the rats had been administrated with water extracts of crude and wine-processed Rhei Radix et Rhizoma respectively. The normal ICR mice were randomly divided into three groups: control group, crude Rhei Radix et Rhizoma group and wine-processed Rhei Radix et Rhizoma group. The influence of water extracts of crude and wine-processed Rhei Radix et Rhizoma on the activities of Na+, K-ATPase, Ca2+ -ATPase and succinic dehydrogenase(SDH) in the mice were compared. RESULTS: Compared with the crude one,the wine-processed Rhei Radix et Rhizoma significantly decreased the inflammation scores (P <0. 05), and promoted the tissue repair of acetic acid burning mouth ulcers rats model. The wine-processed one could also obviously reduce and normalize the level of leucocyte and neutrophilic granulocyte, lower the TNF-α level (P <0. 05), and relieve inflammatory exudation of the lung tissue. The inhibitory effects of wine-processed Rhei Radix et Rhizoma on the activities of SDH, Ca2+-ATPase and Na+, K + -ATPase were weaker than those of the crude one (P > 0. 05). CONCLUSION: After having been processed with wine, the efficacy of Rhei Radix et Rhizoma on upper-energizer disease is enhanced, and the inhibition on the activity of energy metabolism enzyme in liver tends to be weakened.

Modulating the phenotype and function of bone marrow-derived macrophages via mandible and femur osteoblasts.

Various studies have been investigated the phenotypic and functional distinctions of craniofacial and long bone cells involved in bone regeneration. However, the process of bone tissue regeneration after bone grafting involves complicated interactions between different cell types at the donor-recipient site. Additionally, differences in alterations of the immune microenvironment at the recipient site remained to be explored. Osteoblasts (OBs) and macrophages (MØ) play essential roles in the bone restoration and regeneration processes in the bone and immune systems, respectively. The modulation of MØ on OBs has been extensively explored in the literature, whereas limited research has been conducted on the influence of OBs on the MØ phenotype and function. In the present study, OBs from the mandible and femur (MOBs and FOBs, respectively) promoted cranial defect regeneration in rats, with better outcomes noted in the MOBs-treated group. After MOBs transplantation, a significant inflammatory response was induced, accompanied by an early increase in IL-10 secretion. And then, there was an upregulation in M2-MØ-related cell markers and inflammatory factor expression. Condition media (CM) of OBs mildly inhibited apoptosis in MØ, enhanced their migration and phagocytic functions, and concurrently increased iNOS and Arg1 expression, with MOB-CM demonstrating more pronounced effects compared to FOB-CM. In conclusion, our investigation showed that MOBs and FOBs have the ability to modulate MØ phenotype and function, with MOBs exhibiting a stronger regulatory potential. These findings provide a new direction for improving therapeutic strategies for bone regeneration in autologous bone grafts from the perspective of the immune microenvironment.

Enhancing diabetic wound healing with a pH/glucose dual-responsive hydrogel for ROS clearance and antibacterial activity.

Currently, the treatment of diabetic wounds in clinical practice is still unsatisfactory due to the risks of oxidative damage and bacterial infection during the healing process. An optimal wound dressing should exhibit robust capabilities in scavenging reactive oxygen species (ROS) and combatting bacterial growth. In this study, we utilized borax as a crosslinker and prepared a pH/glucose dual-responsive composite hydrogel based on poly(vinyl alcohol) (PVA), sodium alginate (SA), and tannic acid (TA). This hydrogel, loaded with cerium dioxide, serves as an effective ROS scavenger, promoting wound closure by reducing the level of ROS in the wound area. Additionally, the hydrogel can release the antibacterial drug ofloxacin in response to the low pH and high glucose microenvironment in infected wounds. Results from skin defect model in diabetic mice demonstrated this ROS-scavenging and antibacterial hydrogel can suppress inflammation and accelerate wound healing. In summary, our work provides a new perspective on a local and stimulus-responsive drug delivery strategy for treating diabetic wounds.

Potential Effects of Orally Ingesting Polyethylene Terephthalate Microplastics on the Mouse Heart.

Polyethylene terephthalate microplastics (PET MPs) are widespread in natural environment, and can enter organisms and accumulate in the body, but its toxicity has not been well studied. Therefore, in order to investigate the toxic effects of PET microplastics on mammals, this study investigated the toxic effects of PET MPs on ICR mice and H9C2 cells by different treatment groups. The results indicated the cardiac tissue of mice in the PET-H (50 µg/mL) group showed significant capillary congestion, myocardial fiber breakage, and even significant fibrosis compared to the PET-C (control) group (P < 0.01). Results of the TUNEL assay demonstrated significant apoptosis in myocardial tissue in the PET-H and PET-M (5 µg/mL) groups (P < 0.01). Meanwhile, Western blotting showed increased expression of the apoptosis-related protein Bax and decreased expression of PARP, caspase-3, and Bcl-2 proteins in both myocardial tissues and H9C2 cells. In addition, flow cytometry confirmed that PET MPs decreased the mitochondrial membrane potential and apoptosis in H9C2 cells; however, this trend was reversed by N-acetylcysteamine application. Moreover, PET MP treatment induced the accumulation of reactive oxygen species (ROS) in H9C2 cells, while the MDA level in the myocardial tissue was elevated, and the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were decreased (P < 0.01), indicating a change in the redox environment. In conclusion, PET MPs promoted cardiomyocyte apoptosis by inducing oxidative stress and activating mitochondria-mediated apoptotic processes, ultimately leading to myocardial fibrosis. This study provides ideas for the prevention of PET MP toxicity and promotes thinking about enhancing plastic pollution control.

Self-Cross-Linkable Maleic Anhydride Terpolymer Coating with Inherent High Antimicrobial Activity and Low Cytotoxicity.

Developing coating materials with low cytotoxicity and high antimicrobial activity has been recognized as an effective way to prevent medical device-associated infections. In this study, a maleic anhydride terpolymer (PPTM) is synthesized and covalently attached to silicone rubber (SR) surface. The formed coating can be further cross-linked (SPM) through the self-condensation of pendent siloxane groups of terpolymer. No crack or delamination of SPM was observed after 500 cycles of bending and 7 day immersion in deionized water. The sliding friction force of a catheter was reduced by 50% after coating with SPM. The SPM coating without adding any extra antibacterial reagents can kill 99.99% of Staphylococcus aureus and Escherichia coli and also significantly reduce bacterial coverage, while the coating displayed no antimicrobial activity when maleic anhydride groups of SPM were aminated or hydrolyzed. The results of the repeated disinfection tests showed that the SR coated with SPM could maintain 87.3% bactericidal activity within 5 cycles. Furthermore, the SPM coating only imparted slight toxic effect (>85% viability) on L929 cells after 36 h of coculture, which is superior to the coating of aminated SPM conjugated with the antimicrobial peptide E6. The terpolymer containing maleic anhydride units have great potential as a flexible and durable coating against implant infections.

[Influence of Polystyrene Microplastics on the Formation and Structural Change of Pseudomonas aeruginosa Biofilm].

Microplastic pollution in the water environment is becoming increasingly serious, impacting the growth and development of aquatic organisms. There are limited studies on the mechanisms of microplastic effects on biofilm formation. Therefore, in this study, the effects of polystyrene microplastics (PS-MPs) were investigated on the biofilm formation and development of Pseudomonas aeruginosa. Different concentrations and particle sizes of PS-MPs were selected for exposure tests to explore the effects on biofilm biomass, oxidative stress levels, biofilm structure, and population sensing system. The results showed that PS-MPs induced severe oxidative stress and inhibited biofilm formation and development, and the smaller the particle size, the stronger the inhibitory effect was. The inhibition effect was 0.1 µm>0.5 µm≈1 µm>5 µm. PS-MPs caused severe physical damage through contact with bacteria. The thickness of the biofilm was significantly reduced, damaging the structural stability. The bacteria in the biofilm secreted extracellular polymers to resist the stress of PS-MPs. Meanwhile, PS-MPs interfered with the QS system of P. aeruginosa; down-regulated the expression levels of key genes lasI, lasR, rhlI, and rhlR; inhibited the synthesis and secretion of signal molecules and related virulence factors; and ultimately affected the formation and structural stability of biofilms.

Applications and perspectives of quaternized cellulose, chitin and chitosan: A review.

Recently, increasing attention has been paid to natural polysaccharides for their low cost, biocompatibility and biodegradability. Quaternization is a modification method to improve the solubility and antibacterial ability of natural polysaccharides. Water-soluble derivatives of cellulose, chitin and chitosan offer the prospect of diverse applications in a wide range of fields, such as antibacterial products, drug delivery, wound healing, sewage treatment and ion exchange membranes. By combining the inherent properties of cellulose, chitin and chitosan with the inherent properties of the quaternary ammonium groups, new products with multiple functions and properties can be obtained. In this review, we summarized the research progress in the applications of quaternized cellulose, chitin and chitosan in recent five years. Moreover, ubiquitous challenges and personal perspectives on the further development of this promising field are also discussed.

A dual grafted fluorinated hydrocarbon amine weak anion exchange resin polymer for adsorption of perfluorooctanoic acid from water.

Perfluorooctanoic acid (PFOA) is a persistent and recalcitrant organic contaminant of exceptional environmental concern, and its removal from water has increasingly attracted global attention due to its wide distribution and strong bioaccumulation. Adsorption is considered an effective technique for PFOA removal and more efficient PFOA sorbents are still of interest. This study developed a dual grafted fluorinated hydrocarbon amine weak anion exchange (WAX) polymeric resin (Sepra-WAX-KelF-PEI) for PFOA removal from water. This polymer was synthesized by a two-step amine grafting reaction procedure involving first the reaction of the Sepra-WAX hydrocarbon polymer with poly(vinylidinefluoride-chlorotrifluoroethylene) (Kel-F 800) and then a second reaction with polyethyleneimine (PEI). Characterization of the synthesized polymers was performed using scanning electron microscopy and elemental analysis (F and Cl) by energy dispersive X-ray spectroscopy. The PFOA adsorption performance evaluations were conducted by packed column flow analyses with on-line detection. The results show the breakthrough of the Sepra-WAX-KelF-PEI synthesized with optimum stoichiometry was two times better than the starting anion exchange polymer Sepra-WAX, and six times better than powdered activated carbon, when using the same column size. The adsorption mechanisms of this novel adsorbent including hydrophobic interaction and electrostatic interaction were also clarified in this study. The adsorption kinetic parameters of the two optimum synthesized sorbents were determined using the Thomas model, the Yoon-Nelson model, and batch isotherm studies, and compared with those found with activated carbon and the starting WAX resin. Good agreement of the batch isotherm and column studies with respect to adsorption capacities trends between all three polymers (Sepra-WAX, Sepra-WAX-KelF, and Sepra-WAX-KelF-PEI) were noted.

Iodinated cyanine dye-based nanosystem for synergistic phototherapy and hypoxia-activated bioreductive therapy.

Photodynamic therapy (PDT) has been applied in cancer treatment by utilizing reactive oxygen species (ROS) to kill cancer cells. However, the effectiveness of PDT is greatly reduced due to local hypoxia. Hypoxic activated chemotherapy combined with PDT is expected to be a novel strategy to enhance anti-cancer therapy. Herein, a novel liposome (LCT) incorporated with photosensitizer (PS) and bioreductive prodrugs was developed for PDT-activated chemotherapy. In the design, CyI, an iodinated cyanine dye, which could simultaneously generate enhanced ROS and heat than other commonly used cyanine dyes, was loaded into the lipid bilayer; while tirapazamine (TPZ), a hypoxia-activated prodrug was encapsulated in the hydrophilic nucleus. Upon appropriate near-infrared (NIR) irradiation, CyI could simultaneously produce ROS and heat for synergistic PDT and photothermal therapy (PTT), as well as provide fluorescence signals for precise real-time imaging. Meanwhile, the continuous consumption of oxygen would result in a hypoxia microenvironment, further activating TPZ free radicals for chemotherapy, which could induce DNA double-strand breakage and chromosome aberration. Moreover, the prepared LCT could stimulate acute immune response through PDT activation, leading to synergistic PDT/PTT/chemo/immunotherapy to kill cancer cells and reduce tumor metastasis. Both in vitro and in vivo results demonstrated improved anticancer efficacy of LCT compared with traditional PDT or chemotherapy. It is expected that these iodinated cyanine dyes-based liposomes will provide a powerful and versatile theranostic strategy for tumor target phototherapy and PDT-induced chemotherapy.

Mechanistically Scoping Cell-Free and Cell-Dependent Artificial Scaffolds in Rebuilding Skeletal and Dental Hard Tissues.

Rebuilding mineralized tissues in skeletal and dental systems remains costly and challenging. Despite numerous demands and heavy clinical burden over the world, sources of autografts, allografts, and xenografts are far limited, along with massive risks including viral infections, ethic crisis, and so on. Per such dilemma, artificial scaffolds have emerged to provide efficient alternatives. To date, cell-free biomimetic mineralization (BM) and cell-dependent scaffolds have both demonstrated promising capabilities of regenerating mineralized tissues. However, BM and cell-dependent scaffolds have distinctive mechanisms for mineral genesis, which makes them methodically, synthetically, and functionally disparate. Herein, these two strategies in regenerative dentistry and orthopedics are systematically summarized at the level of mechanisms. For BM, methodological and theoretical advances are focused upon; and meanwhile, for cell-dependent scaffolds, it is demonstrated how scaffolds orchestrate osteogenic cell fate. The summary of the experimental advances and clinical progress will endow researchers with mechanistic understandings of artificial scaffolds in rebuilding hard tissues, by which better clinical choices and research directions may be approached.

Antibacterial Potential of Termite-Associated Streptomyces spp.

Twenty-one strains of termite-associated actinomycetes were tested for their activities against three bacteria. The results showed that nine strains showed bacteriostatic activities against at least one tested bacterium, and the actinomycete YH01, which was isolated from the body surface of the queen of Odontotermes formosanus, had potent antibacterial activity. The YH01 was further identified as Streptomyces davaonensis. Two metabolites roseoflavin (1) and 8-methylamino-8-demethyl-d-riboflavin (2) were isolated and purified from S. davaonensis YH01. Their structures were determined by NMR, MS, and the related literature. The metabolite 1 showed strong inhibition activities against Bacillus subtilis (MIC = 1.56 µg/mL) and Staphylococcus aureus (MIC = 3.125 µg/mL), which were comparable to referenced gentamycin sulfate, with MIC values of 1.56 and 1.56 µg/mL, respectively. Furthermore, the anti-MRSA potential of compound 1 was determined against nine kinds of MRSA strains, with inhibition zones in the ranges of 12.7-19.7 mm under a concentration of 15 µg/6 mm discs and 18.3-22.7 mm under a concentration of 30 µg/6 mm discs. However, metabolite 1 had no inhibitory effect on Gram-negative bacteria. These results suggested that roseoflavin produced by YH01 holds promise for use against Gram-positive bacteria, especially to MRSA.

Tuning osteoporotic macrophage responses to favour regeneration by Cu-bearing titanium alloy in Porphyromonas gingivalis lipopolysaccharide-induced microenvironments.

Guided bone regeneration in inflammatory microenvironments of osteoporotic patients with large alveolar bone defects remains a great challenge. Macrophages are necessary for alveolar bone regeneration via their polarization and paracrine actions. Our previous studies showed that Cu-bearing Ti6Al4V alloys are capable of regulating macrophage responses. When considering the complexity of oral microenvironments, the influences of Cu-bearing Ti6Al4V alloys on osteoporotic macrophages in infectious microenvironments are worthy of further investigations. In this study, we fabricated Ti6Al4V-Cu alloy by selective laser melting technology and used Porphyromonas gingivalis lipopolysaccharide (P.g-LPS) to imitate oral pathogenic bacterial infections. Then, we evaluated the impacts of Ti6Al4V-Cu on osteoporotic macrophages in infectious microenvironments. Our results indicated that Ti6Al4V-Cu not only inhibited the P.g-LPS-induced M1 polarization and pro-inflammatory cytokine production of osteoporotic macrophages but also shifted polarization towards the pro-regenerative M2 phenotype and remarkably promoted anti-inflammatory cytokine release. In addition, Ti6Al4V-Cu effectively promoted the activity of COMMD1 to potentially repress NF-κB-mediated transcription. It is concluded that the Cu-bearing Ti6Al4V alloy results in ameliorated osteoporotic macrophage responses to create a favourable microenvironment under infectious conditions, which holds promise to develop a GBR-barrier membrane for alveolar bone regeneration of osteoporosis patients.

A facile strategy towards heterogeneous preparation of thermoplastic cellulose grafted polyurethane from amorphous regenerated cellulose paste.

Cellulose is an abundant feedstock with renewability and biodegradability. However, it is still challenging to manufacture natural cellulose products by environmentally friendly thermoplastic processing methods. Herein, we proposed a green approach for the heterogeneous preparation of thermoplastic cellulose grafted polyurethane (RCP-g-PU) from amorphous regenerated cellulose paste (RCP) via hydroxyl/isocyanate chemistry. First, amorphous RCP was fabricated through dissolving cellulose in sodium hydroxide aqueous solution and regenerating in polyethylene glycol, resulting in the enhancement of the accessibility of hydroxy groups in cellulose chains. Subsequently, a series of thermoplastic RCP-g-PU with the melt flow temperatures ranging from 160 °C to 226 °C were feasibly synthesized by adding hexamethylene diisocyanate into RCP without using other organic solvents. Eventually, the resultant RCP-g-PU can be directly hot-pressed into transparent films with flexibility and foldability. The reported methodology represents a sustainable route to achieve thermoplastic cellulose derivatives.

Osteogenic and angiogenic characterization of mandible and femur osteoblasts.

Craniofacial autologous bone grafts offer superior outcomes to long bone grafts in the reconstruction of maxillofacial bone defects, but the mechanism responsible for this superiority has not yet been illustrated clearly. Osteoblasts play vital roles in bone development and regeneration. However, presently, only a few studies have compared the osteogenic ability of osteoblasts from craniofacial and long bones, and the results are contradictory. Additionally, the angiogenic characteristics of osteoblasts from these different bones remain unknown. We obtained osteoblasts from the rat mandible (MOBs) and femur (FOBs) to investigate their proliferative capacity and osteogenic potential, and using a co-culture system with human umbilical vein endothelial cells (HUVECs), we explored their angiogenic capabilities in vitro. FOBs exhibited higher alkaline phosphatase activity and increased matrix mineralization and expressed more osteogenic related marker genes, while MOBs proliferated at the highest rate and showed elevated expression of angiogenesis-related factors. Conditioned media from MOBs enhanced the expression of angiogenesis-related factors in HUVECs. Furthermore, the conditioned media generated from MOBs showed stronger promotion of proliferation, migration, and tube-like structure formation in HUVECs, suggesting that MOBs had a stronger pro-angiogenic effect on HUVECs than FOBs. Taken together, these results indicate that osteoblasts possess skeletal site-specific differences in osteogenic and angiogenic capabilities, and this might lead to a better understanding of the molecular impact of bone cells from different bone entities on maxillofacial bone reconstructions.

Liquid chromatography with alkylammonium formate ionic liquid mobile phases and fluorescence detection.

Fluorescence detection of various pharmaceuticals and the amino acid tryptophan (low molecular weight organic compounds) as well as the enzyme lactate dehydrogenase LDH (high molar mass compound) has been studied in aqueous solutions using alkyl ammonium formate ionic liquids as the primary solvent component. It was expected that the high viscosity of such ionic liquid-water mixtures would enhance fluorescence. Pharmaceuticals such as riboflavin and naproxen showed no such enhancement in the presence of ethylammonium formate (EAF) or isopropylammonium formate (IPAF) but the fluorescence of warfarin was substantially enhanced by a factor of 4 with 80% EAF and a factor of 7 with 70% IPAF. However, this improved fluorescence using alkylammonium formates did not seem to be general for other coumarin compounds except for bromadiolone which showed a similar fluorescence enhancement using EAF. Enhancement of tryptophan fluorescence was also seen for both EAF and IPAF. During the reversed phase elution of LDH on a polymeric HPLC column, remarkable enhancements in LDH peak intensity and activity were observed by incorporating 6% PEG 8000 in the organic mobile phase that contained either 20% acetonitrile or IPAF. Using higher concentrations of PEG 8000 is not recommended, not only because of the high viscosity, but also because the stabilizing effect of PEG 8000 is gradually reduced at higher concentrations.

[Influence of culture mode on bacterial cellulose production and its structure and property].

Acetobacter xylinum NUST4.2 has been applied in the studies to examine the production, structure and thermal property of bacterial cellulose (BC) produced in stationary culture and in the stirred tank reactor. These differences are as follows: BC yield reached 7.5 g/L in stationary culture for 6 days and its productivity was 0.052 g/L/h. BC production reached 3.13 g/L in the stirred tank reactor for 72h and its productivity was 0.043 g/L/h. SEM showed that there was almost no difference between network structure built of entangled cellulose ribbons produced in static culture and in the reactor. But the cellulose ribbons produced in static culture were a much more entangled and denser network with curved and overlapping cellulose ribbons in comparison with that one produced in the stirred tank reactor. Also the thickness of the cellulose ribbons seems to differ between the two BC samples, with the one from static culture distinguished by the slightly thinner ribbons. FT-IR revealed that there was no effect of stirring on the chemical structure of BC, but intermolecular hydrogen bond of cellulose was weakened. Furthermore, BC synthesized in static culture displayed I(alpha)-rich cellulose. XRD results indicated that no remarkable change in the cellulose crystallographic form of the BC samples. Nevertheless, BC produced in static culture was characterized by a higher crystallinity, higher I(alpha) content and higher crystalline size than cellulose that was produced in the reactor. All of these results revealed that stirring in the reactor interfere strongly in the process of nascent microfibrils crystallization, favoring the formation of smaller size microfibrils and increased I(beta), the more stable allomorph. Compared with cotton cellulose, the changes of thermal decomposition behavior in the BC samples were that BC produced in static culture displayed better thermal stability, but BC produced in the stirred reactor displayed better flame retarding.

Nanomedicine-based paclitaxel induced apoptotic signaling pathways in A562 leukemia cancer cells.

In the present study, we have synthesized an amphiphilic pH-sensitive structure of poly(ethylene glycol) methyl ether-b-(poly lactic acid-co-poly(b-amino esters)) (MPEG-b-(PLA-co-PAE)) to load paclitaxel to increase the therapeutic efficacy in leukemia. The micelles exhibit excellent drug-loading capacities for paclitaxel (PTX) and exhibited a typical pH-responsive drug release pattern. The release of PTX from the micelles was significantly accelerated by decreasing pH from 7.4 to 5.0 which just fitted the pathological process. The most important advantage of this design is that the polymeric micelles provide an effective approach for rapid transport of cargo into the cytosol, which significantly increases the antitumor efficacy of PTX against K562 cancer cells. Paclitaxel-loaded polymer micelles (PTX-M) showed significantly higher cytotoxic effect than that of free PTX. The PTX-M exhibited a superior apoptosis effect in cancer cells compared to that of free PTX at all time points. We have showed that the PTX-M activated upstream of apoptosis signaling and inhibited the anti-apoptotic factors. The PTX-M remarkably increased the upregulation of Bax, caspase-3, caspase-9, and PARP-1 expression and downregulated the Bcl-2 expression in K562 cancer cells. The results show that PTX-M induced cell apoptosis through intrinsic apoptotic signaling pathway. Importantly, PTX had a remarkably prolonged plasma circulation time after administration of PTX-M. Overall, this novel cancer specific, pH-responsive, and potentially in vivo stable unimolecular micelles may provide a very promising approach for targeted cancer therapy in the effective treatment of Leukemia.

Clinical Features and Peripheral Blood T Lymphocyte Subsets in Hand, Foot, and Mouth Disease According to Different Pathogens.

OBJECTIVE: To investigate the changes in lymphocyte subsets that are caused by infection with different pathogens in children with hand, foot, and mouth disease. METHODS: T lymphocyte subsets were measured in the patients' peripheral blood, and serum, throat swab, and fecal samples were tested for enterovirus. RESULTS: Fecal and throat swab samples exhibited similar positive detection rates, and were significantly more likely to be positive, compared to serum samples (P < 0.01). The EV71-positive group exhibited significantly lower CD4 + TM cell counts (QR: 1.058), compared to the CD4 + TM cell counts in the CoxA16-positive group (QR: 1.391; P < 0.05). CONCLUSIONS: Throat swab and fecal samples exhibited significantly higher positive detection rates, compared to serum samples. In addition, EV71-infected children exhibited significantly lower CD4+ T-cell counts, compared to CoxA16-infected children, which suggests that EV71 infection may be associated with a poorer prognosis.

Morphological influence of cellulose nanoparticles (CNs) from cottonseed hulls on rheological properties of polyvinyl alcohol/CN suspensions.

The present work describes the isolation of cellulose nanoparticles (CNs) with different morphologies and their influence on rheological properties of CN and CN-poly (vinyl alcohol) (PVA) suspensions. Cottonseed hulls were used for the first time to extract three types of CNs, including fibrous cellulose nanofibers, rod-like cellulose nanocrystals and spherical cellulose nanoparticles through mechanical and chemical methods. Rheology results showed that the rheological behavior of the CN suspensions was strongly dependent on CN concentration and particle morphology. For PVA/CN systems, concentration of PVA/CN suspension, morphology of CNs, and weight ratio of CN to PVA were three main factors that influenced their rheology behaviors. This research reveals the importance of CN morphology and composition concentration on the rheological properties of PVA/CN, providing new insight in preparing high performance hydrogels, fibers and films base on PVA/CN suspension systems.