Acute exposure to polystyrene nanoplastics induces unfolded protein response and global protein ubiquitination in lungs of mice.

Inhaling microplastics (MPs) and nanoplastics (NPs) in the air can damage lung function. Xenobiotics in the body can cause endoplasmic reticulum (ER) stress, and the unfolded protein response (UPR) activation alleviates ER stress. Degradation of unfolded or misfolded proteins is an important pathway for recovering cellular homeostasis. The UPR and protein degradation induced by MPs/NPs in lung tissues are not well understood. Here, we investigated the UPR and protein ubiquitination in the lungs of mice exposed to polystyrene (PS)-NPs and their possible molecular mechanisms leading to protein ubiquitination. Mice were intratracheally administered with 5.6, 17, and 51 mg/kg PS-NPs once for 24 h. Exposure to PS-NPs elevated protein ubiquitination in the lungs of mice in a dose-dependent manner. PS-NPs activated three branches of UPR including inositol-requiring protein 1α (IRE1α), eukaryotic translation initiator factor 2α (eIF2α), and activating transcription factor 6α (ATF6α) in the lungs of mice. However, activated IRE1α did not trigger X-box binding protein 1 (XBP1) mRNA splicing. Exposure to PS-NPs induced an increase in the levels of E3 ubiquitin ligase hydroxymethyl glutaryl-coenzyme A reductase degradation protein 1 (HRD1) and carboxy terminus of Hsc70 interacting protein (CHIP) in the lungs of mice and BEAS-2B cells. ATF6α siRNA inhibited the levels of HRD1 and CHIP proteins induced by PS-NPs in BEAS-2B cells. These results suggest that ATF6α plays a critical role in increasing ubiquitination of unfolded or misfolded proteins by alleviating PS-NPs induced ER stress through UPR to achieve ER homeostasis in the lungs of mice.

Combined effects of polystyrene nanoplastics and lipopolysaccharide on testosterone biosynthesis and inflammation in mouse testis.

Microplastics (MPs)/nanoplastics (NPs), as a source and vector of pathogenic bacteria, are widely distributed in the natural environments. Here, we investigated the combined effects of polystyrene NPs (PS-NPs) and lipopolysaccharides (LPS) on testicular function in mice for the first time. 24 male mice were randomly assigned into 4 groups, control, PS-NPs, LPS, and PS-NPs + LPS, respectively. Histological alterations of the testes were observed in mice exposed to PS-NPs, LPS or PS-NPs + LPS. Total sperm count, the levels of testosterone in plasma and testes, the expression levels of steroidogenic acute regulatory (StAR) decreased more remarkable in testes of mice treated with PS-NPs and LPS than the treatment with LPS or PS-NPs alone. Compared with PS-NPs treatment, LPS treatment induced more sever inflammatory response in testes of mice. Moreover, PS-NPs combined with LPS treatment increased the expression of these inflammatory factors more significantly than LPS treatment alone. In addition, PS-NPs or LPS treatment induced oxidative stress in testes of mice, but their combined effect is not significantly different from LPS treatment alone. These results suggest that PS-NPs exacerbate LPS-induced testicular dysfunction. Our results provide new evidence for the threats to male reproductive function induced by both NPs and bacterial infection in human health.

Polystyrene nanoplastics promote CHIP-mediated degradation of tight junction proteins by activating IRE1α/XBP1s pathway in mouse Sertoli cells.

Microplastics (MPs) and nanoplastics (NPs) widely exist in human living environment and enter the body through water, food chain and breathing. Several studies have shown that MPs or NPs disrupt the blood-testis barrier in rodents. However, the molecular mechanism by which MPs and NPs damage the blood-testis barrier remains unclear. In the present study, our aim was to investigate the molecular mechanism of the destruction of blood-testis barrier induced by polystyrene (PS)-NPs. Mice were treated with 50 µg/kg·day PS-NPs by tail vein injection once daily for two consecutive days. The results showed that PS-NPs exposure significantly decreased the levels of tight junction (TJ) proteins ZO-2, occludin and claudin-11 in testis of mice. In vitro, we used TM4 Sertoli cells to explore the underlying mechanism of the decrease in TJ proteins induced by PS-NPs. We found that PS-NPs activated IRE1α and induced its downstream XBP1 splicing, which in turn elevated the expression of the E3 ubiquitin ligase CHIP, then CHIP triggers proteasomal degradation of ZO-2, occludin, and claudin-11 proteins. Our findings suggest that IRE1α/XBP1s/CHIP pathway is a pivotal mechanism of TJ proteins degradation induced by PS-NPs in mouse Sertoli cells. In conclusion, our results reveal that the degradation of TJ proteins is one of the mechanisms of blood-testis barrier destruction caused by acute exposure to PS-NPs.

Near-infrared light-responsive nanoparticles for improved anticancer efficacy through synergistic chemo-photothermal therapy.

Combined treatment is more effective than single treatment against most forms of cancer. The synergistic chemo-thermotherapy mediated by nanoparticles has superior advantages of lesser adverse effects as a promising cancer therapy modality. In this study, we report a theranostic carrier system co-encapsulating Doxorubicin (DOX) and Indocyanine green (ICG) into the D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS). Full physicochemical characterization studies of the DOX/ICG-loaded TPGS nanoparticles (TNPs) are performed. TNPs have a mean size around 60 nm with superior photostability, and entrapment efficiency of drugs in TNPs was 75.0% for ICG and 68.3% for DOX. TNPs also exhibit a longer sustained release with around 63% of the entrapped drug in 24 h. In vitro studies, TNPs could effectively enhance cellular uptake of DOX and ICG, which permitted high therapeutic efficacy against cancer cells. Further, we investigate antitumor efficacy of TNPs along with its impact on major organs in vivo, TNPs also exhibit a complete inhibition of tumor growth and minimal side effects after irradiation. Collectively, these results suggest that near-infrared light-responsive TNPs can further enhance antitumor effects by synergistic chemo-photothermal therapy.

Risk of chemotherapy-induced febrile neutropenia with early discontinuation of pegfilgrastim prophylaxis in US clinical practice.

PURPOSE: Accumulating evidence suggests that not all cancer chemotherapy patients who receive first-cycle pegfilgrastim prophylaxis continue to receive it in subsequent cycles and that these patients may be subsequently at higher risk of febrile neutropenia (FN). Additional evidence from US clinical practice is warranted. METHODS: Data from two US private healthcare claims repositories were employed. The source population comprised adults who received "intermediate-risk" or "high-risk" chemotherapy regimens for solid cancers or non-Hodgkin's lymphoma and first-cycle pegfilgrastim prophylaxis. From the source population, all patients who did not receive second-cycle pegfilgrastim prophylaxis ("comparison patients") were matched (1:1) to those who received it ("pegfilgrastim patients") based on cancer, regimen, and propensity score. Odds ratios (OR) for FN-broad and narrow definitions-during the second chemotherapy cycle were estimated for comparison patients versus pegfilgrastim patients using generalized estimating equations. RESULTS: A total of 2245 comparison patients (5.3 % of source population) were matched to pegfilgrastim patients; cohorts were well-balanced on baseline characteristics. Second-cycle FN incidence proportions for comparison and pegfilgrastim patients were 3.8 versus 2.2 % based on broad definition and 2.6 versus 0.8 % based on narrow definition; corresponding OR were 1.7 (95 % CI 1.2-2.5, p = 0.002) and 3.5 (95 % CI 2.0-6.0, p < 0.001). Results were similar within cancer/regimen-subgroups and were robust when using alternative methods for confounding adjustment. CONCLUSIONS: In this retrospective evaluation of cancer chemotherapy patients who received first-cycle pegfilgrastim prophylaxis in US clinical practice, a clinically relevant minority did not receive second-cycle prophylaxis. Second-cycle FN odds among this subset were significantly higher than they were among those who continued prophylaxis.

Pluronic-poly (acrylic acid)-cysteine/Pluronic L121 mixed micelles improve the oral bioavailability of paclitaxel.

The aim of the study is to synthesize a thiolated Pluronic copolymer, Pluronic-poly (acrylic acid)-cysteine copolymer, to construct a mixed micelle system with the Pluronic-poly (acrylic acid)-cysteine copolymer and Pluronic L121 (PL121) and to evaluate the potential of these mixed micelles as an oral drug delivery system for paclitaxel. Compared with Pluronic-poly (acrylic acid)-cysteine micelles, drug-loading capacity of Pluronic-poly (acrylic acid)-cysteine/PL121 mixed micelles was increased from 0.4 to 2.87%. In vitro release test indicated that Pluronic-poly (acrylic acid)-cysteine/PL121 mixed micelles exhibited a pH sensitivity. The permeability of drug-loaded micelles in the intestinal tract was studied with an in situ perfusion method in rats. The presence of verapamil and Pluronic both improved the intestinal permeability of paclitaxel, which further certified the inhibition effect of thiolated Pluronic on P-gp. In pharmacokinetic study, the area under the plasma concentration-time curve (AUC0→∞) of paclitaxel-loaded mixed micelles was four times greater than that of the paclitaxel solution (p < 0.05). In general, Pluronic-poly (acrylic acid)-cysteine/PL121 micelles were proven to be a potential oral drug delivery system for paclitaxel.

[Effect of hOGG1 expression level on oxidative DNA damage among workers exposed to nickel in stainless steel production environment].

OBJECTIVE: To study the excision repair capacity of human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) for 8-OH-dG and the oxidative DNA damage among workers exposed to nickel in stainless steel production environment. METHODS: A total of 231 workers exposed to nickel in a stainless steel production enterprise were recruited as nickel exposure group, and another 75 water pump workers in that enterprise were recruited as control group. The workplace occupational hazard factors were determined. Double-antigen sandwich ELISA was used to determine urinary 8-OH-dG level; RT-PCR was used to determine hOGG1 mRNA level. Pearson correlation was used to analyze the correlation between urinary 8-OH-dG level and hOGG1 mRNA level. RESULTS: Level of 8-OH-dG was compared between different types of nickel-exposed workers and control workers; rolling mill workers showed no significant difference from the control group (P > 0.05), while steel making workers and steel slag disposing workers showed significant differences from the control group (P < 0.05). Level of 8-OH-dG was also compared between nickel-exposed workers with different working years and control workers; nickel-exposed workers with 0∼5 and 6∼10 working years showed no significant differences from the control group (P > 0.05), while other exposed workers showed significant differences from the control group (P < 0.05). Different types of nickel-exposed workers all showed significant differences from the control group in hOGG1 mRNA level (P < 0.05). Nickel-exposed workers with 0∼5 working years showed no significant difference from the control group in hOGG1 mRNA level (P > 0.05), while other exposed workers showed significant differences from the control group (P < 0.05). Pearson correlation analysis showed that urinary 8-OH-dG level was positively correlated with hOGG1 mRNA level (r = 0.993) in different types of nickel-exposed workers, and the correlation was significant at α = 0.01 (P < 0.05); urinary 8-OH-dG level also showed a positive correlation with hOGG1 mRNA level in nickel-exposed workers with different working years (r = 0.968), and the correlation was significant at α = 0.01 (P < 0.05). CONCLUSION: Exposure to nickel increases oxidative DNA damage among steel workers, and hOGG1 shows active excision repair capacity for 8-OH-dG.

Microplastics alter cadmium accumulation in different soil-plant systems: Revealing the crucial roles of soil bacteria and metabolism.

Cadmium (Cd) and microplastics (MPs) gradually increased to be prevalent contaminants in soil, it is important to understand their combined effects on different soil-plant systems. We studied how different doses of polylactic acid (PLA) and polyethylene (PE) affected Cd accumulation, pakchoi growth, soil chemical and microbial properties, and metabolomics in two soil types. We found that high-dose MPs decreased Cd accumulation in plants in red soil, while all MPs decreased Cd bioaccumulation in fluvo-aquic soil. This difference was primarily attributed to the increase in dissolved organic carbon (DOC) and pH in red soil by high-dose MPs, which inhibited Cd uptake by plant roots. In contrast, MPs reduced soil nitrate nitrogen and available phosphorus, and weakened Cd mobilization in fluvo-aquic soil. In addition, high-dose PLA proved detrimental to plant health, manifesting in shortened shoot and root lengths. Co-exposure of Cd and MPs induced the shifts in bacterial populations and metabolites, with specific taxa and metabolites closely linked to Cd accumulation. Overall, co-exposure of Cd and MPs regulated plant growth and Cd accumulation by driving changes in soil bacterial community and metabolic pathways caused by soil chemical properties. Our findings could provide insights into the Cd migration in different soil-plant systems under MPs exposure. ENVIRONMENTAL IMPLICATION: Microplastics (MPs) and cadmium (Cd) are common pollutants in farmland soil. Co-exposure of MPs and Cd can alter Cd accumulation in plants, and pose a potential threat to human health through the food chain. Here, we investigated the effects of different types and doses of MPs on Cd accumulation, plant growth, soil microorganisms, and metabolic pathways in different soil-plant systems. Our results can contribute to our understanding of the migration and transport of Cd by MPs in different soil-plant systems and provide a reference for the control of combined pollution in the future research.

A novel Anaerobic Cathodic Dynamic Membrane Bioreactor (AnCDMBR) for efficient mitigating fouling and recovering bioenergy from municipal wastewater.

Concerns regarding membrane fouling and suboptimal bioenergy recovery have constrained the implementation of anaerobic membrane bioreactor (AnMBR) for treating low-strength municipal wastewater. This study presents a novel anaerobic cathodic dynamic membrane bioreactor (AnCDMBR) designed to address these challenges. A self-formed cathodic dynamic membrane (CDM) on inexpensive carbon cloth was developed to function as both a membrane and biocathode to achieve dual-function effects of mitigating membrane fouling and accelerating organics conversion. Compared with common dynamic membrane (1.52 kPa/d) and commercial membranes (7.52 kPa/d), the developed CDM presented a significantly reduced fouling rate (1.02 kPa/d), exhibiting the potential as a substitute for high-cost conductive membranes. Furthermore, efficient and stable biomethanation occurred in AnCDMBR with a superior methane yield rate of 0.26 L-CH4/g-COD (CH4 content > 95 %), which was 1.42 times higher than the control, linked to the higher activities of microbial metabolism and methanogenic-related key enzymes. Further analysis revealed that electrostimulation-induced niche differentiation of microbiota regulated interspecies interactions between electroactive microorganisms and complex anaerobic digestion microbiomes, facilitating organic matter conversion to methane and leading to superior bioenergy recovery. This study offered a new strategy for effectively mitigating fouling and recovering bioenergy from low-strength wastewater, potentially expanding the application of AnMBRs.

Polystyrene nanoplastics inhibit StAR expression by activating HIF-1α via ERK1/2 MAPK and AKT pathways in TM3 Leydig cells and testicular tissues of mice.

Microplastics (MPs) and nanoplastics (NPs) are widely found in water, food and air, and have been found in human blood, lung and feces. Several studies in vivo have shown that MPs and NPs decrease testosterone level. However, the molecular mechanism of MPs and NPs leading to testosterone reduction remains unclear. In the present study, mice were treated with 50 µg/kg·day polystyrene (PS)-NPs by tail vein injection once daily for two consecutive days, the mRNA and protein levels of steroidogenic acute regulatory protein (StAR) decreased significantly in testis. TM3 Leydig cells were treated with non-toxic doses of PS-NPs, hypoxia-inducible factor-1α (HIF-1α) mRNA translation was induced by PS-NPs through mTOR/4E-BP1 pathway, which was activated by the ERK1/2 MAPK and AKT pathways. Simultaneously, increased HIF-1α protein inhibited StAR transcription. Additionally, reactive oxygen species production induced by PS-NPs played a central role in the activation of ERK1/2 MAPK/mTOR and AKT/mTOR signaling pathways. These results suggest that PS-NPs down-regulate StAR expression by increasing HIF-1α, which is induced by activation of mTOR/4E-BP1 through the ERK1/2 MAPK and AKT signaling pathways. Our findings provide new insight into the potential molecular mechanism by which PS-NPs impair testosterone synthesis and male reproductive function.

Circ_0062491 alleviates LPS-induced apoptosis and inflammation in periodontitis by regulating miR-498/SOCS6 axis.

Periodontitis is a prevalent chronic inflammatory disease. Circular RNAs (circRNAs) have been revealed to play roles in the inflammatory response. Hence, this work aimed to explore the role and mechanism of circ_0062491 in periodontitis progression. Human periodontal ligament cells (PDLCs) were isolated from the periodontal ligament (PDL) of the healthy teeth with orthodontic requirement after tooth extraction. In vitro experiments were conducted by cell counting Kit-8 (CCK-8) assay, flow cytometry, Western blot, and ELISA to determine cell viability, apoptosis, and inflammatory response. The binding between miR-498 and circ_0062491 or SOCS6 was confirmed using dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Circ_0062491 expression was decreased in periodontitis and LPS-induced PDLCs. Restoration of circ_0062491 attenuated LPS-induced apoptosis and inflammation in PDLCs in vitro. Mechanistically, circ_0062491 functioned as a sponge for miR-498, and miR-498 directly targeted SOCS6. Rescue experiments showed that miR-498 up-regulation reversed the protective action of circ_0062491 on PDLCs under LPS treatment. Moreover, silencing of miR-498 protected PDLCs from LPS-induced apoptosis and inflammation, which were abolished by SOCS6 knockdown. Circ_0062491 protected PDLCs from LPS-induced apoptosis and inflammation, suggesting a new target for the amelioration of periodontitis patients.

Effects of microplastics accumulation on performance of membrane bioreactor for wastewater treatment.

The effective interception of membrane leads to the accumulation of microplastics (MPs) in membrane bioreactor (MBR) process for long-term operation. However, the influence of MPs accumulation on the performance of MBR hasn't been well understood. In this study, the accumulation of polypropylene microplastics (PP-MPs) in two MBRs run for 3 yr with or without discharging sludge was simulated by operating the lab-scale MBRs for 84 days. The variations of pollutant removal, membrane fouling, composition of soluble microbial product (SMP) and extracellular polymeric substance (EPS), and microbial community of MBRs were systematically investigated. The results show that the removal efficiency of COD and NH4+-N was not depressed by PP-MPs accumulation. However, the presence of PP-MPs in the range of 0.14-0.30 g/L could inhibit the growth of microorganisms, enhance the secretion of SMP and EPS, and reduce the microbial richness and diversity. In the contrary, the high concentration of PP-MPs (2.34-5.00 g/L) exhibited the opposite effects and mitigated membrane fouling, suggesting the important role of MPs concentration. It was also found that the exposure to high concentration of PP-MPs enhanced relative abundance of Clostridia, and inhibited the growth of Proteobacteria. The findings of this study provide a foresight to understand the effects of MPs accumulation on the performance of MBRs.

Diagnosis, Prevention, and Treatment of Radiotherapy-Induced Xerostomia: A Review.

In patients with head and neck cancer, irradiation (IR)-sensitive salivary gland (SG) tissue is highly prone to damage during radiotherapy (RT). This leads to SG hypofunction and xerostomia. Xerostomia is defined as the subjective complaint of dry mouth, which can cause other symptoms and adversely affect the quality of life. In recent years, diagnostic techniques have constantly improved with the emergence of more reliable and valid questionnaires as well as more accurate equipment for saliva flow rate measurement and imaging methods. Preventive measures such as the antioxidant MitoTEMPO, botulinum toxin (BoNT), and growth factors have been successfully applied in animal experiments, resulting in positive outcomes. Interventions, such as the new delivery methods of pilocarpine, edible saliva substitutes, acupuncture and electrical stimulation, gene transfer, and stem cell transplantation, have shown potential to alleviate or restore xerostomia in patients. The review summarizes the existing and new diagnostic methods for xerostomia, along with current and potential strategies for reducing IR-induced damage to SG function. We also aim to provide guidance on the advantages and disadvantages of the diagnostic methods. Additionally, most prevention and treatment methods remain in the stage of animal experiments, suggesting a need for further clinical research, among which we believe that antioxidants, gene transfer, and stem cell transplantation have broad prospects.

Complex polymeric nanomicelles co-delivering doxorubicin and dimethoxycurcumin for cancer chemotherapy.

Combinational therapy is a new trend in medical sciences to achieve a maximum therapeutic response of the drugs with a comparatively low incidence of severe adverse effects. To overcome the challenges of conventional formulations for cancer chemotherapy, a polymer-based complex nanomicellar system, namely CPM-DD, was developed co-delivering the anti-cancer agent doxorubicin (DOX) and potent antioxidant dimethoxycurcumin (DiMC). The optimal mass ratio of DOX/DiMC in CPM-DD was determined as 1:6 due to the synergistic antiproliferative effect from in vitro cytotoxicity assay, while the biocompatible diblock copolymer of mPEG2000-PLA5000 was selected for drug entrapment at an optimal feeding ratio of 9:1 to both drugs together. The uniform particles of CPM-DD with suitable particle size (∼30 nm) and stable drug loading content (>9%) could be reliably obtained by self-assembly with the encapsulation yield up to 95%. Molecular dynamics simulation revealed the interaction mechanism responsible for forming these complex nanomicelles. The acid-base interaction between two drugs would significantly improve their binding with the copolymer, thus leading to good colloidal stability and controlled drug release characteristics of CPM-DD. Systematic evaluation based on the MCF-7 breast tumor-bearing nude mice model further demonstrated the characteristics of tissue biodistribution of both drugs delivered by CPM-DD, which were closely related to the drug loading pattern and greatly responsible for the improved anti-cancer potency and attenuated toxicity of this complex formulation. Therefore, all the findings indicated that CPM-DD would be a good alternative to the conventional formulations of DOX and worthy of clinical application for cancer chemotherapy.

Waterproof and Breathable Wound Dressing Composited By Expanded Polytetrafluoroethylene Backing and Hydrogel.

Wound dressings with waterproof, breathable, and bacterial-resistant properties are still rarely realized. In this work, a newly hydrogel-based dressing is designed with a backing of expanded polytetrafluoroethylene (ePTFE) film. The ePTFE grafting with polyvinylpyrrolidone (PVP) brush is composited with hydrogel successfully with an adhesion energy of ≈80 kJ m-2 . In this resultant composite, the ePTFE backing contributes excellent breathability, water resistance, and bacterial barrier property. The water vapor transmission rate of the composite is 4.83 × 103  g m-2 × 24 h, which can maintain the moist environment of wound and relieve pain by evaporating water. Notably, it can withstand 500 mm water column for over 300 s, which is obviously better than the commonly used nonwoven fabric backing materials. It can also prevent the invasion of bacteria, because the pores of ePTFE backing are smaller than those of most common bacterial. As a result, the composite with an ePTFE film backing has a positive effect in accelerating wound healing, promoting the reconstruction of intact epidermis and reducing inflammation.

Clinical Reference Strategy for the Selection of Treatment Materials for Maxillofacial Bone Transplantation: A Systematic Review and Network Meta-Analysis.

Bone graft materials have mixed effects of bone repair in the field of oral maxillofacial surgery. The qualitative analyses performed by previous studies imply that autogenous odontogenic materials and autogenous bone have similar effects on bone repair in clinical jaw bone transplantation. This retrospective systematic assessment and network meta-analysis aimed to analyze the best effect of clinical application of autogenous odontogenic materials and autogenous, allogeneic, and xenogeneic bone grafts in bone defect repair. A systematic review was performed by searching the PubMed, Cochrane Library, and other journal databases using selected keywords and Medical Subject Headings search terms. 10 Papers (n = 466) that met the inclusion criteria were selected. The assessment of heterogeneity did not reveal any overall statistical difference or heterogeneity (P = 0.051 > 0.05), whereas the comparison between autogenous and allogeneic bone grafts revealed local heterogeneity (P = 0.071 < 0.1). Risk of bias revealed nine unclear studies and one high-risk study. The overall consistency was good (P = 0.065 > 0.05), and the local inconsistency test did not reveal any inconsistency. The publication bias was good. The confidence regarding the ranking of bone graft materials after GRADE classification was moderate. The effects on bone repair in the descending order were as follows: autogenous odontogenic materials, xenogeneic bone, autogenous bone, and allogeneic bone. This result indicates that the autogenous odontogenic materials displayed stronger effects on bone repair compared to other bone graft materials. Autogenous odontogenic materials have broad development prospects in oral maxillofacial surgery.

Supramolecular hydrogels from cisplatin-loaded block copolymer nanoparticles and α-cyclodextrins with a stepwise delivery property.

A stepwise anticancer drug delivery system based on an injectable supramolecular hydrogel was presented. In this system, poly(ethylene glycol)-b-poly(acrylic acid) (PEG-b-PAA) block copolymer nanoparticles containing cisplatin were released by erosion of the hydrogels and then the cisplatin was released from the nanoparticles by exchanging with chloride ions. By mixing α-cyclodextrins (α-CDs) and the PEG-b-PAA micelles with their PAA cores loaded with the cisplatin in water, the novel supramolecular hydrogels were generated by threading α-CDs onto the PEG segments and forming physical cross-links of molecular necklaces. The gelation properties could be tuned by changing concentrations of the polymers and cisplatin, their feeds, and by adding PEG homopolymers or Pluronic copolymers as additives. Structures and properties of the supramolecular hydrogels containing cisplatin were studied by wide-angle X-ray diffraction (XRD) and rheology measurements, respectively. The thixotropic effect of the hydrogels and their reversible sol-gel transition were confirmed. In vitro hydrogel erosion experiments were conducted and cisplatin release in saline and pure water was quantified. Hydrogel erosion produced discrete nanoparticles from which cisplatin was released completely in saline. In contrast, the hydrogels were eroded into nanoparticles in pure water, but no cisplatin could be released. In vitro cytotoxicity studies showed that the cisplatin-loaded hydrogels inhibited the growth of human bladder carcinoma EJ cells with a similar potency as that of the free cisplatin, whereas the hydrogels without cisplatin showed no cytotoxicity. These results suggested that the cisplatin-coordinated PEG-b-PAA/α-CD supramolecular hydrogels hold great potential as an injectable system for sustained delivery of cisplatin in cancer therapy.

Amphiphilic toothbrushlike copolymers based on poly(ethylene glycol) and poly(epsilon-caprolactone) as drug carriers with enhanced properties.

Amphiphilic poly(ethylene glycol)-b-poly(2-hydroxyethyl methacrylate-g-poly(epsilon-caprolactone)) (PEG-b-P(HEMA-g-PCL)) toothbrushlike copolymers were synthesized and evaluated as drug delivery carriers. Two toothbrushlike polymers were synthesized via ring-opening polymerization of epsilon-caprolactone (CL) initiated by poly(ethylene glycol)-b-poly(2-hydroxyethyl methacrylate) (PEG-b-PHEMA) macromolecular initiators, and their molecular structures and physical properties were characterized using (1)H NMR, gel permeation chromatography (GPC), and differential scanning calorimetric analysis (DSC). The melting points and crystallizable temperature have been decreased obviously, implying that the PCL cores of PEG-b-P(HEMA-g-PCL) toothbrushlike copolymer micelles with shorter PCL segments were unlikely to crystallize at room temperature for drug delivery application. Also the micellization properties of toothbrushlike copolymers in aqueous solution were investigated by fluorescence spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM). Compared with the micelles from linear PEG-b-PCL block copolymers, the micelles of PEG-b-P(HEMA-g-PCL)s exhibited higher loading capacity to the anticancer drug, doxorubicin (DOX), and the drug-loaded micelles were highly stable in aqueous solution. In vitro DOX release data and confocal laser scanning microscopy (CLSM) studies showed that DOX-loaded toothbrushlike copolymer micelles could be effectively internalized by bladder carcinoma EJ cells, and the DOX could be released into endocytic compartments and finally transported to the nucleus. Such toothbrushlike copolymer micelles can be analogues of linear PEG-b-PCL diblock copolymers, but demonstrated better properties of loading and release due to their hydrophobic PCL cores do not crystallize at delivery conditions.

De novo transcriptome analysis of Pleurotus djamor to identify genes encoding CAZymes related to the decomposition of corn stalk lignocellulose.

CAZymes play a very important role in the biotransformation of corn stalk biomass, which is an important resource for sustainable development. Pleurotus djamor can produce CAZymes related to the decomposition of corn stalk lignocellulose biomass in sole corn stalk substrate; however, little is known about their encoding genes. In order to identify CAZymes encoding genes, RNA high-throughput sequencing of P. djamor was performed in this study. The results showed that a core set of 70 upregulated genes encoding putative CAZymes were revealed. They encode 19 kinds of CAZymes in total, of which there are 4 EGLs, 8 CBHs, 5 BGLs, and 12 LPMOs related to cellulose degradation, 8 XYNs, 1 XYL, 2 AGUs, 3 ABFs, 2 AGLs, and 2 AXEs related to hemicellulose degradation, and 5 LACCs, 2 MnPs, 5 VPs, 3 CDHs, 1 AAO, 1 GOX, 1 AOX, 2 GAOXs, and 3 GLOXs related to lignin degradation. This variety suggests that CAZymes may play a very important role in decomposing the lignocellulose biomass of corn stalk. This is the first study to report the de novo transcriptome sequencing of P. djamor, which will produce a dataset of genes encoding CAZymes, thereby laying the foundation to elucidate the degradation mechanism of corn stalk biomass and boost the biotransformation of corn stalk biomass resources.

Trajectory of absolute neutrophil counts in patients treated with pegfilgrastim on the day of chemotherapy versus the day after chemotherapy.

PURPOSE: Risk of infection increases with severity and duration of chemotherapy-induced neutropenia (CIN). Pegfilgrastim is approved for use on the day after chemotherapy to reduce incidence of infection, as manifested by febrile neutropenia (FN), in patients receiving myelosuppressive chemotherapy. In this study, we compared severity and duration of absolute neutrophil count (ANC) suppression in patients who received pegfilgrastim on the same day as chemotherapy versus the next day. METHODS: We combined individual patient data from four Amgen-sponsored clinical trials in which patients with cancer were randomized to receive pegfilgrastim either the same day as chemotherapy or the next day. Severity and duration of ANC suppression were calculated using area over the curve (AOC, the area over the ANC-time response curve and below a given clinical threshold). AOC of ANC and incidences of CIN and FN were compared by day of pegfilgrastim use. RESULTS: The analysis included 95 same-day patients and 97 next-day patients. Despite similar ANC at baseline, ANC at nadir was higher among next-day patients than same-day patients. Mean AOC of ANC (cutoff 0.5 × 10(9)/L) among next-day patients was lower by 0.30 (95 % confidence interval: 0.16, 0.43) 10(9)/L × day than same-day patients in cycle 1. Next-day patients had lower incidences of CIN than same-day patients, but there were no significant differences in incidences of FN. CONCLUSIONS: Patients who received pegfilgrastim the day after chemotherapy had less severe and shorter suppression of ANC than patients who received pegfilgrastim the same day as chemotherapy.