Toward net-zero sustainable aviation fuel with wet waste-derived volatile fatty acids.

With the increasing demand for net-zero sustainable aviation fuels (SAF), new conversion technologies are needed to process waste feedstocks and meet carbon reduction and cost targets. Wet waste is a low-cost, prevalent feedstock with the energy potential to displace over 20% of US jet fuel consumption; however, its complexity and high moisture typically relegates its use to methane production from anaerobic digestion. To overcome this, methanogenesis can be arrested during fermentation to instead produce C2 to C8 volatile fatty acids (VFA) for catalytic upgrading to SAF. Here, we evaluate the catalytic conversion of food waste-derived VFAs to produce n-paraffin SAF for near-term use as a 10 vol% blend for ASTM "Fast Track" qualification and produce a highly branched, isoparaffin VFA-SAF to increase the renewable blend limit. VFA ketonization models assessed the carbon chain length distributions suitable for each VFA-SAF conversion pathway, and food waste-derived VFA ketonization was demonstrated for >100 h of time on stream at approximately theoretical yield. Fuel property blending models and experimental testing determined normal paraffin VFA-SAF meets 10 vol% fuel specifications for "Fast Track." Synergistic blending with isoparaffin VFA-SAF increased the blend limit to 70 vol% by addressing flashpoint and viscosity constraints, with sooting 34% lower than fossil jet. Techno-economic analysis evaluated the major catalytic process cost-drivers, determining the minimum fuel selling price as a function of VFA production costs. Life cycle analysis determined that if food waste is diverted from landfills to avoid methane emissions, VFA-SAF could enable up to 165% reduction in greenhouse gas emissions relative to fossil jet.

Highly Responsive and Self-Powered Photodetector Based on PtSe2/MoS2 Heterostructure.

In recent years, 2D materials and their heterostructures have started to offer an ideal platform for high-performance photodetection devices. In this work, a highly responsive, self-powered photodetector based on PtSe2/MoS2 van der Waals heterostructure is demonstrated. The device achieves a noteworthy wide band spectral response from visible (405 nm) range to the near infrared region (980 nm). The remarkable photoresponsivity and external quantum efficiency up to 4.52 A/W, and 1880% are achieved, respectively, at 405 nm illumination with fast response time of 20 ms. In addition, the photodetector exhibits a decent photoresponsivity of 33.4 mA/W at zero bias, revealing the photodetector works well in the self-driven mode. Our work suggests that a PtSe2/MoS2 heterostructure could be a potential candidate for the high-performance photodetection applications.

Induction of immunogenic cell death by novel platinum-based anticancer agents.

Traditional platinum-based anticancer drugs, led by cisplatin, play an important role in chemotherapy. However, the development of platinum compounds is limited due to serious toxicity and side effects. In recent years, studies have showed that immunogenic cell death (ICD) may be one of the potential action mechanisms of classical platinum drugs, such as oxaliplatin. This strategy combining chemotherapy and immunotherapy can effectively utilize the body's immune system to help platinum compounds to fight against tumors, and the dose can be appropriately reduced to limit toxic side effects. The induction of ICD by platinum compounds has become a research hotspot and one of the future development directions of metal drugs. Here, the progress of platinum compounds were collected and comprehensively summarized, their capacity of ICD induction and mechanism of action are exposed, providing reference for the design and synthesis of new anticancer platinum ICD inducers.

SERD-NHC-Au(I) complexes for dual targeting ER and TrxR to induce ICD in breast cancer.

The development of selective estrogen receptor degraders (SERDs) has brought new ideas for the clinical treatment of ER-positive advanced breast cancer. The successful application of combinational therapy inspired the exploration of other targets to prevent breast cancer progression. Thioredoxin reductase (TrxR) is an important enzyme that can regulate redox balance in cells and it was considered as a potential target for anticancer treatment. In this study, we firstly combine a clinical SERD candidate--G1T48 (NCT03455270), with a TrxR inhibitor--N-heterocyclic carbene gold(I) [NHC-Au(I)] to form dual targeting complexes that can regulate both signaling pathways. The most efficacious complex 23 exhibited significant antiproliferative profile through degrading ER and inhibiting TrxR activity. Interestingly, it can induce immunogenic cell death (ICD) caused by ROS. This is the first evidence to elucidate the role of ER/TrxR-ROS-ICD axis in ER positive breast cancer and this research may inspire new drug development with novel mechanisms. The in vivo xenograft study demonstrated that complex 23 had excellent antiproliferative activity toward MCF-7 cells in mice model.

Comparison of Microfat, Nanofat, and Extracellular Matrix/Stromal Vascular Fraction Gel for Skin Rejuvenation: Basic Animal Research.

BACKGROUND: Although stromal vascular fraction (SVF) cells and adipose-derived stem cells have well-defined antiaging effects on skin, certain disadvantages have limited their clinical application. OBJECTIVES: The aim of this study was to evaluate the effects of microfat, nanofat, and SVF-gel in improving ultraviolet (UV)-induced photoaged skin injury in nude mice. METHODS: After successfully establishing a photoaging model by UVA and UVB irradiation in nude mice, the back of each mouse was divided into 2 regions and randomly injected under the dermis with 0.5 mL of microfat, nanofat, SVF-gel, and phosphate-buffered saline. Inflammatory infiltration, dermis thickness, hydroxyproline content, Type I/Type III collagen ratio, elastic fiber morphology, skin cell proliferation, and adipocyte viability were measured. The overall structure of the skin was also observed by scanning electron microscopy. RESULTS: In the microfat group, the grafts survived well, with intact structure and viable adipocytes and little infiltration of inflammatory cells. Microfat promoted skin cell proliferation, collagen content increased, the ratio of Type I and III collagen reversed, and new oxytalan fibers formed, which to some extent improved the photoaging skin. In the nanofat and SVF-gel groups, a large amount of inflammatory cell infiltration and foam cell deposition in the grafts and dermis led to fibrosis and proliferation of skin tissue. Although the skin thickness and collagen content were also increased, these factors did not improve the photoaging skin. CONCLUSIONS: Microfat survives well, and improves photoaged skin injury in nude mice by promoting skin tissue regeneration and supplementing the capacity of subcutaneous adipose tissue.

Large-scale growth of few-layer two-dimensional black phosphorus.

Two-dimensional materials provide opportunities for developing semiconductor applications at atomistic thickness to break the limits of silicon technology. Black phosphorus (BP), as a layered semiconductor with controllable bandgap and high carrier mobility, is one of the most promising candidates for transistor devices at atomistic thickness1-4. However, the lack of large-scale growth greatly hinders its development in devices. Here, we report the growth of ultrathin BP on the centimetre scale through pulsed laser deposition. The unique plasma-activated region induced by laser ablation provides highly desirable conditions for BP cluster formation and transportation5,6, facilitating growth. Furthermore, we fabricated large-scale field-effect transistor arrays on BP films, yielding appealing hole mobility of up to 213 and 617 cm2 V-1 s-1 at 295 and 250 K, respectively. Our results pave the way for further developing BP-based wafer-scale devices with potential applications in the information industry.

mir-145-5p is a suppressor of colorectal cancer at early stage, while promotes colorectal cancer metastasis at late stage through regulating AKT signaling evoked EMT-mediated anoikis.

BACKGROUND: miR-145-5P is generally considered as a tumor suppressor at early stage of colorectal cancer, but up-regulation occurs in the progressive and later stages which is associated with metastasis, indicating miR-145-5p may play dual role in colorectal cancer (CRC). To explore the detailed mechanism of miR-145-5p in carcinogenic is of importance. METHODS: The expression pattern of miR-145-5p in CRC patients was downloaded from TCGA database, and the probable mechanism involved in the carcinogenic effect of miR-145-5p was predicted by bioinformatics analysis. Then, interference of miR-145-5p on SW480 and SW620 cells was conducted, and the influences on tumor cell viability, invasion ability, epithelial-mesenchymal transition (EMT), anoikis, and relative protein expression were examined respectively. RESULTS: A total of 522 CRC patients' data indicated that miR-145-5p expression was significantly higher in metastatic CRC than that in non-metastatic CRC, and higher expression of miR-145-5p was correlate with worse prognosis. Overexpression of miR-145-5P-5p enhanced the proliferation and invasion ability of SW620, but inhibited them in SW480. EMT was induced in SW620 after miR-145-5p overexpression and mesenchymal-epithelial transition (MET) was induced in SW480, resulted in the decreased apoptotic rate in SW620 and elevated apoptotic rate in SW480 respectively. Western blot results showed that AKT signaling pathway was involved in the miR-145-5p evoked EMT-mediated anoikis process in SW620 and SW480 cells. CONCLUSION: miR-145-5p is a tumor suppressor at early stage of CRC, and an oncogene at advanced stage of CRC. AKT signaling evoked EMT-mediated anoikis might be the pathway by which miR-145-5P regulates CRC cell invasion and metastasis.

Association of polymorphisms in endothelial dysfunction-related genes with susceptibility to essential hypertension in elderly Han population in Liaoning province, China.

Hypertension is a complex disease which is mainly influenced by genetic factors. Recently, genome-wide association study (GWAS) found three novel endothelial dysfunction-related sites: Vascular endothelial growth factor A (VEGFA) rs9472135, Faciogenital dysplasia 5 (FGD5) rs11128722, Zinc Finger C3HC-type Containing 1 (ZC3HC1) rs11556924. Endothelial dysfunction is one of the early events in pathophysiology of essential hypertension. To investigate the association of endothelial dysfunction-related genes with essential hypertension, we conducted a case-control study of 431 patients with hypertension and 345 controls. The polymorphisms were detected using Taqman Probe. The alleles and genotypes of ZC3HC1 rs11556924 and VEGFA rs9472135 were not statistically different between the two groups, while the allele of FGD5 rs11128722 was different [P = 0.045, OR = 1.265, 95% CI = (1.009-1.586)], especially in the male [P = 0.035, OR = 1.496, 95% CI = (1.037-2.158)]. Analyzing the different of genotype distribution of 3 SNPs in the two groups under different genetic models, the genotypes of FGD5 rs11128722 showed difference in male under dominant model [P = 0.049, OR = 1.610, 95% CI = (1.018-2.544)]. The polymorphism of FGD5 rs11128722 had a significant difference in Body Mass Index (BMI) among different genotypes; In the additive genetic model, BMI of GA genotype was higher than that of GG (P = 0.038); GA + AA was higher than GG in the dominant genetic model (P = 0.011). In our study, we found that the polymorphisms of VEGFA rs9472135 and ZC3HC1 rs11556924 may not significantly associated with the risk of essential hypertension, and FGD5 rs11128722 may increase the risk of it, especially in elderly men.

How Universal Is the Wetting Aging in 2D Materials.

Previous studies indicate that 2D materials such as graphene, WS2, and MoS2 deposited on oxidized silicon substrate are susceptible to aging due to the adsorption of airborne contamination. As a result, their surfaces become more hydrophobic. However, it is not clear how ubiquitous such a hydrophobization is, and the interplay between the specific adsorbed species and resultant wetting aging remains elusive. Here, we report a pronounced and general hydrophilic-to-hydrophobic wetting aging on 2D InSe films, which is independent of the substrates to synthesize these films (silicon, glass, nickel, copper, aluminum oxide), though the extent of wetting aging is sensitive to the layer of films. Our findings are ascribed to the occurrence and enrichment of airborne contamination that contains alkyl chains. Our results also suggest that the wetting aging effect might be universal to a wide range of 2D materials.

Clinical and Genetic Risk Factors of Long-Term Outcomes after Encephaloduroarteriosynangiosis in Moyamoya Disease in China.

OBJECTIVES: This retrospective study was conducted to analyze the associations between ring finger protein 213 p.R4810K variant, clinical features and long-term outcomes in patients with moyamoya disease (MMD) after encephaloduroarteriosynangiosis treatment. MATERIALS AND METHODS: A total of 2,545 patients with MMD in China were included in this study (median of follow-up duration: 32.00 months). Multiple Cox regression models were used to assess the associations between p.R4810K variant, clinical features and long-term outcomes. RESULTS: For all patients, in multivariate Cox analysis, no association was observed between p.R4810K and long-term outcomes. Pediatric onset (HR, 0.38; 95%CI, 0.25-0.59) and headache (HR, 0.26; 95%CI, 0.08-0.83) were inversely and hypertension (HR, 1.43 95%CI, 1.06-1.94), diabetes (HR, 1.55; 95%CI, 1.00-2.40), bilateral lesions (HR, 2.73; 95%CI, 1.12-6.65) and posterior cerebral artery involvement (HR, 1.44; 95%CI, 1.08-1.90) were positively associated with follow-up stroke (all P < 0.05). Pediatric onset (HR, 0.46; 95%CI, 0.26-0.82) was inversely and hyperlipidemia (HR, 1.83; 95%CI, 1.23-2.73), smoking (HR, 1.86; 95%CI, 1.13-3.07), high Suzuki angiographic stage (HR, 1.71, 95%CI, 1.09-2.70), poor admission neurologic status (HR, 8.93; 95%CI, 6.49-12.29) and follow-up stroke (HR, 8.31; 95%CI, 6.01-11.49) were positively associated with poor neurologic outcome at the last follow-up visit (all P < 0.05). The factors were not consistent in the different groups of age at onset. CONCLUSIONS: In our study, p.R4810K may play no role in long-term outcomes in Chinese MMD. Clinical features including age at onset, initial symptoms, risk factors of stroke, imaging, poor admission neurologic status were associated with poor outcomes in MMD after EDAS.

Validation and Extension Study Exploring the Role of RNF213 p.R4810K in 2,877 Chinese Moyamoya Disease Patients.

OBJECTIVE: To validate, update, and extend the role of RNF213 p.R4810K (G>A) for predicting the phenotype of moyamoya disease (MMD) patients and explore the different effects on pediatric and adult groups. METHODS: A total of 2,877 patients conducted from 2004 to 2018 were included. Review Manage 5.3 and SPSS 20.0 were applied to complete all statistical analyses. Information on age at onset, sex, initial symptom, family history and complications were obtained via retrospective chart review. Angiographic records were evaluated. RESULTS: In China, geographic proximity to Korea or Japan may affect the carrying rate of RNF213 p.R4810K. The proportion of patients with the following characteristics was significantly higher (P <0.017) in the GA than in the GG group: female, age at onset < 18 years, infarct after transient ischemic attack, family history of MMD, and posterior cerebral artery involvement. For pediatric patients, GA showed more cerebral hemorrhage (CH) (odds ratios (ORs) [95% confidence intervals (CIs)] = 3.99 (1.61-9.88), P = 0.003), more patients were in the Suzuki early and intermediate stage (P = 0.001; P = 0.001, respectively), while for the adult group, GA indicated more female (OR [95% CIs] = 1.43 [1.15-1.79], P = 0.001), fewer patients with diabetes (0.58 [0.38-0.86], P = 0.007) and intermediate Suzuki stage (P = 3.70 × 10-4). CONCLUSIONS: The incidence and carrying rates of RNF213 p.R4810K in various regions for Chinese MMD patients were obviously different. RNF213 p.R4810K has different predictive effects on phenotypes of pediatric and adult patients.

Blood Impairs Viability of Fat Grafts and Adipose Stem Cells: Importance of Washing in Fat Processing.

BACKGROUND: Fat processing plays a pivotal role in graft survival. Each component of the blood in lipoaspirate affects fat survival in different ways, but the mechanisms are not clear. OBJECTIVES: The aim of this study was to investigate, by various experimental methods, the effect of blood on the viability of fat grafts and adipose stem cells (ASCs). METHODS: Blood and fat samples were obtained from 6 female patients undergoing aesthetic liposuction. For the in vivo experiment, we compared fat mixed with normal saline or various ratios of blood in nude mice. The samples were explanted at 2 and 8 weeks to evaluate the gross volume retention and histologic and immunohistochemical characteristics. For in vitro experiments, ASCs were pretreated with hemoglobin at different concentrations and for different times. We then assessed the proliferation, migration, adipogenesis, and reactive oxygen species production of ASCs. RESULTS: Blood in the graft led to a decrease in graft viability, as evaluated by general observation and histologic and immunohistochemical morphology in vivo. In vitro experiments showed inhibited proliferation, migration, and adipogenesis, and increased reactive oxygen species production in ACSs, after hemoglobin treatment, suggesting impaired ASC viability. CONCLUSIONS: This study suggests that blood impairs the viability of fat grafts and ASCs and provides evidence that washing to remove blood is important in fat processing.

Comparison of Microfat, Nanofat, and Extracellular Matrix/Stromal Vascular Fraction Gel for Skin Rejuvenation: Basic Research and Clinical Applications.

BACKGROUND: Over the past 2 decades, fat grafting has been extensively applied in the field of tissue regeneration. OBJECTIVES: The aim of this study was to investigate the therapeutic potential of microfat, nanofat, and extracellular matrix/stromal vascular fraction gel (SVF-gel) in skin rejuvenation. METHODS: Microfat was harvested by a cannula with multiple 0.8-mm smooth side holes and processed with a fat stirrer to remove fibers. Nanofat and SVF-gel were prepared according to previously reported methods, and their structure and viability were evaluated. Then, SVF cells from the 3 types of samples were isolated and characterized, and the cell viability was compared. RESULTS: The microstructure of the 3 samples showed distinct differences. The microfat group showed a diameter of 100 to 120.0 µm under the microscope and presented a botryoid shape under calcein acetoxymethyl (calcein-AM)/propidium iodide staining. Scanning electron microscopy analysis showed that the microfat maintained an integral histologic structure. In the nanofat group, no viable adipocytes and no normal histologic structure were observed, but high levels of free lipids were noted. The SVF-gel group showed uniform dispersion of cells with different sizes and parts of the adipose histologic structure. Cell count and culture revealed that the number of viable SVF cells decreased distinctly in the nanofat group compared with the microfat group. In contrast, the number of viable SVF cells in the SVF-gel group increased moderately. Clinical applications with microfat showed marked improvements in skin wrinkles. CONCLUSIONS: Microfat can preserve the integrity of the histologic structure and presents the advantages of subcutaneous volumetric restoration and improvement of skin quality in skin rejuvenation compared with the nanofat and SVF-gel.

Universal Strategy for HF-Free Facile and Rapid Synthesis of Two-dimensional MXenes as Multifunctional Energy Materials.

Two-dimensional MXenes are promising for various energy-related applications such as energy storage devices and electrocatalysis of water-splitting. MXenes prepared from hydrofluoric (HF) acid etching have been widely reported. Nonetheless, the acute toxicity of HF acid impedes the large-scale fabrication of MXenes and their wide utilization in energy-related applications. It is thus greatly encouraging to explore a more innocuous protocol for MXenes synthesis. Thereby, a universal strategy based on thermal-assisted electrochemical etching route is developed to synthesize MXenes (e.g., Ti2CT x, Cr2CT x, and V2CT x). Furthermore, the cobalt ion doped MXenes show an exceptionally enhanced capability of hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) activity, demonstrating their multifunctionalities, which is comparable to the commercialized catalysts. Moreover, we successfully exploited our MXenes as cathodes for the novel aqueous rechargeable battery, with proficient retention and excellent electrical output performance. This work paves a nontoxic and HF-free route to prepare various MXenes and demonstrates practical applications of the materials.

Leptin promotes fatty acid oxidation and OXPHOS via the c-Myc/PGC-1 pathway in cancer cells.

Alteration in cellular energy metabolism plays a critical role in the development and progression of cancer. Leptin is a hormone secreted by adipose tissue. Recent reports have shown that leptin can induce cancer cell proliferation and regulate cell energy metabolism, but the regulatory mechanism is still unclear. Here, we showed that leptin could promote cell proliferation and maintain high adenosine triphosphate levels in HCT116 and MCF-7 cells. The expression levels of carnitine palmitoyl transferase 1A (CPT1A), pyruvate dehydrogenase, succinate dehydrogenase subunit A and mitochondrial respiratory chain-associated proteins NADH dehydrogenase 1 (ND1), NADH:ubiquinone oxidoreductase subunit B8, and mitochondrial transcription factor A (TFAM) were distinctly increased in leptin-treated HCT116 and MCF-7 cells, while fatty acid synthase and lactate dehydrogenase expression were downregulated. Simultaneously, we found that c-Myc and peroxisome proliferator-activated receptor gamma co-activator 1 (PGC-1) protein expression levels were significantly increased. These results indicated that leptin boosted fatty acid ß-oxidation and the tricarboxylic acid cycle, enhanced oxidative phosphorylation (OXPHOS) activity, and inhibited fatty acid synthesis and glycolysis in tumor cells. Gene transfection experiments revealed that leptin could induce the expression of c-Myc. Moreover, the expressions of PGC-1, CPT1A, and TFAM proteins were downregulated in HCT116 cells with low expression of c-Myc, and the expression levels of these proteins were increased in HCT116 cells overexpressing c-Myc. These findings suggest that leptin plays an important role in the regulation of energy metabolism in tumor cells. It may regulate fatty acid oxidation and OXPHOS of tumor cells by regulating the c-Myc/PGC-1 pathway. Targeting metabolic pathways for cancer treatment has been investigated as potential preventive or therapeutic methods. This study has important implications for the clinical therapy of tumor cell metabolism through hormone regulation.

A Strategy for Quality Control of Vespa magnifica (Smith) Venom Based on HPLC Fingerprint Analysis and Multi-Component Separation Combined with Quantitative Analysis.

As a folk medicine of the Jingpo minority in Yunnan province, the venom of Vespa magnifica has been commonly used for the treatment of rheumatoid arthritis. Quality standardization of the wasp venom is a necessary step for its pharmaceutical research and development. To control the quality of the wasp venom, a method based on high-performance liquid chromatography (HPLC) was developed for chemical fingerprint analysis. In the chromatographic fingerprinting, chemometrics procedures, including similarity analysis (SA), hierarchical clustering analysis (HCA), and principal component analysis (PCA), were applied to classify 134 batches (S1-S134) of wasp venom from different origins. The HPLC fingerprint method displayed good precision (Relative standard deviation, RSD < 0.27%), stability (in 16 h, RSD < 0.34%), and repeatability (RSD < 1.00%). Simultaneously, four compounds (VMS1, VMS2, VMS3, and VMS4) in the wasp venom were purified and identified. VMS1 was 5-hydroxytryptamine, and the other compounds were three peptides that were sequenced as follows: Gly-Arg-Pro-Hyp-Gly-Phe-Ser-Pro-Phe-Arg-Ile-Asp-NH2 (VMS2), Ile-Asn-Leu-Lys-Ala-Ile-Ala-Ala-Leu-Ala-Lys-Lys-Leu-Leu-NH2 (VMS3), and Phe-Leu-Pro-Ile-Ile-Gly-Lys-Leu-Leu-Ser-Gly-Leu-Leu-NH2 (VMS4). The quantifications for these components were 110.2 mg/g, 26.9 mg/g, 216.3 mg/g, and 58.0 mg/g, respectively. The results of this work indicated that the combination of the chemical fingerprint and quantitative analysis offers a reasonable way to evaluate the quality of wasp venom.

Walnut oil promotes healing of wounds and skin defects in rats via regulating the NF-kB pathway.

The effects of walnut oil on wound healing and skin injury repair was observed in Sprague-Dawley (SD) rats, and mechanism of action was investigated. Normal SD rats were divided into an experimental group and a control group. Each group was observed at4 time points (day [D]3, D7, D14, and D21). In both groups, a skin wound was created on the back of the rats, with the spine as the central axis. In the experimental group, the wound was covered with walnut oil, and then bandaged and fixed with sterile gauze. In the control group, the wound was bandaged with vaseline gauze. At each corresponding time point, the wound area and wound healing time of each rat were examined. Epithelial cells of the wound tissues were observed using haematoxylin and eosin staining and immunohistochemical analysis,and the numbers of inflammatory cells and capillaries were counted. A western blot method was used to detect the expression of nuclear factor (NF)-κB and epidermal growth factor (EGF) in the wound tissues of both groups. Meanwhile, enzyme-linked immunosorbent analysis (ELISA) was used to detect the expression of transforming growth factor (TGF)-ß1 and matrix metalloproteinase (MMP)-1 in rat sera. A total of 48 SD rats completed the experiment. Healing time of residual wounds in the experimental group was 10.0±3.5 days, which was significantly shorter than that in the control group (18.0±6.0 days) (p<0.05). The wound healing rates in the experimental group were 54.14 % (D3) and 91.2 3% (D7), whereas those in the control group were 22.12% (D3) and 54.84% (D7 (p<0.05).Histological examinations revealed no epithelial cells on D3, D7, D14, and D21 in both the experimental and control groups. However, the number of inflammatory cells decreased significantly and the number of capillaries increased significantly in the experimental group compared to control (p<0.05). NF-κB expression was significantly lower, EGF expression significantly higher in the in the experimental group. Conversely, ELISA showed a significant increase in the expression of TGF-ß1 and MMP-1 in rat sera in the experimental group. So we conclude that walnut oil has significant effects in promoting the healing of skin defect wounds in SD rats.

Exposure to difenoconazole inhibits reproductive ability in male marine medaka (Oryzias melastigma).

Difenoconazole (DFZ) is a triazole fungicide which has been detected in the aquatic environment, including estuaries and embayments. However, few studies addressing the reproductive toxicity and transgenerational effects of DFZ on marine fishes are available. The present study was conducted to investigate the effects of DFZ on male marine medaka (Oryzias melastigma). After exposure of the embryo to 1, 10, 100 and 1000ng/L DFZ for 180days, the gonadosomatic index was significantly decreased in the 1000ng/L treatment. The number of sperm was reduced while the abundances of spermatocytes and spermatogonia in the testes were increased in all the treatments. The mRNA levels of salmon-type gnrh (sgnrh), the luteinizing hormone (lhß) and the follicle-stimulating hormone (fshß) genes in the brain all exhibited a significant down-regulation, the expression of androgen receptors (arα and arß) was decreased and that of estrogen receptor ß and cytochrome P450 aromatase (cyp19B) was increased in the testes. The expression levels of cyp19A and cyp19B were increased in the liver. The decrease of ars mRNA levels might be one of the reasons causing the reduction of sperm. The down-regulation of sgnrh, lhß and fshß mRNA levels suggested that DFZ might impact the spermatogenesis via the brain-pituitary-gonad pathway. The decrease of the fertilization success, the hatch ability and the swim-up success in the F1 generation indicated that DFZ pollution at environmental levels might cause a decrease of wild fish populations.

Intramolecular cyclization of the antimicrobial peptide Polybia-MPI with triazole stapling: influence on stability and bioactivity.

Cationic antimicrobial peptides have attracted increasing attention as a novel class of antibiotics to treat infectious diseases caused by pathogenic bacteria. However, susceptibility to protease is a shortcoming in their development. Cyclization is one approach to increase the proteolytic resistance of peptides. Therefore, to improve the proteolytic resistance of Polybia-MPI, we have synthesized the MPI cyclic analogs C-MPI-1 (i-to-i+4) and C-MPI-2 (i-to-i+6) by copper(I)-catalyzed azide-alkyne cycloaddition. Compared with MPI, C-MPI-1 displayed sustained antimicrobial activity and had enhanced anti-trypsin resistance, while C-MPI-2 displayed no antimicrobial activity. The relationship between peptide structure and bioactivity was further investigated by probing the secondary structure of the peptides by circular dichroism. This showed that C-MPI-1 adopted an α-helical structure in aqueous solution and, interestingly, had increased α-helical conformation in 30 mM sodium dodecyl sulfate and 50% trifluoroethyl alcohol compared with MPI. C-MPI-2 that was not α-helical in structure, suggesting that the propensity for α-helix conformation may play an important role in cyclic peptide design. In addition, scanning electron microscopy, propidium iodide uptake, and membrane permeabilization assays indicated that MPI and the optimized analog C-MPI-1 had membrane-active action modes, indicating that the peptides would not be susceptible to conventional resistance mechanisms. Our study provides additional insight into the influence of intramolecular cyclization at various positions on peptide structure and biological activity. In conclusion, the design and synthesis of cyclic analogs via click chemistry offer a new strategy for the development of stable antimicrobial agents. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Reproductive effects of life-cycle exposure to difenoconazole on female marine medaka (Oryzias melastigma).

Difenoconazole (DFZ) is a widely used triazole fungicide which has been detected in some estuaries and embayments. This study was conducted to investigate the effects of DFZ on ovarian development in female marine medaka (Oryzias melastigma). After 180 days exposure of the embryo to DFZ (0, 1, 10, 100 and 1000 ng/L), the gonadosomatic index and percentage of mature oocytes produced were significantly reduced in the 1, 10 and 100 ng/L treatments but not the 1000 ng/L treatment compared to the control, thus exhibiting a U-shaped dose response curve. The relative mRNA levels of brain follicle-stimulating hormone, ovarian cytochrome P450 aromatase (CYP19s), hepatic estrogen receptors and vitellogenin, and the ratio of 17ß-estradiol to testosterone in the muscle, also showed a U-shaped dose response, which was consistent with the development of oocytes. In addition, glutathione S-transferase activity in the ovary showed a U-shaped dose-response. These results gave an explanation for this U-shaped dose-response. The egg number produced, the hatch ability and the swim-up success in the F1 generation all showed a U-shaped dose response, indicating that exposure to DFZ at low concentrations can cause a decrease of fecundity and viability of the next generation. Thus, a more extensive evaluation of the impact of DFZ on marine fish reproduction at realistic environmental concentrations is needed.