Optimization and Detection of Freshness Biomarkers of Atlantic Salmon Subjected to Different Vacuum Packaging Conditions during Storage at 0 °C by Metabolomics and Molecular Docking.

The freshness of Atlantic salmon is influenced mainly by tissue metabolism, which in turn is affected by storage time and conditions. The alterations in taste profiles and nutritional values of salmon when packaged using vacuum methods have not been fully understood, and the factors contributing to these changes require further research. In this work, the extraction method for flavor nutrients from salmon was optimized via the Plackett-Burman (PB) test. A sensitive and rapid targeted metabolomics method for the simultaneous determination of 34 nutrients was successfully established via ultra-performance liquid chromatography-triple quadrupole/linear ion trap composite mass spectrometry (UHPLC-QTRAP/MS), and various nutritional compositions during storage at 0 °C under different vacuum conditions (0 kPa or -90 kPa) for 4 and 8 days were analyzed. Results showed that storage time had a significant effect on salmon metabolism. The total amino acids decreased by 62.95% and 65.89% at 0 kPa and -90 kPa, respectively. Notably, a marked reduction in histidine after 8 days at -90 kPa may have diminished bitterness, while decreased levels of umami-tasting amino acids like glutamine and aspartic acid affected the overall flavor profile. Overall, the packaging conditions at 0 °C and 0 kPa were more suitable for the preservation of most nutrients in salmon. Pathway enrichment analysis revealed that the reduction in substances was mainly related to the alanine, aspartate, and glutamate metabolism pathways. Alanine, inosine, and histidine, whose levels changed significantly, can bind to the typical umami taste receptor TIR1/TIR3 and can be biomarkers to monitor and determine the freshness or spoilage of salmon after 4-8 days of storage. This study revealed the changes in small-molecule nutrients in salmon during storage under different packaging conditions, which provides a reference for the packaging preservation technology of fresh salmon and new ideas for the evaluation of salmon quality and determination of freshness.

Botulinum toxin type A-targeted SPP1 contributes to neuropathic pain by the activation of microglia pyroptosis.

BACKGROUND: Neuropathic pain (NP) is the primary symptom of various neurological conditions. Patients with NP often experience mood disorders, particularly depression and anxiety, that can severely affect their normal lives. Microglial cells are associated with NP. Excessive inflammatory responses, especially the secretion of large amounts of pro-inflammatory cytokines, ultimately lead to neuroinflammation. Microglial pyroptosis is a newly discovered form of inflammatory cell death associated with immune responses and inflammation-related diseases of the central nervous system. AIM: To investigate the effects of botulinum toxin type A (BTX-A) on microglial pyroptosis in terms of NP and associated mechanisms. METHODS: Two models, an in vitro lipopolysaccharide (LPS)-stimulated microglial cell model and a selective nerve injury model using BTX-A and SPP1 knockdown treatments, were used. Key proteins in the pyroptosis signaling pathway, NLRP3-GSDMD, were assessed using western blotting, real-time quantitative polymerase chain reaction, and immunofluorescence. Inflammatory factors [interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α] were assessed using enzyme-linked immunosorbent assay. We also evaluated microglial cell proliferation and apoptosis. Furthermore, we measured pain sensation by assessing the delayed hind paw withdrawal latency using thermal stimulation. RESULTS: The expression levels of ACS and GSDMD-N and the mRNA expression of TNF-α, IL-6, and IL-1ß were enhanced in LPS-treated microglia. Furthermore, SPP1 expression was also induced in LPS-treated microglia. Notably, BTX-A inhibited SPP1 mRNA and protein expression in the LPS-treated microglia. Additionally, depletion of SPP1 or BTX-A inhibited cell viability and induced apoptosis in LPS-treated microglia, whereas co-treatment with BTX-A enhanced the effect of SPP1 short hairpin (sh)RNA in LPS-treated microglia. Finally, SPP1 depletion or BTX-A treatment reduced the levels of GSDMD-N, NLPRP3, and ASC and suppressed the production of inflammatory factors. CONCLUSION: Notably, BTX-A therapy and SPP1 shRNA enhance microglial proliferation and apoptosis and inhibit microglial death. It improves pain perception and inhibits microglial activation in rats with selective nerve pain.

Analysis of drug-induced posterior reversible encephalopathy syndrome using the food and drug administration adverse drug events reporting system database.

OBJECTIVE: In this retrospective pharmacovigilance study, we gathered data on drug-induced posterior reversible encephalopathy syndrome (PRES). Our goal was to identify the primary suspect drugs in PRES by analyzing the Food and Drug Administration Adverse Events Reporting System (FAERS) database. METHODS: We identified and analyzed reports of PRES listed in the FAERS database between 2004 and 2021. Using the reporting odds ratio and 95% confidence interval, we evaluated the safety signals for each of the drugs associated with PRES. RESULTS: We reviewed 11,077 reports of adverse events corresponding to PRES. The primary suspect drug categories were antineoplastics, immunosuppressants, and glucocorticoids. PRES was 24.77% more likely to occur in females than in males. Drug-induced PRES usually occurs in individuals with cancer, those who have undergone an organ/stem cell transplant, and those with autoimmune conditions. CONCLUSION: Our results show that the drugs most commonly suspected to cause PRES were antineoplastics, immunosuppressants, and glucocorticoids. Future studies are needed to illuminate the pathophysiological alterations that underlie PRES. In the meantime, prescribers and patients should be made aware of the potential risks of PRES associated with pharmaceutical therapy, and the summaries of product characteristics for individual drugs should be updated to include this information.

Aurora kinase B disruption suppresses pathological retinal angiogenesis by affecting cell cycle progression.

PURPOSE: The detrimental effects of pathological angiogenesis on the visual function are indisputable. Within a prominent role in chromosome segregation and tumor progression, aurora kinase B (AURKB) assumes a prominent role. However, its role in pathological retinal angiogenesis remains unclear. This study explores this latent mechanism. METHODS: To inhibit AURKB expression, we designed specific small interfering RNAs targeting AURKB and transfected them into vascular endothelial cells. Barasertib was selected as the AURKB inhibitor. The anti-angiogenic effects of both AURKB siRNA and barasertib were assessed in vitro by cell proliferation, transwell migration, and tube formation. To evaluate the angiogentic effects of AURKB in vivo, neonatal mice were exposed to 75% oxygen followed by normoxic repositioning to establish an oxygen-induced retinopathy (OIR) model. Subsequently, phosphate-buffered saline and barasertib were administered into OIR mice via intravitreal injection. The effects of AURKB on cell cycle proteins were determined by western blot analysis. RESULTS: We found that AURKB was overexpressed during pathological angiogenesis. AURKB siRNA and barasertib significantly inhibited endothelial cell proliferation, migration, and tube formation in vitro. Furthermore, AURKB inhibition attenuated retinal angiogenesis in the OIR model. A possible mechanism is the disruption of cell cycle by AURKB inhibition. CONCLUSION: In conclusion, AURKB significantly influenced pathological retinal angiogenesis, thereby presenting a promising therapeutic target in ocular neovascular diseases.

Exosomes incorporated with black phosphorus quantum dots attenuate retinal angiogenesis via disrupting glucose metabolism.

Black phosphorus quantum dots (BPQDs) have shown potential in tumor therapy, however, their anti-angiogenic functions have not been studied. Although BPQDs are easily degraded to non-toxic phosphrous, the reported toxicity, poor stability, and non-selectivity largely limit their further application in medicine. In this study, a vascular targeting, biocompatible, and cell metabolism-disrupting nanoplatform is engineered by incorporating BPQDs into exosomes modified with the Arg-Gly-Asp (RGD) peptide (BPQDs@RGD-EXO nanospheres, BREs). BREs inhibit endothelial cells (ECs) proliferation, migration, tube formation, and sprouting in vitro. The anti-angiogenic role of BREs in vivo is evaluated using mouse retinal vascular development model and oxygen-induced retinopathy model. Combined RNA-seq and metabolomic analysis reveal that BREs disrupt glucose metabolism, which is further confirmed by evaluating metabolites, ATP production and the c-MYC/Hexokinase 2 pathway. These BREs are promising anti-angiogenic platforms for the treatment of pathological retinal angiogenesis with minimal side effects.

Tailored Synthesis of Catalytically Active Cerium Oxide for N, N-Dimethylformamide Oxidation.

Cerium oxide nanopowder (CeOx) was prepared using the sol-gel method for the catalytic oxidation of N, N-dimethylformamide (DMF). The phase, specific surface area, morphology, ionic states, and redox properties of the obtained nanocatalyst were systematically characterized using XRD, BET, TEM, EDS, XPS, H2-TPR, and O2-TPO techniques. The results showed that the catalyst had a good crystal structure and spherelike morphology with the aggregation of uniform small grain size. The catalyst showed the presence of more adsorbed oxygen on the catalyst surface. XPS and H2-TPR have confirmed the reduction of Ce4+ species to Ce3+ species. O2-TPR proved the reoxidability of CeOx, playing a key role during DMF oxidation. The catalyst had a reaction rate of 1.44 mol g-1cat s-1 and apparent activation energy of 33.30 ± 3 kJ mol-1. The catalytic performance showed ~82 ± 2% DMF oxidation at 400 °C. This work's overall results demonstrated that reducing Ce4+ to Ce3+ and increasing the amount of adsorbed oxygen provided more suitable active sites for DMF oxidation. Additionally, the catalyst was thermally stable (~86%) after 100 h time-on-stream DMF conversion, which could be a potential catalyst for industrial applications.

Long-term results of extended Boari flap technique for management of complete ureteral avulsion: A case report.

BACKGROUND: Ureteroscopy is well-established as a primary treatment modality for urolithiasis. Ureteral avulsion, particularly complete or full-length avulsion with a resultant long segment of the ureter left attached to the ureteroscope, is a rare but devastating complication of the procedure. Management of this complication is challenging. Moreover, general consensus regarding the optimal management is undetermined. We report our experience of managing a complete ureteral avulsion case via an extended Boari flap technique with long-term results. CASE SUMMARY: A 41-year-old female patient subjected to complete ureteral avulsion caused by ureteroscopy was referred to our hospital. A modified, extended Boari flap technique was successfully performed to repair the full-length ureteral defect. Maximal mobilization of the bladder and affected kidney followed by psoas hitch and downward nephropexy maximized the probability of a tension-free anastomosis. Meticulous blood supply preservation to the flap also contributed to the success. During the 4-year study period, no complications except for a mild urinary frequency and a slightly lower maximum urinary flow rate were reported. The patient was satisfied with the surgical outcomes. CONCLUSION: The extended Boari flap procedure is a feasible and preferred technique to manage complete ureteral avulsion, particularly in emergencies.

Role of glucose metabolism in ocular angiogenesis (Review).

Glucose metabolism, the major source of energy, plays a crucial role in physiological cell function and the maintenance of homeostasis. Glucose acts as the predominant source of metabolic fuel in the generation of ATP and is involved in biosynthesis and epigenetics. Thus, glucose metabolism maintains a key role in cell function, homeostasis, energy generation, biosynthesis and epigenetics. An increasing number of studies have revealed that glucose metabolism is intricately involved in angiogenesis, with the disruption of angiogenesis contributing to several vascular diseases. Ocular vascular diseases are common ophthalmological disorders, and the prevalence of these disorders is increasing annually. Ocular vascular diseases largely occur from abnormal congenital development or acquired disturbances to the vasculature. Thus, identifying the process of occurrence and development of physiological and pathological angiogenesis is of utmost importance, and this involves understanding the inseparable role of intercellular communications between vascular cells. Although vascular endothelial growth factor (VEGF) is a well­recognized therapeutic target for the management of ocular vascular diseases, VEGF­based therapy fails to achieve the desired therapeutic effects in several cases, partly due to drug resistance and non­compliance. In the present review, current knowledge on the processes and roles of glucose metabolism in governing both physiological and pathological ocular angiogenesis are summarized, highlighting vascular glucose metabolism as a promising strategy for maintaining or restoring the physiological functions of the vasculature, thus potentially ameliorating ocular vascular diseases.

Construction of Development Momentum Index of Financial Technology by Principal Component Analysis in the Era of Digital Economy.

The purpose is to study applying mathematical analysis in financial technology (FinTech) development in the era of digital economy. An Evaluation Index System (EIS) for the current situation of Chinese FinTech enterprises is established by considering the impact of the era of the digital economy on the development of FinTech. Specifically, the Principal Component Analysis (PCA) is introduced to construct the principal component prediction model based on functional data. Then, six Chinese State-owned Enterprises (SOEs) are selected. Their stock prices are predicted using the proposed model through an empirical study. The results show that selecting three principal components to evaluate the financial situations of six SOEs is reasonable. The accumulated variance values of the first three principal components of the stock's closing price and opening price are all greater than 85%. Thus, the selected three principal components can obtain the potential information of the original data. The gap between the actual value and the proposed model-predicted value of the stocks of the six SOEs is relatively small. The Root Mean Square Error (RMSE) of China National Petroleum Corporation (CNPC) is 0.105, more than 10%. The predicted values of Huadian Energy and China Shenhua are 9.4% and 8.5%, respectively, second only to CNPC. Therefore, the proposed principal component prediction model based on functional data can predict the closing price of stocks well. The accuracy is relatively high and matches well with financial data analysis. This research has important implications for the development of FinTech.

Graphene quantum dots rescue angiogenic retinopathy via blocking STAT3/Periostin/ERK signaling.

BACKGROUND: Pathological retinal angiogenesis resulting from a variety of ocular diseases including oxygen induced retinopathy, diabetic retinopathy and ocular vein occlusion, is one of the major reasons for vision loss, yet the therapeutic option is limited. Multiple nanoparticles have been reported to alleviate angiogenic retinopathy. However, the adverse effect cannot be ignored due to the relatively large scale. Graphene quantum dots (GQDs) have shown potential in drug delivery and have been proved biocompatible. In this study, Graphene quantum dots are extensively investigated for their application in angiogenic retinopathy therapy. RESULTS: We showed that GQDs were biocompatible nanomaterials in vitro and in vivo. The nanoparticles have a dose-dependent inhibitory effect on proliferation, migration, tube formation and sprouting of human umbilical vein endothelial cells (HUVECs). Further data show that GQDs could inhibit pathological retinal neovascularization in an oxygen-induced retinopathy (OIR) model. The data of RNA sequencing suggested that periostin is involved in this process. GQDs inhibit the expression of periostin via STAT3, and further regulated cell cycle-related protein levels through ERK pathway. The signaling pathway was conformed in vivo using OIR mouse model. CONCLUSIONS: The present study indicated that GQDs could be a biocompatible anti-angiogenic nanomedicine in the treatment of pathological retinal neovascularization via disrupting periostin/ERK pathway and subsequent cell cycle.

[Emission Characterstics of VOCs and n-alkanes from Diesel Forklifts].

Non-road diesel vehicle exhaust is an important emission source that affects air quality in China, yet knowledge regarding its chemical composition and potential influence factors remains limited. Six typical forklifts were selected to study the effect of diesel particulate filters (DPF) on the emission characteristics of volatile organic compounds (VOCs) and n-alkanes using online monitoring of gaseous components combined with offline analysis. The results showed that oxygenated volatile organic compounds (OVOCs), olefins, alkanes, aromatic hydrocarbons, and halogenated hydrocarbons accounted for 26%-37%, 16%-36%, 19%-22%, 13%-21%, and 4%-7% of the measured VOCs in forklift exhaust, respectively. The VOCs emission factors of low-power and high-power forklifts were(2.47±0.33)g·kg-1 and (1.48±0.24)g·kg-1, respectively. The forklift exhaust emission factors of total VOCs without and with DPF were(1.94±0.58)g·kg-1and (2.08±0.79)g·kg-1, respectively. Our results showed that DDF exerted minor impact on VOCs emission. However, it is worth noting that DPF can efficiently remove some types of OVOCs components. For example, the emission factors of acetaldehyde and acetone of the forklifts with DPF were reduced by 19% and 26%, respectively, compared to that of those without DPF. The carbon numbers of n-alkane fractions showed a bimodal distribution of C7-C17 and C24-C31, respectively, with C15 being the dominant peak carbon. The average emission factors of n-alkanes were (115±34) mg·kg-1 (without DPF) and (53.7±19)mg·kg-1 (with DPF), respectively, with a decrease of 53%, indicating that DPF can effectively reduce the emission of n-alkane in the exhaust of forklifts. Our results can provide scientific support for the precise control of non-road construction machinery exhaust emissions and the further improvement of regional air quality.

Comparative analysis of the clinical outcomes between wavefront-guided and conventional femtosecond LASIK in myopia and myopia astigmatism.

AIM: To compare the clinical outcomes of wavefront guided femtosecond LASIK (WFG LASIK) and conventional femtosecond LASIK (NWFG LASIK) in eyes with myopia and myopia astigmatism. METHODS: This was a retrospective, nonrandomized, comparative investigation enrolling 236 eyes of 122 patients (18-50y) with low & moderate and high myopia. The WFG group including 97 eyes (50 patients) undergone WFG LASIK and the NWFG group including 139 eyes (72 patients) undergone conventional LASIK. Mean efficacy index, high order aberrations (HOAs), pupil size and the quality of visual questionnaire were evaluated 6mo postoperatively. RESULTS: There is no difference between WFG group (-0.054±0.049 in logMAR) and NWFG group (-0.040±0.056) in uncorrected distance visual acuity (UDVA) postoperatively. The myopia astigmatism is higher in WFG group than that in NWFG group (P<0.05). However, the mean efficacy index (MEI) in the WFG group (1.09±0.106) is better than that in the NWFG group (1.036±0.124; P<0.001). Increased HOAs were observed in NWFG group (0.30±0.196) than that in WFG group (0.146±0.188; P<0.001). The pupil size is larger in WFG group (5.15±0.76 mm) than that in NWFG group (4.32±0.52 mm). The patients are satisfied with the clinical surgery, yet WFG group showed better visual quality using the questionnaire survey. Meanwhile, high myopia would result in worse MEI, HOAs and visual quality than low & moderate myopia. CONCLUSION: WFG and NWFG FS-LASIK are both effective and safe procedures to correct low & moderate and high myopia, but WFG FS-LASIK gives a better postoperative MEI, aberrometric control and predictable outcome. Meanwhile, WFG FS-LASIK is better than NWFG FS-LASIK in correction of myopia astigmatism. Low & moderate myopia allow better clinical outcomes than high myopia using any surgical method.

The effect of charge on the uptake and resistance to reduction of platinum(IV) complexes in human serum and whole blood models.

cis- and trans-Platinum(iv) complexes with diaminetetracarboxylate coordination spheres possess the highly desirable property of exhibiting unusual resistance to reduction by blood serum components and endogenous reductants such as ascorbate. At the same time they are rapidly reduced in the intracellular environment of cancer cells. Consequently, they can potentially be tuned to remain intact in vivo until arrival at the tumour target where they are rapidly reduced to yield the active platinum(ii) species. However, in order to achieve this, uptake must be largely restricted to tumour cells and therefore uptake by healthy cells including red blood cells must be prevented. In this proof of concept study, we report on the effect of net charge as a means of controlling the uptake by red blood cells. Using 1H NMR spectroscopy we found that modifying the net charge of the complex does not influence the rate of reduction of the complexes by an excess of ascorbate. Using XANES spectroscopy we found that modifying the net charge of the platinum(iv) complexes decreased the extent of reduction in whole blood, although probably not to the degree needed for the optimal delivery to tumours. Therefore, it is likely to be necessary to adopt higher charges and/or additional strategies to keep platinum(iv) prodrugs out of blood cells.

A comprehensive analysis of metabolomics and transcriptomics reveals new biomarkers and mechanistic insights on DEHP exposures in MCF-7 cells.

Di-(2-ethylhexyl) phthalate (DEHP) is one of the most important environmental pollutants and affects multiple pathways upon human exposure. DEHP could induce MCF-7 cell proliferation at a very low dose; however, the possible linkage between DEHP and the cell proliferation effect is still unclear. Here, we carried out a comprehensive metabolome and transcriptome analysis to depict the possible molecular mechanisms of the effect of DEHP exposure on MCF-7 proliferation. In this paper, MCF-7 cells treated with DEHP at a dose of 1 µM for 48 h were selected for metabolome and transcriptome analysis. Untargeted and targeted metabolomics identified 8 differential metabolites, including amino acids, purine, pyrimidine and nucleotides. The metabolite changes were associated with 9 metabolic pathways. Disorders in riboflavin, histidine, beta-alanine metabolism, and nitrogen metabolism caused by DEHP exposure are important concerns for MCF-7 proliferation. Moreover, a transcriptomics study of the MCF-7 cells found a total of 500 differentially expressed genes (DEGs). KEGG enrichment analyses showed that pathways in cancer had stronger responses. The results of integrated analysis of the interactions between the DEGs and metabolites revealed significant changes in the purine metabolism pathway, which will shed light on the mechanism of MCF-7 cell proliferation after DEHP exposure. Overall, this study depicts the possible contribution of DEHP exposure to MCF-7 cell proliferation and highlights the power of omics platforms to deepen the mechanistic understanding of toxicity caused by endocrine disrupting chemicals.

UPLC-QTOF analysis reveals metabolomic changes in the flag leaf of wheat (Triticum aestivum L.) under low-nitrogen stress.

Wheat is one of the most important grain crop plants worldwide. Nitrogen (N) is an essential macronutrient for the growth and development of wheat and exerts a marked influence on its metabolites. To investigate the influence of low nitrogen stress on various metabolites of the flag leaf of wheat (Triticum aestivum L.), a metabolomic analysis of two wheat cultivars under different induced nitrogen levels was conducted during two important growth periods based on large-scale untargeted metabolomic analysis using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF). Multivariate analyses-such as principle components analysis (PCA) and orthogonal partial least square discriminant analysis (OPLS-DA)-were used for data analysis. PCA yielded distinctive clustering information among the samples, classifying the wheat flag samples into two categories: those under normal N treatment and low N treatment. By processing OPLS-DA, eleven secondary metabolites were shown to be responsible for classifying the two groups. The secondary metabolites may be considered potential biomarkers of low nitrogen stress. Chemical analyses showed that most of the identified secondary metabolites were flavonoids and their related derivatives, such as iso-vitexin, iso-orientin and methylisoorientin-2″-O-rhamnoside, etc. This study confirmed the effect of low nitrogen stress on the metabolism of wheat, and revealed that the accumulation of secondary metabolites is a response to abiotic stresses. Meanwhile, we aimed to identify markers which could be used to monitor the nitrogen status of wheat crops, presumably to guide appropriate fertilization regimens. Furthermore, the UPLC-QTOF metabolic platform technology can be used to study metabolomic variations of wheat under abiotic stresses.

Protective effect of HSF1 on mice with LPS-induced acute lung injury and screening of relevant differentially-expressed genes / 中国病理生理杂志

AIM:To study the protective effect of heat shock factor1(HSF1) on the mice with lipopolysaccha-ride (LPS)-induced acute lung injury(ALI),and to screen the relevant differentially-expressed genes. METHODS:ALI mouse model was established by LPS intracheal instillation. The macroscopic and pathological changes of the lung tissue were observed,and the concentrations of total protein,TNF-α, IL-β, IL-6 and VEGF in the bronchoalveolar lavage fluid (BALF) were analyzed. Differentially-expressed genes in the lung tissues of HSF1 +/ +mice and HSF1 -/- mice with ALI induced by LPS were screened by gene chips. The key gene was verified by real-time qPCR. RESULTS:The macroscopic and pathological changes of the lung injury in HSF1 -/- +LPS mice were more serious than those in HSF1 +/ ++LPS mice.The concentrations of total protein,VEGF,TNF-α,IL-1β and IL-6 in the BALF of HSF1 -/- +LPS mice were significantly higher than those of HSF1 +/ ++LPS mice(P<0.05). Compared with the HSF1 +/ +mice,a total of 918 differentially-ex-pressed genes were indentified in the HSF1 -/- mice, among which the expression levels of 65 genes had obvious diffe-rence,with 28 genes up-regulated,including Atg7,ccr1,cxcr2,Tbl1xr1,Mmp9,Pparg,Plcb2,Arrb2,Cntn1,Col4a6, etc, and 37 genes down-regulated,including Fgfr1,Fgfr2,Map4k4,Ddx58,Tfg,Stat3,Smad4,Lamc1,Sdc3,etc. The results of real-time qPCR showed that the mRNA level of CXCR2 in HSF1 -/- + LPS mice was significantly higher than that in HSF1 +/ ++ LPS mice,which was consistent with the results of gene chips. CONCLUSION:HSF1 has protective effect on the mice with LPS-induced ALI. CXCR2 may be involved in the protective effect of HSF1 on this process.

Control of Methicillin-Resistant Staphylococcus aureus Pneumonia Utilizing TLR2 Agonist Pam3CSK4.

The spread of methicillin-resistant Staphylococcus aureus (MRSA) is a critical health issue that has drawn greater attention to the potential use of immunotherapy. Toll-like receptor 2 (TLR2), a pattern recognition receptor, is an essential component in host innate defense system against S. aureus infection. However, little is known about the innate immune response, specifically TLR2 activation, against MRSA infection. Here, we evaluate the protective effect and the mechanism of MRSA murine pneumonia after pretreatment with Pam3CSK4, a TLR2 agonist. We found that the MRSA-pneumonia mouse model, pretreated with Pam3CSK4, had reduced bacteria and mortality in comparison to control mice. As well, lower protein and mRNA levels of TNF-α, IL-1ß and IL-6 were observed in lungs and bronchus of the Pam3CSK4 pretreatment group. Conversely, expression of anti-inflammatory cytokine IL-10, but not TGF-ß, increased in Pam3CSK4-pretreated mice. Our additional studies showed that CXCL-2 and CXCL1, which are necessary for neutrophil recruitment, were less evident in the Pam3CSK4-pretreated group compared to control group, whereas the expression of Fcγ receptors (FcγⅠ/Ⅲ) and complement receptors (CR1/3) increased in murine lungs. Furthermore, we found that increased survival and improved bacterial clearance were not a result of higher levels of neutrophil infiltration, but rather a result of enhanced phagocytosis and bactericidal activity of neutrophils in vitro and in vivo as well as increased robust oxidative activity and release of lactoferrin. Our cumulative findings suggest that Pam3CSK4 could be a novel immunotherapeutic candidate against MRSA pneumonia.

Plant Polyphenol-Assisted Green Synthesis of Hollow CoPt Alloy Nanoparticles for Dual-Modality Imaging Guided Photothermal Therapy.

Theranostic nanomedicines that integrate diagnostic and therapeutic moieties into a single nanoscale platform are playing an increasingly important role in fighting cancer. Here, a facile and green synthetic strategy for hollow CoPt alloy nanoparticles (HCPA-NPs) using plant polyphenols as assisted agents is reported for the first time. This novel strategy enables size-controlled synthesis of HCPA-NPs through the control of the molecular sizes of polyphenols. It is also a versatile strategy for synthesizing other hollow alloy nanoparticles with various metal compositions due to the diverse metal-chelating ability of the polyphenols. Further studies show that HCPA-NPs have good biocompatibility and can be successfully implemented for magnetic resonance and photoacoustic dual-modal imaging guided photothermal therapy. This work brings new insights for the green synthesis of hollow nanoparticles and extends these biocompatible nanoparticles for theranostic applications.

CT imaging of ovarian yolk sac tumor with emphasis on differential diagnosis.

Ovarian yolk sac tumors (YSTs) are rare neoplasms. No radiological study has been done to compare the imaging findings between this type of tumor and other ovarian tumors. Here we analyzed the CT findings of 11 pathologically proven ovarian YSTs and compared their imaging findings with 18 other types of ovarian tumors in the same age range. Patient age, tumor size, tumor shape, ascites and metastasis of two groups did not differ significantly (P > 0.05). A mixed solid-cystic nature, intratumoral hemorrhage, marked enhancement and dilated intratumoral vessel of two groups differed significantly (P < 0.05). The area under the ROC curve of four significant CT features was 0.679, 0.707, 0.705, and 1.000, respectively. Multivariate logistic regression analysis identified two independent signs of YST: intratumoral hemorrhage and marked enhancement. Our results show that certain suggestive CT signs that may be valuable for improving the accuracy of imaging diagnosis of YST and may be helpful in distinguishing YST from other ovarian tumors.

A further analysis of the relationship between yellow ripe-fruit color and the capsanthin-capsorubin synthase gene in pepper (Capsicum sp.) indicated a new mutant variant in C. annuum and a tandem repeat structure in promoter region.

Mature pepper (Capsicum sp.) fruits come in a variety of colors, including red, orange, yellow, brown, and white. To better understand the genetic and regulatory relationships between the yellow fruit phenotype and the capsanthin-capsorubin synthase gene (Ccs), we examined 156 Capsicum varieties, most of which were collected from Northwest Chinese landraces. A new ccs variant was identified in the yellow fruit cultivar CK7. Cluster analysis revealed that CK7, which belongs to the C. annuum species, has low genetic similarity to other yellow C. annuum varieties. In the coding sequence of this ccs allele, we detected a premature stop codon derived from a C to G change, as well as a downstream frame-shift caused by a 1-bp nucleotide deletion. In addition, the expression of the gene was detected in mature CK7 fruit. Furthermore, the promoter sequences of Ccs from some pepper varieties were examined, and we detected a 176-bp tandem repeat sequence in the promoter region. In all C. annuum varieties examined in this study, the repeat number was three, compared with four in two C. chinense accessions. The sequence similarity ranged from 84.8% to 97.7% among the four types of repeats, and some putative cis-elements were also found in every repeat. This suggests that the transcriptional regulation of Ccs expression is complex. Based on the analysis of the novel C. annuum mutation reported here, along with the studies of three mutation types in yellow C. annuum and C. chinense accessions, we suggest that the mechanism leading to the production of yellow color fruit may be not as complex as that leading to orange fruit production.