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In this paper, a simple model predictive control (MPC) based on state space averaging model for three-level flying capacitor boost converter (FCBC) is presented. The proposed MPC with constant switching frequency is used as the inner loop controller to control the inductor current and flying capacitor voltage. A new outer loop control strategy for the output voltage is proposed to provide a suitable inductor current reference to improve the dynamic response of the output voltage. Compared with the previous control method for three-level FCBC, the proposed control method shows better dynamic performance. The proposed control method is demonstrated through simulations and experimental results.

This paper proposes a new flying capacitor voltages estimation method based on peak inductor current detection and output voltage measurement for flying capacitor multilevel DC-DC converters. The proposed method is easy to implement and can be applied to flying capacitor multilevel DC-DC converters with different number of levels. When the proposed method is used in the active flying capacitor voltage balancing method based on a proportional controller, a good voltage-balancing dynamic performance can be obtained. Effectiveness of the proposed method has been verified by simulation and experimental results in a four-level flying capacitor boost converter prototype.

COVID-19 is an emerging infectious disease that is extremely contagious and can cause serious consequences and even death.Convalescent plasma, an unregistered therapy, from which the antibodies mig...

Asymptomatic/subclinical gonococcal infections in females continue to be prevalent within the general population, thus emerging as a global health problem. However, the reasons for these clinical manifestations are unknown. Our group had previously found out that in females, asymptomatic gonococcal infections correlate with higher serum progesterone (P4) levels and lower IL-1β levels in cervical secretions. We used murine infection model and THP-1 cells to determine whether P4 exerts anti-inflammatory effects on gonococcal infections. In the murine infection model, P4 (1 mg/day) inhibited the inflammatory effects induced by gonococcal infections which led to decreased neutrophil infiltration, reduced polymorphonuclear neutrophils (PMNs) numbers, IL-1β, TNF-α, and IL-6 levels in vaginal secretions. In addition, P4 down-regulated the mRNA and protein levels of NLRP3, associated with lower mRNA levels of pro-IL-1β, repressed caspase-1 activity in genital tissues and THP-1 cells. Moreover, P4 suppressed the phosphorylation levels of NF-κB and attenuated Neisseria gonorrhoeae (N. gonorrhoeae, gonococci or GC)-induced ROS generation. This is consistent with the two signals required for activation of the NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome. In conclusion, our result shows that P4 suppresses the gonococci induced-inflammation, especially through the NLRP3 inflammasome pathway, and partially explains the pathogenesis of asymptomatic GC infection in women.

Background Evidence has been shown that triptolide was effective in the treatment of psoriasis; however, the mechanisms remain poorly understood. Thus, this study aimed to investigate the role of triptolide on the proliferation and differentiation of HaCaT cells which are treated with IL22 to mimic abnormal proliferation/differentiation in keratinocyte of psoriasis. Materials and Methods HaCaT cells were transfected with miR-181b-5p antagomir for 24 h, and then exposed to 10 μM Triptolide for 24 h, following by 100 ng/mL of IL22 for 24 h. In addition, the proliferation and cell cycle distribution in HaCaT cells were assessed by immunofluorescence or flow cytometry assays, respectively. Results Triptolide obviously upregulated the level of miR-181b-5p in HaCaT cells. In addition, triptolide significantly inhibited IL22-induced proliferation of HaCaT cells via inducing cell cycle arrest. Moreover, IL22 markedly inhibited the differentiation of HaCaT cells, and this phenomenon was reversed by triptolide treatment. In contrast, the effects of triptolide on the proliferation and differentiation in IL22-stimulated HaCaT cells were notably reversed by miR-181b-5p antagomir. Moreover, dual-luciferase assay showed that E2F5 was the direct target of miR-181b-5p in HaCaT cells. Meanwhile, upregulation of miR-181b-5p obviously decreased the level of E2F5 in HaCaT cells. Conclusion In this study, we found that triptolide could inhibit the proliferation and promote the differentiation in IL22-stimulated keratinocytes via upregulating miR-181b-5p. These data indicated that triptolide may be a potential agent for the treatment of psoriasis.

Psoriasis is a common autoimmune and chronic inflammatory skin disorder globally affecting 0.51–11.43% of adults. Inflammation-associated cell death in keratinocytes plays a key role in the process of integrate inflammatory cascade in psoriasis. Necroptosis is a regulated necrotic cell death mediated by receptor interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like pseudokinase (MLKL), which participates in many human inflammatory diseases. However, the mechanism and function of programmed necrosis in psoriasis is not well-illustrated. In the current study, we provide evidence for the involvement of necroptosis in psoriasis. RIPK1 and MLKL were significantly upregulated and localized in all layers of the epidermis in human psoriatic lesions, while RIPK3 and phosphorylated MLKL were mainly expressed in keratinocytes, which located in the upper layers. Increased tendency of necroptosis was also found in IMQ-induced psoriasiform skin of mice. Further, we discovered that both the inhibitor of RIPK1 R-7-Cl-O-Necrostatin-1 (Nec-1s) and MLKL-inhibitor necrosulfonamide (NSA) suppressed necroptosis in HaCaT cells and IMQ mouse models, powerfully blocked IMQ-induced inflammatory responses in vivo, and significantly downregulated the production of inflammatory factors like IL-1β, IL-6, IL-17A, IL-23a, CXCL1, and CCL20. These findings promote the development of new therapies for the treatment of necroptosis-activated pathologies for psoriasis.

Aromatic polyimide fibers (PI) are usually produced in two steps. The precursor fibers of polyamic acid (PAA) are fabricated first, and then the fabricated fibers are converted into PI fibers through thermal treatment. In the second step (thermal treatment), the mechanical properties of the obtained PI fibers are remarkably affected. Here, the PAA fibers derived from 3,3&rsquo, 4,4&rsquo, biphenyltetra-carboxylic dianhydride and p-phenylenediamine are fabricated by a dry-jet wet-spinning method. Then, the PI fibers are prepared by heating PAA fibers from room temperature to 300, 350 and 400 &deg, C under different heating rates, ranging from 1 &deg, C/min to 80 &deg, C/min. When the heating rate is low, the crystallization lags behind the imidization process, and begins only when the imidization degree reaches a high level. As the heating rate increases, the crystallization tends to occur simultaneously with the imidization process, and the degree of crystallinity of the PI fibers also greatly increases. Our findings suggest that a high heating rate causes the polymer chains to undergo high mobility during thermal treatment. The tensile modulus of the PI fiber further demonstrates a high dependence on the heating rate. Moreover, a short annealing process after treatment proves to be efficient in releasing residual stress and improving tensile strength.

Uropathogenic Escherichia coli (UPEC), a Gram-negative bacterial pathogen, is a major causative agent of urinary tract infections (UTIs). However, the molecular mechanisms of how UPEC causes infections have not been determined. Recent studies indicated that certain enteric Gram-negative bacteria interact with and hijack innate immune receptors DC-SIGN (CD209a) and SIGNR1 (CD209b), often expressed by antigen-presenting cells (APCs), such as macrophages, leading to dissemination and infection. It was not known whether UPEC could utilize DC-SIGN receptors to promote its infection and dissemination similarly to the enteric pathogens. The results of this study reveal that UPEC interacts with CD209-expressing macrophages and transfectants. This interaction is inhibited by anti-CD209 antibody, indicating that CD209s are receptors for UPEC. Additionally, in contrast to the results of previous studies, mice lacking SIGNR1 are more susceptible to infection of this uropathogen, leading to prolonged bacterial persistence. Overall, the results of our study indicate that the innate immune receptor CD209s participate in the clearance of UPEC during UTIs.

In order to obtain drug delivery carriers with good stability in blood and high cellular uptake efficiency, carboxyl groups and tertiary amine groups were respectively introduced into polyurethane to synthesize two kinds of amphiphilic polyurethanes with opposite charges (PUC and PUN). Their structures were characterized by Fourier transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (1H NMR) spectroscopy and gel permeation chromatography (GPC). PUC-PUN co-assembled nanomicelles were prepared by electrostatic interaction between PUC and PUN micelles, which showed acid-sensitive property. When the pH of the solution was decreased from 7.4 to 6.5, PUC-PUN-1 micelles showed negative-to-positive charge-reversal property among these micelles. The results of stability and cell experiments demonstrated that PUC-PUN-1 micelles not only had excellent stability in simulated normal physiological environment but also could obviously enhance the cellular uptake efficiency. PUC-PUN-1 micelles had low cytotoxicity against SGC-7901 and MGC-803 cells, whereas PUC-PUN-1/DOX micelles had higher cytotoxicity compared to pure DOX and PUN-1/DOX micelles. Moreover, the results of in vivo antitumor activity experiments showed that PUC-PUN-1/DOX micelles had better tumor inhibition ability and safety than pure DOX. In addition, the results of in vitro drug release experiments indicated that PUC-PUN-1/DOX micelles had almost no burst release or leakage of drugs in pH 7.4 environment. However, the drug release was accelerated in pH 5.0, which followed Fickian diffusion mechanism.

The optical limiting performances of few-layer transitional metal dichalcogenides (TMDs) nanosheets in the VB group (VS2, VSe2, NbS2, NbSe2, TaS2, and TaSe2) were systematically investigated for the first time, to the best of our knowledge. It was found that these TMDs nanosheets showed a normalized transmittance in the range of 20%–40% at the input energy of 1.28 GW/cm2. Ultralow initial threshold FS (0.05–0.10 J/cm2) and optical limiting threshold FOL (0.82–2.23 J/cm2) were achieved in the TMDs nanosheets, which surpassed most of the optical limiting materials. This work showed the potential of TMDs beyond MoS2 in optical limiting field.

Previous studies have reported that flue gas desulfurization (FGD) gypsum can be used as an amendment for saline-alkali soils. However, little information is available regarding the effects of FGD gypsum on soil quality and crop production at large scales. Thus, we evaluated the changes in the soil salinity, sodicity, soluble ion levels, paddy rice (Oryza sativa L.) yield and heavy metal levels in soil and rice after reclamation with FGD gypsum and paddy planting over three years. Data (90 samples) were also collected from three neighbouring saline-sodic fields (1780 ha). As expected, soil salinity and sodicity decreased significantly after two years of reclamation. The levels of electrical conductivity (EC) and the sodium absorption ratio (SAR) decreased rapidly in the first year, and the pH and exchangeable sodium percentage (ESP) decreased substantially in the second year. Averaged across the experimental sites, the mean EC, pH, ESP and SAR levels of the soils two years after reclamation decreased by 38.6%, 14.6%, 61.2% and 87.8%, respectively, compared to those of the initial soils. In addition, the concentrations of water-soluble Na+ and CO32− + HCO3− were 97.5% and 96.8% lower, respectively, two years after reclamation than the concentrations before reclamation. The paddy rice yield increased over time with reclamation; the mean level in the second year was 7.4 t ha−1 or 80% of the yield harvested from the managed fields of neighbouring farmers. Moreover, the heavy metal (Cd, Cr, Hg, Pb and As) contents of both soils and rice were lower than the established standards and below detectable limits after FGD gypsum application. These results confirm that FGD gypsum is a safe and effective way to reclaim saline-sodic soils and worthy of widespread application on the Songnen Plain in Northeast China and in similar ecological areas.

NbTe2 crystal is quasi-2D layered semimetal with charge density wave ground state showing a distorted-1T structure at room temperature. Here we report the anisotropic magneto-transport properties of NbTe2. An anomalous linear magnetoresistance up to 30% at 3 K in 9 T was observed, which can be well explained by quantum linear magnetoresistance model. Our results reveal that a large quasi-2D Fermi surface and small Fermi pockets with linearly dispersive bands coexist in NbTe2. The comparison with the isostructural material TaTe2 provides more information about the electronic structure evolution with charge density wave transitions in NbTe2 and TaTe2., 5 pages, 4 figures

We report a new type of amide bond-bearing cathepsin B-sensitive gemcitabine (GEM) prodrugs, capable of in situ covalently targeting circulating albumin and then making a hitchhike to the tumor. Specially, less plasma-enzyme deactivation, long plasma half-life, independence on nucleoside transporters, outstanding tumor targeting, and site-specific drug release are achieved, and as such these multifunctional advantages contribute to the dramatically increased in vivo antitumor efficacy.

Alopecia is a common disease affecting more than half of the world total number of people. Alopecia exists in different types, but one of the most common of these types is the Androgenic Alopecia which has affected approximately 51% of the total number of males ranging between the age bracket of 40 years and 75 years. This type of alopecia is more common in females who are above the age of 65 years and above. Despite this widespread effect, much has not been done regarding identifying the possible drugs for treating this disease. At present, there exist only two possible medications that have been scientifically approved to cure this disease, include finasteride and minoxidil. Also, another possible form of treatment has been the case of hair transplantation. Despite the new possible treatment options available for treatment of different types of hair loss, there is a need for the invention for more efficient management and treatment options that are less costly, environmentally friendly, and most importantly human consumption friendly. Due to the recent evaluation that low-level laser therapy stimulated hair growth. This systematic review and meta-analysis was to determine whether the use of low-level laser therapy is an effective therapy for treatment of the Androgenic alopecia and also to some degree we reviewed the level of the patient's satisfaction. Some earlier studies had shown that the use of low-level laser therapy stimulated the hair growth when mice were treated with chemotherapy which was induced by the alopecia and also the other type of alopecia called alopecia areata. The researchers hypothesized that the primary mechanism of treating Androgenic alopecia to be the stimulation of the epidermal stem cells which are in the hair follicle making them bulge and shift the follicles into the anagen phase.

Plasma is an ionized gas that consists of positively and negatively charged particles, neutral atoms, and photons. Recent developments in plasma sources have made it possible to generate room-temperature plasma in the "open air", thus enabling the application of plasma in vivo. Using nonthermal plasma, active agents can be efficiently delivered to target cells without creating thermal damage. Also known as cold atmospheric pressure plasma (CAP), nonthermal atmospheric pressure plasma offers innovative medical applications. In this context, it has also gained wide attention in the field of dermatology. The complex and variable mixture of active agents in plasma - predominantly reactive oxygen and nitrogen species (ROS, RNS) - can control or trigger complex biochemical reactions, achieving the desired effects in a dose-dependent manner. The objective of the present review is to present potential applications of plasma in dermatology and analyze its potential mechanisms of action.

Cervical cancer is one of the most common malignant tumors in women all over the world. However, the exact etiology of cervical cancer remains unclear. The receptor for activated protein kinase C (RACK1) is reported to be involved in tumorigenesis and tumor progression. Besides, the prognostic value of RACK1 in several kinds of tumors has been identified. However, there are limited studies on the functional role of RACK1 in cervical cancer. In this study, we tested the expression level of RACK1 by immunohistochemistry and western blot technologies and find that it is upregulated in cervical cancer. Colony formation and CCK8 assays indicate that RACK1 promotes cell proliferation in CaSki cervical cancer cells. While the silence of RACK1 decreases the cell proliferation in CCK8 analysis. β-galactosidase staining suggests that RACK1 decreases cell senescence in cervical cancer cells. Invasion and migration assay show that RACK1 promotes the invasion and migration of cervical cancer cells. Also, when RACK1 was silenced, it exerts the opposite result. Furthermore, the mRNA expression levels of MMP‑3, MMP‑9 and MMP‑10 were upregulated in RACK1‑overexpressed CaSki cells by qPCR analysis. RACK1 also induces S phase accumulation in cell cycle analysis and suppresses cell apoptosis in cervical cancer cells. Flow cytometry analysis of mitochondria functions suggests that RACK1 increases the mitochondrial membrane potential (Δψm) levels to prevent mitochondrial apoptosis in cervical cancer cells. To explore the possible mechanism of RACK1, we tested and found that RACK1 upregulates the expression of NF-κB, cyclin D1 and CDK4 and downregulates the expression of p53, p38, p21 and STAT1 in cervical cancer cells. These results suggest that RACK1 promotes cell growth and invasion and inhibits the senescence and apoptosis in cervical cancer cells probably by affecting the p53 pathway.

Rational design of prodrugs for efficient albumin binding shows distinct advantages in drug delivery in terms of drug availability, systemic circulation, and potential targeting effect. And fatty acids are good candidates due to their high affinity to albumin. However, how the alkyl chain length of fatty acids affects the binding dynamics between prodrugs and albumin, despite its importance, is still unclear. In the present study, three prodrugs of didanosine (DDI) and fatty acids were designed and synthesized to evaluate the effect of the alkyl chain length on prodrug-albumin binding process, including capric acid-didanosine (CA-DDI), myristic acid-didanosine (MA-DDI), and stearic acid-didanosine (SA-DDI). The binding dynamics between these prodrugs with bovine serum albumin (BSA) were studied by fluorometry, circular dichroism (CD), UV analysis, and molecular docking. It turned out that DDI itself showed poor binding affinity to BSA. In contrast, CA-DDI, MA-DDI, and SA-DDI demonstrated significantly improved binding affinity. Interestingly, the binding affinity between DDI prodrugs and BSA was correlated with the alkyl chain length of fatty acids, and the binding constant significantly increased with the extension of alkyl chain length (KCA-DDI = 5.86 × 103 M−1, KMA-DDI = 8.57 × 103 M−1, and KSA-DDI = 11.42 × 103 M−1 at 298 K).

In this study, we show that the polymorph type of cellulose is an important factor for its pyrolysis behavior. By using TGA, XRD and FTIR, we characterized the pyrolysis kinetics and char yields of amorphous cellulose, cellulose II and cellulose I. All these celluloses with various polymorphs were regenerated from the same source material, microcrystalline cellulose; thus, the lattice difference among these samples was the only factor affecting their thermal pyrolysis. We found that the char yield of cellulose I was the highest among all cellulose polymorphs. With the addition of 5% phosphoric acid, the char yield of cellulose I at 800 °C was as high as 37.4%. The char yield of cellulose I at 800 °C is more than 10% higher than that of cellulose II regardless the addition of additives. This study highlights that the lattice structures of cellulose affects both its thermal pyrolysis kinetics and the char yield. For improving the char yield of cellulose, both structural factors and impregnated additives play independent and important roles.

A simple and rapid UPLC–MS/MS method to simultaneously determine gemcitabine and its L-carnitine ester derivative (2'-deoxy-2', 2'-difluoro-N-((4-amino-4-oxobutanoyl) oxy)-4-(trimethyl amm-onio) butanoate-cytidine, JDR) in rat plasma was developed and validated. The conventional plasma sample preparation method of nucleoside analogues is solid-phase extraction (SPE) which is time-consuming and cost-expensive. In this study, gradient elution with small particles size solid phase was applied to effectively separate gemcitabine and JDR, and protein precipitation pretreatment was adopted to remove plasma protein and extract the analytes with high recovery(>81%). Method validation was performed as per the FDA guidelines, and the standard curves were found to be linear in the range of 5–4000 ng/ml for JDR and 4–4000 ng/ml for gemcitabine, respectively. The lower limit of quantitation (LLOQ) of gemcitabine and JDR was 4 and 5 ng/ml, respectively. The intra-day and inter-day precision and accuracy results were within the acceptable limits. Finally, the developed method was successfully applied to investigate the pharmacokinetic studies of JDR and gemcitabine after oral administration to rats.

Amphiphilic polyurethanes based on methoxy poly(ethylene glycol) (mPEG) and poly(ϵ-caprolactone) diol (PCL) with different arm numbers such as two, three and four were successfully synthesized. Their structures were confirmed by Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance spectroscopy (1H NMR) and gel permeation chromatography (GPC). The effects of arm number on properties of amphiphilic polyurethanes were studied. Pyrene fluorescence probe technique and dynamic light scattering (DLS) analyses showed that the CMC value and the micellar size of the resultant amphiphilic polyurethanes decreased and the micellar stability against dilution enhanced with increasing the arm number of polyurethane. Using indometacin (IMC) as a model drug, the results indicated that the drug loading capacity and in vitro drug sustained release effect of polyurethane with four arms were better than those of polyurethanes with two and three arms.

Novel organic cation transporter 2 (OCTN2, SLC22A5) is responsible for the uptake of carnitine through the intestine and, therefore, might be a promising molecular target for designing oral prodrugs. Poor permeability and rapid metabolism have greatly restricted the oral absorption of gemcitabine. We here describe the design of intestinal OCTN2-targeting prodrugs of gemcitabine by covalent coupling of l-carnitine to its N4-amino group via different lipophilic linkages. Because of the high OCTN2 affinity, the hexane diacid-linked prodrug demonstrated significantly improved stability (3-fold), cellular permeability (15-fold), and oral bioavailability (5-fold), while causing no toxicity as compared to gemcitabine. In addition, OCTN2-targeting prodrugs can simultaneously improve the permeability, solubility, and metabolic stability of gemcitabine. In summary, we present the first evidence that OCTN2 can act as a new molecular target for oral prodrug delivery and, importantly, the linkage carbon chain length is a key factor in modifying the affinity of the substrate for OCTN2.

Objective Individuals with Parkinson disease are more likely to develop melanoma, and melanoma patients are reciprocally at higher risk of developing Parkinson disease. Melanoma is strongly tied to red hair/fair skin, a phenotype of loss-of-function polymorphisms in the MC1R (melanocortin 1 receptor) gene. Loss-of-function variants of MC1R have also been linked to increased risk of Parkinson disease. The present study is to investigate the role of MC1R in dopaminergic neurons in vivo. Methods Genetic and pharmacological approaches were employed to manipulate MC1R, and nigrostriatal dopaminergic integrity was determined by comprehensive behavioral, neurochemical, and neuropathological measures. Results MC1Re/e mice, which carry an inactivating mutation of MC1R and mimic the human redhead phenotype, have compromised nigrostriatal dopaminergic neuronal integrity, and they are more susceptible to dopaminergic neuron toxins 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Furthermore, a selective MC1R agonist protects against MPTP-induced dopaminergic neurotoxicity. Interpretation Our findings reveal a protective role of MC1R in the nigrostriatal dopaminergic system, and they provide a rationale for MC1R as a potential therapeutic target for Parkinson disease. Together with its established role in melanoma, MC1R may represent a common pathogenic pathway for melanoma and Parkinson disease. Ann Neurol 2017;81:395–406

Distinguishing SiC (0001) Si-face from SiC (000-1) C-face without any damages is extremely important because the two polar faces have different physical and chemical properties which seriously influence the quality of a homoepitaxy or heteroepitaxy thin film on it. Here, a convenient and nondestructive detection method is developed to distinguish the Si-face and C-face of a (0001) oriented SiC wafer by employing a pull-off force measurement using atomic force microscopy. It is found that the pull-off force from a Si-face of 6H-SiC is about two times of that from a C-face, no matter it is a two-face chemical mechanical polishing or etched 6H-SiC wafer. The method developed here is suitable to identify polar faces of materials only if the two polar faces having different surface energy.

Psoriasis is one of the most common immune-mediated inflammatory diseases of the skin. The identification of the pivotal molecular mechanisms responsible for the disease pathogenesis may lead to the development of novel therapeutic options. The present study aimed to identify pivotal differentially expressed genes (DEGs) and methylated DEGs in psoriasis. The raw data from gene microarrays were obtained from the Gene Expression Omnibus database. The data were processed using packages in Bioconductor. In total, 352 upregulated and 137 downregulated DEGs were identified. The upregulated DEGs were primarily enriched in the 'innate immune defense' response and the 'cell cycle'. The down-regulated DEGs were primarily enriched in 'cell adhesion' and 'tight junction pathways'. A total of 95 methylated DEGs were identified, which were significantly enriched in the 'interleukin (IL)-17 signaling pathway' and the 'response to interferon'. Based on a comprehensive evaluation of all algorithms in cytoHubba, the key epigenetic-associated hub genes (S100A9, SELL, FCGR3B, MMP9, S100A7, IL7R, IRF7, CCR7, IFI44, CXCL1 and LCN2) were screened out. In order to further validate these genes, the present study constructed a model of imiquimod (IMQ)-induced psoriasiform dermatitis using mice. The levels of these hub genes were increased in the IMQ group. The knockdown of methylation-regulating enzyme ten-eleven translocation (TET) 2 expression in mice attenuated the expression levels of S100A9, SELL, IL7R, MMP9, CXCL1 and LCN2. Furthermore, the hydroxymethylated level of S100A9 was highly expressed in the IMQ group and was significantly decreased by TET2 deficiency in mice. On the whole, using an integrative system bioinformatics approach, the present study identified a series of characteristic enrichment pathways and key genes that may serve as potential biomarkers in psoriasis.

Long non-coding RNAs (LncRNAs) can act as competing endogenous RNA (ceRNA) involving in tumor initiation and progression. Nevertheless, the prognostic roles of lncRNAs in lncRNA-related ceRNA network of melanoma remain elusive. In this study, RNA sequence profiles were downloaded from The Cancer Genome Atlas (TCGA) database, and there were 2020 differentially expressed messenger RNAs (DEmRNAs), 438 differentially expressed lncRNAs (DElncRNAs) and 65 differentially expressed microRNAs (DEmiRNAs) between primary and metastasis melanoma patients. A ceRNA regulatory network was constructed based on the DElncRNAs-DEmiRNAs and DEmiRNAs-DEmRNAs interactions, which contained 39 lncRNAs, 10 miRNAs, and 16 mRNAs. Furthermore, univariate and multivariate Cox regression analysis were carried out to establish a 7-lncRNA prognostic signature. Subsequently, the area under the curve (AUC) value of the receiver operating characteristic (ROC) curve and the Kaplan-Meier risk survival analysis revealed the significant performance of this signature. Finally, pathway enrichment analyses implied that lncRNA MIR205HG and MIAT were associated with multiple cancer-related pathways, especially epidermis development and immune response. The current study provides novel insights into the lncRNA-related ceRNA network and the potential of lncRNAs to be candidate prognostic biomarkers and therapeutic targets in melanoma.

Neisseria gonorrhoeae (N. gonorrhoeae, gonococci, or GC), the etiologic agent of gonorrhea, is a human-obligate bacterial pathogen. The GC surface contains pili that mediate the adherence to host cells. Studies have shown that GC pili, coded by pilin genes, undergo remarkable changes during human experimental gonorrhea, possibly generated by DNA phase variation during infection. The question that arises is whether the changes in pilins can alter the adherence capacity of N. gonorrhoeae to host cells. In this study, six variants initially isolated from male volunteers infected with one single clone of GC were examined for their adherence patterns with human Chang conjunctiva cells. In this study, we showed that the variants showed distinct adherence patterns to this cell line under light microscopy and scanning electron microscopy. Moreover, two reisolates showed higher adherence capacities than that of the input strain. The results provide an additional example as to how the pilus variation may play a role in the pathogenesis of N. gonorrhoeae.

BACKGROUND Limited studies have assessed the risk of metabolic syndrome in pediatric psoriasis. This study was aimed to investigate the association of obesity and metabolic syndrome with pediatric psoriasis in Afghanistan. METHODS A case-control study was conducted from March to December 2018 at the dermatology department of Maiwand Teaching Hospital in Kabul city. Participants were children aged less than 18 years; 113 children with psoriasis and 113 children without psoriasis were compared. Height, weight, waist circumference, and blood pressure were measured. Blood samples were taken following overnight fasting to test serum levels of glucose, triglyceride, cholesterol, and high-density lipoprotein cholesterol. Analyses were done using Chi-square test and independent t test. Odds ratio and 95% confidence interval were calculated. RESULTS The mean age was 13.9 ± 3.7 and 13.4 ± 3.4 years in the psoriasis and control groups, respectively. Males comprised 54.9% of the psoriasis group and 41.6% of the control group. Family history of skin disorders was higher among children with psoriasis compared to the control group (23.0% vs. 13.7%; P

Our previous work has demonstrated that soluble polyimide with relatively weak interaction can be transformed from neutral polymer to associative polymer by increasing molecular weight. Thus, it is necessary to find another way to vary the relatively weak interaction strength, i.e. variation of solvent quality. Herein, viscoelastic behaviors are examined for 2,2-bis(3,4-dicarboxy-phenyl) hexafluoropropane dianhydride (6FDA)-2,2′-bis(trifluoromethyl)-4,4′-diam (TFDB) polyimide (PI), with a relatively low molecular weight (Mw) of 88 000 g mol−1, dissolved in cyclohexanone (CYC). The scaling relationship between viscosity (η0–ηs) and volume fraction is in good agreement with the associative polymer theory proposed by Rubinstein and Semenov. Oscillatory rheological results indicate that the PI solution tends to become a gel with increased volume fraction. The synchrotron radiation small-angle X-ray scattering results imply the existence of dense aggregates in the concentrated PI/CYC solutions. Shear thickening and thinning behaviors are observed in the solutions, and the shear thickening behavior of polyimide solution has not been reported in literature. Their mechanisms are studied by conducting dynamic and steady rheological experiments. Thus, enhancing the relatively weak interaction strength can also make the low Mw polyimide show associative polymer behavior. This work can help us to gain deep insight into polyimide solution properties from dilute to semidilute entangled solutions, and will guide the preparation of polyimide solutions for different processing.

DNA methylation and hydroxymethylation are the most common epigenetic modifications associated with the cell cycle and the inflammatory response. The present study aimed to investigate the role of 5‑hydroxymethyl‑cytosine (5‑hmC) and ten‑eleven translocation‑2 (TET2) in keratinocytes. Following TET2 knockdown, dot blot analysis was performed to assess the levels of 5‑hmC in keratinocytes, using HaCaT cells. Subsequently, the viability and cell cycle of HaCaT cells were assessed by MTT, Cell Counting Kit‑8 assay and flow cytometric assays. Cyclin‑dependent kinase inhibitor 2A and proinflammatory cytokine protein and mRNA expression levels were also detected. The present results suggested that TET2 may play an important role in regulating cellular proliferation by mediating DNA hydroxymethylation in HaCaT cells. In addition, TET2 knockdown decreased the production of proinflammatory cytokines, including lipocalin 2, S100 calcium binding protein A7, matrix metallopeptidase 9, C‑X‑C motif chemokine ligand 1, interferon regulatory factor 7 and interleukin‑7 receptor. The present study suggested that TET2 regulated cell viability, apoptosis and the expression of inflammatory mediators in keratinocytes. Collectively, the results indicated that TET2 knockdown may relieve inflammatory responses in the skin.

Intestinal mono-carboxylate transporter 1 (MCT1) plays an important role in the oral absorption of short-chain fatty acids that were used as oxidative metabolite. However, the prodrug strategy targeting intestinal MCT1 for oral delivery is rarely exploited. The oral bioavailability of Gemcitabine (Gem) is low mainly due to its poor intestinal permeability and rapid metabolism. Herein, a facile di-acid mono-amidation strategy was firstly developed to target MCT1 for oral chemotherapy. The N4-amino group of Gem is mono-amidated with di-acids containing different carbon chain lengths, which could recognize intestinal MCT1 and are bio-activated at physiological pH independent of the hydrolysis enzymes. The adipic acid-Gem shows higher MCT1 affinity, better gastrointestinal tract stability (3-fold), improved oral bioavailability (8.8-fold), and less gastrointestinal toxicity in comparison to Gem. Moreover the bio-activation rate of the prodrugs decreases with the increased fatty acid chain length of the linkage under physiological conditions. In summary, we present the first evidence that MCT1 could act as a new target for oral prodrug delivery, and that the linkage could modify the bio-activation rate for achieving optimal oral bioavailability. Our findings provide novel knowledge to rationally design intestinal transporter-targeting oral carrier prodrug.

Here, we report the crystal structures and properties of Rb

Solvent species influence the interactions of dissolved polymers in solution and consequently induce changes in solution properties. A soluble polyimide was synthesized through polycondensation, and four solvents, namely, N,N-dimethylacetamide (DMAc), N-methyl pyrrolidone (NMP), N,N-dimethylformamide (DMF), and dimethyl sulfoxide (DMSO), were selected to investigate systematically the influence of solubility parameter on solution power law behaviors. The power law relationship between specific viscosity and concentration was established using rheology and applying concepts from the Zimm, Rouse-Zimm, and Doi-Edwards models. All power law exponents were higher than theoretical predictions, and in the three concentration regions, i.e. dilute, semidilute unentangled, and semidilute entangled, the exponents increase, decrease, and increase, respectively, with respect to solubility parameter. Arguments derived from the listed models are proposed to explain these trends. The influences of solubility parameter on the overlap and entanglement concentrations are also discussed.

$\mathrm{N}{\mathrm{a}}_{0.35}{({\mathrm{C}}_{3}{\mathrm{N}}_{2}{\mathrm{H}}_{10})}_{0.426}\mathrm{F}{\mathrm{e}}_{2}\mathrm{S}{\mathrm{e}}_{2}$ exhibits a large orthorhombic distortion at room temperature without magnetic ordering, hence providing an ideal platform to investigate the correlation between nematicity and superconductivity. We show that its nematicity is stabilized by ``nematic'' ordered 1,3-diaminopropane (1,3- DIA) molecules in between the FeSe layers, and the C2 twofold rotational symmetry is preserved down to 10 K without phase transition. The superconductivity occurs at 46.5 K even though the orthorhombic distortion is much larger than that for \ensuremath{\beta}-FeSe and most of the other pnictide superconductors at low temperatures. First principles calculations reveal that this ``artificial'' orthorhombic distortion has a selective effect on the band structure, which behaves differently on splitting the iron $3{d}_{xz}$ and $3{d}_{yz}$ orbitals around the \cyrchar\CYRG{} and M points in the Brillouin zone. Our finding strongly supports that the nematic state is irrelevant to the emergent superconductivity, at least in high-${T}_{c}$ iron selenide superconductors.

Transition metal dichalcogenides (TMDs), an emerging optical limiting material, exhibit excellent optical limiting properties for high energy laser. Generally, TMDs materials showed better laser protection with the decrease of lateral sizes. However, in this work, TiS2 nanosheets showed exceptional lateral size-dependent optical limiting property contrary to the reported TMDs nanosheets. TiS2 nanosheets with similar thickness and varied lateral sizes of 50 nm, 100 nm, 150 nm, 350 nm were obtained. Larger size TiS2 nanosheets displayed better optical limiting performance and TiS2 nanosheets with ultra-low normalized transmittance (as low as 12%) were developed. It was interesting to find that both two-photon absorption (TPA) and reverse saturable absorption (RSA) were exhibited in large TiS2 nanosheets (350 nm) with a bandgap of 2.67 eV, while in small TiS2 nanosheets (50 nm) with a bandgap of 3.51 eV, only TPA existed. Furthermore, the TiS2 nanosheets incorporated polymethyl methacrylate (PMMA) sample with an extremely low content of 0.066 wt‰ TiS2 nanosheets exhibited a low normalized transmittance of 18%, along with a low initial threshold (0.03 J/cm2) and low optical threshold (0.57 J/cm2), which showed great potential for practical use of the TiS2 nanosheets in optical limiting field.

A challenge to polymer scientists is to design new materials with superior overall performance in heat-resistance, cold-resistance, strength, and toughness. Here we report the synthesis of hyperbranched polymers containing epoxy and imide structure (EHPI-n, n = 6, 12, and 24) with various molecular weights and degrees of branching using a new synthetic diimide dicarboxylic acid. EHPI-n significantly decreases the gelation time and accelerates the curing of EHPI-n/diglycidyl ether of bisphenol-A (DGEBA). Both EHPI-6 and EHPI-12 significantly reduce the viscosity, activation energy, and average particle size of EHPI-n/DGEBA blends due to the disentangling function and compatibility of the EHPI-n. The toughness property, including elongation at break, impact strength, critical strain energy value (GIC) and critical stress intensity factor (KIC) of 12 wt % EHPI-12/DGEBA composites are improved over the neat DGEBA, by 144.72 %, 197.9 %, 168.4 % and 72.6 %, respectively, while their mechanical properties, including tensile strength, storage modulus and flexural strength are enhanced by 61.2 %, 89.9 %, 44.2 %. The heat-resistant index and β-relaxation peak temperatures of the composites are improved 14 °C and 15 °C, respectively, indicating both outstanding high-temperature resistance and outstanding low-temperature resistance. The simultaneous improvement on multiple performances is attributable to an in-situ homogeneous reinforcing and toughening mechanism, which is explained by free volume fraction, microstructure and surface micrograph. The EHPI-n present great potential as advanced materials for aerospace and wind turbine.

Background: In recent years, several reports have tried to prove this connection between rs1800872 polymorphism in interleukin-10 and cervical cancer among different populations, but the results are debatable. Thus, we collected all the published literature and conducted an integrated meta-analysis, which provided better evidence-based medicine for the relationship between rs1800872 polymorphism in interleukin-10 and risk of cervical cancer. Methods: We systematically performed our search on PubMed, EMBASE, Web of Science, WanFang database, and CNKI for all papers related to this research, published up to August 1, 2020. Summary odds ratios (OR) with 95% confidence interval (95% CI) were calculated in allelic, homozygous, heterozygous, dominant, and recessive model to appraise the association. Results: The meta-analysis included 8 studies containing 1393 cervical cancer cases and 1307 controls. The aggregate data under heterozygous model and dominant inheritance model (OR = 0.66, 95% CI: 0.55--0.80) indicated a significant association between rs1800872 and the low risk of cervical cancer in the entire population. And the aggregated data under the dominant inheritance model shows that rs1800872 is significantly associated with the reduction in the risk of cervical tumors in the entire population. Conclusion: Our conclusion is that the AC/AA + AC variant of Rs1800872 indicates a protective effect in the development of cervical cancer.

The shape memory polyurethane/sepiolite nanocomposites were prepared with sepiolite dispersed uniformly in polyurethane based on poly(e-caprolactone). The influence of sepiolite on the structure of polyurethane was investigated by dynamic mechanical analysis, differential scanning calorimetry, X-ray diffraction, and polarized optical microscopy. The results show that sepiolite has little effect on the ordering of hard segments, but can act as a nucleating agent enhancing the crystallinity of soft segments. The maximum crystallinity of soft segments can be achieved when the content of sepiolite is 3 wt%. The results of shape memory test demonstrate that the addition of sepiolite improves the shape fixity ratio of polyurethane. The shape fixity ratio of polyurethane composite with 3 wt% of sepiolite reaches the maximum of 86.2%. The crystallinity of the soft segments can be adjusted by varying sepiolite content, which has a potential to realize controllability of shape memory properties. POLYM. COMPOS., 2016. © 2016 Society of Plastics Engineers

Lipooligosacharide (LOS) of Neisseria gonorrhoeae (gonococci, GC) is involved in the interaction of GC with host cells. Deletion of the alpha-oligosaccharide (alpha-OS) moiety of LOS (lgtF mutant) significantly impairs invasion of GC into epithelial cell lines. GC opacity (Opa) proteins, such as OpaI, mediate phagocytosis and stimulate chemiluminescence responses in neutrophils in part through interaction with members of the carcinoembryonic antigen (CEA) family, which includes CEACAM3 (CD66d), a human neutrophil specific receptor for phagocytosis of bacteria. In the present work, we examined the effects of OpaI-expressing lgtF mutant on phagocytosis by HeLa-CEACAM3 cells and chemiluminescence responses in neutrophils. The results showed that lgtF mutant even expressing OpaI completely lost the ability to promote either phagocytosis mediated by CEACAM3 interaction in HeLa cells or chemiluminescence responses in neutrophils. These data indicated that Opa proteins in the lgtF mutant, which might result from the conformational change, cannot be functional.

BACKGROUND The identification and use of novel compounds alone or in combination hold promise for the fight against NRAS mutant melanoma. MATERIAL AND METHODS We screened a kinase-specific inhibitor library through combining it with α-Mangostin in NRAS mutant melanoma cell line, and verified the enhancing effect of α-Mangostin through inhibition of the tumorigenesis pathway. RESULTS Within the kinase inhibitors, retinoic acid showed a significant synergistic effect with α-Mangostin. α-Mangostin also can reverse the drug resistance of retinoic acid in RARa siRNA-transduced sk-mel-2 cells. Colony assay, TUNEL staining, and the expressions of several apoptosis-related genes revealed that a-Mangostin enhanced the effect of retinoic acid-induced apoptosis. The combination treatment resulted in marked induction of ROS generation and inhibition of the AKT/S6 pathway. CONCLUSIONS These results indicate that the combination of these novel natural agents with retinoid acid may be clinically effective in NRAS mutant melanoma.

The Lenglongling Mountains (LLM) located in northeastern part of the Tibet Plateau, belong to a marginal area of the East Asian summer monsoon (EASM) and are sensitive to monsoon dynamics. Two tree-ring width chronologies developed from six sites of Picea crassifolia in the LLM were employed to study the regional drought variability. Correlation and temporal correlation analyses showed that relationships between the two chronologies and self-calibrated Palmer Drought Severity Index (sc_PDSI) were significant and stable across time, demonstrating the strength of sc_PDSI in modeling drought conditions in this region. Based on the relationships, the mean sc_PDSI was reconstructed for the period from 1786 to 2013. Dry conditions prevailed during 1817-1819, 1829-1831, 1928-1931 and 1999-2001. Relatively wet periods were identified for 1792-1795 and 1954-1956. Spatial correlations with other fourteen precipitation/drought reconstructed series in previous studies revealed that in arid regions of Northwest China, long-term variability of moisture conditions was synchronous before the 1950s at a decadal scale (1791-1954). In northwestern margin of the EASM, most of all selected reconstructions had better consistency in low-frequency variation, especially during dry periods, indicating similar regional moisture variations and analogous modes of climate forcing on tree growth in the region.

The rheological behavior of waterborne polyurethane dispersion (PUD) thickened by the hyperbranched waterborne polyurethane (HWPU) was studied by rheological measurements. The results showed that the flow activation energy depended on the structure and concentration of HWPU. Based on the relationship between the structure, concentration and flow activation energy, we could infer that during HWPU associating thickening process PUD experienced Duckweed state (appropriate HWPU-latex particles linker), 3D network structure (HWPU-latex particles three-dimensional network) or Bead-like texture (HWPU monomolecular micelles or multi-molecular micelles). The role of interaction between particles in the structure of thickening system was explored by dynamic light scattering, refraction analysis and fluorescence spectroscopy. The combination of hydrophobic groups of HWPU with latex particles resulted in associating thickening, while the intramolecular or intermolecular association of HWPU might lead to a decrease in thickening efficiency or no thickening.