Identification of the HLA-A*11:463 allele in a Chinese patient and his father.

HLA-A*11:463 has one nucleotide change from HLA-A*11:01:01:01 at nucleotide 508 changing Lysine (146) to Glutamine.

Shikonin exerts an anti-leukemia effect against FLT3-ITD mutated acute myeloid leukemia cells via targeting FLT3 tyrosine kinase and its downstream pathways.

INTRODUCTION: Acute myeloid leukemia (AML) with internal tandem duplication (ITD) mutations in Fms-like tyrosine kinase 3 (FLT3) has an unfavorable prognosis. Recently, using newly emerging inhibitors of FLT3 has led to improved outcomes of patients with FLT3-ITD mutations. However, drug resistance and relapse continue to be significant challenges in the treatment of patients with FLT3-ITD mutations. This study aimed to evaluate the anti-leukemic effects of shikonin (SHK) and its mechanisms of action against AML cells with FLT3-ITD mutations in vitro and in vivo. METHODS: The CCK-8 assay was used to analyze cell viability, and flow cytometry was used to detect cell apoptosis and differentiation. Western blotting and real-time polymerase chain reaction (RT-PCR) were used to examine the expression of certain proteins and genes. Leukemia mouse model was created to evaluate the anti-leukemia effect of SHK against FLT3-ITD mutated leukemia in vivo. RESULTS: After screening a series of leukemia cell lines, those with FLT3-ITD mutations were found to be more sensitive to SHK in terms of proliferation inhibition and apoptosis induction than those without FLT3-ITD mutations. SHK suppresses the expression and phosphorylation of FLT3 receptors and their downstream molecules. Inhibition of the NF-κB/miR-155 pathway is an important mechanism through which SHK kills FLT3-AML cells. Moreover, a low concentration of SHK promotes the differentiation of AML cells with FLT3-ITD mutations. Finally, SHK could significantly inhibit the growth of MV4-11 cells in leukemia bearing mice. CONCLUSION: The findings of this study indicate that SHK is a promising drug for the treatment of FLT3-ITD mutated AML.

Whole-transcriptome sequencing with ceRNA regulation network construction and verification in glioblastoma.

OBJECTIVES: To explore the key genes involved in the occurrence and development of glioblastoma (GBM) by analyzing whole-transcriptome sequencing and biologic data from GBM and normal cerebral cortex tissues and to search for important noncoding RNA (ncRNA) molecular markers based on the competitive endogenous RNA (ceRNA) network. METHODS: Ten GBM and normal cerebral cortex tissues were collected for full transcriptome sequencing, screened for differentially expressed (DE) mRNAs, miRNAs, lncRNAs, and circRNAs, and subjected to bioinformatic analysis. We constructed a Protein-Protein Interaction (PPI) network and a circRNA/lncRNA-miRNA-mRNA regulatory network and identified them using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Finally, The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases were used to validate and conduct a survival analysis of the target genes. RESULTS: A total of 5341 DEmRNAs, 259 DEmiRNAs, 3122 DElncRNAs, and 2135 DEcircRNAs were identified. Enrichment analysis showed that target genes regulated by DEmiRNA, DElncRNA, and DEcircRNA were closely related to chemical synaptic transmission and ion transmembrane transport. A PPI network analysis screened 10 hub genes that directly participate in tumor cell mitosis regulation. In addition, the ceRNA composite network showed that hsa-miR-296-5p and hsa-miR-874-5p were the central nodes of the network, and the reliability of relevant key molecules was successfully verified through RT-qPCR identification and the TCGA database. The CGGA database survival analysis produced 8 DEmRNAs closely related to GBM patient survival prognosis. CONCLUSIONS: This study revealed the important regulatory functions and molecular mechanisms of ncRNA molecules and identified hsa-miR-296-5p and hsa-miR-874-5p as key molecules in the ceRNA network. They may play an important role in GBM pathogenesis, treatment, and prognosis.

Experimental Investigation of Cobalt Deposition on 304 Stainless Steel in Borated and Lithiated High-Temperature Water.

The radioactive corrosion products 58Co and 60Co in the primary loops of pressurized water reactors (PWRs) are the main sources of radiation doses to which workers in nuclear power plants are exposed. To understand cobalt deposition on 304 stainless steel (304SS), which is the main structural material used in the primary loop, the microstructural characteristics and chemical composition of a 304SS surface layer immersed for 240 h in borated and lithiated high-temperature water containing cobalt were investigated with scanning electron microscopy (SEM), X-ray diffraction (XRD), laser Raman spectroscopy (LRS), X-ray photoelectron spectroscopy (XPS), glow discharge optical emission spectrometry (GD-OES), and inductively coupled plasma emission mass spectrometry (ICP-MS). The results showed that two distinct cobalt deposition layers (an outer layer of CoFe2O4 and an inner layer of CoCr2O4) were formed on the 304SS after 240 h of immersion. Further research showed that CoFe2O4 was formed on the metal surface by coprecipitation of the iron preferentially dissolved from the 304SS surface with cobalt ions from the solution. The CoCr2O4 was formed by ion exchange between the cobalt ions entering the metal inner oxide layer and (Fe, Ni) Cr2O4. These results are useful in understanding cobalt deposition on 304SS and have a certain reference value for exploring the deposition behavior and mechanism of radionuclide cobalt on 304SS in the PWR primary loop water environment.

Variation of Aroma Components of Pasteurized Yogurt with Different Process Combination before and after Aging by DHS/GC-O-MS.

Pasteurized yogurt is a healthy yogurt that can be stored in ambient temperature conditions. Dynamic headspace sampling (DHS) combined with gas chromatography-olfactory mass spectrometry (GC-O-MS), sensory evaluation, electronic nose (E-nose), and partial least squares discriminant analysis (PLS-DA) were used to analyze the flavor changes of pasteurized yogurt with different process combinations before and after aging. The results of odor profiles showed that the sensory descriptors of fermented, sweet, and sour were greatly affected by different process combinations. The results of odor-active compounds and relative odor activity value (r-OAV) showed that the combination of the production process affected the overall odor profile of pasteurized yogurt, which was consistent with the sensory evaluation results. A total of 15 odor-active compounds of 38 volatile compounds were detected in pasteurized yogurt samples. r-OAV results revealed that hexanal, (E)-2-octenal, 2-heptanone, and butanoic acid may be important odor-active compounds responsible for off-odor in aged, pasteurized yogurt samples. PLS-DA and variable importance of projection (VIP) results showed that butanoic acid, hexanal, acetoin, decanoic acid, 1-pentanol, 1-nonanal, and hexanoic acid were differential compounds that distinguish pasteurized yogurt before and after aging.

Characterization of Key Odor-Active Off-Flavor Compounds in Aged Pasteurized Yogurt by Sensory-Directed Flavor Analysis.

The purpose of this study was to determine the key odor-active compounds contributing to the off-flavor of aged pasteurized yogurt (APY) using sensory-directed flavor analysis. Additionally, different extraction methods were compared to determine their effects on the volatile compounds, including dynamic headspace sampling (DHS), solid-phase microextraction, and stir bar sorptive extraction, and DHS was found to be suitable for this study. The results showed that comprehensive two-dimensional gas chromatography-olfactometry-mass spectrometry analysis (GC × GC-O-MS) had more advantages in separating and identifying the volatile compounds than the traditional GC-O-MS. A total of 17 odor-active compounds were determined in the fresh pasteurized yogurt and APY samples by DHS coupled with GC × GC-O-MS. The dynamic headspace dilution analysis demonstrated that 2-heptanone and hexanal were the most vital components in APY with the highest flavor dilution factor. Furthermore, the spiking and omission experimental results revealed that the odor-active compounds, such as 2-heptanone, butanoic acid, pentanoic acid, hexanal, and (E)-2-heptenal, were the key odor-active off-flavor contributors in APY. Therefore, these compounds could be used as potential indicators to determine the freshness of pasteurized yogurt.

Effects of Elevated CO2 on the Fitness of Three Successive Generations of Lipaphis erysimi.

To assess the effect of elevated CO2 on the development, fecundity, and population dynamic parameters of L. erysimi, the age-stage, two-sex life table was used to predict the individual fitness and population parameters of three successive generations of L. erysimi in this study. The results show that a significantly longer total pre-adult stage before oviposition (TPOP) was observed in the third generation compared with the first generation of L. erysimi under the 800 µL/L CO2 treatment. The fecundity is significantly lower in the 800 µL/L CO2 treatment than that in the 400 µL/L CO2 treatment in the third generation of L. erysimi, which indicates that elevated CO2 had a negative effect on the individual fitness parameters of L. erysimi. Additionally, the life expectancy (exj) is significantly lower under the 800 µL/L CO2 treatment than that under the 400 µL/L CO2 treatment in the three successive generations. A significantly higher intrinsic rate of increase (r) and finite rate of increase (λ) were found in the second generation compared with those in the first and third generations of L. erysimi under the 800 µL/L CO2 treatment. Moreover, significantly lower r and λ were observed under the 800 µL/L CO2 treatment compared with those under the 400 µL/L and 600 µL/L CO2 treatments in the first generation of L. erysimi, which indicates that elevated CO2 has a short-term effect on the population parameters (r and λ) of L. erysimi. Our experiment can provide the data for the comprehensive prevention and control of L. erysimi in the future with increasing CO2 levels.

Characterization of key aroma-active compounds in Hanyuan Zanthoxylum bungeanum by GC-O-MS and switchable GC × GC-O-MS.

The present study sought to characterize the composition of volatile aroma compounds and key aroma-active compounds of dried Hanyuan Zanthoxylum bungeanum. The volatile aroma compounds were analyzed by the solid-phase microextraction (SPME) combined with gas chromatography-olfactometry-mass spectrometry (GC-O-MS) and two-dimensional comprehensive gas chromatography-olfactometry-mass spectrometry (GC × GC-O-MS). The key aroma-active compounds were analyzed by the aroma extract dilution analysis and odor activity value. A total of 72 volatile compounds were identified by GC-O-MS, of which 28 were aroma-active. Meanwhile, 116 volatile compounds were identified by GC × GC-O-MS, of which 43 were aroma-active. These results revealed that myrcene, (+)-limonene, (E)-ß-ocimene, ß-cubebene, Germacrene D, cineole, linalool, and linalyl acetate were the key aroma-active compounds of dried Hanyuan Zanthoxylum bungeanum.

An efficient multi-enzyme cascade platform based on mesoporous metal-organic frameworks for the detection of organophosphorus and glucose.

An efficient colorimetric detection platform based on multi-enzyme cascade has been developed for detection of organophosphorus. Firstly, the dual-enzyme platform was prepared and applied for sensitive glucose detection (detection limit 0.32 µM). And then three enzymes, including acetylcholinesterase, horseradish peroxidase and choline oxidase were encapsulated in cruciate flower-like zeolitic imidazolate framework-8 (CF-ZIF-8) through one-step co-precipitation to construct detection platform with acetylcholine chloride as substrate. The acephate inhibited the activity of acetylcholinesterase, obstructed the cascade reaction and reduced the production of H2O2, resulting in the changes of color intensity for the colorimetric detection. With suitable size and porous structure, CF-ZIF-8 provided a good microenvironment for guaranteeing the activity and spatial proximity of enzymes. The multi-enzyme platform displayed great performances with the detection limit of 0.23 nM for acephate. It was applied to the detection of acephate in Chinese cabbage and romaine, verifying the practicability of this platform.

Synergetic PtNP@Co3O4 hollow nanopolyhedrals as peroxidase-like nanozymes for the dual-channel homogeneous biosensing of prostate-specific antigen.

In this paper, novel synergetic PtNP@Co3O4 hollow nanopolyhedrals with peroxidase-like activities are designed and prepared, which can be used as electrochemical and colorimetric signal labels for the enzyme-free dual-channel homogeneous sensing of prostate-specific antigen. When prostate-specific antigens are present, the aptamer-modified PtNP@Co3O4 hollow nanopolyhedrals and magnetic beads form sandwich structures, which have excellent peroxidase-like activities, because of the synergetic effect of PtNP@Co3O4 hollow nanopolyhedrals. The sandwich structures can be separated from the mixture by the magnetic effect of the magnetic beads and catalyze the redox reactions between H2O2 and TMB, generating quantitative electrochemical and colorimetric responses in homogeneous solution simultaneously. Under the optimized conditions, the linear range of both electrochemical (0.01 to 10 ng/ml) and colorimetric (0.01-15 ng/ml) channels can satisfy the demand of prostate-specific antigen detection in clinic (4 ng/ml), and the electrochemical and colorimetric channels have a low detection limit of 0.0079 ng/ml and 0.01 ng/ml respectively without using natural enzymes. The strategy by using synergetic PtNP@Co3O4 hollow nanopolyhedrals as signal probes provides a promising scheme for developing simple, rapid, reliable, and ultrasensitive dual-channel homogeneous biosensors, which has a great potential as a powerful tool in prostate cancer diagnosis.

Application of topical gentamicin-a new era in the treatment of genodermatosis.

BACKGROUND: The clinical use of gentamicin always lies in its antimicrobial activity in the past as an aminoglycoside antibiotic. However, in the past decade, there were considerable interests in therapeutic approaches in treating hereditary diseases. Some of the genodermatosis is caused by nonsense mutations that create premature termination codons and lead to the production of truncated or non-functional proteins. Gentamicin could induce readthrough of nonsense mutations and enable the synthesis of full-length proteins. We focus on previous publications on topical application of gentamicin and review its utility in genetic skin diseases. DATA SOURCES: We search the MEDLINE through PubMed, EMBASE databases, and the Clinical Trials Registry Platform from January 1960 to July 2020 using the key search terms "gentamicin, topical gentamicin, genodermatosis, genetic skin diseases". RESULTS: The application of gentamicin in genodermatosis yielded promising results, both in vivo and in vitro, including Nagashima-type palmoplantar keratosis, epidermolysis bullosa, Hailey-Hailey disease, hereditary hypotrichosis simplex of the scalp, etc. CONCLUSIONS: Topical gentamicin is a potential treatment option for genodermatosis caused by nonsense mutation.

An InR/mir-9a/NlUbx regulatory cascade regulates wing diphenism in brown planthoppers.

Wing polymorphism significantly contributes to the ecological success of some insect species. For example, the brown planthopper (BPH) Nilaparvata lugens, which is one of the most destructive rice pests in Asia, can develop into either highly mobile long-winged or highly fecund short-winged adult morphs. A recent study reported a highly provocative result that the Hox gene Ultrabithorax (Ubx) is expressed in BPH forewings and showed that this wing development gene is differentially expressed in nymphs that develop into long-winged versus short-winged morphs. Here, we found that Ubx may be a mir-9a target, and used dual luciferase reporter assays and injected micro RNA (miRNA) mimics and inhibitors to confirm the interactions between mir-9a and NlUbx. We measured the mir-9a and NlUbx expression profiles in nymphs and found that the expression of these two biomolecules was negatively correlated. By rearing BPH nymphs on host rice plants with different nutritional status, we were able to characterize a regulatory cascade between insulin receptor genes, mir-9a, and NlUbx that regulate wing length in BPHs. When host quality was low, NlInR1 expression in the nymph terga increased and NlInR2 expression decreased; this led to a higher mir-9a level, which in turn reduced the NlUbx transcript level and ultimately resulted in longer wing lengths. Beyond extending our understanding of the interplay between host plant status and genetic events that modulate polymorphism, we demonstrated both the upstream signal and miRNA-based regulatory mechanism that control Ubx expression in BPH forewings.

Time-dependent stress evidence in dynamic allocation of physiological metabolism of Nilaparvata lugens in response to elevated CO2.

To assess the time-dependent stress evidence in dynamic allocation of physiological metabolism of Nilaparvata lugens nymphs in response to elevated CO2, we measured the time-dependent allocation of nutrient compositions and physiological metabolism in the bodies of N. lugens at 1h, 4h and 12h under elevated CO2. Elevated CO2 significantly increased the contents of nutrient compositions (protein, glucose and total amino acids) and catalase (CAT) enzyme activity in the body of N. lugens at 12h relative to 1h and 4h (P < 0.05). Significantly higher genes expression levels of acetylcholinesterase (AChE), heat shock protein (HSP70) and vitellogenin gene (vg) were observed in the body of N. lugens compared with those in ambient CO2 at 4h (P < 0.05). These results showed that there was an instantaneous reaction of N. lugens nymphs to elevated CO2, which indicated N. lugens may enhance stress defense response to future increasing CO2 levels.

The effect of taste and taste perception on satiation/satiety: a review.

As the prevalence of being overweight and obesity has increased worldwide, there is an increasing concern about satiation/satiety that can be achieved by eating. The ability of an individual to perceive tastes in the mouth is believed to be one of the many factors that influence food intake; the taste may affect appetite regulation and energy intake, playing an important role in promoting satiation/satiety. Satiation/satiety is actually induced by food and may be related to physiological and psychological factors such as several basic tastes, the exposure time of the taste and the cognition of different groups and individuals. This paper reviews the mechanism by which taste regulates satiation/satiety and demonstrates how taste and the taste perception of food prompt the brain to send satiation/satiety signals. Existing problems in taste and satiation/satiety and the prospective application of related research in the food industry are addressed, providing a scientific basis and theoretical guidance for the development and utilization of satiation/satiety from the perspective of taste.

Application of vacuum-ultraviolet (VUV) for phenolic homologues removal in humic acid solution: Efficiency, pathway and DFT calculation.

Vacuum-ultraviolet (VUV) photo-initiated oxidation of phenolic homologues in simulative natural water were investigated, including phenol, o-dihydroxybenzene (ODB), m-dihydroxybenzene (MDB), p-dihydroxybenzene (PDB), paranitrophenol (PNP) and o-chlorophenol (OCP). Results showed the phenolic homologues removal rate reached at least 90% in pure water, which was dependent on temperature, pH, concentration of HA, and functional group of HA. Experimental results indicated that 0.2 mg/L HA might be a critical point. Additionally, the rate constant of the six phenolic homologues reduced by 76.85%, 77.81%, 71.91%, 79.15%, and 55.69%, respectively in the MDB solution, and 79.73%, 82.80%, 95.36%, 80.38%, and 92.64%, respectively in the benzoic acid (BA) solution, compared to the rate constant in pure water. Moreover, quantum chemistry calculation indicated that the variances between phenolic compounds in removal rate were attributed to the substituent on the benzene ring. And, to some extent, the carboxy group of HA was supposed to arose the suppression for phenolic homologues removal rate. Mechanism involved phenolic homologues degradation using vacuum-ultraviolet (VUV) was summarized, where it underwent the formation of quinone structures, ring opening, short-chain organic acid, even eventually the transformation into NO3- and Cl- of PNP and OCP.

Silver Nanoparticle Conjugated Star PCL-b-AMPs Copolymer as Nanocomposite Exhibits Efficient Antibacterial Properties.

The traditional antibiotics have specific intracellular targets and disinfect in chemical ways, and the drug-resistance induced by the antibiotics has grown into an emerging threat. It is urgent to call for novel strategies and antibacterial materials to control this situation. Herein, we report a class of silver-decorated nanocomposite AgNPs@PCL-b-AMPs as potent nanoantibiotic, constructed by ring-opening polymerization of the monomers ε-caprolactone, Z-Lys-N-carboxyanhydrides (NCAs), and Phe-NCAs, then decorated with AgNPs, and characterized by SEM, TEM, and DLS. The biological assays revealed that the nanocomposite possessed strong antibacterial efficacy against both Gram-positive and Gram-negative bacteria including clinical isolated bacteria MRSA, VRE, P. aeruginosa, and K. pneumonia, exhibiting a MIC value range in 2-8 µg/mL. Importantly, the S. aureus and P. aeruginosa treated with the nanocomposite did not show drug-resistance even after 21 passages. Also, in vivo anti-infective assays showed that the nanocomposite was able to effectively kill bacteria in the infected viscera of mice. The study of the sterilization mechanism showed that the nanocomposite exhibited a multimodal antimicrobial mechanism, including irreversibly damaging the membrane structure, making the leakage of intracellular ions and subsequently inducing generation of the reactive oxygen species (ROS), ultimately sterilizing the bacteria. The nanocomposite exhibits effective broad-spectrum antibacterial properties and shows low toxicity to the mammalian cells/animal. Overall, the AgNPs@PCL-b-AMPs gained in this work show great potential as a highly promising antibacterial material for biomedical applications including drug-resistant bacterial infection.

Molecular Aggregation of Naphthalene Diimide(NDI) Derivatives in Electron Transport Layers of Inverted Perovskite Solar Cells and Their Influence on the Device Performance.

One of key factors to design applicable electron transport layers (ETLs) for perovskite solar cells is the morphology of ETLs since a good morphology would help to facilitate the carrier transport at two interfaces (perovskite\ETL and ETL\cathode). However, one drawback of most organic ETL small molecules is the internal undesired accumulation, which would cause the formation of inappropriate morphology and rough ETL surface. Here, by elaborately designing the side chains of NDI derivatives, the molecular interaction could be modified to achieve the aggregation in different degrees, which would eventually affect the accumulation of molecules and surface qualities of ETLs. By speculating from the comparison between the absorption spectra of solutions and films, the sequence of extent of molecule interaction and aggregation was built among three NDI derivatives, which is further confirmed by direct evidence of atomic force microscopy (AFM) images. Then, carrier exaction abilities are simply studied by steady-state photoluminescence spectroscopy. The carrier transport process is also discussed based on cyclic voltammetry, time-resolved photoluminescence spectroscopy and mobility. NDIF1 are proven to have the appropriate internal aggregation to smooth the contact with cathode and low series resistance, and a device performance of 15.6 % is achieved. With the ability of preventing the thermal diffusion of Ag towards the perovskite surface due to the strong interaction between molecules, NDIF2 at high concentration shows the highest fill factor (80 %).