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Gas hydrates usually contain a certain number of empty cages that will both affect the hydrate stability and reduce the gas storage capacity. In this work, by MD simulations, we found that the hydrate stability is related to the cage occupancy, the empty cage types, and especially the distribution of empty cages. With the decrease of overall occupancy, the stability of hydrate becomes worse. Under the same overall occupancy, the more concentrated the empty cages are, the more unstable the hydrate is and hence the faster it decomposes. The methane molecules may migrate between distorted cages during the decomposition, resulting in a temporary increase in the stability of hydrate. Hydrates with different empty cage distributions show different decomposition mechanisms: when empty cages are concentrated, the melting rate is fast first due to the rapid decomposition of empty cages, but the remaining filled cages will reduce the melting rate; when empty cages are separated on the contrary, the early melting is slow because of the high local occupancy, and the following melting will be accelerated because of the high melting surface area. It indicates that the empty cage distribution plays a controlling role in hydrate decomposition kinetics at different stages.

Dysregulated NLRP3 inflammasome activity results in uncontrolled inflammation, which is the basis of many chronic diseases. Although the regulatory mechanism has been gradually clarified after a long period of research, the metabolic regulation of NLRP3 inflammasome is still a mystery. Here, we find that ALDOA, as a monitor of glycolysis, regulates NLRP3 inflammasome by sensing changes in glycolytic flux to participate in the formation of AXIN-based AMPK-activation complex on the lysosomal surface. In this process, ALDOA restricts PRKN/parkin-dependent mitophagy through controlling AMPK activation to maintain mitochondrial damage caused by NLRP3 agonists. Furthermore, ALDOA also regulates the transcription of SQSTM1/p62, a receptor for mitophagy, through AMPK-FOXO3 signaling. In addition to studying the mechanism by which ALDOA regulated NLRP3 inflammasome, we also screened ALDOA inhibitors and found that LYG-202, a synthetic flavonoid compound, inhibited ALDOA enzyme activity by occupying the position involved in Schiff base intermediate formation, thus preventing FBP from combining with ALDOA. In vitro, LYG-202 suppressed NLRP3 inflammasome via activating the AMPK-mitophagy signaling pathway. In vivo, LYG-202 attenuated sterile inflammation and fulminant hepatitis, and suppressed the activation of NLRP3 inflammasome activation. Therefore, our study demonstrated that the glycolytic enzyme ALDOA maintained NLRP3 inflammasome activation by monitoring the glycolytic flux to control AMPK activation during the classical activation of NLRP3. ABBREVIATIONS: ALDOA: aldolase A; AMPK: AMP-activated protein kinase; ATG: autophagy related; ATG5: autophagy related 5; ATP: adenosine triphosphate; BMDMs: bone marrow-derived macrophages; CALCOCO2: calcium binding and coiled-coil domain 2; CASP1: caspase 1; CQ: chloroquine; FOXO3: forkhead box O3; IL1B: interleukin 1 beta; LPS: lipopolysaccharide; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MT: mutant; mtDNA: mitochondrial DNA; MTORC1: mechanistic target of rapamycin kinase complex 1; mtROS: mitochondrial reactive oxygen species; NLRP3: NLR family, pyrin domain containing 3; OPTN: optineurin; PBS: phosphate-buffered saline; PRKN/Parkin: parkin RBR E3 ubiquitin protein ligase; SN: supernatant; SQSTM1/p62: sequestosome 1; STK11/LKB1: serine/threonine kinase 11; TOMM20: translocase of outer mitochondrial membrane 20; ULK1: unc-51 like autophagy activating kinase 1; v-ATPase: vacuolar type H+-ATPase; WT: wild-type.

Dietary fiber intake helps to maintain gut homeostasis. Fiber deficiency causes commensals to utilize mucins as an energy source to destroy mucus layer, thus promoting susceptibility to inflammatory bowel disease. Here, we reported that oroxylin A, a natural flavonoid, ameliorated low-grade colonic inflammation caused by fiber deficiency, alleviated colitis, and further prevented colitis-associated colon cancer in mice. The anti-inflammatory effect of oroxylin A was due to its alteration of gut microbiota. We found that the levels of Eubacterium coprostanoligenes was significantly increased by oroxylin A and the colonized Eubacterium coprostanoligenes significantly protected against colitis and carcinogenesis in colon of mice. Together, our results in this study suggest that oroxylin A may reduce the susceptibility to intestinal diseases by increasing the level of Eubacterium coprostanoligenes which could provide a therapeutic alternation for the treatment of intestinal diseases.

Liver fibrosis is an important risk factor for progression from chronic liver injury to hepatocellular carcinoma. Clinically, there is a serious lack of therapeutic drugs for liver fibrosis. Previous studies have confirmed that GL-V9, a new synthesized flavonoid derivative, exhibits anti-inflammatory activity, but whether it has anti-hepatic fibrosis remains unclear. This study aims to investigate the anti-fibrotic activities and potential mechanisms of GL-V9.Bile duct ligation (BDL) and carbon tetrachloride (CClGL-V9 attenuated hepatic histopathological injury, collagen accumulation and decreased the expression of fibrotic genes in vivo. In vitro, GL-V9 promoted senescence and inhibited the expression of fibrogenic genes in HSCs. Mechanistic studies revealed that GL-V9 induced senescence by upregulating GATA4 expression in HSCs. Further studies confirmed that GL-V9 stabilized GATA4 by promoting autophagic degradation of P62.GL-V9 exerted potent anti-fibrotic effect both in vivo and in vitro by stabilizing GATA4, thereby promoting the senescence of HSCs, avoiding its activation and ultimately inhibiting liver fibrosis. This indicated that the flavonoid GL-V9 is a potential therapeutic candidate for the treatment of liver fibrosis.

The expression of GGCT (γ-glutamyl cyclotransferase) is upregulated in various human cancers. γ-glutamyl cyclotransferase enzyme activity was originally purified from human red blood cells (RBCs), but the physiological function of GGCT in RBCs is still not clear. Here we reported that Ggct deletion in mice leads to splenomegaly and progressive anaemia phenotypes, due to elevated oxidative damage and the shortened life span of Ggct-/- RBCs. Ggct-/- RBCs have increased reactive oxygen species (ROS), and are more sensitive to H2 O2 -induced damage compared to control RBCs. Glutathione (GSH) and GSH synthesis precursor l-cysteine are decreased in Ggct-/- RBCs. Our study suggests a critical function of Ggct in RBC redox balance and life span maintenance through regulating GSH metabolism.

Single-cell profiling methods are developed to dissect heterogeneity of cell populations. Recently, multiple enzymatic or chemical treatments have been integrated into single-cell multi-omics profiling methods with high compatibility. These methods have been verified to identify rare or new cell types with high confidence. Single-cell multi-omics analysis can also provide tools to solve the complex regulatory network associated with genome coding, epigenome regulation, and transcripotome expression in a single cell. However, acquiring high-quality single-cell data still faces inherent technical challenges, and co-assays with some other layers of cell identify such as transcription factors binding, histone modifications etc., profiles need new technological breakthroughs to facilitate a more thorough understanding of a single cell. In this review, we summarize the recent advances of single-cell multi-omics methods and discuss the challenges and opportunities in this filed., Single-cell multi-omics profiling methods are developed to dissect heterogeneity of cell populations.

A series of Tm3+/Dy3+ co-doped Ba3LaNa(PO4)3F (BLNPF) phosphors were synthesized successfully via a high-temperature solid-reaction, and luminescence properties were investigated. Upon near violet excitation, BLNPF:Tm3+, Dy3+ phosphors exhibit Tm3+:1D2-3F4 and Dy3+:4F9/2-6HJ (J⬰=⬰15/2, 13/2, 11/2) transitions with different luminescence intensity. The emitting color of the obtained products was found to shift from blue to white as a result of efficient energy transfer (ET) from Tm3+ to Dy3+ ions. According to photoluminescence emission intensity, the positive effect of activator on ET efficiency was calculated and the maximum ET efficiency was found around 72.6% with Dy3+ concentration was 0.04. By means of Dexter⬢s theoretical model, furthermore, dipole-dipole interaction was confirmed as the mechanism of energy transfer from Tm3+ to Dy3+ ions. The results suggested that BLNPF:Tm3+, Dy3+ phosphor might be a promising single-phased white-light-emitting phosphor for UV white-light LED.

Objective. Ureteropelvic junction obstruction (UPJO) represents to a leading cause of fetal hydronephrosis, which is associated with urinary tract infection (UTI) and urinary stone disease. This study is aimed at investigating risk factors of UTI in pediatric patients with UPJO after primary unilateral pyeloplasty. Methods. The records of a consecutive series of patients undergoing primary pyeloplasty at a single institution between June 2015 and November 2021 were retrospectively reviewed. Demographic and clinical characteristics, including age, gender, weight, height, body mass index (BMI), creatinine (Cr), blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), neutrophil ratio, lymphocyte ratio, neutrophil/lymphocyte ratio, renal pelvis anteroposterior diameter (APD), renal cortex thickness, caliectasis, open or laparoscopic pyeloplasty, and internal drainage or external drainage, were collected and analyzed. The incidence of postoperative UTI and its risk factors was analyzed. Results. A total of 504 patients were enrolled in the study, and they were classified into the UTI group ( n = 188 ) and non-UTI group ( n = 361 ). Univariate analysis of the incidence of UTI revealed that age, gender, weight, height, BMI, surgical modality, Cr level, BUN level, neutrophil ratio, lymphocyte ratio and neutrophil/lymphocyte ratio, renal cortex thickness, and postoperative drainage modality were associated with UTI incidence after pyeloplasty in pediatric patients with UPJO. Multivariate analysis revealed that male gender, weight < 11.5 (kg), height < 83 (cm), BMI < 17.09 , BUN > 4.08 (mmol/L), and internal drainage were risk factors of postoperative UTI in pediatric patients with UPJO. Conclusion. Our study demonstrated that male gender, weight < 11.5 (kg), height < 83 (cm), BMI < 17.09 , BUN > 4.08 (mmol/L), and internal drainage were risk factors of UTI in pediatric patients with UPJO after primary unilateral pyeloplasty, which may provide reference for prophylactic antibiotics for those patients with risk factors.

The decomposition process of methane hydrate in pure water and methanol aqueous solution was studied by molecular dynamics simulation. The effects of temperature and pressure on hydrate structure and decomposition rate are discussed. The results show that decreasing pressure and increasing temperature can significantly enhance the decomposition rate of hydrate. After adding a small amount of methanol molecules, bubbles with a diameter of about 2 nm are formed, and the methanol molecules are mainly distributed at the gas-liquid interface, which greatly accelerates the decomposition rate and gas-liquid separation efficiency. The radial distribution function and sequence parameter analysis show that the water molecules of the undecomposed hydrate with ordered ice-like configuration at a temperature of 275 K evolve gradually into a long-range disordered liquid structure in the dynamic relaxation process. It was found that at temperatures above 280 K and pressures between 10 atm and 100 atm, the pressure has no significant effect on hydrate decomposition rate, but when the pressure is reduced to 1 atm, the decomposition rate increases sharply. These findings provided a theoretical insight for the industrial exploitation of hydrates.

Electrolyte solution can effectively inhibit the formation of hydrate. In this work, molecular dynamics simulations of hydrate nucleation and growth in aqueous NaCl solutions were performed to study the effect of ions on hydrate formation. We found that the electrolyte ions can inhibit hydrate formation on both the nucleation and the growth stage. Hydrates prefer nucleation in a region with low ionic concentration because the availability of water molecules in the ionized hydration layer is reduced. The slight change in orientation distribution of water around methane molecules in a NaCl solution system may be another factor to inhibit nucleation. The induction time is approximately proportional to the ionic strength, indicating that the charge has a more obvious inhibitory effect on hydrate formation. In hydrate growth stage, ions are excluded from the hydrate phase and a certain amount of free water molecules exist around the hydrate cluster. The ions near the hydrate can reduce its growth rate, causing a higher crystallinity of hydrate formed in salt solution. Finally, a dual influence of the ions on methane mass transfer was found to be that the ions increase the apparent concentration of methane to facilitate nucleation, but inhibit their diffusion at the same time.

The inclusion complex of avobenzone and (2-hydroxy)propyl-β-cyclodextrin (2-HP-β-CD) was prepared successfully. The effects of the inclusion behavior of avobenzone with 2-HP-β-CD were investigated in both solution and the solid state with the following methods: UV–vis spectrophotometry (UV–vis), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TG), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM), proton nuclear magnetic resonance (1H-NMR) and two-dimensional rotational frame nuclear overhauser effect spectroscopy (2D ROESY). The photostability of avobenzone and its inclusion complex were both investigated by UV–vis spectrophotometry. The Benesi-Hildebrand’s method showed that avobenzone formed 1:2 stoichiometric inclusion complex with 2-HP-β-CD. The solubility, thermal stability and the photostability of avobenzone were all improved after encapsulating by the 2-HP-β-CD. Therefore, it can be a potentially promising way to promote its cosmetic preparations in UVA sunscreen.

We describe here the results from the testing of a small molecule first-in-class apolipoprotein E4 (ApoE4)-targeted sirtuin1 (SirT1) enhancer, A03, that increases the levels of the neuroprotective enzyme SirT1 while not affecting levels of neurotoxic sirtuin 2 (SirT2) in vitro in ApoE4-transfected cells. A03 was identified by high-throughput screening (HTS) and found to be orally bioavailable and brain penetrant. In vivo, A03 treatment increased SirT1 levels in the hippocampus of 5XFAD-ApoE4 (E4FAD) Alzheimer’s disease (AD) model mice and elicited cognitive improvement while inducing no observed toxicity. We were able to resolve the enantiomers of A03 and show using in vitro models that the L-enantiomer was more potent than the corresponding D-enantiomer in increasing SirT1 levels. ApoE4 expression has been shown to decrease the level of the NAD-dependent deacetylase and major longevity determinant SirT1 in brain tissue and serum of AD patients as compared to normal controls. A deficiency in SirT1 level has been recently implicated in increased tau acetylation, a dominant post-translational modification and key pathological event in AD and tauopathies. Therefore, as a novel approach to therapeutic development for AD, we targeted identification of compounds that enhance and normalize brain SirT1 levels.

Cucumis melo L. var. agrestis Naud., commonly known as ‘Field Muskmelon,’ is an annual invasive weed in many parts of China. However, there is very little available information about the chloroplast genome of this species. Here, we first report and characterize its complete chloroplast genome sequence based on Illumina paired-end sequencing data. The complete plastid genome was 155,402 bp, which contained inverted repeats (IR) of 25,514 bp separated by a large single-copy (LSC) and a small single copy (SSC) of 86,287 bp and 18,087 bp, respectively. The complete chloroplast genome contains 133 genes, comprising 87 protein-coding genes, 37 tRNA genes, 8 rRNA genes and 1 pseudogene. The overall GC content of the plastome is 36.9%. The phylogenetic analysis of 16 selected chloroplast genomes demonstrated that C. melo var. agrestis Naud was close to congeneric species C. xhytivus.

5-Hydroxymethylcytosine (5hmC) is an important epigenetic mark that regulates gene expression. Charting the landscape of 5hmC in human tissues is fundamental to understanding its regulatory functions. Here, we systematically profiled the whole-genome 5hmC landscape at single-base resolution for 19 types of human tissues. We found that 5hmC preferentially decorates gene bodies and outperforms gene body 5mC in reflecting gene expression. Approximately one-third of 5hmC peaks are tissue-specific differentially-hydroxymethylated regions (tsDhMRs), which are deposited in regions that potentially regulate the expression of nearby tissue-specific functional genes. In addition, tsDhMRs are enriched with tissue-specific transcription factors and may rewire tissue-specific gene expression networks. Moreover, tsDhMRs are associated with single-nucleotide polymorphisms identified by genome-wide association studies and are linked to tissue-specific phenotypes and diseases. Collectively, our results show the tissue-specific 5hmC landscape of the human genome and demonstrate that 5hmC serves as a fundamental regulatory element affecting tissue-specific gene expression programs and functions., Charting the landscape of 5hmC in human tissues is fundamental to understanding its regulatory functions. Here, we systematically profiled the whole-genome 5hmC landscape at single-base resolution for 19 types of human tissues and found 5hmC shows tissue-specific patterns.

The synthesized Ca9La(PO4)7:Dy3+,Eu3+(CLPO:Dy3+,Eu3+) phosphors were analyzed by phase structure, optical performance, thermal stability and lifetime. The XRD pattern indicated that both the matrix and rare earth ion-doped phosphors were pure phases, and the crystal structure was confirmed as trigonal system. Upon 351 nm excitation, Dy3+-doped CLPO phosphors performed two strong emission peaks at 481 nm and 573 nm. The energy transfer phenomenon from Dy3+ to Eu3+ can be found in the Dy3+, Eu3+ co-doped CLPO phosphors, and the color was tuned from red to blue upon 395 nm excitation with Eu3+ concentration decreasing. The energy transfer characteristic was evidenced by the excitation spectra, emission spectrum and decay time of the synthesized phosphors, and the mechanism of energy transfer from Dy3+ to Eu3+ was evaluated as a dipole–quadrupole interaction. In addition, temperature-dependent spectra were performed and the activation energy was further evaluated about 0.1902 eV. The results indicate the potential application of CLPO:Dy3+,Eu3+ phosphors in white LEDs.

Emerging evidence suggests that oroxylin A exhibits antitumor effects by inducing cell apoptosis. However, the involved molecular mechanisms have not been elucidated. Here we report that the apoptosis induced by oroxylin A was dependent on p62-mediated activation of caspase-8 in hepatocellular carcinoma cells. Furthermore, oroxylin A also caused p62/SQSTM1 proteolysis at Asp329 by activating caspase-8. Further studies confirm that mutation in p62 (D329H and D329G) was resistant to oroxylin A-mediated p62 cleavage and apoptosis. Due to the absence of the KIR domain that interacts with Keap1, the cleaved p62 reduced the stability of Nrf2, thereby causing oxidative stress and increasing ROS levels. In vivo, p62 similarly contributed to oroxylin A-exerted antitumor effect in xenograft model inoculated SMMC-7721 tumor. In conclusion, our findings indicated that oroxylin A triggered apoptosis through caspase-8 activation and p62/SQSTM1 proteolysis. Keywords: Oroxylin A, Apoptosis, Caspase-8, p62/SQSTM1, Proteolysis

The effect of temperature on CO2 uptake behavior of dry salt water was investigated by kinetics measurements and molecular dynamics simulations. The gas uptake capacity was found to be dramatically decreased at 279 K by the direct cooling adsorption procedure. By means of simulations, it was realized that the orientation of water and the hydrogen bond network structure near the silica surface are sensitive to temperature. With the temperature decreased, the water layer becomes local-structured by forming more hydrogen bonds, facilitating the capture of CO2 by forming the hydrate precursor easily. The change of the structure is irreversible once the CO2 uptake process occurred; hence, the gas uptake can carry on continuously even if the temperature rises. A cooling stimulation procedure was found to efficiently trigger the gas uptake process at temperatures higher than 279 K. By using this method, gas adsorption can be induced because the energy barrier of nucleation is reduced. This technology can save a ...

High-resolution detection of genome-wide 5-hydroxymethylcytosine (5hmC) sites of small-scale samples remains challenging. Here, we present hmC-CATCH, a bisulfite-free, base-resolution method for the genome-wide detection of 5hmC. hmC-CATCH is based on selective 5hmC oxidation, chemical labeling and subsequent C-to-T transition during PCR. Requiring only nanoscale input genomic DNA samples, hmC-CATCH enabled us to detect genome-wide hydroxymethylome of human embryonic stem cells in a cost-effective manner. Further application of hmC-CATCH to cell-free DNA (cfDNA) of healthy donors and cancer patients revealed base-resolution hydroxymethylome in the human cfDNA for the first time. We anticipate that our chemical biology approach will find broad applications in hydroxymethylome analysis of limited biological and clinical samples.

Decreasing bone marrow (BM) microvessel density and circulating angiogenic cytokine levels are promising strategies for the treatment of relapsed and resistant acute myeloid leukemia (AML). Previous studies have reported that wogonoside could inhibit the progression of AML and suppress angiogenesis in a solid tumor, but the correlation of these two effects was ignored. In this research, we determined whether wogonoside could inhibit angiogenesis in this hematologic malignancy. We found that wogonoside could inhibit tumor growth and progression, and prolong the survival of nude mice inoculated with U937/MDR. Besides, reducing BM angiogenesis might cause therapeutic effect against resistant AML. Therefore, coculture between AML cells and BM stromal cells was established to imitate their crosstalk. Then, the effect of wogonoside on BM angiogenesis was tested in vitro and in vivo. We found that wogonoside could suppress microvessel formation in the chicken chorioallantoic membrane assay model and matrigel plug assay. The mechanism research revealed that wogonoside could block the JAK2-STAT3 pathway in AML cells and stromal cells to break their positive feedback. We detected several cytokines related to AML or angiogenesis and found that secreted interleukin-8 was a significant angiogenic cytokine to induce BM angiogenesis. These findings supported that new diagnostics and promising treatment strategies could be developed in relapsed and resistant AML patients.

Cyclodextrins (CD) solutions were mixed with hydrophobic SiO2 powders to form a dry-cyclodextrin-water (DCD) emulsion, and the effects of CDs with different concentrations and structures on gas adsorption kinetics were investigated, respectively. α-CD was found to enhance effectively both CH4 and CO2 gases adsorption capacity of DCD, while β-CD was generally negative to guest gas adsorption with one exception related to CH4 under lower concentration. Through analyzing dual interfacial effect of gas inclusion, the dominant competition between gas hydration and gas inclusion was speculated as the main reason for the different CD concentration dependence for CH4 and CO2 adsorption kinetics. Furthermore, based on considering the cooperative control of gas diffusion, hydration reaction, inclusion reaction and inclusion sedimentation, a diffusion-reaction-blocking model was suggested to describe the kinetic process. CH4 gases were found to prefer to exist in DCD with free form, while CO2 gases with adsorption form mainly. The selectiveness closely related to guest gas further illustrated the ‘CD concentration quenching’ appearing in CO2 adsorption rather than CH4 adsorption.

The inclusion complexes of trans-polydatin and three cyclodextrins (CDs), namely β-cyclodextrin (β-CD), methyl-β-cyclodextrin (Me-β-CD) and (2-hydroxy) propyl-β-cyclodextrin (HP-β-CD) were prepared. The effects of the inclusion behavior of trans-polydatin with three kinds of CDs were investigated in both solution and the solid state with the following methods: phase-solubility, X-ray diffraction (XRD), thermogravimetric analysis (TG), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM), proton nuclear magnetic resonance (1H-NMR) and two-dimensional rotational frame nuclear overhauser effect spectroscopy (2D ROESY). The results indicated that trans-polydatin formed a 1 : 1 stoichiometric inclusion complex with CDs. Meanwhile, the solubility and thermal stability of the inclusion complexes were improved after encapsulating by CDs. Furthermore, the photostability of trans-polydatin was enhanced after forming the inclusion complexes. The antioxidant activities results showed that the antioxidant performance of the inclusion complexes was enhanced in comparison to the native trans-polydatin. Therefore, it can be a potentially promising way to promote its drug bioavailability or phytochemical preparations.

The use of sunscreen is recently growing and their efficacy and safety must be taken into account since they are applied on the skin frequently. In this work, an organic ultraviolet (UV) ray absorbent, cinnamic acid (CA) was intercalated into Zn-Ti layered double hydroxide (LDH) by anion-exchange reaction. ZnTi-CA-LDH, a new type of host-guest UV-blocking material has been synthesized. Detailed structural and surface morphology of ZnTi-CA-LDH were characterized by XRD, FT-IR, SEM and TEM. ZnTi-CA-LDH exhibits a superior UV blocking ability compared to pure CA and ZnTi-CO3-LDH. The thermal stability of the intercalated ZnTi-CA-LDH was investigated by TG-DTA, which showed that the thermostability of CA was markedly enhanced after intercalation into ZnTi-CO3-LDH. The EPR data showed greatly decreased photocatalytic activity compared to common inorganic UV blocking agents TiO2 and ZnO. Furthermore, the sample was formulated in a sunscreen cream to study the matrix protective effect towards UV rays.

ZnTi-layered double hydroxides (LDHs) with varying Zn/Ti ratio have been synthesized by coprecipitation of zinc and titanium salts from homogeneous solution. The obtained ZnTi-LDHs possess high crystallinity and hierarchical structure with improved UV-absorbance property. The UV–vis spectra show that the UV absorbing properties of ZnTi-LDHs is stronger and broader than both MgAl-LDH and ZnAl-LDH due to the existence of Ti. Moreover, the UV absorption property increased with the content of Ti, which can be ascribed to the decrease in the band gap energy, as clearly confirmed by density functional theory calculations. When irradiated by UV rays, the property of the samples with generated free radicals (OH and O2−) was evaluated by means of electron spin resonance (EPR). ZnTi-LDHs generated a relatively lower active radicals in contrast with TiO2 and ZnO, which implied an increased safety used as sunscreens. Therefore, this work provides a detailed understanding of UV shielding properties of ZnTi-LDHs which was unrevealed previously, and demonstrates the expansive application prospects of ZnTi-LDHs in the field of sunscreens.

Two kinds of dry water (DW) particles are prepared by mixing water and hydrophobic silica particles with nanometer or micrometer dimensions, and the two DW particles are found to have similar size distributions regardless of the size of the silica shell. The CO2 uptake kinetics of DW with nanometer (nanoshell) and micrometer shells (microshell) are measured, and both uptake rate and capacity show the obvious size effect of the silica shell. The DW with a microshell possesses a larger uptake capacity, whereas the DW with a nanoshell has a faster uptake rate. By comparing the uptake kinetics of soluble NH3 and CO2 further, we found that the microshell enhances the stability and the dispersion degree of DW and the nanoshell offers a shorter path for the transit of guest gas into the water core. Furthermore, molecular dynamics simulation is introduced to illustrate the nanosize effect of the silica shell on the initial step of the gas uptake. It is found that the concentration of gas molecules close to the silica shell is higher than that in the bulk water core. With the increase in the size of the silica shell, the amount of CO2 in the silica shell decreases, and it is easier for the gas uptake to reach steady state.

Juvenile myoclonic epilepsy (JME), the most common genetic epilepsy, remains enigmatic because it is considered one disease instead of several diseases. We ascertained three large multigenerational/multiplex JME pedigrees from Honduras with differing JME subsyndromes, including Childhood Absence Epilepsy evolving to JME (CAE/JME; pedigree 1), JME with adolescent onset pyknoleptic absence (JME/pA; pedigree 2), and classic JME (cJME; pedigree 3). All phenotypes were validated, including symptomatic persons with various epilepsies, asymptomatic persons with EEG 3.5–6.0 Hz polyspike waves, and asymptomatic persons with normal EEGs. Two‐point parametric linkage analyses were performed with 5185 single‐nucleotide polymorphisms on individual pedigrees and pooled pedigrees using four diagnostic models based on epilepsy/EEG diagnoses. Haplotype analyses of the entire genome were also performed for each individual. In pedigree 1, haplotyping identified a 34 cM region in 2q21.2–q31.1 cosegregating with all affected members, an area close to 2q14.3 identified by linkage (Z max = 1.77; pedigree 1). In pedigree 2, linkage and haplotyping identified a 44 cM cosegregating region in 13q13.3–q31.2 (Z max = 3.50 at 13q31.1; pooled pedigrees). In pedigree 3, haplotyping identified a 6 cM cosegregating region in 17q12. Possible cosegregation was also identified in 13q14.2 and 1q32 in pedigree 3, although this could not be definitively confirmed due to the presence of uninformative markers in key individuals. Differing chromosome regions identified in specific JME subsyndromes may contain separate JME disease‐causing genes, favoring the concept of JME as several distinct diseases. Whole‐exome sequencing will likely identify a CAE/JME gene in 2q21.2–2q31.1, a JME/pA gene in 13q13.3–q31.2, and a cJME gene in 17q12.

Elastic materials are candidates for process intensification of gas storage by forming gas hydrate. In this work, molecular dynamics simulations of hydrate nucleation in elastic silica double layers were performed to study the effect of elastic confined spaces on hydrate formation. It is found that in narrow confined spaces, hexagonal rings dominated the hydrogen bond network of water molecules established rapidly by a multisite nucleation mechanism. With molecules added, a bilayer water structure was formed finally because elastic space can adapt the volume expansion. In medium and wide confined spaces, hydrates were formed from a series of "pseudo cages" which are considered as precursors of complete hydrate cages. Moreover, the induction time for nucleation was a minimum when the elasticity of the silica layer changes: nucleation is fastest in the weak-elastic system. When the elasticity increases, it becomes hard to adapt the volume expansion during nucleation and also difficult to nucleate in very weak-elastic systems because of the fluctuation of the layers.

The inclusion complexes of

In juvenile myoclonic epilepsy, data are limited on the genetic basis of networks promoting convulsions with diffuse polyspikes on electroencephalography (EEG) and the subtle microscopic brain dysplasia called microdysgenesis.Using Sanger sequencing, we sequenced the exomes of six members of a large family affected with juvenile myoclonic epilepsy and confirmed cosegregation in all 37 family members. We screened an additional 310 patients with this disorder for variants on DNA melting-curve analysis and targeted real-time DNA sequencing of the gene encoding intestinal-cell kinase ( ICK). We calculated Bayesian logarithm of the odds (LOD) scores for cosegregating variants, odds ratios in case-control associations, and allele frequencies in the Genome Aggregation Database. We performed functional tests of the effects of variants on mitosis, apoptosis, and radial neuroblast migration in vitro and conducted video-EEG studies in mice lacking a copy of Ick.A variant, K305T (c.914A→C), cosegregated with epilepsy or polyspikes on EEG in 12 members of the family affected with juvenile myoclonic epilepsy. We identified 21 pathogenic ICK variants in 22 of 310 additional patients (7%). Four strongly linked variants (K220E, K305T, A615T, and R632X) impaired mitosis, cell-cycle exit, and radial neuroblast migration while promoting apoptosis. Tonic-clonic convulsions and polyspikes on EEG resembling seizures in human juvenile myoclonic epilepsy occurred more often in knockout heterozygous mice than in wild-type mice (P=0.02) during light sleep with isoflurane anesthesia.Our data provide evidence that heterozygous variants in ICK caused juvenile myoclonic epilepsy in 7% of the patients included in our analysis. Variant ICK affects cell processes that help explain microdysgenesis and polyspike networks observed on EEG in juvenile myoclonic epilepsy. (Funded by the National Institutes of Health and others.).

Tumor cells recruit vascular endothelial cells and circulating endothelial progenitor cells to form new vessels to support their own growth and metastasis. VEGF, PDGF-BB and FGF-2 are three major pro-angiogenic factors and applied to promote angiogenesis. In this research, we demonstrated that anlotinib, a potent multi-tyrosine kinases inhibitor (TKI), showed a significant inhibitory effect on VEGF/PDGF-BB/FGF-2-induced angiogenesis in vitro and in vivo. Wound healing assay, chamber directional migration assay and tube formation assay indicated that anlotinib inhibited VEGF/PDGF-BB/FGF-2-induced cell migration and formation of capillary-like tubes in endothelial cells. Furthermore, anlotinib suppressed blood vessels sprout and microvessel density in rat aortic ring assay and chicken chorioallantoic membrane (CAM) assay. Importantly, according to our study, the anti-angiogenic effect of anlotinib is superior to sunitinib, sorafenib and nintedanib, which are three main anti-angiogenesis drugs in clinic. Mechanistically, anlotinib inhibits the activation of VEGFR2, PDGFRβ and FGFR1 as well their common downstream ERK signaling. Therefore, anlotinib is a potential agent to inhibit angiogenesis and be applied to tumor therapy.

Macrophage polarization is involved in the process of inflammation. Regulation of macrophage polarization is considered to be an effective method for the treatment of various inflammatory diseases. In our study, we investigated the potential molecular mechanism of the flavonoid compound LZ205, which exhibits anti-inflammatory property. Results showed that LZ205 significantly reduced M1 macrophage-associated proinflammatory cytokines secretion by regulating PI3K/AKT/mTOR signaling pathway without affecting M2 macrophage-associated cytokines mRNA levels. In vivo studies showed that LZ205 significantly inhibited M1 macrophages polarization in DSS-induced colitis and alum-induced murine peritonitis. Consistent with in vitro studies, LZ205 significantly blocked expression of PI3K, p-AKT and p-mTOR in colon tissues and peritoneal macrophages. Taken together, LZ205 exerts anti-inflammatory effect by inhibiting M1 macrophage polarization via regulating PI3K/AKT/mTOR signaling pathway.

Dielectric spectra of 4A zeolite particles bulked in deionized water (4A/W) or cyclohexane (4A/C) were measured respectively under different temperatures, and two dielectric relaxations were found in both of 4A/W and 4A/C. Because of existence of water molecules in pores, both low and high frequency relaxation times (τLFR and τHFR) of 4A/W decreased more sharply than 4A/C with increasing temperature. According to the temperature dependence of τLFR and τHFR, the activation energies of Na+ interacting with framework under hydrated and dehydrated environments were calculated respectively, and the original properties of Na+ in dehydrated zeolite were obtained by analyzing the dielectric properties of 4A/C. Furthermore, a transient state of Na+ motion with temperature was found in 4A/C system.

The cycloaddition of epoxide and CO2 to synthesize cyclic carbonate catalyzed by VO(IV) porphyrin was achieved under 1.4 MPa at 150°C. The effects of reaction temperature, time, CO2 pressure, co-catalyst and porphyrin framework were investigated. The catalytic results showed that moderate to high yields of cyclic carbonates were obtained under the optimal reaction conditions. Copyright © 2015 John Wiley & Sons, Ltd.