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BACKGROUND: Non-recombining regions of the Y-chromosome recorded the evolutionary traces of male human populations and are inherited haplotype-dependently and male-specifically. Recent whole Y-chromosome sequencing studies have identified previously unrecognized population divergence, expansion and admixture processes, which promotes a better understanding and application of the observed patterns of Y-chromosome genetic diversity. RESULTS: Here, we developed one highest-resolution Y-chromosome single nucleotide polymorphism (Y-SNP) panel targeted for uniparental genealogy reconstruction and paternal biogeographical ancestry inference, which included 639 phylogenetically informative SNPs. We genotyped these loci in 1033 Chinese male individuals from 33 ethnolinguistically diverse populations and identified 256 terminal Y-chromosomal lineages with frequency ranging from 0.0010 (singleton) to 0.0687. We identified six dominant common founding lineages associated with different ethnolinguistic backgrounds, which included O2a2b1a1a1a1a1a1a1-M6539, O2a1b1a1a1a1a1a1-F17, O2a2b1a1a1a1a1b1a1b-MF15397, O2a2b2a1b1-A16609, O1b1a1a1a1b2a1a1-F2517, and O2a2b1a1a1a1a1a1-F155. The AMOVA and nucleotide diversity estimates revealed considerable differences and high genetic diversity among ethnolinguistically different populations. We constructed one representative phylogenetic tree among 33 studied populations based on the haplogroup frequency spectrum and sequence variations. Clustering patterns in principal component analysis and multidimensional scaling results showed a genetic differentiation between Tai-Kadai-speaking Li, Mongolic-speaking Mongolian, and other Sinitic-speaking Han Chinese populations. Phylogenetic topology inferred from the BEAST and Network relationships reconstructed from the popART further showed the founding lineages from culturally/linguistically diverse populations, such as C2a/C2b was dominant in Mongolian people and O1a/O1b was dominant in island Li people. We also identified many lineages shared by more than two ethnolinguistically different populations with a high proportion, suggesting their extensive admixture and migration history. CONCLUSIONS: Our findings indicated that our developed high-resolution Y-SNP panel included major dominant Y-lineages of Chinese populations from different ethnic groups and geographical regions, which can be used as the primary and powerful tool for forensic practice. We should emphasize the necessity and importance of whole sequencing of more ethnolinguistically different populations, which can help identify more unrecognized population-specific variations for the promotion of Y-chromosome-based forensic applications.
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Cromossomos Humanos Y , População do Leste Asiático , Polimorfismo de Nucleotídeo Único , Humanos , China , Cromossomos Humanos Y/genética , População do Leste Asiático/genética , Genética Populacional , Haplótipos , FilogeniaRESUMO
The extraction of salinity gradient energy in the capacitive mixing (CapMix) technique can be enhanced by using polyelectrolyte-coated electrodes. The micromechanism of polyelectrolyte (PE) coating enhancing the salinity energy extraction is studied by using a statistical thermodynamic theory. When PE takes same charge sign as the coated electrodes, the extraction efficiency can be boosted owing to the enhanced response of electrical double layer (EDL) to external cell voltage (V0). For the optimal case studied, the extraction efficiency was boosted from 0.25 to 1.25% by PE coatings. Owing to counterion adsorption and the enhanced response of EDL, the extraction energy density presented a local maximum at V0 = 0, which is higher than another local maximum value when V0 ≠ 0. This provides important guidance on the two approaches of CapMix in terms of capacitive Donnan potential (CDP, V0 = 0) and capacitive double-layer expansion (CDLE, V0 ≠ 0). Under the effects of PE coating, the extraction efficiency by CDLE can be improved to about 11% by CDP for the optimal studied case. The synergistic effect of grafting conditions can significantly elevate the energy density and extraction efficiency of the CDP process.
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Piperlongumine (1) increases reactive oxygen species (ROS) levels and induces apoptosis in cancer cells through various pathways. Nitric oxide (NO) donors have demonstrated potent anticancer activities with exogenous NO being oxidized by ROS in the tumor microenvironment to form highly reactive N-oxides (RNOS). This amplifies oxidative stress cascade reactions, ultimately inducing cancer cell apoptosis. To exploit this synergy, a series of NO-releasing piperlongumine derivatives (2-5) were designed and synthesized. These compounds were expected to release NO in cancer cells, simultaneously generating piperlongumine derivative fragments to enhance the anticancer effects. Compound 6, structurally similar to compounds 2-5 but not releasing NO, served as a control. Among these derivatives, compound 5 exhibited the most potent antiproliferative activity against HCT-116 cells and efficiently released NO in this cell line. Further investigation revealed that compound 5 inhibited colon cancer cell proliferation by modulating ß-catenin expression, which is a pivotal protein in the Wnt/ß-catenin signaling pathway. These findings highlight compound 5 as a promising candidate for colon cancer treatment targeting the Wnt/ß-catenin pathway.
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Neoplasias do Colo , Dioxolanos , Óxido Nítrico , Via de Sinalização Wnt , beta Catenina , Dioxolanos/farmacologia , Dioxolanos/química , Humanos , Óxido Nítrico/metabolismo , Neoplasias do Colo/tratamento farmacológico , beta Catenina/metabolismo , Estrutura Molecular , Via de Sinalização Wnt/efeitos dos fármacos , Células HCT116 , Apoptose/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Proliferação de Células/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Ensaios de Seleção de Medicamentos Antitumorais , PiperidonasRESUMO
The polysilicate aluminum ferric (PSAF) was synthesized via copolymerization of polysilicic acid (PSi), AlCl3 and FeCl3 for treating oily wastewater from Daqing gas field. This study investigated the effects of key preparation factors such as the degree of PSi's preactivation and the ratio of (Fe + Al)/Si and Al/Fe on both polymerization and coagulation performance exhibited by PSAF. To determine the optimal timing for introducing Al3+ and Fe3+, zeta potential, viscosity and particle size were investigated. Additionally, infrared spectroscopy, X-ray powder diffraction, polarizing microscopy and scanning electron microscope analysis were employed to investigate the structure and morphology of PSAF. The results indicate that under conditions characterized by a SiO2 mass fraction of 2.5% and pH = 4.5, an optimal timing for introducing Al3+ and Fe3+ is at 100 min when PSi exhibits moderate polymerization along with sufficient stability. When considering molar ratios such as (Al + Fe)/Si being 6:4 and Al/Fe being 5:5, respectively, PSAF falls within a "stable zone" enabling storage period up to 32 days. Moreover, Jar test results demonstrate that at a dosage of 200 mg/L PSAF for oily wastewater treatment in gas fields could reach the maximum turbidity removal efficiency up to 99.5% while oil removal efficiency reach 88.6% without pH adjustment. The copolymerization facilitates the formation of larger PSAF aggregates with positive potential, thereby augmenting the coagulants' adsorption bridging and charge neutralization capabilities. As a result, PSAF has great potential as a practical coagulant for treating oil-containing wastewater in industrial settings.
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Águas Residuárias , Purificação da Água , Alumínio/química , Dióxido de Silício , Polímeros , Ferro/química , Purificação da Água/métodos , Compostos Férricos/químicaRESUMO
In this work, we have analyzed the neuroprotective activity of marrubiin against MPTP-induced Parkinson's disease (PD) in rat brains. MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) a neurotoxin was administered intraperitoneally (i.p.,) to rats and then treated using marrubiin. After marrubiin treatment, rats were trained, and tested for behavioral analyses like cognitive performance, open field test, rotarod test, grip strength test, beam walking test, the status of body weight, and striatal levels of neurotransmitters like dopamine, norepinephrine, serotonin, DOPAC, homovanillic acid, 5-hydroxy indole acetic acid, the status of oxidative stress markers like LPO, protein carbonyl content (PCC), Xanthine oxidase (XO), and status of antioxidant enzyme levels like SOD, CAT, GPX in the striatum and hippocampal tissues, status of neuroinflammatory markers like TNF-α, IL1ß, IL-6, and status of histological architecture in brain striatum were also analyzed. All these parameters were significantly (p < 0.05) abnormal in MPTP-induced rats. Marrubiin (MB) treated shows significant (p < 0.05) near normal behavioral restoration in cognitive performance, open field, rotarod, grip strength, and beam walking tests. Furthermore, the status of body weight, and levels of neurotransmitters, were also significantly (p < 0.05) reversed to near normalcy in marrubiin-treated rats. Similarly, oxidative stress, antioxidant enzyme levels in the striatum and hippocampal tissues, TNF-α, IL1ß, IL-6 levels, and histological architecture were noted to be restored to near normalcy in marrubiin-treated rats. Collectively, our preliminary results highlight the neuroprotective ability of marrubiin. However, the cellular and biochemical mechanisms of marrubiin's neuroprotective ability have to be studied in detail.
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Cyclophosphamide (CP) is widely used in clinical fields. Beside its therapeutic effects, CP shows toxicity depending on dose and administration schedule. In this study, the urinary metabolic profiles were investigated in mice intraperitoneally injected with high-dose CP (150 mg/kg body weight) once a week over four weeks using nuclear magnetic resonance (NMR)-based metabolomics. Twenty-six metabolites were identified as potential biomarkers by multivariate statistical analysis. A decrease in isoleucine, alanine, N-acetylglutamic acid, proline, methionine, valine, phenylacetylglulamine, dimethylamine, hippurate, acetic acid, lactate, α-oxoglutarate, citrate, malonic acid, creatinine, niacin, ß-hydroxybutyrate, and betaine, whereas an increase in leucine, glutamate, glycine, taurine, phenylacetylglycine, glucose, creatine, and choline were observed in the urine of high-dose CP-treated mice. Metabolites related to amino acid metabolism, energy metabolism, and gut microbial metabolism were changed markedly in the urine. Further metabolic pathway analysis suggested that seven metabolic pathways, including alanine, aspartate, and glutamate metabolism, arginine biosynthesis, glyoxylate, and dicarboxylate metabolism, glycine, serine and threonine metabolism, d-glutamine and d-glutamate metabolism, arginine, and proline metabolism, citrate cycle, as well as the gut microbiota metabolism, were significantly involved in response to high-dose CP treatment. These findings help to predict the toxicity of CP and understand the biological mechanism of the toxicity of CP.
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Alanina , Metabolômica , Camundongos , Animais , Espectroscopia de Prótons por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Glicina , Ciclofosfamida/toxicidade , Prolina , ArgininaRESUMO
BACKGROUND: Despite increasing knowledge on the neuroimaging patterns of eating disorder (ED) symptoms in non-clinical populations, studies using whole-brain machine learning to identify connectome-based neuromarkers of ED symptomatology are absent. This study examined the association of connectivity within and between large-scale functional networks with specific symptomatic behaviors and cognitions using connectome-based predictive modeling (CPM). METHODS: CPM with ten-fold cross-validation was carried out to probe functional networks that were predictive of ED-associated symptomatology, including body image concerns, binge eating, and compensatory behaviors, within the discovery sample of 660 participants. The predictive ability of the identified networks was validated using an independent sample of 821 participants. RESULTS: The connectivity predictive of body image concerns was identified within and between networks implicated in cognitive control (frontoparietal and medial frontal), reward sensitivity (subcortical), and visual perception (visual). Crucially, the set of connections in the positive network related to body image concerns identified in one sample was generalized to predict body image concerns in an independent sample, suggesting the replicability of this effect. CONCLUSIONS: These findings point to the feasibility of using the functional connectome to predict ED symptomatology in the general population and provide the first evidence that functional interplay among distributed networks predicts body shape/weight concerns.
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Transtorno da Compulsão Alimentar , Conectoma , Humanos , Conectoma/métodos , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Cognição , Transtorno da Compulsão Alimentar/psicologiaRESUMO
Surfactants are commonly utilized in chemical flooding processes alongside salt to effectively decrease interfacial tension (IFT). However, the underlying microscopic mechanism for the synergistic effect of salt and surfactants on oil displacement remains ambiguous. Herein, the structure and properties of the interface between water and n-dodecane are studied by means of molecular dynamics simulations, considering three types of anionic surfactants and two types of salts. As the salt concentration (ρsalt) increases, the IFT first decreases to a minimum value, followed by a subsequent increase to higher values. The salt ions reduce the IFT only at low ρsalt due to the salt screening effect and ion bridging effect, both of which contribute to a decrease in the nearest head-to-head distance of surfactants. By incorporating salt doping, the IFTs can be reduced by at most 5%. Notably, the IFTs of different surfactants are mainly determined by the hydrogen bond interactions between oxygen atoms in the headgroup and water molecules. The presence of a greater number of oxygen atoms corresponds to lower IFT values. Specifically, for alkyl ethoxylate sulfate, the ethoxy groups play a crucial role in reducing the IFTs. This study provides valuable insights into formulating anionic surfactants that are applicable to oil recovery processes in petroleum reservoirs using saline water.
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BACKGROUND: Previous studies have revealed that functional health literacy plays a less important role than communicative and critical health literacy (CRHL) and that communicative literacy and CRHL contribute more to better patient self-management. Although improving health literacy has been identified as an approach to fostering community involvement and empowerment, CRHL may be regarded as the neglected domain of health literacy, rarely achieving any focus or interventions that claim to be working toward this outcome. Considering this research background, close scholarly attention needs to be paid to CRHL and its associated factors. OBJECTIVE: This study aimed to assess CRHL and identify essential factors closely associated with the status of CRHL among Chinese patients and to provide some implications for clinical practice, health education, medical research, and public health policy making. METHODS: We conducted this cross-sectional study, which lasted from April 8, 2022, to September 23, 2022, following the steps below. We first designed a 4-section survey questionnaire and then recruited Mandarin Chinese-speaking patients from Qilu Hospital of Shandong University, China, using randomized sampling. Subsequently, we administered the questionnaire via wenjuanxing, the most popular web-based survey platform in China, between July 20, 2022, and August 19, 2022. Finally, we used latent class modeling to analyze the valid data collected to classify the patient participants and identify the factors potentially associated with different CRHL levels. RESULTS: All data in the 588 returned questionnaires were valid. On the basis of the collected data, we classified the patient participants into 3 latent classes of limited, moderate, and adequate CRHL and identified 4 factors associated with limited CRHL, including middle and old age, male sex, lower educational attainment, and low internal drive to maintain one's health. CONCLUSIONS: Using latent class modeling, we identified 3 classes of CRHL and 4 factors associated with limited CRHL among the Chinese study participants. These literacy classes and the predicting factors ascertained in this study can provide some implications for clinical practice, health education, medical research, and health policy making.
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Letramento em Saúde , Humanos , Masculino , Estudos Transversais , Escolaridade , Educação em Saúde , Inquéritos e QuestionáriosRESUMO
Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disorder characterized by an enhanced accumulation of lipids, which affects around 40% of the world's population. The T. fuciformis fungus possesses immunomodulatory activity and other beneficial properties that may alleviate steatosis through a different mechanism. The present study was designed to evaluate the effect T. fuciformis crude polysaccharides (TFCP) on inflammatory and lipid metabolism gene expression, oxidative stress, and lipid profile. Mice were divided into groups receiving (a) a normal chow diet (NCD), (b) a methionine-choline-deficient (MCD) diet, and (c) a MCD diet with TFCP. Liver histopathology was performed, and the hepatic gene expression levels were estimated using qRT-PCR. The lipid profiles, ALT, AST, and efficient oxidative enzymes were analyzed using ELISA. The TFCP administration in the MCD-fed mice suppressed hepatic lipid accumulation, lipid metabolism-associated genes (HMGCR, FABP, SREBP, ACC, and FAS), and inflammation-associated genes (IL-1ß, TLR4, TNF-α, and IL-6) whilst enhancing the expression of HNF4α genes. TFCP mitigated against oxidative stress and normalized healthy lipid profiles. These results highlighted that TFCP prevents NAFLD through the inhibition of oxidative stress and inflammation, suggesting TFCP would potentially be an effective therapeutic agent against NAFLD progression.
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Antimicrobial peptides that target the integrity of bacterial envelopes can eradicate pathogens with little development of resistance, but they often inflict nonselective toxicity toward mammalian cells. The prevailing approach to optimize the selectivity of cationic peptides has been to modify their composition. Instead, we invent a new generation of broad-spectrum antibacterial nanoconstructs with negligible mammalian cell toxicity through a competitive displacement of counter polyanions from the complementary polycations. The nanoconstruct, which has a highly cationic Au nanoparticles (NPs) core shielded by polymeric counterions, is inert in nonbacterial environments. When exposed to negatively charged bacterial envelopes, this construct sheds its polyanions, triggering a cationic Au NP/bacterial membrane interaction that rapidly kills Gram-positive and Gram-negative bacteria. The anionic charge and hydrophilicity of the polyanion provides charge neutralization for the peptide-decorated Au NP core, but it is also bacteria-displaceable. These results provide a foundation for the development of other cationic particles and polymeric counterion combinations with potent antimicrobial activity without toxicity.
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Peptídeos Catiônicos Antimicrobianos , Nanopartículas Metálicas , Animais , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Ouro , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Testes de Sensibilidade MicrobianaRESUMO
Scale formation is a significant problem in a wide range of industries, including water treatment, food processing, power plants, and oilfield production. While surface modification provides a promising methodology to address this challenge, it has generally been believed that surface coatings with the lowest surface energy, such as fluorocarbon coatings, are most suitable for antiscaling applications. In contrast to this general knowledge, here we show that a liquid-like coating featuring highly mobile linear poly(dimethylsiloxane) (LPDMS) brush chains can bring an even better antiscaling performance than conventional perfluoroalkylsilane coatings, despite the fact that the former has much higher surface energy than the latter. We demonstrate that the LPDMS brush coating can more effectively inhibit heterogeneous nucleation of scale on a substrate compared with common perfluoroalkylsilane or alkylsilane coatings, and the dynamic liquid-like characteristic of the LPDMS brush coating is speculated to be responsible for its excellent nucleation inhibiting ability by reducing the affinity and effective interface interaction between the substrate and the scale nucleus. Our findings reveal the great prospect of using liquid-like coating to replace environmentally hazardous fluorine-containing organic ones as a green and cost-effective solution to address the scale problem with enhanced antiscaling performance.
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Fluorocarbonos , Purificação da Água , DimetilpolisiloxanosRESUMO
Untethered microrobots provide the prospect for performing minimally invasive surgery and targeted delivery of drugs in hard-to-reach areas of the human body. Recently, inspired by the way the prokaryotic flagella rotates to drive the body forward, numerous studies have been carried out to study the swimming properties of helical swimmers. In this study, the resistive force theory (RFT) was applied to analyze the influence of dimensional and kinematical parameters on the propulsion performance of conventional helical swimmers. The propulsion efficiency index was applied to quantitatively evaluate the swimming performance of helical swimmers. Quantitative analysis of the effect of different parameters on the propulsion performance was performed to optimize the design of structures. Then, RFT was modified to explore the tapered helical swimmers with the helix radius changing uniformly along the axis. Theoretical results show that the helical swimmer with a constant helix angle exhibits excellent propulsion performance. The evaluation index was found to increase with increased tapering, indicating that the tapered structures can produce more efficient motion. Additionally, the analysis method extended from RFT can be used to analyze the motion of special-shaped flagella in microorganisms.
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With the rapid development of the global navigation satellite system (GNSS), high-rate GNSS has been widely used for high-precision GNSS coseismic displacement retrieval. In recent decades, relative positioning (RP) and precise point positioning (PPP) are mainly adopted to retrieve coseismic displacements. However, RP can only obtain relative coseismic displacements with respect to a reference station, which might be subject to quaking during a large seismic event. While PPP needs a long (re)convergence period of tens of minutes. There is no convergence time needed in the variometric approach for displacements analysis standalone engine (VADASE) but the derived displacements are accompanied by a drift. Temporal point positioning (TPP) method adopts temporal-differenced ionosphere-free phase measurements between a reference epoch and the current epoch, and there is almost no drift in the displacement derived from TPP method. Nevertheless, the precise orbit and clock products should be applied in the TPP method. The studies in recent years are almost based on the postprocessing precise orbits and clocks or simulated real-time products. Since 2013, international GNSS service (IGS) has been providing an open-access real-time service (RTS), which consists of orbit, clock and other corrections. In this contribution, we evaluated the performance of real-time coseismic displacement retrieval based on TPP method with IGS RTS correction products. At first, the real-time precise orbit and clock offsets are derived from the RTS correction products. Then, the temporal-differenced ionosphere-free (IF) combinations are formed and adopted as the TPP measurements. By applying real-time precise orbit and clock offsets, the coseismic displacement can be real-timely retrieved based on TPP measurements. To evaluate the accuracy, two experiments including a stationary experiment and an application to an earthquake event were carried out. The former gives an accuracy of 1.8 cm in the horizontal direction and 4.1 cm in the vertical direction during the whole period of 15-min. The latter gives an accuracy of 1.2 cm and 2.4 cm in the horizontal and vertical components, respectively.
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Regulatory T cells (Tregs) characterized by the expression of the master transcription factor forkhead box protein p3 (Foxp3) suppress anticancer immunity, thereby hindering protective immunosurveillance of tumours and hampering effective antitumour immune responses in tumour-bearing hosts, constitute a current research hotspot in the field. However, Tregs are also essential for the maintenance of the immune tolerance of the body and share many molecular signalling pathways with conventional T cells, including cytotoxic T cells, the primary mediators of tumour immunity. Hence, the inability to specifically target and neutralize Tregs in the tumour microenvironment without globally compromising self-tolerance poses a significant challenge. Here, we review recent advances in characterizing tumour-infiltrating Tregs with a focus on the functional roles of costimulatory and inhibitory receptors in Tregs, evaluate their potential as clinical targets, and systematically summarize their roles in potential treatment strategies. Also, we propose modalities to integrate our increasing knowledge on Tregs phenotype and function for the rational design of checkpoint inhibitor-based combination therapies. Finally, we propose possible treatment strategies that can be used to develop Treg-targeted therapies.
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Neoplasias/etiologia , Neoplasias/patologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Microambiente Tumoral/imunologia , Animais , Gerenciamento Clínico , Suscetibilidade a Doenças , Metabolismo Energético , Regulação Neoplásica da Expressão Gênica , Humanos , Imunomodulação , Imunoterapia , Terapia de Alvo Molecular , Neoplasias/terapia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Microambiente Tumoral/genéticaRESUMO
Surface wettability regulation plays a crucial role in antifouling and related applications. For regulating surface wettability, one of the effective approaches is to modulate the surface charge distribution. Herein, we report a theoretical study for unraveling the mechanistic relation between surface charge distribution and ionic substrate wettability. Specifically, acetonitrile liquids at ambient condition in contact with various ionic substrates are considered. At different surface charge distributions, the interfacial thermodynamic properties are investigated by means of molecular density functional theory. We find that the variation of the spatial interval among the discrete charges strongly alters the substrate-acetonitrile interaction and leads to an oscillation in the interfacial tension, indicating that the substrate can be tuned from a solvophobic one to a solvophilic one. This trend can be further enhanced by increasing the charge quantity. The underlying mechanisms are extensively discussed and expatiated. Our work provides theoretical guidance to engineer and regulate surface wettability.
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Geometrical confinement has a large impact on gas solubilities in nanoscale pores. This phenomenon is closely associated with heterogeneous catalysis, shale gas extraction, phase separation, etc. Whereas several experimental and theoretical studies have been conducted that provide meaningful insights into the over-solubility and under-solubility of different gases in confined solvents, the microscopic mechanism for regulating the gas solubility remains unclear. Here, we report a hybrid theoretical study for unraveling the regulation mechanism by combining classical density functional theory (CDFT) with machine learning (ML). Specifically, CDFT is employed to predict the solubility of argon in various solvents confined in nanopores of different types and pore widths, and these case studies then supply a valid training set to ML for further investigation. Finally, the dominant parameters that affect the gas solubility are identified, and a criterion is obtained to determine whether a confined gas-solvent system is enhance-beneficial or reduce-beneficial. Our findings provide theoretical guidance for predicting and regulating gas solubilities in nanopores. In addition, the hybrid method proposed in this work sets up a feasible platform for investigating complex interfacial systems with multiple controlling parameters.
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Microbes, especially the uncultured microbes, have been considered as an important resource for discovery of novel cellulases. In this study, a novel bifunctional cellulase/hemicellulase (ZFYN184) was identified by functional screening of a soil metagenomic library. Sequence analysis indicated that ZFYN184 shared at best 39% identity with glycoside hydrolase family 44 (GH44) proteins and contained a glutamic acid residue at 235 acting as the catalytic proton donor in hydrolysis of polysaccharides. The recombinant ZFYN184 was expressed in Escherichia coli BL21 (DE3), and the biochemical profiles of the enzyme, including optimum pH and temperature, pH and thermal stabilities, tolerance to various additives, and substrate specificity, were determined. ZFYN184 possessed strong endo-ß-1,4-glucanase and endo-1,4-ß-mannanase activities, as well as weak xylanase activity, while all these hydrolytic activities were derived from a single catalytic domain in this GH44 enzyme. KEY POINTS: ⢠Discovery a novel bifunctional glycosyl hydrolase from uncultured microorganism. ⢠ZFYN184 contains a single catalytic domain belonged to GH44.
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Celulase , Celulases , Celulase/genética , Celulase/metabolismo , Clonagem Molecular , Estabilidade Enzimática , Glicosídeo Hidrolases/metabolismo , Concentração de Íons de Hidrogênio , Solo , Especificidade por SubstratoRESUMO
BACKGROUND A high-salt diet may result in chronic disease and changes in the intestinal microbiota. This pilot study aimed to investigate the microbial composition of the intestine in Wistar rats given intragastric high-salt infusions for four weeks. MATERIAL AND METHODS Six 4-week-old male Wistar rats were fed standard chow and divided into the high-salt group (n=3) and the control study group (n=3). Rats in the high-salt group were given 1 ml of 10% NaCl solution intragastrically three times per week for four weeks. The fecal pellets were collected, and the microbiota was characterized using 16S rRNA gene sequencing that targeted the V4 region. The relative abundance of microbial populations was compared using linear discriminant analysis effect size (LEfSe) statistical analysis for the identification of biomarkers between two or more groups, principal component analysis (PCA), and linear discriminant analysis (LDA). Microbial genome prediction was performed using the phylogenetic investigation of communities by reconstructing the unobserved states (PICRUSt) bioinformatics software. RESULTS There was no significant difference in the alpha diversity of the fecal microbiota between the high-salt group and the control group. However, PCA showed structural segregation between the two groups. Further analysis using LEfSe showed that the intestinal contents in the high-salt group had significantly reduced populations of Lactobacillus and Prevotella NK3B31, and a significant increase in Alloprevotella and Prevotella 9, without physiological or pathological changes. CONCLUSIONS A pilot study in Wistar rats showed that high-salt intake was associated with a change in the composition of the intestinal microbiota.
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Microbioma Gastrointestinal/efeitos dos fármacos , Cloreto de Sódio na Dieta/efeitos adversos , Animais , Bactérias/genética , Fezes/microbiologia , Intestinos/microbiologia , Masculino , Filogenia , Projetos Piloto , RNA Ribossômico 16S/análise , Ratos , Ratos Wistar , Cloreto de Sódio/metabolismo , Estômago/microbiologiaRESUMO
Tousled like kinase 1 (TLK1), a member of DNA repair family, participates in the regulation of chromatin assembly and is associated with early menopause and premature ovarian insufficiency (POI) in European women. However, whether the sequence variant in the TLK1 gene was causative for POI is still elusive. Here we performed direct sequencing of the TLK1 gene in 192 patients with sporadic POI. All exons and exon-intron boundaries of TLK1 were amplified and sequenced. Six known single-nucleotide polymorphisms were identified in POI, including rs149844334, rs11553951, rs757600673, rs2277339, rs113416007 and rs17283147. No novel variant was identified, which indicates that sequence variants in the coding region of TLK1 might be uncommon in Chinese women with POI. The role of TLK1 in POI pathogenesis needs to be further explored in larger cohorts from Chinese and other ethnic populations.